PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study.

Adult and child B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) differ in terms of incidence and prognosis. These disparities are mainly due to the molecular abnormalities associated with these two clinical entities. A genome-wide analysis using oligo SNP arrays recently demonstrated that PAX5 (paired-box domain 5) is the main target of somatic mutations in childhood BCP-ALL being altered in 38.9% of the cases. We report here the most extensive analysis of alterations of PAX5 coding sequence in 117 adult BCP-ALL patients in the unique clinical protocol GRAALL-2003/GRAAPH-2003. Our study demonstrates that PAX5 is mutated in 34% of adult BCP-ALL, mutations being partial or complete deletion, partial or complete amplification, point mutation or fusion gene. PAX5 alterations are heterogeneous consisting in complete loss in 17%, focal deletions in 10%, point mutations in 7% and translocations in 1% of the cases. PAX5 complete loss and PAX5 point mutations differ. PAX5 complete loss seems to be a secondary event and is significantly associated with BCR-ABL1 or TCF3-PBX1 fusion genes and a lower white blood cell count.

Decreased motivational properties of morphine in mouse models of cancerous- or inflammatory-chronic pain: implication of supraspinal neuropeptide FF(2) receptors.

Our main purpose was to evaluate the influence of cancer pain on the rewarding properties of morphine. Opioids are very addictive when used by healthy persons, conversely the occurrence of an opioid addiction seems very low when patients suffering from cancer are treated with morphine. We investigated the reinforcing properties of morphine in the place preference paradigm on a new model of mice suffering from a cancer pain induced by syngenic melanoma cells injected in the hind paw. These data were compared with mice suffering either from a short-term- or a chronic-inflammatory pain induced respectively by injection of carrageenan or complete Freund's adjuvant. Remarkably, mice suffering from cancer pain or chronic inflammatory pain did not develop any preference for the environment associated with the injection of morphine. In mice injected with melanoma cells, the specific binding of [(125)I]EYWSLAAPQRF-NH(2), an agonist of neuropeptide FF(2) receptors, was increased in several brain areas involved in the rewarding properties of opiates, including the shell of the nucleus accumbens, the major islands of Calleja, the ventral endopiriform nucleus and the amygdaloid area. Our study is the first to reveal a modification of morphine rewarding properties under cancer pain in rodents. We postulate that anti-opioid neuropeptides might contribute to the suppression of morphine rewarding effects in this murine model of cancer pain.

[An exceptional cause of renal colic. Castleman's tumor. Lymphonodular angiofollicular hyperplasia]. / Une cause exceptionnelle de colique néphrétique. Tumeur de Castleman. Hyperplasie lymphonodulaire angio-folliculaire.

The case of a 38-year-old man with renal colic due to compression by an abdominopelvic mass is reported. Histologic examination of the mass led to the diagnosis of giant lymph node hyperplasia or Castleman disease. Surgical removal of the lesion ensured complete recovery with no recurrence after 32 months follow up. Giant lymph node hyperplasia usually develops in the mediastinum, but superficial and abdominopelvic forms are seen occasionally. Pathogenic hypotheses are discussed. Outcome is usually favorable following surgical excision but rare multifocal forms with a potentially poor prognosis have been reported.

In situ immunologic characterization of follicular lymphomas.

