Take-Home Points

• With EHR implementation there are small changes in the level of billing coding.
• Although these changes may be statistically significant they are relatively minor.
• In the general internal medicine department, level 4 coding increased by 1.2% while level 3 coding decreased by 0.5%.
• In the orthopedics department, level 4 coding increased by 3.3% while level 3 coding decreased by 3.1%.
• Reports in the lay media regarding dramatic up-coding after EHR implementation may be misleading.

The Health Information Technology for Economic and Clinical Health (HITECH) Act, which was signed into law in 2009, mandated that hospitals that care for Medicare patients either begin using electronic health records (EHRs) or pay a nontrivial penalty.¹ By now, the majority of orthopedic surgeons have implemented EHRs in their practices.² Despite ongoing debate in the orthopedic literature,³ EHRs are expected to improve coordination of care, reduce duplicate testing, and reduce costs over the long term as healthcare insurance coverage is extended to millions more Americans.

In early coverage, however, media reported that EHR implementation at some hospitals was correlated with substantial increases in Medicare payments.⁴ Journalists suggested the billion dollars more paid by Medicare to hospitals in 2010 than in 2005 were partly attributable to up-coding facilitated by EHRs.⁵ The secretary of the Department of Health and Human Services (DHHS) and the attorney general of the Department of Justice also weighed in on this controversy by expressing their concerns in a letter to the presidents of 5 hospital associations.⁶ The inspector general of DHHS also published a report critical of Medicare officials’ oversight of EHRs.⁷Responding to the critical reception of EHR implementations, investigators studied the validity of the early reports and anecdotes. Some initial reports cited the emergency department (ED) as an area at high risk for using the convenience of EHRs to up-code visits.⁵ The DHHS Office of the Inspector General noted that, between 2001 and 2010, the proportion of claims for lower reimbursement categories of American Medical Association Current Procedural Terminology (CPT) codes decreased while the proportion for higher-paid billing codes increased for all visit types.⁸ Addressing these concerns, the American Hospital Association⁹ issued a brief that noted that any observed coding increases were more likely attributable to more ED use by Medicare patients and increased average illness severity. In a thoughtful perspective, Pitts¹⁰ conceded that, though utilization and illness severity may explain part of the trend, the trend may also be related to technological innovations and changes in culture and practice style in the ED.

Because these studies and reports variously suggested that EHR implementation affects patient volume and up-coding, and because none of the reports specifically addressed orthopedics, we conducted a study to determine whether any significant up-coding or change in patient volumes occurred around the time of EHR implementation in ambulatory practices at our academic medical center. In a recent national study, Adler-Milstein and Jha¹¹ compared billing data of hospitals that adopted EHRs and hospitals that did not. Although both groups showed increased billing trends, the increases were not significantly different between the EHR adopters and nonadopters. To more effectively control for the confounding differences between groups of EHR adopters and nonadopters, we studied individual departments during EHR implementation at our institution.

Methods

In 2011, our academic medical center began the transition to EHRs (Epic). We examined our center’s trends in patient volumes and billing coding around the time of the transition in the outpatient practice of the general internal medicine (GIM) department (EHR transition, October 2011) and the outpatient practice of the orthopedics department (EHR transition, March 2012). These departments were chosen because they are representative of a GIM practice and a subspecialty practice, and because a recent study found that GIM practitioners and orthopedic surgeons were among those specialists who used EHRs the most.¹²

After this study was approved by our Human Investigations Committee, we began using CPT codes to identify all outpatient visits (new, consultation, and return) on a monthly basis. We compared the volume of patient visits and the billing coding level in the GIM and orthopedics departments before and after EHR implementation. Pearson χ² test was used when appropriate, and statistical analyses were performed with SPSS for Windows Version 16.0.

Results

In the GIM department, mean monthly volume of patient visits in the 12 months before EHR implementation was similar to that in the 12 months afterward (613 vs 587; P = .439). Even when normalized for changes in provider availability (maternity leave), the decrease in volume of patient visits after EHR implementation in the GIM department was not significant (6.9%; P = .107). Likewise, in the orthopedics department, mean monthly volume of patient visits in the 17 months before EHR implementation was similar to that in the 7 months afterward (2157 vs 2317; P = .156). In fact, patient volumes remained constant during the EHR transition (Figure 1).

EHR implementation brought small changes in billing coding levels. In the GIM department, the largest change was a 1.2% increase in level 4 billing coding—an increase accompanied by a 0.5% decrease in level 3 coding.

Discussion

It is remarkable that the volumes of patient visits in the GIM and orthopedics departments at our academic center were not affected by EHR implementation.

Rather than reduce scheduling during the EHR transition, surgeons in our practice either added or lengthened clinic sessions, and the level of ancillary staffing was adjusted accordingly. As staffing costs at any given time are multifactorial and vary widely, estimating the cost of these staffing changes during the EHR transition is difficult. We should note that extending ancillary staff hours during the transition very likely increased costs, and it is unclear whether they were higher or lower than the costs that would have been incurred had we reduced scheduling or tried some combination of these strategies.

Although billing coding levels changed with EHR implementation, the changes were small. In the GIM department, level 4 CPT coded visits as percentages of all visits increased to 59.5% from 58.3%, and level 5 visits increased to 6.2% from 6.0%; in the orthopedics department, level 4 visits increased to 40.2% from 37.1%, and level 5 visits increased to 5.5% from 3.8% (Table). The 1.2% and 0.2% absolute increases in level 4 and level 5 visits in the GIM department represent 2.1% and 3.3% relative increases in level 4 and level 5 visits, and the 3.3% and 1.7% absolute increases in the orthopedics department represent 8.4% and 44.7% relative increases in level 4 and level 5 visits after EHR implementation.

Although the absolute increases in level 4 and level 5 visits were relatively minor, popular media have raised the alarm about 43% and 82% relative increases in level 5 visits after EHR implementation in some hospitals’ EDs.⁴ Although our orthopedics department showed a 44.7% relative increase in level 5 visits after EHR implementation, this represented an increase of only 1.7% of patient visits overall. Our findings therefore indicate that lay media reports could be misleading. Nevertheless, the small changes we found were statistically significant.

One explanation for these small changes is that EHRs facilitate better documentation of services provided. Therefore, what seem to be billing coding changes could be more accurate reports of high-level care that is the same as before. In addition, because of meaningful use mandates that coincided with the requirement to implement EHRs, additional data elements are now being consistently collected and reviewed (these may not necessarily have been collected and reviewed before). In some patient encounters, these additional data elements may have contributed to higher levels of service, and this effect could be especially apparent in EDs.

Some have suggested a potential for large-scale up-coding during EHR transitions. Others have contended that coding level increases are a consequence of a time-intensive data entry process, collection and review of additional data, and more accurate reporting of services already being provided. We are not convinced that large coding changes are attributable solely to EHR implementation, as the changes at our center have been relatively small.

Nevertheless, minor coding level changes could translate to large changes in healthcare costs when scaled nationally. Although causes may be innocuous, any increases in national healthcare costs are concerning in our time of limited budgets and scrutinized healthcare utilization.

This study had its limitations. First, including billing data from only 2 departments at a single center may limit the generalizability of findings. However, we specifically selected a GIM department and a specialty (orthopedics) department in an attempt to capture a representative sample of practices. Another limitation is that we investigated billing codes over only 2 years, around the implementation of EHRs in these departments, and therefore may have captured only short-term changes. However, as patient volumes and billing are subject to many factors, including staffing changes (eg, new partners, new hires, retirements, other departures), we attempted to limit the effect of confounding variables by limiting the period of analysis.

Overall, changes in patient volume and coded level of service during EHR implementation at our institution were relatively small. Although the trend toward higher billing coding levels was statistically significant, these 0.2% and 1.7% increases in level 5 coding hardly deserve the negative attention from lay media. These small increases are unlikely caused by intentional up-coding, and more likely reflect better documentation of an already high level of care. We hope these findings allay the concern that up-coding increased dramatically with EHR implementation.

Am J Orthop. 2017;46(3):E172-E176. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• With EHR implementation there are small changes in the level of billing coding.
• Although these changes may be statistically significant they are relatively minor.
• In the general internal medicine department, level 4 coding increased by 1.2% while level 3 coding decreased by 0.5%.
• In the orthopedics department, level 4 coding increased by 3.3% while level 3 coding decreased by 3.1%.
• Reports in the lay media regarding dramatic up-coding after EHR implementation may be misleading.

The Health Information Technology for Economic and Clinical Health (HITECH) Act, which was signed into law in 2009, mandated that hospitals that care for Medicare patients either begin using electronic health records (EHRs) or pay a nontrivial penalty.¹ By now, the majority of orthopedic surgeons have implemented EHRs in their practices.² Despite ongoing debate in the orthopedic literature,³ EHRs are expected to improve coordination of care, reduce duplicate testing, and reduce costs over the long term as healthcare insurance coverage is extended to millions more Americans.

In early coverage, however, media reported that EHR implementation at some hospitals was correlated with substantial increases in Medicare payments.⁴ Journalists suggested the billion dollars more paid by Medicare to hospitals in 2010 than in 2005 were partly attributable to up-coding facilitated by EHRs.⁵ The secretary of the Department of Health and Human Services (DHHS) and the attorney general of the Department of Justice also weighed in on this controversy by expressing their concerns in a letter to the presidents of 5 hospital associations.⁶ The inspector general of DHHS also published a report critical of Medicare officials’ oversight of EHRs.⁷Responding to the critical reception of EHR implementations, investigators studied the validity of the early reports and anecdotes. Some initial reports cited the emergency department (ED) as an area at high risk for using the convenience of EHRs to up-code visits.⁵ The DHHS Office of the Inspector General noted that, between 2001 and 2010, the proportion of claims for lower reimbursement categories of American Medical Association Current Procedural Terminology (CPT) codes decreased while the proportion for higher-paid billing codes increased for all visit types.⁸ Addressing these concerns, the American Hospital Association⁹ issued a brief that noted that any observed coding increases were more likely attributable to more ED use by Medicare patients and increased average illness severity. In a thoughtful perspective, Pitts¹⁰ conceded that, though utilization and illness severity may explain part of the trend, the trend may also be related to technological innovations and changes in culture and practice style in the ED.

Because these studies and reports variously suggested that EHR implementation affects patient volume and up-coding, and because none of the reports specifically addressed orthopedics, we conducted a study to determine whether any significant up-coding or change in patient volumes occurred around the time of EHR implementation in ambulatory practices at our academic medical center. In a recent national study, Adler-Milstein and Jha¹¹ compared billing data of hospitals that adopted EHRs and hospitals that did not. Although both groups showed increased billing trends, the increases were not significantly different between the EHR adopters and nonadopters. To more effectively control for the confounding differences between groups of EHR adopters and nonadopters, we studied individual departments during EHR implementation at our institution.

Methods

In 2011, our academic medical center began the transition to EHRs (Epic). We examined our center’s trends in patient volumes and billing coding around the time of the transition in the outpatient practice of the general internal medicine (GIM) department (EHR transition, October 2011) and the outpatient practice of the orthopedics department (EHR transition, March 2012). These departments were chosen because they are representative of a GIM practice and a subspecialty practice, and because a recent study found that GIM practitioners and orthopedic surgeons were among those specialists who used EHRs the most.¹²

After this study was approved by our Human Investigations Committee, we began using CPT codes to identify all outpatient visits (new, consultation, and return) on a monthly basis. We compared the volume of patient visits and the billing coding level in the GIM and orthopedics departments before and after EHR implementation. Pearson χ² test was used when appropriate, and statistical analyses were performed with SPSS for Windows Version 16.0.

Results

In the GIM department, mean monthly volume of patient visits in the 12 months before EHR implementation was similar to that in the 12 months afterward (613 vs 587; P = .439). Even when normalized for changes in provider availability (maternity leave), the decrease in volume of patient visits after EHR implementation in the GIM department was not significant (6.9%; P = .107). Likewise, in the orthopedics department, mean monthly volume of patient visits in the 17 months before EHR implementation was similar to that in the 7 months afterward (2157 vs 2317; P = .156). In fact, patient volumes remained constant during the EHR transition (Figure 1).

EHR implementation brought small changes in billing coding levels. In the GIM department, the largest change was a 1.2% increase in level 4 billing coding—an increase accompanied by a 0.5% decrease in level 3 coding.

Discussion

It is remarkable that the volumes of patient visits in the GIM and orthopedics departments at our academic center were not affected by EHR implementation.

Rather than reduce scheduling during the EHR transition, surgeons in our practice either added or lengthened clinic sessions, and the level of ancillary staffing was adjusted accordingly. As staffing costs at any given time are multifactorial and vary widely, estimating the cost of these staffing changes during the EHR transition is difficult. We should note that extending ancillary staff hours during the transition very likely increased costs, and it is unclear whether they were higher or lower than the costs that would have been incurred had we reduced scheduling or tried some combination of these strategies.

Although billing coding levels changed with EHR implementation, the changes were small. In the GIM department, level 4 CPT coded visits as percentages of all visits increased to 59.5% from 58.3%, and level 5 visits increased to 6.2% from 6.0%; in the orthopedics department, level 4 visits increased to 40.2% from 37.1%, and level 5 visits increased to 5.5% from 3.8% (Table). The 1.2% and 0.2% absolute increases in level 4 and level 5 visits in the GIM department represent 2.1% and 3.3% relative increases in level 4 and level 5 visits, and the 3.3% and 1.7% absolute increases in the orthopedics department represent 8.4% and 44.7% relative increases in level 4 and level 5 visits after EHR implementation.

Although the absolute increases in level 4 and level 5 visits were relatively minor, popular media have raised the alarm about 43% and 82% relative increases in level 5 visits after EHR implementation in some hospitals’ EDs.⁴ Although our orthopedics department showed a 44.7% relative increase in level 5 visits after EHR implementation, this represented an increase of only 1.7% of patient visits overall. Our findings therefore indicate that lay media reports could be misleading. Nevertheless, the small changes we found were statistically significant.

One explanation for these small changes is that EHRs facilitate better documentation of services provided. Therefore, what seem to be billing coding changes could be more accurate reports of high-level care that is the same as before. In addition, because of meaningful use mandates that coincided with the requirement to implement EHRs, additional data elements are now being consistently collected and reviewed (these may not necessarily have been collected and reviewed before). In some patient encounters, these additional data elements may have contributed to higher levels of service, and this effect could be especially apparent in EDs.

Some have suggested a potential for large-scale up-coding during EHR transitions. Others have contended that coding level increases are a consequence of a time-intensive data entry process, collection and review of additional data, and more accurate reporting of services already being provided. We are not convinced that large coding changes are attributable solely to EHR implementation, as the changes at our center have been relatively small.

Nevertheless, minor coding level changes could translate to large changes in healthcare costs when scaled nationally. Although causes may be innocuous, any increases in national healthcare costs are concerning in our time of limited budgets and scrutinized healthcare utilization.

This study had its limitations. First, including billing data from only 2 departments at a single center may limit the generalizability of findings. However, we specifically selected a GIM department and a specialty (orthopedics) department in an attempt to capture a representative sample of practices. Another limitation is that we investigated billing codes over only 2 years, around the implementation of EHRs in these departments, and therefore may have captured only short-term changes. However, as patient volumes and billing are subject to many factors, including staffing changes (eg, new partners, new hires, retirements, other departures), we attempted to limit the effect of confounding variables by limiting the period of analysis.

Overall, changes in patient volume and coded level of service during EHR implementation at our institution were relatively small. Although the trend toward higher billing coding levels was statistically significant, these 0.2% and 1.7% increases in level 5 coding hardly deserve the negative attention from lay media. These small increases are unlikely caused by intentional up-coding, and more likely reflect better documentation of an already high level of care. We hope these findings allay the concern that up-coding increased dramatically with EHR implementation.

Am J Orthop. 2017;46(3):E172-E176. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• With EHR implementation there are small changes in the level of billing coding.
• Although these changes may be statistically significant they are relatively minor.
• In the general internal medicine department, level 4 coding increased by 1.2% while level 3 coding decreased by 0.5%.
• In the orthopedics department, level 4 coding increased by 3.3% while level 3 coding decreased by 3.1%.
• Reports in the lay media regarding dramatic up-coding after EHR implementation may be misleading.

