Case of the Month

Answer to September's Case of the Month.

A. Malignant PEComa

Histologic sections demonstrate a mesenchymal neoplasm comprised of polygonal perivascular epithelioid cells with granular, eosinophilic-to-clear cytoplasm and large vesicular nuclei with macro-nucleoli. Background showed areas of hemorrhage, focal spindle cell morphology, rare cells with adipocyte morphology, many multinucleated giant cells with pleomorphic nuclei, scattered highly pleomorphic cells, and a focal area of coagulative necrosis. No mitotic figures were identified.  The epithelioid cell component was approximately 90 percent of the tumor volume. Immunostains showed that the epithelioid cells were positive for MART-1 and HMB-45 and focally positive for actin. Desmin was positive in rare cells. The epithelioid cells were negative for pankeratin, AE1/AE3, Cam 5.2, cytokeratin 7, epithelial membrane antigen (EMA), CD10, RCC, CD117, S-100, PAX8, GATA3, and calretinin. Multinucleated cells were highlighted by CD68 and CD163 stains. FISH was negative for TFE3 translocation.

The PEComa family includes angiomyolipoma (AML), lymphangiomyomatosis of the lung, the clear cell “sugar” tumors of lung and other organs, and a rare group of morphologically and immunophenotypically similar tumors occurring throughout the body in soft tissues, viscera, and bones. Most PEComas are benign and predominantly affect women. Folpe et al. described the criteria for classifying PEComas into benign, uncertain malignant potential (size >5 cm or nuclear pleomorphism/multinucleated giant cells only) and malignant (two or more of: size >5 cm, infiltrative, high nuclear grade and cellularity, mitotic rate ≥1/50 HPF, necrosis or vascular invasion).

Renal AMLs account for 1 percent of renal tumors and are commonly associated with tuberous sclerosis complex. Apart from the classic variant, other rare morphologic variants include epithelioid, atypical, oncocytic, clear cell, and cystic. This case demonstrates a morphologic and immunohistochemical neoplasm with melanocytic and myogenic phenotype and >2 criteria for malignant PEComa, supporting a final diagnosis of malignant PEComa.

Submitted by Swati Satturwar, Genitourinary Pathology Fellow, and Rajiv Dhir, Executive Vice-Chair, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Further Reading

1. G Martignoni et al., “Mesenchymal tumors occurring mainly in adults,” WHO Classification of the Urinary System and Male Genital Organs, 4^th Edition, 62. IARC: 2016.
2. LA Doyle et al., “PEComa,” WHO Classification of Soft Tissue and Bone Tumors, 5^th Edition, 312. IARC: 2019.
3. AL Folpe, DJ Kwiatkowski, Hum Pathol, 41, 1 (2009). PMID: 19604538.
4. O Mete, TH van der Kwast, Arch Pathol Lab Med, 135, 665 (2011). PMID: 21526965.
5. Y Yang et al,. J Int Med Res, 48 (2020). PMID: 33070694.