Refractory celiac disease type 2: how to diagnose and treat?

Refractory celiac disease is an uncommon condition which might be associated to poor prognosis. It is often treated with immunosuppressive medications, with poor results. It is divided in type 1 and type 2, the latter carrying a high risk for lymphoma and mortality. A case of a 41 year old female patient with refractory celiac disease type 2 is reported. She was treated with oral budesonide for six months, achieving histological remission.

Multifocal Pseudotumorous Form of Neuroparacoccidioidomycosis in an Immunocompetent Patient: A Clinicopathological Review Based on a Case Report

Neuroparacoccidiodimycosis (NPDM) is an uncommon granulomatous disease, which more frequently affects immunocompromised male patients over 30 years of age in the course of chronic lung disease. Paracoccidioides brasiliensis (PB) is an endemic fungus in Brazil, and grows as thick-walled yeast (with round to oval bodies) measuring 10 µm to 60 µm in diameter. Neuroparacoccidiodimycosi may develop many years after transmission and/or primary lung involvement. The authors describe a case of NPDM affecting a male patient, 52 years of age, farmer, heavy smoker, with clinical complaint of headache, asthenia, seizures, and prostration in the previous nine months. Upon physical examination, the patient presented regular general condition, without other relevant physical alterations. Computed tomography (CT) showed multiple bilateral pulmonary nodules associated to enlargement of the mediastinal lymph node. Magnetic resonance imaging (MRI) and CTscans of the central nervous system showed six heterogeneous nodular lesions compromising the frontal and parietal lobes, the largest one measuring 3.8 3.2 3.2 cm. The hypothesis of a neoplastic process compromising the lung and brain was considered. A biopsy of the mediastinal lymph node showed epithelioid granulomas, which exhibited round, thin-walled fungal structures in Grocott silver stain. The stereotactic biopsy of the frontal lesion was constituted by necrotic tissue admixed with some round to oval, thin-walled fungi measuring 10 µm to 60 µm, compatible with PB (identified on Grocott silver stain/confirmed in culture). The diagnosis of NPDM was then established. The employed therapeutic regimen was intravenous amphotericin B, itraconazole, and sulfamethoxazole-trimetropin. After ninety days of clinical follow-up, no episodes of seizures/neurological deficits were identified, and a marked decrease in the number and size of the lung and brain lesions were found.

Refractory celiac disease type 2: how to diagnose and treat?

SUMMARY Refractory celiac disease is an uncommon condition which might be associated to poor prognosis. It is often treated with immunosuppressive medications, with poor results. It is divided in type 1 and type 2, the latter carrying a high risk for lymphoma and mortality. A case of a 41 year old female patient with refractory celiac disease type 2 is reported. She was treated with oral budesonide for six months, achieving histological remission.

Intra-Axial Metastatic Angiosarcoma of the Central Nervous System Associated with Anemia, Pulmonary Tuberculosis and Short Survival

Introduction Angiosarcoma (AG) is a malignant mesenchymal neoplasm that predominantly affects the soft tissues and, to variable degrees, expresses themorphological and functional characteristics of the endothelium. The incidence of sarcomas of the central nervous system(CNS) is low (0.5% to 2.7%), and AGs involving the brain are even rarer. Case Description A 45-year-old male patient presented with complaints of headache, nausea, and vomiting. An examination showed bilateral papilledema and a right lung pleurotomy. The patient's previous history included drug addiction, pulmonary tuberculosis, lung abscess, pleural empyema, and pulmonary artery embolization for severe hemoptysis. Computed tomography/magnetic resonance imaging scans revealed a large intra-axial lesion extending into the right parietal and temporal lobes, with hemorrhagic zones. The patient underwent surgical resection of the lesion. Microscopy showed a poorly-differentiated, high-grade malignant tumor composed of plump/epithelioid cells forming small vascular spaces and solid nests, compatible with AG.In the postoperative period, the patient developed recurrent hemoptysis. A biopsy of the tissues adjacent to the pleurotomy determined the diagnosis of pulmonary AG. At 30 days after the resection, the patient died from hemoptysis, hemothorax, lung atelectasis, and intracranial hypertension related to the recurrence of the brain tumor. Conclusion Angiosarcoma is a rare neoplasia related to short survival due to the high proliferative index, which must be considered in patients presenting hemorrhagic tumors. No specific genetic abnormalities have been described for this neoplasia.

