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

Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin
We report the clinical usage of the “second-generation” proteins ISL LIM homeobox 1 (ISL1), INSM transcriptional repressor 1 (INSM1), and secretagogin (SECG) as immunohistochemical markers of neuroendocrine differentiation since their introduction in clinical routine and compare the results with the established proteins chromogran in A (CGA) and synaptophysin (SYP). In total, 161 tumors, including 139 NENs and 22 “non-NENs” (unrelated tumors with an initial suspicion of NEN), were informatively stained for ISL1, and subsets were also interrogated for INSM1 and/or SECG. Diffuse or focal positive immu...
Source: Endocrine Pathology - August 18, 2020 Category: Pathology Source Type: research

Structure, Function, and Morphology in the Classification of Pituitary Neuroendocrine Tumors: the Importance of Routine Analysis of Pituitary Transcription Factors
AbstractThe traditional approach to the diagnosis of primary adenohypophyseal cell proliferations uses hormone immunohistochemistry to classify pituitary neuroendocrine tumors (PitNETs). The routine application of immunolocalization of pituitary transcription factors (SF1, PIT1, TPIT, ER α, and recently GATA3) along with adenohypophyseal hormones has taught us critical lessons that are discussed in this communication. We point out that appropriate patient care requires accurate diagnosis and is critical in the era of precision medicine. A misdiagnosis can result in far greater heal th care costs than the cost of accu...
Source: Endocrine Pathology - August 18, 2020 Category: Pathology Source Type: research

Impact of Molecular Testing on the Management of Indeterminate Thyroid Nodules Among Western and Asian Countries: a Systematic Review and Meta-analysis
This study examined the influence of molecular tests on the treatment of indeterminate nodules, particularly the differences between Western and Asian countries. Electronic databases including PubMed and Web of Science were searched for relevant articles from 2010 to March 2019. We computed meta-analysis of proportion and their 95% confidence intervals (CIs) utilizing the random-effect model. We used independent samplest test to compare the resection rate (RR), rate of malignancy (ROM), rate of preoperative molecular testing (RMT), and rate of positive test (RP) between subgroups. We included a total of 34 studies with 797...
Source: Endocrine Pathology - August 6, 2020 Category: Pathology Source Type: research

Long Noncoding RNA Expression in Adrenal Cortical Neoplasms
AbstractLong noncoding RNAs (lncRNAs) consist of nucleic acid molecules that are greater than 200 nucleotides in length and they do not code for specific proteins. A growing body of evidence indicates that these lncRNAs have important roles in tumorigenesis. Separating adrenal cortical adenomas from carcinomas is often a difficult problem for the surgical pathologist. This is especially true when only small needle biopsies are available for examination. We used in situ hybridization (ISH) analysis to study normal adrenal cortical tissues and adrenal cortical tumors to determine the role of specific lncRNAs in tumor develop...
Source: Endocrine Pathology - July 27, 2020 Category: Pathology Source Type: research

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature
AbstractThe exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic r...
Source: Endocrine Pathology - July 21, 2020 Category: Pathology Source Type: research

Correlation of ThyroSeq Results with Surgical Histopathology in Cytologically Indeterminate Thyroid Nodules
AbstractThe ThyroSeq next-generation sequencing test refines the risk of malignancy in cytologically indeterminate thyroid nodules. Specific genetic alterations have distinct cancer probabilities and clinical phenotypes. There is limited data on the association between specific genetic alterations and histopathologic features. The aim of this study was to evaluate specific ThyroSeq alterations in prognosticating high-risk histopathologic characteristics. We performed a retrospective single-institution study of all patients diagnosed with indeterminate thyroid nodules (May 2016 –December 2019) who had a mutation ident...
Source: Endocrine Pathology - July 14, 2020 Category: Pathology Source Type: research

Pitfalls in Challenging Thyroid Tumors: Emphasis on Differential Diagnosis and Ancillary Biomarkers
AbstractThyroid pathology encompasses a heterogenous group of clinicopathological entities including rare and diagnostically challenging neoplasms. The review is focused on morphological, immunohistochemical, and molecular features of rare thyroid neoplasms that can pose diagnostic problems. The tumors are organized based on growth patterns including thyroid neoplasms with predominantly papillary, follicular, solid, and spindle cell growth pattern, as well as neoplasms with distinct cytological characteristics. A special section is also dedicated to rare thyroid tumors with peculiar patterns including thyroid carcinoma wit...
Source: Endocrine Pathology - July 5, 2020 Category: Pathology Source Type: research

Mixed Sparsely Granulated Lactotroph and Densely Granulated Somatotroph Pituitary Neuroendocrine Tumor Expands the Spectrum of Neuroendocrine Neoplasms in Ovarian Teratomas: the Role of Pituitary Neuroendocrine Cell Lineage Biomarkers
(Source: Endocrine Pathology)
Source: Endocrine Pathology - July 5, 2020 Category: Pathology Source Type: research

Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone –Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases
AbstractSox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The ...
Source: Endocrine Pathology - July 5, 2020 Category: Pathology Source Type: research

Exploring the Inter-observer Agreement Among the Members of the Italian Consensus for the Classification and Reporting of Thyroid Cytology
In conclusion, the present study confirms the reliability of ICCRTC. These data represent a reference for cytopathologists using this system and are useful for the practice of clinicians and surgeons. (Source: Endocrine Pathology)
Source: Endocrine Pathology - July 2, 2020 Category: Pathology Source Type: research

