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Worsening cognitive impairments
The history and findings in this case are suggestive of Alzheimer's disease (AD).
AD is the most common type of dementia. It is characterized by cognitive and behavioral impairment that significantly impairs a patient's social and occupational functioning. The predominant AD pathogenesis hypothesis suggests that AD is largely caused by the accumulation of insoluble amyloid beta deposits and neurofibrillary tangles induced by highly phosphorylated tau proteins in the neocortex, hippocampus, and amygdala, as well as significant loss of neurons and synapses, which leads to brain atrophy. Estimates suggest that approximately 6.2 million people ≥ 65 years of age have AD and that by 2060, the number of Americans with AD may increase to 13.8 million, the result of an aging population and the lack of effective prevention and treatment strategies. AD is a chronic disease that confers tremendous emotional and economic burdens to individuals, families, and society.
Insidiously progressive memory loss is commonly seen in patients presenting with AD. As the disease progresses over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes are also observed in many individuals with AD.
Criteria for the clinical diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are frequently employed. Among individuals who meet the core clinical criteria for probable AD dementia, biomarker evidence may help to increase the certainty that AD is the basis of the clinical dementia syndrome. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid beta for AD. Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD as it enables accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT may be used when MRI is not possible, such as in a patient with a pacemaker.
PET is increasingly being used as a noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, the US Food and Drug Administration approved the first tau PET tracer, 18F-flortaucipir, a significant achievement in improving AD diagnosis.
Currently, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-d-aspartate antagonist are the standard medical treatment for AD. Recently approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021; and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials.
Psychotropic agents are often used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, which can be problematic. Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.
Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.
Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.
Jasvinder Chawla, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of Alzheimer's disease (AD).
AD is the most common type of dementia. It is characterized by cognitive and behavioral impairment that significantly impairs a patient's social and occupational functioning. The predominant AD pathogenesis hypothesis suggests that AD is largely caused by the accumulation of insoluble amyloid beta deposits and neurofibrillary tangles induced by highly phosphorylated tau proteins in the neocortex, hippocampus, and amygdala, as well as significant loss of neurons and synapses, which leads to brain atrophy. Estimates suggest that approximately 6.2 million people ≥ 65 years of age have AD and that by 2060, the number of Americans with AD may increase to 13.8 million, the result of an aging population and the lack of effective prevention and treatment strategies. AD is a chronic disease that confers tremendous emotional and economic burdens to individuals, families, and society.
Insidiously progressive memory loss is commonly seen in patients presenting with AD. As the disease progresses over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes are also observed in many individuals with AD.
Criteria for the clinical diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are frequently employed. Among individuals who meet the core clinical criteria for probable AD dementia, biomarker evidence may help to increase the certainty that AD is the basis of the clinical dementia syndrome. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid beta for AD. Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD as it enables accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT may be used when MRI is not possible, such as in a patient with a pacemaker.
PET is increasingly being used as a noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, the US Food and Drug Administration approved the first tau PET tracer, 18F-flortaucipir, a significant achievement in improving AD diagnosis.
Currently, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-d-aspartate antagonist are the standard medical treatment for AD. Recently approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021; and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials.
Psychotropic agents are often used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, which can be problematic. Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.
Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.
Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.
Jasvinder Chawla, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of Alzheimer's disease (AD).
AD is the most common type of dementia. It is characterized by cognitive and behavioral impairment that significantly impairs a patient's social and occupational functioning. The predominant AD pathogenesis hypothesis suggests that AD is largely caused by the accumulation of insoluble amyloid beta deposits and neurofibrillary tangles induced by highly phosphorylated tau proteins in the neocortex, hippocampus, and amygdala, as well as significant loss of neurons and synapses, which leads to brain atrophy. Estimates suggest that approximately 6.2 million people ≥ 65 years of age have AD and that by 2060, the number of Americans with AD may increase to 13.8 million, the result of an aging population and the lack of effective prevention and treatment strategies. AD is a chronic disease that confers tremendous emotional and economic burdens to individuals, families, and society.
Insidiously progressive memory loss is commonly seen in patients presenting with AD. As the disease progresses over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes are also observed in many individuals with AD.
Criteria for the clinical diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are frequently employed. Among individuals who meet the core clinical criteria for probable AD dementia, biomarker evidence may help to increase the certainty that AD is the basis of the clinical dementia syndrome. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid beta for AD. Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD as it enables accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT may be used when MRI is not possible, such as in a patient with a pacemaker.
PET is increasingly being used as a noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, the US Food and Drug Administration approved the first tau PET tracer, 18F-flortaucipir, a significant achievement in improving AD diagnosis.
Currently, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-d-aspartate antagonist are the standard medical treatment for AD. Recently approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021; and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials.
Psychotropic agents are often used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, which can be problematic. Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.
Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.
Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.
Jasvinder Chawla, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 73-year-old male restaurant manager presents with concerns of progressively worsening cognitive impairment. The patient's symptoms began approximately 2 years ago. At that time, he attributed them to normal aging. Recently, however, he has begun to have increasing difficulties at work. On several occasions, he has forgotten to place important supply orders and has made errors with staff scheduling. His wife reports that he frequently misplaces items at home, such as his cell phone and car keys, and has been experiencing noticeable deficits with his short-term memory. In addition, he has been "unlike himself" for quite some time, with uncharacteristic episodes of depression, anxiety, and emotional lability. The patient's past medical history is significant for mild obesity, hypertension, and dyslipidemia. There is no history of neurotoxic exposure, head injuries, strokes, or seizures. His family history is negative for dementia. Current medications include rosuvastatin 40 mg/d and metoprolol 100 mg/d. His current height and weight are 5 ft 11 in and 223 lb (BMI 31.1).
No abnormalities are noted on physical exam; the patient's blood pressure, pulse oximetry, and heart rate are within normal ranges. Laboratory tests are within normal ranges, except for elevated levels of fasting blood glucose level (119 mg/dL) and A1c (6.3%). The patient scores 19 on the Montreal Cognitive Assessment test. His clinician orders MRI scanning, which reveals generalized atrophy of brain tissue and an accentuated loss of tissue involving the temporal lobes.
Moderate to severe back pain
The history and findings in this case are suggestive of axial psoriatic arthritis (PsA).
Psoriasis is a complex, chronic, inflammatory, immune-mediated disease that is associated with significant morbidity, reduced quality of life, and increased mortality. Approximately 7.4 million adults in the United States have psoriasis; worldwide, approximately 2%-3% of the population is affected. Patients with psoriasis frequently have comorbidities; PsA, an inflammatory, seronegative musculoskeletal disease, is among the most common. It is estimated that 25%-30% of patients with psoriasis develop PsA.
PsA is a heterogeneous disease. Patients may present with nail and skin changes, peripheral arthritis, enthesitis, dactylitis, and axial spondyloarthritis (SpA), either alone or in combination. Men and women are equally affected by PsA, which typically develops when patients are age 30-50 years. Like psoriasis, PsA is associated with numerous comorbidities, including cardiovascular disease, metabolic syndrome, obesity, diabetes, depression, uveitis, and anxiety.
PsA is a potentially erosive disease. Structural damage and functional impairment occurs within 2 years of initial assessment in approximately 50% of patients; as the disease progresses, patients may experience irreversible joint damage and disability. Axial involvement occurs in 25%-70% of patients with PsA; exclusive axial involvement is uncommon, occurring in 5% of patients. Common symptoms of axial PsA include inflammatory back pain (eg, pain that improves with activity but worsens with rest, morning stiffness lasting longer than 30 minutes). Some patients with axial involvement may be asymptomatic. If untreated, cervical spinal mobility and lateral flexion significantly decline within 5 years in patients with axial PsA. In addition, sacroiliitis worsens over time; 37% and 52% of patients develop grade 2 or higher sacroiliitis within 5 and 10 years, respectively. This highlights the importance of early identification and treatment of patients with axial PsA.
The diagnosis of axial PsA is confirmed by physical examination and imaging. Axial PsA characteristics, including sacroiliitis and spondylitis, are distinguished by the development of syndesmophytes (ie, ossification of the annulus fibrosis). PsA can be differentiated from ankylosing spondylitis by the asymmetric and frequently unilateral presentation of sacroiliitis and syndesmophytes, which frequently presents as nonmarginal, bulky, asymmetric, and discontinuous skipping vertebral levels.
Plain radiography, CT, ultrasound, and MRI are all useful tools for evaluating patients with PsA. MRI and ultrasound may be more sensitive than plain radiography is for detecting early joint inflammation and damage as well as axial changes, including sacroiliitis; however, they are not required for a diagnosis of PsA.
The treatment of axial PsA is based on international guidelines developed by the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Assessment of SpondyloArthritis International Society–European League Against Rheumatism. Treatment focuses on minimizing pain, stiffness, and fatigue; improving and preserving spinal flexibility and posture; enhancing functional capacity; and maintaining the ability to work, with a target of remission or minimal/low disease activity.
