Exhaled nitric oxide and nitric oxide synthase expression in Hodgkin's disease.

Hodgkin's disease (HD) is a malignant lymphoma with frequent mediastinal involvement, characterized by a significant inflammatory infiltration. Exhaled nitric oxide (FENO), is present in healthy humans, and has been proven to be increased in eosinophilic diseases such as allergic asthma. We investigated whether FENO is increased in mediastinal HD and whether NO is produced by lymphoma tissue. To this aim FENO was measured in 56 HD patients, 17 with and 39 without bulky mediastinal involvement, in the period from January 2007 to December 2008. Thirty-seven patients were reassessed after remission. Lymph node biopsies of 10 patients were evaluated for inducible (iNOS) and constitutive (eNOS) nitric oxide synthase expression by immunohistochemistry. FENO resulted significantly related to the mediastinal mass maximum diameter (p=0.009) and was significantly higher in patients with as compared to those without bulky mediastinal disease (38.7 ppb, CI 95% 19.3-58.0, versus 20.7 ppb, CI 95% 16.6-24.7; p=0.009). iNOS and eNOS immunoreactivity was observed in tumour and inflammatory cells (eosinophils and histiocytes). Only in patients with bulky mediastinal HD there was a significant decrease in FENO (from 50.4 ppb CI 95% 18.0-82.8 to 11.1 ppb CI 95% 4.4-17.8, p=0.011). In conclusion, high FENO and NOS expression in lymph-nodes indicate that NO is a component of the inflammatory network of HD. FENO may be proposed for the assessment and follow up of bulky mediastinal HD patients.

Hepatocellular carcinoma complicating primary sclerosing cholangitis in Crohn's disease. A case report.

The prevalence of primary sclerosing cholangitis (PSC) in Crohn's disease (CD) patients is up to 8.5%. Although cholangiocarcinoma may complicate long-standing PSC in one third of the cases if follow-up is extended long enough, hepatocellular carcinoma (HCC) is a rare complication of PSC. The concomitant presence of PSC, HCC and CD have been reported sporadically. We discuss here a case of association of these three conditions.

Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma.

Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.

Association between Crohn's disease and Conn's syndrome. A report of two cases.

The natural history of Crohn's disease (CD) is characterised by periods of remission followed by phases of flares. Persistent or intractable diarrhoea may be associated with ileal disease or arise following ileal resection, resulting in potassium depletion. Medical therapy with steroids presents troublesome side-effects (e.g. hypertension). Conn's syndrome, caused by unilateral aldosterone-producing adenoma, is characterised by clinical features including hypokalaemia and hypertension. Thus, CD and Conn's syndrome may have an overlap of manifestations, and up to now, the simultaneous occurrence of these conditions has not been described. We report here 2 cases of association between CD and Conn's syndrome.

[Intestinal metaplasia, dysplasia, gastric cancer and Helicobacter pylori: epidemiological observations]. / Metaplasia intestinale, displasia, cancro gastrico e Helicobacter pylori: considerazioni epidemiologiche.

Gastric cancer (GC) is the world's second leading cause of cancer-related mortality, and carries a bad prognosis. In 1994, Helicobacter pylori (H. pylori) has been classified by the International Agency for Research on Cancer as a group I carcinogen. There are increasing indications that this infection is associated with both the initiation and progress of gastric carcinoma and lymphoma. Evidence supporting a causal association has been demonstrated by epidemiological data and in experimental animal models. Despite this, there is still lack of final conclusion regarding the association between the infection and the malignancy due both to marked geographic variations and heterogeneity in study designs. Given the high rate of morbidity and mortality associated with GC, any means of reducing the occurrence of the disease or increase its early detection is most desirable. In this paper, the epidemiological aspects on the evidence of a causal relationship between H. pylori and GC are discussed. Prospective cohort studies and interventional trials focused on the effects of H. pylori eradication on lesions predisposing to GC should be performed in order to provide further data.

Acute HIV-1 infection: clinical and biological study of 12 patients.

