What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics
AbstractApproximately one-tenth of the general population exhibit adrenal cortical nodules, and the incidence has increased. Afflicted patients display a multifaceted symptomatology —sometimes with rather spectacular features. Given the general infrequency as well as the specific clinical, histological, and molecular considerations characterizing these lesions, adrenal cortical tumors should be investigated by endocrine pathologists in high-volume tertiary centers. Even so, to distinguish specific forms of benign adrenal cortical lesions as well as to pinpoint malignant cases with the highest risk of poor outcome is ofte...
Source: Endocrine Pathology - February 3, 2021 Category: Pathology Source Type: research
Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates
Abstract
Cancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past decade. However the incidence of familial disease has not been emphasized and is often overlooked in routine practice. A careful clinical documentation of family history or familial syndromes that can be associated with thyroid disease can help identify germline susceptibility-driven thyroid neoplasia. In this review, we summarize a large body of information about both syndromic and non-syndromic familial thyroid carcinom...
Source: Endocrine Pathology - January 25, 2021 Category: Pathology Source Type: research
Genomics and Epigenomics of Medullary Thyroid Carcinoma: From Sporadic Disease to Familial Manifestations
AbstractOur understanding of the genomics and epigenomics of medullary thyroid carcinoma (MTC) has advanced since the initial recognition ofRET as a driver of MTC tumorigenesis in familial MTC. We now have insight into the frequency and prognostic significance of specificRET mutations in sporadic MTC. For example, the most commonRET mutation in sporadic MTC is theRET Met918Thr mutation, the same mutation that underlies MEN2B and a poor prognosticator. This mutation is relatively infrequent in medullary thyroid microcarcinomas but is over-represented in advanced-stage disease.RAS mutations are detected in 70% of sporadic,...
Source: Endocrine Pathology - January 25, 2021 Category: Pathology Source Type: research
Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors
AbstractWell differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal and pancreaticobiliary system are the most common neuroendocrine neoplasms. Studies of the molecular basis of these lesions have identified genetic mutations that predispose to familial endocrine neoplasia syndromes and occur both as germline events and in sporadic tumors. The mutations often involve epigenetic regulators rather than the oncogenes and tumor suppressors that are affected in other malignancies. Somatic copy number alterations and miRNAs have also been implicated in the development and progression of some of these tumors....
Source: Endocrine Pathology - January 18, 2021 Category: Pathology Source Type: research
Clinical Impact of Pathological Features Including the Ki-67 Labeling Index on Diagnosis and Prognosis of Adult and Pediatric Adrenocortical Tumors
AbstractAdrenocortical tumors (ACT) in the adult and pediatric population are generally considered distinct entities due to differences in molecular events related to tumorigenesis, clinical presentation, and outcome. Furthermore, pathological criteria used for diagnosis and prognostication of ACT in adults are usually inadequate for predicting the biological behavior of ACT in children. Here, we analyzed 146 adult and 44 pediatric (< 15y/o) ACT with long-term clinical follow-up and furthered current evidence on the clinical and pathological differences between pediatric and adult tumors. Predilection for female over...
Source: Endocrine Pathology - January 14, 2021 Category: Pathology Source Type: research
A Subset of Large Cell Neuroendocrine Carcinomas in the Gastroenteropancreatic Tract May Evolve from Pre-existing Well-Differentiated Neuroendocrine Tumors
This study suggests that a subset of large cell NECs in the gastroenteropancreatic tract may evolve from pre-existing well-differentiated NETs. (Source: Endocrine Pathology)
Source: Endocrine Pathology - January 12, 2021 Category: Pathology Source Type: research
Genomics of High-Grade Neuroendocrine Neoplasms: Well-Differentiated Neuroendocrine Tumor with High-Grade Features (G3 NET) and Neuroendocrine Carcinomas (NEC) of Various Anatomic Sites
AbstractHigh-grade neuroendocrine neoplasms (HG-NENs) are clinically aggressive diseases, the classification of which has recently been redefined. They now include both poorly differentiated NENs (neuroendocrine carcinoma, NECs) and high proliferating well-differentiated NENs (called grade 3 neuroendocrine tumors, G3 NETs, in the digestive system). In the last decade, the “molecular revolution” that has affected all fields of medical oncology has also shed light in the understanding of HG NENs heterogeneity and has provided new diagnostic and therapeutic tools, useful in the management of these malignancies. Considerin...
Source: Endocrine Pathology - January 12, 2021 Category: Pathology Source Type: research
What Have We Learned from Molecular Biology of Paragangliomas and Pheochromocytomas?
