Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus

“…aIncluding 12 families also described by Leter et al , 2008 and Johannesma et al , 2009.bFor calculation of renal cancer and pneumothorax penetrance the data of 86 FLCN mutation carriers from 21 kindreds for which complete family data were available were used.cSeven families (11, 17, 20, 24, 38, 45 and 50) had familial multiple discoid fibromas, described by Starink et al (2011); two index patients (26 and 39) were diagnosed with pulmonary emphysema and probable tuberous sclerosis complex, respectively.…”

Section: Figurementioning

confidence: 99%

Renal cancer and pneumothorax risk in Birt–Hogg–Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families

Houweling

Gijezen

Jonker³

et al. 2011

Br J Cancer

144

121

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Background:Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant condition caused by germline FLCN mutations, and characterised by fibrofolliculomas, pneumothorax and renal cancer. The renal cancer risk, cancer phenotype and pneumothorax risk of BHD have not yet been fully clarified. The main focus of this study was to assess the risk of renal cancer, the histological subtypes of renal tumours and the pneumothorax risk in BHD.Methods:In this study we present the clinical data of 115 FLCN mutation carriers from 35 BHD families.Results:Among 14 FLCN mutation carriers who developed renal cancer 7 were <50 years at onset and/or had multifocal/bilateral tumours. Five symptomatic patients developed metastatic disease. Two early-stage cases were diagnosed by surveillance. The majority of tumours showed characteristics of both eosinophilic variants of clear cell and chromophobe carcinoma. The estimated penetrance for renal cancer and pneumothorax was 16% (95% minimal confidence interval: 6–26%) and 29% (95% minimal confidence interval: 9–49%) at 70 years of age, respectively. The most frequent diagnosis in families without identified FLCN mutations was familial multiple discoid fibromas.Conclusion:We confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers. The tumours were metastatic in 5 out of 14 patients and tumour histology was not specific for BHD. We found a pneumothorax risk of 29%. We discuss the implications of our findings for diagnosis and management of BHD.

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“…described a family who had developed multiple pure forms of trichodiscomas during childhood, in the absence of associated internal abnormalities. Three case reports followed shortly after, but none subsequently for over 20 years until the recent case series from the Netherlands led by the author of the original report . This recent article reviewed the clinical and histological findings in 27 patients with FMDF from nine families (including the family from the original report).…”

Section: Discussionmentioning

confidence: 99%

“…Familial multiple discoid fibromas (FMDF) is an extremely rare inherited dermatosis that is characterized by multiple discoid fibromas, which typically develop over the face and pinnae during the first two decades of life . There is some resemblance to Birt–Hogg–Dubé syndrome (BHD), an autosomal dominant condition characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothoraces and renal cell cancer.…”

mentioning

confidence: 99%

“…There is some resemblance to Birt–Hogg–Dubé syndrome (BHD), an autosomal dominant condition characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothoraces and renal cell cancer. FMDF is distinguished from BHD by the early age of onset, prominent involvement of the pinnae, histological findings of discoid fibromas without the follicular epithelial component characteristic of the fibrofolliculoma/trichodiscoma spectrum of BHD, and the absence of renal and lung complications . Mutations of the folliculin ( FLCN ) gene, which are responsible for BHD, are not identified in FMDF …”

mentioning

confidence: 99%

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Familial multiple discoid fibromas: unique histological features and therapeutic response to topical rapamycin

Wee¹,

Chong

Natkunarajah³

et al. 2013

Br J Dermatol

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Familial multiple discoid fibromas is a rare genodermatosis that bears some resemblance to Birt-Hogg-Dubé syndrome but is not associated with mutations in the folliculin (FLCN) gene or systemic manifestations. It is characterized by the development of papules over the face and pinnae early in life. Histological findings are of fibrovascular tumours adjacent to hair follicles without features characteristic of fibrofolliculomas, which have recently been termed discoid fibromas. We present siblings with multiple papules over the face and pinnae that developed in childhood. Histological specimens from both siblings demonstrated discoid fibromas, but with some lesions exhibiting an unusual keloidal-like pattern with thick hyalinized collagen fibres surrounded by plump spindle and histiocyte-like cells. FLCN gene mutations were not found. We report on clinical improvement with topical rapamycin solution (1 mg mL(-1)) applied daily to the face for 4 months. Therapeutic response to topical rapamycin may provide a clue to the underlying genetic basis of this condition.

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Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus

Cited by 24 publications

References 27 publications

From Immunotherapy of Cancer to the Discovery of Kidney Cancer Genes: A Personal History

From Immunotherapy of Cancer to the Discovery of Kidney Cancer Genes: A Personal History

Renal cancer and pneumothorax risk in Birt–Hogg–Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families

Familial multiple discoid fibromas: unique histological features and therapeutic response to topical rapamycin

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