Surface markers were studied in a series of follicular lymphomas with immunofluorescence on frozen sections (39 cases) and on cell suspensions (21 cases), and with immunoperoxidase on frozen sections using a panel of 15 monoclonal antibodies (17 cases). With immunofluorescence on frozen sections, 22/39 cases showed monotypic sIg (IgMK: 14 cases, IgML: 7 cases, M: 1 case). In the remaining 17 cases the neoplastic follicles were negative. Nevertheless, even if sIg is not detected, the absence of an extracellular immunoglobulin network is indicative of the neoplastic, and not of the reactive nature of lymphoid follicles. The results obtained with immunofluorescence on frozen sections and on cell suspensions were identical in about half of the cases. In 9/21 cases monotypic sIg were detected by only one of these two methods. All the 17 cases studied with immunoperoxidase on frozen sections using monoclonal antibodies demonstrated monotypic sIg. On low magnification 6/17 sIg+ exhibited a nodular staining pattern while 7/17 cases this staining was diffuse. In 4/17 cases the staining pattern for heavy and light chains was different. A thin mantle zone, with sIgM plus sIgD cells, was observed in only 4 cases. Anti-HLA-DR and Leu-10 were positive in all cases. T cells positive for OKT3 were mainly distributed in the interfollicular areas; OKT4+ cells outnumbered OKT8+ cells. Within the neoplastic follicles, T cells stained mainly for OKT4 and OKT8+ cells were scarce. Leu-7+ cells predominated within the neoplastic nodules in 5 cases. With the anti-dendritic reticulum cell monoclonal antibody, all 17 cases showed a network, usually more loosely arranged than in reactive follicles. In 4 cases, of follicular and diffuse lymphoma, this network was extremely dissociated and in some areas these cells were scanty or lacking. We concluded that immunoperoxidase on frozen sections, using monoclonal antibodies, appears to be the most reliable method for the immunological phenotyping of follicular lymphomas.

[Chronic diarrhea in nonspecific colopathies in children. Trial of etiological classification]. / Diarrhées chroniques des colopathies non spécifiques de l'enfant. Essai de démembrement étiologique.

305 children with non specific colopathies were studied with respect to the etiologic factors which may be responsible for the onset of the diarrheic syndrome. Epidemiologic factors (ethnic group, mode of housing, standard of living, parents's age and profession) did not appear to play a significant role and studies of familial and personal histories did not appear to be of any help. On the contrary, analysis of the diet showed a high incidence of nutritional imbalances (75.2% of cases) especially with respect to hyperprotidic diets. The role of a major and repeated antibiotic therapy and of psychologic problems may be suggested in 46 (15%) and 36 (11.8%) of the 305 cases, respectively. Fiberoptic and histologic investigations of the proctosigmoid mucosa were performed in 67 children: an inflammatory aspect was found in 22. In 21 of these 22 cases, no etiologic factors could be found and these cases, especially those occurring before 6 months of age, might belong to a special clinical entity.

Richter's syndrome. Evidence for the clonal origin of the two proliferations.

A case of Richter's syndrome was investigated by several technics: light and electron microscopy, surface markers, immunohistological studies and immunoelectron microscopy. On light microscopy lymph node proliferation was composed of large lymphoid cells, some exhibiting Reed-Sternberg like features. On electron microscopy many intermediary cells, from small lymphocytes to immunoblasts and plasma cells, were noted. The circulating small lymphocytes were characterized as B cells (SIg +; MRBC+). The lymph node cells shared the same SIg phenotype (IgMK) but the percentage of MRBC was slightly lower. Immunohistological studies showed that lymph node cells were stained exclusively by anti micron and anti kappa antisera. These results are indicative of the B clonal origin of the two cell proliferations. Immunoelectron microscopy showed three staining patterns: 1) cells presenting only surface staining, 2) cells with diffuse staining presumably related to ribosomal fixation, 3) cells with endoplasmic reticulum staining. The significance of these three patterns is discussed with regard to B lymphocyte differentiation.

Granulomatous hepatitis in Q fever.

Liver lesions in 17 patients with serologically diagnosed Q fever are described. A distinctive granulomatous pattern, with granuloma formation plus a fibrinoid ring, was observed in 14 cases. In two cases the fibrinoid material consisted of fibrillar eosinophilic structures without an annular arrangement, interspersed among epithelioid cells. In only one case was a nonspecific granuloma (devoid of fibrinoid material) noted. We conclude that the association of a granuloma with fibrinoid material is highly indicative of Q fever, but serial sections are often necessary to demonstrate this pattern.

[Pulmonary allescheriosis (author's transl)]. / Alleschériose pulmonaire.

