Extranodal NK/T-cell lymphoma, nasal type with extensive cardiopulmonary involvement

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is a rare type of Non-Hodgkin's lymphoma, which usually presents with extranodal involvement and affects the nasal/upper aerodigestive tract in the classical presentation. Herein, we report the case of a 31-year-old, previously healthy, male patient diagnosed with ENKTL-NT with the involvement of the lung parenchyma and heart. Unfortunately, due to the rapid disease progression, the diagnosis was performed only at the autopsy. The authors highlight the rare clinical presentation of this type of lymphoma, as well as the challenging anatomopathological diagnosis in necrotic samples.

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

OBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.

Predictive features for histology of gastric subepithelial lesions / Fatores preditivos da histologia nas lesões subepiteliais gástricas

ABSTRACT BACKGROUND Gastric subepithelial lesion is a relatively common diagnosis after routine upper endoscopy. The diagnostic workup of an undetermined gastric subepithelial lesion should take into consideration clinical and endoscopic features. OBJECTIVE We aimed to investigate the association between patients' characteristics, endoscopic and echographic features with the histologic diagnosis of the gastric subepithelial lesions. METHODS This is a retrospective study with 55 patients, who were consecutively diagnosed with gastric subepithelial lesions, from October 2008 to August 2011. Patients' characteristics, endoscopic and echografic features of each gastric subepithelial lesion were analysed. Histologic diagnosis provided by EUS-guided fine needle aspiration or endoscopic/surgical resection was used as gold standard. RESULTS The probability of gastrointestinal stromal tumors to be located in the cardia was low (4.5%), while for leiomyoma it was high (>95%). In addition, there was a higher risk of gastrointestinal stromal tumors in patients older than 57 years (OR 8.9; 95% CI), with lesions ≥21 mm (OR 7.15; 95% CI), located at 4th layer (OR 18.8; 95% CI), with positive Doppler sign (OR 9; 95% CI), and irregular outer border (OR 7.75; 95% CI). CONCLUSION The location of gastric subepithelial lesions in the gastric cardia lowers the risk of gastrointestinal stromal tumors. While gastric subepithelial lesions occurring in elderly patients, located in the gastric body, with positive Doppler signal and irregular outer border increase the risk of gastrointestinal stromal tumors.

RESUMO CONTEXTO O diagnóstico das lesões subepiteliais gástricas é relativamente comum após a endoscopia digestiva alta de rotina. A posterior investigação diagnóstica de uma lesão subepitelial gástrica indeterminada deve levar em consideração os aspectos clínicos e endoscópicos. OBJETIVO O objetivo foi avaliar a associação entre as características particulares dos pacientes, endoscópicas e ecográficas dos casos de lesões subepiteliais gástricas com os seus diagnósticos histológicos finais. MÉTODOS Estudo retrospectivo com 55 pacientes, consecutivamente diagnosticados com lesão subepitelial gástrica de outubro de 2008 a agosto de 2011. As características do paciente, endoscópica e ecográfica de cada caso com lesão subepitelial gástrica foram analisadas. O diagnóstico histológico fornecido pela punção aspirativa com agulha fina guiada por ecoendoscopia e/ou a ressecção endoscópica/cirúrgica foram utilizadas como padrão-ouro. RESULTADOS A probabilidade de tumor estromal gastrintestinal ser localizado na cárdia foi baixa (4,5%), enquanto que para o leiomioma foi elevada (>95%). Além disso, houve um maior risco de tumor estromal gastrintestinal em pacientes acima de 57 anos (OR 8,9; IC 95%), com lesão ≥21 mm (OR 7,15; IC 95%), localizada na 4ª camada (OR 18,8; IC 95%), com sinal positivo no Doppler (OR 9; IC 95%), e borda externa irregular (OR 7,75; IC 95%). CONCLUSÃO A localização de uma lesão subepitelial gástrica na cárdia reduz o risco de tumor estromal gastrintestinal. Enquanto que lesões subepiteliais gástricas que ocorrem em pacientes idosos, localizadas no corpo gástrico, com sinal positivo no Doppler e com borda externa irregular aumentam significativamente o risco de tumor estromal gastrintestinal.

