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European Respiratory Review : An... Sep 2020Birt-Hogg-Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene , encoding the protein...
Birt-Hogg-Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene , encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.
Topics: Birt-Hogg-Dube Syndrome; Cysts; Humans; Lung Diseases; Pneumothorax; Tomography, X-Ray Computed
PubMed: 32943413
DOI: 10.1183/16000617.0042-2020 -
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 -
Tidsskrift For Den Norske Laegeforening... Apr 2020Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant genetic disorder characterised by pulmonary cysts, fibrofolliculomas and renal tumours. The pulmonary cysts may...
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant genetic disorder characterised by pulmonary cysts, fibrofolliculomas and renal tumours. The pulmonary cysts may lead to pneumothorax, and in cases of primary, spontaneous pneumothorax the syndrome should be excluded. The renal tumours are frequently malignant, but slow-growing. Screening and family assessment enable discovery of renal cancer at an early stage. The syndrome is underdiagnosed and little known.
Topics: Birt-Hogg-Dube Syndrome; Humans; Kidney Neoplasms; Lung Diseases; Pneumothorax; Skin Neoplasms
PubMed: 32321218
DOI: 10.4045/tidsskr.18.0848 -
Arquivos Brasileiros de Oftalmologia 2020The purpose of this study was to report a series of cases of solitary fibrofolliculoma, a lesion seldom observed in the lids. Demographics, as well as clinical and... (Review)
Review
PURPOSE
The purpose of this study was to report a series of cases of solitary fibrofolliculoma, a lesion seldom observed in the lids. Demographics, as well as clinical and histological aspects of the lesion were evaluated.
METHODS
This was a retrospective case series spanning a period of 18 years. All the included patients were diagnosed with solitary fibrofolliculoma confirmed by histological examination. Data regarding patient demographics, signs, and symptoms, course of the disease, location of the lesion, clinical and histological diagnosis, and outcome were collected.
RESULTS
Eleven cases of solitary fibrofolliculoma were diagnosed in the study period. The median age of patients was 51 ± 16.3 years (range: 27-78 years). Most patients were females (7/11; 64%). Five of the patients (45%) were asymptomatic; four (36%) reported bleeding, one (9%) had referred itching, and one (9%) rubbing of the lesion. The lesion occurred in a wide range of locations; one of them was located in the lids. The diagnosis for all lesions was histological based on characteristic findings of a hair follicle occasionally dilated and containing keratin material surrounded by a moderately well-circumscribed thick mantle of fibrous tissue. The infundibular follicular epithelium extended out into this fibrous mantle forming epithelial strands or cords. There were no relapses after exeresis.
CONCLUSION
Solitary fibrofolliculoma is a rare lesion, seldom affecting the eyelids. We reported 11 cases, and the third case reported thus far in the literature affecting the lids. Diagnosis may be easily missed due to the nonspecific symptoms and clinical appearance. Therefore, it is necessary to perform excisional biopsy and histological examination for the recognition of this lesion.
Topics: Adult; Aged; Female; Hair Diseases; Hair Follicle; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Skin; Skin Neoplasms
PubMed: 33470275
DOI: 10.5935/0004-2749.20200092 -
Gene Jan 2018Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dubé (BHD) syndrome that predisposes... (Review)
Review
Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dubé (BHD) syndrome that predisposes to fibrofolliculomas, lung cysts and spontaneous pneumothorax, and an increased risk for developing kidney tumors. Although the encoded protein, folliculin (FLCN), has no sequence homology to known functional domains, x-ray crystallographic studies have shown that the C-terminus of FLCN has structural similarity to DENN (differentially expressed in normal cells and neoplasia) domain proteins that act as guanine nucleotide exchange factors (GEFs) for small Rab GTPases. FLCN forms a complex with folliculin interacting proteins 1 and 2 (FNIP1, FNIP2) and with 5' AMP-activated protein kinase (AMPK). This review summarizes FLCN functional studies which support a role for FLCN in diverse metabolic pathways and cellular processes that include modulation of the mTOR pathway, regulation of PGC1α and mitochondrial biogenesis, cell-cell adhesion and RhoA signaling, control of TFE3/TFEB transcriptional activity, amino acid-dependent activation of mTORC1 on lysosomes through Rag GTPases, and regulation of autophagy. Ongoing research efforts are focused on clarifying the primary FLCN-associated pathway(s) that drives the development of fibrofolliculomas, lung cysts and kidney tumors in BHD patients carrying germline FLCN mutations.