The Health Information Technology for Economic and Clinical Health (HITECH) Act, which was signed into law in 2009, mandated that hospitals that care for Medicare patients either begin using electronic health records (EHRs) or pay a nontrivial penalty.¹ By now, the majority of orthopedic surgeons have implemented EHRs in their practices.² Despite ongoing debate in the orthopedic literature,³ EHRs are expected to improve coordination of care, reduce duplicate testing, and reduce costs over the long term as healthcare insurance coverage is extended to millions more Americans.

In early coverage, however, media reported that EHR implementation at some hospitals was correlated with substantial increases in Medicare payments.⁴ Journalists suggested the billion dollars more paid by Medicare to hospitals in 2010 than in 2005 were partly attributable to up-coding facilitated by EHRs.⁵ The secretary of the Department of Health and Human Services (DHHS) and the attorney general of the Department of Justice also weighed in on this controversy by expressing their concerns in a letter to the presidents of 5 hospital associations.⁶ The inspector general of DHHS also published a report critical of Medicare officials’ oversight of EHRs.⁷Responding to the critical reception of EHR implementations, investigators studied the validity of the early reports and anecdotes. Some initial reports cited the emergency department (ED) as an area at high risk for using the convenience of EHRs to up-code visits.⁵ The DHHS Office of the Inspector General noted that, between 2001 and 2010, the proportion of claims for lower reimbursement categories of American Medical Association Current Procedural Terminology (CPT) codes decreased while the proportion for higher-paid billing codes increased for all visit types.⁸ Addressing these concerns, the American Hospital Association⁹ issued a brief that noted that any observed coding increases were more likely attributable to more ED use by Medicare patients and increased average illness severity. In a thoughtful perspective, Pitts¹⁰ conceded that, though utilization and illness severity may explain part of the trend, the trend may also be related to technological innovations and changes in culture and practice style in the ED.

Because these studies and reports variously suggested that EHR implementation affects patient volume and up-coding, and because none of the reports specifically addressed orthopedics, we conducted a study to determine whether any significant up-coding or change in patient volumes occurred around the time of EHR implementation in ambulatory practices at our academic medical center. In a recent national study, Adler-Milstein and Jha¹¹ compared billing data of hospitals that adopted EHRs and hospitals that did not. Although both groups showed increased billing trends, the increases were not significantly different between the EHR adopters and nonadopters. To more effectively control for the confounding differences between groups of EHR adopters and nonadopters, we studied individual departments during EHR implementation at our institution.

Methods

In 2011, our academic medical center began the transition to EHRs (Epic). We examined our center’s trends in patient volumes and billing coding around the time of the transition in the outpatient practice of the general internal medicine (GIM) department (EHR transition, October 2011) and the outpatient practice of the orthopedics department (EHR transition, March 2012). These departments were chosen because they are representative of a GIM practice and a subspecialty practice, and because a recent study found that GIM practitioners and orthopedic surgeons were among those specialists who used EHRs the most.¹²

After this study was approved by our Human Investigations Committee, we began using CPT codes to identify all outpatient visits (new, consultation, and return) on a monthly basis. We compared the volume of patient visits and the billing coding level in the GIM and orthopedics departments before and after EHR implementation. Pearson χ² test was used when appropriate, and statistical analyses were performed with SPSS for Windows Version 16.0.

Results

In the GIM department, mean monthly volume of patient visits in the 12 months before EHR implementation was similar to that in the 12 months afterward (613 vs 587; P = .439). Even when normalized for changes in provider availability (maternity leave), the decrease in volume of patient visits after EHR implementation in the GIM department was not significant (6.9%; P = .107). Likewise, in the orthopedics department, mean monthly volume of patient visits in the 17 months before EHR implementation was similar to that in the 7 months afterward (2157 vs 2317; P = .156). In fact, patient volumes remained constant during the EHR transition (Figure 1).

EHR implementation brought small changes in billing coding levels. In the GIM department, the largest change was a 1.2% increase in level 4 billing coding—an increase accompanied by a 0.5% decrease in level 3 coding.

Discussion

It is remarkable that the volumes of patient visits in the GIM and orthopedics departments at our academic center were not affected by EHR implementation.

Rather than reduce scheduling during the EHR transition, surgeons in our practice either added or lengthened clinic sessions, and the level of ancillary staffing was adjusted accordingly. As staffing costs at any given time are multifactorial and vary widely, estimating the cost of these staffing changes during the EHR transition is difficult. We should note that extending ancillary staff hours during the transition very likely increased costs, and it is unclear whether they were higher or lower than the costs that would have been incurred had we reduced scheduling or tried some combination of these strategies.

Although billing coding levels changed with EHR implementation, the changes were small. In the GIM department, level 4 CPT coded visits as percentages of all visits increased to 59.5% from 58.3%, and level 5 visits increased to 6.2% from 6.0%; in the orthopedics department, level 4 visits increased to 40.2% from 37.1%, and level 5 visits increased to 5.5% from 3.8% (Table). The 1.2% and 0.2% absolute increases in level 4 and level 5 visits in the GIM department represent 2.1% and 3.3% relative increases in level 4 and level 5 visits, and the 3.3% and 1.7% absolute increases in the orthopedics department represent 8.4% and 44.7% relative increases in level 4 and level 5 visits after EHR implementation.

Although the absolute increases in level 4 and level 5 visits were relatively minor, popular media have raised the alarm about 43% and 82% relative increases in level 5 visits after EHR implementation in some hospitals’ EDs.⁴ Although our orthopedics department showed a 44.7% relative increase in level 5 visits after EHR implementation, this represented an increase of only 1.7% of patient visits overall. Our findings therefore indicate that lay media reports could be misleading. Nevertheless, the small changes we found were statistically significant.

One explanation for these small changes is that EHRs facilitate better documentation of services provided. Therefore, what seem to be billing coding changes could be more accurate reports of high-level care that is the same as before. In addition, because of meaningful use mandates that coincided with the requirement to implement EHRs, additional data elements are now being consistently collected and reviewed (these may not necessarily have been collected and reviewed before). In some patient encounters, these additional data elements may have contributed to higher levels of service, and this effect could be especially apparent in EDs.

Some have suggested a potential for large-scale up-coding during EHR transitions. Others have contended that coding level increases are a consequence of a time-intensive data entry process, collection and review of additional data, and more accurate reporting of services already being provided. We are not convinced that large coding changes are attributable solely to EHR implementation, as the changes at our center have been relatively small.

Nevertheless, minor coding level changes could translate to large changes in healthcare costs when scaled nationally. Although causes may be innocuous, any increases in national healthcare costs are concerning in our time of limited budgets and scrutinized healthcare utilization.

This study had its limitations. First, including billing data from only 2 departments at a single center may limit the generalizability of findings. However, we specifically selected a GIM department and a specialty (orthopedics) department in an attempt to capture a representative sample of practices. Another limitation is that we investigated billing codes over only 2 years, around the implementation of EHRs in these departments, and therefore may have captured only short-term changes. However, as patient volumes and billing are subject to many factors, including staffing changes (eg, new partners, new hires, retirements, other departures), we attempted to limit the effect of confounding variables by limiting the period of analysis.

Overall, changes in patient volume and coded level of service during EHR implementation at our institution were relatively small. Although the trend toward higher billing coding levels was statistically significant, these 0.2% and 1.7% increases in level 5 coding hardly deserve the negative attention from lay media. These small increases are unlikely caused by intentional up-coding, and more likely reflect better documentation of an already high level of care. We hope these findings allay the concern that up-coding increased dramatically with EHR implementation.

Am J Orthop. 2017;46(3):E172-E176. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

A suggestion for Congress: keep what’s working in the Patient Protection and Affordable Care Act (PPACA), adjust what isn’t working – just make the whole thing better and call it what you will.

A good thing, but needing work

The PPACA, which is also referred to as Obama care, had a lot in it that any reasonable person would consider good. Let’s take a look. As Dr Valerie Arkoosh wrote in our journal in 2012,² the law attempted to expand access to health care to the embarrassingly large 30 million or more Americans who were not insured. How would it do this? By expanding Medicaid, enhancing consumer protections in the private health insurance market, requiring large employers to offer insurance or pay a fine, giving tax credits to increase affordability of insurance for small businesses, creating state-based competitive market places, and requiring individuals to purchase health insurance plans (the so-called insurance mandate), thereby creating a pool of large numbers of healthy people who would help defray the costs of those not so fortunate.The law also guaranteed insurability despite any preexisting condition, surely a step in the right direction. Likewise, the need for employers to provide health insurance, the state-based health insurance exchanges, and especially the individual mandate to buy insurance or pay a fine, were all steps in the right direction.

And the law went further – it also addressed preventive care. Medicare and all new insurance plans would have to cover, without copay, co-insurance, or deductible, high-certainty preventive services such as screening for breast, cervical, colorectal, lung, and skin cancers, the annual well-woman visit, breast cancer preventative medications, and many others.³ Medicare recipients would be eligible for one non-copay annual wellness visit to their caregiver. Beyond providing increased access to health care, the PPACA added incentives to caregivers who were coming out of training programs to serve in underserved areas and benefit from a decrease in their med school loans or in their loan repayments.

Finally, and especially important, under the PPACA, our age-old insurance system of fee for service, which tends to incentivize more care, would change to incentivizing high-quality, outcomes-based care , thus replacing “quantity of care” with quality of care. So what’s wrong with the features of the law outlined in the preceding paragraphs? Well, of course, for every 100 ideas, only a few will be implemented and actually pay off. Certainly some of the PPACA could have been better implemented, and perhaps the task now facing Congress, if it could ever abandon its current pitched-camp approach, should be to take the ideas that health care policy scientists have established as being valid and find a way to make them work. Surely that would be best for all players, rather than carping about the repeal-replace approach versus staying with the PPACA.

So my response to the repeal-replace assertion? Retain, review, and refine.

Practitioner-friendly content

Health care calamities notwithstanding, we have a line-up of articles in this issue that uniformly address some of the pressing needs many of us face in our daily practice. Barry and colleagues examined the patterns of care with regard to whole brain radiotherapy technique and delivery at US-based academic centers. Their results show some interesting differences in the way younger and older practitioners deliver that care, with older practitioners placing more importance on tumor histopathology when considering brain irradiation. Speaking of access to care in the context of health reform, how often do our cancer patients use the emergency department? Lash and colleagues looked at the ED-use numbers from two databases in California and found that patients go to the ED at higher rates than previously reported and with notable variability by cancer type. Now we need to examine the reasons for those visits and establish ways to identify predictors of ED use to improve patient quality of care and rein in the higher costs of ED use.

In regard to symptom management, we can never have enough about nausea and vomiting prevention. Schwartzberg and colleagues report on a trial in which they evaluated the clinical benefits of APF530, a subcutaneous formulation of granisetron, compared with ondansetron in patients who had received cisplatin therapy. This longer-acting formulation of granisetron performed very well against a standard of care and might give our patients another option in the clinic for highly emetogenic chemotherapy.

Still on the topic of symptom management, preventing and treating mTOR-inhibitor–associated stomatitis (mIAS) is the subject of a review by Ramchandran and colleagues. The inhibitors have been approved for treatment in renal cell, neuroendocrine, and breast cancers, but of course, many of our newer molecules have some associated toxicity. Based on their literature scan, the authors report that management of mIAS should focus on three major approaches: prevention, early aggressive treatment, and, when needed, more aggressive pain management. Early recognition and diagnosis of mIAS facilitate early intervention to limit potential sequelae of mIAS and minimize the need for mTOR inhibitor dose reduction and interruption.

In a way, stress management could also fall under the symptom management category. I often remember being told during my training that we should always discuss with your patients their level of anxiety and depression. But I think sometimes we are so busy addressing the cancer, its treatment, and treatment side effects, we overlook the fact that the patient is suffering psychologically and might need additional intervention in the form of talk therapy and/or medication. Ramírez-Solá and colleagues describe in our How We Do It section the process of developing and implementing a psychosocial distress management program at their institution in Puerto Rico. The authors also summarize the results of a pilot study to validate the Patient Health Questionnaire (PHQ-9) as a measure to improve the process of emotional distress management in particular.

In recent years, the number of approvals and new indications for therapies for different cancer types has increased significantly. We highlight two such approvals in this issue. One is the PARP inhibitor, rucaparib, which was approved in both the platinum-sensitive and -resistant settings for BRCA1- and BRCA2-mutant patients with ovarian cancer. The other is the new CD38 antibody daratumumab, which was originally approved as a single-agent therapy for relapsed myeloma and which has now received a second approval with demonstrated improvement of progression-free survival when given with the lenalidomide-dexamethasone or bortezomib-dexamethasone combinations.

When it comes to new therapies, immunotherapies are at the cutting edge. Who hasn’t heard of the new checkpoint inhibitor drugs for a range of cancers that have either been approved or are in trial? Until now, we have used these immunotherapies as single agents, but Jane de Lartigue writes of the potential of combining more than one immunotherapy drug and/or combining an immune checkpoint inhibitor with a chemotherapy drug. The key behind this concept is that the more antigenic differentiation and tumor infiltrating lymphocytes in the system, the better the immunotherapy might work.

In the previous issue of the journal, one of our Editors, Thomas Strouse, discussed the issue of physician aid in dying (PAD)⁴ and asserted he had come to view “active non-participation” in legal PAD as a “toxic form of patient abandonment.” This is, of course, a very challenging and complex topic, and one that we likely have to address on a weekly basis with some of our cancer patients: if palliative care and end-of-life is the goal, how can we most humanely achieve that ethically and legally in concert with our patients’ wishes? Is it right or wrong to aid in some way in the dying process? Dr Alva Weir responds to Dr Strouse’s editorial, taking the view point that physician-assisted suicide is toxic abandonment. Dr Strauss responds, and I encourage you to read this very interesting exchange that highlights the point-counterpoint views of physician involvement in the dying process.

We round off the issue with a bumper crop of Case Reports. They include two that document diagnostic challenges: one in a patient with pulmonary sarcomatoid carcinoma presenting as a necrotizing cavitary lung lesion and another in which atraumatic splenic rupture is the initial presentation of CML. Also included is a report on a case of primary cardiac prosthetic valve-associated lymphoma and another on how a collaborative effort between oncologists and dermatologists contributed to the resolution of palmoplantar exacerbation of psoriasis in a patient who had been treated with nivolumab.

Going digital

I will close by remarking that the Journal of Community and Supportive Oncology, or JCSO, will be going digital only after this print issue. We will continue publishing the same content as a bimonthly digital issue, posting articles directly to our website, and mailing out our regular electronic newsletters. So visit the website, www.jcso-online.com, where you can read the articles as soon as they are posted and also find instructions for downloading the app for the digital edition – it’s quick, easy, and free, in case you were wondering. For a shortcut to the download the app, you can also use http://bit.ly/2nCEPIa.

Finally, if you would like to submit a paper to us for consideration for publication, you can do so by going to www.editorialmanager.com/jso/. We will consider submissions in original research, reviews, How We Do It, case reports, and tumor board summaries – you’ll find all the information you need to submit a paper at the EditorialManager platform. And let’s not forget social media – we’re on Twitter where our handle is @jcs_onc, my personal Twitter handle is @davidhenrymd, so connect with us – follow us, like us, and retweet us.

A suggestion for Congress: keep what’s working in the Patient Protection and Affordable Care Act (PPACA), adjust what isn’t working – just make the whole thing better and call it what you will.

A good thing, but needing work

The PPACA, which is also referred to as Obama care, had a lot in it that any reasonable person would consider good. Let’s take a look. As Dr Valerie Arkoosh wrote in our journal in 2012,² the law attempted to expand access to health care to the embarrassingly large 30 million or more Americans who were not insured. How would it do this? By expanding Medicaid, enhancing consumer protections in the private health insurance market, requiring large employers to offer insurance or pay a fine, giving tax credits to increase affordability of insurance for small businesses, creating state-based competitive market places, and requiring individuals to purchase health insurance plans (the so-called insurance mandate), thereby creating a pool of large numbers of healthy people who would help defray the costs of those not so fortunate.The law also guaranteed insurability despite any preexisting condition, surely a step in the right direction. Likewise, the need for employers to provide health insurance, the state-based health insurance exchanges, and especially the individual mandate to buy insurance or pay a fine, were all steps in the right direction.