AbstractRecent advances in molecular genetics and genomics have led to increased understanding of the aetiopathogenesis of pheochromocytomas and paragangliomas (PPGLs). Thus, pan-genomic studies now provide a comprehensive integrated genomic analysis of PPGLs into distinct molecularly defined subtypes concordant with tumour genotypes. In addition, new embryological discoveries have refined the concept of how normal paraganglia develop, potentially establishing a developmental basis for genotype –phenotype correlations for PPGLs. The challenge for modern pathology is to translate these scientific discoveries into routine ...
Source: Endocrine Pathology - January 12, 2021 Category: Pathology Source Type: research
Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?
AbstractMolecular pathology has advanced our understanding of many tumors and offers opportunities to identify novel therapies. In the pituitary, the field has uncovered several genetic mutations that predispose to pituitary neuroendocrine tumor (PitNET) development, includingMEN1, CDKN1B,PRKRI α, AIP, GPR101, and other more rare events; however, these genes are only rarely mutated in sporadic PitNETs. Recurrent genetic events in sporadic PitNETs includeGNAS mutations in a subset of somatotroph tumors and ubiquitin-specific peptidase mutations (e.g.,USP8,USP48) in some corticotroph tumors; to date, neither of these has re...
Source: Endocrine Pathology - January 12, 2021 Category: Pathology Source Type: research
Diagnostic and Predictive Role of DLL3 Expression in Gastroenteropancreatic Neuroendocrine Neoplasms
AbstractGastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare and heterogeneous subgroup of tumors with a challenging management because of their extremely variable biological and clinical behaviors. Due to their different prognosis, there is an urgent need to identify molecular markers which would enable to discriminate between grade 3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), despite both being diagnosed mainly on the basis of proliferation index and cell differentiation. DLL3, a negative Notch regulator, is a promising molecular target highly expressed in several tumors with neur...
Source: Endocrine Pathology - January 6, 2021 Category: Pathology Source Type: research
Dopamine β-hydroxylase: An Essential and Optimal Immunohistochemical Marker for Pheochromocytoma and Sympathetic Paraganglioma
(Source: Endocrine Pathology)
Source: Endocrine Pathology - January 6, 2021 Category: Pathology Source Type: research
Capsular Invasion Matters Also in “Papillary Patterned” Tumors: A Study on 121 Cases of Encapsulated Conventional Variant of Papillary Thyroid Carcinoma
AbstractPapillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Some PTCs with classical papillae can be totally or partially encapsulated, and these tumors are called “encapsulated” (conventional) variant of papillary thyroid carcinoma. We aimed to investigate the clinicopathological features of this variant, comparing with non-encapsulated conventional type PTC. Among 823 thyroidectomy specimens with PTC diagnosed between 2015 and 2018, 121 tumors from 105 p atients (12.75%) were reclassified as encapsulated conventional PTC. In 76 patients, tumors were unifocal. Size, cystic changes, backgro...
Source: Endocrine Pathology - January 4, 2021 Category: Pathology Source Type: research
Genomics and Epigenomics in Parathyroid Neoplasia: from Bench to Surgical Pathology Practice
AbstractThe majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually a straightforward diagnosis in endocrine pathology when in the appropriate clinical setting, although subsets of cases will exhibit atypical histological features that may warrant additional immunohistochemical and genetic analyses to estimate the malignant potential. Parathyroid carcinomas on the other hand, are bona fide malignant tumors characterized by their unequivocal invasion demonstrated through routine histology or metastasis. The ultimate...
Source: Endocrine Pathology - December 2, 2020 Category: Pathology Source Type: research
The Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer
AbstractThe influence of chronic lymphocytic thyroiditis (CLT) on clinicopathological features and behavior of differentiated thyroid carcinoma (DTC) is still debated. In the present study, we aimed to evaluate the prognosis of DTC on the presence of CLT. A total of 649 total thyroidectomized patients (379 female, 270 male) with DTC, who had follow-up data for at least 36 months were included. Clinical, histopathological data, preoperative thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (Tg-ab), thyroid-stimulating hormone (TSH) levels, and presence of recurrent/persistent disease (R/PD) were evaluated retro...
Source: Endocrine Pathology - November 13, 2020 Category: Pathology Source Type: research
Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion
AbstractWhile minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samples including miFTC, eaFTC, and wiFTC tumors, as well as histologically normal thyroid adjacent to benign follicular adenomas, were selected from a cohort (n = 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expr...
Source: Endocrine Pathology - October 16, 2020 Category: Pathology Source Type: research