Topics: Birt-Hogg-Dube Syndrome; Humans; Mutation; Proto-Oncogene Proteins; Signal Transduction; Tumor Suppressor Proteins
PubMed: 28970150
DOI: 10.1016/j.gene.2017.09.044 -
EClinicalMedicine Sep 2022Birt-Hogg-Dubé syndrome is a rare genetic tumor syndrome characterized by renal cell cancer, lung bullae, pneumothorax, and fibrofolliculoma. Patients with such orphan...
BACKGROUND
Birt-Hogg-Dubé syndrome is a rare genetic tumor syndrome characterized by renal cell cancer, lung bullae, pneumothorax, and fibrofolliculoma. Patients with such orphan tumor disorders are at risk of not receiving a timely diagnosis. In the present, gender-sensitive study, we analyzed the delay between onset of symptoms and diagnosis of Birt-Hogg-Dubé syndrome.
METHODS
Clinical data of 158 patients from 91 unrelated families were collected. mutation testing was performed in index patients and family members.
FINDINGS
The occurrence of the first symptom (fibrofolliculoma, pneumothorax or renal cell cancer) was rarely followed by a timely diagnosis of Birt-Hogg-Dubé syndrome and did so significantly less often in female (1.3%) compared to male (11.4%) patients (chi-square 6.83, p-value 0.009). Only 17 out of 39 renal cell cancers (7/17 female, 10/22 male patients) were promptly recognized as a symptom of Birt-Hogg-Dubé syndrome. Patients in which renal cell cancer was initially not recognized as a symptom of Birt-Hogg-Dubé syndrome waited 9.7 years (females SD 9.2, range 1-29) and 8.8 years (males, SD 4.1, range 2-11) for their diagnosis, respectively. Four (three female, one male) patients developed renal cell cancer twice before the genetic tumor syndrome was diagnosed. The delay between fibrofolliculoma or pneumothorax as a first symptom and diagnosis of Birt-Hogg-Dubé syndrome was considerable but not significantly different between females and males (18.1/17.19 versus 16.1/18.92 years). Furthermore, 73 patients were only diagnosed due to family history (delay 15.1 years in females and 17.4 years in males).
INTERPRETATION
The delay between onset of symptoms and diagnosis of Birt-Hogg-Dubé syndrome can be substantial and gender-dependent, causing considerable health risks for patients and their families. It is therefore important to create more awareness of Birt-Hogg-Dubé syndrome and resolve gender biases in diagnostic work-up.
FUNDING
None declared.
PubMed: 35875814
DOI: 10.1016/j.eclinm.2022.101572 -
Korean Journal of Ophthalmology : KJO Sep 2007To report the first case of a solitary eyelid fibrofolliculoma and to review the literature. (Review)
Review
PURPOSE
To report the first case of a solitary eyelid fibrofolliculoma and to review the literature.
METHODS
A 37-year-old female patient visited the outpatient department with a lesion in the right upper lid that had been growing steadily for a year. The patient had visited the local clinic, and under the diagnosis of chalazion had received incision and curettage twice, but the lesion had recurred.
RESULTS
The 5x5 mm lesion was located near the upper lid margin. It was a red, hemispheric, smooth nodule, relatively solid to palpation and not painful. Excision and biopsy were performed, and through a histological exam, the diagnosis of fibrofolliculoma was later confirmed.
CONCLUSIONS
Solitary fibrofolliculoma is rare, and to the authors' knowledge, a lesion arising in the eyelid has not yet been reported. Fibrofolliculoma should be included in the differential diagnosis when a localized mass lesion arising in the eyelid is encountered.
Topics: Adult; Chalazion; Diagnosis, Differential; Eyelid Neoplasms; Female; Fibroma; Humans; Ophthalmologic Surgical Procedures
PubMed: 17804924
DOI: 10.3341/kjo.2007.21.3.169