We observed 12 patients with acute human immunodeficiency virus type 1 (HIV-1) infection. The clinical syndrome was characterized by fever (all cases), generalized lymphadenopathy (11), arthralgias and myalgias (9), sore throat (9), rash (7), splenomegaly (6), and other less frequent signs and symptoms. All patients had a spontaneous resolution of their symptoms within 5-30 days. Anti-HIV-1 serum antibodies, as measured by enzyme immunoassay (EIA) at the onset of clinical illness, were negative in every patient. HIV antigen (p24), on the contrary, was detectable in nine cases. Western blot IgM and IgG analysis was serially performed: IgMs were positive in nine cases and IgGs in three. The CD4+/CD8+ ratio was low in all patients because CD8+ were remarkably increased and CD4+ slightly reduced. A laterocervical lymph nodes biopsy was performed in four patients. The morphological and immunohistological pattern of the acute HIV-1-related lymphadenopathy did not correspond to any of the typical ones. The envelope virus protein gp120/160 was found in interfollicular and follicular lymphocytes, in endothelial cells, and in interdigitating and dendritic reticulum cells. The p17 and p24 core virus proteins were mainly detected in endothelial, interdigitating, and dendritic reticulum cells, but in only a few lymphocytes. The follow-up suggests a rapid evolution to ARC and AIDS in patients showing an acute symptomatic HIV infection.

Differential expression of transforming growth factors-beta1, -beta2 and -beta3 in human colon carcinoma.

Transforming growth factor (TGF)-beta is a protein family which affects multiple cellular functions including survival, proliferation, differentiation and adhesion. Among the three known isoforms, TGF-beta1 is commonly overexpressed in solid malignancies. Recent studies in knock-out mice demonstrated non-redundant roles of different TGF-beta isoforms in development. The present study was performed to assess tumour-associated expression of the three TGF-beta isoforms in colon carcinoma. We report that colon carcinoma progression is associated with gradual and significant increases in expression of TGF-beta1 and TGF-beta2 mRNA and proteins. By contrast, TGF-beta3 expression was detected in normal colonic mucosa and, at slightly higher levels, in tumour tissues. In addition, plasma levels of both TGF-beta1 and TGF-beta2 were significantly higher in cancer patients when compared with unaffected individuals. Taken together, our results indicate distinct expression patterns of the three TGF-beta isoforms in colon carcinoma cells and possible systemic effects of TGF-beta1 and TGF-beta2 in tumour patients.

An immunoenzyme technique for the identification of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors using digoxigenated-GM-CSF.

A method for detecting granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors has been devised using human macrophages and a GM-CSF/IL-3-dependent human megakaryoblastic leukemia cell line (M-07e). Recognition of the factor-binding site was accomplished by linking recombinant human (rh) unglycosylated GM-CSF previously labeled with digoxigenated compounds. Digoxigenates were able to link amino and sulphydryl groups of the soluble factor and an immunoperoxidase technique using monoclonal anti-digoxigenin antibody was employed to demonstrate the interaction. To support morphological data cross-linking analysis was performed with M-07e cells using digoxigenated-rh-GM-CSF. Macrophages and M-07e cells incubated with digoxigenated-rh-GM-CSF showed intense positivity by the immunoperoxidase technique. In cross-linking, M07e cells showed a 96 kDa band corresponding to receptor plus bound factor. This technique permits a high degree of specificity in the detection of GM-CSF receptors with good morphological preservation of cellular detail.

Long-term survival of thymoma patients by histologic pattern and proliferative activity.