And the law went further – it also addressed preventive care. Medicare and all new insurance plans would have to cover, without copay, co-insurance, or deductible, high-certainty preventive services such as screening for breast, cervical, colorectal, lung, and skin cancers, the annual well-woman visit, breast cancer preventative medications, and many others.³ Medicare recipients would be eligible for one non-copay annual wellness visit to their caregiver. Beyond providing increased access to health care, the PPACA added incentives to caregivers who were coming out of training programs to serve in underserved areas and benefit from a decrease in their med school loans or in their loan repayments.

Finally, and especially important, under the PPACA, our age-old insurance system of fee for service, which tends to incentivize more care, would change to incentivizing high-quality, outcomes-based care , thus replacing “quantity of care” with quality of care. So what’s wrong with the features of the law outlined in the preceding paragraphs? Well, of course, for every 100 ideas, only a few will be implemented and actually pay off. Certainly some of the PPACA could have been better implemented, and perhaps the task now facing Congress, if it could ever abandon its current pitched-camp approach, should be to take the ideas that health care policy scientists have established as being valid and find a way to make them work. Surely that would be best for all players, rather than carping about the repeal-replace approach versus staying with the PPACA.

So my response to the repeal-replace assertion? Retain, review, and refine.

Practitioner-friendly content

Health care calamities notwithstanding, we have a line-up of articles in this issue that uniformly address some of the pressing needs many of us face in our daily practice. Barry and colleagues examined the patterns of care with regard to whole brain radiotherapy technique and delivery at US-based academic centers. Their results show some interesting differences in the way younger and older practitioners deliver that care, with older practitioners placing more importance on tumor histopathology when considering brain irradiation. Speaking of access to care in the context of health reform, how often do our cancer patients use the emergency department? Lash and colleagues looked at the ED-use numbers from two databases in California and found that patients go to the ED at higher rates than previously reported and with notable variability by cancer type. Now we need to examine the reasons for those visits and establish ways to identify predictors of ED use to improve patient quality of care and rein in the higher costs of ED use.

In regard to symptom management, we can never have enough about nausea and vomiting prevention. Schwartzberg and colleagues report on a trial in which they evaluated the clinical benefits of APF530, a subcutaneous formulation of granisetron, compared with ondansetron in patients who had received cisplatin therapy. This longer-acting formulation of granisetron performed very well against a standard of care and might give our patients another option in the clinic for highly emetogenic chemotherapy.

Still on the topic of symptom management, preventing and treating mTOR-inhibitor–associated stomatitis (mIAS) is the subject of a review by Ramchandran and colleagues. The inhibitors have been approved for treatment in renal cell, neuroendocrine, and breast cancers, but of course, many of our newer molecules have some associated toxicity. Based on their literature scan, the authors report that management of mIAS should focus on three major approaches: prevention, early aggressive treatment, and, when needed, more aggressive pain management. Early recognition and diagnosis of mIAS facilitate early intervention to limit potential sequelae of mIAS and minimize the need for mTOR inhibitor dose reduction and interruption.

In a way, stress management could also fall under the symptom management category. I often remember being told during my training that we should always discuss with your patients their level of anxiety and depression. But I think sometimes we are so busy addressing the cancer, its treatment, and treatment side effects, we overlook the fact that the patient is suffering psychologically and might need additional intervention in the form of talk therapy and/or medication. Ramírez-Solá and colleagues describe in our How We Do It section the process of developing and implementing a psychosocial distress management program at their institution in Puerto Rico. The authors also summarize the results of a pilot study to validate the Patient Health Questionnaire (PHQ-9) as a measure to improve the process of emotional distress management in particular.

In recent years, the number of approvals and new indications for therapies for different cancer types has increased significantly. We highlight two such approvals in this issue. One is the PARP inhibitor, rucaparib, which was approved in both the platinum-sensitive and -resistant settings for BRCA1- and BRCA2-mutant patients with ovarian cancer. The other is the new CD38 antibody daratumumab, which was originally approved as a single-agent therapy for relapsed myeloma and which has now received a second approval with demonstrated improvement of progression-free survival when given with the lenalidomide-dexamethasone or bortezomib-dexamethasone combinations.

When it comes to new therapies, immunotherapies are at the cutting edge. Who hasn’t heard of the new checkpoint inhibitor drugs for a range of cancers that have either been approved or are in trial? Until now, we have used these immunotherapies as single agents, but Jane de Lartigue writes of the potential of combining more than one immunotherapy drug and/or combining an immune checkpoint inhibitor with a chemotherapy drug. The key behind this concept is that the more antigenic differentiation and tumor infiltrating lymphocytes in the system, the better the immunotherapy might work.

In the previous issue of the journal, one of our Editors, Thomas Strouse, discussed the issue of physician aid in dying (PAD)⁴ and asserted he had come to view “active non-participation” in legal PAD as a “toxic form of patient abandonment.” This is, of course, a very challenging and complex topic, and one that we likely have to address on a weekly basis with some of our cancer patients: if palliative care and end-of-life is the goal, how can we most humanely achieve that ethically and legally in concert with our patients’ wishes? Is it right or wrong to aid in some way in the dying process? Dr Alva Weir responds to Dr Strouse’s editorial, taking the view point that physician-assisted suicide is toxic abandonment. Dr Strauss responds, and I encourage you to read this very interesting exchange that highlights the point-counterpoint views of physician involvement in the dying process.

We round off the issue with a bumper crop of Case Reports. They include two that document diagnostic challenges: one in a patient with pulmonary sarcomatoid carcinoma presenting as a necrotizing cavitary lung lesion and another in which atraumatic splenic rupture is the initial presentation of CML. Also included is a report on a case of primary cardiac prosthetic valve-associated lymphoma and another on how a collaborative effort between oncologists and dermatologists contributed to the resolution of palmoplantar exacerbation of psoriasis in a patient who had been treated with nivolumab.

Going digital

I will close by remarking that the Journal of Community and Supportive Oncology, or JCSO, will be going digital only after this print issue. We will continue publishing the same content as a bimonthly digital issue, posting articles directly to our website, and mailing out our regular electronic newsletters. So visit the website, www.jcso-online.com, where you can read the articles as soon as they are posted and also find instructions for downloading the app for the digital edition – it’s quick, easy, and free, in case you were wondering. For a shortcut to the download the app, you can also use http://bit.ly/2nCEPIa.

Finally, if you would like to submit a paper to us for consideration for publication, you can do so by going to www.editorialmanager.com/jso/. We will consider submissions in original research, reviews, How We Do It, case reports, and tumor board summaries – you’ll find all the information you need to submit a paper at the EditorialManager platform. And let’s not forget social media – we’re on Twitter where our handle is @jcs_onc, my personal Twitter handle is @davidhenrymd, so connect with us – follow us, like us, and retweet us.

A suggestion for Congress: keep what’s working in the Patient Protection and Affordable Care Act (PPACA), adjust what isn’t working – just make the whole thing better and call it what you will.

A good thing, but needing work

The PPACA, which is also referred to as Obama care, had a lot in it that any reasonable person would consider good. Let’s take a look. As Dr Valerie Arkoosh wrote in our journal in 2012,² the law attempted to expand access to health care to the embarrassingly large 30 million or more Americans who were not insured. How would it do this? By expanding Medicaid, enhancing consumer protections in the private health insurance market, requiring large employers to offer insurance or pay a fine, giving tax credits to increase affordability of insurance for small businesses, creating state-based competitive market places, and requiring individuals to purchase health insurance plans (the so-called insurance mandate), thereby creating a pool of large numbers of healthy people who would help defray the costs of those not so fortunate.The law also guaranteed insurability despite any preexisting condition, surely a step in the right direction. Likewise, the need for employers to provide health insurance, the state-based health insurance exchanges, and especially the individual mandate to buy insurance or pay a fine, were all steps in the right direction.

And the law went further – it also addressed preventive care. Medicare and all new insurance plans would have to cover, without copay, co-insurance, or deductible, high-certainty preventive services such as screening for breast, cervical, colorectal, lung, and skin cancers, the annual well-woman visit, breast cancer preventative medications, and many others.³ Medicare recipients would be eligible for one non-copay annual wellness visit to their caregiver. Beyond providing increased access to health care, the PPACA added incentives to caregivers who were coming out of training programs to serve in underserved areas and benefit from a decrease in their med school loans or in their loan repayments.

Finally, and especially important, under the PPACA, our age-old insurance system of fee for service, which tends to incentivize more care, would change to incentivizing high-quality, outcomes-based care , thus replacing “quantity of care” with quality of care. So what’s wrong with the features of the law outlined in the preceding paragraphs? Well, of course, for every 100 ideas, only a few will be implemented and actually pay off. Certainly some of the PPACA could have been better implemented, and perhaps the task now facing Congress, if it could ever abandon its current pitched-camp approach, should be to take the ideas that health care policy scientists have established as being valid and find a way to make them work. Surely that would be best for all players, rather than carping about the repeal-replace approach versus staying with the PPACA.

So my response to the repeal-replace assertion? Retain, review, and refine.

Practitioner-friendly content

Health care calamities notwithstanding, we have a line-up of articles in this issue that uniformly address some of the pressing needs many of us face in our daily practice. Barry and colleagues examined the patterns of care with regard to whole brain radiotherapy technique and delivery at US-based academic centers. Their results show some interesting differences in the way younger and older practitioners deliver that care, with older practitioners placing more importance on tumor histopathology when considering brain irradiation. Speaking of access to care in the context of health reform, how often do our cancer patients use the emergency department? Lash and colleagues looked at the ED-use numbers from two databases in California and found that patients go to the ED at higher rates than previously reported and with notable variability by cancer type. Now we need to examine the reasons for those visits and establish ways to identify predictors of ED use to improve patient quality of care and rein in the higher costs of ED use.

In regard to symptom management, we can never have enough about nausea and vomiting prevention. Schwartzberg and colleagues report on a trial in which they evaluated the clinical benefits of APF530, a subcutaneous formulation of granisetron, compared with ondansetron in patients who had received cisplatin therapy. This longer-acting formulation of granisetron performed very well against a standard of care and might give our patients another option in the clinic for highly emetogenic chemotherapy.

Still on the topic of symptom management, preventing and treating mTOR-inhibitor–associated stomatitis (mIAS) is the subject of a review by Ramchandran and colleagues. The inhibitors have been approved for treatment in renal cell, neuroendocrine, and breast cancers, but of course, many of our newer molecules have some associated toxicity. Based on their literature scan, the authors report that management of mIAS should focus on three major approaches: prevention, early aggressive treatment, and, when needed, more aggressive pain management. Early recognition and diagnosis of mIAS facilitate early intervention to limit potential sequelae of mIAS and minimize the need for mTOR inhibitor dose reduction and interruption.

In a way, stress management could also fall under the symptom management category. I often remember being told during my training that we should always discuss with your patients their level of anxiety and depression. But I think sometimes we are so busy addressing the cancer, its treatment, and treatment side effects, we overlook the fact that the patient is suffering psychologically and might need additional intervention in the form of talk therapy and/or medication. Ramírez-Solá and colleagues describe in our How We Do It section the process of developing and implementing a psychosocial distress management program at their institution in Puerto Rico. The authors also summarize the results of a pilot study to validate the Patient Health Questionnaire (PHQ-9) as a measure to improve the process of emotional distress management in particular.

In recent years, the number of approvals and new indications for therapies for different cancer types has increased significantly. We highlight two such approvals in this issue. One is the PARP inhibitor, rucaparib, which was approved in both the platinum-sensitive and -resistant settings for BRCA1- and BRCA2-mutant patients with ovarian cancer. The other is the new CD38 antibody daratumumab, which was originally approved as a single-agent therapy for relapsed myeloma and which has now received a second approval with demonstrated improvement of progression-free survival when given with the lenalidomide-dexamethasone or bortezomib-dexamethasone combinations.

When it comes to new therapies, immunotherapies are at the cutting edge. Who hasn’t heard of the new checkpoint inhibitor drugs for a range of cancers that have either been approved or are in trial? Until now, we have used these immunotherapies as single agents, but Jane de Lartigue writes of the potential of combining more than one immunotherapy drug and/or combining an immune checkpoint inhibitor with a chemotherapy drug. The key behind this concept is that the more antigenic differentiation and tumor infiltrating lymphocytes in the system, the better the immunotherapy might work.

In the previous issue of the journal, one of our Editors, Thomas Strouse, discussed the issue of physician aid in dying (PAD)⁴ and asserted he had come to view “active non-participation” in legal PAD as a “toxic form of patient abandonment.” This is, of course, a very challenging and complex topic, and one that we likely have to address on a weekly basis with some of our cancer patients: if palliative care and end-of-life is the goal, how can we most humanely achieve that ethically and legally in concert with our patients’ wishes? Is it right or wrong to aid in some way in the dying process? Dr Alva Weir responds to Dr Strouse’s editorial, taking the view point that physician-assisted suicide is toxic abandonment. Dr Strauss responds, and I encourage you to read this very interesting exchange that highlights the point-counterpoint views of physician involvement in the dying process.

We round off the issue with a bumper crop of Case Reports. They include two that document diagnostic challenges: one in a patient with pulmonary sarcomatoid carcinoma presenting as a necrotizing cavitary lung lesion and another in which atraumatic splenic rupture is the initial presentation of CML. Also included is a report on a case of primary cardiac prosthetic valve-associated lymphoma and another on how a collaborative effort between oncologists and dermatologists contributed to the resolution of palmoplantar exacerbation of psoriasis in a patient who had been treated with nivolumab.

Going digital

I will close by remarking that the Journal of Community and Supportive Oncology, or JCSO, will be going digital only after this print issue. We will continue publishing the same content as a bimonthly digital issue, posting articles directly to our website, and mailing out our regular electronic newsletters. So visit the website, www.jcso-online.com, where you can read the articles as soon as they are posted and also find instructions for downloading the app for the digital edition – it’s quick, easy, and free, in case you were wondering. For a shortcut to the download the app, you can also use http://bit.ly/2nCEPIa.

Finally, if you would like to submit a paper to us for consideration for publication, you can do so by going to www.editorialmanager.com/jso/. We will consider submissions in original research, reviews, How We Do It, case reports, and tumor board summaries – you’ll find all the information you need to submit a paper at the EditorialManager platform. And let’s not forget social media – we’re on Twitter where our handle is @jcs_onc, my personal Twitter handle is @davidhenrymd, so connect with us – follow us, like us, and retweet us.

BOSTON – Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

copyright Zerbor/Thinkstock

[email protected]

BOSTON – Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

copyright Zerbor/Thinkstock

[email protected]

BOSTON – Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

copyright Zerbor/Thinkstock

[email protected]

I recently read with interest Dr Thomas Strouse’s article written to support physician aid in dying. Within the article he made the following statement: “I have come to view ‘active non-participation’ in legal PAD [physician aid in dying] – that is, decisions by individual physicians and/or health systems not only to not provide, but also not refer patients to possibly willing providers and systems without regard for specific clinical contexts – as a toxic form of patient abandonment.”¹ Within the article, Dr Strouse lays out for us thoughtful precautions in the aid-in-dying laws, attempting to demonstrate that no vulnerable population is abused. Such precautions are important but provide the same result for all participants: the death of a patient. This is the central problem with aid in dying. Certainly there is nothing wrong with dying, and we all will have that opportunity. Though most of us would choose to put that moment off a while, for some, the suffering in this life makes death seem a welcome relief.

What is a physician’s central responsibility in the care of his or her patients near the end of their lives?

