Renal oncocytosis

Nagashima, Yoji; Mitsuya, Toshiyuki; Shioi, Ko-ich; Noguchi, Sumio; Kishida, Takeshi; Hamano, Atsushi; Ohgo, Yoshiharu; Tsuura, Yukio; Ogawa, Teiichiro; Aoki, Ichiro; Yao, Masahiro

doi:10.1111/j.1440-1827.2005.01813.x

Cited by 22 publications

(8 citation statements)

References 19 publications

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“…These tumors are bilateral multifocal with diverse histologies that include HOCT (50%), chromophobe renal cell carcinoma (34%), clear cell renal cell carcinoma (9%), oncocytoma (5%) and papillary renal cell carcinoma (2%) . Multifocal renal oncocytosis, composed of cells electron‐microscopically filled with mitochondria and observed in the surrounding normal kidney of BHD‐associated renal tumors in 50–58% of patients, is possibly a pre‐cancer lesion . Small papillary tufts are often observed in the peripheral of the tumor and are helpful for diagnosis of BHD‐associated renal tumor .…”

Section: Clinical Features Of Bhd Syndromementioning

confidence: 99%

Birt–Hogg–Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome

Hasumi

et al. 2015

Int J of Urology

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Abbreviations & Acronyms AMPK = adenosine monophosphate-activated protein kinase BHD syndrome = Birt-Hogg -Dub e syndrome FLCN = folliculin FNIP1 = folliculininteracting protein 1 FNIP2 = folliculininteracting protein 2 HOCT = hybrid oncocytic/ chromophobe tumors mTOR = mammalian target of rapamycin mTORC1 = mammalian target of rapamycin complex 1 VHL = von Hippel-Lindau Abstract: Birt-Hogg-Dub e syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt-Hogg-Dub e syndrome-associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron-sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for BirtHogg-Dub e syndrome patients. The folliculin gene (FLCN) that is responsible for BirtHogg-Dub e syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin-interacting protein 1 (FNIP1) and folliculin-interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP-activated protein kinase-mediated energy sensing, Ppargc1a-driven mitochondrial oxidative phosphorylation and mTORC1-dependent cell proliferation. Birt-Hogg-Dub e syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/ FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer.Key words: Birt-Hogg-Dub e syndrome, folliculin, kidney cancer, mitochondria, mTORC1.In 1977, three Canadian physicians, Birt, Hogg and Dub e, reported kindred with skin nodules that they named fibrofolliculoma.1 In 1999, the development of lung cysts and renal tumors in this kindred were reported, and this disorder was thereafter called BHD syndrome.2 In 2002, FLCN was identified as a novel tumor suppressor gene responsible for BHD syndrome, and a genetic test of FLCN is used as a diagnostic tool for BHD syndrome.3 Among the clinical triad of BHD syndrome, the management of kidney cancer is a key for the overall survival of BHD patients. Although FLCN was a totally novel protein with unknown function and no known domains at the time of discovery, recent studies using murine models have uncovered important roles for FLCN in cell metabolism. [4][5][6][7][8][9][10] In the present review article, we describe the clinical features and management of BHD syndrome, as well ...

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Section: Clinical Features Of Bhd Syndromementioning

confidence: 99%

Birt–Hogg–Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome

Hasumi

et al. 2015

Int J of Urology

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“…HOCT are defined as tumors having a mixture of cells with the morphological features of those seen in chromophobe renal cell carcinoma (CHRCC) and renal oncocytoma (RO). Most frequently, these tumors have been described in patients with BirtHogg-Dubé syndrome (BHD) [1][2][3] or in association with renal oncocytosis [4][5][6][7] without evidence of BHD. In the present study, we describe the clinicopathologic, immunohistochemical, genetic, and ultrastructural features of HOCT in a cohort of 14 patients without evidence of BHD or renal oncocytosis.…”