BK Polyomavirus-associated nephropathy managed by screening policy in a real-life setting.

BACKGROUND: BK polyomavirus-associated nephropathy (PyVAN) is an important complication after kidney transplantation. Prevalence ranges from 1% to 10%, and graft loss occurs in approximately 50% of the cases. There is no effective treatment, so early viral detection with immunosuppression tapering is the current strategy to prevent PyVAN. AIMS: To verify the frequency of PyVAN in a single center and evaluate the response to immunosuppressive adjustments through graft survival analysis. METHODS: Retrospective evaluation of a cohort of kidney transplant recipients with biopsy-proven PyVAN, compared with no-PyVAN patients regarding clinical aspects, immunosuppression, and graft survival over at least 2 years. RESULTS: There were 1404 kidney transplants analyzed in the study period, 58 with biopsy-proven PyVAN. Cumulative incidence was 4.1%. Median time from transplantation to PyVAN diagnosis was 6 (1-41) months. PyVAN was associated with recipient male gender (P = .041) and deceased donation (P = .005). Graft survival was inferior for PyVAN compared to no-PyVAN patients, 81.8% vs 75.2%, P = .019. Thirteen (22.4%) PyVAN patients lost their grafts, nine (15.5%) losses attributed to BKPyV infection. Three patients with BKPyV-associated graft losses were submitted to a successful second kidney transplant, with no evidence of viral replication during follow-up. CONCLUSION: PyVAN still is an important cause of kidney graft failure. Even though implementing active vigilance and immunosuppressive adjustment, this real-life single-center study demonstrated inferior graft survival in PyVAN patients compared to non-PyVAN.

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review / Patogênese, achados histopatológicos e modalidades de tratamento da glomerulopatia por lipoproteínas: Uma revisão

Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review.

Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

Cancer: but what if it were a disease caused by an association between microorganisms? / Câncer: e se for uma doença causada por uma associação entre microrganismos?

ABSTRACT Despite the advances in knowledge of the neoplasm behavior, the exact understanding of the biological processes that involve the malignant tumors is not yet fully elucidated. Mechanisms such as subversion of phagocytosis, cytokines and chemokines expression, blocking of immunity and apoptosis regulation are recognized ways of tumor survival. Several of these mechanisms are also used as survival strategies of microorganisms. This article makes an analogy and compares the biological behavior of bacteria, viruses and neoplasms, showing several common points in their mechanisms of growth and survival, questioning cancer as a distinct living organism and introducing the hypothesis of synergy between viruses and bacteria in the development of neoplasms. Up to now, there are no experimental studies that effectively investigate the association between more than one microorganism as an etiologic factor of cancer.

RESUMO Apesar dos avanços no conhecimento do comportamento das neoplasias, o entendimento exato dos processos biológicos que envolvem os tumores malignos ainda não está totalmente elucidado. Mecanismos como subversão da fagocitose, expressão de citoquinas e quimiocinas, bloqueio da imunidade e regulação da apoptose são vias conhecidas de sobrevivência dos cânceres. Vários desses mecanismos também são utilizados como estratégias de sobrevivência de microrganismos. Este artigo faz uma analogia e compara o comportamento biológico das bactérias, dos vírus e das neoplasias, mostrando vários pontos em comum nos seus mecanismos de crescimento e sobrevivência, questionando o câncer como um organismo vivo distinto e introduzindo a hipótese de sinergia entre vírus e bactérias no desenvolvimento das neoplasias. Não há, até o momento, estudos experimentais que investiguem efetivamente a associação entre mais de um microrganismo como fator etiológico do câncer.

A brief contextualization on IgG4 tubulointerstitial nephritis based on a case report in south Brazil. / Uma breve contextualização sobre a nefrite tubulo-intersticial por IgG4 com base em um relato de caso no sul do Brasil.