As program director for the hematology and oncology fellowship at my institution, I impress upon my fellows the importance of goal-oriented decision-making. I specifically teach them that there are only four goals worth achieving in any therapeutic or diagnostic decision making: to cure the disease; to help patients live longer despite the disease; to maximize the patient’s quality of life, and to prevent impending disasters. I know of no other worthwhile goal in any decision we are to make for our patients. I can point to none of these goals that physician aid in dying achieves. When it comes to physician-assisted suicide, some would argue that selecting an early death is a way of “maximizing quality of life.” And certainly our task is to make life the best it can be for our patients while they live through the dying process, but I am unaware of any published quality of life formula that calculates the end of life as a positive measure.

The question for us is the role of the doctor. Dr Strouse raises two issues with those whom he accuses of toxic abandonment. The first is whether physicians should provide aid in death, and the second is whether physicians should refer for the same service if they believe it is wrong for their patients.

It certainly has not been well established that physician-assisted suicide is a good thing rather than a tragic thing. A 2012 statement from the Ethics, Professionalism and Human Rights Committee of the American College of Physicians suggests otherwise: “After much consideration, the College concluded that making physician-assisted suicide legal raised serious ethical, clinical and social concerns and that the practice might undermine patient trust; distract from reform in end-of-life care; and be used in vulnerable patients, including those who are poor, are disabled, or are unable to speak for themselves or minority groups who have experienced discrimination.”² The disability rights group, Not Dead Yet, has agreed with the ACP: “It cannot be seriously maintained that assisted suicide laws can or do limit assisted suicide to people who are imminently dying, and voluntarily request and consume a lethal dose, free of inappropriate pressures from family or society. Rather, assisted suicide laws ensure legal immunity for physicians who already devalue the lives of older and disabled people and have significant economic incentives to at least agree with their suicides, if not encourage them, or worse.”³

Such statements sound prophetic within both our present cost containment health care culture and in the real world of personal family economic pressures that can lead a patient toward the understanding that a right to die is actually a “duty to die.”

As society is driving physicians to be technicians to carry out their bidding, physicians should be clinging tightly to their role as trusted advocates for their patients. Certainly our patients have fears and pain that would at times lead them to prefer death to living, but a patient’s move to nonexistence is not the task of the physician. Our task as physicians was well described recently by Yang and Curlin: “Many patients with terminal illnesses fear unbearable pain or other symptoms. The physician’s role is to care for them in their illness so as to relieve pain or otherwise help them bear up under the symptoms they endure. Many patients loathe the prospect of abject debility. The physician’s role is to maintain solidarity with those whose health is diminished, not to not to imply that debility renders a patient’s life not worth living.”⁴

Statements such as these by reasoned people suggest we, as a country, have no consensus for the question whether aid in dying is possibly good or seriously bad for our patients. So it is quite reasonable for compassionate physicians to refuse to administer lethal medicines to their patients in order to “do no harm.”

The second question Dr Strouse explores is whether physicians who disapprove of physician-assisted suicide are abandoning their patients because they do not refer them to a provider who will provide such services. Dr Edmund Pelligrino, a well-respected medical ethicist, in his discussion of moral absolutes in medicine establishes the moral absolute, “Do not kill” and then addresses the ethical problem of complicity in killing. “Formal cooperation is absolutely and always, forbidden. This is the case when the physician shares the evil intent, partakes directly and freely, or in any way facilitates an intrinsically evil act like abortion or assisted suicide.”⁵ Though personally I would not use the word, “evil,” as he does, since evil implies motive; I would substitute the word “harm” and suggest that we should never be complicit in an act that we feel brings the harm of death to our patients. I would suggest that the expectation that physicians referring for aid in dying is analogous with the patient who comes to me demanding a chemotherapy that I know would cause her harm. I would refuse to give it to her and refuse to send her to a doctor who would be willing to give to her. Referral to produce harm is complicity with causing the harm itself. Our society should never go there. Our society should never ask a physician to cross the boundary line of conscience that is the ultimate protection for vulnerable patients.

I know what it is like to watch our patients suffer. I know what it is like to watch our loved ones suffer. I pushed the morphine at my father’s bedside until he quit screaming in pain. But I did not kill him. I cared for him. Such is the physician’s role. If society decides to allow patients the autonomy to end their lives early and wishes to provide skilled technical help in doing so, let it do so at their peril. But let it choose and train technicians to do it. Do not compromise the one person whom our patients should trust totally to never do them harm.

Alva B Weir, III, MD, FACP ([email protected])
West Cancer Center, Memphis, Tennessee

I recently read with interest Dr Thomas Strouse’s article written to support physician aid in dying. Within the article he made the following statement: “I have come to view ‘active non-participation’ in legal PAD [physician aid in dying] – that is, decisions by individual physicians and/or health systems not only to not provide, but also not refer patients to possibly willing providers and systems without regard for specific clinical contexts – as a toxic form of patient abandonment.”¹ Within the article, Dr Strouse lays out for us thoughtful precautions in the aid-in-dying laws, attempting to demonstrate that no vulnerable population is abused. Such precautions are important but provide the same result for all participants: the death of a patient. This is the central problem with aid in dying. Certainly there is nothing wrong with dying, and we all will have that opportunity. Though most of us would choose to put that moment off a while, for some, the suffering in this life makes death seem a welcome relief.

What is a physician’s central responsibility in the care of his or her patients near the end of their lives?

As program director for the hematology and oncology fellowship at my institution, I impress upon my fellows the importance of goal-oriented decision-making. I specifically teach them that there are only four goals worth achieving in any therapeutic or diagnostic decision making: to cure the disease; to help patients live longer despite the disease; to maximize the patient’s quality of life, and to prevent impending disasters. I know of no other worthwhile goal in any decision we are to make for our patients. I can point to none of these goals that physician aid in dying achieves. When it comes to physician-assisted suicide, some would argue that selecting an early death is a way of “maximizing quality of life.” And certainly our task is to make life the best it can be for our patients while they live through the dying process, but I am unaware of any published quality of life formula that calculates the end of life as a positive measure.

The question for us is the role of the doctor. Dr Strouse raises two issues with those whom he accuses of toxic abandonment. The first is whether physicians should provide aid in death, and the second is whether physicians should refer for the same service if they believe it is wrong for their patients.

It certainly has not been well established that physician-assisted suicide is a good thing rather than a tragic thing. A 2012 statement from the Ethics, Professionalism and Human Rights Committee of the American College of Physicians suggests otherwise: “After much consideration, the College concluded that making physician-assisted suicide legal raised serious ethical, clinical and social concerns and that the practice might undermine patient trust; distract from reform in end-of-life care; and be used in vulnerable patients, including those who are poor, are disabled, or are unable to speak for themselves or minority groups who have experienced discrimination.”² The disability rights group, Not Dead Yet, has agreed with the ACP: “It cannot be seriously maintained that assisted suicide laws can or do limit assisted suicide to people who are imminently dying, and voluntarily request and consume a lethal dose, free of inappropriate pressures from family or society. Rather, assisted suicide laws ensure legal immunity for physicians who already devalue the lives of older and disabled people and have significant economic incentives to at least agree with their suicides, if not encourage them, or worse.”³

Such statements sound prophetic within both our present cost containment health care culture and in the real world of personal family economic pressures that can lead a patient toward the understanding that a right to die is actually a “duty to die.”

As society is driving physicians to be technicians to carry out their bidding, physicians should be clinging tightly to their role as trusted advocates for their patients. Certainly our patients have fears and pain that would at times lead them to prefer death to living, but a patient’s move to nonexistence is not the task of the physician. Our task as physicians was well described recently by Yang and Curlin: “Many patients with terminal illnesses fear unbearable pain or other symptoms. The physician’s role is to care for them in their illness so as to relieve pain or otherwise help them bear up under the symptoms they endure. Many patients loathe the prospect of abject debility. The physician’s role is to maintain solidarity with those whose health is diminished, not to not to imply that debility renders a patient’s life not worth living.”⁴

Statements such as these by reasoned people suggest we, as a country, have no consensus for the question whether aid in dying is possibly good or seriously bad for our patients. So it is quite reasonable for compassionate physicians to refuse to administer lethal medicines to their patients in order to “do no harm.”

The second question Dr Strouse explores is whether physicians who disapprove of physician-assisted suicide are abandoning their patients because they do not refer them to a provider who will provide such services. Dr Edmund Pelligrino, a well-respected medical ethicist, in his discussion of moral absolutes in medicine establishes the moral absolute, “Do not kill” and then addresses the ethical problem of complicity in killing. “Formal cooperation is absolutely and always, forbidden. This is the case when the physician shares the evil intent, partakes directly and freely, or in any way facilitates an intrinsically evil act like abortion or assisted suicide.”⁵ Though personally I would not use the word, “evil,” as he does, since evil implies motive; I would substitute the word “harm” and suggest that we should never be complicit in an act that we feel brings the harm of death to our patients. I would suggest that the expectation that physicians referring for aid in dying is analogous with the patient who comes to me demanding a chemotherapy that I know would cause her harm. I would refuse to give it to her and refuse to send her to a doctor who would be willing to give to her. Referral to produce harm is complicity with causing the harm itself. Our society should never go there. Our society should never ask a physician to cross the boundary line of conscience that is the ultimate protection for vulnerable patients.

I know what it is like to watch our patients suffer. I know what it is like to watch our loved ones suffer. I pushed the morphine at my father’s bedside until he quit screaming in pain. But I did not kill him. I cared for him. Such is the physician’s role. If society decides to allow patients the autonomy to end their lives early and wishes to provide skilled technical help in doing so, let it do so at their peril. But let it choose and train technicians to do it. Do not compromise the one person whom our patients should trust totally to never do them harm.

Alva B Weir, III, MD, FACP ([email protected])
West Cancer Center, Memphis, Tennessee

I recently read with interest Dr Thomas Strouse’s article written to support physician aid in dying. Within the article he made the following statement: “I have come to view ‘active non-participation’ in legal PAD [physician aid in dying] – that is, decisions by individual physicians and/or health systems not only to not provide, but also not refer patients to possibly willing providers and systems without regard for specific clinical contexts – as a toxic form of patient abandonment.”¹ Within the article, Dr Strouse lays out for us thoughtful precautions in the aid-in-dying laws, attempting to demonstrate that no vulnerable population is abused. Such precautions are important but provide the same result for all participants: the death of a patient. This is the central problem with aid in dying. Certainly there is nothing wrong with dying, and we all will have that opportunity. Though most of us would choose to put that moment off a while, for some, the suffering in this life makes death seem a welcome relief.

What is a physician’s central responsibility in the care of his or her patients near the end of their lives?

As program director for the hematology and oncology fellowship at my institution, I impress upon my fellows the importance of goal-oriented decision-making. I specifically teach them that there are only four goals worth achieving in any therapeutic or diagnostic decision making: to cure the disease; to help patients live longer despite the disease; to maximize the patient’s quality of life, and to prevent impending disasters. I know of no other worthwhile goal in any decision we are to make for our patients. I can point to none of these goals that physician aid in dying achieves. When it comes to physician-assisted suicide, some would argue that selecting an early death is a way of “maximizing quality of life.” And certainly our task is to make life the best it can be for our patients while they live through the dying process, but I am unaware of any published quality of life formula that calculates the end of life as a positive measure.

The question for us is the role of the doctor. Dr Strouse raises two issues with those whom he accuses of toxic abandonment. The first is whether physicians should provide aid in death, and the second is whether physicians should refer for the same service if they believe it is wrong for their patients.

It certainly has not been well established that physician-assisted suicide is a good thing rather than a tragic thing. A 2012 statement from the Ethics, Professionalism and Human Rights Committee of the American College of Physicians suggests otherwise: “After much consideration, the College concluded that making physician-assisted suicide legal raised serious ethical, clinical and social concerns and that the practice might undermine patient trust; distract from reform in end-of-life care; and be used in vulnerable patients, including those who are poor, are disabled, or are unable to speak for themselves or minority groups who have experienced discrimination.”² The disability rights group, Not Dead Yet, has agreed with the ACP: “It cannot be seriously maintained that assisted suicide laws can or do limit assisted suicide to people who are imminently dying, and voluntarily request and consume a lethal dose, free of inappropriate pressures from family or society. Rather, assisted suicide laws ensure legal immunity for physicians who already devalue the lives of older and disabled people and have significant economic incentives to at least agree with their suicides, if not encourage them, or worse.”³

Such statements sound prophetic within both our present cost containment health care culture and in the real world of personal family economic pressures that can lead a patient toward the understanding that a right to die is actually a “duty to die.”

As society is driving physicians to be technicians to carry out their bidding, physicians should be clinging tightly to their role as trusted advocates for their patients. Certainly our patients have fears and pain that would at times lead them to prefer death to living, but a patient’s move to nonexistence is not the task of the physician. Our task as physicians was well described recently by Yang and Curlin: “Many patients with terminal illnesses fear unbearable pain or other symptoms. The physician’s role is to care for them in their illness so as to relieve pain or otherwise help them bear up under the symptoms they endure. Many patients loathe the prospect of abject debility. The physician’s role is to maintain solidarity with those whose health is diminished, not to not to imply that debility renders a patient’s life not worth living.”⁴

Statements such as these by reasoned people suggest we, as a country, have no consensus for the question whether aid in dying is possibly good or seriously bad for our patients. So it is quite reasonable for compassionate physicians to refuse to administer lethal medicines to their patients in order to “do no harm.”

The second question Dr Strouse explores is whether physicians who disapprove of physician-assisted suicide are abandoning their patients because they do not refer them to a provider who will provide such services. Dr Edmund Pelligrino, a well-respected medical ethicist, in his discussion of moral absolutes in medicine establishes the moral absolute, “Do not kill” and then addresses the ethical problem of complicity in killing. “Formal cooperation is absolutely and always, forbidden. This is the case when the physician shares the evil intent, partakes directly and freely, or in any way facilitates an intrinsically evil act like abortion or assisted suicide.”⁵ Though personally I would not use the word, “evil,” as he does, since evil implies motive; I would substitute the word “harm” and suggest that we should never be complicit in an act that we feel brings the harm of death to our patients. I would suggest that the expectation that physicians referring for aid in dying is analogous with the patient who comes to me demanding a chemotherapy that I know would cause her harm. I would refuse to give it to her and refuse to send her to a doctor who would be willing to give to her. Referral to produce harm is complicity with causing the harm itself. Our society should never go there. Our society should never ask a physician to cross the boundary line of conscience that is the ultimate protection for vulnerable patients.

I know what it is like to watch our patients suffer. I know what it is like to watch our loved ones suffer. I pushed the morphine at my father’s bedside until he quit screaming in pain. But I did not kill him. I cared for him. Such is the physician’s role. If society decides to allow patients the autonomy to end their lives early and wishes to provide skilled technical help in doing so, let it do so at their peril. But let it choose and train technicians to do it. Do not compromise the one person whom our patients should trust totally to never do them harm.

Alva B Weir, III, MD, FACP ([email protected])
West Cancer Center, Memphis, Tennessee

Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype that has an aggressive course with average survival of 11-13 months.¹ In clinical practice, the possible presentations of this rare cancer are not widely known, resulting in a misdiagnosis. That is what happened with our patient, who presented with necrotizing cavitary lung lesion and soft tissue necrotizing lymphadenitis. The clinical picture was reminiscent of tuberculosis or granulomatosis with polyangiitis and was further confounded by negative computed-tomography (CT)-guided biopsy and bronchoscopy findings, which added to the delay in diagnosis. With the currently available knowledge, the diagnosis of PSC depends largely on evaluation of the surgically resected specimen, which in most cases is avoided until there is a high suspicion of PSC. Biopsy is not useful due to extensive necrosis, as will be seen in our case. Consequently, most of the data in the literature is based on case series of autopsy specimen, and the clinical characteristics of PSC remain unclear. The rarity of PSC has prevented its characterization in literature. We report here a rare presentation of PSC with necrotizing lung lesion, to add to the paucity of the current data.

Case presentation and summary

A 58-year-old homeless man presented to the Upstate University Hospital, Syracuse, New York, with a 25-pound weight loss during the previous month and associated productive cough and hemoptysis for a week and a painful mass in the nape of his neck. He denied any fever, chest pain, sick contacts, or joint pain. He had a history of about 40 pack-years of smoking, and his brother had recently been diagnosed with lung cancer. A tender fluctuant mass was detected in the nape of his neck on examination (Figure 1).

