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Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (30%) compared with that of Western countries (75∼90%), which appear to be underestimated.To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses.We studied 31 patients (47.0±13.2years old, range 15-71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs).FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn't done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD.Skin lesions appear to be more prevalent than previously reported (30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs.

A 32-year-old female presented for evaluation and removal of a mole on her left scalp. She stated that the mole was present since early childhood, and did not undergo any recent change or cause pain or pruritus. There was no personal history of any skin cancer.

Trichodiscomas are benign tumors of the skin which develop around a hair follicle. They usually present on the face, neck, or trunk region. The authors report a rare case of a 63-year-old man who presented with a tumor on the left lower eyelid that was histologically proven to be a trichodiscoma of conjunctival origin.Trichodiscomas are benign tumors of the skin appendage which develop around a hair follicle. Although conjunctival hair follicles are rudimentary and do not give rise to hair, rarely a benign proliferation of these cells can result in trichodiscoma of the conjunctiva.

A 50-year-old woman presented with groups of multiple small, round, whitish papules on her cheeks. Biopsy was take from one of the papules. There was no significant prior medical history and this was the first presentation to a dermatologist. Review the high-quality, interactive digital Aperio slides at http://virtualacp.com/JCPCases/jclinpath-2019-206165\_1/ and http://virtualacp.com/JCPCases/jclinpath-2019-206165\_2/ and consider your diagnosis. 1. Fibrous papule 2. Fibrofolliculoma/trichodiscoma 3. Basaloid follicular hamartoma 4. Trichofolliculoma 5. Pan-folliculoma B Fibrofolliculoma/trichodiscoma The diagnosis is fibrofolliculoma. The histological examination shows a non-encapsulated fibrous lesion with central keratin-filled follicular structures. Thin strands of epithelium extended from the follicles, with some joining sebaceous ducts or anastomosing with other strands. A sclerotic fibrous proliferation of mucinous connective tissue …

In our routine and consultative pathology practices, we have noticed that a relatively high proportion of spindle cell predominant trichodiscomas demonstrate a remarkable stromal admixture of adipose tissue, which along with spindle cells, prominent collagen bundles and myxoid change closely resembles spindle cell lipoma (SCL). To clarify their possible relationship to SCL, 25 cases of trichodiscoma and fibrofolliculoma with stromal "lipomatous metaplasia" were collected and examined using immunohistochemical stains [CD34 and retinoblastoma-1 (RB1) protein] and fluorescence in situ hybridization (RB1 deletion). The patients ranged in age from 35 to 81 years (median 64 years). The male to female ratio was almost equal (14:11). All tumors with a known location were situated on the face with a special predilection for the nose. All cases were sporadic, with all patients having a single lesion and showing no clinical features of Birt-Hogg-Dube syndrome. No case with available follow-up presented with a recurrence or an otherwise aggressive clinical course. Spindle cell stroma was immunohistochemically positive for CD34 in 16 of 20 cases, and 18 of 19 cases showed loss of RB1 staining in lesional spindle cells. Fluorescence in situ hybridization analysis detected RB1 gene heterozygous deletion in 6 of 20 cases. We conclude that despite the SCL-like appearance of the investigated cases, the majority of them supposedly represent genuine spindle cell predominant trichodiscomas with adipose tissue admixture. However, there was a subset of histopathologically indistinguishable cases with proved RB1 deletion, which likely represent SCL with trichodiscoma/fibrofolliculoma-like epithelial/adnexal induction rather than spindle cell predominant variant of trichodiscoma.

Birt-Hogg-Dube syndrome is a rare autosomal dominant disease caused by a mutation in the FLCN gene and presents with a triad of multiple fibrofolliculomas, trichodiscomas, and masses that clinically resemble fibroepithelial polyps (acrochordones), accompanied by an increased risk of kidney tumors and lung cysts. The paper provides a literature review supplemented by clinical cases and the morphological pattern of skin lesions. It presents the clinical and morphological features of cutaneous manifestations of the syndrome and gives diagnostic criteria.

Familial multiple trichodiscomas is a condition characterized by multiple asymptomatic skin papules. The inheritance pattern has not been established. The skin lesions usually appear in childhood. The diagnosis of the cutaneous papules is established by pathologic evaluation. Birt-Hogg-Dube syndrome is excluded by not detecting any aberration in the folliculin gene locus. Including our patient, 15 index individuals and their families are described. There is no systemic organ involvement or associated malignancies in individuals with this condition.

Fibrofolliculoma and trichodiscoma represent different stages of the same follicular neoplasm. Some patients with multiple lesions have the Birt–Hogg–Dube syndrome.

