Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome

Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro‐omi; Ota, Satoshi; Michal, Michal; Hes, Ondřej; Nakatani, Yukio

doi:10.1016/j.anndiagpath.2014.03.002

Cited by 11 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although all patients in the present family had this substitution, the younger son did not have BHDS-associated renal tumors, as the most threatening and relatively late-onset clinical phenotype (4-6). Similar results have also been found in Asian populations, and Kuroda et al indicated that BHDS-associated renal tumors often occur with late onset in Japanese subjects (22). Therefore, we cannot eliminate the possibility that the present 33-year-old son may also develop renal neoplasms in his advanced age; hence, the use of annual CT or MRI scans for renal neoplasm monitoring is recommended for this patient.…”

Section: Discussionsupporting

confidence: 60%

Birt-Hogg-Dubé Syndrome with Clear Cell Renal Cell Carcinoma in a Chinese Family

et al. 2014

View full text Add to dashboard Cite

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis that presents as a clinical triad including follicular hamartomas, renal neoplasms and lung cysts associated with an increased risk of pneumothorax. FLCN gene defects have been identified as being responsible for BHDS. We herein report the case of a 67-year-old woman with the full-blown BHDS phenotype, characterized by skin lesions, multiple lung bullae and renal neoplasms. In her family history, one of the patient's sons exhibited a similar phenotype, without renal neoplasms. Due to the relatively late age of onset of renal neoplasms among variable BHDS phenotypes, follow-up imaging is recommended for the son who has not yet developed renal neoplasms.

show abstract

Section: Discussionsupporting

confidence: 60%

Birt-Hogg-Dubé Syndrome with Clear Cell Renal Cell Carcinoma in a Chinese Family

et al. 2014

View full text Add to dashboard Cite

show abstract

“…A few cystic tubules were composed of low columnar benign‐looking cells that were intermingled in the peripheries or the centers of the tumors. That is, intratumoral peripheral small papillary tufts were associated with fibrotic stroma or thick‐walled blood vessels (Fig. a,b, arrows).…”

Section: Resultsmentioning

confidence: 99%

Distinctive expression patterns of glycoprotein non‐metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome

Furuya

Hong²,

Tanaka

et al. 2015

Cancer Science

Self Cite

View full text Add to dashboard Cite

Birt–Hogg–Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

show abstract

“…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 . Usually, the progression of these tumors is slow and nephron‐sparing surgery is indicated for these types of tumor, although there is one case report of metastasis .…”

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

Self Cite

View full text Add to dashboard Cite

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 ...

show abstract

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome

Cited by 11 publications

References 33 publications

Birt-Hogg-Dubé Syndrome with Clear Cell Renal Cell Carcinoma in a Chinese Family

Birt-Hogg-Dubé Syndrome with Clear Cell Renal Cell Carcinoma in a Chinese Family

Distinctive expression patterns of glycoprotein non‐metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome

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

Contact Info

Product

Resources

About