Molecular characterization by array comparative genomic hybridization and DNA sequencing of 194 desmoid tumors.

Desmoid tumors are fibroblastic/myofibroblastic proliferations. Previous studies reported that CTNNB1 mutations were detected in 84% and that mutations of the APC gene were found in several cases of sporadic desmoid tumors lacking CTNNB1 mutations. Forty tumors were analyzed by comparative genomic hybridization (CGH). Karyotype and fluorescence in situ hybridization revealed a nonrandom occurrence of trisomy 8 associated with an increased risk of recurrence. We report the first molecular characterization including a large series of patients. We performed array CGH on frozen samples of 194 tumors, and we screened for APC mutations in patients without CNNTB1 mutation. A high frequency of genomically normal tumors was observed. Four relevant and recurrent alterations (loss of 6q, loss of 5q, gain of 20q, and gain of Chromosome 8) were found in 40 out of 46 tumors with chromosomal changes. Gain of Chromosomes 8 and 20 was not associated with an increased risk of recurrence. Cases with loss of 5q had a minimal common region in 5q22.5 including the APC locus. Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome. A better understanding of the pathogenetic pathways in the initiation and progression of desmoid tumors requires studies of 8q and 20q gains, as well as of 6q and 5q losses, and study of the Wnt/beta-catenin pathway.

Study of the reactive dendritic cells in small B-cell lymphoproliferations of the skin.

Distinguishing between low-grade primary cutaneous B-cell lymphoma (LG-pCBCL) and cutaneous lymphoid hyperplasia (CLH) based on histological features is often difficult. CLH lesions contain numerous reactive cells of the histiocyte lineage [Langerhans cells (LC), dermal dendritic cells (DDC), and macrophages], which are also often present in CBCL. The aim of this study was to determine whether immunohistochemical detection of those cells could help differentiate between CLH and LG-pCBCL. We determined the percentages of those histiocytic cells in the dermal infiltrates of 45 cases of cutaneous lymphoproliferations comprising 16 CLH and 29 LG-pCBCL (19 follicle-center cell lymphomas and 10 marginal zone lymphomas) by immunohistochemical labeling with antibodies to CD1a, FXIIIa, and CD68 to respectively detect LC, DDC, and macrophages. To avoid observer-dependent bias, an automated morphometric analysis method was used to recognize immunoreactive cells and calculate their percentages within the infiltrate. FXIIIa(+) cells were significatively more frequent in CLH than in LG-pCBCL, whereas CD1a(+) and CD68(+) cell frequencies were comparable in the two groups. The results of our study suggest that DDC might play an important role in the genesis of cutaneous lymphomas.

[Nodular lymphocyte predominance Hodgkin's disease and its differential diagnosis]. / La maladie de Hodgkin nodulaire à prédominance lymphocytaire et ses diagnostics différentiels.

Nodular lymphocyte predominance Hodgkin's disease (NLPHD), previously called nodular paragranuloma, is a rare entity recognized as a clinico-pathological entity distinct from classic Hodgkin's lymphoma. It is an indolent B cell lymphoma derived from a germinal center cell. NLPHD may closely resemble lymphocyte-rich classic Hodgkin's disease (LR-CHD) or T-cell or histiocyte-rich large B-cell lymphoma (TCRLBCL). A reproducible distinction between these entities is difficult but the classification is prognostically relevant. NLPHD is characterized by neoplastic "popcorn" cells CD20+ CD30- CD15- EMA+ Bcl6+ scattered within a nodular background predominantly composed of small B lymphocytes. LR-CHD neoplastic proliferation is composed of CD20+/- CD30+ CD15+/- EMA- Bcl6+/- Reed Sternberg or Hodgkin's cells, scattered within numerous CD3+ T cells. TCRLBCL is an agressive lymphoma composed of CD20+ CD30- CD15- EMA+/- Bcl6+/- polymorphic neoplastic cells, scattered within a mixture of CD3+ T cells and histiocytes. Epstein Barr virus is detectable within half cases of LR-CHD, but never in NLPHD and rarely in TCRLBCL. The transcription factors BOB1, PU-1, BSAP and IRF4 are new markers that could be useful for differential diagnosis.

[Non tuberculous mycobacterial diseases]. / Les mycobactéries non tuberculeuses.

Mycobacteria species other than members of Mycobacterium tuberculosis complex are called non tuberculous mycobacteria (NTM) or "atypical" mycobacteria. To date, about 80 mycobacterial species have been described. They are usually opportunistic pathogens with variable degrees of virulence. Tuberculosis is the commonest mycobacterial disease in the world, followed by leprosy and Buruli ulcer. Before the AIDS epidemic, NTM diseases were confined to the lungs (M. kansasii, M. intracellulare and M. avium), the skin (M. marinum) or cervical lymph nodes (M. scrofulaceum). The outbreak of AIDS epidemic has dramatically changed the epidemiology of NTM diseases. Between 25 to 50% of AIDS patients in Europe and USA are infected with NTM. NTM infections are usually disseminated in patients with profound immunodeficiency. The inflammatory response and the prognosis of NTM diseases depend on the immunological status and the NTM species. Diagnosis may be difficult, especially in AIDS patients in whom numerous diseases are often associated. Diagnostic criteria involve clinical, radiological, microbiological and pathological findings. Identification of Mycobacterium species in cultures is the gold standard. Pathological examination has several interests: it may reveal an NTM disease, it provides a more rapid assessment of the infection than cultures, and helps to evaluate the virulence of NTM species identified by cultures.