Mandible lymphoma: an aggressive osteolytic lesion

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin's lymphoma. In oral cavity represents approximately 2% of all malignancies. Case presentation: This report describes a rare mandibular involvement of DLBCL. A 56 year-old man was referred for evaluation of left mandible pain. In the anamnesis, the patient informed to be treating tooth pain in lasting 6 months. On oral evaluation, an intense mobility of the left mandibular second molar and a swelling in posterior left mandible were observed. Computed tomography showed a large osteolytic lesion affecting both mandibular body and ramus. An incisional biopsy was performed and according to histopathological and imumnohistochemical features, DLBCL was diagnosed. The treatment consisted of 8 cycles of R-CHOP and adjuvant radiotherapy. He is asymptomatic after 6 years. Conclusion: This case showed a rare bone presentation of DLBCL and such tumor should be considered as differential diagnosis of osteolytic lesion of the mandible.

Bronchial carcinoid tumors: second primary neoplasms and outcomes of surgical treatment / Tumores carcinoides brônquicos: segunda neoplasia primária e desfechos do tratamento cirúrgico

ABSTRACT Objective: To analyze determinants of prognosis in patients with bronchial carcinoid tumors treated surgically and the potential concomitance of such tumors with second primary neoplasms. Methods: This was a retrospective analysis of 51 bronchial carcinoid tumors treated surgically between 2007 and 2016. Disease-free survival (DFS) was calculated by the Kaplan-Meier method, and determinants of prognosis were evaluated. Primary neoplasms that were concomitant with the bronchial carcinoid tumors were identified by reviewing patient charts. Results: The median age was 51.2 years, 58.8% of the patients were female, and 52.9% were asymptomatic. The most common histology was typical carcinoid (in 80.4%). Five-year DFS was 89.8%. Ki-67 expression was determined in 27 patients, and five-year DFS was better among the patients in whom Ki-67 expression was ≤ 5% than among those in whom it was > 5% (100% vs. 47.6%; p = 0.01). Concomitant primary neoplasms were observed in 14 (27.4%) of the 51 cases. Among the concomitant primary neoplasms that were malignant, the most common was lung adenocarcinoma, which was observed in 3 cases. Concomitant primary neoplasms were more common in patients who were asymptomatic and in those with small tumors. Conclusions: Surgical resection is the mainstay treatment of bronchopulmonary carcinoid tumors and confers a good prognosis. Bronchial carcinoid tumors are likely to be accompanied by second primary neoplasms.

RESUMO Objetivo: Analisar os determinantes do prognóstico em pacientes com tumores carcinoides brônquicos tratados cirurgicamente e possível segunda neoplasia primária concomitante. Métodos: Trata-se de uma análise retrospectiva de 51 tumores carcinoides brônquicos tratados cirurgicamente entre 2007 e 2016. A sobrevida livre de doença (SLD) foi calculada pelo método de Kaplan-Meier, e os determinantes do prognóstico foram avaliados. As neoplasias primárias concomitantes aos tumores carcinoides brônquicos foram identificadas por meio da análise dos prontuários dos pacientes. Resultados: A mediana de idade foi de 51,2 anos, 58,8% dos pacientes eram do sexo feminino e 52,9% eram assintomáticos. A classificação histológica mais comum foi carcinoide típico (em 80,4%). A SLD em cinco anos foi de 89,8%. A expressão de Ki-67 foi determinada em 27 pacientes, e a SLD em cinco anos foi melhor nos pacientes nos quais a expressão de Ki-67 foi ≤ 5% do que naqueles nos quais a expressão de Ki-67 foi > 5% (100% vs. 47,6%; p = 0,01). Neoplasias primárias concomitantes foram observadas em 14 (27,4%) dos 51 casos. Entre as neoplasias primárias malignas concomitantes, a mais comum foi o adenocarcinoma pulmonar, observado em 3 casos. Neoplasias primárias concomitantes foram mais comuns em pacientes assintomáticos e naqueles com tumores pequenos. Conclusões: A resseção cirúrgica é o principal tratamento de tumores carcinoides broncopulmonares e propicia um bom prognóstico. É provável que tumores carcinoides brônquicos se relacionem com segunda neoplasia primária.

