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INTRODUCTION: Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment. AREAS COVERED: We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA. EXPERT OPINION: NFPA is a heterogeneous group of tumors, in respect to their origin and clinical course. In recent years, research on pathology and molecular biology have advanced our knowledge of NFPA pathogenesis. NFPA exhibit, in the majority of cases, an indolent behavior, with satisfactory response to treatment. In aggressive cases, multimodal management is needed; however, even this approach may be insufficient, so the development of new treatments is warranted for better management. In this setting, the understanding of the mechanisms involved in the genesis and progression of NFPA is crucial for the identification and development of directed treatments with higher chances of response.

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BACKGROUND: To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis. METHODS: We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method. RESULTS: There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival. CONCLUSIONS: The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The WHO histological classification, the Masaoka-Koga system and surgery treatment were associated with overall survival. WHAT THIS STUDY ADDS: To determine prognosis factors in TETs.

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La Clasificación de Tumores del Sistema Nervioso Central de la OMS 2016 incorpora biomarcadores moleculares junto a las características histológicas clásicas, en un diagnóstico integrado, con el fin de definir distintas entidades de gliomas con la mayor precisión posible. Los estudios de perfiles moleculares en el genoma han revelado las alteraciones genéticas características y los perfiles epigenéticos asociados con diferentes tipos de gliomas. Estas características moleculares pueden usarse para refinar la clasificación del glioma, mejorar la predicción de los resultados obtenidos con los tratamientos actuales y futuros en los pacientes, y como guía de un tratamiento personalizado. Asimismo, tener una aproximación pronóstica en cada paciente. Este cambio de paradigma ha modificado la forma en que se diagnostica el glioma y sus implicancias en la práctica diaria en la indicación de los diferentes tratamientos al paciente. Aquí, sintéticamente, revisamos y destacamos los biomarcadores moleculares clínicamente relevantes. Intentamos dejar plasmado cómo los avances en la genética molecular de los gliomas pueden promover y allanar el camino hacia la medicina de precisión en neurooncología.

The Classification of Tumors of the Central Nervous System of the WHO 2016 incorporates molecular biomarkers together with the classical histological characteristics, in an integrated diagnosis, in order to define different glioma entities with the highest possible accuracy. Studies of molecular profiles in the genome have revealed characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine the classification of gliomas, improve the prediction of the results obtained with current and future treatments in patients and as a guide for a personalized treatment. Also, have a prognostic approach in each patient. This paradigm shift has modified the way glioma is diagnosed and its implications in daily practice in the indication of different treatments to the patient. Here, synthetically, we review and highlight clinically relevant molecular biomarkers. We try to capture how advances in the molecular genetics of gliomas can promote and pave the way to precision medicine in neuro-oncology.

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Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.

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BACKGROUND: Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. METHODS: We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only. RESULTS: We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens. CONCLUSION: In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.

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BACKGROUND: Cutaneous non-mycosis fungoides non-Sezary syndrome T/NK cell lymphomas (non-MF/non-SS CTCL) are rare. In 2005, a consensus of the World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC) classifications for primary cutaneous lymphomas was established. These guidelines were then adopted into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008. This study aims to assess the applicability of the WHO 2008 classification in a retrospective series of CTCL cases registered in a reference academic center in Brazil. METHODS: Twenty-seven patients with non-MF/non-SS CTCL were studied. Clinical, histopathological and immunophenotypical features based on an extensive panel of antibodies were applied to classify the cases according to the WHO, 2008. RESULTS: Overall, diagnostic categories included eight (29.6%) cutaneous anaplastic large-cell lymphoma, five (18.5%) lymphomatoid papulosis, six (22.2%) extranodal natural killer (NK)/T-cell lymphoma, nasal type, five (18.5%) adult T-cell leukemia/lymphoma, one (3.7%) cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma and two (7.4%) of peripheral T-cell lymphoma not otherwise specified (NOS). CONCLUSIONS: The WHO classification (2008) was applicable to most cases of non-MF/non-SS CTCL, while some cases remained unclassified and were considered NOS-peripheral T-cell lymphoma. An unexpected high frequency of NK/T-cell lymphoma nasal type was observed.

