Birt‐Hogg‐Dubé‐syndrome and Hornstein‐Knickenberg‐syndrome are the same. Different sectioning technique as the cause of different histology

Abstract

The autosomal dominant inherited syndromes of Hornstein and Knickenberg (HKS), and Birt, Hogg and Dube (BHDS) are both characterized clinically by the overall spread of multiple flesh coloured papules of the skin. However, it is a matter of debate if colonic neoplasms (adenomas as well as adenocarcinomas) are associated findings in the HKS or rather in the BHDS. Furthermore, histological differences are said to exist between the skin lesions in the two syndromes: whereas perifollicular fibromas were described in the HKS, fibrofolliculomas and trichodiscomas were found in the BHDS. In the present study, we report on a father and his daughter in whom we initially diagnosed a BHDS. We then examined a greater number of the papular lesions in histologic sections cut vertically as well as horizontally to the epidermis. Our results indicate that the histologic differences between the skin lesions in the two syndromes are artificial ones, caused by interpretation of different sectioning planes, and that consequently HKS and BHDS are the same. Therefore, it is necessary to look for colonic polyps in the syndrome in question, regardless if one prefers the name HKS or BHDS for it.

Multiple facial angiofibromas: A cutaneous manifestation of Birt-Hogg-Dubé syndrome

“…2,3,7 Flecked chorioretinopathy with constricted visual fields may represent an additional extracutaneous feature of BHDS. 8,20 Although there are several reports of colonic polyps and carcinomas in BHDS families, 9,16,24 Zbar et al 3 found no significant association with colonic neoplasia in a case-control study of BHDS patients (n = 111) and unaffected family members (n = 112).…”

“…25 More recently, several authors have proposed that BHDS and HKS represent a single entity with variable systemic manifestations, emphasizing that different histologic sectioning techniques may explain the different findings in skin biopsy specimens (see above). 6,9 Both angiofibromas and fibrofolliculomas present as multiple small, firm, dome-shaped facial papules. Although the former are often pink or telangiectatic and the latter whitish in color, there is clinical overlap, as evidenced by patients with multiple fibrofolliculomas who were initially diagnosed clinically as having angiofibromas.…”

“…In addition, the existence of perifollicular fibromas (a folliculocentric lesion related to the angiofibroma) in patients with BHDS has been a subject of debate. Several authors have emphasized the frequent misdiagnosis of fibrofolliculomas as perifollicular fibromas, particularly when employment of a horizontal histologic sectioning plane made the epithelial strands less apparent 4,6,9,13 ; however, Godbolt et al 14 expressed the opinion that these two types of lesions exist on a spectrum and can both be seen in BHDS.…”

Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus

“…The distinction between the two diagnoses has been ascribed to variations in sectioning technique: deeper sectioning of the trichodiscoma would reveal the epithelial strands on the basis of which the lesion should better be reclassified as fibrofolliculoma. 14 It has also been postulated that the anatomic site and ''age'' of the lesion may be responsible for the apparent histologic differences between fibrofolliculoma and trichodiscoma. Indeed, in more recent classifications of pilosebaceous tumors fibrofolliculoma and trichodiscoma are commonly listed as a single entity.…”

Birt-Hogg-Dubé Syndrome

“…Recently, it was proposed that PFFs represent transversely cut FFs. 28 Most likely, PPFs represent part of the spectrum of FF and TD. Further histologic studies of a large group of patients and identification of the genes involved in BHD may allow us to elucidate how FF, TD, and PFF are biologically related.…”