Endocrine Pathology Society Hubert Wolfe Award for 2021: Call for Nominations
(Source: Endocrine Pathology)
Source: Endocrine Pathology - October 23, 2021 Category: Pathology Source Type: research

TERT Promoter Mutated Follicular Thyroid Carcinomas Exhibit a Distinct microRNA Expressional Profile with Potential Implications for Tumor Progression
(Source: Endocrine Pathology)
Source: Endocrine Pathology - October 21, 2021 Category: Pathology Source Type: research

Two Pituitary Neuroendocrine Tumors (PitNETs) with Very High Proliferation and TP53 Mutation — High-Grade PitNET or PitNEC?
This report expands the spectrum of pituitary neuroendocrine neo plasms. (Source: Endocrine Pathology)
Source: Endocrine Pathology - October 20, 2021 Category: Pathology Source Type: research

Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data
This study aimed to investigate the incidence, clinical presentations, outcomes, and genetic backgrounds of primary versus secondary ATCs. We searched for ATCs in our institutional databases and the Surveillance, Epidemiology, and End Result (SEER) database. We also performed a systematic review and meta-analysis to analyze the genetic alterations of primary and secondary ATCs. From our multi-institutional database, 22 primary and 23 secondary ATCs were retrieved. We also identified 620 and 24 primary and secondary ATCs in the SEER database, respectively. Compared to primary ATCs, secondary ATCs were not statistically diff...
Source: Endocrine Pathology - September 24, 2021 Category: Pathology Source Type: research

TERT Copy Number Alterations, Promoter Mutations and Rearrangements in Adrenocortical Carcinomas
AbstractMolecular characterization of adrenocortical carcinomas (ACC) by The Cancer Genome Atlas (TCGA) has highlighted a high prevalence ofTERT alterations, which are associated with disease progression. Herein, 78 ACC were profiled using a combination of next generation sequencing (n = 76) and FISH (n = 9) to assess forTERT alterations. This data was combined with TCGA dataset (n = 91). A subset of borderline adrenocortical tumors (n = 5) and adrenocortical adenomas (n = 7) were also evaluated. The most common alteration involving theTERT gene involved...
Source: Endocrine Pathology - September 22, 2021 Category: Pathology Source Type: research

Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm
In conclusion, our findings underscored that the two neoplastic components of this Ov-MiNEN share a substantially identical molecular profile and they progress from a preexisting ovarian endometriotic lesion, in a patient with a coexisting preneoplastic proliferation of the endometrium, genotypically and phenotypically related to the ovarian neoplasm. Moreover, this study supports the inclusion of MiNEN in the spectrum ovarian and, possibly, of all gynecological NENs, among which they are currently not classified. (Source: Endocrine Pathology)
Source: Endocrine Pathology - August 3, 2021 Category: Pathology Source Type: research

High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid
In conclusion, our study reinforces the role of theDICER1 mutation in the development of pediatric thyroid tumors. Gene fusions rarely occur in pediatric follicular-patterned tumors. Mutation or gene fusion alone could not distinguish benign from malignant follicular-patterned tumors in pediatric patients. (Source: Endocrine Pathology)
Source: Endocrine Pathology - July 27, 2021 Category: Pathology Source Type: research

Pendred Syndrome with C Cell Hyperplasia
(Source: Endocrine Pathology)
Source: Endocrine Pathology - July 27, 2021 Category: Pathology Source Type: research

Reconsideration of Clinicopathologic Prognostic Factors in Pancreatic Neuroendocrine Tumors for Better Determination of Adverse Prognosis
In conclusion, threshold values of 5  cm and 10 cm for tumor size, 10% for Ki67 proliferation index, and 10/2 mm2 for mitotic count and vascular and lymphatic invasion assessed separately are potential prognostic candidates for better stratification of panNETs. (Source: Endocrine Pathology)
Source: Endocrine Pathology - July 20, 2021 Category: Pathology Source Type: research

Analyzing Genetic Differences Between Sporadic Primary and Secondary/Tertiary Hyperparathyroidism by Targeted Next-Generation Panel Sequencing
AbstractSecondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from...
Source: Endocrine Pathology - July 3, 2021 Category: Pathology Source Type: research

Co-occurrence of Pituitary Neuroendocrine Tumors (PitNETs) and Tumors of the Neurohypophysis
AbstractBetween 1996 and 2020, 12,565 cases were enrolled in the German Registry of Pituitary Tumors including 10,084 PitNETs (10,067 adenomas and 19 carcinomas obtained surgically and 193 adenomas diagnosed at autopsy) as well as 69 spindle cell tumors of the neurohypophysis (64 surgical specimens and 5 autopsies). In six patients (1 post mortem and 5 surgical specimens), PitNETs as well as posterior lobe tumors were found in the specimens. Two of the PitNETs were sparsely granulated prolactin-producing tumors, combined in one case with a granular cell tumor and in one case with a pituicytoma. One of the PitNETs revealed ...
Source: Endocrine Pathology - June 15, 2021 Category: Pathology Source Type: research