Medications for symptomatic relief include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and sacroiliac joint injections with glucocorticoids for mild disease; however, long-term treatment with systemic glucocorticoids is not recommended. If patients remain symptomatic or if erosive disease or other indications of high disease activity is observed, guidelines recommend initiation of a TNF inhibitor. Disease-modifying antirheumatic drugs, such as methotrexate, are not routinely prescribed for patients with axial disease because they have not been shown to be effective.
If symptoms of axial PsA are not controlled by NSAIDs, tumor necrosis factor (TNF) inhibitors are recommended. However, interleukin 17A inhibitors may be used in preference to TNF inhibitors in patients with significant skin involvement. In the United States, adalimumab, certolizumab pegol, golimumab, and infliximab are recommended over etanercept for patients with axial SpA in the presence of concomitant inflammatory bowel disease (IBD) or recurrent uveitis (although there is no evidence for golimumab) because etanercept has contradictory results for uveitis and has not been shown to have efficacy in IBD.
If patients fail to respond to a first trial of a TNF inhibitor, trying a second TNF inhibitor before switching to a different class of biologic is recommended by US guidelines. A Janus kinase inhibitor (tofacitinib) may be considered for patients who do not respond to TNF inhibitors.
Nonpharmacologic therapies (ie, exercise, physical therapy, massage therapy, occupational therapy, acupuncture) are recommended for all patients with active PsA.
Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.
Herbert S. Diamond, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of axial psoriatic arthritis (PsA).
Psoriasis is a complex, chronic, inflammatory, immune-mediated disease that is associated with significant morbidity, reduced quality of life, and increased mortality. Approximately 7.4 million adults in the United States have psoriasis; worldwide, approximately 2%-3% of the population is affected. Patients with psoriasis frequently have comorbidities; PsA, an inflammatory, seronegative musculoskeletal disease, is among the most common. It is estimated that 25%-30% of patients with psoriasis develop PsA.
PsA is a heterogeneous disease. Patients may present with nail and skin changes, peripheral arthritis, enthesitis, dactylitis, and axial spondyloarthritis (SpA), either alone or in combination. Men and women are equally affected by PsA, which typically develops when patients are age 30-50 years. Like psoriasis, PsA is associated with numerous comorbidities, including cardiovascular disease, metabolic syndrome, obesity, diabetes, depression, uveitis, and anxiety.
PsA is a potentially erosive disease. Structural damage and functional impairment occurs within 2 years of initial assessment in approximately 50% of patients; as the disease progresses, patients may experience irreversible joint damage and disability. Axial involvement occurs in 25%-70% of patients with PsA; exclusive axial involvement is uncommon, occurring in 5% of patients. Common symptoms of axial PsA include inflammatory back pain (eg, pain that improves with activity but worsens with rest, morning stiffness lasting longer than 30 minutes). Some patients with axial involvement may be asymptomatic. If untreated, cervical spinal mobility and lateral flexion significantly decline within 5 years in patients with axial PsA. In addition, sacroiliitis worsens over time; 37% and 52% of patients develop grade 2 or higher sacroiliitis within 5 and 10 years, respectively. This highlights the importance of early identification and treatment of patients with axial PsA.
The diagnosis of axial PsA is confirmed by physical examination and imaging. Axial PsA characteristics, including sacroiliitis and spondylitis, are distinguished by the development of syndesmophytes (ie, ossification of the annulus fibrosis). PsA can be differentiated from ankylosing spondylitis by the asymmetric and frequently unilateral presentation of sacroiliitis and syndesmophytes, which frequently presents as nonmarginal, bulky, asymmetric, and discontinuous skipping vertebral levels.
Plain radiography, CT, ultrasound, and MRI are all useful tools for evaluating patients with PsA. MRI and ultrasound may be more sensitive than plain radiography is for detecting early joint inflammation and damage as well as axial changes, including sacroiliitis; however, they are not required for a diagnosis of PsA.
The treatment of axial PsA is based on international guidelines developed by the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Assessment of SpondyloArthritis International Society–European League Against Rheumatism. Treatment focuses on minimizing pain, stiffness, and fatigue; improving and preserving spinal flexibility and posture; enhancing functional capacity; and maintaining the ability to work, with a target of remission or minimal/low disease activity.
Medications for symptomatic relief include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and sacroiliac joint injections with glucocorticoids for mild disease; however, long-term treatment with systemic glucocorticoids is not recommended. If patients remain symptomatic or if erosive disease or other indications of high disease activity is observed, guidelines recommend initiation of a TNF inhibitor. Disease-modifying antirheumatic drugs, such as methotrexate, are not routinely prescribed for patients with axial disease because they have not been shown to be effective.
If symptoms of axial PsA are not controlled by NSAIDs, tumor necrosis factor (TNF) inhibitors are recommended. However, interleukin 17A inhibitors may be used in preference to TNF inhibitors in patients with significant skin involvement. In the United States, adalimumab, certolizumab pegol, golimumab, and infliximab are recommended over etanercept for patients with axial SpA in the presence of concomitant inflammatory bowel disease (IBD) or recurrent uveitis (although there is no evidence for golimumab) because etanercept has contradictory results for uveitis and has not been shown to have efficacy in IBD.
If patients fail to respond to a first trial of a TNF inhibitor, trying a second TNF inhibitor before switching to a different class of biologic is recommended by US guidelines. A Janus kinase inhibitor (tofacitinib) may be considered for patients who do not respond to TNF inhibitors.
Nonpharmacologic therapies (ie, exercise, physical therapy, massage therapy, occupational therapy, acupuncture) are recommended for all patients with active PsA.
Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.
Herbert S. Diamond, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of axial psoriatic arthritis (PsA).
Psoriasis is a complex, chronic, inflammatory, immune-mediated disease that is associated with significant morbidity, reduced quality of life, and increased mortality. Approximately 7.4 million adults in the United States have psoriasis; worldwide, approximately 2%-3% of the population is affected. Patients with psoriasis frequently have comorbidities; PsA, an inflammatory, seronegative musculoskeletal disease, is among the most common. It is estimated that 25%-30% of patients with psoriasis develop PsA.
PsA is a heterogeneous disease. Patients may present with nail and skin changes, peripheral arthritis, enthesitis, dactylitis, and axial spondyloarthritis (SpA), either alone or in combination. Men and women are equally affected by PsA, which typically develops when patients are age 30-50 years. Like psoriasis, PsA is associated with numerous comorbidities, including cardiovascular disease, metabolic syndrome, obesity, diabetes, depression, uveitis, and anxiety.
PsA is a potentially erosive disease. Structural damage and functional impairment occurs within 2 years of initial assessment in approximately 50% of patients; as the disease progresses, patients may experience irreversible joint damage and disability. Axial involvement occurs in 25%-70% of patients with PsA; exclusive axial involvement is uncommon, occurring in 5% of patients. Common symptoms of axial PsA include inflammatory back pain (eg, pain that improves with activity but worsens with rest, morning stiffness lasting longer than 30 minutes). Some patients with axial involvement may be asymptomatic. If untreated, cervical spinal mobility and lateral flexion significantly decline within 5 years in patients with axial PsA. In addition, sacroiliitis worsens over time; 37% and 52% of patients develop grade 2 or higher sacroiliitis within 5 and 10 years, respectively. This highlights the importance of early identification and treatment of patients with axial PsA.
The diagnosis of axial PsA is confirmed by physical examination and imaging. Axial PsA characteristics, including sacroiliitis and spondylitis, are distinguished by the development of syndesmophytes (ie, ossification of the annulus fibrosis). PsA can be differentiated from ankylosing spondylitis by the asymmetric and frequently unilateral presentation of sacroiliitis and syndesmophytes, which frequently presents as nonmarginal, bulky, asymmetric, and discontinuous skipping vertebral levels.
Plain radiography, CT, ultrasound, and MRI are all useful tools for evaluating patients with PsA. MRI and ultrasound may be more sensitive than plain radiography is for detecting early joint inflammation and damage as well as axial changes, including sacroiliitis; however, they are not required for a diagnosis of PsA.
The treatment of axial PsA is based on international guidelines developed by the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Assessment of SpondyloArthritis International Society–European League Against Rheumatism. Treatment focuses on minimizing pain, stiffness, and fatigue; improving and preserving spinal flexibility and posture; enhancing functional capacity; and maintaining the ability to work, with a target of remission or minimal/low disease activity.
Medications for symptomatic relief include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and sacroiliac joint injections with glucocorticoids for mild disease; however, long-term treatment with systemic glucocorticoids is not recommended. If patients remain symptomatic or if erosive disease or other indications of high disease activity is observed, guidelines recommend initiation of a TNF inhibitor. Disease-modifying antirheumatic drugs, such as methotrexate, are not routinely prescribed for patients with axial disease because they have not been shown to be effective.