The patient had presented 9 months earlier with persistent cough and hemoptysis, and at that visit was found to have a cavitary lesion in the right lung measuring 2 cm (0.8 in). He had undergone a computed-tomograpghy (CT)-guided biopsy of the lesion, which had shown acute and chronic inflammation with fibrosis, and he had negative bronchoscopy findings. The patient tested negative for tuberculosis during the first visit but he left the hospital against the medical advice of the physicians and he was lost to follow-up until his re-presentation.

On physical examination at his re-presentation, the patient seemed cachectic, with a blood pressure of 94/62 mm of Hg. The mass in the nape of his neck was about 3 cm (1.2 in) long, with erythema of the surrounding skin (Figure 1). Bronchial breath sounds were heard in the right upper lobe of the lung, likely due to the underlying cavitary lesion (Figure 2).

Given the patient’s advanced disease, he was started on palliative radiotherapy with radiosensitizing chemotherapy with carboplatin (target AUC 6) and paclitaxel (135 mg/m² over 24 hours). His symptoms of hemoptysis improved transiently after the first cycle, but he became hypotensive and drowsy during the second cycle of therapy, and the family decided to make the patient comfort care and withdraw all further treatment. He was discharged to hospice.

Discussion

PSC is a rare variant of non-small-cell carcinoma lung cancer, accounting for up to 0.4% of lung malignancy.¹ It was recently subtyped by the World Health Organization as a non-small cell lung carcinoma with certain amount of differentiation resembling sarcoma or containing elements of sarcoma.^2-4 It is not known why both elements co-exist in the tumor, but Franks and colleagues some theories have been postulated in the literature, including possible origin from a single, aberrant stem cell with progenies differentiating in two separate pathways.³

Sarcomatoid carcinoma consists of spectrum of tumors including pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and blastoma.^3,4 It usually shows male preponderance, and association with smoking.³ The diagnosis commonly occurs in the sixth decade of life, except for pulmonary blastoma, which is more common in the fourth decade and with equal gender distribution.⁴

The presenting symptoms can be variable and nonspecific, but predominantly include chest pain, cough, hemoptysis, and/or weight loss.⁵ Radiologically, pulmonary sarcomatoid cancer presenting as a necrotizing cavitary lesion in the lung is a rare finding, seldom reported in the past.^6,7 The presentation in our case, with necrotizing lymphadenitis, was reminiscent of an infectious or autoimmune etiology such as tuberculosis or granulomatosis with polyangiitis. The presence of extensive necrosis in the lesion and the characteristic heterogeneity of the tumor had resulted in inconclusive biopsy findings during the previous presentation. In clinical practice, there is over-reliance on biopsy findings to make the distinction between cancer and other mimicking conditions. This is especially true for rare tumors such as PSC, which often results in misdiagnosis and a delay in administering the proper treatment.

Transbronchial biopsy in cases such as the present case, carries little benefit because the diagnosis depends on the site from which the biopsy is taken and whether the biopsied tissue is representative of the entire mass. The diagnosis can be suspected based on the clinical and radiological findings but confirmation requires a surgical resection to delineate the accurate cytology and architecture.^5,6,8 Huang and colleagues showed a misdiagnosis rate of PSC of >70% preoperatively.⁴ Resective surgery is feasible only in patients with high index of suspicion for a malignancy, which in most cases requires previous confirmation with a biopsy. The rarity of this cancer, its unusual presentations, and the lack of specific testing preclude early diagnosis and timely treatment of this fatal condition.

Initial treatment options for localized or with limited spread disease is resective surgery. The role of chemo- or radiation therapy is not known, but they have not previously shown promising results,^6,8 except in some cases when they are used as postoperative adjuvant chemotherapy⁴ or in bulky, locally invasive tumors.¹ The recurrence rate after surgery is very high, resulting in a poor 5-year survival rate.^1,8 Experimental therapies, such as antibodies that target epidermal growth factor receptor mutations, have not shown much success either.⁸ In conclusion, the outlook for patients with PSC with the current available knowledge and treatment protocols, is dismal.

Most of the current knowledge and data in the literature is based on cases from autopsy or early-stage surgical resections rather than on patients with advanced cancer.⁵ Moreover, the role of surgical resection in PSC is questionable, given the high recurrence rate. Subsequently, the clinical and pathological manifestations have yet to be well characterized.⁴ There has been advance with the publication of more studies recently. Cytokeratin markers such as CAM 5.2 and AE1/AE3 are commonly useful to support the diagnosis when suspected.³ Other markers, including the carcinoembryonic antigen, CD15, and thyroid transcription factor-1 may be variably positive, based on the differentiation of the cancer. Other exciting prospects in the study of PSC include the suggestion of a modified vimentin histologic score for better characterization of the cancer and the discovery of high platelet-derived growth factor receptor beta immunohistochemistry expression in PSC as a potential target for future therapy.

Conclusion

Pulmonary sarcomatoid lung cancer can present with a predominant necrotizing picture that mimics diseases such as tuberculosis. In such case, transbronchial biopsy carries little benefit because the diagnosis depends on whether the biopsied tissue is representative of the entire mass, often confounded by the extensive necrosis. More data is needed to determine prognostic factors and appropriate therapeutic strategies.

Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype that has an aggressive course with average survival of 11-13 months.¹ In clinical practice, the possible presentations of this rare cancer are not widely known, resulting in a misdiagnosis. That is what happened with our patient, who presented with necrotizing cavitary lung lesion and soft tissue necrotizing lymphadenitis. The clinical picture was reminiscent of tuberculosis or granulomatosis with polyangiitis and was further confounded by negative computed-tomography (CT)-guided biopsy and bronchoscopy findings, which added to the delay in diagnosis. With the currently available knowledge, the diagnosis of PSC depends largely on evaluation of the surgically resected specimen, which in most cases is avoided until there is a high suspicion of PSC. Biopsy is not useful due to extensive necrosis, as will be seen in our case. Consequently, most of the data in the literature is based on case series of autopsy specimen, and the clinical characteristics of PSC remain unclear. The rarity of PSC has prevented its characterization in literature. We report here a rare presentation of PSC with necrotizing lung lesion, to add to the paucity of the current data.

Case presentation and summary

A 58-year-old homeless man presented to the Upstate University Hospital, Syracuse, New York, with a 25-pound weight loss during the previous month and associated productive cough and hemoptysis for a week and a painful mass in the nape of his neck. He denied any fever, chest pain, sick contacts, or joint pain. He had a history of about 40 pack-years of smoking, and his brother had recently been diagnosed with lung cancer. A tender fluctuant mass was detected in the nape of his neck on examination (Figure 1).

The patient had presented 9 months earlier with persistent cough and hemoptysis, and at that visit was found to have a cavitary lesion in the right lung measuring 2 cm (0.8 in). He had undergone a computed-tomograpghy (CT)-guided biopsy of the lesion, which had shown acute and chronic inflammation with fibrosis, and he had negative bronchoscopy findings. The patient tested negative for tuberculosis during the first visit but he left the hospital against the medical advice of the physicians and he was lost to follow-up until his re-presentation.

On physical examination at his re-presentation, the patient seemed cachectic, with a blood pressure of 94/62 mm of Hg. The mass in the nape of his neck was about 3 cm (1.2 in) long, with erythema of the surrounding skin (Figure 1). Bronchial breath sounds were heard in the right upper lobe of the lung, likely due to the underlying cavitary lesion (Figure 2).

Given the patient’s advanced disease, he was started on palliative radiotherapy with radiosensitizing chemotherapy with carboplatin (target AUC 6) and paclitaxel (135 mg/m² over 24 hours). His symptoms of hemoptysis improved transiently after the first cycle, but he became hypotensive and drowsy during the second cycle of therapy, and the family decided to make the patient comfort care and withdraw all further treatment. He was discharged to hospice.

Discussion

PSC is a rare variant of non-small-cell carcinoma lung cancer, accounting for up to 0.4% of lung malignancy.¹ It was recently subtyped by the World Health Organization as a non-small cell lung carcinoma with certain amount of differentiation resembling sarcoma or containing elements of sarcoma.^2-4 It is not known why both elements co-exist in the tumor, but Franks and colleagues some theories have been postulated in the literature, including possible origin from a single, aberrant stem cell with progenies differentiating in two separate pathways.³

Sarcomatoid carcinoma consists of spectrum of tumors including pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and blastoma.^3,4 It usually shows male preponderance, and association with smoking.³ The diagnosis commonly occurs in the sixth decade of life, except for pulmonary blastoma, which is more common in the fourth decade and with equal gender distribution.⁴

The presenting symptoms can be variable and nonspecific, but predominantly include chest pain, cough, hemoptysis, and/or weight loss.⁵ Radiologically, pulmonary sarcomatoid cancer presenting as a necrotizing cavitary lesion in the lung is a rare finding, seldom reported in the past.^6,7 The presentation in our case, with necrotizing lymphadenitis, was reminiscent of an infectious or autoimmune etiology such as tuberculosis or granulomatosis with polyangiitis. The presence of extensive necrosis in the lesion and the characteristic heterogeneity of the tumor had resulted in inconclusive biopsy findings during the previous presentation. In clinical practice, there is over-reliance on biopsy findings to make the distinction between cancer and other mimicking conditions. This is especially true for rare tumors such as PSC, which often results in misdiagnosis and a delay in administering the proper treatment.

Transbronchial biopsy in cases such as the present case, carries little benefit because the diagnosis depends on the site from which the biopsy is taken and whether the biopsied tissue is representative of the entire mass. The diagnosis can be suspected based on the clinical and radiological findings but confirmation requires a surgical resection to delineate the accurate cytology and architecture.^5,6,8 Huang and colleagues showed a misdiagnosis rate of PSC of >70% preoperatively.⁴ Resective surgery is feasible only in patients with high index of suspicion for a malignancy, which in most cases requires previous confirmation with a biopsy. The rarity of this cancer, its unusual presentations, and the lack of specific testing preclude early diagnosis and timely treatment of this fatal condition.

Initial treatment options for localized or with limited spread disease is resective surgery. The role of chemo- or radiation therapy is not known, but they have not previously shown promising results,^6,8 except in some cases when they are used as postoperative adjuvant chemotherapy⁴ or in bulky, locally invasive tumors.¹ The recurrence rate after surgery is very high, resulting in a poor 5-year survival rate.^1,8 Experimental therapies, such as antibodies that target epidermal growth factor receptor mutations, have not shown much success either.⁸ In conclusion, the outlook for patients with PSC with the current available knowledge and treatment protocols, is dismal.

Most of the current knowledge and data in the literature is based on cases from autopsy or early-stage surgical resections rather than on patients with advanced cancer.⁵ Moreover, the role of surgical resection in PSC is questionable, given the high recurrence rate. Subsequently, the clinical and pathological manifestations have yet to be well characterized.⁴ There has been advance with the publication of more studies recently. Cytokeratin markers such as CAM 5.2 and AE1/AE3 are commonly useful to support the diagnosis when suspected.³ Other markers, including the carcinoembryonic antigen, CD15, and thyroid transcription factor-1 may be variably positive, based on the differentiation of the cancer. Other exciting prospects in the study of PSC include the suggestion of a modified vimentin histologic score for better characterization of the cancer and the discovery of high platelet-derived growth factor receptor beta immunohistochemistry expression in PSC as a potential target for future therapy.

Conclusion

Pulmonary sarcomatoid lung cancer can present with a predominant necrotizing picture that mimics diseases such as tuberculosis. In such case, transbronchial biopsy carries little benefit because the diagnosis depends on whether the biopsied tissue is representative of the entire mass, often confounded by the extensive necrosis. More data is needed to determine prognostic factors and appropriate therapeutic strategies.

Pulmonary sarcomatoid carcinoma (PSC) is a rare histological subtype that has an aggressive course with average survival of 11-13 months.¹ In clinical practice, the possible presentations of this rare cancer are not widely known, resulting in a misdiagnosis. That is what happened with our patient, who presented with necrotizing cavitary lung lesion and soft tissue necrotizing lymphadenitis. The clinical picture was reminiscent of tuberculosis or granulomatosis with polyangiitis and was further confounded by negative computed-tomography (CT)-guided biopsy and bronchoscopy findings, which added to the delay in diagnosis. With the currently available knowledge, the diagnosis of PSC depends largely on evaluation of the surgically resected specimen, which in most cases is avoided until there is a high suspicion of PSC. Biopsy is not useful due to extensive necrosis, as will be seen in our case. Consequently, most of the data in the literature is based on case series of autopsy specimen, and the clinical characteristics of PSC remain unclear. The rarity of PSC has prevented its characterization in literature. We report here a rare presentation of PSC with necrotizing lung lesion, to add to the paucity of the current data.

Case presentation and summary

A 58-year-old homeless man presented to the Upstate University Hospital, Syracuse, New York, with a 25-pound weight loss during the previous month and associated productive cough and hemoptysis for a week and a painful mass in the nape of his neck. He denied any fever, chest pain, sick contacts, or joint pain. He had a history of about 40 pack-years of smoking, and his brother had recently been diagnosed with lung cancer. A tender fluctuant mass was detected in the nape of his neck on examination (Figure 1).

The patient had presented 9 months earlier with persistent cough and hemoptysis, and at that visit was found to have a cavitary lesion in the right lung measuring 2 cm (0.8 in). He had undergone a computed-tomograpghy (CT)-guided biopsy of the lesion, which had shown acute and chronic inflammation with fibrosis, and he had negative bronchoscopy findings. The patient tested negative for tuberculosis during the first visit but he left the hospital against the medical advice of the physicians and he was lost to follow-up until his re-presentation.

On physical examination at his re-presentation, the patient seemed cachectic, with a blood pressure of 94/62 mm of Hg. The mass in the nape of his neck was about 3 cm (1.2 in) long, with erythema of the surrounding skin (Figure 1). Bronchial breath sounds were heard in the right upper lobe of the lung, likely due to the underlying cavitary lesion (Figure 2).

Given the patient’s advanced disease, he was started on palliative radiotherapy with radiosensitizing chemotherapy with carboplatin (target AUC 6) and paclitaxel (135 mg/m² over 24 hours). His symptoms of hemoptysis improved transiently after the first cycle, but he became hypotensive and drowsy during the second cycle of therapy, and the family decided to make the patient comfort care and withdraw all further treatment. He was discharged to hospice.

Discussion

PSC is a rare variant of non-small-cell carcinoma lung cancer, accounting for up to 0.4% of lung malignancy.¹ It was recently subtyped by the World Health Organization as a non-small cell lung carcinoma with certain amount of differentiation resembling sarcoma or containing elements of sarcoma.^2-4 It is not known why both elements co-exist in the tumor, but Franks and colleagues some theories have been postulated in the literature, including possible origin from a single, aberrant stem cell with progenies differentiating in two separate pathways.³

Sarcomatoid carcinoma consists of spectrum of tumors including pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and blastoma.^3,4 It usually shows male preponderance, and association with smoking.³ The diagnosis commonly occurs in the sixth decade of life, except for pulmonary blastoma, which is more common in the fourth decade and with equal gender distribution.⁴

The presenting symptoms can be variable and nonspecific, but predominantly include chest pain, cough, hemoptysis, and/or weight loss.⁵ Radiologically, pulmonary sarcomatoid cancer presenting as a necrotizing cavitary lesion in the lung is a rare finding, seldom reported in the past.^6,7 The presentation in our case, with necrotizing lymphadenitis, was reminiscent of an infectious or autoimmune etiology such as tuberculosis or granulomatosis with polyangiitis. The presence of extensive necrosis in the lesion and the characteristic heterogeneity of the tumor had resulted in inconclusive biopsy findings during the previous presentation. In clinical practice, there is over-reliance on biopsy findings to make the distinction between cancer and other mimicking conditions. This is especially true for rare tumors such as PSC, which often results in misdiagnosis and a delay in administering the proper treatment.

