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An 86-year-old woman presented with nodular thickening of her scalp over an oval area of approximately 12.0 cm in greatest dimension. The nodular area had a purplish discoloration and appeared like a bruise, and there was no crusting. The patient had otherwise no significant past medical history. A wide local excision was performed. Pathologic examination revealed a 10.0 cm, gray-white to purple, rubbery, nodular scalp mass with strands of hair extending from the surface.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 29, and is an angiosarcoma.
Criteria for Diagnosis and Comments:
This is a case of angiosarcoma. Histologic features include an infiltrative pattern of neoplastic epithelioid cells originating in the dermis. Mitoses are readily appreciated. The tumor forms solid nests of varying size with a vague pattern of anastomosing and vasoformative channels lined by cells with hyperchromatic, pleomorphic nuclei and sparse cytoplasm. The tumor shows invasion of soft tissues and skin adnexal structures. Immunoperoxidase studies show the neoplastic cells positive for CD31 and CD34, with patchy and weak coexpression of keratin AE1/AE3. Staining for S-100 protein was negative.
Angiosarcoma is a rare malignant neoplasm (less than one percent of all soft tissue tumors) that can involve many organs and tissue sites. Soft tissue angiosarcomas may be subdivided into cutaneous (more common) and deeply situated (very uncommon) neoplasms. Cutaneous angiosarcoma arises most frequently (>50%) in the skin and soft tissues of the head and neck region, usually on the scalp and forehead of elderly individuals with a peak incidence in the seventh to eighth decade of life. Cutaneous angiosarcoma is often correctly diagnosed only when the tumor has become large, invasive, or developed distant metastasis. Purple papules and plaques with the potential to extend beyond the clinically defined borders are often seen.
Tumors most often occur in the upper regions of the scalp. Angiosarcoma of the face often presents with nodules demonstrating ulceration, purple papules or plaques, and bruise-like maculae. A second important group of cutaneous angiosarcomas occurs in the skin of the breast, in patients who have received wide local excision and adjuvant radiotherapy for breast carcinoma, with an unusually short latency period (often less than 2 years). The incidence of angiosarcomas occurring in the setting of chronic lymphedema is decreasing as fewer radical mastectomies are being performed.
Clinically, angiosarcoma is often confused with cellulitis, edema, bruising, benign tumors, or infection, which may lead to a delay in diagnosis. Local recurrence is very common and less than 20% of patients survive five years. A tumor size of 5.0 cm or larger is the only reproducible prognostic indicator for angiosarcoma.
Recommended therapy consists of surgical resection with wide margins as primary treatment, possibly including the outer table of the cranial vault. Other therapeutic considerations include chemotherapy and radiotherapy, but the overall role of radiation in modulating disease outcome has not been well documented. Chemotherapy has been used as an adjunct to radiotherapy with doxorubicin and ifosfamide.
Significant variability in the histologic appearance of angiosarcoma accounts for the diagnostic difficulties often encountered by the pathologist. The histologic spectrum ranges from well-differentiated lesions with only minimal atypia to poorly differentiated tumors that will frequently require immunohistochemical stains to establish the correct diagnosis. The most reliable markers of angiosarcoma include CD31, CD34 and FLI1. Angiosarcomas, especially those with epithelioid features, frequently coexpress low molecular weight cytokeratins. Histologic features the pathologist should look for include infiltrative growth around dermal components, hyperchromatic endothelial cells with intraluminal endothelial stratification, proliferative activity, and interlacing/anastomosing vascular channels. An exclusively spindled or epithelioid growth pattern can be seen.
A number of other entities should be included in the differential diagnosis, but the combination of clinical history/presentation, typical histologic findings and matching immunophenotype will lead to the correct diagnosis in most cases. Spindle cell hemangioma is a non-infiltrative, circumscribed, vascular lesion that frequently occurs in patients with Maffucci syndrome (enchondromas, chondrosarcomas, spindle cell hemangiomas, angiosarcomas). This benign and likely reactive tumor is histologically heterogeneous, with thick-walled vessels, thrombosis, cavernous hemangioma-like areas, and zones containing spindled pericytic cells and epithelioid endothelial cells. There is no significant atypia, mitotic activity or infiltrative growth.
Malignant melanoma is expected to stain positively for one or more of the melanoma markers such as S-100 protein, HMB-45 or Melan-A, and the lesion would grossly often appear pigmented.
Squamous cell carcinoma can form pseudovascular spaces and thus mimic angiosarcoma, but associated epithelial dysplasia, individual keratinizing cells, and eosinophilic cytoplasm offer initial diagnostic clues, which will be supported by a typical immunophenotype (positive for low and high molecular weight cytokeratins and p63, negative for endothelial markers). Grossly, such large lesion would be expected to show crusting.
Kaposi sarcoma is often associated with thick-walled, peripheral blood vessels and a chronic inflammatory cell infiltrate, and it lacks the atypia, mitotic activity, and epithelioid morphology of angiosarcoma. Typical features include short fascicles of spindle cells that form slit-like vascular channels containing red blood cells.
Almost all Kaposi sarcomas express the HHV-8 latency-associated nuclear antigen (LANA), a marker not expressed by other vascular lesions, including angiosarcoma. Classic Kaposi sarcoma usually occurs in elderly men and on the lower extremities, often with a history of immunosuppression or AIDS.