IgG4-related disease (IgG4RD) is a recent inflammatory process of supposed autoimmune etiology, which is characterized by elevated serum IgG4 levels, dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and storiform fibrosis. Tubulointerstitial nephritis is the most common renal manifestation, with different degrees of kidney dysfunction and variable clinical findings. Herein, the authors describe a new case of IgG4 tubulointerstitial nephritis (IgG4TN), and discuss clinic and pathologic criteria. Male patient, 72 years-old, was admitted on hospital service with clinical complaint of asthenia, loss of strength, emaciation, and anosmia. Previous history included type 2 diabetes mellitus. Laboratorial data included normochromic anemia, proteinuria, and creatinine elevation. Bilateral kidney ultrassonography/computed tomography revealed a heterogenous parenchyma, with diffuse irregular dense zones, areas of fibrosis on upper poles, and hydronephrosys. Kidney biopsy showed a dense interstitial lymphoplasmacytic infiltrate, with more than 50 plasma cell per high power field, irregular areas of fibroblastic and collagenous fibrosis, focal tubulitis, and normal glomeruli. Immunofluorescence revealed mild granular deposition of C3c and IgG in the tubular basement membrane. Immunohistochemestry was positive for CD138, lambda and Kappa light chains, and IgG4 (around forty five IgG4 positive plasma cells per high power field). IgG4 serum level was increased. The diagnosis of IgG4TN was then established. The patient received corticotherapy and strict control of glycemia with insulin, with marked improvement of symptoms and creatinine levels.

Uma breve contextualização sobre a nefrite tubulo-intersticial por IgG4 com base em um relato de caso no sul do Brasil / A brief contextualization on IgG4 tubulointerstitial nephritis based on a case report in south Brazil

Resumo A Doença relacionada a IgG4 (IgG4RD) é um processo inflamatório recente de etiologia supostamente autoimune, que se caracteriza por níveis séricos elevados de IgG4, um denso infiltrado mononuclear rico em plasmócitos IgG4 positivos e fibrose estoriforme. A nefrite túbulo-intersticial é a manifestação renal mais comum, com diferentes graus de disfunção renal e achados clínicos variáveis. Aqui, os autores descrevem um novo caso de nefrite túbulo-intersticial associada a IgG4 (NTIgG4), e discutem critérios clínicos e patológicos. Paciente masculino, 72 anos, foi admitido no serviço hospitalar com queixa clínica de astenia, perda de força, emagrecimento e anosmia. A história prévia incluía Diabetes mellitus tipo 2. Os dados laboratoriais incluíam anemia normocrômica, proteinúria e elevação da creatinina. A ultrassonografia/tomografia computadorizada renal bilateral revelou um parênquima heterogêneo, com zonas densas e difusas irregulares, áreas de fibrose nos polos superiores e hidronefrose. A biópsia renal mostrou um infiltrado mononuclear intersticial denso, com mais de 50 plasmócitos por campo de grande aumento, áreas irregulares de fibrose fibroblástica e colagênica, tubulite focal e glomérulos normais. A imunofluorescência revelou deposição granular leve de IgG e C3c na membrana basal tubular. A imuno-histoquímica foi positiva para CD138, cadeias leves Kappa e lambda, e IgG4 (cerca de quarenta e cinco plasmócitos IgG4 positivos por campo de grande aumento). O nível sérico de IgG4 estava aumentado. O diagnóstico de NTIgG4 foi então estabelecido. O paciente recebeu corticoterapia e controle rigoroso da glicemia com insulina, com melhoria significativa dos sintomas e dos níveis de creatinina.

