Bone & Soft Tissue Pathology
Case 2 -
Sporadic Cutaneous Angiosarcoma, High Risk for Aggressive Behavior
Andrea T. Deyrup
Click on each slide thumbnail image for an enlarged view
Sporadic Cutaneous Angiosarcoma, High Risk for Aggressive Behavior.
The patient is a 45 male who presented with a 1.8 x 1.7cm bump on his forehead. Clinically this was
thought to be a cyst. Past medical history and clinical examination were noncontributory. The lesion
was biopsied and then excised. The images are from the resection specimen.
Case 2 - Slide 1
Case 2 - Figure 1
The tumor extends from the deep reticular dermis to subcutaneous tissue and displays a vaguely nodular architecture.
Case 2 - Figure 2
Higher magnification view of the tumor.
Case 2 - Figure 3
The nodules are composed of sheets of spindled cells aranged in short fascicles. Intratumoral and peripheral collections of lymphocytes can be appreciated.
Case 2 - Figure 4
The tumor cells have indistinct cell borders, lightly eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli.
Case 2 - Figure 5
Focally, tumor cells dissect through dermal collagen forming anastamosing channels.
The tumor extends from the deep reticular dermis to the subcutaneous tissue and displays a vaguely
nodular architecture, most evident at the periphery. The nodules are composed of sheets of
spindled cells arranged in short fascicles with indistinct cell borders, lightly eosinophilic cytoplasm
and vesicular nuclei with prominent nucleoli. Focally, a vasoformative pattern consisting of
anastomosing vessels dissecting through collagen can be appreciated. Mitotic activity is brisk and there
are foci of necrosis. A peripheral lymphocytic response is evident.
The tumor cells are positive for CD31 and Fli-1 and negative for CD34, cytokeratins AE1/AE3 and S100
Angiosarcomas occur in diverse clinical settings that are best conceptualized as several different
diseases, united by certain common histologic features, rather than as a single disease entity. Well
recognized forms of angiosarcoma include 1) cutaneous angiosarcoma occurring in sun-exposed skin
("sporadic" cutaneous angiosarcoma),
2) cutaneous angiosarcoma arising in lymphedema (e.g.
Stewart Treves syndrome),
3) angiosarcoma of deep soft
and 5) angiosarcoma associated with foreign
material.  Clinical presentation, patient demographics, prognostic factors and treatment
considerations show some overlap; however, subclassification according to type is necessary for clearest
interpretation of data.
Sporadic cutaneous angiosarcomas (SCA) primarily affect older male patients (1.5M:1F; mean 69 years)
and typically arise in the head and neck (~70%) and trunk (~20%).
 Patients present
with a several month history of enlarging red to violaceous plaques or papules that may be
multifocal.  The lesions may be mistaken for "bruises" and delay in diagnosis is not uncommon.
Grossly, cutaneous angiosarcomas are ill-defined, hemorrhagic lesions. Microscopically, several
different histologic patterns can be seen in SCA. The most easily recognized appearance consists of
anastomosing thin-walled blood vessels lined by enlarged, hyperchromatic endothelial cells that dissect
through the dermal collagen and around adnexal structures. The endothelial cells may display
stratification and tufting into the vascular lumen. At the other extreme, cutaneous angiosarcomas may
be composed almost entirely of solid sheets of epithelioid to spindled cells. "Epithelioid", in this
context, implies a polygonal cell shape, abundant eosinophilic cytoplasm, and oval to round nucleus with
prominent nucleoli and irregular nuclear membranes. As such, epithelioid angiosarcomas are cytologically
high grade. The third histologic pattern consists of a mixture of the vasoformative and solid
appearances. The incidence of these 3 patterns depends somewhat on referral patterns: in our
experience, the solid pattern was most common as opposed to Morgan and colleagues who reported a larger
percentage of vasoformative tumors.  In all three histologic variants, mitotic activity is
usually brisk and foci of necrosis may be seen.
Depending on the particular morphology of each case, the differential diagnosis for SCA includes
benign vascular lesions, Kaposi sarcoma, carcinoma, atypical fibroxanthoma/superficial malignant fibrous
histiocytoma (MFH), and melanoma. Distinguishing a well-differentiated angiosarcoma from a benign
vascular lesion can be quite difficult. Clues to a diagnosis of malignancy include diffuse permeation of
the surrounding tissue, infiltration of tumor cells through dermal collagen, endothelial stratification
and hyperchromatic, atypical cells.
