Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas.

Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation.     

Stress and seborrheic dermatitis

BACKGROUND: It is widely accepted that episodes of seborrheic dermatitis are frequently induced by stress, as stated in all general reviews of the subject. However, there have been no studies to confirm this view. PATIENTS AND METHODS: This prospective study was performed in two phases. An initial questionnaire collected information on patients' identity, somatic and psychiatric history and seborrheic dermatitis characteristics. Information on triggering episodes was sought by means of an open question and patients were then asked if they had experienced stress during the week or month prior to the active episode. A second questionnaire containing the same questions (except for history) was completed four months later. The two questionnaires contained psychopathological evaluation scales designed to detect symptoms of anxiety and depression among patients (HAD: Hospital Anxiety and Depression scale; Beck; STAI: State-Trait Anxiety Inventory) and determine their perceived stress (PSS: Perceived Stress Scale by Cohen and Williamson). RESULTS: Eighty-two patients (36 women and 46 men) were included in the study. 82% of patients presented involvement of scalp, 33% of the face, 19% of the chest and 13% of other sites (ears, skinfolds). Patients themselves identified stress as the main triggering factor, whether for episodes in general, for the first episode or for the current episode. A stressful event was in fact found in the majority of cases. The fact that stress was recognised as a triggering factor for episodes was not associated with a higher depression score (HAD or Beck) but was associated with a higher anxiety score (STAI). The psychological effects of the disease were pronounced in 11% of patients, moderate in 20%, mild in 35%, and nil in 25%, with 9% of patients stating no opinion. Patients with facial involvement were more depressed in terms of Beck Depression Index score. Two characteristics noted at inclusion were predictive for the onset of at least one further episode or persistence of an ongoing episode four months later: patients' designation of stress as the cause of the previous episode, and STAI score. DISCUSSION: This study confirms that seborrheic dermatitis is often preceded by a stressful event and that stress tends to suggest a poor prognosis. This is the first study to show a possible link between stressful life events and episodes of seborrheic dermatitis. It suggests the need to confirm these results through a study comparing patients with seborrheic dermatitis and subjects without the disease. It also shows that depression is more common among patients with facial involvement and that anxiety is an aggravating factor.     

Differentiation of antitumor-specific cytotoxic T lymphocytes from autologous tumor infiltrating lymphocytes in non-Hodgkin's lymphomas.

The present study describes a new culture protocol allowing the activation and proliferation of autologous tumor infiltrating T lymphocytes (TIL), and the generation of antitumor specific CTL in non-Hodgkin's lymphoma (NHL). Cells from eight patients with indolent NHL were used. We performed 3-week co-cultures of TIL with irradiated autologous malignant B cells in the presence of low doses of IL-1beta, IL-2 and IL-12. The proliferation, phenotype and cytotoxicity, and antitumor specificity of T cells recovered were studied. T-cell clonality was analyzed using TCRgamma gene rearrangement amplification by a multiplex PCR. Under these culture conditions, TIL proliferated, and the CD8+ T lymphocytes that were in a minority at the beginning of the culture increased dramatically in 6 out of 8 cases. In two cases, CD4+ T lymphocytes expanded. We showed that an oligoclonal selection of reactive T cells occurred in culture. Specific cytotoxicity developed against autologous malignant B cells in the 6 cases where there was an expansion of CD8+ T lymphocytes. Inhibition experiments performed with mAb directed against HLA class I and II molecules, CD4, CD8 and TCRgammadelta showed that the cytotoxic effector cells were CD8+ T lymphocytes probably expressing TCRalphabeta+. Cytokine secretion was analyzed in culture medium, and we detected significant levels of IFN-gamma, TNF-alpha, and IL-10 and no IL-4 (except in one case). Our results demonstrate that memory T cells from lymphoma patients can be amplified and differentiated into antitumor cytotoxic cells using a combination of the cytokines IL-1beta, IL-2, and IL-12 in association with non modified tumor cells.     