Abstract IgG4-related disease (IgG4RD) is a recent inflammatory process of supposed autoimmune etiology, which is characterized by elevated serum IgG4 levels, dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and storiform fibrosis. Tubulointerstitial nephritis is the most common renal manifestation, with different degrees of kidney dysfunction and variable clinical findings. Herein, the authors describe a new case of IgG4 tubulointerstitial nephritis (IgG4TN), and discuss clinic and pathologic criteria. Male patient, 72 years-old, was admitted on hospital service with clinical complaint of asthenia, loss of strength, emaciation, and anosmia. Previous history included type 2 diabetes mellitus. Laboratorial data included normochromic anemia, proteinuria, and creatinine elevation. Bilateral kidney ultrassonography/computed tomography revealed a heterogenous parenchyma, with diffuse irregular dense zones, areas of fibrosis on upper poles, and hydronephrosys. Kidney biopsy showed a dense interstitial lymphoplasmacytic infiltrate, with more than 50 plasma cell per high power field, irregular areas of fibroblastic and collagenous fibrosis, focal tubulitis, and normal glomeruli. Immunofluorescence revealed mild granular deposition of C3c and IgG in the tubular basement membrane. Immunohistochemestry was positive for CD138, lambda and Kappa light chains, and IgG4 (around forty five IgG4 positive plasma cells per high power field). IgG4 serum level was increased. The diagnosis of IgG4TN was then established. The patient received corticotherapy and strict control of glycemia with insulin, with marked improvement of symptoms and creatinine levels.

Aggressive papillary tumor of endolymphatic sac: case report of a rare neoplasia / Tumor papilar agressivo do saco endolinfático: relato de caso de uma rara neoplasia

ABSTRACT Aggressive papillary endolymphatic sac tumor (ELST) is a rare neoplasm, occasionally related to von Hippel-Lindau disease, characterized by locally aggressive growth with temporal bone destruction. The authors report a case of ELST in a female patient exhibiting fifth through eighth cranial nerve paralysis. Computed tomography (CT) revealed a large lytic process involving the right temporal bone. The patient underwent surgical resection. At microscopy, a neoplastic process was identified exhibiting monomorphic columnar cells with mild atypias, arranged in a papillary pattern. The lesion exhibited positivity for A31/AE3, epithelial membrane antigen (EMA), and vimentin; and negativity for synaptophysin, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), thyroglobulin, transthyretin, chromogranin, thyroid transcription factor 1 (TTF-1), trans-acting T-cell specific transcription factor GATA-3, and intestinal transcription factor CDX-2. The diagnosis of ELST was then established. Six years after surgical resection, lesion recurrence was observed.

RESUMO O tumor papilar agressivo do saco endolinfático (TPASE) é uma neoplasia rara, ocasionalmente relacionada com a doença de von Hippel-Lindau, que se caracteriza pelo crescimento agressivo local com destruição do osso temporal. Os autores relatam um caso de TPASE em paciente do sexo feminino, exibindo paralisia do quinto ao oitavo par craniano. A tomografia computadorizada (TC) revelou grande processo lítico comprometendo o osso temporal direito. A paciente foi submetida a ressecção cirúrgica. À microscopia, identificou-se processo neoplásico que exibiu células cilíndricas monomórficas com atipias leves, dispostas em padrão papilar. A lesão apresentou positividade para AE1/ AE3, antígeno da membrana epitelial (EMA) e vimentina; e negatividade para sinaptofisina, proteína ácida fibrilar glial (GFAP), enolase específica do neurônio (NSE), tireoglobulina, transtirretina, cromogranina, fator de transcrição da tireoide 1 (TTF-1), fator de transcrição de ação trans específico de células GATA-3 e fator de transcrição intestinal CDX-2. O diagnóstico de TPASE foi então estabelecido. Após seis anos da ressecção cirúrgica, foi identificada recorrência da lesão.

Associação entre o tamanho tumoral e Achados clínicos e imuno-histoquímicos no adenoma funcionante de hipófise / Association between tumor size and clinical and immunohistochemical findings in functioning hypophyseal adenomas