We performed DNA flow cytometry and analysis of the argyrophilic nucleolar organizer regions (AgNORs) in formalin-fixed, paraffin-embedded sections from 60 surgically resected thymomas. The results were correlated with histologic pattern, stage, associated clinical features, and survival to assess which parameters could best predict prognosis. On univariate analysis, the 10-year survival rates were 86% for predominantly lymphocytic type but only 42% for predominantly epithelial, mixed lymphoepithelial, or spindle cell thymomas (p = 0.006); survival rates were 85% for noninvasive but only 34% for invasive thymomas (p = 0.0002); 73% for diploid but only 38% for aneuploid cases (p = 0.005); 88% for thymomas with 5.75 AgNORs per cell or fewer but only 34% for thymomas with more than 5.75 AgNORs per cell (p < 0.0001). On multivariate survival analysis, tumor stage (p < 0.001) and AgNOR counts (p = 0.009) retained independent prognostic significance. The 16 patients with predominantly lymphocytic type and 5.75 AgNORs per cell or fewer were all alive at the end of the observation period. In conclusion, the histologic type of the American classification and the proliferative activity evaluated by AgNOR analysis are the best predictors of long-term survival for patients with thymoma. Both predictors can be easily evaluated in the same histologic section, are highly reproducible, and permit identification of a group of patients with a favorable outcome regardless of other clinicopathological features.

Prolactin in autoimmunity and antitumor defence.

Prolactin (PRL) enhances inflammatory and antitumor responses in vitro and thus exhibits Th1-type cytokine-like effects. Evidence from experimental models indicates that inhibition of PRL release by bromocriptine downregulates immune reactions and ameliorates autoimmune diseases in which Th1 responses are predominant. A direct effect of locally produced PRL in some Th1 diseases, such as rheumatoid arthritis, supports this concept. Paradoxically, however, hyperprolactinemia can also be associated with conditions such as pregnancy, where remission of Th1-mediated diseases is known to occur in the context of a Th2-dominated milieu. This reversal of the Th1-promoting effect of PRL may be due to major changes in the levels of other hormones that can annul and/or override the PRL-mediated proinflammatory state. Nevertheless, PRL, as an immunopotentiating agent, may have a powerful therapeutic role in cancer and other immunocompromised patients.

Acid hydrolases in B-chronic lymphocytic leukemia (B-CLL): a comparison with normal peripheral B lymphocytes and normal B-cell subset with the phenotype of B-leukaemic cells.

The acid phosphatase (AP), beta-glucuronidase (BG), and alpha-naphthyl-acetate esterase (ANAE) distribution and the morphology of stage 0 B-CLL lymphocytes were studied. The results were compared with the same hydrolase equipment and morphology of normal B-cell populations showing the B-CLL-like phenotype, and thus regardable as the possible counterpart of leukaemic cells. The functional and structural characters of the former were strikingly different from those of the latter. In fact the normal B-cell population with B-CLL-like phenotype showed an homogeneous enzyme pattern with predominant ANAE and a strictly lymphocytic cell morphology. In contrast, the leukaemic cells showed various and unrelated morphological and cytochemical features, thus forming apparent subgroups of B-CLL. The development of an irregular "switch on" mechanism in the blocked malignant cell clone, may account for these functional and structural maturation discrepancies. Moreover, the fact that in the leukaemic cells ANAE activity could be demonstrated only after the appearance of the other hydrolases, makes it a marker of functionally differentiated B lymphocytes.

Immunologic cell markers of peripheral blood and lymph node lymphocytes in chronic lymphocytic leukemia.

The immunologic phenotype of the lymphocytes of 100 patients with chronic lymphocytic leukaemia (CLL) was investigated. Peripheral blood lymphocytes (PBL) were examined in all cases; in 46 patients with lymphadenopathy, a lymph node was biopsied and the histologic and immunologic patterns were assessed: 24 had a lymphocytic-lymphoplasmocytoid histology and 22 the follicular variant of lymphocytic lymphoma (mantle zone lymphoma, MZL). For comparison, lymph node suspensions from 19 patients with non-leukemic centrocytic lymphoma (CCL) were also studied. Significant differences in the PBL immunologic features were found between stage O and stage I patients. The phenotype of the lymphocytes of patients with lymphocytic histology was similar to that of stage 0 CLL patients, whereas major differences were found between these patients and those with mantle zone histology. This enables these patients to be recognized easily on immunologic grounds.

MIB-1, Ki67, and PCNA scores and DNA flow cytometry in intermediate grade malignant lymphomas.