Comparação entre os perfis de expressão de microRNAs em Linfomas de Hodgkin Clássico / Comparison between microRNA expression profiles in Classic Hodgkin Lymphoma

Introdução: Linfoma de Hodgkin (LH) é um dos linfomas mais frequentes no mundo ocidental, com cerca de 3 a 4 novos casos a cada 100 mil pessoas. Os microRNAs são pequenas moléculas que regulam a transcrição gênica e estão associadas ao desenvolvimento e progressão das neoplasias. Em LH clássico (LHC), alguns microRNAs já foram identificados a partir de células infectadas pelo EBV. Além destes, outros microRNAs já foram descritos em LHC, tanto em estudos onde foram realizadas esta avaliação em culturas celulares como utilizando a massa tumoral total de linfonodos, mas com pouca correlação com o comportamento biológico. Objetivo: O presente estudo tem como objetivo principal avaliar o perfil de expressão de microRNA em LHC, comparando casos livres de doença após a terapia com casos que exibiram recidivas. Material e métodos: Foram avaliados 106 pacientes com o diagnóstico de LHC, sendo coletados dados clínicos e avaliados os marcadores imuno-histoquímicos CD30, CD15, CD20 e CD15 destes casos, além da presença de EBV por CISH. Vinte casos foram selecionados para a avaliação da expressão de 377 microRNAs, 10 casos com recidiva e 10 casos sem evidência de doença. Como grupos comparadores, foram selecionadas 8 amostras de linfonodos reativos, 4 com hiperplasia folicular e 4 com hiperplasia paracortical. Os resultados do perfil de expressão foram submetidos ao método de agrupamento hierárquico não supervisionado. Resultados e discussão: Os parâmetros clínico-patológicos desta coorte não diferiram daqueles encontrados na literatura. A sobrevida global e a sobrevida livre de progressão foram de 92,1% e 83,6% em 5 anos, respectivamente. Os fatores associados ao prognóstico em análise multivariada foram idade, níveis séricos de albumina e DHL e estadiamento. O perfil de expressão dos microRNAs de todos os casos de LHC possibilitaram a separação completa dos mesmos em relação aos linfonodos reativos, independentemente do tipo de hiperplasia. Na comparação entre os casos de LHC, foram identificados 3 microRNAs diferencialmente expressos: miR-502-3p e miR-363, ambos hipoexpressos no grupo que continha todos os casos com recidivas e miR-886-5p, hiperexpresso neste grupo. Os dois primeiros microRNAs estão associados a supressão tumoral, através da inibição da proliferação e migração celular. O miR-886-5p é associado ao aumento da proliferação celular e inibição da apoptose. Em linfomas, este já foi descrito como estando hiperexpresso em linfomas T, incluindo linfoma anaplásico de grandes células. Conclusão: Os LHC possuem um perfil distinto de expressão de microRNAs, com muitos deles envolvendo mecanismos fundamentais na oncogênese, como ciclo celular e apoptose. Os microRNAs encontrados diferencialmente expressos nos casos recidivados no presente estudo podem estar associados ao comportamento menos indolente destas neoplasias, podendo ser alvo de futuras investigações, incluindo seu uso como potenciais alvos de terapia

Introduction: Hodgkin lymphoma (HL) is one of the most common lymphomas in the western world, with about 3 to 4 new cases per 100,000 people. MicroRNAs are small molecules that regulate gene transcription and are associated with the development and progression of neoplasms. In classic HL (CHL), some microRNAs have already been identified from EBV-infected cells. In addition, other microRNAs have already been described in CHL, both in studies where this evaluation was performed in cell cultures and using whole lymph node tumor tissue, but with little correlation with biological behavior. Objective: The present study aims to evaluate the microRNA expression profile in CHL, comparing disease-free cases after therapy with cases that showed recurrences. A total of 106 patients diagnosed with CHL were evaluated. Clinical data were collected and the immunohistochemical markers CD30, CD15, CD20 and CD15 of these cases were evaluated, as well as the presence of EBV by CISH. Twenty cases were selected for the analysis of the expression of 377 microRNAs, 10 cases with recurrences and 10 cases without evidence of disease. For comparison, 8 samples of reactive lymph nodes were selected, 4 with follicular hyperplasia and 4 with paracortical hyperplasia. The expression profile results were submitted to the unsupervised hierarchical clustering method. Results and discussion: The clinico-pathological parameters of this cohort did not differ from those found in the literature. Overall survival and progression-free survival were 92.1% and 83.6% at 5 years, respectively. Factors associated with prognosis in multivariate analysis were age, serum albumin and DHL levels, and staging. The microRNA expression profile of all CHL cases allowed their complete separation from reactive lymph nodes, regardless of the type of hyperplasia. When comparing the cases of CHL, 3 differentially expressed microRNAs were identified: miR-502-3p and miR-363, both hypoexpressed in the group containing all relapsed cases and miR-886-5p, hyperexpressed in this group. The first two microRNAs are associated with tumor suppression through inhibition of cell proliferation and migration. The miR-886-5p is associated with increased cell proliferation and inhibition of apoptosis. In lymphomas, it has been described as being overexpressed in T-cell lymphomas, including anaplastic large cell lymphoma. Conclusion: CHLs have a distinct microRNA expression profile, with many involving key mechanisms in oncogenesis, such as cell cycle and apoptosis. The differentially expressed microRNAs found in the relapsed cases in the present study may be associated with the less indolent behavior of these neoplasms and may be the subject of future investigations, including their use as potential therapeutic targets