Introdução: Os adenomas de hipófi se (AH) correspondem a cerca de 10% a 15% dos tumores intracranianos. Em geral, são lesões com padrão de crescimento expansivo, não encapsuladas, as quais determinam alterações clínicas como distúrbios hormonais, cefaleia e desordens do campo visual. Os AH podem ser classificados radiologicamente como microadenomas, quando medem até 10,0 mm, ou macroadenomas quando excedem esta dimensão. Objetivo: Estimar a associação entre tamanho tumoral com queixa clínica principal, perfi l imuno-histoquímico e recidiva em casos de AH. Método: O presente estudo retrospectivo e analítico avaliou 66 casos de AH, sendo determinadas as seguintes variáveis: sexo, idade, tamanho tumoral, queixa clínica principal, expressão imuno-histoquímica dos anticorpos Prolactina, GH, FSH, LH, ACTH e TSH, e recidiva da neoplasia. Resultados: A média de idade foi igual a 51,8 ± 14,6 anos, com predomínio de mulheres (n=41/62,1%) e de macrodenomas (n=41/62,1%). Cefaleia foi o sintoma mais frequente (n=25/37.9%). A análise imuno-histoquímica foi realizada em 37 casos da amostra, sendo os adenomas com expressão de LH os mais comuns (n=14/37,8%). Nove pacientes (13,6%) apresentaram recidiva da lesão, sendo 5 casos de macroadenoma. O tamanho tumoral esteve associado com a presença de alterações visuais (p=0,019), não sendo encontrada associação desta variável com idade (p=0,620), sexo (p=0,987), expressão imuno-histoquímica dos anticorpos (p=0,198) e recidiva (p=0,721). Conclusão: Os AH representam um grupo de neoplasias relativamente heterogêneas quando avaliados diferentes aspectos anatomopatológicos, clínicos e radiológicos. A classifi cação do tamanho tumoral em microadenoma ou macroadenoma não é fator preditivo do perfi l imuno-histoquímico ou taxa de recidiva.

Background: Hypophyseal adenomas (HA) account for about 10% to 15% of intracranial tumors. They are generally non-encapsulated lesions with an expansive growth pattern, which determine clinical changes such as hormonal disorders, headache and disorders of the visual fi eld. HA can be classifi ed radiographically as microadenomas when measuring up to 10.0 mm, or macroadenomas when they exceed this size. Aim: To estimate the association between tumor size and main clinical complaints, immunohistochemical profi le and relapse in cases of HA. Methods: This retrospective and analytical study evaluated 66 cases of HA, taking the following variables: gender, age, tumor size, main clinical complaint, immunohistochemical expression of prolactin antibodies, GH, FSH, LH, ACTH and TSH, and relapsing neoplasm. Results: Mean age was 51.8 ± 14.6 years, with a predominance of women (n = 41/62.1%) and macrodenomas (n = 41/62.1%). Headache was the most common symptom (n = 25/37.9%). Immunohistochemical analysis was performed on 37 cases of the sample, with LH-expressing tumors being the most common (n = 14/37.8%). Nine patients (13.6%) had recurrence of the injury, 5 cases of macroadenoma. Tumor size was associated with presence of visual disturbances (p = 0.019), but there was no association between this variable and age (p = 0.620), sex (p = 0.987), immunohistochemical expression of antibodies (p = 0.198) and recurrence ( p = 0.721). Conclusion: HA represent a relatively heterogeneous group of neoplasms when different pathological, clinical and radiological aspects are evaluated. The classifi cation of tumor size as microadenoma or macroadenoma is not predictive of the immunohistochemical profi le or relapse rate.

A relação entre a profundidade de invasão e a presença de metástases cervicais no carcinoma epidermoide de cabeça e pescoço / Relationship between depth of invasion and presence of cervical metastases in squamous cell carcinoma of head and neck

Introdução: O carcinoma epidermoide (CEC) representa cerca de 95% dos casos de câncer de cabeça e pescoço, e atualmente corresponde à sexta neoplasia maligna mais prevalente no Brasil. O processo acomete preferentemente homens, e, muitas vezes, o diagnóstico é estabelecido em estágios avançados de doença. Determinadas características anatomopatológicas do tumor, como tamanho e presença de metástases, podem ser correlacionadas com o tempo de sobrevida livre de doença. Objetivo: Estimar a relação entre o grau de diferenciação e a profundidade de invasão com a presença de metástases em linfonodos cervicais em casos de CEC de cabeça e pescoço. Método: Foram avaliados 47 casos distintos de CEC acometendo lábio, língua, palato ou laringe, previamente submetidos à ressecção cirúrgica, sendo determinadas as seguintes variáveis: sexo, idade, tamanho tumoral, grau de diferenciação, profundidade de invasão e presença de metástases em linfonodos cervicais. Resultados: A média de idade correspondeu a 61,9 ± 10,6 anos e o tamanho tumoral médio foi igual a 3,03 ± 1,70 cm. O processo foi mais frequente em 37 homens (78,7%), sendo que 09 destes pacientes apresentaram metástases nodais (24,32%). A presença de metástases esteve associada à profundidade de invasão (p=0,026), não sendo encontrada relação com idade (p=0,591), sexo (p=0,137), topografi a (p=0,394), tamanho tumoral (p=0,612) e grau de diferenciação (p=0,452). Conclusão: O CEC de cabeça e pescoço predomina em homens, e a determinação histopatológica precisa da profundidade de invasão tumoral constitui fator preditivo da presença de metástases nodais.

