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Anais Brasileiros de Dermatologia 2015Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or... (Review)
Review
Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.
Topics: Acanthoma; Adenoma; Diagnosis, Differential; Female; Follicular Cyst; Hair Diseases; Hair Follicle; Humans; Male; Neoplasms, Basal Cell; Skin Neoplasms; Syndrome
PubMed: 26734858
DOI: 10.1590/abd1806-4841.20154114 -
Dermatology Online Journal Nov 200427-year-old woman presented with multiple growths on her face and upper body, which she has had for several years. She also reported that her mother and maternal...
27-year-old woman presented with multiple growths on her face and upper body, which she has had for several years. She also reported that her mother and maternal grandmother have similar lesions and that her mother has been diagnosed with Birt-Hogg-Dube syndrome. Histopathologic features of one papule demonstrated basaloid cells emanating from a dilated follicular infundibula surrounded by a well-circumscribed fibromucinous stroma. Birt-Hogg-Dube syndrome is an autosomal-dominant-inherited condition characterized by fibrofolliculomas, trichodiscomas, and acrochordons. It is associated with renal tumors, spontaneous pneumothoraces, and possibly intestinal polyps. Treatment includes evaluation for associated renal, lung, and intestinal findings as well as cosmetic removal of skin lesions.
Topics: Adult; Female; Humans; Skin Neoplasms; Syndrome
PubMed: 15748585
DOI: No ID Found -
Annals of Dermatology Feb 2022Birt-Hogg-Dube syndrome (BHDS) is a rare disorder characterized by the triad of cutaneous lesions, renal tumors, lung cysts and inactivation of the gene (). Here, we...
Birt-Hogg-Dube syndrome (BHDS) is a rare disorder characterized by the triad of cutaneous lesions, renal tumors, lung cysts and inactivation of the gene (). Here, we present three female patients diagnosed with BHDS. First case a 55-year-old female had flesh moles histopathology compatible with angiofibroma, multiple cysts in the lung and kidneys, gene mutations ('c.1285dupC [p.His429Profs*]' 11th exon and 'c.653G>A [p.Arg258His]' 7th exon). The second case a 76-year-old female had trichodiscoma on her skin, multiple cysts in the lung, spontaneous pneumothorax, gene mutation 'c.1285dupC (p.His429Profs*27) 11th exon' and, her son had renal carcinoma history under 50 years of age. Our third case, also the daughter of case 2, had dermal papules histopathology compatible with trichodiscoma, spontaneous pneumothorax, gene mutation 'c.1285dupC (p.His429Profs*27) 11th exon' and, parotid oncocytoma. Through our cases, we document the first case of two mutations ('c.1285dupC [p.His429Profs*]' 11th exon and 'c.653G>A [p.Arg258His]' 7th exon) in the same gene and the 11th known case of parotid oncocytoma associated with BHDS in the light of the literature.
PubMed: 35221599
DOI: 10.5021/ad.2022.34.1.66 -
Orphanet Journal of Rare Diseases Jul 2021Birt-Hogg-Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin...
BACKGROUND
Birt-Hogg-Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS.
MATERIALS AND METHODS
The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations.
RESULTS
BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41).
CONCLUSIONS
All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.
Topics: Angiomyolipoma; Birt-Hogg-Dube Syndrome; Estrone; Female; Humans; Kidney Neoplasms; Male; Mutation; Poland; Proto-Oncogene Proteins; Tumor Suppressor Proteins
PubMed: 34229741
DOI: 10.1186/s13023-021-01931-0 -
Actas Dermo-sifiliograficas Apr 2012Birt-Hogg-Dubé syndrome is a rare autosomal dominant genodermatosis that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts,... (Review)
Review
Birt-Hogg-Dubé syndrome is a rare autosomal dominant genodermatosis that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The most common histological types found in renal tumors from patients with the syndrome are oncocytoma-chromophobe carcinoma hybrids and pure forms of chromophobe carcinoma, oncocytic carcinoma, and clear cell or papillary cell carcinoma. The syndrome is linked to mutations in the FLCN gene, which encodes folliculin and is preferentially expressed in the skin, kidney, and lung. The syndrome can exhibit a high degree of clinical variability, and the skin lesions that are a warning sign for dermatologists may be absent in up to 70% of cases. Consequently, although skin lesions and mutations in FLCN are the main diagnostic criteria for Birt-Hogg-Dubé syndrome, a diagnosis can be made based on noncutaneous manifestations, with or without known family history of the syndrome, even in the absence of histological confirmation of fibrofolliculomas or trichodiscomas.