Characteristics of follicular and mantle cell lymphoma in Brazil: prognostic impact of clinical parameters and treatment conditions in two hospitals

ABSTRACT Objective: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. Methods: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. Results: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. Conclusion: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.

Primary angiosarcoma of the femur in a patient with Takayasu arteritis / Angiossarcoma primário do fêmur em um paciente com arterite de Takayasu

ABSTRACT Primary osseous angiosarcoma is a rare entity with variable biological behavior and poor prognosis. Little is known about the oncologic treatment and its etiology is still unknown. This study presents a case of lytic lesion in the right femur with dissemination to other bones, such as the vertebral column and skull, and to the lungs and central nervous system. Orthopedic surgery was performed in order to improve quality of life. Surgical specimen confirmed the diagnosis of high-grade malignant osseous angiosarcoma. Despite oncologic and orthopedic treatment, the patient had rapid and aggressive progression with a poor outcome.

RESUMO O angiossarcoma ósseo (AO) é uma patologia rara de comportamento biológico variável e com prognóstico reservado. Pouco se conhece sobre o seu tratamento oncológico e sua etiologia ainda é desconhecida. Os autores apresentam um caso de lesão lítica em fêmur proximal que se disseminou para outros ossos (tais como coluna e crânio), pulmão e sistema nervoso central. Foi instituído tratamento ortopédico, com vistas a uma melhoria da qualidade de vida e ao conforto do paciente. O diagnóstico de AO maligno de alto grau foi confirmado pelo espécime cirúrgico. Apesar disso e do tratamento oncológico feito, o paciente apresentou uma evolução rápida e agressiva com desfecho desfavorável.

Lipoma arborescens of the elbow: a case with features of a high-grade tumor / Lipoma arborescens do cotovelo: um caso com características de tumor de alto grau

ABSTRACT Lipoma arborescens (LA) is an uncommon non-neoplastic disorder that may affect almost any joint, mainly the knee. LA is very rare in the elbow, and there are only a few cases reported in the literature. This study aimed to describe a case of LA in the elbow, presenting with features of a high-grade tumor. The authors report the case of a 51-years-old male who presented to this institution with pain and swelling on the left elbow. The patient had a seven-year history of investigation, with inconclusive diagnosis. Magnetic resonance imaging (MRI) showed an expansive mass with local aggressiveness. Due to these characteristics, it was not possible to discard soft tissue sarcoma at the differential diagnosis. After biopsy and a multidisciplinary team meeting, the authors opted for surgical resection. The final anatomopathological result confirmed the diagnosis of LA. Despite not being a true neoplasm, LA can cause many symptoms and functional impairment of the affected joint. It is important to keep this diagnosis in mind when any expansive mass surrounding a joint is observed.

RESUMO O lipoma arborescens (LA) é uma doença não neoplásica incomum que pode afetar quase todas as articulações, principalmente o joelho. O LA é muito raro no cotovelo e há apenas alguns casos relatados na literatura. O objetivo deste estudo é descrever um caso de LA no cotovelo que apresentava características de tumor de alto grau. Os autores relatam o caso de um homem de 51 anos que se apresentou à instituição com dor e inchaço no cotovelo esquerdo. O paciente tinha sete anos de história de investigação com diagnóstico inconclusivo. As características da ressonância magnética (RM) mostraram uma massa expansiva com agressividade local. Devido a essas características, não foi possível descartar sarcoma de tecido mole no diagnóstico diferencial. Após a biópsia e uma reunião de equipe multidisciplinar, optou-se pela ressecção cirúrgica. O resultado anatomopatológico final confirmou o diagnóstico de LA. Mesmo que não seja uma neoplasia verdadeira, o LA pode causar muitos sintomas com comprometimento funcional da articulação afetada. É importante ter em mente esse diagnóstico quando qualquer massa expansiva em torno de uma articulação for observada.