Background: Squamous cell carcinoma (SCC) accounts for about 95% of cases of head and neck cancer, and currently represents the sixth most prevalent malignancy in Brazil. The process preferably occurs in men, and often the diagnosis is established in advanced stages of disease. Certain pathological tumor characteristics, such as size and presence of metastases, can be correlated with the survival time free of disease. Aim: To estimate the relationship between the degree of differentiation and depth of invasion and the presence of metastasis in cervical lymph nodes in cases of SCC of the head and neck. Method: A total of 47 different cases of SCC affecting lip, tongue, palate, or larynx, previously submitted to surgical resection, were assessed according to the following variables: gender, age, tumor size, degree of differentiation, depth of invasion and metastasis in cervical lymph nodes. Results: The mean age was 61.9 ± 10.6 years and the average tumor size was 3.03 ± 1.70 cm. The process was more frequent in 37 men (78.7%), while 9 of these patients had node metastasis (24.32%). The presence of metastases was associated with depth of invasion (p = 0.026), but no relationship was found with age (p = 0.591), sex (p =0.137), topography (p = 0.394), tumor size (p = 0.612) and degree of differentiation (p = 0.452). Conclusion: SCC of the head and neck is more prevalent among men, and accurate histopathological determination of tumor invasion depth is predictive of the presence of nodal metastases.

Relationship between age and progesterone receptor expression with presence of central nervous system metastases in breast invasive ductal carcinoma / Relação entre idade e expressão do receptor de progesterona com presença de metástases no sistema nervoso central no carcinoma ductal invasivo da mama

ABSTRACTIntroduction:Breast invasive carcinoma of no special type (NST) is characterized by great morphological heterogeneity, and accounts for about 70%-80% of malignant breast tumors. The main prognostic factors are tumor size, degree of differentiation, and status of axillary lymph nodes. NST represents 15%-18% of central nervous system metastases (CNSm), and generally the response to systemic treatment/chemotherapy is unsatisfactory.Objective:To estimate the association between clinical and pathological findings of NST with CNSm.Method:Clinical data of 171 specimens of lumpectomy/mastectomy with axillary dissection in NST were evaluated, as well as the following pathological variables: tumor size, histological grade, nodal status, expression of estrogen (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER-2/neu) oncogene (c-erb B2), and presence of CNSm. The cases of CNSm in NST underwent resection, and the primary site was identified by immunohistochemistry.Results:The prevalence of CNSm was 9.4% (n = 16), and was related to age (p = 0.01), and the expression of PR (p = 0.004). Although cases of NST with CNSm showed correlation with greater tumor size, higher histological grade and nodal metastases, there was no statistical association (p = 0.221, p = 0.224 and p = 0.99, respectively). Expression of ER and c-erb-B2 was not significant between the two groups (p = 0.072 and p = 0.31, respectively).Conclusion:This study showed that younger patients and the expression of RP correlate with the presence of CNSm. The evaluation of specific pathological findings in NST can help establish risk factors and/or clinical parameters associated with the development of CNSm.