If symptoms of axial PsA are not controlled by NSAIDs, tumor necrosis factor (TNF) inhibitors are recommended. However, interleukin 17A inhibitors may be used in preference to TNF inhibitors in patients with significant skin involvement. In the United States, adalimumab, certolizumab pegol, golimumab, and infliximab are recommended over etanercept for patients with axial SpA in the presence of concomitant inflammatory bowel disease (IBD) or recurrent uveitis (although there is no evidence for golimumab) because etanercept has contradictory results for uveitis and has not been shown to have efficacy in IBD.
If patients fail to respond to a first trial of a TNF inhibitor, trying a second TNF inhibitor before switching to a different class of biologic is recommended by US guidelines. A Janus kinase inhibitor (tofacitinib) may be considered for patients who do not respond to TNF inhibitors.
Nonpharmacologic therapies (ie, exercise, physical therapy, massage therapy, occupational therapy, acupuncture) are recommended for all patients with active PsA.
Herbert S. Diamond, MD, Professor of Medicine (retired), Temple University School of Medicine, University of Pittsburgh; Chairman, Department of Medicine Emeritus, Western Pennsylvania Hospital, Pittsburgh, PA.
Herbert S. Diamond, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 38-year-old nonsmoking woman presents with complaints of moderate to severe back pain of approximately 6 months' duration. She also reports morning back/neck stiffness that lasts for approximately 45 minutes and pain/stiffness in her wrists and fingers. The patient states that her back pain improves with exercise (walking and stretching) and worsens in the evening and during long periods of rest. On occasion, she is awakened during the early morning hours because of her back pain. The patient has a 15-year history of moderate to severe psoriasis and a history of irritable bowel disease (IBD). Current medications include cyclosporine 3 mg/d, topical roflumilast 0.3%/d, and loperamide 3 mg as needed. The patient is 5 ft 5 in and weighs 183 lb (BMI of 30.4).
Physical examination reveals psoriatic plaques on the hands, elbows, and knees and nail dystrophy (onycholysis and pitting). Vital signs are within normal ranges. Pertinent laboratory findings include white blood count of 12,000 mcL (> 50% polymorphonuclear leukocytes), erythrocyte sedimentation rate of 19 mm/h, and c-reactive protein of 3 mg/dL. Rheumatoid factor, antinuclear antibody, and anti-citrullinated protein antibody antibody were negative.
Weight gain and excessive fatigue
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Cushing syndrome (CS).
CS is a rare endocrine disease caused by prolonged exposure to high circulating cortisol levels. Exogenous hypercortisolism is the most common cause of CS. It is largely iatrogenic and results from the prolonged use of glucocorticoids. Less frequently, endogenous CS may occur as the result of excessive production of cortisol by adrenal glands. Endogenous CS can be ACTH-dependent or ACTH-independent. ACTH-dependent CS results from ACTH-secreting pituitary adenomas (Cushing disease) and ectopic ACTH secretion by neoplasms, whereas adrenal hyperplasia, adenoma, and carcinoma are the primary causes of ACTH-independent CS.
The annual incidence and prevalence of CS are unknown; the reported incidence of newly diagnosed cases has ranged from 1.2 to 2.4 per million people per year. Women are affected more often than are men, with a peak of incidence in the third to fourth decade of life. CS is associated with various metabolic, psychiatric, musculoskeletal, and cardiovascular comorbidities. Untreated, it is associated with increased mortality, typically as the result of cardiovascular and infectious complications; however, even in appropriately treated patients, mortality is elevated.
The chronic elevations of glucocorticoid concentrations in CS result in its characteristic phenotype, which includes weight gain, moon-shaped face, buffalo hump, muscle weakness, increased bruising, skin atrophy, red abdominal striae, menstrual irregularities, hirsutism, and acne. It is also associated with numerous comorbidities including diabetes, hypertension, hypercholesterolemia, and osteoporosis. Patients often experience mental health complications, such as depression, emotional lability, and cognitive dysfunction.
Given the rarity of CS and the fact that these symptoms overlap with other conditions, delayed diagnosis is common. The current obesity epidemic also poses diagnostic challenges because true CS can be difficult to differentiate from metabolic syndrome. The duration of hypercortisolism appears to be the most significant factor associated with the degree of morbidity and preterm mortality in CS; thus, an accurate diagnosis as early as possible is important.
Screening and diagnostic tests for CS evaluate cortisol secretion. Available options include late-night salivary cortisol (LNSC), impaired glucocorticoid feedback with overnight 1-mg DST or low-dose 2-day dexamethasone test (LDDT) and increased bioavailable cortisol with 24-hour UFC.
A 2021 consensus statement by Fleseriu and colleagues provides recommendations for the diagnosis of CS. If CS is suspected: begin with UFC, LNSC, or both; DST is an option if LNSC not feasible. If CS because of adrenal tumor is suspected: begin with DST because LNSC has lower specificity in these patients. To confirm CS, any of these tests can be used.
An individualized approach is recommended for the treatment of CS. The optimal approach for iatrogenic CS is to slowly taper exogenous steroids. Chronic exposure to steroids can suppress adrenal functioning; as such, recovery may take several months. Surgical resection is the first-line option for hypercortisolism because of Cushing disease, adrenal tumor, or ectopic tumor. Patients should be closely monitored after surgery to evaluate for possible recurrence. Radiotherapy may be recommended after failed transsphenoidal surgery or in Cushing disease with mass effect or invasion of surrounding structures. Medical therapy, such as pasireotide, cabergoline, and mifepristone, are also sometimes used. In addition, the treatment of comorbidities, such as obesity and type 2 diabetes, hypertension, osteoporosis, psychiatric issues, and electrolyte disorders, is critical.
Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.
Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Cushing syndrome (CS).
CS is a rare endocrine disease caused by prolonged exposure to high circulating cortisol levels. Exogenous hypercortisolism is the most common cause of CS. It is largely iatrogenic and results from the prolonged use of glucocorticoids. Less frequently, endogenous CS may occur as the result of excessive production of cortisol by adrenal glands. Endogenous CS can be ACTH-dependent or ACTH-independent. ACTH-dependent CS results from ACTH-secreting pituitary adenomas (Cushing disease) and ectopic ACTH secretion by neoplasms, whereas adrenal hyperplasia, adenoma, and carcinoma are the primary causes of ACTH-independent CS.
The annual incidence and prevalence of CS are unknown; the reported incidence of newly diagnosed cases has ranged from 1.2 to 2.4 per million people per year. Women are affected more often than are men, with a peak of incidence in the third to fourth decade of life. CS is associated with various metabolic, psychiatric, musculoskeletal, and cardiovascular comorbidities. Untreated, it is associated with increased mortality, typically as the result of cardiovascular and infectious complications; however, even in appropriately treated patients, mortality is elevated.
The chronic elevations of glucocorticoid concentrations in CS result in its characteristic phenotype, which includes weight gain, moon-shaped face, buffalo hump, muscle weakness, increased bruising, skin atrophy, red abdominal striae, menstrual irregularities, hirsutism, and acne. It is also associated with numerous comorbidities including diabetes, hypertension, hypercholesterolemia, and osteoporosis. Patients often experience mental health complications, such as depression, emotional lability, and cognitive dysfunction.
Given the rarity of CS and the fact that these symptoms overlap with other conditions, delayed diagnosis is common. The current obesity epidemic also poses diagnostic challenges because true CS can be difficult to differentiate from metabolic syndrome. The duration of hypercortisolism appears to be the most significant factor associated with the degree of morbidity and preterm mortality in CS; thus, an accurate diagnosis as early as possible is important.
Screening and diagnostic tests for CS evaluate cortisol secretion. Available options include late-night salivary cortisol (LNSC), impaired glucocorticoid feedback with overnight 1-mg DST or low-dose 2-day dexamethasone test (LDDT) and increased bioavailable cortisol with 24-hour UFC.
A 2021 consensus statement by Fleseriu and colleagues provides recommendations for the diagnosis of CS. If CS is suspected: begin with UFC, LNSC, or both; DST is an option if LNSC not feasible. If CS because of adrenal tumor is suspected: begin with DST because LNSC has lower specificity in these patients. To confirm CS, any of these tests can be used.
An individualized approach is recommended for the treatment of CS. The optimal approach for iatrogenic CS is to slowly taper exogenous steroids. Chronic exposure to steroids can suppress adrenal functioning; as such, recovery may take several months. Surgical resection is the first-line option for hypercortisolism because of Cushing disease, adrenal tumor, or ectopic tumor. Patients should be closely monitored after surgery to evaluate for possible recurrence. Radiotherapy may be recommended after failed transsphenoidal surgery or in Cushing disease with mass effect or invasion of surrounding structures. Medical therapy, such as pasireotide, cabergoline, and mifepristone, are also sometimes used. In addition, the treatment of comorbidities, such as obesity and type 2 diabetes, hypertension, osteoporosis, psychiatric issues, and electrolyte disorders, is critical.
Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.
Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Cushing syndrome (CS).