Topics: Adenoma, Oxyphilic; Birt-Hogg-Dube Syndrome; Carcinoma, Renal Cell; Cysts; Diagnosis, Differential; Fibroma; Genes, Dominant; Germ-Line Mutation; Humans; Kidney Neoplasms; Lung Diseases; Pneumothorax; Proto-Oncogene Proteins; Skin Neoplasms; Tumor Suppressor Proteins
PubMed: 21937013
DOI: 10.1016/j.ad.2011.07.009 -
Urology Sep 2023To characterize the clinical manifestations and genetic basis of a familial cancer syndrome in patients with lipomas and Birt-Hogg-Dubé-like clinical manifestations...
PRDM10 RCC: A Birt-Hogg-Dubé-like Syndrome Associated With Lipoma and Highly Penetrant, Aggressive Renal Tumors Morphologically Resembling Type 2 Papillary Renal Cell Carcinoma.
OBJECTIVE
To characterize the clinical manifestations and genetic basis of a familial cancer syndrome in patients with lipomas and Birt-Hogg-Dubé-like clinical manifestations including fibrofolliculomas and trichodiscomas and kidney cancer.
METHODS
Genomic analysis of blood and renal tumor DNA was performed. Inheritance pattern, phenotypic manifestations, and clinical and surgical management were documented. Cutaneous, subcutaneous, and renal tumor pathologic features were characterized.
RESULTS
Affected individuals were found to be at risk for a highly penetrant and lethal form of bilateral, multifocal papillary renal cell carcinoma. Whole genome sequencing identified a germline pathogenic variant in PRDM10 (c.2029 T>C, p.Cys677Arg), which cosegregated with disease. PRDM10 loss of heterozygosity was identified in kidney tumors. PRDM10 was predicted to abrogate expression of FLCN, a transcriptional target of PRDM10, which was confirmed by tumor expression of GPNMB, a TFE3/TFEB target and downstream biomarker of FLCN loss. In addition, a sporadic papillary RCC from the TCGA cohort was identified with a somatic PRDM10 mutation.
CONCLUSION
We identified a germline PRDM10 pathogenic variant in association with a highly penetrant, aggressive form of familial papillary RCC, lipomas, and fibrofolliculomas/trichodiscomas. PRDM10 loss of heterozygosity and elevated GPNMB expression in renal tumors indicate that PRDM10 alteration leads to reduced FLCN expression, driving TFE3-induced tumor formation. These findings suggest that individuals with Birt-Hogg-Dubé-like manifestations and subcutaneous lipomas, but without a germline pathogenic FLCN variant, should be screened for germline PRDM10 variants. Importantly, kidney tumors identified in patients with a pathogenic PRDM10 variant should be managed with surgical resection instead of active surveillance.
Topics: Humans; Carcinoma, Renal Cell; Birt-Hogg-Dube Syndrome; Proto-Oncogene Proteins; Kidney Neoplasms; Lipoma; Transcription Factors; Skin Neoplasms; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; DNA-Binding Proteins; Membrane Glycoproteins
PubMed: 37331486
DOI: 10.1016/j.urology.2023.04.035 -
International Journal of General... 2022Birt-Hogg-Dubé syndrome (BHD), also named Hornstein-Knickenberg syndrome, is a rare autosomal dominant disease characterized by lung cysts, recurrent pneumothoraxes,... (Review)
Review
BACKGROUND
Birt-Hogg-Dubé syndrome (BHD), also named Hornstein-Knickenberg syndrome, is a rare autosomal dominant disease characterized by lung cysts, recurrent pneumothoraxes, renal cell carcinoma and skin fibrofolliculomas.