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As síndromes mielodisplásicas (SMDs) são caracterizadas por uma desordem clonal de células primordiais (stem cell) e hematopoese ineficaz que levam à displasia de uma ou mais linhagens celulares da medula óssea, citopenias periféricas e instabilidade genética, as quais aumentam o risco de transformação à leucemia mieloide aguda. Esse grupo heterogêneo de doenças hematopoéticas pode surgir como doença primária, que possui etiologia variada e não completamente definida, ou secundária ao tratamento quimioterápico ou radioterápico para outras neoplasias. O surgimento e aprimoramento de tecnologias de diagnóstico geraram uma melhor compreensão dos processos envolvidos na gênese e evolução das SMDs, o que possibilitou o desenvolvimento de marcadores de diagnóstico e acompanhamentos cada vez mais precoces e específicos. No ano de 2008, a Organização Mundial da Saúde (OMS) redefiniu os critérios para classificação das SMDs, dividindo-as em sete subgrupos. Nessa classificação foram incluídos novos aspectos imunofenotípicos, genéticos, citomorfológicos e moleculares, o que tornou o domínio e o acesso a tecnologias de ponta imprescindíveis para a realização do diagnóstico das SMDs. Apesar dos avanços tecnológicos, alguns pontos, como as bases moleculares da transformação de SMD para LMA, ainda não estão bem esclarecidos, fazendo necessária a continuação de estudos nessa área. Diante disso, essa revisão busca compilar dados atuais dos aspectos moleculares e laboratoriais das SMDs.

Myelodysplastic syndromes (MDSs) are characterized by a stem cell clonal disorder and ineffective hematopoiesis which causes dysplasia in one or more bone marrow hematopoietic cell lineages, peripheral cytopenia and genetic instability with enhanced risk to transform into acute myeloid leukemia (AML). This heterogeneous group of hematopoietic diseases can develop as primary diseases, which posses a variable and not completely defined etiology, or as secondary to chemotherapy or radiotherapy for other neoplasias. The evolution of diagnostic tests has improved comprehension of the process involved in the genesis and evolution of MDSs, making the development of earlier and more specific tests for diagnosis and follow ups possible. In 2008, the World Health Organization (WHO) redefined the criteria for the classification of MDSs, dividing them into seven subgroups. This classification included new immunophenotypic, genetic, cytomorphologic and molecular features, which are essential for the diagnosis of MDSs and for a better comprehension of the disease. Despite technological advances, some details, such as the molecular basis of the transformation of MDS to AML, are still not completely understood, which makes further studies in this field necessary. Hence, the objective of this review is to make a compilation of recent molecular and laboratory aspects of MDS.

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A análise diagnóstica da medula óssea compreende classicamente a citologia. Mais recentemente, tornou- se rotina o estudo histológico. Desde o início, tentou- se integrar estes dados, pois, enquanto a citologia fornece uma análise mais detalhada das características das células e permite quantificá- las, a biópsia, por analisar o tecido como um todo, permite o estudo da estrutura do tecido hemopoético, seu estroma e a ocorrência de estruturas estranhas à medula, como granulomas, fibrose e metástases de neoplasias. Com o desenvolvimento de novas tecnologias e o melhor conhecimento das diversas entidades, principalmente em onco- hematologia, além do desenvolvimento de terapias alvo- específicas, tornou- se importante o estudo citogenético/molecular em algumas patologias. Nas leucemias agudas e síndromes linfoproliferativas, a imunofenotipagem tem contribuído de modo decisivo para a classificação correta das diversas neoplasias pelos critérios da OMS. Assim, o diagnóstico hematológico se tornou uma atividade multidisciplinar que integra profissionais de diversas especialidades. Assim se consegue tratar os pacientes de modo mais adequado, além de poder rastrear a doença residual após o tratamento. Isto levou a novas definições de remissão: hematológica, fenotípica, citogenética e molecular. O estudo da medula óssea é importante em algumas hemopatias benignas, como anemias carenciais, que podem se manifestar como pancitopenias. Este estudo deve ser complementado com exames sorológicos e bioquímicos. A mielocultura tem permitido o diagnóstico de infecções, especialmente nos indivíduos imunossuprimidos.