Sporadic cutaneous angiosarcomas that are primarily spindled may mimic a sarcomatoid squamous cell
carcinoma; fortunately, unlike epithelioid angiosarcomas which may express cytokeratins, this antigen is
rarely seen in spindled SCA. Kaposi sarcoma also enters the differential diagnosis in spindled SCA and
can be excluded by the minimal cytologic atypia seen in that entity, as well as a positive
immunohistochemical stain for HHV-8.
Poorly differentiated angiosarcomas may be interpreted as atypical fibroxanthoma/superficial malignant
fibrous histiocytoma. However, that is a diagnosis of exclusion and should only be made once the
appropriate immunohistochemical panel has been evaluated. In addition, the frequent association of
hemorrhage with angiosarcoma and focal vasoformation aid in diagnosis.
Predominantly epithelioid and/or solid angiosarcomas raise a differential diagnosis of poorly
differentiated carcinoma or melanoma. Carcinoma being much more common than angiosarcoma, it is easy to
interpret a positive cytokeratin stain as evidence of epithelial differentiation. A negative panel of
melanocytic markers generally excludes melanoma. However, a reasonable degree of suspicion and
willingness to perform endothelial immunostains are important when epithelial or melanocytic stains are
equivocal. Cutaneous angiosarcoma expresses the usual endothelial markers including CD31, CD34, and
Fli-1. It is important to recognize, however, that histiocytes are also positive for CD31 and
intralesional histiocytes can lead to misdiagnosis of a vascular neoplasm. 
Grading in Cutaneous Angiosarcomas
Histologic grade, as determined by established grading criteria, does not appear to correlate with
clinical behavior in cutaneous angiosarcomas.
. By multivariate analysis, Morgan and
colleagues determined that tumor diameter, depth of invasion, and positive margins correlated with
survival. Recently, we have shown that the presence of epithelioid morphology and/or necrosis is
associated with a worse prognosis: patients without these two features ("low risk for aggressive
behavior) had a 3-year survival of 77% compared to 24% for patients with either of these histologic
findings ("high risk of aggressive behavior").
Complete surgical excision is the recommended primary therapy for cutaneous angiosarcomas.
 However, due to the infiltrative, ramifying nature of these tumors and frequent
multifocality, it may be nearly impossible to achieve negative surgical margins, particularly in
anatomically constrained sites such as the head and neck. Adjuvant radiation therapy has been shown to
reduce mortality in cutaneous angiosarcomas in these tumors. Cutaneous angiosarcomas most commonly
metastasize to lymph node and lung. Cause of death may be metastatic disease or disease progression.
Due to the presence of necrosis in the current case, this patient would be considered high risk. In
fact, 2 years after diagnosis, the patient presented with lung metastases. He received 6 cycles of d
oxorubicin and paclitaxel and is currently disease-free (2 years after final chemotherapy treatment).
- Think outside the box: use a broad range of immunohistochemical stains if the diagnosis
- Criteria for
prognosis continue to evolve: keep up to date on the literature.
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- Brenn T, Fletcher CD: Radiation-associated cutaneous atypical vascular lesions and angiosarcoma: clinicopathologic analysis of 42 cases. Am J Surg Pathol 2005, 29:983-996
- Deyrup AT, McKenney JK, Tighiouart M, et al.: Sporadic Cutaneous Angiosarcomas: A Proposal for Risk Stratification Based on 69 Cases. Am J Surg Pathol 2008, 32:72-77
- Holden CA, Spittle MF, Jones EW: Angiosarcoma of the face and scalp, prognosis and treatment. Cancer 1987, 59:1046-1057
- Jennings TA, Peterson L, Axiotis CA, et al.: Angiosarcoma associated with foreign body material. A report of three cases. Cancer 1988, 62:2436-2444
- McKenney JK, Weiss SW, Folpe AL: CD31 expression in intratumoral macrophages: a potential diagnostic pitfall. Am J Surg Pathol 2001, 25:1167-1173
- Meis-Kindblom JM, Kindblom LG: Angiosarcoma of soft tissue: a study of 80 cases. Am J Surg Pathol 1998, 22:683-697
- Morgan MB, Swann M, Somach S, et al.: Cutaneous angiosarcoma: a case series with prognostic correlation. J Am Acad Dermatol 2004, 50:867-874
- Pawlik TM, Paulino AF, McGinn CJ, et al.: Cutaneous angiosarcoma of the scalp: a multidisciplinary approach. Cancer 2003, 98:1716-1726
- Stewart FW, Treves N: Lymphangiosarcoma in postmastectomy lymphedema. Cancer 1949, 1:64