CS is a rare endocrine disease caused by prolonged exposure to high circulating cortisol levels. Exogenous hypercortisolism is the most common cause of CS. It is largely iatrogenic and results from the prolonged use of glucocorticoids. Less frequently, endogenous CS may occur as the result of excessive production of cortisol by adrenal glands. Endogenous CS can be ACTH-dependent or ACTH-independent. ACTH-dependent CS results from ACTH-secreting pituitary adenomas (Cushing disease) and ectopic ACTH secretion by neoplasms, whereas adrenal hyperplasia, adenoma, and carcinoma are the primary causes of ACTH-independent CS.
The annual incidence and prevalence of CS are unknown; the reported incidence of newly diagnosed cases has ranged from 1.2 to 2.4 per million people per year. Women are affected more often than are men, with a peak of incidence in the third to fourth decade of life. CS is associated with various metabolic, psychiatric, musculoskeletal, and cardiovascular comorbidities. Untreated, it is associated with increased mortality, typically as the result of cardiovascular and infectious complications; however, even in appropriately treated patients, mortality is elevated.
The chronic elevations of glucocorticoid concentrations in CS result in its characteristic phenotype, which includes weight gain, moon-shaped face, buffalo hump, muscle weakness, increased bruising, skin atrophy, red abdominal striae, menstrual irregularities, hirsutism, and acne. It is also associated with numerous comorbidities including diabetes, hypertension, hypercholesterolemia, and osteoporosis. Patients often experience mental health complications, such as depression, emotional lability, and cognitive dysfunction.
Given the rarity of CS and the fact that these symptoms overlap with other conditions, delayed diagnosis is common. The current obesity epidemic also poses diagnostic challenges because true CS can be difficult to differentiate from metabolic syndrome. The duration of hypercortisolism appears to be the most significant factor associated with the degree of morbidity and preterm mortality in CS; thus, an accurate diagnosis as early as possible is important.
Screening and diagnostic tests for CS evaluate cortisol secretion. Available options include late-night salivary cortisol (LNSC), impaired glucocorticoid feedback with overnight 1-mg DST or low-dose 2-day dexamethasone test (LDDT) and increased bioavailable cortisol with 24-hour UFC.
A 2021 consensus statement by Fleseriu and colleagues provides recommendations for the diagnosis of CS. If CS is suspected: begin with UFC, LNSC, or both; DST is an option if LNSC not feasible. If CS because of adrenal tumor is suspected: begin with DST because LNSC has lower specificity in these patients. To confirm CS, any of these tests can be used.
An individualized approach is recommended for the treatment of CS. The optimal approach for iatrogenic CS is to slowly taper exogenous steroids. Chronic exposure to steroids can suppress adrenal functioning; as such, recovery may take several months. Surgical resection is the first-line option for hypercortisolism because of Cushing disease, adrenal tumor, or ectopic tumor. Patients should be closely monitored after surgery to evaluate for possible recurrence. Radiotherapy may be recommended after failed transsphenoidal surgery or in Cushing disease with mass effect or invasion of surrounding structures. Medical therapy, such as pasireotide, cabergoline, and mifepristone, are also sometimes used. In addition, the treatment of comorbidities, such as obesity and type 2 diabetes, hypertension, osteoporosis, psychiatric issues, and electrolyte disorders, is critical.
Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.
Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 37-year-old woman presents with reports of insomnia, weight gain (approximately 12 lb over the last 9 months), and excessive fatigue. The patient's medical history is significant for hypertension (diagnosed 4 years earlier) and depression (diagnosed 7 years earlier). Her current medications include lisinopril 10 mg/d, bupropion 75 mg/d, and venlafaxine 75 mg/d. There is no history of alcohol or drug abuse; family history is unremarkable. The patient's height and weight are 5 ft 5 in and 182 lb (body mass index of 30.3).
During physical examination, facial hirsutism is observed along with increased adipose tissue in the face (moon-shaped face), upper back at the base of the neck (buffalo hump), and abdomen. Vertical red abdominal striae are present. Several bruises are observed on the patient's thighs and arms; when questioned, she reports noting an increased tendency to bruise in recent months.
Pertinent laboratory findings include urinary free cortisol excretion (UFC) 324 mcg/24 h, 1-mg dexamethasone suppression test (DST) with a cortisol value of 3.64 mcg/dL (100.42 nmol/L), and adrenocorticotropic hormone (ACTH) level of 84.9 pg/mL.
Three-month history of fever
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of pleomorphic mantle cell lymphoma (MCL).
MCL is a rare, clinically and biologically heterogeneous B-cell non-Hodgkin lymphoma. It accounts for approximately 5%-7% of all lymphomas. In North America and Europe, its incidence is akin to that of noncutaneous, peripheral T-cell lymphomas. The typical age at diagnosis is between 60 and 70 years. Approximately 70% of all cases are seen in men.
Little is known about risk factors for the development of MCL. Factors that have been associated with the development of other lymphomas (eg, familial risk, immunosuppression, other immune disorders, chemical and occupational exposures, and infectious agents) have not been convincingly identified as predisposing factors for MCL, with the possible exception of family history.
MCL is usually associated with reciprocal chromosomal translocation between chromosomes 11 and 14, t(11;14)(q13:q32), resulting in overexpression of cyclin D1, which plays a key role in tumor cell proliferation through cell-cycle dysregulation, chromosomal instability, and epigenetic regulation. Tumor cells (monoclonal B cells) express surface immunoglobulin, immunoglobulin M, or immunoglobulin D. Cells are usually CD5+ and pan B-cell antigen positive (eg, CD19, CD20, CD22) with no expression of CD10 and CD23. Histologic features include small-to-medium lymphocytes with scant cytoplasm, clumped chromatin, inconspicuous nucleoli, and prominent nuclear clefts. Cytologic subtypes include classic MCL, the blastoid variant (large cells, dispersed chromatin, and a high mitotic rate), and the pleomorphic variant (cells of varying size, although many are large, with pale cytoplasm, oval irregular nuclei, and prominent nucleoli). Blastoid and pleomorphic MCL typically have a more aggressive natural history and are associated with inferior clinical outcomes.
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), an accurate pathologic diagnosis of the subtype is the most important initial step in the management of B-cell lymphomas, including pleomorphic MCL. The basic pathologic exam is the same for all subtypes, although additional testing may be needed in certain cases. An incisional or excisional lymph node biopsy is recommended. Fine-needle aspiration biopsy alone is typically not sufficient for the initial diagnosis of lymphoma; however, its diagnostic accuracy is significantly improved when it is used in combination with immunohistochemistry and flow cytometry. Immunohistochemistry is essential to differentiate MCL subtypes.
Essential workup procedures include a complete physical exam, with particular attention to node-bearing areas, including the Waldeyer ring, as well as the size of the liver and spleen, and assessment of performance status and B symptoms (fever, night sweats, unintentional weight loss). Laboratory studies should include complete blood count with differential, measurement of serum lactate dehydrogenase, hepatitis B virus testing, and a comprehensive metabolic panel. Required imaging studies include PET/CT (or chest/abdominal/pelvic CT with oral and intravenous contrast if PET/CT is not available) and multigated acquisition scanning or echocardiography when anthracyclines and anthracenedione-containing regimens are indicated.
A watch-and-wait approach may be appropriate for some patients with indolent MCL; however, patients with aggressive MCL, such as pleomorphic histology, require chemoimmunotherapy at diagnosis. For patients who relapse or achieve an incomplete response to first-line therapy, the NCCN guidelines recommend second-line treatment with a Bruton tyrosine kinase (BTK) inhibitor–containing regimen. Available BTK inhibitors include acalabrutinib, ibrutinib ± rituximab, zanubrutinib, and pirtobrutinib. Chemoimmunotherapy with lenalidomide + rituximab is another second-line option and may be particularly helpful for patients in whom a BTK inhibitor is contraindicated. Anti-CD19 CAR T-cell therapy is a recommended option for the third line and beyond.
Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.
Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of pleomorphic mantle cell lymphoma (MCL).
MCL is a rare, clinically and biologically heterogeneous B-cell non-Hodgkin lymphoma. It accounts for approximately 5%-7% of all lymphomas. In North America and Europe, its incidence is akin to that of noncutaneous, peripheral T-cell lymphomas. The typical age at diagnosis is between 60 and 70 years. Approximately 70% of all cases are seen in men.
Little is known about risk factors for the development of MCL. Factors that have been associated with the development of other lymphomas (eg, familial risk, immunosuppression, other immune disorders, chemical and occupational exposures, and infectious agents) have not been convincingly identified as predisposing factors for MCL, with the possible exception of family history.
MCL is usually associated with reciprocal chromosomal translocation between chromosomes 11 and 14, t(11;14)(q13:q32), resulting in overexpression of cyclin D1, which plays a key role in tumor cell proliferation through cell-cycle dysregulation, chromosomal instability, and epigenetic regulation. Tumor cells (monoclonal B cells) express surface immunoglobulin, immunoglobulin M, or immunoglobulin D. Cells are usually CD5+ and pan B-cell antigen positive (eg, CD19, CD20, CD22) with no expression of CD10 and CD23. Histologic features include small-to-medium lymphocytes with scant cytoplasm, clumped chromatin, inconspicuous nucleoli, and prominent nuclear clefts. Cytologic subtypes include classic MCL, the blastoid variant (large cells, dispersed chromatin, and a high mitotic rate), and the pleomorphic variant (cells of varying size, although many are large, with pale cytoplasm, oval irregular nuclei, and prominent nucleoli). Blastoid and pleomorphic MCL typically have a more aggressive natural history and are associated with inferior clinical outcomes.
