Many Faces of Cellular Angiofibroma: Variable Morphology of Rare Sarcomatous Transformation. Erem AS, Gjeorgjievski SG, Hanley KZ, Turashvili G.

Summary: Background: Cellular angiofibromas (CAFs) are benign mesenchymal neoplasms of the vulva and lower genitourinary tract. Recurrences, cytologic atypia, and sarcomatous transformation are extremely uncommon. We aimed to describe detailed clinicopathologic features of CAF with and without sarcomatous transformation in a female population. Design: We are presenting complete resection specimens of CAFs, retrieved from our institution's surgical and consultation files between 2010 and 2022. Clinical data was obtained from the electronic medical records, and microscopic slides were reviewed. Results: A total of 17 CAFs were identified. The median age at diagnosis was 49 years (32-68). All tumors were located within the subcutis and ranged in size from 0.5 to 5 cm (median 3 cm). CAFs were histologically characterized by bland spindle cell proliferation, variable amounts of adipose tissue, mast cells, and numerous medium-sized thick-walled vessels. Infiltrative borders were seen in 4, fascicular growth in 9, and chronic perivascular or stromal inflammation in 15 cases. Stromal edema in 8 cases and fat entrapment in 9 were common. Rare histologic features included myxoid changes (3), vascular thrombosis (1), and hemangiopericytoma-like vasculature (4). Cytologic atypia was seen in 3 cases, presenting as scattered multinucleated cells. CD34 was expressed in 12 cases and desmin in two. Rb-1 expression was lost in 2 cases. Six CAFs had sarcomatous transformation, ranging from 10-80% of overall tumor volume. Abrupt transition between sarcoma and CAF was seen in 4 cases, gradual transition in 2 cases, and 1 CAF had multiple sarcomatous foci. Three of 6 cases showed increased mitotic activity (up to 28 per 10 HPF), whereas the remaining 3 had ≤3 mitoses per 10 HPF. Diffuse p16 expression was present in 2 cases with sarcomatous transformation, which was not seen in any of the CAFs lacking sarcomatous transformation. Only 1 case of CAF with sarcomatous transformation recurred upon re-excision. Conclusion: Common histologic features of CAF include fascicular growth, stromal edema, and myxoid changes. Infiltrative borders are uncommon, while perivascular and stromal inflammation is frequently present. A subset of CAFs in female patients is associated with sarcomatous transformation (seen in 35% of our cases) with rare local recurrences but no distant metastases. Diffuse expression of p16 may have diagnostic significance in CAFs with sarcomatous transformation.