Vulvovaginogingival syndrome. New characteristic grouping of plurimucous erosive lichen planus

The triple association of a chronic painful erosive vulvitis, an erosive or desquamative vaginitis and an erosive vestibular gingivitis constitutes a hitherto unreported syndrome. The first 19 cases of this affection seen in the H?pital Tarnier over the last three years are presented and analyzed, the etiology of these erosive mucosal lesions, limited to three body regions, being lichen planus in each case. Detection of mucosal erosion at one of these three sites now requires clinical investigation of the other two, and biopsy of least one of them from the edge of an eroded zone, as well as search for other-possible mucocutaneous areas of lichen planus. Clinical onset is often asynchronous, one lesion appearing before the others, the simplest to recognize being gingival erosive lichen. In one case, however, peri-erosive lamellar detachments suggested chronic desquamative gingivitis of possible benign pemphigoid origin. Erosive lichen planus of vulva and vagina has not been reported previously. Knowledge of this syndrome allows correlation between lichen planus and certain cases of erosive gingivitis, erythroplastic vulvitis and desquamative vaginitis.     

Phenotypic and genotypic heterogeneity in large granular lymphocyte expansion

The cellular heterogeneity of large granular lymphocyte expansions has been illustrated by the phenotypic and genotypic findings in five patients. In one patient whose circulating cells were CD2+, CD3-, CD5-, CD7+, CD8-, CD11+, Leu7+, CD16+, and displayed strong natural killer activity, no rearrangement of the T cell receptor beta-chain gene and T cell rearranging gene gamma was detected. The four other patients presented with neutropenia without overt lymphocytosis. In these patients the circulating lymphocytes expressed a predominant T cell phenotype CD2+, CD3+, CD5+, CD7+, CD8+, Leu7+. In three of them the presence of a T cell clone was demonstrated on the basis of a unique pattern of rearrangement of the T cell receptor beta-chain genes.     

Cobalamin (vitamin B12) and B12 binding proteins in hypereosinophilic syndromes and secondary eosinophilia

Serum cobalamin (vitamin B12) and unsaturated B12 binding capacity (UBBC) have been measured in 24 cases of hypereosinophilia: 16 were cases of hypereosinophilic syndrome (HES) and 8 of secondary eosinophilia. The two groups were similar with respect to absolute eosinophil counts. Serum cobalamin and UBBC were found to be markedly increased in most cases of HES and normal in secondary eosinophilia. This elevation of UBBC was mainly related to the increase of R binders (transcobalamins I and III). The elevated serum cobalamin and R binders in HES were due neither to a higher intracellular content of R binders nor to an increased release of these binders from eosinophils of HES. Pure fractions of eosinophils obtained from HES and secondary eosinophilia did not exhibit any difference in vitamin B12 binders. On the other hand, neutrophil-rich fractions from the same patients showed a higher content of intracellular B12 binding proteins than pure eosinophil fractions, irrespective of the cause of eosinophilia. These findings suggest that the increased serum vitamin B12 and UBBC could reflect an expanded pool of both eosinophils and neutrophils in HES and, thus, provide an additional argument for the inclusion of this syndrome in the group of myeloproliferative disorders.     

Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients

We report on the characteristics of 21 patients with hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL), an entity recognized since 1994 in the Revised European American Lymphoma (REAL) classification. Median age was 34 years. Patients had splenomegaly (n = 21), hepatomegaly (n = 15), and thrombocytopenia (n = 20). Histopathologic findings were homogeneous and showed the presence of medium-sized lymphoma cells within the sinusoids of splenic red pulp, liver, and bone marrow. Marrow involvement was usually mild but could be demonstrated by phenotyping in all patients. Cells were CD3+CD5-, expressed the gammadelta T-cell receptor, and had a nonactivated cytotoxic cell phenotype (TIA-1+, granzyme B-). Most patients were CD4-/CD8- (16 of 18); CD56+ (15 of 18), expressed the Vdelta1epitope (Vd1+/Vd2-/Vd3-) (9 of 12); and were negative for Epstein-Barr virus (EBV) (18 of 20). Isochromosome arm 7q was documented in 9 of 13 patients. Eight patients had previously undergone kidney transplantation or had a history of systemic lupus, Hodgkin disease, or malaria. Prognosis was poor; median survival time was 16 months, and all but 2 patients ultimately died despite consolidative or salvage high-dose therapy. In conclusion, HSgammadeltaTCL is a disease with distinctive clinical, histopathologic, and phenotypic characteristics. Bone marrow biopsy with combined phenotyping is sufficient for diagnosis, and splenectomy is therefore unwarranted. Current treatment modalities appear to be ineffective in most patients.