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Angiosarcomas and morbid obesity: An enormous problem

DII small banner By Warren R. Heymann, MD
Feb. 26, 2017

localized lymphedema
Localized lymphedema. A, Case 7 showed many polypoid lesions that varied in size and were localized throughout the vulva, pubis, and perineum. B, Case 9 showed multiple small polypoid lesions with cauliflower-like morphology in the penis and scrotum. C, Case 3 showed multiple lesions in pubis and scrotum; note the scrotal swelling. D, Case 13 showed large pendulous and polypoid lesions involving the vulva and lower abdomen. (A to D, Hematoxylin-eosin stain.)
Credit: JAAD
More than a third of US adults are obese (body mass index, BMI > 30), per the CDC website. Patients with severe obesity (BMI > 40) or morbid obesity (BMI > 50) have far more serious health consequences than those who are moderately obese. It was estimated that as of 2010, 6.6% of adult Americans (15.5 million) had a BMI >40 (1). The Mayo Clinic website lists the following as complications due to obesity:

* High triglycerides and low high-density lipoprotein (HDL) cholesterol

* Type 2 diabetes

* High blood pressure

* Metabolic syndrome

* Heart disease

* Stroke

* Cancer, including cancer of the uterus, cervix, endometrium, ovaries, breast, colon, rectum, esophagus, liver, gallbladder, pancreas, kidney and prostate

* Breathing disorders, including sleep apnea

* Gallbladder disease

* Gynecological problems, such as infertility and irregular periods

* Erectile dysfunction and sexual health issues

* Nonalcoholic fatty liver disease

* Osteoarthritis

Cutaneous angiosarcoma appears in three clinical settings: 1) as violaceous lesions on the head or scalp of elderly patients; 2) in areas of chronic lymphedema due to any cause; and 3) following exposure to ionizing radiation. Morbid obesity may give rise to massive localized lymphedema (MLL) which is now recognized as fertile ground for the development of an angiosarcoma. The classical form of lymphedema-associated angiosarcoma is the Stewart-Treves syndrome following a mastectomy. As opposed to Stewart-Treves syndrome that involves the upper extremities, obesity-related angiosarcomas usually involve the lower abdomen, thighs and legs. The prognosis is similar for all types, resulting in the demise of most patients (2).  Although rare, a characteristic case involving the abdominal wall of 44-year-old man was presented by Salas et al. Confirmatory studies included routine microscopy with irregular vascular channels, lined by atypical endothelial cells, staining positive with CD34, CD32, and D2-40 (3). Lim et al detail the case of a morbidly obese 66 year-old woman who developed a highly aggressive epithelioid angiosarcoma presenting as ulcerated, necrotic, hemorrhagic confluent papules on a lymphedematous abdominal pannus (4).

Amplifications of MYC are frequently seen in secondary angiosarcomas (arising in irradiated sites and chronic lymphedema) and less frequently in primary cutaneous angiosarcoma. Harker et al reported amplifications of the MYC oncogene by FISH analysis in two morbidly obese patients with angiosarcomas. The authors suggest that such studies could prove beneficial in cases where the diagnosis of angiosarcoma is equivocal. The etiology of angiosarcomas in the context of chronic lymphedema is speculative. Perhaps it is related to vascular growth factors, impaired immunosurveillance, aberrant antigenic presentation, upregulation of MYC or other proto-oncogenes such as KIT and RET, with concurrent downregulation of tumor suppressor genes such as CDKN2C (5).

Therapy for angiosarcomas focuses on aggressive surgical resection plus adjuvant radio/chemotherapy (2). Further studies will be necessary to determine the utility of other adjuvant therapies, such as propranolol or bevacizumab, for patients with morbid obesity-associated angiosarcoma, as has been reported for other angiosarcomas (6, 7).

It is imperative that dermatologists biopsy any suspicious lesions within areas of chronic lymphedema in morbidly obese patients. While that seems so obvious, a major impediment in providing optimal care is doing the exam itself. Patients are often embarrassed and decline disrobing. They are frequently wheelchair bound, requiring an assistant’s help to lift skin folds adequately to get a proper view. Chronic elephantiasic changes, intertrigo, and cellulitis may obscure underlying pathology. It may take an enormous effort to perform an adequate examination in our largest patients, but they deserve nothing less.

1. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the US. Int J Obes (lond); 2013: 37: 889-91.
2. Shon W, et al. Cutaneous angiosarcoma arising in massive localized lymphedema of the morbidly obese. J Cutan Pathol 2011; 38: 560-4.
3. Salas S, et al. Chronic lymphedema due to morbid obesity: An exceptional cause of abdominal wall angiosarcoma. Virchows Arch 2008; 453: 217-9.
4. Lim G, et al. Abdominal pannus with verrucous nodules, ecchymosis, and ulcerations in the setting of lymphedema. Int J Dermatol 2017; 56: e16-8.
5. Harker D, et al. MYC amplification in angiosarcomas arising in the setting of chronic lymphedema of morbid obesity. J Cutan Pathol 2017; 44: 15-9.
6. Chow W, et al. Growth attenuation of cutaneous angiosarcoma with propranol-mediated beta blockade. JAMA Dermatol 2015; 1226-9.
7. Biswas B, Dabkara D. Bevacizumab in advanced angiosarcoma: What is the reality? J Clin Oncol 2016; 34: 764.

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