AIMS: To verify the correlation between MIB-1, Ki67, and proliferating cell nuclear antigen (PCNA-PC10) scores and S-phase fraction in intermediate grade non-Hodgkin's lymphomas (Working Formulation F); and their reliability in differently processed tissues. METHODS: Forty one non-Hodgkin's lymphomas were classified as (F) intermediate grade malignant lymphomas according to the Working Formulation; mitotic counts and percentage of large cells were assessed for each case. Sections from formalin fixed, paraffin wax embedded tissues were stained with anti MIB-1 monoclonal antibody, after microwave oven processing, and anti-PCNA (PC10) monoclonal antibody using an avidin-biotin immunoperoxidase (ABC) method. One thousand cells from 10 representative fields were scored. Frozen sections from surgical specimens were stained with Ki67 monoclonal antibody using the ABC method; the fraction of Ki67 positive cells was calculated scoring 1000 cells. Flow cytometry analysis (FCM) was performed on cell suspensions from fresh tissues. Correlations between data were estimated using linear regression. RESULTS: A linear correlation was found between MIB-1 and Ki67 scores (r = 0.92; p < 0.00001); between MIB-1 and PCNA scores (r = 0.79; p < 0.00001); and between MIB-1 score and S-phase fraction (r = 0.51; p = 0.0006). A linear correlation was also found between Ki67 and PCNA scores (r = 0.85; p < 0.00001); between Ki67 score and S-phase fraction (r = 0.6; p = 0.0002); and between PCNA score and S-phase fraction (r = 0.74; p < 0.00001). A correlation was found between mitotic counts and MIB-1 (r = 0.56; p = 0.0001), PCNA (r = 0.51; p = 0.0007), or Ki67 scores (r = 0.47; p = 0.002); between the percentage of large cells and MIB-1 (r = 0.49; p = 0.0009), PCNA (r = 0.6; p = 0.00003), and Ki67 scores (r = 0.53; p = 0.0003) and S-phase fraction (r = 0.55; p = 0.0002). CONCLUSION: MIB-1, Ki67, and PCNA (PC10) scores and S-phase fraction are highly correlated and equally well represent the proliferative activity of intermediate grade non-Hodgkin's lymphomas in differently processed material. MIB-1 and PCNA stains can be applied even on small biopsy specimens. MIB-1 produces homogenous staining without background; it also strongly stains mitotic figures. It can be performed on routinely processed tissues, permitting the simultaneous evaluation of the morphology and tumour cell kinetics. The wide standard deviations of the proliferative indices found for intermediate grade NHL suggest that this category probably includes various degrees of malignancy.

Can Ki67 immunostaining predict response to radiotherapy in oral squamous cell carcinoma?

AIMS: To determine whether immunohistochemical evaluation of the abatement of proliferating cells after a first course of radiotherapy could predict the final response to treatment in oral squamous cell carcinoma (SCC). METHODS: Frozen sections from 31 cases of histologically confirmed oral SCC were stained with the monoclonal antibody Ki67 at diagnosis and after 10 Gy of radiotherapy. The percentage difference of Ki67 positive cells among the biopsy specimens taken at the beginning and after 10 Gy was correlated with the clinical response obtained at the end of the treatment and its significance determined. RESULTS: The percentage of Ki67 positive cells at diagnosis had no significant correlation with the final therapeutic result of radiotherapy. By contrast, the 32% difference of proliferating cells after 10 Gy of radiotherapy significantly differentiated responders from non-responders (p < 0.05). Furthermore, the abatement of the growth fraction after 10 Gy of radiotherapy was significantly correlated with the complete response (p < 0.01). CONCLUSIONS: These data show that the immunohistochemical evaluation of the abatement of Ki67 positive cells after 10 Gy of radiotherapy provides an independent variable of responsiveness to radiotherapy, allowing a reliable prediction of the final therapeutic result to be made.

Isochromosome 6p and deletion of 6q characterize two related cytogenetic clones in a patient with immunoblastic lymphoma.