RESUMOIntrodução:O carcinoma ductal invasivo de tipo histológico não especial (CDINE) caracteriza-se por grande heterogeneidade morfológica, sendo responsável por cerca de 70%-80% dos tumores malignos de mama. Os principais fatores prognósticos são o tamanho tumoral, o grau de diferenciação e o status dos linfonodos axilares. O CDINE corresponde a 15%-18% das metástases no sistema nervoso central (MSNC) e, geralmente, sua resposta aos tratamentos sistêmicos/quimioterápicos é pouco satisfatória.Objetivo:Estimar a relação entre achados clínicos e anatomopatológicos do CDINE com a presença de MSNC.Método:Foram avaliadas as informações clínicas de 171 espécimes de setorectomia/mastectomia com esvaziamento axilar por CDINE, sendo determinadas as seguintes variáveis anatomopatológicas: tamanho tumoral, grau histológico, status nodal, expressão dos receptores de estrogênio (RE) e progesterona (RP) e de oncoproteína HER-2/neu/receptor do fator de crescimento epidérmico humano (c-erb-B2) e presença de MSNC. Os casos de MSNC em CDINE foram submetidos a ressecção e comprovação do sítio primário pela técnica de imuno-histoquímica.ResultadosA prevalência de MSNC foi igual a 9,4% (n = 16) e apresentou correlação com faixa etária (p = 0,01) e expressão dos RP (p = 0,004). Embora os casos de CDINE com MSNC estivessem relacionados com maior tamanho tumoral, maior grau histológico e metástases nodais, não foi encontrada associação estatística (p = 0,221, p = 0,224 e p = 0,99, respectivamente). A expressão de RE e c-erb-B2 não foi significativa entre os dois grupos (p = 0,072 e p = 0,31, respectivamente).Conclusão:O presente estudo mostrou que as pacientes mais jovens e a expressão dos RP relacionam-se com a presença de MSNC. A avaliação de achados anatomopatológicos específicos no CDINE pode ajudar a estabelecer fatores de risco e/ou parâmetros clínicos associados ao desenvolvimento de MSNC.

Relationship between the presence of liver metastases with histological grading, depth of invasion and nodal involvement in sporadic adenocarcinoma of the large intestine / Relação entre presença de metástases hepáticas com grau histológico, profundidade de invasão e envolvimento nodal no adenocarcinoma esporádico de intestino grosso

ABSTRACTIntroduction:Large intestine adenocarcinoma (LIA) is the most common cancer of the gastrointestinal tract, and corresponds to the fifth most common malignancy in Brazil. The main prognostic factors related to LIA are depth of tumor invasion and perivisceral lymph nodes status.Objective:To estimate the relationship between pathological findings and the presence of liver metastases (LM) in LIA cases.Method:We evaluated 51 cases of LIA, previously submitted to surgical resection, in order to determine the following variables: topography, tumor size, macroscopic appearance, degree of differentiation, depth of invasion, nodal status, and presence of LM.Results:The average age was 64.8 years, with predominance of men (n = 26/51.0%) and lesions in the sigmoid colon (n = 18/35.3%). The main general characteristics of the sample were ulcerative-vegetative lesions (n = 20/39.2%), no annular tumors (n = 3/64.7%), moderately differentiated tumor (n = 44/86.3%), absence of mucinous areas (n = 40/78.4%), and mesocolon invasion (n = 29/56.9%). LM were found in 14 cases (27.5%), and is associated with presence of nodal metastases (p = 0.005). Tumor size (p = 0.72), macroscopic appearance (p = 0.362), histological grade (p = 0.147), and depth of invasion (p = 0.195) showed no association with LM presence.Conclusion:LIA has a wide anatomical and pathological heterogeneity. In this study, the presence of LM associated with LIA was related to perivisceral lymph nodes status, with no relation to tumor size, degree of differentiation, and depth of invasion, which suggests that identifying neoplastic angiolymphatic invasion is a possible predictor of liver involvement.

