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Discover the most talked about and latest scientific content & concepts.

Concept: Adenoma

27

Primary multiple pleomorphic adenomas in a unilateral parotid gland in previously untreated patients is a rare finding, and little is known about the etiology and pathogenesis. Here, a highly unusual case of a primary multifocal pleomorphic adenoma consisting of 15 individual nodules is presented. It is shown that all nodes are clonally related and thus share a common cell of origin excluding an independent multifocal pathogenesis. Most likely, multifocal pleomorphic adenoma represents parasitic nodules that have been detached from a main nodule, which may have been the result of undisclosed trauma.

Concepts: Adenoma, Parotid gland, Warthin's tumor, Pleomorphic adenoma

27

The role of the Wnt signaling pathway in the tumorigenesis of sessile serrated adenoma (SSA) of the colorectum remains controversial. Using 2 antibodies targeting different epitopes (C-terminus and N-terminus), β-catenin expression in 35 SSAs and 30 right-sided hyperplastic polyps (RHPs) was examined by immunohistochemistry. Samples of 10 normal colorectal mucosa, 32 left-sided hyperplastic polyps, 27 traditional serrated adenomas (TSAs), and 40 traditional adenomas (TAs) were used as controls. Expression of adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC), key regulators of β-catenin, was also examined by immunohistochemistry. Using the C-terminus antibody, no nuclear staining of β-catenin was observed in any SSAs or RHPs. However, with the N-terminus antibody, accumulation of β-catenin was seen in 40.0% of SSAs and 33.3% of RHPs. The average immunoreactivity score of APC in SSAs (67.0 ± 21.6) and RHPs (69.2 ± 24.4) was significantly higher than that in TAs (22.0 ± 18.0) and TSAs (49.5 ± 23.1; all P < .05). In contrast, MCC was more frequently lost in right-sided-polyps such as SSA and RHP than in left-sided polyps such as left-sided hyperplastic polyp, TSA, and TA. Our results suggest that Wnt signaling is activated in SSA and its possible precursor lesion RHP. The present study also implied that the specific molecular form of β-catenin may participate in the Wnt signaling activation of right-sided serrated polyps. Moreover, loss of MCC expression but not APC may contribute to the early activation of Wnt signaling in right-sided serrated polyps.

Concepts: Antibody, Protein, Anatomical pathology, Colorectal cancer, Colon, Adenocarcinoma, Familial adenomatous polyposis, Adenoma

4

The cyclic AMP (cAMP) signaling pathway is one of the major players in the regulatory activity of growth and hormonal secretion in adrenocortical cells. Although its role in the pathogenesis of adrenocortical hyperplasia associated with Cushing´s syndrome has been clarified, a clear involvement of the cAMP signaling pathway and of one of its major downstream effectors, the protein kinase A (PKA), in sporadic adrenocortical adenomas remained elusive until recently. During the last year, a report by our group and three additional independent groups showed that somatic mutations of PRKACA, the gene coding for the catalytic subunit α of protein kinase A (PKA), are a common genetic alteration in patients with Cushing´s syndrome due to adrenal adenomas, occurring in 35-65% of the patients. In vitro studies revealed that those mutations are able to disrupt the association between catalytic and regulatory subunits of PKA, leading to a cAMP-independent activity of the enzyme. Despite somatic PRKACA mutations are a common finding in patients with clinical manifest Cushing´s syndrome, the pathogenesis of adrenocortical adenomas associated with subclinical hypercortisolism seems to rely on a different molecular background. In this review, the role of cAMP/PKA signaling pathway in regulation of adrenocortical cell function and its alterations in cortisol-producing adrenocortical adenomas will be summarized, with particular focus on recent developments.

Concepts: Signal transduction, Adenosine triphosphate, Enzyme, Hormone, Protein kinase, Cortisol, Adrenal cortex, Adenoma

4

This case report of a woman with an ectopic parathyroid adenoma suggests that simultaneous positron-emission tomography (PET) and MRI might be superior to PET-CT for lesion localization.

