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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.

Infantile digital fibromatosis or inclusion body fibromatosis is a rare, benign fibroproliferative lesion with recurrent potential that occurs on the digits of infants. A highly characteristic morphologic finding is the presence of paranuclear inclusion within the tumoral cells. We report here a case occurring in an 8-month-old infant with 2 asynchronous lesions of the toes., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Mucocutaneous papillomas can be manifestations of an autosomal dominant condition known as Cowden syndrome (CS). We report the case of a 22-year-old man with oral and cutaneous papules and a past history of thyroid malignancy. It is important to recognize oral manifestations of CS; they can lead to early diagnosis of the condition.

Birt-Hogg-Dube is a rare syndrome which is sporadic or hereditary with a dominant autosomal transmission. Various organs, in particular the skin, can be affected. In the presently reported case, skin was covered by hundreds of small molluscoid papules corresponding to trichodiscomas, fibrofolliculomas and skin tags.

We report the case of a woman with 3 different types of gastrointestinal tumors--stromal, fibrous, and fatty--and a germline defect of the platelet-derived growth factor receptor alpha (PDGFRA) gene (V561D). The patient, now 52 years old, presented in 1977 at age 22 years with a gastric tumor and a duodenal lipoma. Subsequently, she developed obstructing small intestinal fibrous tumors that required 3 laparotomies and intestinal resections. Most recently (in 2002), more than 100 fibrous tumors were resected and also multiple small intestinal lipomas and multiple gastric KIT, PDGFRalpha, and CD34-positive stromal tumors. The nosology of the fibrous tumors was not clear. The lesions were hypocellular and featured poorly outlined spindle, stellate, and polygonal CD34 positive, and KIT- and PDGFRalpha-negative cells. They extended through the muscularis propria, expanded the subserosa, and occasionally extended into the mesentery but did not metastasize. The patient is currently asymptomatic; radiologic study in June 2007 revealed postoperative changes only. None of the patient's primary relatives have had similar tumors.

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 syndrome's spectrum of skin changes.

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.

The syndrome of Birt-Hogg-Dubè (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.

Turcot syndrome is characterized by an association of malignant brain tumors and colon cancer developing in the patient's teens. Since the mechanism of carcinogenesis in Turcot syndrome is still unclear, we analysed genetic changes in tumors from a Turcot patient with no family history of the condition. All tumors, including one astrocytoma, three colon carcinomas, and two colon adenomas, exhibited severe replication error (RER), and all colon tumors showed somatic mutations at repeated regions of TGFbetaRII, E2F-4, hMSH3, and/or hMSH6 genes. Somatic APC mutations were detected in three of three colon carcinomas, and somatic p53 mutations were detected in the astrocytoma and two of three colon carcinomas, both of which showed two mutations without allele loss. We also found that normal colon mucosa, normal skin fibroblasts and normal brain tissue from this patient showed respective high frequencies of RER, in contrast to usual HNPCC patients in which RER was very rare in normal tissues. These results suggest that extreme DNA instability in normal tissues causes the early development of multiple cancer in Turcot syndrome. A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. Additional unknown germline mutation may contribute to the genetic instability in normal tissues.

Starting from one case of Gardner's syndrome of their own observation, and in light of Watne's results, the authors argue that in the syndrome just named--and in familial polyposis in a broader sense--genetic factors do not play a predominant role; rather, polyps seem to result from the prolonged action of noxious agents. At any rate, said action can be neutralized, and possibly prevented either with a surgical modification of the distal gut or by treatment with a chemical substance identified as ascorbic acid. In view of these considerations, the authors recommend preventive medical therapy.