Mandible metastasis of small cell lung cancer mimicking a residual cyst

Small cell lung carcinoma (SCLC) is an uncommon tumor characterized by an aggressive behavior with early metastasis, usually to the contralateral lung, liver, brain, and bones. There are only five cases of this particular tumor metastasizing to the oral cavity described in the English literature. We present the case of metastatic SCLC in the mandible with radiographic findings resembling a residual cyst. A 66-year-old man with previous diagnosis and treatment for a SCLC was referred to the Stomatology Department with a history of persistent pain in the mandible 1 year after the inferior right pre-molar tooth extraction. The radiographic exam showed a well-delimited radiolucent area on that extracted tooth's region resembling a residual cyst. Biopsy was performed yielding the diagnosis of metastatic SCLC. The patient was referred to the clinical oncologist for chemotherapy. Although uncommon, this tumor should be included in the differential diagnosis of jawbone lesions, particularly when the patient presents a previous diagnosis of SCLC.

Inflammatory pseudotumor-like follicular dendritic cell tumor: an underdiagnosed neoplasia

Follicular dendritic cell (FDC) tumor is an uncommon neoplasm. It generally presents as a slow-growing, painless mass, without systemic symptoms. Histological features usually include low grade spindle cell proliferation. This tumor occurs primarily in lymph nodes, especially cervical and axillary, however, involvement of extranodal sites such as the tonsils, spleen, liver, and gastrointestinal tract has been reported. Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) is a rare, distinctive histological subtype of this low-grade malignant neoplasm, with consistent Epstein-Barr virus (EBV) association. The differential diagnosis with other fibro-inflammatory tumor proliferations, as inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT), may be challenging. In the present article, two cases of IPT-like FDCT of the spleen are presented, with a broad overview of the literature: one 77-year-old male and one 70-year-old female. A large immunohistochemical panel should be used for diagnosis, as no single specific and totally sensitive markers are available, including markers for CD21, CD23, CD35, CNA42, and clusterin. Individual cases may express one or more of these markers, so that all of them should be investigated. In situ hybridization for EBV is constantly positive. Immunostaining for ALK should be negative, as it is present in roughly half of the cases of IMT. This panel should be used in combination of clinical, laboratory, and topographic evidences. Importantly, inclusion of this lesion as a possible option in clinical and pathological investigation represents the basis for a correct diagnosis (AU)

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed. Methods: We evaluated the gene expression profile of AT/RT samples to find new genetic factors contributing to the pathophysiology of the disease. We found target genes significantly differentially expressed between AT/RT and medulloblastoma (MB), the most common embryonal brain tumor. The mRNA expression was validated by quantitative real-time PCR and, at the protein level, expression was validated by immunohistochemistry in an independent set of tumors. Results: The Neural cell adhesion molecule 1 (NCAM1) gene was found to be consistently downregulated in AT/RT samples when compared to MB and normal brain tissue. Immunohistochemistry showed that the expression of NCAM1 in AT/RT was significantly lower than that of MB. Conclusion: NCAM1 is an important molecule involved in neuron-to-neuron and neuron-to-muscle adhesion during development. Downregulation of NCAM1 has been implicated in several human cancers suggesting that it might have a tumor repressor role. In this study we found a significantly reduced expression of NCAM1 in AT/RT when compared to MB and we suggest that this feature can be used as a diagnostic marker, along with demonstration of SMARCB1 (INI1) or SMARCA4 (BRG1) inactivation. The roles of NCAM1 in the pathophysiology of AT/RT are still to be determined (AU)

