Laparoscopic power morcellation appears capable of spreading fulminant uterine malignancies when used to remove uterine fibroids from women who have unsuspected uterine cancers.

A new Food and Drug Administration literature review of 23 studies found consistent evidence that women who undergo surgery using laparoscopic power morcellators (LPMs) for fibroids that were assumed to be benign may have an occult uterine sarcoma or leiomyosarcoma. In the FDA’s literature review of 12 studies from 2014 to 2016, women who received power morcellation were at a significantly increased risk of death, compared with those whose fibroids were removed by other methods.

The findings reaffirm the agency’s 2014 warnings about LPMs:

• LPMs are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.

• LPMs are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal, or in candidates for en bloc tissue removal.

• Boxed warning: Uterine tissue may contain unsuspected cancer. The use of LPMs during fibroid surgery may spread cancer and decrease long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Laparoscopic power morcellation appears capable of spreading fulminant uterine malignancies when used to remove uterine fibroids from women who have unsuspected uterine cancers.

A new Food and Drug Administration literature review of 23 studies found consistent evidence that women who undergo surgery using laparoscopic power morcellators (LPMs) for fibroids that were assumed to be benign may have an occult uterine sarcoma or leiomyosarcoma. In the FDA’s literature review of 12 studies from 2014 to 2016, women who received power morcellation were at a significantly increased risk of death, compared with those whose fibroids were removed by other methods.

The findings reaffirm the agency’s 2014 warnings about LPMs:

• LPMs are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.

• LPMs are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal, or in candidates for en bloc tissue removal.

• Boxed warning: Uterine tissue may contain unsuspected cancer. The use of LPMs during fibroid surgery may spread cancer and decrease long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Laparoscopic power morcellation appears capable of spreading fulminant uterine malignancies when used to remove uterine fibroids from women who have unsuspected uterine cancers.

A new Food and Drug Administration literature review of 23 studies found consistent evidence that women who undergo surgery using laparoscopic power morcellators (LPMs) for fibroids that were assumed to be benign may have an occult uterine sarcoma or leiomyosarcoma. In the FDA’s literature review of 12 studies from 2014 to 2016, women who received power morcellation were at a significantly increased risk of death, compared with those whose fibroids were removed by other methods.

The findings reaffirm the agency’s 2014 warnings about LPMs:

• LPMs are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.

• LPMs are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal, or in candidates for en bloc tissue removal.

• Boxed warning: Uterine tissue may contain unsuspected cancer. The use of LPMs during fibroid surgery may spread cancer and decrease long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Research suggests an association between adverse childhood events and poorer cardiometabolic health across the lifespan, a new scientific statement from the American Heart Association declares, although it acknowledges various limitations in understanding the connection.

Studies haven’t confirmed a cause-and-effect relationship or the full extent of excess risk, and it’s not clear why some people who experience childhood trauma are more resilient than others. There’s also scant information about any link to higher cardiometabolic death rates.

SOURCE: Suglia S et al. Circulation. 2017 Dec 18. doi: 10.1161/CIR.0000000000000536

Research suggests an association between adverse childhood events and poorer cardiometabolic health across the lifespan, a new scientific statement from the American Heart Association declares, although it acknowledges various limitations in understanding the connection.

Studies haven’t confirmed a cause-and-effect relationship or the full extent of excess risk, and it’s not clear why some people who experience childhood trauma are more resilient than others. There’s also scant information about any link to higher cardiometabolic death rates.

SOURCE: Suglia S et al. Circulation. 2017 Dec 18. doi: 10.1161/CIR.0000000000000536

Research suggests an association between adverse childhood events and poorer cardiometabolic health across the lifespan, a new scientific statement from the American Heart Association declares, although it acknowledges various limitations in understanding the connection.

Studies haven’t confirmed a cause-and-effect relationship or the full extent of excess risk, and it’s not clear why some people who experience childhood trauma are more resilient than others. There’s also scant information about any link to higher cardiometabolic death rates.

SOURCE: Suglia S et al. Circulation. 2017 Dec 18. doi: 10.1161/CIR.0000000000000536

Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to clinic-based administration, according to a study published online Dec. 12 in Contraception.

Researchers randomized 401 women aged 15-44 years – who had requested depot medroxyprogesterone acetate – to four injections over the year, administered by clinic staff at one of three Planned Parenthood health centers or self-administered at home.

The self-administered group performed the first injection at the clinic under supervision, then received instructions and three doses for home use.

At the 12-month follow-up, the rates of continuous use of the contraceptive – defined as reporting two additional doses on the 6-month survey and at least one additional dose on the 12-month survey – were 69% in the self-administration group and 54% in the clinic group (P = .005).

A significantly greater proportion of women in the self-administration group reported receiving at least four shots over the study period, compared with the clinic administration group (78% vs. 64%; P = .008). The authors also noted that 64% of the self-administration group reported receiving five doses – an additional poststudy shot – compared with 52% of the clinic group.

The self-administered injection was well received by women in that group, with 97% saying it was very or somewhat easy to administer, and 87% saying they would recommend self-injection to a friend.

