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Background The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype, with scarce available data describing their clinical and microscopic aspects. Therefore, in this study we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. Methods Cases diagnosed as mature T/NK cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. Results A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T cell lymphoma nasal type, but was absent in the other subtypes. Conclusion Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogenous group of neoplasms has a very aggressive clinical behaviour.

The aim of this study was to describe the clinicopathological and immunohistochemical features of four cases of anaplastic large cell lymphoma (ALCL) diagnosed through oral manifestations. Clinical data were collected from charts of a single oral pathology laboratory over a 5-year period (2014–2019) and all cases were evaluated by conventional hematoxylin and eosin staining and an extended immunohistochemical panel comprising CD45, CD20, CD3, CD4, CD7, CD30, CD99, CD138, cytokeratin AE1/AE3, EMA, ALK, MUM-1 and Ki-67. The study included 3 male (75%) and 1 female (25%) patients, with a median age of 44 years. The most common intraoral affected site was the alveolar ridge (50%). Clinically, all cases were characterized as an ulcerated bleeding mass. Microscopically, proliferation of anaplastic large lymphoid cells with medium to large-sized, abundant amphophilic to eosinophilic cytoplasm and eccentric nuclei were observed. All cases were positive for CD30, while two cases strongly express ALK. Two patients died of the disease. Careful correlation of clinical, morphological and immunohistochemical data are necessary to establish the diagnosis of oral manifestation of ALCL since its microscopical features may mimic other malignant tumors. Clinicians and pathologists should consider ALCL in the differential diagnosis when evaluating oral ulcerated swellings exhibiting large lymphoid cells in patients with lymphadenopathy.

Resumo A úlcera mucocutânea associada ao Vírus Epstein Barr é uma doença linfoproliferativa indolente de linfócitos B que foi descrita em 2010 por Stefan D. Dojcinov e cols. Pode ocorrer em associação com etiologias imunossupressoras, incluindo deficiência imune primária, infecção pelo vírus da Imunodeficiência Humana (HIV), pacientes pós transplantes e em uso de metotrexato ou antagonistas TNF-alfa. Os pacientes apresentam quadro clínico de úlcera de surgimento insidioso, com localização cutânea ou de mucosas, preferencialmente de orofaringe. Os achados histopatológicos da lesão revelam áreas ulceradas com infiltrado polimórfico de linfócitos, plasmócitos, histiócitos e eosinófilos em meio a células grandes, pleomórficas que lembram células de Hodgkin e de Reed-Sternberg. O epitélio adjacente geralmente mostra núcleos atípicos e hiperplasia pseudoepiteliomatosa. As células grandes pleomórficas mostram positividade para CD20, CD30, Oct-2, PAX5 e EBV. Estas células podem ser também positivas para MUM1, focalmente positivas para Bcl-6 e não costumam expressar CD10. Apesar da presença de células muito atípicas, o curso clínico é indolente, sem progressão para doença disseminada, sendo essencial diferenciá-la de doenças linfoproliferativas malignas. Descrevemos dois casos de pacientes com diagnóstico de úlcera mucocutânea associada ao vírus Epstein Barr (EBV) para adicionar aos poucos casos já descritos na literatura.

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.

Background: A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkin’s lymphoma (cHL). Patients and methods: The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. Results: There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein‐Barr viruspositive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. Conclusion: CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.

