Soluble MIC-A, IPI, and response to treatment strongly predict survival in patients with germinal center diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma. MIC-A and MIC-B are the natural ligands for NKG2D, a receptor expressed in NK cells. MIC-A soluble isoforms (sMICA) have been described in different malignancies. OBJECTIVES: To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. MATERIALS AND METHODS: sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. RESULTS: Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. CONCLUSIONS: Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.

The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self.

Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion of nonstructural protein 1 (NS1) by infected cells. NS1 is highly immunogenic, and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. We demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which present cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV-associated autoimmune manifestations.

Expression of BAFF and BAFF receptors in primary Sjögren's syndrome patients with ectopic germinal center-like structures.

B cell-activating factor (BAFF) is an essential cytokine in primary Sjögren's syndrome (pSS) physiopathology. It has been reported that pSS patients develop germinal center-like (GC-like) structures in their minor salivary glands (MSGs). BAFF, BAFF-R, TACI, and BCMA expression was analyzed in MSGs from 29 subjects (nonspecific chronic sialadenitis and focal lymphocytic sialadenitis with the presence [pSS-GC(+)] or absence [pSS-GC(-)] of GC-like structures). Twenty-four percent of patients showed ectopic GC-like structures and a high focus score [p < 0.001 vs pSS-GC(-)]. BAFF serum levels (sBAFF) were high in pSS patients (p = 0.025 vs healthy subjects). However, the pSS-GC(-) group showed higher sBAFF levels than pSS-GC(+) patients. BAFF and BAFF-R glandular expression levels were higher in pSS-GC(+) patients, without significant differences compared to pSS-GC(-) patients. Soluble levels of BAFF correlated with anti-La/SSB antibodies and disease duration. Our results showed that BAFF could contribute to focal lymphocytic infiltration. The role of BAFF-binding receptors in MSGs is proposed as a mechanism for the possible establishment of ectopic GC-like structures and disease progression in some patients. In conclusion, this study supports previous evidence that considers the active BAFF system role in the pathogenesis of pSS and the need for strong biomarkers in this disease.

Discriminant analysis and machine learning approach for evaluating and improving the performance of immunohistochemical algorithms for COO classification of DLBCL.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.

Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas.

Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Limited data exists concerning its expression in B-cell lymphomas, and comparison with other GC-associated antigens is lacking. Its role in the differential diagnosis of B-cell lymphomas, particularly in the distinction of follicular lymphoma (FL) versus marginal zone lymphoma (MZL), remains to be determined. We evaluated MEF2B expression, in comparison with additional GC markers, LIM domain-only transcription factor 2 (LMO2), and human GC-associated lymphoma (HGAL), in a variety of B-cell lymphomas, with particular emphasis on their utility in differentiating FL from MZL. MEF2B was positive in all FL and Burkitt lymphomas, 8/9 mantle cell lymphomas, 2/24 splenic MZL, 1/10 chronic lymphocytic leukemia/small lymphocytic lymphomas, and 38/44 diffuse large B-cell lymphoma (DLBCL), but was negative in all extranodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and B-lymphoblastic lymphomas. Focusing on low-grade FL versus MZL, MEF2B was 100% sensitive and 95% specific for FL, which was similar to BCL6, but superior to LMO2 (sensitivity 87%, specificity 86%) and HGAL (sensitivity 97%, specificity 86%). Importantly, MEF2B was positive in 4/4 FL with plasmacytoid differentiation, which were CD10, only weakly BCL6, and included 1 case that lacked both LMO2 and HGAL expression. MEF2B was positive in 22/25 (88%) GC-type DLBCL, but was also positive in 16/19 (61%) non-GC-type DLBCL. MEF2B shows superior sensitivity and specificity than LMO2 and HGAL in the differential diagnosis of FL versus MZL and is particularly useful in FL with plasmacytoid differentiation, which may have morphologic and immunophenotypic overlap with MZL. MEF2B, however, is not specific for GC-derived B-cell lymphomas as it is also apparently positive in most mantle cell lymphoma and many non-GC-type DLBCL.

Effects of early and late adverse experiences on morpho-quantitative characteristics of Sprague-Dawley rat spleen subjected to stress during adulthood.