Transbronchial biopsy in cases such as the present case, carries little benefit because the diagnosis depends on the site from which the biopsy is taken and whether the biopsied tissue is representative of the entire mass. The diagnosis can be suspected based on the clinical and radiological findings but confirmation requires a surgical resection to delineate the accurate cytology and architecture.^5,6,8 Huang and colleagues showed a misdiagnosis rate of PSC of >70% preoperatively.⁴ Resective surgery is feasible only in patients with high index of suspicion for a malignancy, which in most cases requires previous confirmation with a biopsy. The rarity of this cancer, its unusual presentations, and the lack of specific testing preclude early diagnosis and timely treatment of this fatal condition.

Initial treatment options for localized or with limited spread disease is resective surgery. The role of chemo- or radiation therapy is not known, but they have not previously shown promising results,^6,8 except in some cases when they are used as postoperative adjuvant chemotherapy⁴ or in bulky, locally invasive tumors.¹ The recurrence rate after surgery is very high, resulting in a poor 5-year survival rate.^1,8 Experimental therapies, such as antibodies that target epidermal growth factor receptor mutations, have not shown much success either.⁸ In conclusion, the outlook for patients with PSC with the current available knowledge and treatment protocols, is dismal.

Most of the current knowledge and data in the literature is based on cases from autopsy or early-stage surgical resections rather than on patients with advanced cancer.⁵ Moreover, the role of surgical resection in PSC is questionable, given the high recurrence rate. Subsequently, the clinical and pathological manifestations have yet to be well characterized.⁴ There has been advance with the publication of more studies recently. Cytokeratin markers such as CAM 5.2 and AE1/AE3 are commonly useful to support the diagnosis when suspected.³ Other markers, including the carcinoembryonic antigen, CD15, and thyroid transcription factor-1 may be variably positive, based on the differentiation of the cancer. Other exciting prospects in the study of PSC include the suggestion of a modified vimentin histologic score for better characterization of the cancer and the discovery of high platelet-derived growth factor receptor beta immunohistochemistry expression in PSC as a potential target for future therapy.

Conclusion

Pulmonary sarcomatoid lung cancer can present with a predominant necrotizing picture that mimics diseases such as tuberculosis. In such case, transbronchial biopsy carries little benefit because the diagnosis depends on whether the biopsied tissue is representative of the entire mass, often confounded by the extensive necrosis. More data is needed to determine prognostic factors and appropriate therapeutic strategies.

Nivolumab is a full human immunoglobulin antibody to the programmed cell death 1 (PD-1) immune checkpoint receptor on T cells. This programmed cell death inhibitor is a targeted immunotherapy used to treat patients with melanoma, among other malignancies.¹ More recently, nivolumab has been used for advanced non-small-cell lung cancer (NSCLC) after failure of previous chemotherapeutic agents. It was approved by the US Food and Drug Administration for the NSCLC indication in 2015.²

PD-1 inhibitors are efficacious in treating advanced malignancies, although their immune-mediated functions can lead to undesirable side effects. Patients treated with nivolumab have been reported to develop thyroid disease,^1,3,4 diabetes,³ hypophysitis,^1,3 hypopituitarism,³ and pneumonitis,^4,2 as well as other autoimmune conditions.³ Although nivolumab is often used to treat skin diseases such as melanoma, it can have many cutaneous side effects including pruritus,^1,3-6 rash,^1,3,4,6,7 vitiligo,^1,3,7,6 mouth sores,³ injection site reactions,^3,6 and alopecia.⁵ Herein, we describe a patient who was treated with nivolumab and developed an exacerbation of pre-existing psoriasis.

Case presentation and summary

A 57-year-old man with metastatic NSCLC and a history of plaque psoriasis presented to the dermatology clinic for evaluation of new lesions on his palms and soles. The patient had been previously treated with numerous therapies for NSCLC, including chemotherapy and radiation. Previous chemotherapeutic agents included the cisplatin plus etoposide combination, with doxetaxel and pemetrexed. The patient was not able to tolerate the chemotherapy and instead opted for hospice care. After several months, he chose to restart therapy, and was started on the programmed cell death (PD)-1 inhibitor, nivolumab, at a dose of 3 mg/kg for a total of 6 cycles. He received his first dose 5 weeks before his current presentation to the clinic, and his second dose 2 weeks before.

The patient reported a 20-year history of plaque psoriasis, characterized by psoriatic plaques on the elbows and shins and for which he was treated with topical therapies with good effect. Every few months, he would develop one or two small plaques of psoriasis on his palms and soles. The lesions were inconsequential to the patient, as he never experienced more than one or two small palmoplantar lesions at a time. One week after his second cycle of nivolumab, the patient developed an eruption of lesions on his palms and soles. He observed that the lesions seemed to be similar to his previous palmoplantar psoriatic plaques but with significantly greater skin involvement. The patient denied any new-onset joint pain.

The results of a physical examination revealed a cachectic man in no acute distress, with more than 30 erythematous circular to oval circumscribed plaques with yellow to whitish scales on the bilateral palms (Figure 1) and soles (Figure 2).

A clinical diagnosis of exacerbation of pre-existing psoriasis owing to nivolumab therapy was made. The patient was started on clobetasol 0.05% ointment twice daily under occlusion with plastic wrap to the affected areas, and he was continued on nivolumab for his NSCLC.

Discussion

Treatment with nivolumab can lead to a range of autoimmune side effects, and as shown in this case, psoriasis is one of the cutaneous findings that could be exacerbated by treatment with nivolumab. To date, two cases of exacerbation of psoriasis in patients treated with nivolumab for melanoma have been reported in the literature.^8,9 In the first case, the patient had well-controlled plaque psoriasis at baseline and he subsequently developed psoriatic plaques on the trunk and extremities after the second infusion of nivolumab for metastatic melanoma. A biopsy showed regular acanthosis with hyperkeratosis and parakeratosis in addition to dilated vessels in the papillary dermis.⁸ In the second case, the patient had a history of psoriasis vulgaris with no active lesions. Three weeks after his first course of nivolumab for metastatic oral mucosal melanoma, he developed new, well-circumscribed erythematous scaly plaques on the trunk and extremities that were clinically diagnosed as psoriasis.⁹ In a third case, a patient without a prior history of psoriasis experienced a psoriasiform eruption on the trunk and extremities after the fourth dose of nivolumab for oral mucosal melanoma.¹⁰ Thus, our case is the third reported case of exacerbation of preexisting psoriasis in a patient treated with nivolumab. Furthermore, our patient is the first reported case of a patient treated with nivolumab for NSCLC to develop this adverse event. Whereas the previously reported cases were characterized by widespread trunk and extremity involvement, our patient developed focal exacerbation of the palmoplantar areas.

Additional studies are needed to more clearly characterize the specific cutaneous toxicities of nivolumab and to determine if particular skin reactions may indicate a better response to the anticancer agent. Side effects such as psoriasis can often be managed with topical therapies and may not require withdrawal of the medication. We encourage the collaboration of dermatologists and oncologists to enhance the diagnosis and management of these cutaneous side effects in cancer patients.

Nivolumab is a full human immunoglobulin antibody to the programmed cell death 1 (PD-1) immune checkpoint receptor on T cells. This programmed cell death inhibitor is a targeted immunotherapy used to treat patients with melanoma, among other malignancies.¹ More recently, nivolumab has been used for advanced non-small-cell lung cancer (NSCLC) after failure of previous chemotherapeutic agents. It was approved by the US Food and Drug Administration for the NSCLC indication in 2015.²

PD-1 inhibitors are efficacious in treating advanced malignancies, although their immune-mediated functions can lead to undesirable side effects. Patients treated with nivolumab have been reported to develop thyroid disease,^1,3,4 diabetes,³ hypophysitis,^1,3 hypopituitarism,³ and pneumonitis,^4,2 as well as other autoimmune conditions.³ Although nivolumab is often used to treat skin diseases such as melanoma, it can have many cutaneous side effects including pruritus,^1,3-6 rash,^1,3,4,6,7 vitiligo,^1,3,7,6 mouth sores,³ injection site reactions,^3,6 and alopecia.⁵ Herein, we describe a patient who was treated with nivolumab and developed an exacerbation of pre-existing psoriasis.

Case presentation and summary

A 57-year-old man with metastatic NSCLC and a history of plaque psoriasis presented to the dermatology clinic for evaluation of new lesions on his palms and soles. The patient had been previously treated with numerous therapies for NSCLC, including chemotherapy and radiation. Previous chemotherapeutic agents included the cisplatin plus etoposide combination, with doxetaxel and pemetrexed. The patient was not able to tolerate the chemotherapy and instead opted for hospice care. After several months, he chose to restart therapy, and was started on the programmed cell death (PD)-1 inhibitor, nivolumab, at a dose of 3 mg/kg for a total of 6 cycles. He received his first dose 5 weeks before his current presentation to the clinic, and his second dose 2 weeks before.

The patient reported a 20-year history of plaque psoriasis, characterized by psoriatic plaques on the elbows and shins and for which he was treated with topical therapies with good effect. Every few months, he would develop one or two small plaques of psoriasis on his palms and soles. The lesions were inconsequential to the patient, as he never experienced more than one or two small palmoplantar lesions at a time. One week after his second cycle of nivolumab, the patient developed an eruption of lesions on his palms and soles. He observed that the lesions seemed to be similar to his previous palmoplantar psoriatic plaques but with significantly greater skin involvement. The patient denied any new-onset joint pain.

The results of a physical examination revealed a cachectic man in no acute distress, with more than 30 erythematous circular to oval circumscribed plaques with yellow to whitish scales on the bilateral palms (Figure 1) and soles (Figure 2).

A clinical diagnosis of exacerbation of pre-existing psoriasis owing to nivolumab therapy was made. The patient was started on clobetasol 0.05% ointment twice daily under occlusion with plastic wrap to the affected areas, and he was continued on nivolumab for his NSCLC.

Discussion

Treatment with nivolumab can lead to a range of autoimmune side effects, and as shown in this case, psoriasis is one of the cutaneous findings that could be exacerbated by treatment with nivolumab. To date, two cases of exacerbation of psoriasis in patients treated with nivolumab for melanoma have been reported in the literature.^8,9 In the first case, the patient had well-controlled plaque psoriasis at baseline and he subsequently developed psoriatic plaques on the trunk and extremities after the second infusion of nivolumab for metastatic melanoma. A biopsy showed regular acanthosis with hyperkeratosis and parakeratosis in addition to dilated vessels in the papillary dermis.⁸ In the second case, the patient had a history of psoriasis vulgaris with no active lesions. Three weeks after his first course of nivolumab for metastatic oral mucosal melanoma, he developed new, well-circumscribed erythematous scaly plaques on the trunk and extremities that were clinically diagnosed as psoriasis.⁹ In a third case, a patient without a prior history of psoriasis experienced a psoriasiform eruption on the trunk and extremities after the fourth dose of nivolumab for oral mucosal melanoma.¹⁰ Thus, our case is the third reported case of exacerbation of preexisting psoriasis in a patient treated with nivolumab. Furthermore, our patient is the first reported case of a patient treated with nivolumab for NSCLC to develop this adverse event. Whereas the previously reported cases were characterized by widespread trunk and extremity involvement, our patient developed focal exacerbation of the palmoplantar areas.

Additional studies are needed to more clearly characterize the specific cutaneous toxicities of nivolumab and to determine if particular skin reactions may indicate a better response to the anticancer agent. Side effects such as psoriasis can often be managed with topical therapies and may not require withdrawal of the medication. We encourage the collaboration of dermatologists and oncologists to enhance the diagnosis and management of these cutaneous side effects in cancer patients.

Nivolumab is a full human immunoglobulin antibody to the programmed cell death 1 (PD-1) immune checkpoint receptor on T cells. This programmed cell death inhibitor is a targeted immunotherapy used to treat patients with melanoma, among other malignancies.¹ More recently, nivolumab has been used for advanced non-small-cell lung cancer (NSCLC) after failure of previous chemotherapeutic agents. It was approved by the US Food and Drug Administration for the NSCLC indication in 2015.²

PD-1 inhibitors are efficacious in treating advanced malignancies, although their immune-mediated functions can lead to undesirable side effects. Patients treated with nivolumab have been reported to develop thyroid disease,^1,3,4 diabetes,³ hypophysitis,^1,3 hypopituitarism,³ and pneumonitis,^4,2 as well as other autoimmune conditions.³ Although nivolumab is often used to treat skin diseases such as melanoma, it can have many cutaneous side effects including pruritus,^1,3-6 rash,^1,3,4,6,7 vitiligo,^1,3,7,6 mouth sores,³ injection site reactions,^3,6 and alopecia.⁵ Herein, we describe a patient who was treated with nivolumab and developed an exacerbation of pre-existing psoriasis.

Case presentation and summary

A 57-year-old man with metastatic NSCLC and a history of plaque psoriasis presented to the dermatology clinic for evaluation of new lesions on his palms and soles. The patient had been previously treated with numerous therapies for NSCLC, including chemotherapy and radiation. Previous chemotherapeutic agents included the cisplatin plus etoposide combination, with doxetaxel and pemetrexed. The patient was not able to tolerate the chemotherapy and instead opted for hospice care. After several months, he chose to restart therapy, and was started on the programmed cell death (PD)-1 inhibitor, nivolumab, at a dose of 3 mg/kg for a total of 6 cycles. He received his first dose 5 weeks before his current presentation to the clinic, and his second dose 2 weeks before.

The patient reported a 20-year history of plaque psoriasis, characterized by psoriatic plaques on the elbows and shins and for which he was treated with topical therapies with good effect. Every few months, he would develop one or two small plaques of psoriasis on his palms and soles. The lesions were inconsequential to the patient, as he never experienced more than one or two small palmoplantar lesions at a time. One week after his second cycle of nivolumab, the patient developed an eruption of lesions on his palms and soles. He observed that the lesions seemed to be similar to his previous palmoplantar psoriatic plaques but with significantly greater skin involvement. The patient denied any new-onset joint pain.

The results of a physical examination revealed a cachectic man in no acute distress, with more than 30 erythematous circular to oval circumscribed plaques with yellow to whitish scales on the bilateral palms (Figure 1) and soles (Figure 2).

A clinical diagnosis of exacerbation of pre-existing psoriasis owing to nivolumab therapy was made. The patient was started on clobetasol 0.05% ointment twice daily under occlusion with plastic wrap to the affected areas, and he was continued on nivolumab for his NSCLC.

Discussion

Treatment with nivolumab can lead to a range of autoimmune side effects, and as shown in this case, psoriasis is one of the cutaneous findings that could be exacerbated by treatment with nivolumab. To date, two cases of exacerbation of psoriasis in patients treated with nivolumab for melanoma have been reported in the literature.^8,9 In the first case, the patient had well-controlled plaque psoriasis at baseline and he subsequently developed psoriatic plaques on the trunk and extremities after the second infusion of nivolumab for metastatic melanoma. A biopsy showed regular acanthosis with hyperkeratosis and parakeratosis in addition to dilated vessels in the papillary dermis.⁸ In the second case, the patient had a history of psoriasis vulgaris with no active lesions. Three weeks after his first course of nivolumab for metastatic oral mucosal melanoma, he developed new, well-circumscribed erythematous scaly plaques on the trunk and extremities that were clinically diagnosed as psoriasis.⁹ In a third case, a patient without a prior history of psoriasis experienced a psoriasiform eruption on the trunk and extremities after the fourth dose of nivolumab for oral mucosal melanoma.¹⁰ Thus, our case is the third reported case of exacerbation of preexisting psoriasis in a patient treated with nivolumab. Furthermore, our patient is the first reported case of a patient treated with nivolumab for NSCLC to develop this adverse event. Whereas the previously reported cases were characterized by widespread trunk and extremity involvement, our patient developed focal exacerbation of the palmoplantar areas.

Additional studies are needed to more clearly characterize the specific cutaneous toxicities of nivolumab and to determine if particular skin reactions may indicate a better response to the anticancer agent. Side effects such as psoriasis can often be managed with topical therapies and may not require withdrawal of the medication. We encourage the collaboration of dermatologists and oncologists to enhance the diagnosis and management of these cutaneous side effects in cancer patients.