PURPOSE
This study summarizes the clinical and genetic information of Chinese BHD patients from all available reported cases and explores the relationship between the clinical and genetic spectrum in the hope of improving the prognosis of Chinese BHD patients.
METHODS
Relative studies were collected by searching PubMed, Cochrane Library, Embase, OVID medicine, SinoMed, Web of Science, China National Knowledge Infrastructure, Wanfang Data and China Hospital Knowledge Database from January 1, 1977 to December 31, 2021. The search strategy included the following term keys: (Birt-Hogg-Dubé syndrome OR Hornstein-Kinckenberg syndrome OR familial pulmonary cysts OR familial spontaneous pneumothorax OR fibrofolliculomas OR trichodiscomas OR inherited renal cancer syndromes OR ) AND (Chinese OR China).
RESULTS
In total, 287 Chinese patients from 143 families described in 31 references were included in this article. Chinese BHD patients tended to present more pulmonary symptoms but fewer skin lesions and renal malignancies, which appeared to be atypical when compared with Caucasian patients. The mutation spectrum among Chinese BHD patients was established with the mutational hot spot c.1285depC/delC as the most frequent mutation. In addition, this mutation spectrum also showed some differences from other races, with a relatively frequent large deletion c.872-429_1740+1763del (exon 9-14 deletion) reported only in Chinese individuals but no observation of the two mutational hot spots found in Japanese individuals. We also attempted to establish potential pheno-genotype correlations in Chinese BHD patients, but the results were negative.
CONCLUSION
To improve the prognosis of BHD patients, physicians need to increase their awareness of BHD by focusing on the family history of pneumothorax as well as skin lesions in patients with lung cysts and promptly advising patients on genetic sequencing.
PubMed: 35637701
DOI: 10.2147/IJGM.S359660 -
Annals of Translational Medicine Nov 2020Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disease that has been characterized by skin lesions, multiple pulmonary cysts, spontaneous pneumothorax, and renal...
BACKGROUND
Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disease that has been characterized by skin lesions, multiple pulmonary cysts, spontaneous pneumothorax, and renal tumors, but the patients in Asian countries may show fewer symptoms. We aimed to explore and summarize the clinical features of BHD patients in East Asia to facilitate early diagnosis and timely interventions.
METHODS
We collected and analyzed the clinical data of patients diagnosed with BHD in our hospital by reviewing medical records. We performed a systematic literature search regarding the presenting clinical features in BHD patients from China, Japan, and Korea and then reviewed the publications that were identified.
RESULTS
In our hospital, 10 patients were diagnosed with BHD from April 2015 to September 2019. After reviewing the literature, we recruited 38 articles, including 12, 20, and 6 reports from China, Japan, and Korea, respectively. A total of 166 patients were included in this study, and 100 of them (60.2%) were females. Multiple pulmonary cysts were present in 145 patients (87.3%), and 124 patients (74.7%) had a history of pneumothorax on at least one occasion. Skin biopsy confirmed fibrofolliculomas (FFs) alone in 22 patients (13.3%), trichodiscomas (TDs) alone in 3 patients (1.8%), and both FFs and TDs in 7 patients (4.2%). Renal carcinoma only occurred in 12 (7.2%) patients. The most frequent genetic mutations in East Asian patients were c.1285delC on exon 11 (18.4%), c.1285dupC on exon 11 (18.4%), and c.1347_1353dupCCACCCT on exon 12 (8.2%).
CONCLUSIONS
Our findings suggested that pulmonary cysts are the most frequent radiological findings, and pneumothorax is the most common symptom in East Asian patients with BHD, and that skin lesions and kidney involvement are less frequent. To make an early diagnosis and minimize the severity of complications, careful observation, and timely genetic examination of the gene is essential.
PubMed: 33313181
DOI: 10.21037/atm-20-1129