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Notes: The proband was evaluated for abdominal pain at age 61 years and found to have bilateral solid renal masses. He underwent a partial left nephrectomy. Two benign renal cysts were present, and two renal cell adenocarcinomas measuring 5.3 cm and 0.7 cm in greatest diameters were found. Histologically, both tumors contained both clear and granular cell types. He had a total right nephrectomy 2 months later. Fourteen or 15 lesions were scattered over the surface of this kidney, so an adrenal-sparing radical right nephrectomy was performed. On sectioning, the diameter of the largest tumor was 4 cm, and histologically this was described as renal cell carcinoma, clear cell type, Fuhrman grade II. One year later, the patient shows no evidence of recurrent disease.The proband's past medical history was notable for gastroesophageal reflux, degenerative disk disease, hyperlipidemia, and mild hyperglycemia. A genetics consultation was requested because of a family history of renal cancers in three maternal relatives (〈link href="#f3-1"〉Fig. 1). On examination, the proband was a nondysmorphic man of normal stature with no unusual findings, except for widespread skin findings (〈link href="#f3-2"〉Fig. 2). On his face were innumerable, small, slightly yellowish or flesh-colored papules on the forehead and especially over the cheeks. No intraoral lesions were seen. Around the neck were innumerable, dome-shaped, firm, ivory-colored papules ranging in size from 1 to 10 mm. Very tiny, similar papules were present over the trunk and in the antecubital area. Numerous acrochordons and some cherry angiomas were present. Several biopsies from the neck and upper back were obtained and were thought suggestive of papular mucinosis. The patient's mother had had a skin biopsy of a similar lesion from her face in 1947, interpreted as an adenoma sebaceum. No angiofibromas were evident on our patient's slides nor on physical examination.〈figure xml:id="f3-1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1287-4:IJD_1287_f3-1"/〉Pedigree of family with Birt-Hogg–Dube Syndrome〈figure xml:id="f3-2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1287-4:IJD_1287_f3-2"/〉Photograph of the back of the neck of a 61–year-old man with Birt-Hogg–Dube SyndromeAt this point, diagnoses under consideration included von Hippel-Lindau disease (VHL), a familial chromosome no. 3 translocation, hereditary renal cell cancer (gene unknown), tuberous sclerosis (TS), or Birt-Hogg–Dube syndrome (BHDS). The patient underwent a variety of tests to evaluate these possibilities. He had no evidence of hemangioblastomas of the central nervous system, no liver or pancreatic cysts, no ocular findings for VHL or TS, and no hypomelanotic macules on skin exam. Chromosome analysis from peripheral blood showed a normal 46,XY karyotype. Direct DNA mutational analysis of the VHL gene detected no mutations. Additional biopsies from the patient's skin lesions were obtained, and tissue blocks from 1947 from his mother were resectioned (〈link href="#f3-3 #f3-4"〉Figs 3 and 4). Upon further review, multiple fibrofolliculomas were found in both mother and son in skin biopsies. In aggregate, these data established a diagnosis of BHDS.〈figure xml:id="f3-3"〉3〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1287-4:IJD_1287_f3-3a"/〉〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1287-4:IJD_1287_f3-3b"/〉(A) Skin biopsy from the upper back of the proband showing a dome shaped papule with abundant mucin in the papillary dermis. Follicular changes are suggestive of fibrofolliculoma. (H&E, 12.5X). (B) Mucinosis in the papillary dermis is highlighted with alcian blue stain (ABPAS, 25X)〈figure xml:id="f3-4"〉4〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1287-4:IJD_1287_f3-4a"/〉〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1287-4:IJD_1287_f3-4b"/〉(A) Fibrofolliculoma seen on skin biopsy of a facial papule from the mother of the proband (H&E, 25X). (B) Fibrofolliculoma from the mother of the proband with sebaceous gland enlargement and mucin deposition highlighted by alcian blue stain (ABPAS, 25X)In addition to the renal cancers, the patient's and/or cousin's medical record reported that others in the family had the same skin manifestations, including his mother, maternal grandmother, maternal uncle, and two maternal first cousins by report. Cousin III.6′s medical record showed a clinical diagnosis initially of ‘‘sebaceous hyperplasia’' and upon skin biopsy was said to have ‘‘innumerable trichoepitheliomas over his face’'. He was treated with liquid nitrogen with good results. Unfortunately, we were not able to obtain tissue for review on the other renal cancers in relatives. Additional findings of note are a spontaneous pneumothorax in our patient's daughter and melanoma in our patient's brother and son. This family has been invited to participate in genetic studies underway at the National Cancer Institute.

Notes: [Auszug] Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia. Cytogenetic studies indicate that cells from ...

Notes: Abstract Recently, a novel tumor suppressor gene, p73, was isolated and mapped to chromosome 1p36, a region commonly associated with loss of heterozygosity in neuroblastoma and other human malignancies, including breast cancer. The p73 gene shares considerable homology with the common tumor suppressor gene p53, both in composition and function. This study examines the potential participation of p73 in the pathogenesis of sporadic and hereditary breast cancers. Mutation analysis of 29 hereditary breast cancer cases revealed five independent silent mutations in the hereditary cases that are unlikely to play a role in tumor development. Mutation analysis of 48 sporadic breast tumors did not identify any unique variants. Eleven common polymorphisms scattered throughout the gene were also detected. Thus, mutations in the p73 gene appear to play little if any role in hereditary or sporadic breast cancer.