Introduction: Birt-Hogg-Dube Syndrome (BHDS) is a rare autosomal dominant genodermatosis, characterized by cutaneous lesions, kidney tumors and lung cysts. Aims and objectives: We present the case of a Greek family with a history of recurrent pneumothorax proved to be BHDS. Methods: A 46 year-old male presented with a 5-day history of cough and an unremarkable initial clinical examination. His family history was notable for recurrent pneumothoraces (PNX) affecting his twin brother and an older sister, as well as their father and one paternal aunt, which raised serious concern about an increased probability of an inherited genetically determined disease with pulmonary manifestations. Results: High resolution computed tomography of the chest demonstrated several thin-walled lenticular-shaped parenchymal lung cysts which occupied predominantly the lower zones. Skin biopsy of lesions on the face and upper trunk similar in all three siblings, demonstrated histologic characteristics of the type of trichodiscoma and as such consistent with BHD syndrome. Renal ultrasonography and colonoscopy were unremarkable. The family was also offered genetic testing which depicted a mutation of the gene FLCN further documenting the diagnosis. Conclusions: BHDS can develop pneumothorax as a first manifestation and affect other members of the family. Genetic testing is necessary to further document diagnosis and for optimal management.

Two unusual Carney complex patients are described. In one of them, several cutaneous biopsies revealed myxoid lesions that were rather more close to authentic adnexal neoplasms with myxoid stroma than to a "myxoma with an epithelial component." These included lesions resembling trichofolliculoma, infundibular cyst, and trichodiscoma. Additionally, 1 soft tissue myxoma was unique in the sense that it greatly resembled a cardiac myxoma, begging the question whether this could represent an embolus from the patient's cardiac myxoma. Given the large size and complexity and heterogeneity of the cutaneous lesions, the authors suggest that these may represent authentic cutaneous neoplasms accompanied by myxoid stroma and not adnexal elements induced by the stroma. However, the latter mechanism is well recognized and demonstrated by our second patient in whom adnexal-type elements in the cutaneous lesion were clearly induced by the myxoid stroma but were unusually complex by manifesting panfollicular and also sebaceous differentiation.

Background: Birt–Hogg–Dube syndrome (BHDS) (MIM 135150) is an autosomal dominant predisposition to the development of follicular hamartomas (fibrofolliculomas), lung cysts, spontaneous pneumothorax, and kidney neoplasms. Germline mutations in BHD are associated with the susceptibility for BHDS. We previously described 51 BHDS families with BHD germline mutations. Objective: To characterise the BHD mutation spectrum, novel mutations and new clinical features of one previously reported and 50 new families with BHDS. Methods: Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning. We analysed evolutionary conservation of folliculin by comparing human against the orthologous sequences. Results: The BHD mutation detection rate was 88% (51/58). Of the 23 different germline mutations identified, 13 were novel consisting of: four splice site, three deletions, two insertions, two nonsense, one deletion/insertion, and one missense mutation. We report the first germline missense mutation in BHD c.1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas. This mutation occurs in a highly conserved amino acid in folliculin. 10% (5/51) of the families had individuals without histologically confirmed fibrofolliculomas. Of 44 families ascertained on the basis of skin lesions, 18 (41%) had kidney tumours. Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p = 0.0032). Similarly, patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased greater probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p = 0.011). A comprehensive review of published reports of cases with BHD germline mutation is discussed. Conclusion: BHDS is characterised by a spectrum of mutations, and clinical heterogeneity both among and within families.

In 1977, Birt, Hogg, and Dube described a kindred of 70 individuals, some of whom presented with small skin-colored papules, predominantly of the face. These developed in early adulthood and were noted to be inherited in a dominant pattern. The histomorphology of the papules was described as “abnormal hair follicles with epithelial strands extending out from the infundibulum of the hair follicle into a hyperplastic mantle of specialized fibrous tissue.” The authors applied the term fibrofolliculoma (FF) to these lesions. Also described in these patients were trichodiscomas (TD) and acrochordons. Trichodiscoma is a benign tumor of perifollicular mesenchyme. It is thought to represent a proliferation of the haarscheibe (hair disk), a perifollicular “richly vascularized dermal pad covered with thick epidermis containing Merkel cells and supplied by a thick myelinated nerve the branches of which end at the lower epidermal surface and on the blood vessels of the dermal pad.” It is composed of a dermal interfollicular proliferation of spindle cells in a loose connective tissue matrix with varying amounts of mucin. It may have an orientation parallel to the skin surface. The haarscheibe is thought to represent a mechanoreceptor in animal skin. Its significance in humans is uncertain. The acrochordons in the original description of the syndrome were reported to have histologic findings typical of acrochordons. However, a subsequent study suggests that they have pathologic features of fibrofolliculoma and trichodiscoma. Some patients have also been found to have facial lesions indistinguishable from angiofibroma.