Three patients had hereditary multiple trichodiscomas of early onset and dominant inheritance. This report is an analysis of the histologic, histochemical, immunohistochemical, and electron microscopic findings in 27 trichodiscomas, the largest published series so far, to our knowledge. The tumors of perifollicular connective tissue are briefly reviewed and a classification is proposed. Hereditary multiple trichodiscomas are regarded as a new entity that should be distinguished from the syndrome recently described by Birt and associates that is characterized by autosomal dominant inherited fibrofolliculomas as the hallmark, associated with trichodiscomas and acrochordons.

Multiple fibrous histiocytomas of the dermis (dermatofibromas) were found in six males of one family. A number of the tumors fell within the histologic patterns commonly encountered in dermatofibromas, but some were unusually large and others were cytologically atypical. In addition, the proband died of a malignant fibrous histiocytoma of the lung. We believe that this is a syndrome and a familial variant of a common dermal entity.

Multiple familial ossifying fibroma is a very rare jaw lesion. A 31-year-old white woman who had this heritable condition is reported. A differential diagnosis has been discussed to delineate an entity that has not appeared in the previous literature.

Familial polyposis is a systemic defect of growth regulation. Extracolonic expressions are common and serious, about equal in risk to carcinoma of the large intestine. Periodic surveillance of the upper gastrointestinal tract is particularly important. More intensive surveillance of the large intestine may lead to better results in patients with polyposis who have carcinoma of the large intestine develop.

In the present study, a peculiar fibromatosis cutis in two siblings has been reported the dermatosis being characterized by innumerable perifollicular fibromas on face, neck and trunk as well as multiple fibromata pendulantia. Since the father allegedly had skin lesions resembling those of his two affected children, an inherited condition is assumed for the disease manifesting itself rather late in age. In the female patient, several adenomatous colon polyps one being transformed into carcinoma were found. Since the association of distinct epithelial and mesenchymal tumours of the skin and the cranial bones with multiple colon polyps is typical for Gardner's syndrome, we have discussed in detail the possiblity of an unknown variant of it. On the other hand, most features of Gardner's syndrome (cutaneous and subcutaneous epidermoid cysts, desmoid tumours, generalized osteomas, a marked multitude of colon polyps, early manifestation of skin and bone changes) were absent in both cases whereas, to our knowledge, in Gardner's syndrome perifollicular fibromas have never been seen. Since perifollicular fibromas are organoid tumours of the mesenchymal hair sheath being clearly defined both clinically and histologically, they must not be confused with the equally well characterized cutaneous tumours of Gardner's syndrome. We are prone to assume that the (irregular?) ASSOCAITION OF MULTIPLE PERIFOLLICULAR FIBROMAS AND COLON POLYPS Represents a distinct nosological entity neither identical with Gardner's syndrome nor with any other known dermo-intestinal syndrome. Thus, perifollicular fibromatosis should alert the dermatologist to consider periodic thorough examination for intestinal polyps the more as they may change into malignant growth.

An analysis of the findings in 21 patients with the Cowden syndrome or the multiple hamartoma syndrome is presented. The Cowden syndrome is a cancer-associated genodermatosis with characteristic mucocutaneous findings and a wide array of associated abnormalities including a high incidence of breast cancer in female patients. Genetic studies confirmed autosomal dominant inheritance with a high penetrance in both sexes and moderate interfamilial and intrafamilial differences in the expressivity of a number of symptoms. Familial occurrence was present in 4 of the 7 families. There was a strong predominance of female patients (6:1), which may be fortuitous. Mucocutaneous changes were the most constant (100% incidence) and characteristic findings; they almost invariably became manifest in the second decade. Four of our 18 female patients (22%) were treated for breast cancer, a lower incidence than reported previously. No increased incidence of other types of malignancies was found. Craniomegaly (high head circumference) was found to be the most common extracutaneous manifestation (80% incidence); craniomegaly appears to be an important early marker. We also found high incidences of gastrointestinal polyps (approximately 60%) and cutaneous fibromas (76%), while the incidence of thyroid abnormalities, thus far regarded as the most common extracutaneous finding, was similar to that reported previously (62%). G-banded karyotype and preliminary DNA-repair studies revealed no clear abnormalities. No linkage with the loci of HLA, and immunoglobulin haplotypes was found.