The outcome of Hodgkin's lymphoma (HL) has markedly improved over the last few decades, placing HL among the human cancers with highest cure rates. However, data about treatment outcomes in developing countries are scarce. From 1996 to 2005, 370 consecutive patients with HL treated in three public institutions in Rio de Janeiro were identified. A total of 216 patients who presented with advanced stage (IIB-IV) HL were selected for the present analysis. Patients with advanced disease were treated with ABVD, complemented or not by radiation therapy. The median follow-up time of survivors was 6.3 years (1-11.8). Fifteen patients died during first-line treatment. The complete remission rate was 80%. The 5-year progression-free survival (PFS) and the 5-year overall survival (OS) probabilities were 69% and 83%, respectively. The 5-year PFS in low-risk and high-risk patients were 81% and 62% (p=0.003), respectively. The 5-year OS in low-risk and high-risk International Prognostic Score patients were 89% and 78% (p=0.02), respectively. The present study provides a representative estimate of current treatment results for advanced HL in public institutions in an urban area in Brazil. It is clear that full treatment can be given to most patients, although those with very low socio-economic status might require special attention and support. Since Brazil is a large country, with substantial interregional heterogeneity, a nationwide registry of HL patients is currently being implemented. Os resultados do tratamento do linfoma de Hodgkin (LH) melhoraram substancialmente ao longo das últimas décadas e tornaram o LH uma das neoplasias humanas com maior chance de cura. Entretanto, os dados sobre tratamento em países em desenvolvimento são escassos. Entre 1996 e 2005, 370 pacientes consecutivos com LH tratados em três instituições públicas no Rio de Janeiro foram identificados. Destes, 216 em estádio avançado (IIB-IV) foram selecionados para esta análise. Os pacientes foram tratados com o protocolo ABVD (doxorrubicina, bleomicina, vinblastina e dacarbazina). A mediana do tempo de seguimento dos sobreviventes foi de 6,3 anos (1-11,8). Quinze pacientes morreram durante o tratamento de primeira linha. A probabilidade de sobrevida livre de progressão (SLP) em cinco anos e a probabilidade de sobrevida global (SG) em cinco anos foram de 69% e 83%, respectivamente. A SLP nos grupos de baixo risco e de alto risco, de acordo com o "International Prognostic Score", foi de 81% e 62% (p=0,003), respectivamente. A SG em cinco anos nos grupos de baixo risco e de alto risco foi de 89% e 78% (p=0,02), respectivamente. O presente estudo apresenta uma estimativa representativa dos resultados atuais do tratamento do LH avançado em instituições públicas no Brasil. Fica claro que o tratamento completo pode ser oferecido à grande maioria dos pacientes, embora aqueles com baixo status socioeconômico possam exigir atenção especial. Em vista das dimensões continentais do Brasil, com substancial heterogeneidade interregional, um registro nacional de pacientes com LH está sendo implementado.

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.

Immunohistochemistry (IHC) has become an essential part of diagnosis and clinical research in lymphomas. There is considerable heterogeneity, however, in IHC findings regarding expression rate and positivity cut-offs, which creates a degree of uncertainty that has prevented its incorporation for prognostic purposes. The purpose of the present study was to assess intra- and interobserver agreement in scoring bcl-2 expression on IHC. The study materials were 81 diffuse large B-cell lymphomas. Slides were processed in the same laboratory, and were analyzed independently and in a blinded manner by four pathologists twice, at least 1 month apart. The positivity rates ranged from 31% to 41% in the first evaluation, and from 30% to 43% in the second evaluation. The two analyses by the same pathologist gave concordant results in 88-93% of cases (kappa = 0.71-0.83). Complete agreement among all observers varied from 72% to 79%. The experience of the observer did not influence intra-observer concordance. Cooperative analysis of discordant slides led to consensus in all cases. The variation observed in scoring bcl-2 expression is acceptable for use in lymphoma diagnosis and classification. The use of IHC stratification, however, for clinical decisions regarding treatment will require standardization and centralized consensus review, and must await the results of ongoing prospective trials.

Abstract 4632 BACKGROUND The 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 outcome in patients with Hodgkin lymphoma. PATIENTS AND METHODS The aim of the current study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 classic Hodgkin lymphoma patients treated uniformly with the ABVD regimen from 1997 to 2004 in Brazil. The median follow-up was 6.2 years. RESULTS Tissue microarray analysis showed HGAL staining in 188 specimens (81%). The overall survival was better in patients with young age, early-stage, absence of B symptoms, low-risk international prognostic score (IPS) and good performance status. Failure-free survival was superior in patients with early-stage disease, low-risk IPS and HGAL-positive patients. The estimated 5-year failure-free survival for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (P=0.03). When stage, B symptoms and performance status were included along with HGAL in a multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse failure-free survival. CONCLUSION This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical Hodgkin lymphoma. Disclosures: No relevant conflicts of interest to declare.