Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects

Abstract

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

The normal and pathologic renal medulla: A comprehensive overview

“…The Birt-Hogg-Dubé syndrome, which includes fibrofolliculomas and/or trichodiscomas as well as pulmonary bullae with spontaneous pneumothorax, is associated with renal oncocytomatosis and multiple oncocytomas [32,33].…”

Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

“…The clinical association with cutaneous (fibrofolliculoma, trichodiscoma or acrochordon) and pulmonary (cyst and pneumothorax) lesions is very important. The germline mutation of the FLCN gene is very important for the definite diagnosis of BHD syndrome [20]. In HLRCC, tumor cells usually correspond to papillary RCC, type 2 and have eosinophilic prominent nucleoli resembling cytomegalovirus inclusion.…”

Editorial Comment to Case of bilateral and multifocal renal cell carcinoma associated with Birt–Hogg–Dubé syndrome

“…Among them, HOCT is the predominant subtype in renal tumors associated with BHDS. HOCT associated with BHDS often demonstrates the focal clear cell change . Although multifocality or bilaterality frequently occurs in renal tumors associated with BHDS, the discordance of histological subtypes in multiple renal tumors might be characteristic of BHDS .…”

“…As the concept of granular cell RCC is now incorporated into the category of clear cell RCC, the re‐evaluation of this diagnostic name in the previous cases is required. In BHDS, it is well known that various histological subtypes including HOCT, chromophobe RCC, renal oncocytoma, clear cell RCC and papillary RCC can occur . Among them, HOCT is the predominant subtype in renal tumors associated with BHDS.…”

“…Although multifocality or bilaterality frequently occurs in renal tumors associated with BHDS, the discordance of histological subtypes in multiple renal tumors might be characteristic of BHDS . Intratumoral peripheral small papillary tufts or parenchymal abnormalities including oncocytosis or cysts might be a diagnostic clue to renal tumors associated with BHDS . The author referred to the indication of nephron‐sparing surgery for patients with renal tumors greater than 3 cm in size .…”