Three members of a family with a symmetrical distribution of multiple metaphysial lesions presented during childhood with pathological fractures and showed a tendency to spontaneous resolution after maturity. The histological and radiological features suggested multiple non-osteogenic fibromata of bone.

In the Finnish Polyposis Registry with 71 known families and 168 verified adenomatosis coli patients, 19 (11%) cases were complicated by desmoid tumors. Six polyposis patients (3.6%) had a desmoid before colectomy and the cumulative risk of postoperative desmoid tumors was 16% at ten years after colectomy. The median interval between the operation and the diagnosis of desmoid was 2.3 years. Eleven women and eight men were affected; the mean age was 28.5 years. Development of postoperative desmoid tumors was associated with early age at the time of colectomy, 26 years versus 38 years in those without subsequent desmoids (p less than 0.01). In two families more than one polyposis patient were affected by desmoids. All patients with desmoid tumors had other accompanying extracolonic lesions. No deaths from desmoid disease have occurred, even though only four of eight mesenteric tumors and five of nine abdominal wall tumors (53%) were excised without evidence of recurrence. Operative treatment is required in most cases, but resection may involve great hazard especially in mesenteric desmoids.

The cases of 2 siblings with a rare, generalized genodermatosis have been reported, the most conspicuous feature being multiple perifollicular fibromas. In this type of dermal hamartomas, an apparent autosomal dominant trait was noted as well as the association with a small number of colon polyps in one of the patients. The author assumes a distinct dermo-intestinal syndrome not reported hitherto, which can be differentiated from Gardner's syndrome.

A father and his son were seen because of multiple wartlike lesions on their fingers and palms. On histologic examination, these lesions showed changes compatible with vascular fibromas, myxoid fibromas, and, in a few instances, verruca vulgaris. We are not aware of reports of similar cases in the dermatologic literature.

Two familial observations of Birt-Hogg-Dubé syndrome are reported. In fact they were cases of tuberous sclerosis. The authors comment that probably this syndrome is an expression form of tuberous sclerosis.

We have examined 15 members of a family with Gardner's syndrome. In the first and second generations, 4 (possibly 5) of 6 members died of cancer of the colon/rectum. Two of them were known to have plyposis coli. Three members of the third generation had the complete triad of Gardner's syndrome with polyposis coli, soft tissue and hard tissue tumours. Three of 5 children in the fourth generation, aged between 7 and 11 years, probably have polyposis coli, and 2 of them have stigmata of Gardner's syndrome. All members of any family with Gardner's syndrome should be examined regularly at 2--3 year intervals from an age of about 10 years until the diagnosis is established, or if polyposis does not develop, up to the age of 40 years. Proctocolectomy is recommended at the age of 18--20 years or later as soon as the diagnosis is determined.

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 Birt-Hogg-Dubé syndrome is characterized: a) clinically, by an asymptomatic eruption of dome-shaped papules involving the head, neck, chest, back and arms frequently associated with acrochordons; b) histologically, by multiple follicular tumors, namely fibrofolliculomas and trichodiscomas, representing benign proliferations of mesodermal and ectodermal components of the pilar apparatus; c) by the apparent autosomal dominant mode of inheritance. This study is concerned with two families whose various members belonging to two and three generations have the clinical and histological lesions of this syndrome. In several biopsies performed, the main finding was the fibrofolliculoma isolated or associated with perifollicular fibromas; in five biopsies, was noted a typical trichodiscoma associated, in two of them, with a perifollicular fibroma. Clinically, the fibrofolliculomas were indistinguishable from trichodiscomas. We believe that the Birt-Hogg-Dubé syndrome is an autonomous well individualized skin disease. Its existence supports the view of the close interaction between the epithelial and mesodermal components of the pilar complex.