Comprehensive clinicopathologic features in autoimmune atrophic gastritis: Insights from a European cohort of 57 patients.

CONTEXT: Autoimmune atrophic gastritis (AAG) is a frequently underdiagnosed disease due to its broad-spectrum clinical presentation. The diagnosis is based on histological confirmation of corpus-restricted metaplastic chronic atrophic gastritis. OBJECTIVE: To thoroughly describe the histological features of a European cohort of AAG patients. DESIGN: Clinical and pathological data of 57 out of 676 patients diagnosed with AAG were reviewed. RESULTS: Thirty-nine patients were female and eighteen were male. The mean age was 62 years. Antibodies were identified in 32/42 patients (76 %). Vitamin B12 levels were low (< 200 pg/mL) in 37/54 patients (69 %). Serum gastrin levels was elevated (> 115 pg/mL) in all cases tested. Associated autoimmune/inflammatory conditions were identified in 20/57 patients (35 %). Histologically, deep chronic inflammation was present in 46/57 (81 %) patients. Complete destruction of oxyntic glands was observed in 45/57 (79 %) patients. Pyloric metaplasia was present in 54/57 (95 %) patients, intestinal metaplasia in 51/57 (89 %) patients, and pancreatic metaplasia in 20/57 (35 %) patients. Among ECL cell proliferation, linear hyperplasia was present in all 57/57 patients, micronodular hyperplasia in 55/57 patients, and adenomatoid hyperplasia in 10/57 patients. ECL cell dysplasia was identified in 5/57 patients, and neuroendocrine microtumor in 4/57 patients. CONCLUSIONS: The diagnosing of AAG remains challenging due to the greater variability in symptoms than previously recognized. It is important to consider chronic AAG, especially with other concurrent autoimmune conditions. The importance of accurate diagnosis and surveillance is based on the potential development of type 1 gastric neuroendocrine tumor and increased risk of gastric adenocarcinoma.

Müllerian adenosarcoma with sarcomatous overgrowth and heterologous elements: A case report and literature review.

Uterine mullerian adenosarcoma (MA) is a rare biphasic tumour that accounts for less than 0.5% of uterine neoplasms. The age range of presentation is wide, with the median age in the 5th decade of life. It usually has a good prognosis; however, it worsens when it presents with sarcomatous overgrowth, heterologous elements or infiltrates the myometrium. We report the case of a 63-year-old woman presenting with abnormal vaginal bleeding and a sensation of solid material coming out of the cervical canal who was diagnosed with mullerian adenosarcoma with sarcomatous overgrowth (MASO) and presence of heterologous elements after performing a mass biopsy and subsequent hysterectomy. We reviewed the literature, focusing especially on the differential diagnoses to be evaluated, as well as the differences in prognosis and treatment according to whether or not they present histologic features of poor prognosis.

microRNA sequencing for biomarker detection in the diagnosis, classification and prognosis of Diffuse Large B Cell Lymphoma.

Despite being considered a single disease, Diffuse Large B Cell Lymphoma (DLBCL) presents with variable backgrounds, which results in heterogeneous outcomes among patients, with 40% of them still having primary refractory disease or relapse. Thus, novel biomarkers are needed. In addition, multiple factors regarding its pathogenesis remain unclear. In this context, recent investigations point to the relevance of microRNAs (miRNAs) in cancer. However, regarding DLBCL, there is inconsistency in the data reported. Therefore, in this work, the main goals were to determine a miRNA set with utility as biomarkers for DLBCL diagnosis, classification, prognosis and treatment response, as well as to decipher the mechanism of action of deregulated miRNAs in the origin of the disease. We analyzed miRNA expression in a cohort of 78 DLBCL patients and 17 controls using small RNA sequencing and performed a miRNA-mRNA interaction network analysis. This way, we were able to define new miRNA expression signatures for diagnosis, classification, treatment response and prognosis, and we identified plausible mechanisms of action by which deregulated miRNAs could be involved in DLBCL pathogenesis. In summary, our study remarks that miRNAs could play an important role in DLBCL.

Prognostic and therapeutic value of somatic mutations in diffuse large B-cell lymphoma: A systematic review.

Diffuse large B-cell lymphoma (DLBCL), the most common type of Non-Hodgkin lymphoma (NHL), is a highly heterogeneous and aggressive disease. Regardless of this heterogeneity, all patients receive the same first-line therapy, which fails in 30-40 % of patients, who are either refractory or relapse after remission. With the aim of stratifying patients to improve treatment outcome, different clinical and genetic biomarkers have been studied. The present systematic review aimed to identify somatic mutations that could serve as prognosis biomarkers or as therapeutic target mutations in DLBCL. Regarding their role as prognostic markers, mutations in CD58 and TP53 seem the most promising predictors of poor outcome although the combination of different alterations and other prognostic factors could be a more powerful strategy. On the other hand, different approaches regarding targeted therapy have been proposed. Therefore, mutational analysis could help guide treatment choice in DLBCL yet further studies and clinical trials are needed.

DNA methylation epigenotypes in breast cancer molecular subtypes.

