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Immune checkpoint inhibitors have shown remarkable efficacy as new-generation drugs in anti-tumor therapy. However, the nonspecific activation of the immune system leads to a number of adverse side effects, so-called immune-related adverse events (irAEs), including the occurrence of diarrhea and colitis in about one third of treated patients.Endoscopically and histologically, there is significant overlap of immune-mediated colitis with classic IBD, making differentiation difficult.Therapeutically, high-dose glucocorticoids are used in grade 3 (severe) to grade 4 (life-threatening) colitis, in addition to discontinuation of ICI therapy. Steroid-refractory cases (up to 42%) benefit from the TNF inhibitor infliximab. Vedolizumab, analogous to inflammatory bowel disease, represents second-line therapy for infliximab-refractory cases. Little data exist to date on the efficacy of tofacitinib in refractory cases.We describe the case and therapeutic management of severe and persistent immune-mediated colitis after successful immunochemotherapy with pembrolizumab in an 80-year-old man with metastatic non-small cell carcinoma of the lung and pre-existing colitis unclassified and other comorbidities., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background and Objectives: The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit to develop evidence-based, internationally agreed-upon standardized data sets for each anatomic site, to be used throughout the world. Providing global standardization of pathology tumor classification, staging, and other reporting elements will lead to improved patient management and enhanced epidemiological research., Methods: Pheochromocytoma and paraganglioma are uncommon and are frequently overlooked in registry data sets. Malignant criteria have previously been defined only when there was metastatic disease., Results: With recent recognition of a significant inheritance association and the development of risk stratification tools, this data set was created in order to obtain more meaningful outcomes and management data, using similar criteria across the global pathology community. Issues related to key core and non-core elements, especially clinical hormonal status, familial history, tumor focality, proliferative fraction, adverse or risk stratification features, and ancillary techniques, are discussed in the context of daily application to these types of specimens., Conclusions: The ICCR data set, developed by an international panel of endocrine organ specialists, establishes a pathology-standardized reporting guide for pheochromocytoma and paraganglioma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited., (© 2015 Society for Endocrinology.)

Background: Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data., Methods: Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study., Results: Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05)., Conclusions: Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.

Dettmer M, Schmitt A, Steinert H, Moch H, Komminoth P & Perren A (2012) Histopathology 60, 1045-1051 Poorly differentiated oncocytic thyroid carcinoma - diagnostic implications and outcome Aims: Poorly differentiated thyroid carcinomas (PDTC) are an ongoing diagnostic challenge. Although the Turin consensus criteria for PDTC excluded consideration of oncocytic tumours, the World Health Organization (WHO) classification does recognise an oncocytic variant of conventional PDTC. The aims of this study were to establish whether the Turin criteria can be applied to oncocytic PDTC, and to determine if there are prognostic differences between conventional and oncocytic PDTC. Methods and results: We applied the Turin criteria to 129 thyroid carcinomas. We identified 18 oncocytic PDTC and 16 conventional PDTC. Kaplan-Meier analysis revealed a significantly worse outcome for oncocytic PDTC with regard to overall and tumour-specific survival but no difference for relapse-free survival, all of which were confirmed by multivariate analysis. There was no association of survival with gender, age or tumour stage. Conclusions: The Turin criteria can be applied to oncocytic PDTC and patients with this variant have a decreased survival using conventional radioiodine treatment compared to conventional PDTC and might therefore be candidates for novel treatment modalities. [ABSTRACT FROM AUTHOR]