The diagnosis of hematologic diseases has traditionally been based on features of peripheral blood and bone marrow (BM) cytology. Histologic examination of the BM has been used for the staging of neoplasias when aspiration is not possible due to fibrosis. Cytology permits a better evaluation of cell morphology and a quantitative analysis of the different BM lineages. Histology shows the BM structure, topology of cells and the microenvironment, besides identifying pathologic structures such as granulomas, fibrosis, and metastases. More recently, several new technologies have been developed, and the pathophysiology of diseases has been better elucidated. The WHO classification of hematologic malignancies describes entities based on morphology, phenotype, and in many cases, cytogenetic and molecular features. This has made targeted therapy feasible. Therefore, there is need to confirm the diagnosis using data from different techniques. Some methods are also useful to quantify residual disease after treatment, and confirm cure. Thus, several kinds of remission have been defined, such as " hematologic" , " phenotypic" , " cytogenetic" and " molecular" remission. In benign diseases, presenting with cytopenias other than anemia, BM examination is useful together with biochemical and serological tests.

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Os tumores odontogênicos compõem um grupo de lesões incomuns, porém interessantes, que se forma a partir dos tecidos que dão origem aos dentes. Esses tumores vêm sendo estudados há décadas por patologistas e cirurgiões que buscam entender seus mecanismos de formação e desenvolvimento, assim como desenvolver técnicas adequadas de tratamento. Inúmeras foram as tentativas realizadas até hoje para classificar esses tumores odontogênicos, sendo a última a nova Classificação de Tumores Odontogênicos da Organização Mundial da Saúde, publicada em 2005. Assim sendo, este trabalho teve por objetivo determinar a prevalência dos tumores odontogênicos diagnosticados nos Serviços de Anatomia Patológica das Faculdades de Odontologia de Bauru (USP) e de Araçatuba (UNESP) no Brasil, e das Faculdades de Odontologia da UNAM, da UAM-X e do Laboratório privado Peribact no México, compará-las e definir um perfil da ocorrência desses tumores nessas instituições e países seguindo essa nova classificação. Todos os casos diagnosticados como tumores e cistos odontogênicos passíveis de reanálise diagnóstica foram selecionados dos arquivos dessas instituições. Os dados demográficos e os aspectos clínicos de cada lesão foram obtidos a partir dos laudos e das fichas de requisição de exame anatomopatológico e as lâminas examinadas por um avaliador. Os resultados demonstraram que a inclusão do queratocisto no grupo de tumores provocou uma alteração significante na prevalência dessas lesões. O tumor odontogênico queratocístico foi a lesão mais prevalente, seguida pelo odontoma, ameloblastoma e mixoma no Brasil e no México. Quanto aos dados demográficos e localização, nossos achados corroboram com aqueles descritos na maior parte dos trabalhos realizados em todo o mundo, com diferenças pontuais em países como a China. Entretanto, a falta de maiores conhecimentos biomoleculares e genéticos dificulta a compreensão dessas diferenças.

Odontogenic tumors constitute a group of uncommon and particularly interesting lesions, arising from the odontogenic tissues. These tumors have been studied for decades by pathologists and surgeons seeking understand the mechanisms of formation and development, and trying to develop appropriate techniques of treatment. Many were the attempts made so far to classify these odontogenic tumors, the most recent being the new classification of odontogenic tumor of the World Health Organization, published in 2005. Therefore, this study aimed to determine the prevalence of odontogenic tumors diagnosed in five centers of diagnostic pathology: Laboratory of Oral Pathology, Faculty of Dentistry of Bauru USP; Laboratory of Oral Pathology, Faculty of Dentistry of Araçatuba UNESP, in Brazil; and Department of Oral Pathology, Faculty of Dentistry UNAM; Laboratory of Oral Pathology, Faculty of Dentistry of UAM-Xochimilco and Peribact Laboratory, a private laboratory of oral pathology, in Mexico; compare them and develop a profile of the occurrence of these tumors in these institutions and countries, following this new classification. All cases diagnosed as odontogenic cysts and tumors were selected for diagnostic review. The demographic and clinical features were obtained from the records when available. The cases were re-evaluated, and the diagnosis in each case was confirmed or modified when necessary. The results showed that the inclusion of keratocyst in the group of tumors caused a significant change in the prevalence of these lesions. The keratocyst odontogenic tumor was the most prevalent lesion, followed by odontoma, ameloblastoma and myxoma in Brazil and Mexico. Our findings corroborate with those reported arround the world, with occasional differences in countries, such as China. However, the lack of molecular and genetic knowledge precludes a better comprehension of these differences.

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