[1224] Uterine Smooth Muscle Tumors with Features Suggesting Hereditary Leiomyomatosis and Renal Carcinoma (HLRCC) Syndrome: Detailed Morphologic Analysis and Correlation with 2SC Imnohistochemistry

Carolina Reyes, Yevgeniy Karamurzin, Norma Frizzell, Karuna Garg, Ying-Bei Chen, Robert A Soslow. Memorial Sloan-Kettering Cancer Center, New York, NY; University of South Carolina, Columbia, SC

Background: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, an autosomal dominant disorder with affected patients harboring a germline mutation in the fumarate hydratase gene (FH-M), confers a predisposition for skin and uterine leiomyomas and aggressive renal cell carcinomas. Women with HLRCC usually present with multiple fibroids at a young age. Morphologic/immunohistochemical (IHC) correlations were studied with an antibody against S-(2 succino) cysteine (2SC). High levels of modified cysteine residues have been reported in FH-deficient cells and HLRCC tumors, but not in normal tissues or a wide range of non-HLRCC tumors.
Design: Uterine smooth muscle tumors (USMTs) from unselected patients were prospectively analyzed for features suggesting HLRCC (HLRCC-F: prominent eosinophilic macronucleoli with perinucleolar halos) and genetic testing performed as a result in 3 cases. A detailed morphological analysis was undertaken and 2SC IHC was performed with controls from a tissue microarray (TMA) that included leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15).
Results: 8 tumors had HLRCC-F and 2 tested patients had germline FH-M. Patients' ages ranged from 20-50y. 4 had multiple USMTs. Solitary tumors ranged in size from 7-13 cm. All cases had increased cellularity, pericytomatous vasculature and highly fibrillary cytoplasm with pink globules. Mitotic index was 3-4/10HPF. Nuclear atypia was severe in 2 cases. 5 cases had multinucleated cells and 2 had focal pseudoinclusions. Nuclei were round and vesicular, sometimes imparting the impression of an epithelioid neoplasm. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). 3 cases had a neurilemmoma-like pattern. All tumors displayed diffuse granular cytoplasmic labeling with 2SC. Cytoplasmic globules and adjacent myometrium were negative. Of the TMA controls, only 2 tumors were IHC positive and both showed focal HLRCC-F.
Conclusions: 2SC positive, morphologically distinctive USMTs, some in confirmed FH germline mutation carriers, contrast with 2SC negative USMTs without HLRCC-F. This suggests that HLRCC-F is reliably associated with FH abnormalities, including FH-M characteristic of HLRCC. An HLRCC diagnosis should be considered for young women with USMTs that display characteristic morphology so that affected patients and family members can be referred for genetic testing.
Category: Gynecologic & Obstetrics

Tuesday, March 5, 2013 11:00 AM

Proffered Papers: Section E, Tuesday Morning


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