Birt-Hogg-Dube syndrome presenting as multiple oncocytic parotid tumors

Lindor, Noralane M.; Kasperbauer, Jan L.; Lewis, Jean E.; Pittelkow, Mark R.

doi:10.1186/1897-4287-10-13

Cited by 27 publications

(16 citation statements)

References 11 publications

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“…28,30 Other clinical manifestations reported to be associated with FLCN mutations include parotid and thyroid oncocytomas. 17,[55][56][57] Despite the early association by Hornstein and Knickenberg, cohort studies do not find an increased incidence of colon cancer or colon polyps in BHD patients, 29 although one study did find a significantly increased risk for developing colon cancer in patients who carried the FLCN c.1285dupC mutation over patients who carried the c.610delGCinsTA mutation. 58 The possibility that FLCN mutations lead to an increased risk of lung adenocarcinoma has also been raised by at least two Japanese cohorts, 17,59 although the authors themselves caution that this may just be a correlation given the relative frequency of development of this tumor.…”

Section: Clinical Featuresmentioning

confidence: 97%

New Developments in the Pathogenesis of Pulmonary Cysts in Birt–Hogg–Dubé Syndrome

Kennedy

Khabibullin

Boku

et al. 2020

Semin Respir Crit Care Med

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Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant disorder caused by germline loss-of-function mutations in Folliculin gene (FLCN). BHD is characterized by lower lobe-predominant pulmonary cysts with risk of pneumothorax, benign skin tumors (fibrofolliculomas), and renal cell carcinoma, often of an unusual chromophobe/oncocytic hybrid histology. The FLCN protein functions in multiple signaling and metabolic pathways including positive regulation of mechanistic target of rapamycin complex 1 (mTORC1) activity via FLCN's GTPase (GAP) activity for Rag C, positive regulation of Wnt signaling (in mesenchymal cells), and negative regulation of TFE3 nuclear localization. Therefore, FLCN-deficient cells are predicted to have reduced mTORC1 and Wnt activity and enhanced TFE3 activity. Folliculin also has functions in autophagy, mitochondrial biogenesis, cell-cell adhesion, 5′ AMP activated protein kinase activity, and other pathways. The specific contributions of these pathways to the lung manifestations of BHD are largely unknown. This review is focused on the pulmonary manifestations of BHD, highlighting selected recent advances in elucidating the cellular functions of FLCN and current hypotheses related to the pathogenesis of cystic lung disease in BHD, including the “stretch hypothesis.” We also discuss important knowledge gaps in the field, including the genetic, cellular and physical mechanisms of cyst pathogenesis, and the timing of cyst initiation, which may occur during lung development.

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Section: Clinical Featuresmentioning

confidence: 97%

New Developments in the Pathogenesis of Pulmonary Cysts in Birt–Hogg–Dubé Syndrome

Kennedy

Khabibullin

Boku

et al. 2020

Semin Respir Crit Care Med

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“…[2,4] In BHD, the most common renal tumor is a hybrid chromophobe/oncocytic renal cancer. [3] Chromophobe RCCs are derived from intercalated cells that reside in the renal collecting duct; patients with inactivating mutations in the FLCN gene are at risk of developing bilateral chromophobe RCCs with multiple foci. [8] Early diagnosis of BHD is a key to ensure appropriate renal screening and early detection of RCC which significantly decreases mortality in these patients.…”

Section: Ajsmentioning

confidence: 99%

“…Additional findings include pulmonary cysts with an incidence of spontaneous pneumothoraces in 25% of patients. [3] It is important to highlight that BHD is a hereditary renal cell carcinoma (RCC) syndrome and patients have a significantly increased risk of both benign and malignant renal lesions. [2,4] Other less common findings of BHD include lipomas, parathyroid adenomas, salivary tumors, and colonic polyps/tumors.…”

mentioning

confidence: 99%

“…Ultrasound evaluation of the salivary glands is a fast, inexpensive modality which can accurately assess pathology without radiation exposure. [3] The salivary glands on ultrasound are typically homogenous structures that are hyperechoic compared to adjacent muscles. [5] Their evaluation can be challenging due to body habitus, complexity of the surrounding anatomic structures, and the extension of the parotid glands into the deep spaces AJS of the neck.…”

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confidence: 99%

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Birt-Hogg-Dubé Syndrome: A Case Report Describing Sonographic Evaluation of Salivary Gland Oncocytomas

Kapcio

Skalski

Dogra

2019

AJS

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Birt-Hogg-Dubé (BHD) syndrome is a rare hereditary disorder associated with autosomal dominant hereditary epithelial carcinomas, in which patients have an increased incidence of renal cell carcinomas, scattered hamartomas, pulmonary cysts, and spontaneous pneumothoraces. Other less common findings include lipomas, parathyroid adenomas, salivary gland tumors, and colonic polyps/tumors. Early diagnosis of BHD can help establish renal screening and reduce mortality by early detection and more effective treatment of renal cell carcinoma. This case report describes the sonographic features of salivary gland oncocytomas found in a patient with BHD.

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“…Other benign or malignant tumors have occasionally been reported in BHD, such as parotid oncocytomas [176], parathyroid adenomas [125, 177], lipomas [125, 126], breast cancer, melanoma, and others [149, 178], although no formal causal relationship to FLCN gene mutations has been established so far. An association between BHD and colorectal polyps or carcinoma has been suspected [122], but it was not confirmed by colonoscopic screening of 45 BHD patients [153].…”

Section: Birt-hogg-dubé Syndromementioning

confidence: 99%

Cystic Lung Disease in Genetic Syndromes with Deficient Tumor Suppressor Gene Function

Daccord¹,

Nicod²,

Lazor³

2017

Respiration

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Cystic lung diseases constitute a distinct group of rare lung disorders, among which two result from monogenic defects affecting tumor suppressor genes: lymphangioleiomyomatosis, either sporadic or associated with tuberous sclerosis complex, and Birt-Hogg-Dubé syndrome. These disorders have similarities in their clinical expression, including occurrence in young adults, multiple pulmonary cysts, recurrent pneumothorax, skin hamartomas, and renal tumors. However, they markedly differ in their gender distribution, pathogenesis, disease course, and prognosis. Our knowledge on these two rare conditions is rapidly expanding. Management of lymphangioleiomyomatosis has substantially improved in the past decade with the understanding of its pathogenic mechanisms, the discovery of an effective therapy, and development of large cohorts and international guidelines. Birt-Hogg-Dubé syndrome has been described more recently and still awaits deeper understanding of its pathophysiology.

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Birt-Hogg-Dube syndrome presenting as multiple oncocytic parotid tumors

Cited by 27 publications

References 11 publications

New Developments in the Pathogenesis of Pulmonary Cysts in Birt–Hogg–Dubé Syndrome

New Developments in the Pathogenesis of Pulmonary Cysts in Birt–Hogg–Dubé Syndrome

Birt-Hogg-Dubé Syndrome: A Case Report Describing Sonographic Evaluation of Salivary Gland Oncocytomas

Cystic Lung Disease in Genetic Syndromes with Deficient Tumor Suppressor Gene Function

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