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), an accurate pathologic diagnosis of the subtype is the most important initial step in the management of B-cell lymphomas, including pleomorphic MCL. The basic pathologic exam is the same for all subtypes, although additional testing may be needed in certain cases. An incisional or excisional lymph node biopsy is recommended. Fine-needle aspiration biopsy alone is typically not sufficient for the initial diagnosis of lymphoma; however, its diagnostic accuracy is significantly improved when it is used in combination with immunohistochemistry and flow cytometry. Immunohistochemistry is essential to differentiate MCL subtypes.
Essential workup procedures include a complete physical exam, with particular attention to node-bearing areas, including the Waldeyer ring, as well as the size of the liver and spleen, and assessment of performance status and B symptoms (fever, night sweats, unintentional weight loss). Laboratory studies should include complete blood count with differential, measurement of serum lactate dehydrogenase, hepatitis B virus testing, and a comprehensive metabolic panel. Required imaging studies include PET/CT (or chest/abdominal/pelvic CT with oral and intravenous contrast if PET/CT is not available) and multigated acquisition scanning or echocardiography when anthracyclines and anthracenedione-containing regimens are indicated.
A watch-and-wait approach may be appropriate for some patients with indolent MCL; however, patients with aggressive MCL, such as pleomorphic histology, require chemoimmunotherapy at diagnosis. For patients who relapse or achieve an incomplete response to first-line therapy, the NCCN guidelines recommend second-line treatment with a Bruton tyrosine kinase (BTK) inhibitor–containing regimen. Available BTK inhibitors include acalabrutinib, ibrutinib ± rituximab, zanubrutinib, and pirtobrutinib. Chemoimmunotherapy with lenalidomide + rituximab is another second-line option and may be particularly helpful for patients in whom a BTK inhibitor is contraindicated. Anti-CD19 CAR T-cell therapy is a recommended option for the third line and beyond.
Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.
Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
This patient's clinical presentation and laboratory findings are consistent with a diagnosis of pleomorphic mantle cell lymphoma (MCL).
MCL is a rare, clinically and biologically heterogeneous B-cell non-Hodgkin lymphoma. It accounts for approximately 5%-7% of all lymphomas. In North America and Europe, its incidence is akin to that of noncutaneous, peripheral T-cell lymphomas. The typical age at diagnosis is between 60 and 70 years. Approximately 70% of all cases are seen in men.
Little is known about risk factors for the development of MCL. Factors that have been associated with the development of other lymphomas (eg, familial risk, immunosuppression, other immune disorders, chemical and occupational exposures, and infectious agents) have not been convincingly identified as predisposing factors for MCL, with the possible exception of family history.
MCL is usually associated with reciprocal chromosomal translocation between chromosomes 11 and 14, t(11;14)(q13:q32), resulting in overexpression of cyclin D1, which plays a key role in tumor cell proliferation through cell-cycle dysregulation, chromosomal instability, and epigenetic regulation. Tumor cells (monoclonal B cells) express surface immunoglobulin, immunoglobulin M, or immunoglobulin D. Cells are usually CD5+ and pan B-cell antigen positive (eg, CD19, CD20, CD22) with no expression of CD10 and CD23. Histologic features include small-to-medium lymphocytes with scant cytoplasm, clumped chromatin, inconspicuous nucleoli, and prominent nuclear clefts. Cytologic subtypes include classic MCL, the blastoid variant (large cells, dispersed chromatin, and a high mitotic rate), and the pleomorphic variant (cells of varying size, although many are large, with pale cytoplasm, oval irregular nuclei, and prominent nucleoli). Blastoid and pleomorphic MCL typically have a more aggressive natural history and are associated with inferior clinical outcomes.
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), an accurate pathologic diagnosis of the subtype is the most important initial step in the management of B-cell lymphomas, including pleomorphic MCL. The basic pathologic exam is the same for all subtypes, although additional testing may be needed in certain cases. An incisional or excisional lymph node biopsy is recommended. Fine-needle aspiration biopsy alone is typically not sufficient for the initial diagnosis of lymphoma; however, its diagnostic accuracy is significantly improved when it is used in combination with immunohistochemistry and flow cytometry. Immunohistochemistry is essential to differentiate MCL subtypes.
Essential workup procedures include a complete physical exam, with particular attention to node-bearing areas, including the Waldeyer ring, as well as the size of the liver and spleen, and assessment of performance status and B symptoms (fever, night sweats, unintentional weight loss). Laboratory studies should include complete blood count with differential, measurement of serum lactate dehydrogenase, hepatitis B virus testing, and a comprehensive metabolic panel. Required imaging studies include PET/CT (or chest/abdominal/pelvic CT with oral and intravenous contrast if PET/CT is not available) and multigated acquisition scanning or echocardiography when anthracyclines and anthracenedione-containing regimens are indicated.
A watch-and-wait approach may be appropriate for some patients with indolent MCL; however, patients with aggressive MCL, such as pleomorphic histology, require chemoimmunotherapy at diagnosis. For patients who relapse or achieve an incomplete response to first-line therapy, the NCCN guidelines recommend second-line treatment with a Bruton tyrosine kinase (BTK) inhibitor–containing regimen. Available BTK inhibitors include acalabrutinib, ibrutinib ± rituximab, zanubrutinib, and pirtobrutinib. Chemoimmunotherapy with lenalidomide + rituximab is another second-line option and may be particularly helpful for patients in whom a BTK inhibitor is contraindicated. Anti-CD19 CAR T-cell therapy is a recommended option for the third line and beyond.
Timothy J. Voorhees, MD, MSCR, Assistant Professor of Internal Medicine - Clinical, Division of Hematology, The Ohio State University James Comprehensive Cancer Center, Columbus, OH.
Timothy J. Voorhees, MD, MSCR, has disclosed the following relevant financial relationships:
Received research grant from: AstraZeneca; Morphosys; Incyte; Recordati.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 62-year-old man with no significant past medical history presents with a 3-month history of fever, night sweats, upper abdominal pain and bloating, and unintentional weight loss. He does not currently take any medications. His height and weight are 6 ft 2 in and 171 lb (BMI 22).
Physical examination reveals generalized lymphadenopathy and splenomegaly. Subsequently, an excisional lymph node biopsy is performed. Histologic examination of the specimen reveals sheets of mostly large cells of varying sizes, with nuclear overlap and extensive necrosis. Cytology findings include large lymphocytes with pale cytoplasm, clumped chromatin, oval irregular nuclei, and prominent nucleoli. Pertinent findings from immunohistochemical staining include the presence of t(11:14), Ki67 > 30%, CD5 and CD20 positivity, and CD10 and CD23 negativity. Centroblasts are absent.
Complaints of cough and fatigue
The history and findings in this case are suggestive of non–small cell lung cancer (NSCLC) large cell carcinoma.
Lung cancer is the most common cancer worldwide and has the highest mortality rate of all cancers. It comprises two major subtypes: NSCLC and small cell lung cancer (SCLC). Histologically, NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma with or without neuroendocrine features. Large cell carcinoma accounts for 9% of all cases and is frequently associated with poor prognosis. Most patients with NSCLC large cell carcinoma are older than 60 years and are diagnosed with stage III or IV disease. NSCLC large cell carcinoma appears to occur more commonly in men than in women and in patients with a history of smoking. It often presents as a large mass with central necrosis.
NSCLC is often asymptomatic in its early stages. The most frequently reported signs and symptoms of lung cancer include:
• Cough
• Chest pain
• Shortness of breath
• Coughing up blood
• Wheezing
• Hoarseness
• Recurring infections, such as bronchitis and pneumonia
• Weight loss and loss of appetite
• Fatigue
Signs and symptoms of metastatic disease may include bone pain, spinal cord impingement, or neurologic problems, such as headache, weakness or numbness of limbs, dizziness, and seizures.
All patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. After physical examination and a complete blood count, a chest radiograph is often the first test performed. Chest radiographs may show a pulmonary nodule, mass, or infiltrate; mediastinal widening; atelectasis; hilar enlargement; and/or pleural effusion.
Various methods are available to confirm the diagnosis, and the method chosen may be determined at least in part by lesion location. These include:
• Bronchoscopy
• Sputum cytology
• Mediastinoscopy
• Thoracentesis
• Thoracoscopy
• Transthoracic needle biopsy (CT- or fluoroscopy-guided)
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), the diagnosis of NSCLC large cell carcinoma requires a thoroughly sampled resected tumor with immunohistochemical stains that exclude adenocarcinoma (TTF-1, napsin A) and squamous cell (p40, p63) carcinoma. Nonresected specimens or cytology specimens are insufficient for its diagnosis. NSCLC large cell carcinoma lacks the cytologic, architectural, and histochemical features of small cell carcinoma, adenocarcinoma, or squamous cell carcinoma and is undifferentiated.