INTRODUCTION: Identification of gene expression based breast cancer subtypes is considered as a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene expression changes occurring in breast cancer. So far, these epigenetic contributions to sporadic breast cancer subtypes have not been well characterized, and there is only a limited understanding of the epigenetic mechanisms affected in those particular breast cancer subtypes. The present study was undertaken to dissect the breast cancer methylome and deliver specific epigenotypes associated with particular breast cancer subtypes. METHODS: Using a microarray approach we analyzed DNA methylation in regulatory regions of 806 cancer related genes in 28 breast cancer paired samples. We subsequently performed substantial technical and biological validation by Pyrosequencing, investigating the top qualifying 19 CpG regions in independent cohorts encompassing 47 basal-like, 44 ERBB2+ overexpressing, 48 luminal A and 48 luminal B paired breast cancer/adjacent tissues. Using all-subset selection method, we identified the most subtype predictive methylation profiles in multivariable logistic regression analysis. RESULTS: The approach efficiently recognized 15 individual CpG loci differentially methylated in breast cancer tumor subtypes. We further identify novel subtype specific epigenotypes which clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. CONCLUSIONS: Our results provide evidence that well defined DNA methylation profiles enables breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

High-grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication-a comprehensive clinical, radiographic, pathologic, and genomic analysis.

High-grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication (HGNET BCOR ex15 ITD) is a recently proposed tumor entity of the central nervous system (CNS) with a distinct methylation profile and characteristic genetic alteration. The complete spectrum of histologic features, accompanying genetic alterations, clinical outcomes, and optimal treatment for this new tumor entity are largely unknown. Here, we performed a comprehensive assessment of 10 new cases of HGNET BCOR ex15 ITD. The tumors mostly occurred in young children and were located in the cerebral or cerebellar hemispheres. On imaging all tumors were large, well-circumscribed, heterogeneous masses with variable enhancement and reduced diffusion. They were histologically characterized by predominantly solid growth, glioma-like fibrillarity, perivascular pseudorosettes, and palisading necrosis, but absence of microvascular proliferation. They demonstrated sparse to absent GFAP expression, no synaptophysin expression, variable OLIG2 and NeuN positivity, and diffuse strong BCOR nuclear positivity. While BCOR exon 15 internal tandem duplication was the solitary pathogenic alteration identified in six cases, four cases contained additional alterations including CDKN2A/B homozygous deletion, TERT amplification or promoter hotspot mutation, and damaging mutations in TP53, BCORL1, EP300, SMARCA2 and STAG2. While the limited clinical follow-up in prior reports had indicated a uniformly dismal prognosis for this tumor entity, this cohort includes multiple long-term survivors. Our study further supports inclusion of HGNET BCOR ex15 ITD as a distinct CNS tumor entity and expands the known clinicopathologic, radiographic, and genetic features.

[Actinomycotic brain abscess in immunocompetent patient]. / Absceso cerebral actinomicótico en paciente inmunocompetente.

BACKGROUND: The actinomyces is germ commonly found in the normal flora of the oral cavity and gastro-intestinal and uro-genital tracts. Involvement in other locations is a very uncommon event. OBJECTIVES: To describe a patient with an actinomicotyc brain abscess CLINICAL CASE: We report the case of a patient who suffered a seizure and decreased level of consciousness. Imaging tests revealed the presence of lesions both in the lung and in the brain. An urgent craniotomy was performed and the diagnosis of actinomicotyc abscess was obtained. CONCLUSION: We describe the differential characteristics of this type of infection, discussing the diagnostic process and management in detail.

Upregulated Expression of Heparanase and Heparanase 2 in the Brains of Alzheimer's Disease.

BACKGROUND: Heparan sulfate proteoglycans (HSPGs) promote amyloid-ß peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity. OBJECTIVE: To analyze HPSE and HPSE2 expressions at different stages of AD. METHODS: RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain. RESULTS: Both proteins appeared overexpressed at different stages of AD. Immunohistochemistry indicated that the presence of the heparanases was related to AD pathology, with intracellular deposits found in degenerated neurons. At the extracellular level, HPSE was observed only in neuritic plaques with a fragmented core, while HPSE2 appeared in those with compact cores as well. CONCLUSION: Given the involvement of HSPGs in AD pathology, there would seem to be a relationship between the regulation of heparanase expression, the features of the disease, and a possible therapeutic alternative.

Luminal B breast cancer subtype displays a dicotomic epigenetic pattern.

Luminal B breast tumors have aggressive clinical and biological features, and constitute the most heterogeneous molecular subtype, both clinically and molecularly. Unfortunately, the immunohistochemistry correlate of the luminal B subtype remains still imprecise, and it has now become of paramount importance to define a classification scheme capable of segregating luminal tumors into clinically meaningful subgroups that may be used clinically to guide patient management. With the aim of unraveling the DNA methylation profiles of the luminal subtypes currently being most used in the clinical setting, we have quantified the DNA methylation level of 27,578 CpG sites in 17 luminal B (ER+, Ki67 ≥ 20 % or PgR < 20 % and HER2-), 8 luminal A (ER+ and Ki67 > 20 %) and 4 luminal B-HER2+ (ER+ and HER2+) breast cancer samples by using the Illumina Infinium methylation microarray approach. Unsupervised hierarchical clustering revealed that DNA methylation stratifies luminal B samples in two categories with differing epigenetic and clinical features. One subgroup of luminal B samples showed a methylator phenotype and clustered with the lumB-HER tumors, while the other showed less methylated events, clustered with the luminal A. A 3 CpG marker panel capable of discriminating methylator versus non-methylator luminal B samples was identified and further validated in an independent cohort of patients. Our results provide evidence that DNA methylation and, more specifically, a panel of 3 CpG markers, enables the stratification of luminal B samples in two categories with differing epigenetic and clinical features and support the utilization of this panel for therapeutic stratification of patients with luminal breast cancer.