RESUMOIntrodução:O adenocarcinoma de intestino grosso (AIG) é o tumor maligno mais frequente do trato digestivo e corresponde à quinta neoplasia maligna mais comum no Brasil. Os principais fatores prognósticos do AIG são profundidade de invasão neoplásica e status dos linfonodos periviscerais.Objetivo:Estimar a relação entre achados anatomopatológicos e presença de metástases hepáticas (MH) em casos de AIG.Método:Foram avaliados 51 casos de AIG, previamente submetidos à ressecção cirúrgica, e determinadas as seguintes variáveis: topografia, tamanho tumoral, conformação macroscópica, grau histológico, profundidade de invasão, status nodal e presença de MH.Resultados:A média de idade correspondeu a 64,8 anos, com predomínio de homens (n= 26/51,0%) e lesões do cólon sigmoide (n = 18/35,3%). Lesões ulcerovegetantes (n = 20/39,2%), tumores não anelares (n = 3/64,7%), neoplasias moderadamente diferenciadas (n = 44/86,3%), ausência de áreas mucoprodutoras (n= 40/78,4%) e invasão do mesocólon (n = 29/56,9%) foram as principais características gerais da amostra. MH foram encontradas em 14 casos (27,5%), estando associadas à presença de metástases nodais (p = 0,005). Tamanho tumoral (p = 0,72), configuração macroscópica (p = 0,362), grau histológico (p = 0,147) e profundidade de invasão (p = 0,195) não apresentaram associação com a presença de MH.Conclusão:O AIG apresenta heterogeneidade anatomopatológica ampla. No presente estudo, a presença de MH associadas ao AIG esteve relacionada com o status dos linfonodos periviscerais, não havendo relação com tamanho tumoral, grau de diferenciação e profundidade de invasão, sugerindo que a identificação de invasão neoplásica angiolinfática é possível fator preditivo do envolvimento hepático.

Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is expressed in tubular epithelial cells after injury and may have a role in the development of renal graft fibrosis. In this study we evaluated the molecular and protein expressions of KIM-1 in dysfunctional allografts and also mRNA KIM-1 expression in urine as potential biomarkers of graft fibrosis. METHODS: Protein and mRNA levels in renal tissue and urinary sediment cells of 69 kidney transplant recipients that undertook for-cause graft biopsies were evaluated by immunohistochemistry and real-time polymerase chain reaction. The histopathology was classified according to the 2007 Banff schema. RESULTS: KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubular atrophy (IF/TA) compared with biopsies showing acute calcineurin inhibitor nephrotoxicity (CIN) (P <0.05). Kidney tissue KIM-1 mRNA signaling (in) was increased in biopsies with IF/TA compared with all other groups (P <0.05). In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05). Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine. CONCLUSIONS: KIM-1 seems to be a marker of kidney graft fibrosis. Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.

Renal mixed epithelial and stromal tumor: case report / Tumor epitelial-estromal misto do rim: relato de caso

Mixed epithelial and stromal tumor (MEST) represents a recently described biphasic kidney neoplasm, which predominantly affects perimenopausal females. The authors report the case of a young male patient with a MEST exhibiting positivity for estrogen and progesterone receptors. Computed tomography/magnetic resonance imaging (CT/MRI) showed an expansive lesion affecting the right kidney. Grossly, a solid-cystic tumor was identified, which measured 5.7 × 3.5 × 2.4 cm. On microscopic examination, a biphasic tumor constituted by stromal and epithelial elements, without significant atypias, was identified. The stromal element was composed of spindle cells revealing positive immunoexpression for actin, desmin, vimentin, and estrogen receptors. The epithelial component exhibited a predominantly tubular pattern showing positive immunoreaction for cytokeratins. The diagnosis of MEST was then established.

O tumor epitelial e estromal misto (TESM) representa uma neoplasia renal bifásica descrita recentemente que afeta predominantemente mulheres na perimenopausa. Os autores relatam o caso de um paciente jovem, do sexo masculino, com TESM exibindo positividade para receptores de estrogênio e progesterona. A tomografia computadorizada/ressonância magnética (TC/RM) mostrou lesão expansiva no rim direito. Ao exame macroscópico, identificou-se tumor sólido-cístico medindo 5,7 × 3,5 × 2,4 cm. À microscopia, foi encontrado tumor bifásico constituído por elementos estromais e epiteliais, sem atipias significativas. O componente estromal era composto por células fusiformes, exibindo imunoexpressão positiva para actina, desmina, vimentina e receptores de estrogênio. Os elementos epiteliais mostraram padrão predominantemente tubular e exibiram imunorreação positiva para citoqueratinas. O diagnóstico de TESM foi então estabelecido.