Secondary myeloid neoplasms: bone marrow cytogenetic and histological features may be relevant to prognosis

Abstract Background: Secondary myeloid neoplasms comprise a group of diseases arising after chemotherapy, radiation, immunosuppressive therapy or from aplastic anemia. Few studies have addressed prognostic factors in these neoplasms. Method: Forty-two patients diagnosed from 1987 to 2008 with secondary myeloid neoplasms were retrospectively evaluated concerning clinical, biochemical, peripheral blood, bone marrow aspirate, biopsy, and immunohistochemistry and cytogenetic features at diagnosis as prognostic factors. The International Prognostic Scoring System was applied. Statistical analysis employed the Kaplan–Meier method, log-rank and Fisher's exact test. Results: Twenty-three patients (54.8%) were male and the median age was 53.5 years (range: 4–88 years) at diagnosis of secondary myeloid neoplasms. Previous diseases included hematologic malignancies, solid tumors, aplastic anemia, autoimmune diseases and conditions requiring solid organ transplantations. One third of patients (33%) were submitted to chemotherapy alone, 2% to radiotherapy, 26% to both modalities and 28% to immunosuppressive agents. Five patients (11.9%) had undergone autologous hematopoietic stem cell transplantation. The median latency between the primary disease and secondary myeloid neoplasms was 85 months (range: 23–221 months). Eight patients were submitted to allogeneic hematopoietic stem cell transplantation to treat secondary myeloid neoplasms. Important changes in bone marrow were detected mainly by biopsy, immunohistochemistry and cytogenetics. The presence of clusters of CD117+ cells and p53+ cells were associated with low survival. p53 was associated to a higher risk according to the International Prognostic Scoring System. High prevalence of clonal abnormalities (84.3%) and thrombocytopenia (78.6%) were independent factors for poor survival. Conclusion: This study demonstrated that cytogenetics, bone marrow biopsy and immunohistochemistry are very important prognostic tools in secondary myeloid neoplasms.

Splenic diffuse red-pulp small B-cell lymphoma associated with hepatitis B virus: a report of two cases / Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, associado ao vírus da hepatite B: relato de dois casos

ABSTRACT CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.

RESUMO CONTEXTO: Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, é uma doença rara, representando menos do que 1% de todos os linfomas não Hodgkin. Essa entidade é caracterizada por envolvimento de sinusoides da medula óssea e sangue periférico. A maioria dos casos está em estádio avançado ao diagnóstico. Sua patogênese ainda é pouco compreendida. RELATOS DE CASOS: Reportamos dois pacientes com vírus da hepatite B (HBV) crônica não replicante que desenvolveram linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos. Ambos estavam em estádio IV ao diagnóstico e evoluíram com doença agressiva. Ambos alcançaram resposta completa com a quimioterapia, porém um deles evoluiu a óbito por intercorrências infecciosas durante o transplante de medula óssea e o outro optou por não realizar o transplante e encontra-se sem evidência de doença até os dias atuais (três anos após tratamento). Alguns estudos demonstraram a possível associação entre linfomas não Hodgkin B e HBV. Entretanto, o mecanismo pelo qual esse vírus oncogênico interage com linfoma não Hodgkin B ainda é pouco compreendido. HBV é linfotrópico e pode se inserir no genoma do receptor, causando superexpressão de oncogenes e downregulation de genes supressores tumorais. Portanto, o estímulo crônico pelo HBV pode aumentar a proliferação de células B, promovendo expansão monoclonal dessas células, resultando em malignidade. CONCLUSÃO: HBV pode estar implicado na patogênese desse linfoma, entretanto, uma associação direta entre essas duas entidades não pôde ser provada no presente estudo e investigações adicionais são necessárias.

Quantitative analysis of lymph nodes in neck dissection specimens. Morphologic study

ABSTRACT PURPOSE: To quantify the amount of lymph nodes harvested in modified radical neck dissection. METHODS: Cross-sectional anatomical study conducted in 28 non-preserved cadavers. RESULTS: The mean number of lymph nodes found in each nodal level of the 56 modified radical neck dissections performed were: level IA - 1.5 (95% CI: 1.1 - 1.8), level IB - 2.5 (95% CI: 2.1 - 2.9), level IIA - 7.2 (95% CI: 6.0 - 8.5), IIB level - 6.5 (95% CI: 5.5 - 7.4), level III - 6.6 (95% CI: 5.7 - 7.4), level IV - 8.6 (95% CI: 7.1 - 10.1), level V - 11 (95% CI: 9.2 - 12.7), totalizing 43.8 lymph nodes (95% CI: 40.3 - 47.4). CONCLUSION: The results defined a parameter in relation to the minimum recommended nodal yield in a modified radical neck dissection, as well as the number of lymph nodes in each level of this dissection, performed in clinical practice.

Significant differe nces in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation. .

Pathophysiology and molecular aspects of diffuse large B-cell lymphoma

Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multi factorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6,and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma.

