Mielolipoma adrenal gigante associado à deficiência da 21-hidroxilase: associação não usual simulando um carcinoma adrenocortical secretor de androgênios

The objective of this study was to describe a case of giant myelolipoma associated with undiagnosed congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency. Five seven year-old male patient referred with abdominal ultrasound revealing a left adrenal mass. Biochemical investigation revealed hyperandrogenism and imaging exams characterized a large heterogeneous left adrenal mass with interweaving free fat tissue, compatible with the diagnosis of myelolipoma, and a 1.5 cm nodule in the right adrenal gland. Biochemical correlation has brought concerns about differential diagnosis with adrenocortical carcinoma, and surgical excision of the left adrenal mass was indicated. Anatomopathologic findings revealed a myelolipoma and multinodular hyperplasic adrenocortex. Further investigation resulted in the diagnosis of CAH due to 21OH deficiency. Concluded that CAH has been shown to be associated with adrenocortical tumors. Although rare, myelolipoma associated with CAH should be included in the differential diagnosis of adrenal gland masses. Moreover, CAH should always be ruled out in incidentally detected adrenal masses to avoid unnecessary surgical procedures.O objetivo deste trabalho foi descrever um caso de mielolipoma gigante associado à hiperplasia adrenal congênita (HAC) por deficiência da 21-hidroxilase (21OH). Paciente do sexo masculino, 57 anos de idade, encaminhado por achado ultrassonográfico de massa adrenal esquerda. Investigação bioquímica revelou hiperandrogenismo e exames de imagem revelaram grande lesão sólida em adrenal esquerda de aspecto heterogêneo, entremeada de tecido gorduroso, compatível com diagnóstico de mielolipoma, e um nódulo de 1,5 cm na adrenal direita. Os achados bioquímicos sugeriam o diagnóstico de carcinoma adrenocortical, indicando cirurgia para retirada da massa adrenal esquerda. O anatomopatológico confirmou mielolipoma e hiperplasia multinodular do córtex adrenal. A investigação subsequente diagnosticou HAC por deficiência da 21OH. Concluiu-se que a HAC tem sido descrita em associação com tumores adrenocorticais. Apesar de raro, o mielolipoma associado à HAC deve ser incluído nas possibilidades diagnósticas de massa adrenal. Adicionalmente, a HAC deve ser sempre afastada nos casos de massa adrenal de achado incidental, evitando cirurgias desnecessárias.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Expressão de caspase-3 e Bcl-2 em glioblastomas: um estudo imunohistoquímico

The unfavorable prognosis of malignant gliomas can also be explained by the incomplete knowledge of their molecular pathways. Studies regarding the regulatory process of apoptosis in glioblastoma (GBM), the most common malignant glioma, are few, and better knowledge of the expression of pro and anti-apoptotic proteins could collaborate with the development of new treatments founded on molecular basis. The objective of this study was to evaluate by immunohistochemistry the expression of caspase-3 and Bcl-2 in 30 samples of GBMs. The expression of caspase-3 (mean 17.67%) was lower than Bcl-2 (mean 30.92%), a statistically significant result (p<0.0001), suggesting low apoptotic activity in these tumors. Other studies of proteins related to the intrinsic and extrinsic pathway of apoptosis are required to provide additional information of this mechanism in GBMs.O prognóstico desfavorável dos gliomas malignos também pode ser explicado pelo pouco conhecimento dos seus mecanismos moleculares. Estudos relacionados à regulação do processo de apoptose em glioblastoma (GBM), o glioma maligno mais comum, são poucos, e o melhor conhecimento da expressão de proteínas pró e anti-apoptóticas poderia colaborar com o desenvolvimento de novos tratamentos fundamentados sobre a base molecular. O objetivo deste estudo foi avaliar por imunohistoquímica, a expressão de caspase-3 e Bcl-2 em 30 amostras de GBM. A expressão de caspase-3 (média de 17,67%) foi menor que a de Bcl-2 (média de 30,92%), com resultado estatisticamente significante (p<0.0001), sugerindo menor atividade apoptótica nestes tumores. Outros estudos envolvendo proteínas relacionadas à via extrínseca e intrínseca da apoptose são necessários para fornecer informações complementares deste mecanismo em GBMs

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Sudden infant death syndrome in Brazil: fact or fancy?