Section: Introductionmentioning

confidence: 99%

Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases

et al. 2010

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Hybrid oncocytic/chromophobe tumors (HOCT) of the kidney have been described in patients with Birt-Hogg-Dubé syndrome (BHD) and in association with renal oncocytosis without BHD. HOCT in patients without evidence of BHD or renal oncocytosis is exceedingly rare, and these cases have been poorly characterized. We have identified and studied 14 cases of HOCT from previously diagnosed renal oncocytomas (398 cases) and chromophobe renal cell carcinomas (351 cases) without evidence of BHD or renal oncocytosis. Immunohistochemical, ultrastructural, and molecular genetic studies analyzing numerical chromosomal changes, loss of heterozygosity for chromosome 3p, and mutation status of VHL, c-kit, PDGFR, and folliculin (FLCN) genes were performed. HOCTs were identified in nine men and five women (age range 40-79 years). The size of tumors ranged from 2 to 11 cm. All tumors displayed a solid alveolar architecture and were composed of cells with abundant granular eosinophilic oncocytic cytoplasm with perinuclear halos. Occasional binucleated neoplastic cells were present, but irregular, hyperchromatic, wrinkled (raisinoid) nuclei were absent. The cytoplasm contained numerous mitochondria of varying sizes, but only sparse microvesicles with amorphic lamellar content were found. Tumors were positive for CK7 (12/14), AE1-AE3 (14/14), anti-mitochondrial antigen (14/14), E-cadherin (11/13), parvalbumin (12/14), and epithelial membrane antigen (14/14). Tumors were generally negative for racemase, CK20, CD10, and carboanhydrase IX. Interphase fluorescence in situ hybridization revealed multiple chromosomal losses and gains with a median of four (range 1-9) chromosomal aberrations per case. Monosomy of chromosome 20 was common and found in 7 of 14 cases. Monosomy of chromosomes 6 and 9 was present in 4 of 14 cases each, of which two cases displayed monosomy for both chromosomes 6 and 9. Polysomy of chromosomes 10, 21, and 22 was found in 4/14 cases each, of which one case displayed polysomy for all these three chromosomes. No pathogenic mutations were found in the VHL, c-kit, PDGFR, and folliculin (FLCN) genes. (1) We have shown that hybrid oncocytic/chromophobe tumors of the kidney do occur, albeit rarely, outside the Birt-Hogg-Dubé syndrome and without associated renal oncocytosis. (2) These tumors constitute a relatively homogenous group with histomorphologic features of both chromophobe renal cell carcinoma and renal oncocytoma. (3) Sporadic hybrid oncocytic/chromophobe renal tumors are characterized by multiple numerical aberrations (both mono- and polysomies) of chromosomes 1, 2, 6, 9, 10, 13, 17, 21, and 22 and lack of mutations in the VHL, c-kit, PDGFRA, and FLCN genes. (4) The tumors seem to behave indolently as no evidence of malignant behavior was documented in our series, although admittedly, the follow-up was too short to fully elucidate the biological nature of this rare neoplasm. At worst, these tumors could have a low malignant potential, which only can be found out with longer follow-up.

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“…Several papers have described cases with multiple and bilateral renal oncocytomas, but only a few appear to have been renal oncocytosis. [4][5][6][7] Due to the association of different morphologic patterns, renal oncocytosis raises the question of the possibility of a close relationship between renal oncocytoma and chromophobe renal cell carcinoma. Renal oncocytosis may also pose a diagnostic problem in surgical pathology, because of the different prognoses of oncocytoma and chromophobe renal cell carcinoma.…”

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confidence: 99%

Interphase cytogenetic analysis with centromeric probes for chromosomes 1, 2, 6, 10, and 17 in 11 tumors from a patient with bilateral renal oncocytosis

et al. 2008

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Renal oncocytosis

Cited by 22 publications

References 19 publications

Birt–Hogg–Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome

Birt–Hogg–Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome

Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases

Interphase cytogenetic analysis with centromeric probes for chromosomes 1, 2, 6, 10, and 17 in 11 tumors from a patient with bilateral renal oncocytosis

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