When the NSCLC histologic subtype is determined, molecular testing should be performed as part of broad molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available or to appropriately counsel patients regarding the availability of clinical trials. NSCLC diagnostic standards include the detection of EGFR, BRAF, and MET mutations, ERBB2 (HER2) expression, and the analysis of ALK, ROS1, RET, and NTRK translocations. In addition, analysis of programmed death-ligand 1 expression is necessary to identify patients who may benefit from the use of immune checkpoint inhibitors.
Surgery combined with chemotherapy has been shown to improve the prognosis of patients with NSCLC large cell carcinoma. Preferred regimens in various lines of treatment and according to molecular characteristics can be found in the NCCN guidelines.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.
Karl J. D'Silva, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of non–small cell lung cancer (NSCLC) large cell carcinoma.
Lung cancer is the most common cancer worldwide and has the highest mortality rate of all cancers. It comprises two major subtypes: NSCLC and small cell lung cancer (SCLC). Histologically, NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma with or without neuroendocrine features. Large cell carcinoma accounts for 9% of all cases and is frequently associated with poor prognosis. Most patients with NSCLC large cell carcinoma are older than 60 years and are diagnosed with stage III or IV disease. NSCLC large cell carcinoma appears to occur more commonly in men than in women and in patients with a history of smoking. It often presents as a large mass with central necrosis.
NSCLC is often asymptomatic in its early stages. The most frequently reported signs and symptoms of lung cancer include:
• Cough
• Chest pain
• Shortness of breath
• Coughing up blood
• Wheezing
• Hoarseness
• Recurring infections, such as bronchitis and pneumonia
• Weight loss and loss of appetite
• Fatigue
Signs and symptoms of metastatic disease may include bone pain, spinal cord impingement, or neurologic problems, such as headache, weakness or numbness of limbs, dizziness, and seizures.
All patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. After physical examination and a complete blood count, a chest radiograph is often the first test performed. Chest radiographs may show a pulmonary nodule, mass, or infiltrate; mediastinal widening; atelectasis; hilar enlargement; and/or pleural effusion.
Various methods are available to confirm the diagnosis, and the method chosen may be determined at least in part by lesion location. These include:
• Bronchoscopy
• Sputum cytology
• Mediastinoscopy
• Thoracentesis
• Thoracoscopy
• Transthoracic needle biopsy (CT- or fluoroscopy-guided)
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), the diagnosis of NSCLC large cell carcinoma requires a thoroughly sampled resected tumor with immunohistochemical stains that exclude adenocarcinoma (TTF-1, napsin A) and squamous cell (p40, p63) carcinoma. Nonresected specimens or cytology specimens are insufficient for its diagnosis. NSCLC large cell carcinoma lacks the cytologic, architectural, and histochemical features of small cell carcinoma, adenocarcinoma, or squamous cell carcinoma and is undifferentiated.
When the NSCLC histologic subtype is determined, molecular testing should be performed as part of broad molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available or to appropriately counsel patients regarding the availability of clinical trials. NSCLC diagnostic standards include the detection of EGFR, BRAF, and MET mutations, ERBB2 (HER2) expression, and the analysis of ALK, ROS1, RET, and NTRK translocations. In addition, analysis of programmed death-ligand 1 expression is necessary to identify patients who may benefit from the use of immune checkpoint inhibitors.
Surgery combined with chemotherapy has been shown to improve the prognosis of patients with NSCLC large cell carcinoma. Preferred regimens in various lines of treatment and according to molecular characteristics can be found in the NCCN guidelines.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.
Karl J. D'Silva, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of non–small cell lung cancer (NSCLC) large cell carcinoma.
Lung cancer is the most common cancer worldwide and has the highest mortality rate of all cancers. It comprises two major subtypes: NSCLC and small cell lung cancer (SCLC). Histologically, NSCLC is further classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma with or without neuroendocrine features. Large cell carcinoma accounts for 9% of all cases and is frequently associated with poor prognosis. Most patients with NSCLC large cell carcinoma are older than 60 years and are diagnosed with stage III or IV disease. NSCLC large cell carcinoma appears to occur more commonly in men than in women and in patients with a history of smoking. It often presents as a large mass with central necrosis.
NSCLC is often asymptomatic in its early stages. The most frequently reported signs and symptoms of lung cancer include:
• Cough
• Chest pain
• Shortness of breath
• Coughing up blood
• Wheezing
• Hoarseness
• Recurring infections, such as bronchitis and pneumonia
• Weight loss and loss of appetite
• Fatigue
Signs and symptoms of metastatic disease may include bone pain, spinal cord impingement, or neurologic problems, such as headache, weakness or numbness of limbs, dizziness, and seizures.
All patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a central role in treatment selection. After physical examination and a complete blood count, a chest radiograph is often the first test performed. Chest radiographs may show a pulmonary nodule, mass, or infiltrate; mediastinal widening; atelectasis; hilar enlargement; and/or pleural effusion.
Various methods are available to confirm the diagnosis, and the method chosen may be determined at least in part by lesion location. These include:
• Bronchoscopy
• Sputum cytology
• Mediastinoscopy
• Thoracentesis
• Thoracoscopy
• Transthoracic needle biopsy (CT- or fluoroscopy-guided)
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), the diagnosis of NSCLC large cell carcinoma requires a thoroughly sampled resected tumor with immunohistochemical stains that exclude adenocarcinoma (TTF-1, napsin A) and squamous cell (p40, p63) carcinoma. Nonresected specimens or cytology specimens are insufficient for its diagnosis. NSCLC large cell carcinoma lacks the cytologic, architectural, and histochemical features of small cell carcinoma, adenocarcinoma, or squamous cell carcinoma and is undifferentiated.
When the NSCLC histologic subtype is determined, molecular testing should be performed as part of broad molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available or to appropriately counsel patients regarding the availability of clinical trials. NSCLC diagnostic standards include the detection of EGFR, BRAF, and MET mutations, ERBB2 (HER2) expression, and the analysis of ALK, ROS1, RET, and NTRK translocations. In addition, analysis of programmed death-ligand 1 expression is necessary to identify patients who may benefit from the use of immune checkpoint inhibitors.
Surgery combined with chemotherapy has been shown to improve the prognosis of patients with NSCLC large cell carcinoma. Preferred regimens in various lines of treatment and according to molecular characteristics can be found in the NCCN guidelines.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts.
Karl J. D'Silva, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 67-year-old White man presents to the emergency department with reports of cough, dyspnea, fatigue, hoarseness, and unintentional weight loss. The patient states that his symptoms began approximately 3 weeks earlier and have progressively worsened. In the past year, he has been treated twice for respiratory infections (bronchitis and pneumonia approximately 6 and 9 months before the current presentation, respectively). He has a 45-year history of smoking (45 pack-years). The patient's vital signs include temperature of 100.4 °F, blood pressure of 142/80 mm Hg, and pulse ox of 95%. Physical examination reveals rales in the left side of the chest and decreased breath sounds in bilateral bases of the lungs. The patient appears cachexic. He is 6 ft 2 in and weighs 163 lb.
A chest radiograph reveals a large mass in the left lung field. A subsequent CT of the chest reveals encasement of the left upper and lower lobe bronchus with extensive mediastinal lymphadenopathy and areas of necrosis. Immunohistochemical analysis of the resected tumor reveals a malignant, poorly differentiated epithelial neoplasm composed of large, atypical cells. There is no morphologic or immunohistochemical evidence of glandular, squamous, or neuroendocrine differentiation.
Older woman presents with shortness of breath
Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype, has a poor prognosis, and is highly associated with smoking. It accounts for 10%-15% of all lung cancers. Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever. SCLCs usually grow rapidly and metastasize to mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have very large intrathoracic tumors, and distinguishing the primary tumor from lymph node metastases may be difficult.
CT of all common sites of metastasis should be performed to stage the disease. CT scanning of the thorax (lungs and mediastinum) and commonly involved abdominal viscera is the minimum requirement in standard staging workup of SCLC. Intravenous contrast agents should be used whenever possible. In the United States, CT scans of the chest and upper abdomen to include the liver and adrenal glands are standard. The liver is a common site of metastasis.
Most cases of SCLC will present in advanced stages, be inoperable, and have a dismal prognosis. Only about 5% of patients present at an early stage (Ia, Ib, or IIa). The National Comprehensive Cancer Network (NCCN) guidelines recommend that these patients be managed with aggressive chemoradiation therapy; in some, lobectomy associated with mediastinal lymph node dissection may be performed. The NCCN notes that advanced disease is managed primarily with chemotherapy, mainly for palliation and symptom control. Older patients, such as the current patient, who have a good performance status (ECOG 0 or 1) and intact organ function should receive standard carboplatin-based chemotherapy. However, even those who have poor prognostic factors (eg, poor performance status, medically significant concomitant conditions) may still be considered for chemotherapy if appropriate precautions are taken to avoid excessive toxicity and further decline in performance status.