CONTEXT AND OBJECTIVE: The true incidence of sudden infant death syndrome (SIDS) in Brazil is unknown. The aim here was to identify SIDS cases in the city of Ribeirão Preto, State of São Paulo, between 2000 and 2005, in order to estimate its incidence. DESIGN AND SETTING: Retrospective analysis of data on live births and infant deaths in Ribeirão Preto and from autopsies of infants performed at the Death Verification Service of the Interior (SVOI) between 2000 and 2005. RESULTS: There were 47,356 live births and 537 deaths, with infant mortality rates ranging from 12.9‰ to 10.9‰ of live births. Among the 24 infants who died possibly due to SIDS and who were autopsied at the SVOI, six were from families living in the municipality (0.13‰ of live births): three (50%) were diagnosed as SIDS, and one each (16.66%) as indeterminate cause, bronchoaspiration and cerebral edema. Two deaths occurred in the first month of life (33.33%) and one each (16.66%) at two, four, six and eight months. Two deaths each (33.33%) occurred in the months of February and December, one each in August and October (16.66%). Four cases (66.7%) occurred in the summer and one each (16.66%) in winter and spring. There was 5:1 predominance of males over females. CONCLUSIONS: The frequency of SIDS was lower than what has been reported worldwide and in the Brazilian literature, thus suggesting underdiagnosis, indicating the lack of any specific postmortem protocol for SIDS identification and showing the need to implement this

Epithelial–Mesenchymal Transition Signaling and Prostate Cancer Stem Cells: Emerging Biomarkers and Opportunities for Precision Therapeutics

Prostate cancers may reactivate a latent embryonic program called the epithelial–mesenchymal transition (EMT) during the development of metastatic disease. Through EMT, tumors can develop a mesenchymal phenotype similar to cancer stem cell traits that contributes to metastasis and variation in therapeutic responses. Some of the recurrent somatic mutations of prostate cancer affect EMT driver genes and effector transcription factors that induce the chromatin- and androgen-dependent epigenetic alterations that characterize castrate-resistant prostate cancer (CRPC). EMT regulators in prostate cancer comprise transcription factors (SNAI1/2, ZEB1, TWIST1, and ETS), tumor suppressor genes (RB1, PTEN, and TP53), and post-transcriptional regulators (miRNAs) that under the selective pressures of antiandrogen therapy can develop an androgen-independent metastatic phenotype. In prostate cancer mouse models of EMT, Slug expression, as well as WNT/β-Catenin and notch signaling pathways, have been shown to increase stemness potential. Recent single-cell transcriptomic studies also suggest that the stemness phenotype of advanced prostate cancer may be related to EMT. Other evidence correlates EMT and stemness with immune evasion, for example, activation of the polycomb repressor complex I, promoting EMT and stemness and cytokine secretion through RB1, TP53, and PRC1. These findings are helping clinical trials in CRPC that seek to understand how drugs and biomarkers related to the acquisition of EMT can improve drug response