In a patient properly treated for a previous cavitary tuberculosis, we had the surprise, after hemoptyses, to find a sleigh-bell shaped picture suggesting an intra-cavitary aspergilloma with a very special mycosis with Allescheria Boydii. Proof was provided by the presence of the fungus in direct examination and in culture in bronchial secretions. Surgical exeresis did not cure the patient and a secondary recurrence appeared on which antifungal drugs were ineffective. Antigens were made from the strain. They are used for immunoprecipitations tests. Only the patient's serum is positive; 82 serum test (18 concerned patients with visceral mycosis of farmer's lung disease) remained negative. Twenty two observations or pulmonary allescheriosis were recorded in the world. These figures are certainly below the truth. Three practical consequences can be drawn: --for an intra-cavitary mycetoma, with negative anti-aspergillus precipitins, such a disease must be kept in mind and the fungus looked for in bronchial secretions and specific immuno-precipitation test done; --any mycotic growth must be systematically cultured to determine the type of fungus; --for therapy, if diagnosis was made before the intervention, an antifungal treatment either local or general must be associated to the surgical treatment (contrary to aspergilloma treatment).

[Recurrent bronchopneumopathies caused by gastroesophageal reflux in children. Clinical, x-ray and histologic studies of 36 cases]. / Bronchopneumopathies récidivantes par reflux gastro-oesophagiens chez l'enfant. Etude clinique, radiologique et histologique de 36 observations.

The respiratory symptoms of gastro-oesophageal reflux, which sometimes includes massive and fatal inhalation, are well-known in infants. In older children the digestive signs are not clinically evident and the reflux mainly, if not exclusively, can be translated by recurring respiratory symptoms. The series of 36 cases presented in this work concerns children between 3 months and 15 years old, for whom the first signs were respiratory, with often a silent gastro-oesophageal reflux for several months, and even several years in some cases. The physiopathology of the respiratory symptoms concerns principally the repeated alimentary aspiration and/or gastric content during nocturnal decubitus. The pulmonary lesions caused by the reflux can be either localized, with atelectasis, obstructive emphysema or bronchiectasis, or generalized with granulomatous reactions around the food particles. Other respiratory conditions such as asthma or cystic fibrosis can be also associated with gastro-oesophageal reflux. The diagnostic criteria are discussed.

[Dysimmunologic and pseudolymphomatous adenopathies. I. Immunoblastic and plasmocytic lymphadenopathies]. / Les adénopathies dysimmunitaires et pseudo-lymphomateuses. I. Lymphadénopathies immunoblastiques et plasmocytaires.

The authors report 9 cases with pseudo-lymphomatous lesions associated with dysimmunitary features. They discuss the correlations between these cases and similar entities, for instance angio-immunoblastic lymphadenopathy (LAID). It seems that all these anatomoclinical syndromes could be referred to as dysimmunitary and pseudolymphomatous adenopathies (ADPL). The first type--ADPL type I--rich in immunoblasts and plasmocytes is defined. LAID is the most common form. The term "dysimmunitary" reflects not only the biological disturbances which accompany these lesions, but also their possible physiopathological mechanism, type I ADPL being apparently due to problem chiefly affecting humoral immunity.

[Dysimmunologic and pseudolymphomatous adenopathies. II. Lymphadenopathies rich in epithelial cells]. / Les adénopathies dysimmunitaires et pseudo-lymphomateuses. II. Lymphadénopathies riches en cellules épithélioïdes.

Besides the dysimmunitary and pseudo-lymphomatous adenopathies rich in immunoblasts and plasmocytes (ADPL type I) five cases showed similar clinical and biological data but with frequently otorhinolaryngologic location. The lesions are characterized by important structural changes and abundant epithelioid cells are comparable to Lukes' type III immunoblastic lymphadenopathies and to Lennert's lymphoepithelioid lymphomas. They must be distinguished from Hodgkin's granulomas which are rich in epithelioid cells. They are perhaps due to a disturbancy bearing mainly on the cellular immunity.