Unlike non-SCLC, which has seen waves of new drug approvals from the US Food and Drug Administration (FDA), the prognosis for SCLC has not changed substantially in the past two decades and remains poor. However, the FDA approved atezolizumab in combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC. Further, the approval of durvalumab in combination with chemotherapy; and the approval of lurbinectedin, a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the therapeutic options for patients with SCLC.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts
Karl J. D'Silva, MD, has disclosed no relevant financial relationships
Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype, has a poor prognosis, and is highly associated with smoking. It accounts for 10%-15% of all lung cancers. Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever. SCLCs usually grow rapidly and metastasize to mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have very large intrathoracic tumors, and distinguishing the primary tumor from lymph node metastases may be difficult.
CT of all common sites of metastasis should be performed to stage the disease. CT scanning of the thorax (lungs and mediastinum) and commonly involved abdominal viscera is the minimum requirement in standard staging workup of SCLC. Intravenous contrast agents should be used whenever possible. In the United States, CT scans of the chest and upper abdomen to include the liver and adrenal glands are standard. The liver is a common site of metastasis.
Most cases of SCLC will present in advanced stages, be inoperable, and have a dismal prognosis. Only about 5% of patients present at an early stage (Ia, Ib, or IIa). The National Comprehensive Cancer Network (NCCN) guidelines recommend that these patients be managed with aggressive chemoradiation therapy; in some, lobectomy associated with mediastinal lymph node dissection may be performed. The NCCN notes that advanced disease is managed primarily with chemotherapy, mainly for palliation and symptom control. Older patients, such as the current patient, who have a good performance status (ECOG 0 or 1) and intact organ function should receive standard carboplatin-based chemotherapy. However, even those who have poor prognostic factors (eg, poor performance status, medically significant concomitant conditions) may still be considered for chemotherapy if appropriate precautions are taken to avoid excessive toxicity and further decline in performance status.
Unlike non-SCLC, which has seen waves of new drug approvals from the US Food and Drug Administration (FDA), the prognosis for SCLC has not changed substantially in the past two decades and remains poor. However, the FDA approved atezolizumab in combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC. Further, the approval of durvalumab in combination with chemotherapy; and the approval of lurbinectedin, a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the therapeutic options for patients with SCLC.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts
Karl J. D'Silva, MD, has disclosed no relevant financial relationships
Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype, has a poor prognosis, and is highly associated with smoking. It accounts for 10%-15% of all lung cancers. Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever. SCLCs usually grow rapidly and metastasize to mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have very large intrathoracic tumors, and distinguishing the primary tumor from lymph node metastases may be difficult.
CT of all common sites of metastasis should be performed to stage the disease. CT scanning of the thorax (lungs and mediastinum) and commonly involved abdominal viscera is the minimum requirement in standard staging workup of SCLC. Intravenous contrast agents should be used whenever possible. In the United States, CT scans of the chest and upper abdomen to include the liver and adrenal glands are standard. The liver is a common site of metastasis.
Most cases of SCLC will present in advanced stages, be inoperable, and have a dismal prognosis. Only about 5% of patients present at an early stage (Ia, Ib, or IIa). The National Comprehensive Cancer Network (NCCN) guidelines recommend that these patients be managed with aggressive chemoradiation therapy; in some, lobectomy associated with mediastinal lymph node dissection may be performed. The NCCN notes that advanced disease is managed primarily with chemotherapy, mainly for palliation and symptom control. Older patients, such as the current patient, who have a good performance status (ECOG 0 or 1) and intact organ function should receive standard carboplatin-based chemotherapy. However, even those who have poor prognostic factors (eg, poor performance status, medically significant concomitant conditions) may still be considered for chemotherapy if appropriate precautions are taken to avoid excessive toxicity and further decline in performance status.
Unlike non-SCLC, which has seen waves of new drug approvals from the US Food and Drug Administration (FDA), the prognosis for SCLC has not changed substantially in the past two decades and remains poor. However, the FDA approved atezolizumab in combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC. Further, the approval of durvalumab in combination with chemotherapy; and the approval of lurbinectedin, a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the therapeutic options for patients with SCLC.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts
Karl J. D'Silva, MD, has disclosed no relevant financial relationships
A 72-year-old woman presents with shortness of breath, a productive cough, chest pain, some fatigue, anorexia, a recent 18-pound weight loss, and a history of hypertension. She is currently a smoker and has a 45–pack-year smoking history. On physical examination she has some dullness to percussion with some decreased breath sounds. She has a distended abdomen and complains of itchy skin. The chest x-ray shows a left hilar mass and a 5.4-cm left upper-lobe mass. A CT scan reveals a hilar mass with a mediastinal extension.
Shortness of breath and chest pain
Liver biopsy will reveal the cause of the liver dysfunction and confirm whether this patient has small cell lung cancer (SCLC), as suspected, and whether it has spread to the liver. This will affect chemotherapy options.
Most cases of SCLC will present in advanced stages, be inoperable, and have a dismal prognosis. Only about 5% of patients present at an early stage (Ia, Ib, or IIa). The National Comprehensive Cancer Network (NCCN) guidelines recommend that patients with advanced disease be managed with aggressive chemoradiation therapy and immunotherapy.
SCLC is the most aggressive lung cancer subtype. It is almost always associated with smoking. It accounts for 10%-15% of all lung cancers. Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever. About 70% of patients show metastatic spread at presentation, and the liver is one of the most common sites of metastasis.
Unlike non-SCLC, for which the prognosis has improved in part because of several new drug approvals from the US Food and Drug Administration, the prognosis for SCLC has not changed substantially in the past two decades and remains poor. However, with immunotherapy, the outlook may be improving. The NCCN recommends atezolizumab in combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC. Furthermore, the approval of durvalumab in combination with chemotherapy and the approval of lurbinectedin, a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the therapeutic options for patients with advanced SCLC.
Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.
Maurie Markman, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grants from: AstraZeneca; Novis; GSK; Merck
Liver biopsy will reveal the cause of the liver dysfunction and confirm whether this patient has small cell lung cancer (SCLC), as suspected, and whether it has spread to the liver. This will affect chemotherapy options.
Most cases of SCLC will present in advanced stages, be inoperable, and have a dismal prognosis. Only about 5% of patients present at an early stage (Ia, Ib, or IIa). The National Comprehensive Cancer Network (NCCN) guidelines recommend that patients with advanced disease be managed with aggressive chemoradiation therapy and immunotherapy.
SCLC is the most aggressive lung cancer subtype. It is almost always associated with smoking. It accounts for 10%-15% of all lung cancers. Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever. About 70% of patients show metastatic spread at presentation, and the liver is one of the most common sites of metastasis.
Unlike non-SCLC, for which the prognosis has improved in part because of several new drug approvals from the US Food and Drug Administration, the prognosis for SCLC has not changed substantially in the past two decades and remains poor. However, with immunotherapy, the outlook may be improving. The NCCN recommends atezolizumab in combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC. Furthermore, the approval of durvalumab in combination with chemotherapy and the approval of lurbinectedin, a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the therapeutic options for patients with advanced SCLC.
Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.
Maurie Markman, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grants from: AstraZeneca; Novis; GSK; Merck
Liver biopsy will reveal the cause of the liver dysfunction and confirm whether this patient has small cell lung cancer (SCLC), as suspected, and whether it has spread to the liver. This will affect chemotherapy options.
Most cases of SCLC will present in advanced stages, be inoperable, and have a dismal prognosis. Only about 5% of patients present at an early stage (Ia, Ib, or IIa). The National Comprehensive Cancer Network (NCCN) guidelines recommend that patients with advanced disease be managed with aggressive chemoradiation therapy and immunotherapy.
SCLC is the most aggressive lung cancer subtype. It is almost always associated with smoking. It accounts for 10%-15% of all lung cancers. Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever. About 70% of patients show metastatic spread at presentation, and the liver is one of the most common sites of metastasis.
Unlike non-SCLC, for which the prognosis has improved in part because of several new drug approvals from the US Food and Drug Administration, the prognosis for SCLC has not changed substantially in the past two decades and remains poor. However, with immunotherapy, the outlook may be improving. The NCCN recommends atezolizumab in combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC. Furthermore, the approval of durvalumab in combination with chemotherapy and the approval of lurbinectedin, a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the therapeutic options for patients with advanced SCLC.
Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.
Maurie Markman, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grants from: AstraZeneca; Novis; GSK; Merck
A 64-year-old man presents with shortness of breath, a productive cough, chest pain, some fatigue, anorexia, a recent 15-lb weight loss, jaundice, and a history of type 2 diabetes. He is a college professor and has a 35–pack-year smoking history; he quit 3 years ago.