Adrenal Rests in the Uro-genital Tract of an Adult Population
AbstractEctopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approxima...
Source: Endocrine Pathology - June 7, 2021 Category: Pathology Source Type: research

Positive Correlation of Thyroid Nodule Cytology with Molecular Profiling —a Single-Center Experience
AbstractDespite several reports on the association between molecular profiling, aggressive histology, and clinical outcomes, the association between mutation expression and pre-operative cytology is yet to be demonstrated. Therefore, we performed a retrospective, single-center study, including all patients who underwent molecular profiling of thyroid nodules in Bethesda System for Reporting Thyroid Cytopathology (BSRTC) categories III to VI, between 2018 and 2019. Medical records were reviewed to collect demographics, cytology results according to BSRTC, final pathology (presence of malignancy and its type, as well as pres...
Source: Endocrine Pathology - June 4, 2021 Category: Pathology Source Type: research

Middle Ear “Adenoma”: a Neuroendocrine Tumor with Predominant L Cell Differentiation
AbstractThis morphological and immunohistochemical study demonstrates that tumors currently known as “middle ear adenomas” are truly well-differentiated epithelial neuroendocrine tumors (NETs) composed of cells comparable to normal intestinal L cells, and therefore, these tumors resemble hindgut NETs. These tumors show consistent expression of glucagon, pancreatic polypeptide, PYY, and the tran scription factor SATB2, as well as generic neuroendocrine markers and keratins. The same L cell markers are expressed by cells within the normal middle ear epithelium. These markers define a valuable immunohistochemical ...
Source: Endocrine Pathology - May 27, 2021 Category: Pathology Source Type: research

Pathogenic ATM Variant-Harbouring Well-Differentiated Aggressive Type 1 Gastric Neuroendocrine Tumour with High-grade Features (G3 NET): a New Addition to the Clinical and Pathological Spectrum of Gastric Neuroendocrine Neoplasms
We report here a patient with an aggressive well-differentiated high-grade gastric neuroendocrine tumour (gastric grade 3 NET), in a context of autoimmune gastritis. Consistent with grade 3 disease, the tumour had a Ki-67 proliferation index of 30%. Targeted next-generation sequencing identified variants of four genes, including a pathogenicATM variant underlying the differentiation and metastatic potential of the tumour. Liver metastasis was diagnosed during follow-up, and the patient died after 6 years, due to disease progression. (Source: Endocrine Pathology)
Source: Endocrine Pathology - May 21, 2021 Category: Pathology Source Type: research

Cribriform-Morular Thyroid Carcinoma Is a Distinct Thyroid Malignancy of Uncertain Cytogenesis
In this study, we reviewed the demographical, histopathological, and immunohistochemical features of the largest case series, consisting of 33 tumors. The age at time of pathological diagnosis ranged from 18 to 59 (mean 33) years, and all patients except one were female. Sixteen patients had multifocal and fifteen had unifocal disease. The status of focality was unavailable in two patients.  Tumors were well-circumscribed, ranging in size from 0.1 to 8.0 cm. The cribriform component was admixed with morulae in the majority, except seven had a cribriform-predominant architecture and two had predominantly solid gro...
Source: Endocrine Pathology - May 21, 2021 Category: Pathology Source Type: research

INSM1 Expression in Breast Neoplasms with Neuroedocrine Features
In conclusion, INSM1 is as accurate as traditional NE biomarkers to identify NE differentiation in BC. In analogy to standard NE markers, INSM1 could not distinguish NET and NEC from the other BC histotypes with NE differentiation. (Source: Endocrine Pathology)
Source: Endocrine Pathology - May 19, 2021 Category: Pathology Source Type: research

Follicular Epithelial Dysplasia as Hashimoto Thyroiditis-Related Atypia: a Series of 91 Specimens
In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma. (Source: Endocrine Pathology)
Source: Endocrine Pathology - May 15, 2021 Category: Pathology Source Type: research

Intron 4 –5 hTERT DNA Hypermethylation in Merkel Cell Carcinoma: Frequency, Association with Other Clinico-pathological Features and Prognostic Relevance
AbstractMerkel cell carcinoma (MCC) is an aggressive skin tumor with neuroendocrine differentiation, mainly affecting elderly population or immunocompromised individuals. As methylation of the human telomerase reverse transcriptase (mhTERT) has been shown to be a prognostic factor in different tumors, we investigated its role in MCC, in particular in intron 4 –5 where rs10069690 has been mapped and recognized as a cancer susceptibility locus. DNA methylation analysis ofhTERT gene was assessed retrospectively in a cohort of 69 MCC patients from the University of Bologna, University of Turin and University of Insubria....
Source: Endocrine Pathology - April 28, 2021 Category: Pathology Source Type: research

