Case 4 -

Radiation-Induced Epithelioid Angiosarcoma Of The Vagina Eva M. Wojcik Loyola University Medical Center Maywood, IL

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Clinical Summary A 54 year old female with history of cervical squamous cell carcinoma diagnosed15 years earlier for which she underwent a total abdominal hysterectomy followed by radiation therapy was referred to the gynecology- oncology clinic for the evaluation of a pelvic (perirectal) mass. Pap Test (Thin Prep™) of a vaginal cuff was obtained. Case 4 - Figure 1 - Thin Prep™ Papanicolaou stain, high power: This image shows a loose tri-dimensional cluster of spindle cells with a delicate, vacuolated cytoplasm, relatively uniform oval nuclei with irregular nuclear membrane. The chromatin is irregular and occasional nuclear grooves are present. Case 4 - Figure 2 - Thin Prep™ Papanicolaou stain, high power: Throughout the specimen there were single, pleomorphic malignant cells. This image shows a large bi-nucleated cell with rather abundant delicate cytoplasm, nuclei with coarse chromatin and prominent nucleoli. In addition, two naked, similar nuclei are present. Case 4 - Figure 3 - Thin Prep™ Papanicolaou stain, high power: The background is necrotic and appreciated as granular amorphous debris and fragments of red blood cells attached to cells ("clinging diathesis"). In addition, mitotic figures are seen. Case 4 - Figure 4 - Thin Prep™ Papanicolaou stain, high power: Many cells are elongated or spindled. This image presents a cell with eccentrically located nucleus with irregular nuclear membrane, coarse chromatin and prominent nucleolus. The cytoplasm is abundant and contains large vacuoles. Case 4 - Figure 5 - Thin Prep™ Papanicolaou stain, high power: Occasional cells contain other cells, cellular debris or fragments of red blood cells within large cytoplasmic vacuoles. This image demonstrates one of these cells. Necrotic background is appreciated. Angiosarcoma is rare malignant vascular neoplasm representing about 1-2% of all soft tissue sarcomas. It is characterized by atypical, multilayered or solid endothelial proliferation with vasoformative architecture. A wide variety of anatomic locations have been described. The most common sites include soft tissue and skin of head and neck, scalp, breast and extremities, however, angiosarcomas have been reported also in pleura, bone, heart, liver and vagina. Although its pathogenesis is unclear, several etiologic factors have been implicated. Irradiation, as an etiologic factor, has been widely accepted. In addition, chronic lymphadenopathy, particularly after mastectomies, arterio-venous fistulas, foreign bodies (Dacron, steel and plastic) and environmental factors (arsenic, Thorotrast and vinyl chloride) have been associated with angiosarcomas. Angiosarcomas demonstrate marked heterogeneity at different anatomic sites, in terms of patient age, gender, median survival, and response to chemotherapy. Radiation-induced angiosarcoma is a late complication of radiotherapy in patients who have received a significant amount of irradiation. The classification criteria of radiation-induced sarcoma have to include: site of origin must be within the field of previous irradiation, significant amount of irradiation had been used (between 25 and 80 Gy), latency period at least 3-5 years and the secondary sarcoma should be histologically different from the primary neoplasm. Angiosarcomas can present as a wide spectrum of histologic differentiations. It can present as a highly differentiated tumor that resemble hemangioma or as anaplastic tumor that is difficult to be distinguish from a carcinoma or a melanoma. They can have papillary, spindled or epithelioid morphologic features. In general, irregular anastomotic sinusoids and dilated vascular spaces lined by plump and atypical endothelial cells with projection into vascular lumina are characteristic for angiosarcomas. Low-grade tumors are characterized by minimal cellular atypia and few mitotic figures. In contrast, high grade sarcomas show greater pleomorphism, more hyperchromatic nuclei and frequent mitotic figures. Immunohistochemistry is often necessary for the definitive diagnosis, particularly when vasoformative architecture is minimal or absent, such as in high grade epithelioid angiosarcomas. In general, panel approach is recommended as poorly differentiated tumors may not be positive for all vascular markers. Also, it is important to remember that epithelioid tumors may express cytokeratin. Since epithelioid angiosarcoma has to be differentiated from poorly differentiated carcinoma, melanoma and other epithelioid sarcomas, the proposed panel of markers should be performed.   Cyto-keratin CD31 CD34 Fact VIII Ulex Europeus S-100 HMB-45 Epithelioid Angiosarcoma -** + + +* + -*** - Epithelioid sarcoma + - - - - - - Malignant melanoma - - - - - + + Poorly differentiated carcinoma + - - - - - - * High grade angiosarcoma may stain negative for fact VIII ** Some epithelioid angiosarcoma may co-express cytokeratin *** Some epithelioid angiosarcoma may express S-100 Cytological findings reflect the histological variability and differentiation of angiosarcomas. In general, specimens obtained by FNA are cellular, particularly in epithelioid tumors. The background is usually hemorrhagic. Cells are arranged singly, in loose clusters or streaming fascicles. Acinar or rosettoid structures are also seen. Cells can be polygonal, round to oval or spindled. Amount of cytoplasm varies. There are cells with high nuclear/cytoplasmic ratio as well as cells with rather abundant, cyanophilic cytoplasm. Bi-nucleation and multinucleation is common. Nuclei are often irregular with grooves and indentations. Intranuclear and/or cytoplasmic inclusions are present. In high grade tumors, necrosis and mitoses are often seen. References Ng WK, Collins RJ, Law D, Gwi E: Cutaneous epithelioid angiosarcoma: A potential diagnostic trap for cytopathologists. Diagn Cytopathol 1997; 16: 160-167 Liu K, Layfield LJ: Cytomorphologic features of angiosarcoma on fine needle aspiration biopsy. Acta Cytol 1999; 43: 405-415 Wakely PE Jr, Frable WJ, Kneisl JS: Aspiration cytopathology of epithelioid angiosarcoma. Cancer 2000; 90: 245-251 Boucher LD, Swanson PE, Stanley MW, Silverman JF, Raab SS, Geisinger KR: Cytology of angiosarcoma: Findings in fourteen fine-needle aspiration biopsy specimen and one pleural fluid specimen. Am J Clin Pathol 2000; 114: 210-219 Pohar-Marinsek Z, Zidar A: Epithelioid sarcoma in FNAB smears. Diagn Cytopathol 1994; 11: 367-372 Nguyen GK, Husain M: Fine-needle aspiration biopsy cytology of angiosarcoma. Diagn Cytopathol 2000; 23: 143-145 Yoon KJ, Hwal WK, Hyun JC, In AP: Fine needle aspiration cytology of Epithelioid angiosarcoma: Report of a case with nuclear groove and indentations. Acta Cytol 2002; 25: 223-228