[453] Do Cutaneous Leiomyomas Have Similar Morphological and Molecular Alterations to Uterine Tumors in the Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)?

Leomar Y Ballester, Phyu P Aung, Karlena Lara-Otero, W Marston Linehan, Maria J Merino. NIH/NCI, Bethesda, MD

Background: HLRCC is an autosomal dominant syndrome characterized by the development of cutaneous and uterine leiomyomas (CL) and renal cell carcinoma (RCC). It has been associated to mutations in the fumarate hydratase gene, in chromosome 1q42-1q43. Loss of heterozigosity (LOH) in this region is evident in the RCC that develop in these patients. Uterine leiomyomas are frequently found in females with HLRCC, the tumors show LOH in 1q42-1q43 and have a histological appearance distinct from the sporadic leiomyomas (i.e. higher cellularity, eosinophilic nuclei, prominent nucleoli with perinuclear halos and mitosis). CL have been observed in 76% of families with HLRCC, presenting as firm skin-coloured to light brown-coloured papules and nodules predominantly in the chest and arms of the patients.
Design: To describe the morphology of CL in HLRCC and assess if they differ from their sporadic counterparts and if they share morphological and molecular characteristics with uterine leiomyomas. We examined the histological features (circumscription, atypia, mitosis, necrosis, size, nuclear morphology, MIB1 labeling, presence of inflammation) of 100 CL of patients with HLRCC syndrome. Tumors and normal tissues were microdissected and DNA extracted for LOH analysis of the 1q42-1q43 region.
Results: The mean age of the patients was 45.2 years with 66% of the patients being female and 34% males. The most common tumor locations were the arm/forearm (51%), back (30%), chest (11%) and other (4%). The tumors were well-circumscribed and localized to the dermis with a Grenz zone. The mean tumor size was 0.34 ± 0.01 cm. The tumors contained interlacing fascicles of smooth muscle cells with elongated nuclei and abundant eosinophilic cytoplasm. None of the lesions showed the atypical features present in uterine leiomyomas. LOH analysis showed loss of heterozigosity for the 1q42-1q43 region in several of the tumors, similar to the uterine leiomyomas.
Conclusions: Our findings suggest that in HLRCC patients, the CL have the so called “second hit” present in renal tumors and uterine leiomyomas, as evidenced by LOH for 1q42-1q43. However, even when cutaneous leiomyomas share the similar LOH present in uterine leiomyomas, they do not show the characteristic atypical morphologic features of uterine tumors. These findings suggest that other alterations, besides LOH for region 1q may play an important role in the development of leiomyomas in HLRCC patients.
Category: Dermatopathology

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 69, Wednesday Morning

 

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