In pursuit of prognostic factors in children with pilocytic astrocytomas

This study described a 23-year experience in the treatment of children with pilocytic astrocytomas (piloA) with the aim of identifying putative clinical, histopathological, and/or immunohistochemical features that could be related to the outcome of these patients. Clinical data of 31 patients under 18 years of age with piloA were obtained from 1984 to 2006. The mean age at the time of surgery was 7.8 +/- 4.2 years (1 to 17 years), and the mean follow-up was 5.7 +/- 5.4 years (1 to 20 years). The most common site of tumor formation was the cerebellum (17), followed by brainstem (4), optic chiasmatic hypothalamic region (4), cerebral hemisphere (3), cervical spinal cord (2), and optic nerve (1). Gross total resection (GTR) was achieved in 23 (74.1%), mainly in those with tumors located in the cerebellum and cerebral hemispheres (P = 0.02). The global mortality rate was 6.4%. Nine patients were reoperated. Rosenthal fibers, eosinophilic granular bodies, microvascular proliferation, and lymphocytic infiltration were observed in most cases. The mean Ki-67LI was 4.4 +/- 4.5%. In all cases, Gal-3 expression in tumor cells was observed with variable staining pattern. Aside from GTR, no other clinical, histopathological, or immunohistochemical features were found to be related to the prognosis. We postulate that strict follow-up is recommended if piloA is associated with high mitotic activity/Ki67-LI, or if GTR cannot be achieved at surgery. Tumor recurrence or progression of the residual lesion should be strictly observed. In some aspects, childhood piloA remains an enigmatic tumor.CNPQ (Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFAEPA (Fundacao de Assistencia de Ensino e Pesquisa

Peritumoral infiltrate in the prognosis of epidermoid carcinoma of the oral cavity

INTRODUCTION: Patients with squamous cell carcinoma of the oral cavity present deficits in their cellular immunity that contribute to neoplastic growth. Thus, the inflammatory activity, such as the immunological response to the tumor, can be used as a prognostic factor.OBJECTIVES: To evaluate the correlation between peritumoral inflammation and clinical characteristics of the patients, survival, and the disease-free interval.METHODS: The study sample consisted of a retrospective hospital-based cohort of patients undergoing surgery for resection of oral cavity tumor. The inflammatory infiltrate on the slides was evaluated semi-quantitatively, and were divided into minor and major inflammatory processes.RESULTS: This study included 57 tumor samples, with infiltration of lymphocytes, plasma cells, and histiocytes. The log-rank test showed no significance for the survival curves and recurrence of the "minor inflammatory" and "major inflammatory" processes, with p = 0.14 and p = 0.24, respectively. A direct association between age and inflammation (p = 0.04) was observed, as well as an indirect association between the degree of tumor differentiation and inflammation (p = 0.01).CONCLUSION: Although associated with histological differentiation, the peritumoral inflammatory process cannot be considered a prognostic factor in squamous cell carcinoma of the oral cavity, as it is not related to survival and disease-free interval

Squamous Cell Carcinoma Originating from Adult Laryngeal Papillomatosis: Case Report and Review of the Literature

Background. The malignant transformation of laryngeal papillomatosis (LP) into squamous cell carcinoma (SCC) can occur in up to 4% of LP cases. The low-risk HPV types 6 and 11 are those that are most commonly related to LP; however, high-risk HPV types may be present. The present study reviews the literature on cases of malignant transformation of LP in adults and reports a clinical case. Case Report. A 47-year-old male patient exhibiting hoarseness for 4 months presented an exophytic lesion in the right palatine tonsil and a digitiform-like lesion in the right vocal fold. The biopsy revealed a well-differentiated SCC in the vocal cord, which showed a transition zone with a squamous papillomatous lesion. By using the chromogenic in situ hybridization (CISH) test, both lesions showed a positive result for high-risk HPV types 16 and 18 and negative for low-risk HPV types 6 and 11. The final diagnosis was SCC arising from LP. The patient underwent surgical treatment. After 36 months of follow-up, no signs of recurrence were observed. Results. The literature review revealed 25 cases of malignant transformation into SCC of LP with adult onset. Of these, only 9 cases were assessed by CISH and/or PCR for HPV identification, of which 7 were positive. The current study focuses on the eighth case, suggesting the involvement of the high-risk HPV types in its pathogenesis. Conclusions. LP is considered a benign lesion with the potential for malignant transformation, which reinforces the need for its early diagnosis and the constant monitoring of patients with LP