Attenuation of copaiba oil in hepatic damage in rats

PURPOSE: To investigate the copaiba oil on the hepatic damage induced by acetaminophen, comparing against corn oil. METHODS: Fifty four rats were distributed into nine study groups (N=6): control group, that didn't receive the acetaminophen; Acetaminophen Group, that only received the acetaminophen; Prophylactic Copaiba Group 1, that received copaiba oil two hours before the acetaminophen; Prophylactic Copaiba Group 7, that received copaiba oil seven days, once by day, before the acetaminophen; Therapy Copaiba Group, that received the copaiba oil two hours after the acetaminophen, the corn's groups were similar than copaiba oil groups; and N-Acetyl-Cysteine Group, that received the N-Acetyl-Cysteine two hours after the acetaminophen. Euthanasia was performed after 24 hours. The serum levels transaminases, bilirubin and canalicular enzymes were analyzed. RESULTS: The prophylactic copaiba group 7, therapy copaiba group and N-Acetyl-Cysteine Group showed amounts of AST and ALT similar to the control group; and the prophylactic copaiba group 1 and corn's groups showed similar levels to the acetaminophen group. There was no significant difference between the groups regarding the amount of alkaline phosphatase and ɤ GT (p>0.05). The therapy copaiba group showed the highest levels of total bilirubin and was statistically different from the other groups (p<0.01). CONCLUSIONS: Copaiba oil administered prophylactically for seven days and therapeutically 2 hours after the acetaminophen acute intoxication offered a potential hepato protection against paracetamol-induced hepatic damage, normalizing the biochemical parameters similarly to N-Acetyl-Cysteine, and the treatment with corn oil shows no effect on the liver damage. .

Amelanotic corneally displaced malignant conjunctival melanoma: a case report evaluated with impression cytology / Melanoma amelanótico conjuntival maligno deslocado sobre a córnea com citologia de impressão: relato de caso

Here we describe the case of a 65-year-old Caucasian female who presented with an amelanotic malignant conjunctival melanoma and highlight the clinical and pathological features of this rare entity that displayed exclusive corneal invasive growth without evidence of conjunctival tumors other than primary acquired melanosis. Impression cytology aided in the initial diagnosis. The patient underwent surgical treatment. Histopathology and immunohistochemistry revealed an invasive amelanotic melanoma limited to the cornea and exhibiting S-100, Melan A, and HMB-45 positivity. The absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is important for early recognition and appropriate management.

Os autores descrevem o caso de uma mulher branca de 65 anos que apresentava um melanoma amelanótico maligno conjuntival e destacam as características clínicas e patológicas desta entidade rara com crescimento invasivo exclusivo na córnea sem evidência de tumores na conjuntiva além de melanose adquirida primária sem pigmento. A citologia de impressão auxiliou no diagnóstico inicial. A paciente foi submetida a tratamento cirúrgico. A histopatologia e a imuno-histoquímica revelaram um melanoma amelanótico invasivo limitado sobre a córnea exibindo positividade para proteína S-100, Melan A e HMB-45. A ausência de pigmentação retardou sua identificação clínica e seu tratamento precoce. O conhecimento deste melanoma não pigmentado é importante para o reconhecimento precoce e a conduta apropriada.

Efeito do óleo de copaíba nas aminotransferases de ratos submetidos à isquemia e reperfusão hepática com e sem pré-condicionamento isquêmico / Copaiba oil effect in rats aminotrasnferases submitted to hepatic ischemic and reperfusion with and without preconditioning

OBJETIVO: Estudar o efeito do óleo de copaíba nas aminotransferases de ratos submetidos à isquemia e reperfusão (IR) hepática, com e sem pré-condicionamento isquêmico (PCI). MÉTODOS: Foram utilizados 24 Rattus norvegicus albinus machos distribuídos em: Grupo padrão (GP), Grupo copaíba (GC), Grupo isquemia-reperfusão (GIR), Grupo isquemia-reperfusão + copaíba (GIRC), Grupo pré-condicionamento isquêmico (GPCI) e Grupo pré-condicionamento isquêmico + copaíba (GPCIC). Foi administrado 0,63ml/kg/dia de copaíba, durante sete dias, por meio de gavagem nos animais do GC, GIRC e GPCIC. A isquemia hepática foi de 30 minutos e, nos animais submetidos ao PCI, realizou-se isquemia de 10 minutos, seguida de reperfusão de 5 minutos e isquemia de 30 minutos com posterior reperfusão. Os animais foram anestesiados via inalatória com éter etílico. O período de reperfusão foi de 24 horas. No 1º DPO foi realizada coleta de sangue venoso e dosagem das aminotransferases. RESULTADOS: Os níveis de AST não se alteraram nos animais submetidos à administração do óleo de copaíba. O óleo estudado não alterou os valores de ALT no GIRC quando comparado com o GIR, entretanto, houve aumento do nível sérico dessa enzima no GPCIC em comparação com o GPCI. CONCLUSAO: O óleo de copaíba não alterou os níveis de AST nos grupos estudados. Ao se avaliar a ALT, esse óleo não influenciou os valores séricos nos animais submetidos somente à IR hepática, entretanto houve aumento dos níveis dessa enzima no GPCIC em relação ao seu controle. Os valores de ALT não foram diferentes estatisticamente entre os grupos IRC e PCIC.