Unintentional weight loss can present diagnostic challenges, according to researchers from University of Barcelona. So many factors are involved, and so many causes are possible, extensive and invasive investigation often is needed. And because cancer may be the underlying cause of weight loss in patients with few or no symptoms, a swift workup is crucial. Most studies of unintentional weight loss (UWL) have been limited by small sample sizes, short or variable follow-up, or focus on older patients, the researchers say. So they conducted the largest and longest prospective study thus far, following 2,677 patients for >  5 years.

The patients were referred to an outpatient diagnosis unit for evaluation of UWL as a dominant or isolated feature of disease and underwent a standard baseline evaluation with laboratory tests and chest X-ray. Those without identifiable causes 6 months after presentation were followed for 60 more months. Older patients also were given an oral cavity examination, a videofluoroscopy or swallowing study, and a depression and cognitive assessment.

At 6 months, 582 patients had unexplained UWL. Of those, 27 had malignancies: 11 patients had pancreatic cancer; nine had lymphoma. Nearly half of the cancers were digestive; of those, pancreatic cancer accounted for 19%, followed by lung (17%); lymphoma (11%); and kidney, ureteral, and bladder cancers (10%). Of 450 nonmalignant organic disorders, 45% were digestive.

Cancer patients had the highest mortality rate (69% vs 5%-6% in other groups). Decreasing weight was substantially more common in survivors with malignancies (66%) than in the rest of the patients studied, as well as in survivors with nonmalignant organic disorders (10%) than in unexplained UWL and psychosocial disorders. Patients with cancers were older, male, and active smokers, with a greater weight loss than patients in other groups. They also were more likely to have accompanying symptoms and abnormalities on physical examination, lab tests, and chest X-ray.

Cancer evading early diagnosis is a major concern, the researchers say. One of the main findings of the study was the long follow-up of patients with unexplained UWL: a mean of 47.5 months. Based on their findings, occult malignancies detected during a follow-up of up to 66 months after presentation “do not seem to be as rare as thought.” Moreover, autopsies of 13 patients showed malignancies in eight.

However, the fact that only 1 in 20 patients received a cancer diagnosis within that period—most notably within the first 28 months after referral for workup—is “fairly reassuring.” However, they recommend continuing to regularly evaluate patients with UWL for longer periods even if they had a normal evaluation and workup.

Unintentional weight loss can present diagnostic challenges, according to researchers from University of Barcelona. So many factors are involved, and so many causes are possible, extensive and invasive investigation often is needed. And because cancer may be the underlying cause of weight loss in patients with few or no symptoms, a swift workup is crucial. Most studies of unintentional weight loss (UWL) have been limited by small sample sizes, short or variable follow-up, or focus on older patients, the researchers say. So they conducted the largest and longest prospective study thus far, following 2,677 patients for >  5 years.

The patients were referred to an outpatient diagnosis unit for evaluation of UWL as a dominant or isolated feature of disease and underwent a standard baseline evaluation with laboratory tests and chest X-ray. Those without identifiable causes 6 months after presentation were followed for 60 more months. Older patients also were given an oral cavity examination, a videofluoroscopy or swallowing study, and a depression and cognitive assessment.

At 6 months, 582 patients had unexplained UWL. Of those, 27 had malignancies: 11 patients had pancreatic cancer; nine had lymphoma. Nearly half of the cancers were digestive; of those, pancreatic cancer accounted for 19%, followed by lung (17%); lymphoma (11%); and kidney, ureteral, and bladder cancers (10%). Of 450 nonmalignant organic disorders, 45% were digestive.

Cancer patients had the highest mortality rate (69% vs 5%-6% in other groups). Decreasing weight was substantially more common in survivors with malignancies (66%) than in the rest of the patients studied, as well as in survivors with nonmalignant organic disorders (10%) than in unexplained UWL and psychosocial disorders. Patients with cancers were older, male, and active smokers, with a greater weight loss than patients in other groups. They also were more likely to have accompanying symptoms and abnormalities on physical examination, lab tests, and chest X-ray.

Cancer evading early diagnosis is a major concern, the researchers say. One of the main findings of the study was the long follow-up of patients with unexplained UWL: a mean of 47.5 months. Based on their findings, occult malignancies detected during a follow-up of up to 66 months after presentation “do not seem to be as rare as thought.” Moreover, autopsies of 13 patients showed malignancies in eight.

However, the fact that only 1 in 20 patients received a cancer diagnosis within that period—most notably within the first 28 months after referral for workup—is “fairly reassuring.” However, they recommend continuing to regularly evaluate patients with UWL for longer periods even if they had a normal evaluation and workup.

Unintentional weight loss can present diagnostic challenges, according to researchers from University of Barcelona. So many factors are involved, and so many causes are possible, extensive and invasive investigation often is needed. And because cancer may be the underlying cause of weight loss in patients with few or no symptoms, a swift workup is crucial. Most studies of unintentional weight loss (UWL) have been limited by small sample sizes, short or variable follow-up, or focus on older patients, the researchers say. So they conducted the largest and longest prospective study thus far, following 2,677 patients for >  5 years.

The patients were referred to an outpatient diagnosis unit for evaluation of UWL as a dominant or isolated feature of disease and underwent a standard baseline evaluation with laboratory tests and chest X-ray. Those without identifiable causes 6 months after presentation were followed for 60 more months. Older patients also were given an oral cavity examination, a videofluoroscopy or swallowing study, and a depression and cognitive assessment.

At 6 months, 582 patients had unexplained UWL. Of those, 27 had malignancies: 11 patients had pancreatic cancer; nine had lymphoma. Nearly half of the cancers were digestive; of those, pancreatic cancer accounted for 19%, followed by lung (17%); lymphoma (11%); and kidney, ureteral, and bladder cancers (10%). Of 450 nonmalignant organic disorders, 45% were digestive.

Cancer patients had the highest mortality rate (69% vs 5%-6% in other groups). Decreasing weight was substantially more common in survivors with malignancies (66%) than in the rest of the patients studied, as well as in survivors with nonmalignant organic disorders (10%) than in unexplained UWL and psychosocial disorders. Patients with cancers were older, male, and active smokers, with a greater weight loss than patients in other groups. They also were more likely to have accompanying symptoms and abnormalities on physical examination, lab tests, and chest X-ray.

Cancer evading early diagnosis is a major concern, the researchers say. One of the main findings of the study was the long follow-up of patients with unexplained UWL: a mean of 47.5 months. Based on their findings, occult malignancies detected during a follow-up of up to 66 months after presentation “do not seem to be as rare as thought.” Moreover, autopsies of 13 patients showed malignancies in eight.

However, the fact that only 1 in 20 patients received a cancer diagnosis within that period—most notably within the first 28 months after referral for workup—is “fairly reassuring.” However, they recommend continuing to regularly evaluate patients with UWL for longer periods even if they had a normal evaluation and workup.

SAN DIEGO – Young women who received group prenatal visits under the CenteringPregnancy model were significantly more likely than were women receiving traditional prenatal care to elect long-acting reversible contraceptives postpartum, results from a small study show.

CenteringPregnancy (CP) – a group prenatal care model for women with due dates around the same time – has been touted as a way to decrease the incidence of preterm deliveries, but little is known about potential additional benefits for other birth-related outcomes, lead study author

[email protected]

SAN DIEGO – Young women who received group prenatal visits under the CenteringPregnancy model were significantly more likely than were women receiving traditional prenatal care to elect long-acting reversible contraceptives postpartum, results from a small study show.

CenteringPregnancy (CP) – a group prenatal care model for women with due dates around the same time – has been touted as a way to decrease the incidence of preterm deliveries, but little is known about potential additional benefits for other birth-related outcomes, lead study author

[email protected]

SAN DIEGO – Young women who received group prenatal visits under the CenteringPregnancy model were significantly more likely than were women receiving traditional prenatal care to elect long-acting reversible contraceptives postpartum, results from a small study show.

CenteringPregnancy (CP) – a group prenatal care model for women with due dates around the same time – has been touted as a way to decrease the incidence of preterm deliveries, but little is known about potential additional benefits for other birth-related outcomes, lead study author

[email protected]

To the Editor:

Granulomatous cheilitis (GC), also known as Miescher cheilitis, belongs to a larger class of diseases known as orofacial granulomatoses (OFGs), a set of diseases distinguished by their clinical and pathologic features of facial edema and granulomatous inflammation.^1-3 Granulomatous cheilitis, a monosymptomatic variant of a more extensive disease known as Melkersson-Rosenthal syndrome (MRS), presents with labial swelling mimicking angioedema. Timely diagnosis of GC and MRS reduces the number of unnecessary tests, health care costs, and unnecessary patient burden. We present a case of idiopathic persistent swelling of the upper lip that was originally misdiagnosed as angioedema.

A 13-year-old white adolescent boy was referred to the allergy-immunology clinic for an alternate opinion regarding a presumed diagnosis of angioedema. He presented with prominent persistent swelling of the upper lip of 1 year’s duration associated with fissuring and discomfort while eating, which led to weight loss of more than 4.5 kg. The patient denied any history of facial asymmetry, paralysis, dental infections, or gastrointestinal tract symptoms. Additionally, he was not on any medications. His parents reported variable symptomatic worsening associated with egg ingestion, but avoiding egg did not provide any symptomatic relief. The swelling was unresponsive to multiple and prolonged courses of antihistamines and oral glucocorticoids. The patient’s medical history revealed no similar episodes of unexplained swelling, and family history was negative for angioedema. On examination, the upper lip was tender with a firm rubbery consistency. No other areas of swelling were noted. Angular cheilosis and minor labial mucosal ulcerations also were observed (Figure).

The persistent nature of the lip swelling and findings of fissures were not consistent with angioedema. Furthermore, prior laboratory studies did not reveal evidence of hereditary or acquired angioedema, and a complete blood cell count with differential was within reference range. Although the clinical suspicion for egg allergy was low, a blood test for serum-specific IgE showed a mild reactivity to egg allergen. The patient was referred to an oral surgeon for biopsy, which revealed dermal foci of noncaseating granulomas consistent with the preliminary diagnosis of GC.

Intralesional triamcinolone injections were initiated with marked improvement. Shortly after the initial improvement, however, the symptoms recurred, which necessitated several additional intralesional triamcinolone injections, again with remarkable improvement. Approximately 1.5 years later, the patient presented with recurrence of the lip swelling and admitted to having episodic diarrhea and abdominal cramps. He was referred to a pediatric gastroenterologist and a colonoscopy with biopsy confirmed Crohn disease. He was started on azathioprine followed by infliximab. A few months after this treatment was initiated, both his lip swelling and gastrointestinal tract symptoms remarkably improved. He has been maintained on this regimen and in the most recent follow-up had no recurrence of GC. He is scheduled to have another colonoscopy.

Granulomatous cheilitis is a rare chronic inflammatory condition characterized clinically by persistent lip swelling and histologically by granulomatous inflammation in the absence of systemic granulomatous disorders.⁴ Granulomatous cheilitis falls under the umbrella of OFGs. When it is paired with facial paralysis and fissuring of the tongue, it is specifically referred to as MRS. The prevalence of GC has historically been difficult to ascertain. In a review, an estimated incidence of 0.08% in the general population was reported with no predilection for race, sex, or age.^4,5 Initially, the swelling of GC can be misdiagnosed as angioedema; therefore, it is imperative to include OFG and GC in the differential diagnosis of facial angioedema.³ Other possible diagnoses to consider include contact dermatitis, foreign-body reactions, infection, and reactions to medications such as angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs.⁵ Chronic lymphedema and other granulomatous diseases also should be considered in the differential diagnosis. Isolated lymphedema of the head and neck, though rare, typically is seen following surgical or radiological interventions for cancer. Lymphatic fibrosis also can occur in the setting of chronic inflammatory skin conditions but is not typically the first presenting symptom, as was seen in our patient.⁶ Although granulomatous diseases such as sarcoidosis may be difficult to clinically and histologically differentiate from GC, isolated orofacial swelling in sarcoidosis is rare. If clinical suspicion for sarcoidosis does exist, however, a negative chest radiograph as well as serum calcium and angiotensin-converting enzyme levels within reference range may help differentiate GC from sarcoidosis. In our patient, the clinical suspicion for sarcoidosis was low given his clinical history, young age, and race.

The etiology of MRS and GC currently is unknown. Genetic factors, food allergies, infectious processes, and aberrant immunologic functions all have been proposed as possible mechanisms.^1-3,7,8 Genetic factors, such as HLA antigen subtypes, have been investigated but have not shown a definitive correlation.⁸ Numerous food allergens have been suggested as causative factors in OFG via a type of delayed hypersensitivity reaction,⁷ with cinnamon and benzoate reported as 2 of the most cited entities.^9,10 Currently, it is believed that both of these mechanisms may play an exacerbating role to an otherwise unknown disease process.^7,8 The infectious process most often associated with GC is Mycobacterium tuberculosis; however, similar to genetics and food allergens, causality has not been determined.^4,7 At the present time, the best evidence points to an immunologic basis of GC with the inciting event being a random influx of inflammatory cells.^7,11

There is a known association between GC and Crohn disease, especially when oral lesions are present.^1,9 Granulomatous cheilitis can be considered an extraintestinal manifestation of Crohn disease.Up to 20% of OFG patients eventually go on to develop Crohn disease, with some reports being even higher when OFG presents in childhood.^1,9 One study proposed that both GC and Crohn disease patients shared similar histopathologic and immunopathologic features including a helper T cell (T_H1)–predominant inflammatory reaction.¹¹

The treatment of GC is challenging, with most evidence coming from sporadic case reports. Given the relatively high rate of cinnamon and benzoate hypersensitivity seen in GC patients, it has been postulated that a diet lacking in them will improve the disease. At least one study has reported positive clinical outcomes from diets lacking in cinnamon and benzoate and in fact recommended it as a potential first-line treatment.¹⁰ The mainstay of treatment, however, is corticosteroids, but continued use is discouraged due to their large side-effect profile.¹² Currently, the most agreed upon treatment for patients with isolated GC is intralesional triamcinolone injections.¹² Despite the robust initial response often seen with triamcinolone injections, it is not uncommon for the benefit to be short-lived, requiring additional treatments.^1,5,12 Newer medical therapies that have shown promise largely are centered on anti–tumor necrosis factor α medications such as infliximab and adalimumab.^13,14 It is postulated that due to the potential overlapping pathophysiology between Crohn disease and GC, there may be utility in using the same treatments.¹³ In situations where medical therapy fails or in extremely disfiguring cases of GC and MRS, surgical cheiloplasty is performed to reduce lip size and improve cosmetic appearance.¹² In a small study, reduction cheiloplasty gave satisfactory functional and cosmetic outcomes in all 7 patients reviewed at a median follow-up of 6.5 years.¹⁵

This case emphasizes the importance of paying close attention to history and physical examination features in developing any differential diagnosis. In this patient, persistent orofacial swelling with associated mucosal ulcerations were sufficient to exclude drug-induced, idiopathic, hereditary, and acquired angioedema. The clinical history coupled with the biopsy results yielded a confident diagnosis of GC. Furthermore, similar presentations should raise concern for a subclinical inflammatory bowel disease such as Crohn disease.

To the Editor:

Granulomatous cheilitis (GC), also known as Miescher cheilitis, belongs to a larger class of diseases known as orofacial granulomatoses (OFGs), a set of diseases distinguished by their clinical and pathologic features of facial edema and granulomatous inflammation.^1-3 Granulomatous cheilitis, a monosymptomatic variant of a more extensive disease known as Melkersson-Rosenthal syndrome (MRS), presents with labial swelling mimicking angioedema. Timely diagnosis of GC and MRS reduces the number of unnecessary tests, health care costs, and unnecessary patient burden. We present a case of idiopathic persistent swelling of the upper lip that was originally misdiagnosed as angioedema.