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. info:eu-repo/semantics/publishedVersion

Importance The differential diagnosis of extensive open comedones includes inherited genetic syndromes and several acquired conditions. Birt-Hogg-Dube syndrome (BHD) is not typically included in the differential diagnosis of syndromes with comedonal lesions. Given the potentially life-threatening systemic complications associated with BHD, early recognition and diagnosis of the condition is important. Observations We describe comedonal or cystic fibrofolliculomas in 4 patients with BHD. Cutaneous lesions were identified on the face, neck, chest, and abdomen. Conclusions and Relevance Comedonal or cystic fibrofolliculomas are a variant of fibrofolliculomas that have not previously been well characterized in patients with BHD and represent a novel diagnostic clue to its early detection and diagnosis. Expanding the phenotypic features of BHD facilitates earlier diagnosis of the syndrome, which allows for early surveillance of renal cancer in affected patients as well as disease screening in their relatives.

We present three members of a Queensland family with clinical and histopathological features consistent with Birt-Hogg-Dubé syndrome. Two of the three family members were able to be screened for associated disorders. The mother of the family was found to have a solitary colonic polyp, a large ovarian cyst and two chorioretinal scars. No associated disorders were found on investigation of one of the two affected sons.

SUMMARY A 50-year-old woman presented with multiple skin-coloured facial papules. There was a family history of similar lesions. Histology of one of these papules was consistent with fibrofolliculoma. Multiple fibrofolliculomas together with flexural acrochordons suggested the diagnosis of Birt–Hogg–Dube syndrome. Investigations to exclude associated disease revealed changes consistent with multinodular goitre on thyroid ultrasound. The literature regarding the association of Birt–Hogg–Dube syndrome with internal disease is reviewed.

Background: Fibrofolliculomas and trichodiscomas are benign dermal neoplasms that likely derive from the mantle of the hair follicle and can occur sporadically or in association with Birt–Hogg–Dube syndrome (BHDS). Little is known about the pathogenesis and immunophenotypic properties of these entities. Methods: We investigated the histomorphologic and immnophenotypic properties of 15 fibrofolliculomas and trichodiscomas in two patients with BHDS and eight with sporadic disease. Results: We found the following: (1) fibrofolliculomas and trichodiscomas occurring in the setting of BHDS show microscopically contiguous histomorphologic features as compared to those occurring sporadically; (2) the immunophenotypic characteristics of syndromic-associated and sporadic types are identical and consist of (3) perifollicular vimentin (+), CD34 (+) and Factor XIII (–) spindle cells. Conclusions: Despite subtle histomorphologic differences, trichodiscomas and fibrofolliculomas are immunophenotypically similar, and are thus likely derived from a similar histogenic precursor. Given the previously reported CD34 (+) immunophenotype of the hair mantle, our findings would support an origin of these lesions from the mantle of the hair follicle. The proliferation of CD34 (+) spindle cells seen in conjunction with these lesions should not be confused with other CD34 (+) dermal entities.

Trichodiscomas are hamartomatous lesions of the follicular unit and of its surrounding stroma composed of epithelial and mesenchymal tissue elements. The dominating tissue element in trichodiscoma is the central fibrous stroma, encircled by prominent clusters of sebaceous lobules that resemble mitts. Rare variants of trichodiscomas with CD34-positive spindle cell-pedominant stroma have been described. We report a case of spindle cell-predominant trichodiscoma with prominent pseudosarcomatous/ancient features consisting in numerous large atypical spindle cells with frequent multinucleation, with no mitotic activity. The cytological changes were similar to those described in ancient schwannoma and symplastic hemangioma. We propose to call this lesion symplastic trichodiscoma. Only 1 previous case of fibrofolliculoma with pseudosarcomatous/ancient changes has already been reported. Although such lesions can appear worrisome at first glance, their benign evolution, the absence of mitosis, and the phenotypic studies excluding malignant differential diagnoses like atypical fibroxanthoma are reassuring. The precise pathogenesis of the symplastic features in schwannoma as in trichodiscoma/fibrofolliculoma is not known yet.