Around half of the participants in the clinic group said they would be interested in self-administration in the future, but both groups reported similar levels of satisfaction with the injectable contraceptive overall.

“A survey study found that women who had difficulty obtaining or refilling a prescription in the past year were almost twice as likely to be interested in self-administration compared to those without such difficulty, suggesting that self-administration has potential to reduce barriers and disparities in access to effective contraception,” wrote Julia E. Kohn, PhD, MPA, and her colleagues at Planned Parenthood. “It is important to note, however, that potential barriers related to insurance coverage and reimbursement will need to be identified and addressed for self-administration to be successfully put into practice.”

There were three pregnancies. They were in the clinic group in women who had discontinued the contraceptive, and one was a planned pregnancy. There were two reports of pain and two reports of bruising at the injection site, but no serious adverse events were reported.

While the study relied on self-report of successful injections, the authors pointed to a recent study in which all women who reported self-injections had therapeutic levels of depot medroxyprogesterone acetate confirmed by blood testing.

Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.

SOURCE: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009

Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to clinic-based administration, according to a study published online Dec. 12 in Contraception.

Researchers randomized 401 women aged 15-44 years – who had requested depot medroxyprogesterone acetate – to four injections over the year, administered by clinic staff at one of three Planned Parenthood health centers or self-administered at home.

The self-administered group performed the first injection at the clinic under supervision, then received instructions and three doses for home use.

At the 12-month follow-up, the rates of continuous use of the contraceptive – defined as reporting two additional doses on the 6-month survey and at least one additional dose on the 12-month survey – were 69% in the self-administration group and 54% in the clinic group (P = .005).

A significantly greater proportion of women in the self-administration group reported receiving at least four shots over the study period, compared with the clinic administration group (78% vs. 64%; P = .008). The authors also noted that 64% of the self-administration group reported receiving five doses – an additional poststudy shot – compared with 52% of the clinic group.

The self-administered injection was well received by women in that group, with 97% saying it was very or somewhat easy to administer, and 87% saying they would recommend self-injection to a friend.

Around half of the participants in the clinic group said they would be interested in self-administration in the future, but both groups reported similar levels of satisfaction with the injectable contraceptive overall.

“A survey study found that women who had difficulty obtaining or refilling a prescription in the past year were almost twice as likely to be interested in self-administration compared to those without such difficulty, suggesting that self-administration has potential to reduce barriers and disparities in access to effective contraception,” wrote Julia E. Kohn, PhD, MPA, and her colleagues at Planned Parenthood. “It is important to note, however, that potential barriers related to insurance coverage and reimbursement will need to be identified and addressed for self-administration to be successfully put into practice.”

There were three pregnancies. They were in the clinic group in women who had discontinued the contraceptive, and one was a planned pregnancy. There were two reports of pain and two reports of bruising at the injection site, but no serious adverse events were reported.

While the study relied on self-report of successful injections, the authors pointed to a recent study in which all women who reported self-injections had therapeutic levels of depot medroxyprogesterone acetate confirmed by blood testing.

Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.

SOURCE: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009

Self-administration of subcutaneous depot medroxyprogesterone acetate contraceptive is a “feasible and acceptable” alternative to clinic-based administration, according to a study published online Dec. 12 in Contraception.

Researchers randomized 401 women aged 15-44 years – who had requested depot medroxyprogesterone acetate – to four injections over the year, administered by clinic staff at one of three Planned Parenthood health centers or self-administered at home.

The self-administered group performed the first injection at the clinic under supervision, then received instructions and three doses for home use.

At the 12-month follow-up, the rates of continuous use of the contraceptive – defined as reporting two additional doses on the 6-month survey and at least one additional dose on the 12-month survey – were 69% in the self-administration group and 54% in the clinic group (P = .005).

A significantly greater proportion of women in the self-administration group reported receiving at least four shots over the study period, compared with the clinic administration group (78% vs. 64%; P = .008). The authors also noted that 64% of the self-administration group reported receiving five doses – an additional poststudy shot – compared with 52% of the clinic group.

The self-administered injection was well received by women in that group, with 97% saying it was very or somewhat easy to administer, and 87% saying they would recommend self-injection to a friend.

Around half of the participants in the clinic group said they would be interested in self-administration in the future, but both groups reported similar levels of satisfaction with the injectable contraceptive overall.

“A survey study found that women who had difficulty obtaining or refilling a prescription in the past year were almost twice as likely to be interested in self-administration compared to those without such difficulty, suggesting that self-administration has potential to reduce barriers and disparities in access to effective contraception,” wrote Julia E. Kohn, PhD, MPA, and her colleagues at Planned Parenthood. “It is important to note, however, that potential barriers related to insurance coverage and reimbursement will need to be identified and addressed for self-administration to be successfully put into practice.”

There were three pregnancies. They were in the clinic group in women who had discontinued the contraceptive, and one was a planned pregnancy. There were two reports of pain and two reports of bruising at the injection site, but no serious adverse events were reported.

