Histopathological and immunophenotypical characterization of canine multicentric lymphoma in Brazil: a study of 203 cases / Caracterização histopatológica e imunofenotípica do linfoma multicêntrico canino no Brasil: um estudo de 203 casos

The immunophenotype is regarded as an independent prognostic factor in high-grade lymphomas, seeing that lymphomas of T-cell origin are associated with shorter survival time. Although a number of studies have evaluated the immunophenotypical profile of lymphoma in the USA and Europe, Brazilian research on the matter remains scarce. Exact characterization of the histopathological type is crucial to establish proper treatment and prognosis. This study evaluated the database of immunohistochemistry laboratories that perform immunophenotyping of canine lymphoma in Brazil. A total of 203 cases of multicentric lymphoma were classified according to the WHO classification. Immunophenotyping was able to identify 71.4% lymphomas of B-cell line, 27.1% of T-cell line and 1.5% of non-B cells and non-T cell lines. Diffuse large B-cell lymphoma was the most common with 59.1% of the cases. Among T-cell lymphomas, lymphoblastic was the most common (11.33% of the cases). Even though canine lymphomas tend to be high-grade, indolent lymphomas comprised 11.82% of the cases and T-zone lymphoma was the most prevalent (8.86%). The immunophenotype of multicentric lymphoma in Brazil is similar to those in other parts of the world, which suggests similar etiologic factors to the development of this disease.(AU)

O imunofenótipo é considerado um fator prognóstico independente em linfomas de alto grau, visto que os linfomas de origem de células T estão associados a menor tempo de sobrevida. Apesar de vários estudos terem avaliado o perfil imunofenotípico do linfoma nos EUA e na Europa, a pesquisa brasileira sobre o assunto ainda é escassa. A caracterização exata do tipo histopatológico é crucial para estabelecer o tratamento e o prognóstico adequados. Este estudo avaliou a base de dados de laboratórios de imuno-histoquímica que realizam imunofenotipagem do linfoma canino no Brasil. Um total de 203 casos de linfoma multicêntrico foi classificado de acordo com a classificação da OMS. A imunofenotipagem foi capaz de identificar 71,4% dos linfomas da linhagem de células B, 27,1% da linhagem de células T e 1,5% das linhagens de células não B e não T. O linfoma difuso de grandes células B foi o mais comum em 59,1% dos casos. Entre os linfomas de células T, o linfoblástico foi o mais comum (11, 33% dos casos). Embora os linfomas caninos tendam a ser de alto grau, os linfomas indolentes representaram 11,82% dos casos e o linfoma da zona T foi o mais prevalente (8,86%). O imunofenótipo do linfoma multicêntrico no Brasil é semelhante ao de outras partes do mundo, o que sugere fatores etiológicos semelhantes ao desenvolvimento dessa doença.(AU)

Revisão dos aspectos morfológicos e imunoistoquímicos do linfoma difuso de grandes células B (LDGCB) com ênfase em boca / Review of the morphological and immunohistochemical aspects of diffuse large B cell lymphoma (DLBCL) with emphasis on the mouth

Os linfomas compreendem um grupo diverso de neoplasias malignas, provenientes de células do sistema imunológico em diferentes estágios de diferenciação. Objetivo: o propósito deste artigo é facilitar o diagnóstico do linfoma difuso de grandes células B (LDGCB) por meio de seus aspectos clínicos, morfológicos e imunoistoquímicos, além de suas peculiaridades como manifestação primária em boca. Revisão de literatura: foi realizada uma revisão narrativa da literatura por intermédio de artigos selecionados nas bases de dados PubMed, Medline, SciELO e Lilacs, pela busca por palavras-chave. Aspectos relacionados a classificação e manifestações clínicas também foram considerados, a fim de facilitar o entendimento da lesão e de suas particularidades em boca. Verificou-se que o LDGCB representa a variante mais comum em boca. Os sinais e sintomas clínicos relacionados a essa condição podem ser: aumento de volume, dor, ulceração, alteração de cor da mucosa ou até mesmo parestesia. Morfologicamente, os LDGCBs apresentam células grandes, com padrão de crescimento difuso, citoplasma escasso, nucléolos evidentes e mitoses. Na imunoistoquímica, os LDGCBs são geralmente positivos para CD20 e outros marcadores da linhagem B (CD19, CD79a, PAX5 e CD138), dependendo do estágio de maturação em que se encontram as células B. Considerações finais: o diagnóstico do LDGCB em boca representa um desafio contínuo para os patologistas, em função da heterogeneidade de suas características morfológicas e imunofenotípicas.(AU)

Lymphomas comprise a diverse group of malignant neoplasias from cells of the immune system at different stages of differentiation. Objective: this article aimed to facilitate the diagnosis of diffuse large B-cell lymphoma (DLBCL) through its clinical, morphological, and immunohistochemical aspects, as well as its particularities as a primary manifestation in the mouth. Literature Review: hence, a narrative review of the literature was performed using articles selected in the PubMed, Medline, SciELO, and Lilacs databases through keyword search. Aspects related to classification and clinical manifestations were also considered to facilitate the understanding of the lesion and its particularities in the mouth. It was verified that the diffuse large B-cell lymphoma (DLBCL) represents the most common variant in the mouth. The clinical signs and symptoms related to this condition may be increased volume, pain, ulceration, changed mucosal color, or even paresthesia. Morphologically, DLBCL presents large cells with diffuse growth pattern, scarce cytoplasm, evident nucleoli, and mitoses. In immunohistochemistry, DLBCL is usually positive for CD20 and other markers of lineage B (CD19, CD79a, PAX5, and CD138) depending on the maturation stage in which B cells are found. Final considerations: the diagnosis of oral DLBCL represents a continuous challenge for pathologists due to the heterogeneity of its morphological and immunophenotypic characteristics.(AU)

Linfoma difuso de células B grandes: ¿una sola enfermedad? / Diffuse large B-cell lymphoma: a single disease?