Multiple fibrofolliculomas, trichodiscomas, and acrochordons compose the triad of cutaneous lesions characterizing the Birt-Hogg-Dubé syndrome, inherited in an autosomal dominant fashion. We report a case of a family who had the triad of tumors of the Birt-Hogg-Dubé syndrome. Two members were observed clinically and histologically. Biopsies of the facial papules disclosed features of the fibrofolliculoma/trichodiscoma spectrum. Lesions that were clinically acrochordon-like proved to correspond to the same histopathologic spectrum. The characterization of the nature of the acrochordon-like lesions in our patients and the review of the literature allow us to question if acrochordons (skin tags) should be maintained as a component of this association. In light of our conclusion that fibrofolliculoma, trichodiscoma, and the acrochordon-like lesions are histologic variations of a single lesion, we further question whether the term "syndrome" is valid.

We report a case of a 51-year-old Hispanic female who presented with a several year history of multiple flesh colored papules of cosmetic concern on the nose and medial cheeks. Biopsies revealed fibrofolliculoma and trichodiscoma. The patient was referred for genetic testing and was found to be positive for the FLCN gene defect, confirming a diagnosis of Birt-Hogg-Dube syndrome. Further work-up with screening renal ultrasound and CT scan of the thorax and abdomen was unrevealing. For treatment of these skin lesions, dermasanding was attempted initially with only minimal benefit. She subsequently had multiple lesions treated with electrodessication at a low setting and was very pleased with the results. Curettage was not performed and importantly, there has yet to be a recurrence of lesions treated with only hyfrecation.

Background: Trichodiscomas are rare hamartomas of the dermal portion of the hair disc, a specialized component of the perifollicular mesenchyme. They are usually found as asymptomatic multiple skin-colored papules on the face and extremities and may have an autosomal dominant inheritance pattern. However, a solitary variant has been described. Case report: A 78-year-old woman presented with a single, non-pigmented, firm papule on the left tip of the nose, measuring 3.5 mm in diameter. Results: The histological examination revealed the previously described features of a trichodiscoma. The immunohistochemical analysis showed strong immunoreactivity for CD34 in the spindle cell component. Spindle cells were negative for S-100, HMB-45, Melan-A, EMA, neurofilament, desmin, and Factor XIIIa by immunohistochemistry. Conclusions: We report strong reactivity for CD34 in the spindle cell component of a trichodiscoma. We suggest that this lesion be considered in the differential diagnosis of any CD34+ dermal spindle cell proliferation, in which an adjacent epithelial component cannot be entirely excluded.

Background: Mutation in the folliculin gene in Birt–Hogg–Dube (BHD) syndrome leads to a spectrum of benign tumors of the hair follicle, classically including both fibrofolliculoma and trichodiscoma. In addition, lesions clinically indistinguishable from fibrofolliculoma/ trichodiscoma may show histopathologic findings of perifollicular fibroma or angiofibroma. Although some consider perifollicular fibroma to be a variant of angiofibroma, the specific histopathologic findings of perifollicular fibroma are uncommon. Methods: This is a case series. Results: In 4 patients with multiple facial lesions, recognizing perifollicular fibroma would have been helpful in leading to the diagnosis of BHD syndrome. Conclusion: Perifollicular fibroma is on a spectrum with fibrofolliculoma and trichodiscoma; in a patient with multiple lesions, the diagnosis of perifollicular fibroma is suggestive of BHD syndrome.

Birt-Hogg-Dube syndrome (BHDS) is characterized by a clinical triad including cutaneous hamartomas originating from hair follicles, lung cysts/pneumothorax, and kidney tumors. Inactivating mutations of the tumor suppressor gene FLCN are identified in most families with BHDS. Usually, patients are referred for genetic examination by dermatologists because of the presence of typical multiple skin tumors with or without additional symptoms. However, because of phenotypic variability and incomplete penetrance, the clinical presentation of BHDS is not yet fully defined. Criteria for genetic testing and diagnosis that take into account variable manifestations have recently been proposed by the European BHD Consortium. We sequenced the FLCN gene coding region in a series of 19 patients selected for kidney and/or lung manifestations. Overall, FLCN mutations were found in 9 of 19 (47%) families and were detected only in probands who had either >2 components of the clinical triad or a single component (renal or pulmonary) along with a family history of another main BHDS manifestation. Typical cutaneous lesions were present only in 8 of 21 FLCN mutation carriers aged >20 years identified in the mutation-positive families. In addition, we provide clinical and molecular evidence that parotid oncocytoma, so far reported in six BHDS cases, is associated with this condition, based on the observation of a patient with bilateral parotid involvement and marked reduction of the wild-type FLCN allele signal in tumor DNA. Overall, the results obtained in this study contribute to the definition of the phenotypic characteristics that should be considered for BHDS diagnosis and FLCN mutation testing.

