Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons

Abstract

In a sibship of nine, six members had hereditary medullary carcinoma of the thyroid. Two of those with thyroid neoplasms and two without had numerous small papular skin lesions. These proved to be a type of pilar tumor that we named fibrofolliculoma. Further investigation of the total kindred of 70 showed no other evidence of thyroid neoplasm. Skin tumors only appeared after the age of 25 years. Fifteen of 37 members older than the age of 25 years exhibited the typical skin lesions. Obviously, the original sibship was the repository of two dominantly inherited traits. The fibrofolliculoma is characterized by abnormal hair follicles with epithelial strands extending out from the infundibulum of the hair follicle into a hyperplastic mantle of specialized firbrous tissue. Associated skin lesions in this kindred were trichodiscomas and acrochordons.

The Nutrient-Responsive Transcription Factor TFE3 Promotes Autophagy, Lysosomal Biogenesis, and Clearance of Cellular Debris

“…Birt-Hogg-Dube (BHD) syndrome is caused by germline mutations in the tumor suppressor gene folliculin ( FLCN ) and is characterized by the development of fibrofolliculomas, lung cysts, and renal carcinoma 28-30 . Mutations in FLCN lead to the dysregulation of TFE3, as indicated by the constitutively nuclear localization of TFE3 in a BHD cancer cell line 27 .…”

The Folliculin Tumor Suppressor Is a GAP for the RagC/D GTPases That Signal Amino Acid Levels to mTORC1

“…Loss-of-function mutations in FLCN cause a familial cancer syndrome called Birt-Hogg-Dubé (BHD), characterized by hamartomatous tumors of the hair follicle (fibrofolliculomas), kidney, and lung (BIRT et al, 1977; Nickerson et al, 2002). Given that TSC1/2, PTEN, and LKB1—genes linked to other hamartoma syndromes—are bona fide tumor suppressors that impinge on the mTORC1 pathway, FLCN is likely a fregulator of the pathway (Baba et al, 2006; Guertin and Sabatini, 2007).…”

Birt–Hogg–Dubé syndrome: a case report and a review of the literature

“…[1] They reported a family of 70 members with 15 family members who developed fibrofolliculomas, trichodiscomas, and acrochordons on the scalp, forehead, face, neck, and upper torso after the age of 25. They also noticed that the skin changes were inherited in an autosomal dominant way.…”

“…[10,36,38,53,54] Most often, the tumors appear in the third or fourth decade and almost never before 25 years of age. [1,10,53] Fibrofolliculomas are the most frequent, but also trichodiscomas and acrochordons have been described. [1,34] Fibrofolliculomas present as multiple, pale yellow or white, slightly elevated, dome-shaped, and smooth tumors with a diameter of 2–4 mm (Figure 4).…”

“…[1,10,53] Fibrofolliculomas are the most frequent, but also trichodiscomas and acrochordons have been described. [1,34] Fibrofolliculomas present as multiple, pale yellow or white, slightly elevated, dome-shaped, and smooth tumors with a diameter of 2–4 mm (Figure 4). Fibrofolliculomas are predominantly located in the retroauricular area, face, neck, and upper torso and are macroscopically undistinguishable from trichodiscomas.…”