Concepts: Oncology, Medical imaging, Anatomical pathology, Radiology, Medical tests, Adenoma, Parathyroid adenoma

3

Hepatocellular adenomas (HCA) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in HNF1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.

Concepts: Cancer, Oncology, Anatomical pathology, Adenoma

3

Aberrant activation of WNT signalling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumour stem cell phenotype and identify the zinc-finger transcription factor GATA6 as a key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells whereas it restricts BMP signalling to differentiated tumour cells. Genetic deletion of Gata6 from mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumour stem cells. In human tumours, GATA6 competes with β-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been linked to increased susceptibility to development of CRC. Hence, GATA6 creates an environment permissive for CRC initiation by lowering the threshold of BMP signalling required for tumour stem cell expansion.

Concepts: DNA, Gene, Genetics, Gene expression, Cancer, Oncology, Chromosome, Adenoma

2

Predictive tools to identify patients at risk for gene mutations related to pituitary adenomas are very helpful in clinical practice. We therefore aimed to develop and validate a reliable risk category system for aryl hydrocarbon receptor-interacting protein (AIP) mutations in patients with pituitary adenomas.

Concepts: DNA, Mutation, Pituitary adenoma, DNA repair, Types of cancer, Neuroendocrinology, Adenoma

2

Most prolactinomas in females are diagnosed during the reproductive age and the majority are microadenomas. Prolactinomas detected in the postmenopausal period are less common with limited published data on their presentation and prognosis. Our objective was to assess the presenting clinical, biochemical and imaging findings, as well as the outcomes of women diagnosed with a prolactinoma in the postmenopausal period.

Concepts: Female, Estrogen, Menstrual cycle, Woman, Prolactinoma, Adenoma

2

Colorectal cancer (CRC) and adenoma adjacent to cancer exhibit distinct microRNA (miR) alterations in an apparent mucosa-to-adenocarcinoma sequence. The pattern of microRNAs in screen-detected polyps in relation to histologic features and cancer risk has not been investigated. miR expression analysis was performed on normal mucosa (NM), hyperplastic polyps (HPs), tubular adenomas (TAs), tubulovillous adenomas or high-grade dysplasia (TVHGs), and serrated polyps (sessile serrated adenoma/polyps, SSA/Ps, and traditional serrated adenomas, TSAs) in biopsy specimens from 109 patients undergoing screening/surveillance colonoscopy. Generalized linear models were used to identify differentially expressed miRs by histologic type and logistic regression to identify miR predictors of histopathology. False discovery rate (FDR) was used to control for multiple comparisons. We identified 99 miRs differing in at least one of five histopathologic groups (FDR {less than or equal to}0.05). In a comparison of HPNM vs. TVHG, the top most up- and down-regulated miRs in HPNM included miR-145, -143, -107, -194, and -26a (upregulated), and miR-663, -1268, -320b, -1275, and -320b (down-regulated) (FDR P-value < 0.05). miR-145 and -619 showed high accuracy to discriminate low- from high-risk polyps without serrated histology (TVHG vs. HPNM+TA) (CI= 95.6%), whereas miRs-124, -143, and -30a showed high accuracy of separating high-risk polyps (TVHG+TSA) from low-risk polyps (HPNM+TA+SSA/P) (CI=96.0%). For TSAs, miRs-125b and -199a were uniquely downregulated relative to HPNMs, and miR-335, -222 and -214 discriminated between non-serrated and serrated histology. Our data support the presence of CRC-associated miR alterations in screen-detected adenomas that may be useful for risk stratification for surveillance interval planning.

Concepts: Regression analysis, Cancer, Pathology, Anatomical pathology, Histology, Histopathology, Multiple comparisons, Adenoma

2

This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive ultrasound based shear wave elastography method.

Concepts: Optics, Adenoma, Parathyroid adenoma