Challenges in the Diagnosis of Pituitary Neuroendocrine Tumors
AbstractDetailed analysis of cytodifferentiation and hormone production has classified pituitary neuroendocrine tumors (PitNETs) in a formal system that reflects the lineage differentiation of nontumorous adenohypophysial cells as well as subtypes of tumors that have predictive value. In addition, tumors composed of cells that lack terminal differentiation are well characterized. To comply with the proposal to create an overarching classification of neuroendocrine neoplasia, these tumors are now called PitNETs rather than adenomas. The next important step will be to relinquish the term “pituitary carcinoma” for...
Source: Endocrine Pathology - April 17, 2021 Category: Pathology Source Type: research

Challenges in High-grade Neuroendocrine Neoplasms and Mixed Neuroendocrine/Non-neuroendocrine Neoplasms
AbstractThe growth in knowledge of the pathogenesis, molecular background, and immunohistochemical profile of neuroendocrine neoplasms (NENs) has led not only to an increased awareness of these diseases but also to several changes of the nomenclature. In particular, the concept and terminology of high-grade (grade 3) NENs and mixed neoplasms have changed considerably over the last 20  years, creating some confusion among pathologists and clinicians. The aim of this review is to elucidate the diagnostic criteria, including the most important differential diagnoses of high-grade NENs and mixed neuroendocrine/non-neuroen...
Source: Endocrine Pathology - March 31, 2021 Category: Pathology Source Type: research

Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry
AbstractAbdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although few pathologists outside of endocrine tertiary centers will ever diagnose such a lesion, the tumors are well known through the medical community —possible due to a combination of the sheer rarity, their often-spectacular presentation due to excess catecholamine secretion as well as their unrivaled coupling to constitutional susceptibility gene mutations and hereditary syndromes. All PPGLs are thought to harbor malignant potential, and ther efor...
Source: Endocrine Pathology - March 25, 2021 Category: Pathology Source Type: research

Progression of Papillary Thyroid Carcinoma to Anaplastic Carcinoma in Metastatic Lymph Nodes: Solid/Insular Growth and Hobnail Cell Change in Lymph Nodes Are Predictors of Subsequent Anaplastic Transformation
AbstractMost anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after  ≥ 10 years of follow-up served as ...
Source: Endocrine Pathology - March 24, 2021 Category: Pathology Source Type: research

PD-L1 Is Preferentially Expressed in PIT-1 Positive Pituitary Neuroendocrine Tumours
AbstractPituitary neuroendocrine tumours (PitNETs) cause lifelong morbidity, some requiring extensive surgical intervention, radiotherapy, or chemotherapy. A small percentage still cause debilitating disease, resistant to standard treatments, and may benefit from novel therapies. We assessed PD-L1 expression in a large cohort of PitNETs to investigate whether immunotherapy could represent a rational therapeutic choice. Unselected PitNETs undergoing surgical resection were reclassified according to the WHO 2017 system and underwent PD-L1 immunohistochemistry (clone SP263) in tissue microarray format. Membranous expression w...
Source: Endocrine Pathology - March 11, 2021 Category: Pathology Source Type: research

Neuroendocrine Tumors of the Thyroid and Their Mimics
AbstractThis paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary thyroid carcinoma. A brief overview of the understanding of this tumor's identification as a lesion of C cells and its familial and syndromic associations will be presented. Then, a discussion of the various mimics of medullary carcinoma will be given with an approach to the types of tests that can be done to arrive at a correct diagnostic conclusion. This review will focus on practical “tips” for the practicing pathologist. (Source: Endocrine Pathology)
Source: Endocrine Pathology - March 9, 2021 Category: Pathology Source Type: research

The Pangenomic Classification of Pituitary Neuroendocrine Tumors: Quality Histopathology is Required for Accurate Translational Research
(Source: Endocrine Pathology)
Source: Endocrine Pathology - March 3, 2021 Category: Pathology Source Type: research

Molecular Pathology of Non-familial Follicular Epithelial –Derived Thyroid Cancer in Adults: From RAS/BRAF -like Tumor Designations to Molecular Risk Stratification
AbstractThis review addresses the impact of molecular alterations on the diagnosis and prognosis of differentiated thyroid carcinoma (DTC), including papillary, follicular, and well-differentiated carcinoma NOS, as well as oncocytic neoplasms. The molecular characterization of DTC is based upon the well-established dichotomy ofBRAF-like andRAS-like designations, together with a remaining third group, less homogeneous, composed of non-BRAF-/non-RAS-like tumors. The role ofBRAF V600E mutation in risk stratification is discussed in the clinico-pathological context, namely, staging and invasive features of classic papillary th...
Source: Endocrine Pathology - March 2, 2021 Category: Pathology Source Type: research

Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?
AbstractThoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone...
Source: Endocrine Pathology - February 27, 2021 Category: Pathology Source Type: research

Special Issue on Molecular Pathology of Endocrine Neoplasms: Understanding the Basis of Endocrine Pathology Practice
(Source: Endocrine Pathology)
Source: Endocrine Pathology - February 23, 2021 Category: Pathology Source Type: research

Molecular Pathology of Poorly Differentiated and Anaplastic Thyroid Cancer: What Do Pathologists Need to Know
AbstractThe molecular characterization of poorly and anaplastic thyroid carcinomas has been greatly improved in the last years following the advent of high throughput technologies. However, with special reference to genomic data, the prevalence of reported alterations is partly affected by classification criteria. The impact of molecular pathology in these tumors is multifaceted and bears diagnostic, prognostic, and predictive implications although its use in the clinical practice is not completely assessed. Genomic profiling data claim that genetic alterations in poorly differentiated and anaplastic thyroid carcinomas inc...
Source: Endocrine Pathology - February 4, 2021 Category: Pathology Source Type: research

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 ...
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 carcinoma...
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 spora...
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 (
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
AbstractIn the gastro-entero-pancreatic (GEP) tract, neuroendocrine neoplasms (NENs) include well differentiated neuroendocrine tumors (NETs) and high-grade NE carcinomas (NECs), which are thought to make up separate and mutually exclusive tumor entities. Little is known, however, as to whether there may be any pathogenetic link between them. Clustering analysis of a 10-gene panel generated from a previously reported next-generation sequencing analysis on 48 GEP-NENs with clinical annotations was used in the study. Unsupervised cluster analysis showed three histology-independent clusters, namely, C1, C2, and C3, which acco...
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. Co...
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 rout...
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 h...
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,...
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 r...
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 spat...
Source: Endocrine Pathology - October 16, 2020 Category: Pathology Source Type: research

Loss of 5-Hydroxymethylcytosine is an Epigenetic Hallmark of Thyroid Carcinomas with TERT Promoter Mutations
AbstractEpigenetic dysregulation is a hallmark of cancer, and aberrant methylation of cytosine residues plays a crucial role in abnormal gene expression in cancer cells. Recent studies demonstrate that 5-hydroxymethylcytosine (5-hmC) generated through 5-methylcytosine (5-mC) oxidation is significantly depleted in various cancers. However, whether 5-hmC levels change during the stepwise progression of thyroid carcinoma and the mechanisms underlying this effect remain unknown. The aims of this study were (i) to assess 5-hmC levels in normal and cancerous thyroid tissues, and (ii) identify clinicopathologic and genetic factor...
Source: Endocrine Pathology - October 15, 2020 Category: Pathology Source Type: research

Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?
In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nin...
Source: Endocrine Pathology - September 22, 2020 Category: Pathology Source Type: research

Detection of NTRK1/3 Rearrangements in Papillary Thyroid Carcinoma Using Immunohistochemistry, Fluorescent In Situ Hybridization, and Next-Generation Sequencing
In conclusion,NTRK1/3-rearranged PTC shared some unique morphologic features. Pan-TRK IHC showed high specificity and moderate sensitivity forNTRK1/3-rearranged PTC and should be interpreted with caution due to staining heterogeneity. Based on the above findings, we propose an algorithm integrating morphology, IHC, and molecular testing to detectNTRK1/3 rearrangements in PTC. (Source: Endocrine Pathology)
Source: Endocrine Pathology - September 2, 2020 Category: Pathology Source Type: research

Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors
In conclusion, ODF1 was firstly identified as a novel marker for NENs, especially for NETs in the gastrointestinal tract. The expression mechanism and clinical significance of ODF1 in NENs needed fur ther study. (Source: Endocrine Pathology)
Source: Endocrine Pathology - August 31, 2020 Category: Pathology Source Type: research

Effects of CAPTEM (Capecitabine and Temozolomide) on a Corticotroph Carcinoma and an Aggressive Corticotroph Tumor
AbstractCorticotroph carcinomas and aggressive corticotroph tumors can be resistant to conventional therapy, including surgery, radiotherapy, and medical treatment. Recent evidence suggests that temozolomide (an oral alkylating agent) administered with capecitabine (pro-drug of 5-fluorouracil) may improve progression-free survival in patients with high-risk corticotroph tumors and carcinomas. This led to the use of capecitabine and temozolomide (CAPTEM) in two patients, one with a corticotroph carcinoma and the other with an aggressive corticotroph tumor, as well the in vitro analysis of capecitabine and 5-fluorouracil on ...
Source: Endocrine Pathology - August 23, 2020 Category: Pathology Source Type: research