Tilman Schulz

Birt-Hogg-Dube syndrome and Hornstein-Knickenberg syndrome are the same. different sectioning technique as the cause of different histology

The auiosomal dominant inherited syndromes of Horornstein and Knickenberg (HKS). and Birt, Hogg and Dubé (BHDS) are both characterized clinically by the overall spread of multiple flesh coloured papules of the skin. However, it is a mailer of debate il cnlonic neoplasms ladenomas 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 m the HKS, fibroiolliculomas 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.

Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study.

The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation. In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n= 15), as well as in its main differential diagnosis, the morpheiform basal‐cell carcinoma (n=30). Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal‐cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge‐derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered. Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested.

The trichofolliculoma undergoes changes corresponding to the regressing normal hair follicle in its cycle

The trichofolliculoma is a follicularly differentiated hamartoma, usually described as showing many vellus follicles, spreading from a central infundibular cyst. In spite of the well known regressive changes of normal hair follicles during catagen and telogen, the possibility of corresponding changes in the trichofolliculoma has not yet been discussed in the literature. By examining a total of 31 cases of trichofolliculoma it is demonstrated that this hamartoma undergoes an evolutionary process with great morphological changes, which can be attributed to the anagen, catagen, and telogen phase of the foUicular cycle.

Merkel cell hyperplasia in chronic radiation-damaged skin: its possible relationship to fibroepithelioma of Pinkus

Moderate hyperplasia of Merkel cells (MC) in chronic sun‐damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation‐damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal‐cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal‐cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP.

Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell.

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.

Localized Birt-Hogg-Dubé syndrome with prominent perivascular fibromas.

The autosomal dominant Birt-Hogg-Dubé syndrome is a cutaneo-intestinal condition that manifests on the skin in the form of multiple, skin-colored small papules that, histologically, prove to be mantleomas (fibrofolliculomas and trichodiscomas). These cutaneous lesions usually appear in the region of the head, neck, and upper part of the trunk. To date, only a single report in the literature describes the localized occurrence of this syndrome. We now describe a localized form of the Birt-Hogg-Dubé syndrome in a man with multiple mantleomas that were confined to the left half of the face, and which, in part, were arranged in the form of plaques. Another striking finding in this patient was a conspicuous vascular component in the lesions, characterized by a pronounced, well-demarcated fibrosis in the region of cutaneous blood vessel proliferations. Because perivascular fibromas have already been observed in other patients with Birt-Hogg-Dubé-syndrome, the perivascular fibroma, with fibrofolliculoma and trichodiscoma, must be included within this syndromes spectrum of skin changes.

Comparative genomic hybridization (CGH) discloses chromosomal and subchromosomal copy number changes in Merkel cell carcinomas

We analyzed three Merkel cell carcinomas (MCC), applying comparative genomic hybridization (CGH) with DNA from paraffin‐embedded and cultured tumor material as the probes. By this method, numerous changes in chromosome copy numbers were observed in each tumor investigated. Recurrent gains of chromosomes 1, 6, 18q and 20 were detected in two tumors. A third tumor showed complex chromosomal copy number changes, including gain of chromosome 8 and 9. These gains, as well as gain of chromosome 1 in the first two tumors, were confirmed by fluorescence in situ hybridization to paraffin tissue sections. Our results support the view that important genes for MCC development may be located on chromosomes 1, 6, 18q and 20.

Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.