Morpho-quantitative studies of the spleen indicate that the proportions of the compartments and sub-compartments are stable in normal conditions. However, disorders due to stress can influence the number and function of the immune cells in this organ. The aim of this study was to determine, through the model of altering the early mother-infant bond and altering the late social bond through isolation, the effect on the morpho-quantitative characteristics of the spleen in adult Sprague-Dawley rats subjected to intermittent chronic stress in adulthood. Twenty-five newborn female rats were used, kept under the standardized lactation and feeding conditions. The rats were assigned randomly to 2 control groups (C1 and C2) and 3 experimental groups, exposed to early (E1), late (E2) or early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood (C2, E1, E2 and E3). The spleen of each animal was isolated and its morphometric characteristics were determined: volume density (Vv) of the red pulp, white pulp, marginal zone, splenic lymph nodule, periarterial lymphatic sheath and germinal center; areal number density (Na), surface density (Sv), number density (Nv), diameter (D) and total number of splenic lymph nodules. The mass of each compartment was also determined. A one-way analysis of variance (ANOVA) and Scheffé's post hoc test were used for the statistical analysis. The p values were considered significant when they were less than 0.05 (*) and very significant at less than 0.025 (**). There were significant differences in the Vv of the red pulp, white pulp and their sub-compartments between the control and experimental groups. The white pulp increased significantly (P = 0.000) in E1, E2 and E3 compared to C1 and C2. The average Na and D values of the splenic lymph nodules were also higher in the experimental groups. The ANOVA for the mass of the spleen and the red pulp revealed no differences between the groups. The mass of the white pulp and its subcompartments was greater in the experimental groups. A higher proportion of white pulp in the experimental groups could be associated with an increase in spleen immune activity, with alterations depending on certain cell subsets. The chronic stress produced morpho-quantitative changes in the rat spleen, and these depended on the animal's history of stress, whether it had been previously stressed or not, with further exposure to stress in adulthood.

Acquired thrombotic thrombocytopenic purpura due to antibody-mediated ADAMTS13 deficiency precipitated by a localized Castleman's disease: a case report.

Acquired ADAMTS13 inhibitor causing thrombotic thrombocytopenic purpura (TTP) may be precipitated by some infections, inflammatory diseases or neoplasia. We reported a case of refractory TTP precipitated by a newly diagnosed localized Castleman's disease (CD). TTP was initially treated with plasma exchange and immunosuppressive therapy with corticosteroids; however the treatment failed to promote sustained response. During hospitalization, an abdominal tumor was diagnosed and resected; the histological analysis revealed a CD of hyaline-vascular variant rich stroma. After tumor removal, the patient achieved a long-lasting clinical remission and normalized ADAMTS13 activity. This clinical case describes a novel association of acquired ADAMTS13 inhibitor and CD. The antibody to ADAMTS13 developed along with the systemic manifestation of CD and promptly disappeared after the resection of the tumor. There are reports of neoplasia-associated thrombotic microangiopathy however direct evidence of CD-dependent ADAMTS13 inhibitor had not yet been reported.

Diffuse large B-cell lymphoma involving the central nervous system.

Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.

BCL6, MUM1, and CD10 expression in mantle cell lymphoma.

Mantle cell lymphoma (MCL) characteristically express CD20, CD5, and cyclin-D1, carries the translocation t(11;14) (q13;q32) and typically has no expression of germinal center cell markers. So-called aberrant phenotypes such as CD5 negative and cyclin-D1-negative MCL have been described. Also few cases with CD10 and/or BCL-6 protein expression have been reported. We analyzed 127 MCL looking for the frequency of aberrant immunophenotype, CD10, BCL-6, and MUM1 expression. All cases were CD20 and cyclin-D1 positive, 96% expressed CD5, and 98% showed the t(11;14). BCL-6 expression was observed in 12% of the cases and MUM1 in 35%. No one case showed CD10 positivity in 30% or more neoplastic cells. Only 3 cases showed 10% to 20% of tumoral cells positive for CD10. MUM1 expression was observed in 67% of the BCL-6 positive cases. Thirty-two percent of the cases showed a MUM1+/BCL-6-/CD10- phenotype and 56% had a triple-negative-pattern. Aberrant phenotype is infrequent but not rare, and does not rule out a diagnosis of MCL in an otherwise typical case.

Human germinal center-associated lymphoma protein expression is associated with improved failure-free survival in Brazilian patients with classical Hodgkin lymphoma.