Classificação dos tumores hematopoéticos e linfoides de acordo com a OMS: padronização da nomenclatura em língua portuguesa, 4ª edição / Classification of haematopoietic and lymphoid tumors: WHO, standardization of nomenclature in Portuguese, 4th edition

INTRODUÇÃO: A classificação da Organização Mundial da Saúde (OMS) para os tumores do tecido hematopoético e linfoide (4ª edição, 2008) representa uma revisão atualização da 3ª edição publicada em 2001. A tradução da nomenclatura utilizada para identificar as entidades descritas deve ser clara, precisa e uniforme no sentido de reproduzir de forma correta as diversas entidades clinicopatológicas para clínicos, patologistas e pesquisadores envolvidos na área da onco-hematopatologia. OBJETIVO: Os autores apresentam uma proposta de atualização e padronização terminológica em língua portuguesa, com base na OMS/2008.

INTRODUCTION: The World Health Organization (WHO) classification of hematopoietic and lymphoid tissue (4th edition, 2008) tumors constitutes an updated review of the 3rd edition published in 2001. The translation of the nomenclature used to describe the entities should be clear, precise and uniform so that clinicians, pathologists and researchers involved in the onco-hematopathological area may identify them accurately. OBJECTIVE: With this purpose, the authors present an updated proposal and a terminological standardization in Portuguese based on WHO/2008.

Comparação de três protocolos distintos para extração de RNA de amostras fixadas em formalina e emblocadas em parafina / Comparison of three different protocols for extracting RNA from formalin-fixed paraffin-embedded tissues

INTRODUÇÃO: Tecidos fixados em formalina e emblocados em parafina (FFEP) são importantes fontes de amostras para estudos retrospectivos. Apesar de sua capacidade de preservação de proteínas e morfologia celular, a formalina interfere negativamente em testes de biologia molecular por fragmentar e modificar quimicamente os ácidos nucleicos, particularmente o ácido ribonucleico (RNA). OBJETIVO: Comparar a eficiência de três diferentes protocolos de extração de RNA para análise de expressão gênica de tecidos FFEP. MATERIAL E MÉTODOS: Amostras de linfonodo humano FEEP foram submetidas à extração de RNA utilizando-se os kits Ambion e Arcturus Bioscience e o método clássico de Trizol. Após a extração, o RNA foi quantificado e testado quanto à sua capacidade de amplificação pela reação em cadeia da polimerase em tempo real (RT-PCR) utilizando primers do gene endógeno gliceraldeído-3 fosfato desidrogenase (GAPDH). DISCUSSÃO/CONCLUSÃO: Todos os protocolos testados produziram quantidades adequadas e suficientes de RNA total, entretanto, somente os protocolos com uso dos kits Ambion e Arcturus produziram RNA capaz de ser amplificado pela PCR.

INTRODUCTION: Formalin fixed paraffin embedded (FFPE) tissues are an important sample source for retrospective studies. Despite its ability to preserve proteins and cell morphology, formalin hinders Molecular Biology tests once it fragments and chemically modifies nucleic acids, particularly RNA. OBJECTIVE: To compare the efficiency of three different RNA extraction protocols for gene expression analysis of FFEP tissues. MATERIAL AND METHODS: RNA was extracted from FFPE samples of human lymph by means of Ambion and Arcturus Bioscience kits and the classical Trizol method. After extraction, RNA was quantified and tested for amplification through real time polymerase chain reaction (RT-PCR) using glyceraldehydes-3 phosphate dehydrogenase (GAPDH) endogenous gene primers. DISCUSSION/CONCLUSION: All the protocols produced sufficient and adequate amounts of total RNA. However, only protocols using Arcturus and Ambion kits generated suitable RNA for PCR amplification.

Disease progression after R-CHOP treatment associated with the loss of CD20 antigen expression

A case of a follicular lymphoma transformed into a CD20+ is described which progressed with the loss of CD20 expression after 8 cycles of R-CHOP. This phenomenon is not a rare event and has shown poor prognosis. Our purposes are to describe this event and suggest biopsy in relapsed or progressive disease.

Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma / Frequência da proteína Bcl-2 em pacientes com linfoma difuso de grandes células B de alto risco

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9 percent) were GCB-like and 49 (67.1 percent) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37 percent) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37 percent of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

CONTEXTO E OBJETIVO: A expressão gênica e imunoistoquímica do linfoma difuso de grandes células B (LDGCB) vem permitindo a identificação de importantes subgrupos prognósticos: LDGCB do centro germinativo (CG) e LDGCB de células B ativadas (CBA). Entretanto, existem poucos dados disponíveis com LDGCB de alto risco, sendo o prognóstico dos LDGCB do CG melhor que os LDGCB de CBA. A participação do Bcl-2 como preditor de sobrevida nos LDGCB não é clara e sua expressão é variável entre os dois subgrupos de LDGCB. Neste estudo é avaliada a frequência e o prognóstico da expressão da proteína Bcl-2 em LDGCB de alto risco. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo realizado entre portadores de LDGCB tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foi avaliado o impacto prognóstico da expressão das proteínas CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) e Bcl-2 por imunoistoquímica em LDGCB de alto risco. Foram avaliados, para todos os marcadores, 73 pacientes com idade de 18 a 60 anos. RESULTADOS: Vinte e quatro (32,9 por cento) pacientes foram classificados como LDGCB do CG e 49 (67,1 por cento) como LDGCB de CBA, sem diferença nas taxas de remissão completa, sobrevida livre de doença e sobrevida global. Vinte e sete (37 por cento) apresentaram expressão de Bcl-2, o qual foi o único fator preditivo independente de pior prognóstico de sobrevida global à análise multivariada. CONCLUSÃO: A expressão da proteína Bcl-2 ocorreu em 37 por cento dos portadores de LDGCB de alto risco, sem diferença entre os subgrupos de LDGCB do CG ou de CBA.

Are histological alterations observed in the gallbladder precancerous lesions?

INTRODUCTION: Gallbladder cancer, which is characterized by rapid progression and a poor prognosis, is a complex disease to treat. Unfortunately, little is known currently about its etiology or pathogenesis. A better understanding of its carcinogenesis and determining risk factors that lead to its development could help improve the available treatment options. METHOD: Based on this better understanding, the histological alterations (such as acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis, polyps, pyloric metaplasia, intestinal metaplasia, dysplasia, cancer and others) in gallbladders from 1,689 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis were analyzed. The association of these gallbladder histological alterations with clinical data was studied. RESULTS: Gender analysis revealed a greater incidence of inflammatory changes in males, while dysplasia and cancer were only found in women. The incidence of cholesterolosis was greater in the patients 60 years of age and under, and the incidence of adenomyomatosis and gangrene was greater in the elderly patients. A progressive increase in the average age was observed as alterations progressed through pyloric metaplasia, intestinal metaplasia, dysplasia and then cancer, suggesting that the metaplasia-dysplasia-carcinoma sequence may occur in gallbladder cancer. Gallbladder histological alterations were also observed in asymptomatic patients. CONCLUSION: The results of this study suggest that there could be an association between some histological alterations of gallbladder and cancer, and they also suggest that the metaplasia-dysplasia-carcinoma sequence could in fact be true in the case of gallbladder cancer. Nevertheless, further studies directed towards a perfect understanding of gallbladder carcinogenesis are required.

Linfoma do tecido linfóide associado ao brônquio com evolução fatal / Fatal outcome in bronchus-associated lymphoid tissue lymphoma

Primary pulmonary lymphoma is rare. The most common histological type is the bronchus-associated lymphoid tissue lymphoma. This type of lymphoma has an indolent course and excellent response to therapy. One-third of all cases are diagnosed incidentally. However, due to the rarity of this disease, little is known about its natural history in terms of dissemination and evolution. Herein, we report the unusual case of a 61-year-old man who refused treatment after being diagnosed with bronchus-associated lymphoid tissue lymphoma and died 2 years later from massive lung infiltration without dissemination to other organs.

Linfomas primários do pulmão são raros. O tipo histológico mais freqüente é o linfoma do tecido linfóide associado ao brônquio. Este tipo de linfoma tem curso indolente e excelente resposta à terapia. Um terço dos casos é descoberto incidentalmente. Devido à raridade desta doença, no entanto, pouco se conhece sobre sua história natural em termos de disseminação e evolução. Neste relato, descrevemos o caso incomum de um homem de 61 anos que recusou o tratamento após diagnóstico de linfoma do tecido linfóide associado ao brônquio e, 2 anos após o diagnóstico, morreu por infiltração pulmonar maciça sem disseminação para outros órgãos.

The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1

PURPOSE: To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. METHODS: The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS: In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8 percent of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4 percent of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION: Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.