On physical examination, he has dullness to percussion and decreased breath sounds. His laboratory data reveal elevated serum liver enzyme levels. Chest radiography shows a left hilar mass and a 5.6-cm left upper lobe mass. CT reveals a hilar mass with a bilateral mediastinal extension and pneumonia. PET shows activity in the left upper lobe mass, with supraclavicular nodal areas and liver lesions. MRI shows that there are no metastases to the brain.
Woman presents with cough and bronchorrhea
Bronchioalveolar cell carcinoma (BAC) is a variant of non–small cell lung cancer (NSCLC) that, in recent years, has received a new identity in some of the literature. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are relatively new entities that in some published literature have replaced the term BAC. The National Comprehensive Cancer Network recognizes these terms. AIS is defined as a localized adenocarcinoma of < 3 cm that exhibits a lepidic growth pattern, with neoplastic cells along the alveolar structures but without stromal, vascular, or pleural invasion. MIA refers to small, solitary adenocarcinomas < 3 cm with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm of stromal invasion. BAC has unique epidemiologic, pathologic, and clinical features compared with other NSCLC subtypes. For example, although it is smoking-related, the relationship of BAC to smoking is less strong than with other types of NSCLC. About a third of patients with BAC are never-smokers.
There are also some unique radiographic features — its presentation may be confused with pneumonia or other inflammatory conditions in the lung, and only after a patient does not improve after a course of antibiotics should a diagnosis of BAC be considered. Unlike other types of lung cancer where chemotherapy may be the first plan of attack, surgery is often the first choice for treating BAC, particularly when there is no mediastinal node involvement (10%-25% of cases) or distal metastases (5% of cases). BAC usually harbors EGFR mutation. It is responsive to new targeted therapies for lung cancer, particularly osimertinib, afatinib, erlotinib, and gefitinib. Thus, people with BAC are good candidates for genetic testing.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts
Karl J. D'Silva, MD, has disclosed no relevant financial relationships.
Bronchioalveolar cell carcinoma (BAC) is a variant of non–small cell lung cancer (NSCLC) that, in recent years, has received a new identity in some of the literature. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are relatively new entities that in some published literature have replaced the term BAC. The National Comprehensive Cancer Network recognizes these terms. AIS is defined as a localized adenocarcinoma of < 3 cm that exhibits a lepidic growth pattern, with neoplastic cells along the alveolar structures but without stromal, vascular, or pleural invasion. MIA refers to small, solitary adenocarcinomas < 3 cm with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm of stromal invasion. BAC has unique epidemiologic, pathologic, and clinical features compared with other NSCLC subtypes. For example, although it is smoking-related, the relationship of BAC to smoking is less strong than with other types of NSCLC. About a third of patients with BAC are never-smokers.
There are also some unique radiographic features — its presentation may be confused with pneumonia or other inflammatory conditions in the lung, and only after a patient does not improve after a course of antibiotics should a diagnosis of BAC be considered. Unlike other types of lung cancer where chemotherapy may be the first plan of attack, surgery is often the first choice for treating BAC, particularly when there is no mediastinal node involvement (10%-25% of cases) or distal metastases (5% of cases). BAC usually harbors EGFR mutation. It is responsive to new targeted therapies for lung cancer, particularly osimertinib, afatinib, erlotinib, and gefitinib. Thus, people with BAC are good candidates for genetic testing.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts
Karl J. D'Silva, MD, has disclosed no relevant financial relationships.
Bronchioalveolar cell carcinoma (BAC) is a variant of non–small cell lung cancer (NSCLC) that, in recent years, has received a new identity in some of the literature. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are relatively new entities that in some published literature have replaced the term BAC. The National Comprehensive Cancer Network recognizes these terms. AIS is defined as a localized adenocarcinoma of < 3 cm that exhibits a lepidic growth pattern, with neoplastic cells along the alveolar structures but without stromal, vascular, or pleural invasion. MIA refers to small, solitary adenocarcinomas < 3 cm with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm of stromal invasion. BAC has unique epidemiologic, pathologic, and clinical features compared with other NSCLC subtypes. For example, although it is smoking-related, the relationship of BAC to smoking is less strong than with other types of NSCLC. About a third of patients with BAC are never-smokers.
There are also some unique radiographic features — its presentation may be confused with pneumonia or other inflammatory conditions in the lung, and only after a patient does not improve after a course of antibiotics should a diagnosis of BAC be considered. Unlike other types of lung cancer where chemotherapy may be the first plan of attack, surgery is often the first choice for treating BAC, particularly when there is no mediastinal node involvement (10%-25% of cases) or distal metastases (5% of cases). BAC usually harbors EGFR mutation. It is responsive to new targeted therapies for lung cancer, particularly osimertinib, afatinib, erlotinib, and gefitinib. Thus, people with BAC are good candidates for genetic testing.
Karl J. D'Silva, MD, Clinical Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston; Medical Director, Department of Oncology and Hematology, Lahey Hospital and Medical Center, Peabody, Massachusetts
Karl J. D'Silva, MD, has disclosed no relevant financial relationships.
A 50-year-old woman, a never-smoker, presented with complaints of intermittent cough and shortness of breath for 3 months, associated with bronchorrhea (copious watery sputum production). She had lost 15 pounds in the past 2 months and had dyspnea on exertion for 1 month. Her pulse rate was 88/min, respiratory rate 18/min, and oxygen saturation 96% on room air. A chest x-ray (posteroanterior view) showed dense opacity in the right lower zone. Contrast-enhanced CT of the thorax showed diffuse ground-glass opacities around nodules and consolidation involving the apical and basal segments of the right lower lobe. Despite several courses of antimicrobials, bronchodilators, and IV corticosteroid therapy, the patient's condition worsened.
Reports of dysuria and nocturia
The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP).
SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.
SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.
SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered.
The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.
Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP.
Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
Chad R. Tracy, MD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: CVICO Medical Solutions.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP).
SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.
SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.
SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered.
The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.
Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP.
Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
Chad R. Tracy, MD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: CVICO Medical Solutions.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP).
SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.
SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.
SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered.
The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.
According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.
Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP.
Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
Chad R. Tracy, MD, has disclosed the following relevant financial relationships:
Serve(d) as a consultant for: CVICO Medical Solutions.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 69-year-old nonsmoking African American man presents with reports of dysuria, nocturia, and unintentional weight loss. He reveals no other lower urinary tract symptoms, pelvic pain, night sweats, back pain, or excessive fatigue. Digital rectal exam reveals an enlarged prostate with a firm, irregular nodule at the right side of the gland. Laboratory tests reveal a prostate-specific antigen (PSA) level of 2.22 ng/mL; a comprehensive metabolic panel and CBC are within normal limits. The patient is 6 ft 1 in and weighs 187 lb.
A transrectal ultrasound-guided prostate biopsy is performed. Histologic examination reveals immunoreactivity for the neuroendocrine markers synaptophysin, chromogranin A, and expression of transcription factor 1. A proliferation of small cells (> 4 lymphocytes in diameter) is noted, with scant cytoplasm, poorly defined borders, finely granular salt-and-pepper chromatin, inconspicuous nucleoli, and a high mitotic count. Evidence of perineural invasion is noted.
Depression and emotional lability
The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).
AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.
CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD.
Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials.
Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.
Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.
Jasvinder Chawla, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).
AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.
CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD.
Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials.
Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.
Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.
Jasvinder Chawla, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).
AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.
CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD.
Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials.
Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.
Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.
Jasvinder Chawla, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 51-year-old man presents with complaints of progressively worsening cognitive impairments, particularly in executive functioning and episodic memory, as well as depression, apathy, and emotional lability. The patient is accompanied by his wife, who states that he often becomes irritable and "flies off the handle" without provocation. The patient's depressive symptoms began approximately 18 months ago, shortly after his mother's death from heart failure. Both he and his wife initially attributed his symptoms to the grieving process; however, in the past 6 months, his depression and mood swings have become increasingly frequent and intense. In addition, he was recently mandated to go on administrative leave from his job as an IT manager because of poor performance and angry outbursts in the workplace. The patient believes that his forgetfulness and difficulty regulating his emotions are the result of the depression he is experiencing. His goal today is to "get on some medication" to help him better manage his emotions and return to work. Although his wife is supportive of her husband, she is concerned about her husband's rapidly progressing deficits in short-term memory and is uncertain that they are related to his emotional symptoms.
The patient's medical history is notable for nine concussions sustained during his time as a high school and college football player; only one resulted in loss of consciousness. He does not currently take any medications. There is no history of tobacco use, illicit drug use, or excessive alcohol consumption. There is no family history of dementia. His current height and weight are 6 ft 3 in and 223 lb, and his BMI is 27.9.
No abnormalities are noted on physical exam; the patient's blood pressure, pulse oximetry, and heart rate are within normal ranges. Laboratory tests are all within normal ranges, including thyroid-stimulating hormone and vitamin B12 levels. The patient scores 24 on the Mini-Mental State Examination, which is a set of 11 questions that doctors and other healthcare professionals commonly use to check for cognitive impairment. His clinician orders a brain MRI, which reveals a tau-positive neurofibrillary tangle in the neocortex.