The human germinal center-associated lymphoma (HGAL) gene has prognostic value in diffuse large B-cell lymphoma, and expression of its cognate protein is germinal center-specific. A previous study had suggested that HGAL protein expression might also be related to the outcome in patients with Hodgkin lymphoma (HL). The aim of this study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 patients with classic HL treated uniformly with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Tissue microarray analysis showed HGAL staining in 188 specimens (81%). Failure-free survival (FFS) was superior in patients with early-stage disease, low-risk IPS, and HGAL-positive patients. The estimated 5-year FFS for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (p = 0.03). In the multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse FFS. This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical HL.

Frequent expression of multiple myeloma 1/interferon regulatory factor 4 in Burkitt lymphoma.

Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma with endemic, sporadic, and immunodeficiency-associated clinical variants composed of monomorphic medium-sized B cells with a high proliferation rate and a translocation involving the C-MYC locus. Classically, the immunophenotype of Burkitt lymphoma has been considered to be the germinal center type. In most reports, all cases of Burkitt lymphoma are reported to be multiple myeloma 1-negative. multiple myeloma 1 expression is seen in plasma cells and in a small fraction of B cells located in the light zone of germinal centers corresponding to the final step of intra-germinal center B-cell differentiation, and in activated T cells. Therefore, multiple myeloma 1 expression may denote the final step of intra-germinal center B-cell differentiation at the centrocyte stage, as well as the subsequent steps of B-cell maturation toward plasma cells. Unlike most normal germinal center B cells, in which the expression of multiple myeloma 1 and bcl-6 are mutually exclusive, the tumor cells in approximately 50% of multiple myeloma 1-positive DLBCL show coexpression of bcl-6, suggesting that the expression of these proteins may be deregulated. Twenty-five Burkitt lymphoma cases, including 19 associated with HIV, were reported in one of the few studies in the literature; 2 of these cases showed occasional multiple myeloma 1-positive cells, less than the 20% cutoff for positivity. We studied 222 cases of well-characterized Burkitt lymphoma with the classic phenotype and C-MYC translocation and found 90 cases (40.5%) with multiple myeloma 1 nuclear expression, suggesting a late germinal center stage of differentiation.

Vanadium pentoxide inhalation provokes germinal center hyperplasia and suppressed humoral immune responses.

Vanadium, an important air pollutant derived from fuel product combustion, aggravates respiratory diseases and impairs cardiovascular function. In contrast, its effects on immune response are conflicting. The aim of our work was to determine if spleens of vanadium-exposed CD1 mice showed histological lesions that might result in immune response malfunction. One hundred and twelve CD-1 male mice were placed in an acrylic box and inhaled 0.02 M vanadium pentoxide (V2O5); actual concentration in chamber approximately 1.4 mg V2O5/m(3)) for 1 hr/d, twice a week, for 12 wk. Control mice inhaled only vehicle. Eight mice were sacrificed prior to the exposures. Eight control and eight V2O5-exposed mice were sacrificed 24 hr after the second exposure of each week until the 12-wk study was over. Another 8 mice that completed the 12-wk regimen were immunized with recombinant Hepatitis B surface antigen (HBsAg; three times over an 8-wk period) before sacrifice and analyses of their levels of anti-HBsAg antibody (HBSAb) using ELISA. In all studies, at sacrifice, blood samples were obtained by direct heart puncture and the spleen was removed, weighed and processed for H-E staining and quantitation of CD19 cells. The results indicated that the spleen weight of V2O5-exposed animals peaked at 9 wk (546 +/- 45 vs. 274 +/- 27 mg, p < 0.0001) and thereafter progressively decreased (321 +/- 39 mg at 12 wk, p < 0.001; control spleen = 298 +/- 35 mg). Spleens of V2O5-exposed animals showed an increased number of very large and non-clearly delimited germinal centers (that contained more lymphocytes and megakaryocytes) compared to those of control mice. In addition, their red pulp was poorly delimited and had an increase in CD19+ cells within hyperplasic germinal nodes. The mean HBsAb levels in immunized control mice were greater than that in the exposed hosts (i.e., OD = 0.39 +/- 0.03 vs. 0.11 +/- 0.05, p < 0.01). HBsAb avidity dropped to a value of 40 in V2O5-exposed animals vs. 86 in controls (p < 0.0001). We conclude that the chronic inhalation of V2O5, a frequent particle (PM(2.5)) component, induces histological changes and functional damage to the spleen, each of which appear to result in severe effects on the humoral immune response.