OBJETIVOS: Realizar rastreamentos clínico e gênico para Neoplasia Endócrina Múltipla tipo 1 (NEM1) e analisar seu impacto no seguimento clínico desses pacientes no Hospital das Clínicas, SP. MÉTODOS: O diagnóstico clínico de NEM1 foi realizado de acordo com o Consenso sobre neoplasias endócrinas múltiplas. A análise genética para identificação de mutações foi realizada por sequenciamento automático de todas as regiões codificadoras e fronteiras exon/intron do gene MEN1. Os casos afetados foram sub-divididos em 3 grupos e analisados separadamente: casos-índices (grupo I), familiares diagnosticados clinicamente (grupo II) e genicamente (grupo III). RESULTADOS: Um total de 154 casos participou desse estudo, sendo 52 diagnosticados com NEM1: 13 do grupo I, 28 do grupo II e 11 do grupo III. A idade média ao diagnóstico no grupo III (27 anos) foi significativamente menor que a dos grupos I (39,5 anos; p = 0,03) e II (42,4 anos; p = 0,01). A maioria dos pacientes dos grupos I e II apresentou 2 ou 3 tumores, enquanto que 81,8 por cento dos casos do grupo III apresentavam 1 ou nenhum tumor relacionado à NEM1. Além disto, 45,4 por cento dos casos do grupo III eram assintomáticos, não sendo observados nenhuma metástase ou óbito. Os demais 102 familiares sob-risco estudados não herdaram mutação MEN1 e foram excluídos do rastreamento clínico. Um caso de fenocópia NEM1 foi também localizado. DISCUSSÃO: Nossos dados demonstraram importantes benefícios no seguimento dos pacientes NEM1, obtidos pela implementação dos rastreamentos clínico e gênico para essa doença.

Significado prognóstico dos graus histológicos do linfoma de Hodgkin do tipo esclerose nodular / Prognostic significance of histopathological grading of nodular sclerosing HodgkinÆs lymphoma

INTRODUÇAO: A esclerose nodular (EN), do tipo histológico freqüente do linfoma de Hodgkin (LH), apresenta grande variabilidade em sua composição celular. Na década de 80, pesquisadores do British National Lymphoma Investigation (BNLI) propuseram uma subclassificação histológica do LH EN. Eles identificaram dois graus histológicos - o LH EN grau I (LH EN I) e o LH EN grau II (LH EN II) - e demonstraram que os portadores de LH EN II apresentavam menor sobrevida em comparação aos portadores de LH EN I. Outros estudos, entretanto, não reproduziram esses achados. OBJETIVO: Avaliar o significado prognóstico da graduação histológica proposta pelo BNLI. MATERIAIS E MÉTODOS: Estudo retrospectivo que incluiu 69 casos de LH EN. Mais de 90 por cento dos casos foram tratados com terapia combinada ou quimioterapia exclusiva, não havendo diferença no tipo de tratamento oferecido a depender do grau histológico. RESULTADOS: Trinta e cinco casos (51 por cento) foram classificados com EN I e 34 (49 por cento) como EN II. Não observamos diferenças na distribuição de outros fatores prognósticos entre os portadores dos dois graus. Remissão completa após o tratamento inicial foi obtida em 85,7 por cento dos casos de EN I e em 82,4 por cento dos casos de EN II (p = 0,75). A probabilidade estimada de sobrevida global em cinco anos foi de 67 por cento para EN I e de 83,5 por cento para EN II (p = 0,13) e a taxa de sobrevida livre de doença em cinco anos foi de 85,2 por cento versus 87 por cento, respectivamente (p = 0,72). CONCLUSAO: Nesta população de pacientes uniformemente tratados a graduação histológica BNLI não esteve associada com o prognóstico do LH EN.

Contribuição da imuno-histoquímica para a classificação dos linfomas de pequenas células B / Contribution of immunohistochemistry to small B cell lymphomas classification

Nós avaliamos a utilidade de um painel de anticorpos constituído por CD5, CD10, CD23, CD43, bcl-2 e ciclina D1 na classificação de 134 linfomas de pequenas células B. O CD10, positivo nos linfomas foliculares, o CD23, positivo nos linfomas linfocíticos/LLC, e a ciclina D1, expressa nos linfoma do manto, foram os que mais contribuíram na diferenciação destes linfomas, firmando o diagnóstico em 88,1 por cento dos casos. A ausência de aspecto nodular e de células dendríticas, e a presença de centros de proliferação diferencia o linfoma linfocítico/LLC dos outros tipos / We evaluated the usefulness of a panel of antibodies comprising CD5, CD10, CD23, CD43, bcl-2 and cyclin D1 in the classification of 134 small B-cell lymphomas. CD10, positive in follicular lymphomas, CD23, positive in lymphocytic lymphoma/CLL and cyclin D1 expressed in mantle cell lymphoma were the ones that contributed the most in the differentiation of these lymphomas, confirming the diagnosis in 88.1 per cent of the cases. The absence of nodular aspect and dendritic cells and the presence of proliferation centers differentiate the lymphocytic lymphoma/CLL from the other types...