In a case of immunoblastic lymphoma we observed the presence of either a deletion of the long arm of chromosome 6 or of an isochromosome, i(6p), which occurred alternatively in metaphase cells. This suggests a selective pressure for loss of heterozygosity of genes located on 6q and is in accordance with the hypothesis that one or more tumor suppressor genes might be located on the long arm chromosome 6.

Immunoglobulin light chain restriction and clonal rearrangement in nodular paragranuloma.

B-cell clonality was demonstrated in a typical nodular paragranuloma case (NP) by both immunoglobulin (Ig) surface analysis and Ig genes rearrangement studies. On frozen sections, immunostaining for Ig light chain expression revealed a clear-cut predominance of Ig lambda-expressing cells, recognizable as both small lymphocytes and lympho-histiocytic (L&H) cells. Accordingly, molecular analysis of the Ig genes showed a monoclonal rearrangement of the lambda chain gene, although no specific pattern of heavy chain gene rearrangement could be detected by JH analysis. The C lambda rearranged band was identified with two different restriction enzymes, excluding the hypothesis of a genomic polymorphism. Furthermore, the C kappa gene was almost completely deleted, indicating that the developmental hierarchy of Ig genes rearrangement has been respected. The molecular pattern of the C lambda hybridizing band was consistent with monoallelic rearrangement of almost the entire DNA sample, indicating that clonal proliferation was not limited to L&H cells, but also involved surrounding lymphocytes. This finding is in keeping with the immunohistochemical evidence of a lambda light chain restriction on both L&H cells and small lymphocytes, pointing to a close relationship between these two cell types. Our results as a whole suggest that L&H cells and B lymphocytes share a common origin and may both be involved in clonal proliferation in NP.

Biological heterogeneity of diffuse mixed small and large cell non-Hodgkin's lymphomas assessed by DNA flow cytometry and Ki67.

The cell proliferative activity of the clinico-pathologically heterogeneous non-Hodgkin's lymphomas (NHL) included in the intermediate grade F category of the Working Formulation (WF) was investigated. S-phase fraction with flow cytometry on cell suspensions, and Ki67 on frozen tissue sections were performed in 42 F NHL. An avidin-biotin immunocomplex method was used and 1000 cells from 10 representative fields were counted. DNA content, S-phase and Ki67 were also detected in 194 NHL covering the whole spectrum of the WF. DNA content anomalies were found in 52 of 194 NHL. Their incidence, like that of S-phase fraction and Ki67 positive cells, progressively increased from low- to high-grade. A linear correlation was found between Ki67 and S-phase (r = .59). Using the median value of proliferating cells obtained with both procedures as a cut off, two very different groups of lymphomas could be distinguished within a series of 42 F-intermediate NHL: with low and high proliferative cell activity (p < .0001) that were termed F(low) and F(high), respectively. A intermediate group was placed between them. It differed significantly from the others if Ki67 was used but only from the F(high) group if the S-phase fraction analysis was applied. No significant differences were seen when comparing F(low) with the single categories of low-grade NHL and F(high) with H high-grade NHL; no significant differences were found between F(high) and G, and between G and H categories. The existence of distinct groups of NHL in the F category, as defined by biological parameters assessing the cell proliferative activity, indicates that this category includes biologically heterogeneous lymphoma subtypes with different grades of aggressiveness. The results also indicate that the G intermediate category displays proliferation indices similar to those of H high grade category.

Flow cytometry in the bone marrow staging of mature B-cell neoplasms.