RESUMEN Los linfomas no Hodgkin, trastornos hematológicos de alta incidencia, constituyen a su vez, un grupo heterogéneo de neoplasias, dentro de las cuales los linfomas difusos de células B grandes (LDCBG) representan un porcentaje superior al 60% en la mayoría de las series nacionales e internacionales. Estos LDCBG, a su vez, se presentan con características clínicas, perfiles genéticos y respuestas terapéuticas variadas, apreciándose específicamente en relación a su respuesta, que en un subgrupo de ellos se obtienen tasas de sobrevidas libre de progresión, sobrevidas totales y respuestas objetivas adecuadas, y en otro subgrupo se obtienen respuestas de calidad inferior. Por lo que es necesario el diseño de esquemas de tratamiento basados en criterios clínicos, inmunohistoquímicos y de perfil genético, que los agrupen adecuadamente para identificar modalidades terapéuticas diferenciadas para cada uno de ellos y así mejorar e igualar las tasas de respuesta mencionadas. En la actualidad, estas neoplasias son catalogadas como linfomas de alto y bajo riesgo y se están desarrollando esquemas terapéuticos diferentes al R-CHOP convencional, como el R-DA-EPOCH, R2CHOP, IR-CHOP, VR-CHOP y el eveRCHOP que se espera que presenten resultados alentadores.

ABSTRACT Non-Hodgkin's lymphomas are common and comprise a heterogeneous group of neoplasms, with diffuse large B-cell lymphoma (DLBCL) accounting for more than 60% of cases. Moreover, DLBCL presents with a variety of clinical characteristics, genetic profiles, and therapeutic responses. We aimed to improve progression-free survival, total survival, and objective results in an DLBCL subgroup. However, another subgroup demonstrated poor responses. Therefore, it is necessary to design treatment programs based on clinical, immunohistochemical, and genetic profiles, grouping cases properly to identify correct therapeutic modalities for each lymphoma subtype. Currently, these neoplasms are classified as high- and low-risk lymphomas, and therapeutic regimens are being developed to complement conventional R-CHOP, such as R-DA-EPOCH, R2CHOP, IR-CHOP, VR-CHOP, and eveRCHOP, which are expected to improve outcomes.

Intestinal Diffuse Large B-Cell Lymphoma: An Evaluation of Different Staging Systems

The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

Treatment of Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in all countries and all age groups. DLBCL is potentially curable, and the outcome of patients with DLBCL has completely changed with the introduction of therapy involving the monoclonal antibody rituximab in combination with chemotherapy. Nonetheless, relapse is detected after treatment with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone in approximately 30% of patients. It has recently become clear that DLBCL represents a heterogeneous admixture of quite different entities. Gene expression profiling has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses; however, incorporation of this information into treatment algorithms awaits further investigation. Future approaches to DLBCL treatment will use this new genetic information to identify potential biomarkers for prognosis and targets for treatment.

Prognostic Value of Immunohistochemical Biomarkers at Different Cut-off Values in Patients with Diffuse Large B-cell Lymphoma Treated with CHOP Chemotherapy

Many predictive models have been proposed for better stratification of diffuse large B-cell lymphoma (DLBCL). Hans' algorithm has been widely used as standard to sub-classify DLBCL into germinal center B-cell (GCB) and non-GCB origins. However, there have been disagreements in the literature regarding its prognostic significance. Here, we retrospectively analyzed Hans' algorithm and the individual immunohistochemical biomarkers at different cut-off values (5%, 30%, 50% or 75%) in 94 Korean patients with DLBCL treated with combination chemotherapy with cyclophosphamide, daunorubicin, vincristine, and prednisone. No significant differences were observed between the GCB (18 patients, 19.1%) and non-GCB (76, 80.9%) groups. Among individual biomarkers, CD10 negativity (cut point: 30%) and bcl-6 positivity (cut point: 5%) were independent good prognostic markers in progression-free survival (PFS), whereas bcl-6 (cut point: 5%) positivity was an independent good prognostic marker in overall survival irrelevant of international prognostic index. The present study showed the lack of predictability of Hans' algorithm in DLBCL patients, and that CD10, Bcl-6 may have diverse prognostic significance at different cut-off values. Our results suggest that the proposed cut-off value may not be applied universally, and that the optimal cut-off value may need to be optimized for individual laboratory.

Linfoma primario cutáneo difuso de células B grandes, tipo pierna (LPCDCBG-TP), localizado en cuero cabelludo / Diffuse primary large B-Cell cutaneous lymphoma

Los linfomas primarios cutáneos de células B se consideran actualmente como categoría distintiva de los linfomas primarios cutáneos y se reconocen subtipos característicos dentro de ellos. Se presenta un caso de linfoma primario cutáneo difuso de células B grandes, tipo pierna, con localización en el cuero cabelludo, donde se pudo disponer de estudios inmunohistoquímicos para su tipificación, que mostraron positividad para los marcadores CD20, bcl-2 y MUM-1, y negatividad para CD3 y bcl-6. Estos resultados, unidos a las características de las lesiones y el estudio histológico condujeron al diagnóstico final.