Germinal center architecture disturbance during Plasmodium berghei ANKA infection in CBA mice.

BACKGROUND: Immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. One of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. In this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and Peyer's patches) with immunity and pathology was evaluated during Plasmodium berghei ANKA infection in CBA mice. METHODS: CBA mice were infected with 1 x 10(6) P. berghei ANKA-parasitized erythrocytes and killed on days 3, 6-8 and 10 of infection. The spleen, lymph nodes and Peyer's patches were collected, fixed in Carson's formalin, cut in 5 mum sections, mounted in glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed with bright-field microscopy. RESULTS: Early (day 3) strong activation of T cells in secondary lymphoid organs was observed and, on days 6-8 of infection, there was overwhelming activation of B cells, with loss of conventional germinal center architecture, intense centroblast activation, proliferation and apoptosis but little differentiation to centrocytes. In the spleen, the marginal zone disappeared and the limits between the disorganized germinal center and the red pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone. CONCLUSION: The observed alterations, especially the germinal center architecture disturbance (GCAD) with poor centrocyte differentiation, suggest that B cell responses during P. berghei ANKA infection in mice are defective, with potential impact on B cell memory responses.

Intra-abdominal follicular dendritic cell sarcoma.

Follicular dendritic cell (FDC) sarcoma is a very rare condition. We report here an intra-abdominal FDC sarcoma occurring as a mass, dependent on the celiac and left gastric lymph chains, that was completely excised. Eighteen months after surgery a recurrence at the liver pedicle was detected by a CT-scan and fully resected; in order to prevent another disease relapse postoperative radiotherapy was given.

[Cutaneous B cell processes with nodular pattern]. / Procesos linfoides B cutáneos con patrón nodular.

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.

Primary Hodgkin's lymphoma of the caecum.

Extra-nodal Hodgkin's lymphoma (HL) represents 15% of all Hodgkin's lymphomas; the primary intestinal site accounts for 1% and with involvement of the ascending colon being rare. We present the case of a patient of 62 years of age diagnosed as having acute appendicitis. Anatomopathology on the excised appendectomy tissue indicated nodular lymphocytic predominant Hodgkin's lymphoma (NLPHL). The morphology indicated isolated L&H (lymphocytic or histiocytic) cells or in groups, surrounded by T lymphocytes, in an environment of germinal centres together with phenomena that would be interpreted as progressive transformation. Immunohistochemistry staining of the HL cells were positive for CD45, CD20, Bc16, EMA and MUM1 and negative for CD15 and CD30. No complementary treatment was administered. Following a literature search, the present case would appear to be the first of its kind.

Procesos linfoides B cutáneos con patrón nodular / Cutaneous B cell processes with nodular pattern

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.

Procesos linfoides B cutáneos con patrón nodular / Cutaneous B cell processes with nodular pattern

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.(AU)

Procesos linfoides B cutáneos con patrón nodular / Cutaneous B cell processes with nodular pattern

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.(AU)

[Chronic atrophic gastritis: pathogenic mechanisms due to cellular hypersensitivity]. / Gastritis crónica atrófica: Mecanismos patogénicos por hipersensibilidad cellular.

Chronic Atrophic Gastritis of high incidence in Helicobacter pylori infection has not been pathogenically explained yet. Helicobacter Pylori Chronic Active Superficial Gastritis has not been related to Chronic Atrophic Gastritis by some authors, who considered, until some time ago, that they both were independent lesions. In this study, we examined 42 antral or corporal gastric biopsies with Chronic Atrophic Gastritis at different stages, with histological lesions going from "deep lymphoid infiltration" in the proper gastric glands, to the replacement by fibro inflammatory tissue. With immunohystochemistry methods we have been able to prove that the lymphoid cells infiltrating the glandular part of the gastric mucous membrane are composed by CD8+(cytotoxic)T lymphocytes and by B lymphocites antibody secretors. In this study we suggest that cytotoxic T lymphocytes damage and destroy antral and corporal gastric proper glands, with further fibro inflammatory tissue replacement. Similar actions would be produced by B lymphocytes, but by secreting local antibodies against the cells from proper gastric glands.