Pulmonary features of Birt-Hogg-Dubé syndrome: cystic lesions and pulmonary histiocytoma.

BACKGROUND: to describe clinical, radiologic and pathologic features of lung lesions in Birt-Hogg-Dubè syndrome (BHDS) (MIM 135150). METHOD: review of 12 patients of BHDS from 3 unrelated Italian families evaluated at GB Morgagni Hospital, Forlì, from 2005 to 2010. RESULTS: mean age (±SD) at diagnosis was 44.6 (±16) years, 8 (66%) were male. All three index cases presented with a history of recurrent pneumothorax and/or cystic lung lesions evaluated by CT scan request by referring pulmonary physicians, none were diagnosed to have BHDS at the time of initial pulmonary evaluation. One of the three cases was a middle-aged female patient with a clinical phenotype indistinguishable from lymphangioleiomyomatosis (LAM), characterized by cystic lung lesions and kidney angiomyolipoma. In one case of BHDS presenting with recurrent pneumothorax and a solitary lung nodule, surgical lung resection revealed a pulmonary histiocytoma. In one case a novel mutation of BHD gene was detected (c.771 del, exon 7). CONCLUSIONS: BHDS is associated with cystic lung disease largely under-recognized by pulmonary physicians and can mimic LAM and may be associated with lung tumor, pulmonary histiocytoma. In one case we found a novel mutation in exon 7, c.771 del (ref.seq. NM_144997.5) never reported before.

Constitutional FLCN mutations in patients with suspected Birt-Hogg-Dubé syndrome ascertained for non-cutaneous manifestations.

Birt-Hogg-Dubé syndrome (BHDS) is characterized by a clinical triad including cutaneous hamartomas originating from hair follicles, lung cysts/pneumothorax, and kidney tumors. Inactivating mutations of the tumor suppressor gene FLCN are identified in most families with BHDS. Usually, patients are referred for genetic examination by dermatologists because of the presence of typical multiple skin tumors with or without additional symptoms. However, because of phenotypic variability and incomplete penetrance, the clinical presentation of BHDS is not yet fully defined. Criteria for genetic testing and diagnosis that take into account variable manifestations have recently been proposed by the European BHD Consortium. We sequenced the FLCN gene coding region in a series of 19 patients selected for kidney and/or lung manifestations. Overall, FLCN mutations were found in 9 of 19 (47%) families and were detected only in probands who had either >2 components of the clinical triad or a single component (renal or pulmonary) along with a family history of another main BHDS manifestation. Typical cutaneous lesions were present only in 8 of 21 FLCN mutation carriers aged >20 years identified in the mutation-positive families. In addition, we provide clinical and molecular evidence that parotid oncocytoma, so far reported in six BHDS cases, is associated with this condition, based on the observation of a patient with bilateral parotid involvement and marked reduction of the wild-type FLCN allele signal in tumor DNA. Overall, the results obtained in this study contribute to the definition of the phenotypic characteristics that should be considered for BHDS diagnosis and FLCN mutation testing.

[Flow cytometry in micturitional urine: its clinical application in cases of bladder cancer]. / La citometria di flusso sulle urine minzionali: sua applicazione clinica in casi di neoplasia vescicale.

The paper discusses a particular use of flow cytometric analysis, namely the quantitative study of DNA in the cellular sediment obtained from micturitional urine in patients with vesical tumours. Forty cases of carcinoma of varying degrees and stages were studied and, despite the small number of cases, interesting results have emerged regarding the close correlation between the test and the different clinical, cytological and histopathological aspects of the disease, and relating to the relative simplicity of the method used.

Cooperation between fibronectin and heparin in the mobilization of capillary endothelium.

Angiogenesis is indispensable to sustain promotion and growth of metastases. As a contribution to the understanding of the angiogenesis process, the experiments reported showed that: (a) fibronectin is involved in the mobilization of capillary endothelium which is the first event in angiogenesis; (b) antifibronectin serum can block the mobilization, and neutralization of the antiserum can restore it; (c) the combination of fibronectin + heparin is a powerful mobilizer of capillary endothelium, and (d) fragments of the fibronectin and heparin molecules in combination can mobilize capillary endothelium as effectively as the intact molecules. The results are interpreted to indicate that molecules normally present in the extracellular matrix like heparin and fibronectin, may act as angiogenesis effectors when the physiological structure of the tissue is altered, for instance by lytic enzymes released by metastatic neoplastic cells.