[1050] Clinicopathologic Features of Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) Encountered as Sporadic Kidney Cancer

Antoun Toubaji, Hikmat A Al-Ahmadie, Samson W Fine, Anuradha Gopalan, Satish K Tickoo, Victor E Reuter, Ying-Bei Chen. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: HLRCC is an autosomal dominant disorder characterized by skin and uterine leiomyomas and/or renal cell carcinoma (RCC). Unlike other syndromic RCCs, renal cancer of HLRCC is often unilateral and solitary, clinically mimicking sporadic RCC.
Design: We reviewed the clinicopathologic features of 8 patients initially presented as sporadic RCC cases, but were later proved to have Fumarate hydratase (FH) germline mutations, indicating their hereditary background.
Results: There were 5 men and 3 women. Median age was 35.5 yrs (18-61). Presenting symptoms were flank pain (6), hematuria (3), incidentally found mass of kidney or other metastatic sites (3). Only one patient had uterine fibroids at age 32 and one patient had family history of RCC in first-degree relatives. HLRCC was not clinically suspected at time of presentation in any case. 7 patients had unilateral, solitary tumor; one had two tumors in the same kidney. Median tumor size was 6.6 cm (3-15). All patients had advanced diseases (pT3 and lymph nodes or distant metastasis). Histologically, all 8 cases showed mixed architectural patterns. Papillary was the dominant pattern in only 2 cases. In others, the dominant patterns were tubulopapillary (4), tubular (1) and solid (1). Five of 8 tumors contained collecting duct carcinoma (CDC)-like areas (multinodular growth pattern, infiltrating tubules, solid nests or individual cells surrounded by desmoplastic stroma). Intratumoral inflammatory infiltrates were prominent in 3 of these 5 tumors. Prominent tubulocystic component was seen in 3 of the CDC-like tumors, focally resembling tubulocystic carcinoma. Sarcomatoid differentiation was identified in one case. While all tumors exhibited the proposed hallmark of HLRCC (large eosinophilic nucleolus surrounded by a clear halo), this feature was often not uniformly present throughout the tumor. The possibility of HLRCC was raised by the diagnosing pathologists in 7of 8 cases, resulting in genetic counseling and FH mutation test that confirmed the diagnosis. One case initially diagnosed as unclassified RCC in 2006 was retrospectively identified and confirmed.
Conclusions: Renal cancer of HLRCC may clinically resemble a sporadic RCC. Histologically, besides type 2 papillary RCC, it may more often also mimic CDC and tubulocystic carcinoma. Relevant history and evidence of skin/uterine lesions are often difficult to elicit in the routine clinical encounter; it is therefore important for pathologists to be aware of and recognize the histologic features suggestive of these aggressive renal tumors.
Category: Genitourinary (including renal tumors)

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 162, Monday Morning

 

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