Birt-Hogg-Dube syndrome consists of fibrofolliculomas, trichodiscomas, and acrochordons and has been associated with several noncutaneous tumors. We report the first case of Birt-Hogg-Dube syndrome in association with a parotid oncocytoma, a rare salivary gland tumor. (J Am Acad Dermatol 2000;43:1120-2.)

A 36-year-old paraplegic man developed multiple giant fibromyxoid tumors surrounding a meningomyelocele scar that we believe are forme fruste of trichodiscomas. Histologic examination showed a papillated, slightly hyperplastic epidermis surrounding a delicate fibrovascular proliferation set in a stroma of loose fibrillar connective tissue and stellate fibroblasts. A melanocytic nevus was incorporated into one of the lesions. We believe that these giant lesions are connective tissue nevi of the adventitial dermis that comprise a new clinical variant of trichodiscoma. The potential significance of the relationship between these abortive trichodiscomas and abnormalities of the neural crest is discussed.

The syndrome of Birt-Hogg-Dube (BHD) is an autosomal dominant syndrome, characterized by a triad of cutaneous lesions including multiple fibrofolliculomas, trichodiscomas, and acrochordons. There are many clinical expressions, solitary and multiple forms, with or without other skin tumors. In the literature BHD syndrome has been associated with internal malignancy. We describe a patient with multiple firm, skin-colored papules in which the three types of lesion are documented. No signs of systemic disease were present. (C) 1998 Elsevier Science B.V. All rights reserved

Seventeen solitary nasal tumors that fulfilled all diagnostic criteria of so-called neurofollicular hamartoma, apart from distinct S100-positivity, were compared histopathologically and immunohistochemically with seven typical trichodiscomas from a similar clinical setting. Both the S100-negative neurofollicular hamartoma-like tumors and the trichodiscomas expressed an identical CD13-positive/CD34-positive fibrocytic immunophenotype without co-expression of neural/perineural (S100, neurofilament, epithelial membrane antigen), myogenic (desmin, calponin, muscle-specific actin, and alpha-smooth muscle actin), or melanocytic (S100, HMB45, NKI/C3, MelanA) epitopes. Histopathologically, there was striking morphologic overlap between trichodiscoma and S100-negative neurofollicular hamartoma-like tumor, apart from a highly characteristic fascicularly organized cellular fibrocytic stroma in the latter. We conclude that fibrofolliculoma/trichodiscoma and neurofollicular hamartoma-like tumor are morphologic variants of a single hamartomatous entity in which neurofollicular hamartoma-like tumor occupies the cellular pole of the morphologic spectrum. The entity formerly known as neurofollicular hamartoma appears to be nothing but a particularly cellular trichodiscoma with a distinctively organized stroma composed of CD34-positive fibrocytes. We therefore propose the new term spindle cell predominant trichodiscoma (SCPT) for this particular variant of the morphologic fibrofolliculoma/trichodiscoma spectrum.

Birt-Hogg-Dube Syndrome is an autosomal dominant condition characterized by a triad of fibrofolliculomas, trichodiscomas, and acrochordons. Since the first description in 1977, many conditions have been described in association with its clinical triad. Recent epidemiological studies have shown a significant association between the occurrence of lesions in the fibrofolliculoma/trichodiscoma category with renal neoplasms and pneumothoracies. The BHD protein folliculin had recently been identified. The histological findings of the clinical lesions are distinctive. We report a patient with a history of melanoma who presented for routine surveillance. Facial lesions in the fibrofolliculoma/trichodiscoma category were identified. Diagnostic work-up revealed concomitant multinodular goiter, pulmonary cyst, and renal mass. The patient later developed pneumothorax. Clinical manifestations, histological findings, associations, management, and a review of the Birt-Hogg-Dube Syndrome are discussed.

Birt-Hogg-Dube syndrome (BHDS) was originally described in 1977 as the grouping of 3 skin tumors—the fibrofolliculoma, trichodiscoma, and acrochordon—in family members with an autosomal dominant inheritance pattern. In recent years it has become clear that these 3 lesions likely represent only 1 of these tumors, the fibrofolliculoma. More important, evidence now supports a definite susceptibility to malignant renal tumors and pulmonary disease in patients with BHDS. Clinical recognition of this entity is possible in spite of the fact that several syndromes exist that are characterized by the presence of multiple firm facial papules. We will discuss the evolution of BHDS from the original description to the recent discovery of the genetic susceptibility locus, illustrate the clinical differential diagnosis, and highlight the workup needed for newly diagnosed patients and their family members.