BACKGROUND: Even though flow cytometric (FC) analysis of bone marrow aspirates is often performed in hematolymphoid disorders at diagnosis and during disease monitoring, its role has not been defined during the staging of B-non-Hodgkin's lymphoma (B-NHL) and B-cell lymphoproliferative diseases. The goal of this study was to provide an objective evaluation of how FC might help in the detection of bone marrow involvement by the different types of B-cell malignant neoplasms. METHODS: Fifty-four staging and 156 restaging bone marrow biopsies and bone marrow aspirates, obtained from 185 consecutive patients, were analyzed retrospectively. The results of the morphologic examination and FC were reviewed independently, and their ability to detect bone marrow involvement was compared. RESULTS: FC and morphology agreed in 176 cases (83.8%), i.e., both showed 77 positive cases and 99 negative ones. Discrepant results were obtained in 30 cases (14.2%) in which morphologic examination showed 25 (11.9%) positive cases, whereas FC showed no evidence of disease. FC detected involvement in five cases (2.4%) in the presence of a histologically negative bone marrow biopsy. All morphologically undetermined bone marrow cases (four) were negative by FC. CONCLUSIONS: Neither morphologic examination nor FC alone is adequate for the detection of all cases of B-lymphoid neoplasm bone marrow involvement. FC failed to detect bone marrow involvement in those B-NHL cases having focal paratrabecular infiltration, but proved to be more sensitive than histology in detecting small clonal B-cells in B-NHL, which demonstrated fewer than 5% neoplastic infiltrates. The clinical relevance of minimal disease detected by FC alone needs further evaluation because staging of lymphomas currently is based only on morphologic data.

High prognostic impact of growth fraction parameters in advanced stage laryngeal squamous cell carcinoma.

One hundred and two cases of laryngeal squamous cell carcinoma, all treated in the same center with total or supraglottic laryngectomy, bilateral neck dissection and postoperative radiotherapy, were investigated with both Ki67 and MIB-1 monoclonal antibodies. The aim was to determine the prognostic impact of growth fraction markers in a homogeneous series of patients. All samples were stained with Ki67 monoclonal antibody on frozen sections, and with MIB-1 monoclonal antibody on paraffin sections, using the ABC immunoperoxidase method. The percentage of positive cells was compared in each case with the overall and disease-free survival, pathologic stage and histologic grading. The values obtained from Ki67 and MIB-1 counts were similar and highly correlated (r=0.90). Two groups of cases with low and high proliferation rate (59 and 43 respectively) were obtained by splitting up the whole series, on the basis of the median value; 84. 6% of the patients with high proliferation relapsed and/or died due to the tumor within two years from diagnosis whereas, at time of writing, 94% of the patients with low proliferation are alive and well (p<0.00001). No relation was found between growth fraction and histologic grading, pathologic stage (pT and pN) and site of the tumor. Only lymph node involvement was correlated with disease-free survival. Our results indicate that Ki67/MIB-1 index represents an independent variable to determine long-term prognosis in laryngeal squamous cell carcinomas. We recommend its use in diagnostic protocols, to distinguish high risk subsets of patients who might benefit from more aggressive treatments.

Expression of the CD31 antigen in normal B-cells and non Hodgkin's lymphomas.

The role cell adhesion molecules play in the biological and clinical behaviour of non Hodgkin's lymphomas (NHL) has been reported in several studies. This study reports the findings on B-cells taken from various healthy control tissues and compared them to B-cells from 83 malignant B-lymphomas, that had been classified according to the WHO classification. Flow cytometry was used to investigate the surface expression of CD31, an adhesion molecule involved in B-cell development and vascular adhesion mechanisms. Quantification of the fluorescence signals showed specific patterns of CD31 expression on normal B-cell subpopulations and different NHL groups. Our results demonstrate that CD31 expression is modulated during the differentiation process in normal B-cells, high in pre-B-I cells, low in pre-B-II precursors, intermediate in the mature B-cell subpopulations or, depending on the functional state absent in activated follicular centre cells, present in pre- and post- germinal centre cells. When the CD31 expression is evaluated as fluorescence intensity in NHL, it reveals a heterogeneous pattern related to histogenetic derivation (high in small lymphocytic lymphoma, low in follicular lymphoma, intermediate in marginal zone and large cell lymphomas). These observations suggest that CD31 might well play a critical role in the ontogeny and physiology of B-lymphocytes. Therefore, on the basis of these observations we propose the CD31 molecule as an interesting additional useful parameter to be used for the differential diagnosis of NHL and hypothese that it has a pathophysiologic role in NHL evolution.