A 13-year-old white adolescent boy was referred to the allergy-immunology clinic for an alternate opinion regarding a presumed diagnosis of angioedema. He presented with prominent persistent swelling of the upper lip of 1 year’s duration associated with fissuring and discomfort while eating, which led to weight loss of more than 4.5 kg. The patient denied any history of facial asymmetry, paralysis, dental infections, or gastrointestinal tract symptoms. Additionally, he was not on any medications. His parents reported variable symptomatic worsening associated with egg ingestion, but avoiding egg did not provide any symptomatic relief. The swelling was unresponsive to multiple and prolonged courses of antihistamines and oral glucocorticoids. The patient’s medical history revealed no similar episodes of unexplained swelling, and family history was negative for angioedema. On examination, the upper lip was tender with a firm rubbery consistency. No other areas of swelling were noted. Angular cheilosis and minor labial mucosal ulcerations also were observed (Figure).

The persistent nature of the lip swelling and findings of fissures were not consistent with angioedema. Furthermore, prior laboratory studies did not reveal evidence of hereditary or acquired angioedema, and a complete blood cell count with differential was within reference range. Although the clinical suspicion for egg allergy was low, a blood test for serum-specific IgE showed a mild reactivity to egg allergen. The patient was referred to an oral surgeon for biopsy, which revealed dermal foci of noncaseating granulomas consistent with the preliminary diagnosis of GC.

Intralesional triamcinolone injections were initiated with marked improvement. Shortly after the initial improvement, however, the symptoms recurred, which necessitated several additional intralesional triamcinolone injections, again with remarkable improvement. Approximately 1.5 years later, the patient presented with recurrence of the lip swelling and admitted to having episodic diarrhea and abdominal cramps. He was referred to a pediatric gastroenterologist and a colonoscopy with biopsy confirmed Crohn disease. He was started on azathioprine followed by infliximab. A few months after this treatment was initiated, both his lip swelling and gastrointestinal tract symptoms remarkably improved. He has been maintained on this regimen and in the most recent follow-up had no recurrence of GC. He is scheduled to have another colonoscopy.

Granulomatous cheilitis is a rare chronic inflammatory condition characterized clinically by persistent lip swelling and histologically by granulomatous inflammation in the absence of systemic granulomatous disorders.⁴ Granulomatous cheilitis falls under the umbrella of OFGs. When it is paired with facial paralysis and fissuring of the tongue, it is specifically referred to as MRS. The prevalence of GC has historically been difficult to ascertain. In a review, an estimated incidence of 0.08% in the general population was reported with no predilection for race, sex, or age.^4,5 Initially, the swelling of GC can be misdiagnosed as angioedema; therefore, it is imperative to include OFG and GC in the differential diagnosis of facial angioedema.³ Other possible diagnoses to consider include contact dermatitis, foreign-body reactions, infection, and reactions to medications such as angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs.⁵ Chronic lymphedema and other granulomatous diseases also should be considered in the differential diagnosis. Isolated lymphedema of the head and neck, though rare, typically is seen following surgical or radiological interventions for cancer. Lymphatic fibrosis also can occur in the setting of chronic inflammatory skin conditions but is not typically the first presenting symptom, as was seen in our patient.⁶ Although granulomatous diseases such as sarcoidosis may be difficult to clinically and histologically differentiate from GC, isolated orofacial swelling in sarcoidosis is rare. If clinical suspicion for sarcoidosis does exist, however, a negative chest radiograph as well as serum calcium and angiotensin-converting enzyme levels within reference range may help differentiate GC from sarcoidosis. In our patient, the clinical suspicion for sarcoidosis was low given his clinical history, young age, and race.

The etiology of MRS and GC currently is unknown. Genetic factors, food allergies, infectious processes, and aberrant immunologic functions all have been proposed as possible mechanisms.^1-3,7,8 Genetic factors, such as HLA antigen subtypes, have been investigated but have not shown a definitive correlation.⁸ Numerous food allergens have been suggested as causative factors in OFG via a type of delayed hypersensitivity reaction,⁷ with cinnamon and benzoate reported as 2 of the most cited entities.^9,10 Currently, it is believed that both of these mechanisms may play an exacerbating role to an otherwise unknown disease process.^7,8 The infectious process most often associated with GC is Mycobacterium tuberculosis; however, similar to genetics and food allergens, causality has not been determined.^4,7 At the present time, the best evidence points to an immunologic basis of GC with the inciting event being a random influx of inflammatory cells.^7,11

There is a known association between GC and Crohn disease, especially when oral lesions are present.^1,9 Granulomatous cheilitis can be considered an extraintestinal manifestation of Crohn disease.Up to 20% of OFG patients eventually go on to develop Crohn disease, with some reports being even higher when OFG presents in childhood.^1,9 One study proposed that both GC and Crohn disease patients shared similar histopathologic and immunopathologic features including a helper T cell (T_H1)–predominant inflammatory reaction.¹¹

The treatment of GC is challenging, with most evidence coming from sporadic case reports. Given the relatively high rate of cinnamon and benzoate hypersensitivity seen in GC patients, it has been postulated that a diet lacking in them will improve the disease. At least one study has reported positive clinical outcomes from diets lacking in cinnamon and benzoate and in fact recommended it as a potential first-line treatment.¹⁰ The mainstay of treatment, however, is corticosteroids, but continued use is discouraged due to their large side-effect profile.¹² Currently, the most agreed upon treatment for patients with isolated GC is intralesional triamcinolone injections.¹² Despite the robust initial response often seen with triamcinolone injections, it is not uncommon for the benefit to be short-lived, requiring additional treatments.^1,5,12 Newer medical therapies that have shown promise largely are centered on anti–tumor necrosis factor α medications such as infliximab and adalimumab.^13,14 It is postulated that due to the potential overlapping pathophysiology between Crohn disease and GC, there may be utility in using the same treatments.¹³ In situations where medical therapy fails or in extremely disfiguring cases of GC and MRS, surgical cheiloplasty is performed to reduce lip size and improve cosmetic appearance.¹² In a small study, reduction cheiloplasty gave satisfactory functional and cosmetic outcomes in all 7 patients reviewed at a median follow-up of 6.5 years.¹⁵

This case emphasizes the importance of paying close attention to history and physical examination features in developing any differential diagnosis. In this patient, persistent orofacial swelling with associated mucosal ulcerations were sufficient to exclude drug-induced, idiopathic, hereditary, and acquired angioedema. The clinical history coupled with the biopsy results yielded a confident diagnosis of GC. Furthermore, similar presentations should raise concern for a subclinical inflammatory bowel disease such as Crohn disease.

To the Editor:

Granulomatous cheilitis (GC), also known as Miescher cheilitis, belongs to a larger class of diseases known as orofacial granulomatoses (OFGs), a set of diseases distinguished by their clinical and pathologic features of facial edema and granulomatous inflammation.^1-3 Granulomatous cheilitis, a monosymptomatic variant of a more extensive disease known as Melkersson-Rosenthal syndrome (MRS), presents with labial swelling mimicking angioedema. Timely diagnosis of GC and MRS reduces the number of unnecessary tests, health care costs, and unnecessary patient burden. We present a case of idiopathic persistent swelling of the upper lip that was originally misdiagnosed as angioedema.

A 13-year-old white adolescent boy was referred to the allergy-immunology clinic for an alternate opinion regarding a presumed diagnosis of angioedema. He presented with prominent persistent swelling of the upper lip of 1 year’s duration associated with fissuring and discomfort while eating, which led to weight loss of more than 4.5 kg. The patient denied any history of facial asymmetry, paralysis, dental infections, or gastrointestinal tract symptoms. Additionally, he was not on any medications. His parents reported variable symptomatic worsening associated with egg ingestion, but avoiding egg did not provide any symptomatic relief. The swelling was unresponsive to multiple and prolonged courses of antihistamines and oral glucocorticoids. The patient’s medical history revealed no similar episodes of unexplained swelling, and family history was negative for angioedema. On examination, the upper lip was tender with a firm rubbery consistency. No other areas of swelling were noted. Angular cheilosis and minor labial mucosal ulcerations also were observed (Figure).

The persistent nature of the lip swelling and findings of fissures were not consistent with angioedema. Furthermore, prior laboratory studies did not reveal evidence of hereditary or acquired angioedema, and a complete blood cell count with differential was within reference range. Although the clinical suspicion for egg allergy was low, a blood test for serum-specific IgE showed a mild reactivity to egg allergen. The patient was referred to an oral surgeon for biopsy, which revealed dermal foci of noncaseating granulomas consistent with the preliminary diagnosis of GC.

Intralesional triamcinolone injections were initiated with marked improvement. Shortly after the initial improvement, however, the symptoms recurred, which necessitated several additional intralesional triamcinolone injections, again with remarkable improvement. Approximately 1.5 years later, the patient presented with recurrence of the lip swelling and admitted to having episodic diarrhea and abdominal cramps. He was referred to a pediatric gastroenterologist and a colonoscopy with biopsy confirmed Crohn disease. He was started on azathioprine followed by infliximab. A few months after this treatment was initiated, both his lip swelling and gastrointestinal tract symptoms remarkably improved. He has been maintained on this regimen and in the most recent follow-up had no recurrence of GC. He is scheduled to have another colonoscopy.

Granulomatous cheilitis is a rare chronic inflammatory condition characterized clinically by persistent lip swelling and histologically by granulomatous inflammation in the absence of systemic granulomatous disorders.⁴ Granulomatous cheilitis falls under the umbrella of OFGs. When it is paired with facial paralysis and fissuring of the tongue, it is specifically referred to as MRS. The prevalence of GC has historically been difficult to ascertain. In a review, an estimated incidence of 0.08% in the general population was reported with no predilection for race, sex, or age.^4,5 Initially, the swelling of GC can be misdiagnosed as angioedema; therefore, it is imperative to include OFG and GC in the differential diagnosis of facial angioedema.³ Other possible diagnoses to consider include contact dermatitis, foreign-body reactions, infection, and reactions to medications such as angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs.⁵ Chronic lymphedema and other granulomatous diseases also should be considered in the differential diagnosis. Isolated lymphedema of the head and neck, though rare, typically is seen following surgical or radiological interventions for cancer. Lymphatic fibrosis also can occur in the setting of chronic inflammatory skin conditions but is not typically the first presenting symptom, as was seen in our patient.⁶ Although granulomatous diseases such as sarcoidosis may be difficult to clinically and histologically differentiate from GC, isolated orofacial swelling in sarcoidosis is rare. If clinical suspicion for sarcoidosis does exist, however, a negative chest radiograph as well as serum calcium and angiotensin-converting enzyme levels within reference range may help differentiate GC from sarcoidosis. In our patient, the clinical suspicion for sarcoidosis was low given his clinical history, young age, and race.

The etiology of MRS and GC currently is unknown. Genetic factors, food allergies, infectious processes, and aberrant immunologic functions all have been proposed as possible mechanisms.^1-3,7,8 Genetic factors, such as HLA antigen subtypes, have been investigated but have not shown a definitive correlation.⁸ Numerous food allergens have been suggested as causative factors in OFG via a type of delayed hypersensitivity reaction,⁷ with cinnamon and benzoate reported as 2 of the most cited entities.^9,10 Currently, it is believed that both of these mechanisms may play an exacerbating role to an otherwise unknown disease process.^7,8 The infectious process most often associated with GC is Mycobacterium tuberculosis; however, similar to genetics and food allergens, causality has not been determined.^4,7 At the present time, the best evidence points to an immunologic basis of GC with the inciting event being a random influx of inflammatory cells.^7,11

There is a known association between GC and Crohn disease, especially when oral lesions are present.^1,9 Granulomatous cheilitis can be considered an extraintestinal manifestation of Crohn disease.Up to 20% of OFG patients eventually go on to develop Crohn disease, with some reports being even higher when OFG presents in childhood.^1,9 One study proposed that both GC and Crohn disease patients shared similar histopathologic and immunopathologic features including a helper T cell (T_H1)–predominant inflammatory reaction.¹¹

The treatment of GC is challenging, with most evidence coming from sporadic case reports. Given the relatively high rate of cinnamon and benzoate hypersensitivity seen in GC patients, it has been postulated that a diet lacking in them will improve the disease. At least one study has reported positive clinical outcomes from diets lacking in cinnamon and benzoate and in fact recommended it as a potential first-line treatment.¹⁰ The mainstay of treatment, however, is corticosteroids, but continued use is discouraged due to their large side-effect profile.¹² Currently, the most agreed upon treatment for patients with isolated GC is intralesional triamcinolone injections.¹² Despite the robust initial response often seen with triamcinolone injections, it is not uncommon for the benefit to be short-lived, requiring additional treatments.^1,5,12 Newer medical therapies that have shown promise largely are centered on anti–tumor necrosis factor α medications such as infliximab and adalimumab.^13,14 It is postulated that due to the potential overlapping pathophysiology between Crohn disease and GC, there may be utility in using the same treatments.¹³ In situations where medical therapy fails or in extremely disfiguring cases of GC and MRS, surgical cheiloplasty is performed to reduce lip size and improve cosmetic appearance.¹² In a small study, reduction cheiloplasty gave satisfactory functional and cosmetic outcomes in all 7 patients reviewed at a median follow-up of 6.5 years.¹⁵

This case emphasizes the importance of paying close attention to history and physical examination features in developing any differential diagnosis. In this patient, persistent orofacial swelling with associated mucosal ulcerations were sufficient to exclude drug-induced, idiopathic, hereditary, and acquired angioedema. The clinical history coupled with the biopsy results yielded a confident diagnosis of GC. Furthermore, similar presentations should raise concern for a subclinical inflammatory bowel disease such as Crohn disease.

We go to the altar together.

Last month, I wrote about onboarding and the important responsibility that everyone associated with a hospitalist program has to ensure that each new provider quickly comes to believe he or she made a terrific choice to join the group.

Upon reflection, it seems important to address the other side of this equation. I’m talking about the responsibilities that each candidate has when deciding whether to apply for a job, to interview, and to accept or reject a group’s offer.

Leslie Flores is a founding partner at Nelson Flores Hospital Medicine Consultants, a consulting practice that has specialized in helping clients enhance the effectiveness and value of hospital medicine programs.

Also on The Hospital Leader …

Don’t Compare HM Group Part B Costs Hospital to Hospital by Brad Flansbaum, DO, MPH, MHM

Overcoming a Continued Physician Shortage by Danielle Scheurer, MD, MSCR, SFHM

Is Patient-Centered Care Bad for Resident Education? by Vineet Arora, MD, MPP, MHM

We go to the altar together.

Last month, I wrote about onboarding and the important responsibility that everyone associated with a hospitalist program has to ensure that each new provider quickly comes to believe he or she made a terrific choice to join the group.

Upon reflection, it seems important to address the other side of this equation. I’m talking about the responsibilities that each candidate has when deciding whether to apply for a job, to interview, and to accept or reject a group’s offer.

Leslie Flores is a founding partner at Nelson Flores Hospital Medicine Consultants, a consulting practice that has specialized in helping clients enhance the effectiveness and value of hospital medicine programs.

Also on The Hospital Leader …

Don’t Compare HM Group Part B Costs Hospital to Hospital by Brad Flansbaum, DO, MPH, MHM

Overcoming a Continued Physician Shortage by Danielle Scheurer, MD, MSCR, SFHM

Is Patient-Centered Care Bad for Resident Education? by Vineet Arora, MD, MPP, MHM

We go to the altar together.

Last month, I wrote about onboarding and the important responsibility that everyone associated with a hospitalist program has to ensure that each new provider quickly comes to believe he or she made a terrific choice to join the group.

Upon reflection, it seems important to address the other side of this equation. I’m talking about the responsibilities that each candidate has when deciding whether to apply for a job, to interview, and to accept or reject a group’s offer.

Leslie Flores is a founding partner at Nelson Flores Hospital Medicine Consultants, a consulting practice that has specialized in helping clients enhance the effectiveness and value of hospital medicine programs.

Also on The Hospital Leader …

Don’t Compare HM Group Part B Costs Hospital to Hospital by Brad Flansbaum, DO, MPH, MHM

Overcoming a Continued Physician Shortage by Danielle Scheurer, MD, MSCR, SFHM

Is Patient-Centered Care Bad for Resident Education? by Vineet Arora, MD, MPP, MHM