While the study relied on self-report of successful injections, the authors pointed to a recent study in which all women who reported self-injections had therapeutic levels of depot medroxyprogesterone acetate confirmed by blood testing.

Tara Health Foundation supported the study. Pfizer provided the study drug through an investigator-initiated research grant. No disclosures were made.

SOURCE: Kohn JE et al. Contraception. 2017 Dec 7. doi: 10.1016/j.contraception.2017.11.009

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.

“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.

By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).

The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.

For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.

That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.

However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).

The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.

Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.

Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.

“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.

Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.

Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.

Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.

“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.

By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).

The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.

For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.

That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.

However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).

The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.

Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.

Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.

“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.

Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.

Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.

Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.

“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.

By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).

The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.

For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.

That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.

However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).

The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.

Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.

Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.

“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.

Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.

Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.

One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.

Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!

junpinzon/Thinkstock

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at [email protected].

One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.

Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!

junpinzon/Thinkstock

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at [email protected].

One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.

Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!

junpinzon/Thinkstock

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at [email protected].

The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today. 

Management of Acute Coronary Syndromes in Patients with Diabetes is the fifth eNewsletter in this series.

Click here to read the supplement. 

The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today. 

Management of Acute Coronary Syndromes in Patients with Diabetes is the fifth eNewsletter in this series.

Click here to read the supplement. 

The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today. 

Management of Acute Coronary Syndromes in Patients with Diabetes is the fifth eNewsletter in this series.

Click here to read the supplement. 

ATLANTA – Adding caplacizumab to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly improved platelet response and prevented recurrent episodes in an international, randomized, double-blind, phase 3 placebo-controlled trial.

“Patients were 55% more likely to achieve normalization of platelet count in the caplacizumab group, and this was highly significant,” Marie Scully, MD, said during a late-breaking presentation at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

SOURCE: Scully M et al., ASH 2017 Abstract LBA-1.

ATLANTA – Adding caplacizumab to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly improved platelet response and prevented recurrent episodes in an international, randomized, double-blind, phase 3 placebo-controlled trial.

“Patients were 55% more likely to achieve normalization of platelet count in the caplacizumab group, and this was highly significant,” Marie Scully, MD, said during a late-breaking presentation at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

SOURCE: Scully M et al., ASH 2017 Abstract LBA-1.

ATLANTA – Adding caplacizumab to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly improved platelet response and prevented recurrent episodes in an international, randomized, double-blind, phase 3 placebo-controlled trial.

“Patients were 55% more likely to achieve normalization of platelet count in the caplacizumab group, and this was highly significant,” Marie Scully, MD, said during a late-breaking presentation at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

SOURCE: Scully M et al., ASH 2017 Abstract LBA-1.

SAN DIEGO – A history of head injury is associated with increased amyloid deposition in the brain, both globally and in the frontal cortex, according to PET imaging in 329 older adults without dementia.

Previous studies have found an association between head injury and later dementia, but the mechanism isn’t understood. The importance of the new investigation is that it “hints at pathophysiology. We were very excited” to find amyloid in the frontal cortex, “which is also associated with Alzheimer’s disease,” said lead investigator Andrea Schneider, MD, PhD, a neurology resident at Johns Hopkins University, Baltimore.

Increased amyloid deposition was not found in other areas associated with the disease, but frontal cortex involvement “does suggest perhaps a common” denominator, she noted.

M. Alexander Otto/Frontline Medical News

[email protected]

SOURCE: Schneider A et al. ANA 2017 abstract M336WIP

SAN DIEGO – A history of head injury is associated with increased amyloid deposition in the brain, both globally and in the frontal cortex, according to PET imaging in 329 older adults without dementia.

Previous studies have found an association between head injury and later dementia, but the mechanism isn’t understood. The importance of the new investigation is that it “hints at pathophysiology. We were very excited” to find amyloid in the frontal cortex, “which is also associated with Alzheimer’s disease,” said lead investigator Andrea Schneider, MD, PhD, a neurology resident at Johns Hopkins University, Baltimore.

Increased amyloid deposition was not found in other areas associated with the disease, but frontal cortex involvement “does suggest perhaps a common” denominator, she noted.

M. Alexander Otto/Frontline Medical News

[email protected]

SOURCE: Schneider A et al. ANA 2017 abstract M336WIP

SAN DIEGO – A history of head injury is associated with increased amyloid deposition in the brain, both globally and in the frontal cortex, according to PET imaging in 329 older adults without dementia.

Previous studies have found an association between head injury and later dementia, but the mechanism isn’t understood. The importance of the new investigation is that it “hints at pathophysiology. We were very excited” to find amyloid in the frontal cortex, “which is also associated with Alzheimer’s disease,” said lead investigator Andrea Schneider, MD, PhD, a neurology resident at Johns Hopkins University, Baltimore.

Increased amyloid deposition was not found in other areas associated with the disease, but frontal cortex involvement “does suggest perhaps a common” denominator, she noted.

M. Alexander Otto/Frontline Medical News

[email protected]

SOURCE: Schneider A et al. ANA 2017 abstract M336WIP