On the Endless Dilemma of Neuroendocrine Neoplasms of the Breast: a Journey Through Concepts and Entities
AbstractNeuroendocrine differentiation in breast carcinomas has been a matter of discussion since it was first described almost 60  years ago. Indeed, so-called neuroendocrine neoplasms of the breast (Br-NENs) are a less well-defined group of neoplasms than analogous entities in other anatomic sites, such as the lung and the gastroenteropancreatic (GEP) tract. Pure neuroendocrine phenotype is extremely rare, whereas the expres sion of neuroendocrine markers in usual breast carcinomas, both of special and of non-special type, without evident neuroendocrine morphology, is more common. In this context, the diagnostic cri...
Source: Endocrine Pathology - July 1, 2020 Category: Pathology Source Type: research

Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas
In this study, we compared clinical, histological, and genetic characteristics of ITTCs and TCs. We collected 9 ITTCs and 8 TCs with their clinicopathological profiles. Immunohistochemistry for CD5, p63, CD117/c-KIT, Ki-67, p53, TTF-1, thyroglobulin, PAX8, EGFR, and PD-L1/CD274 plus in situ hybridization for EBER was performed. We further investigated mutation status ofKIT,EGFR,BRAF, andTERT promoter using Sanger sequencing. In our study, ITTCs affected significantly younger patients than TCs. After a mean follow-up of 86  months, all patients with ITTC were alive, while two patients with TC had died. Immunohistochemi...
Source: Endocrine Pathology - June 26, 2020 Category: Pathology Source Type: research

Immunohistochemical Staining for SOX10 and SDHB in SDH-Deficient Paragangliomas Indicates that Sustentacular Cells Are Not Neoplastic
(Source: Endocrine Pathology)
Source: Endocrine Pathology - June 18, 2020 Category: Pathology Source Type: research

Images in Endocrine Pathology: Progressive Loss of Sustentacular Cells in a Case of Recurrent Jugulotympanic Paraganglioma over a Span of 5 years
(Source: Endocrine Pathology)
Source: Endocrine Pathology - June 15, 2020 Category: Pathology Source Type: research

High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms
AbstractDysregulations of the NEK2 and PIM1-3 kinase signaling axes have been implicated in the pathogenesis of several cancers, including those with a neuroendocrine phenotype. However, their impact on bronchopulmonary neuroendocrine neoplasms (BP-NENs) has not been investigated. The aim of this pilot study was to determine mRNA and protein levels of NEK2, PIM1, and PIM3 in a group of 49 patients with BP-NENs: 11 typical carcinoids, 5 atypical carcinoids, 11 large cell neuroendocrine carcinomas, 22 small cell lung carcinomas (SCLC). The expression was measured using TaqMan-based RT-PCR and immunohistochemistry. NEK2 and P...
Source: Endocrine Pathology - June 4, 2020 Category: Pathology Source Type: research

Morphologic Variants of Pancreatic Neuroendocrine Tumors: Clinicopathologic Analysis and Prognostic Stratification
AbstractBetter prognostication/stratification of pancreatic neuroendocrine tumors (PanNETs) is needed. In this detailed morpheomic study of 163 resected PanNETs, 11 unusual variants, some of which were not previously recognized, and others scarcely documented in the literature, were identified, and their pathologic characteristics were further analyzed. By behavior and clinicopathologic associations, these variants could be grouped into three prognostically different categories. I.  More aggressive (20%). Included in this group were the variants that in average showed higher grade and stage and adverse outcome includi...
Source: Endocrine Pathology - May 31, 2020 Category: Pathology Source Type: research

Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma
AbstractThe expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performe...
Source: Endocrine Pathology - May 28, 2020 Category: Pathology Source Type: research

Hereditary Parathyroid Disease: Sometimes Pathologists Do Not Know What They Are Missing
AbstractParathyroid gland excision specimens are common and sometimes underestimated cases that many surgical pathologists encounter regularly. In the vast majority of cases, these will be spot diagnoses of sporadic primary parathyroid adenomas or, perhaps, hyperplasias commonly in the setting of renal failure. However, a small but significant number of parathyroid gland excisions may be due to heritable disease. In most cases, hereditary disease is suspected by the referring clinicians. Nevertheless, a subset of these are undetected which is significant, particularly in the setting of the multiple endocrine neoplasia (MEN...
Source: Endocrine Pathology - May 27, 2020 Category: Pathology Source Type: research

Histopathologic Features and Clinical Outcome of Anaplastic Thyroid Carcinoma with a Minor Anaplastic Component
AbstractAlthough prior studies have reported that patients with anaplastic thyroid carcinoma (ATC) with a focal anaplastic component may have a prolonged survival compared to other ATC patients, the outcome data are limited. We evaluated a cohort of ATC resected between 2003 and 2018. Tumor slides were reviewed to confirm the diagnosis and to identify cases with a minor ATC component (defined as comprising
Source: Endocrine Pathology - May 21, 2020 Category: Pathology Source Type: research

Amyloid-Rich Pancreatic Neuroendocrine Tumors: a Potential Diagnostic Pitfall in Endoscopic Ultrasound –Guided Fine Needle Aspiration Cytology (EUS-FNAC)
We describe the diagnostic clues of the amyloid-rich variant of PanNETs in endoscopic ultrasound (EUS) –guided fine needle aspiration cytology (EUS-FNAC). Three cases of PanNETs with an amyloid-rich stromal component were retrieved and retrospectively reviewed. For every case, the pancreatic lesion was investigated by a EUS-FNAC procedure. The final diagnosis was supported by immunocytochemistry an d Congo red staining. All cases had similar EUS-FNAC features: neoplastic cells were entrapped in an eosinophilic, homogeneous dense and amorphous matrix. The neuroendocrine nature was confirmed by immunoexpression of syna...
Source: Endocrine Pathology - May 11, 2020 Category: Pathology Source Type: research

Long Non-coding RNAs in Pulmonary Neuroendocrine Neoplasms
In this study, INSM1 expression was detected by immunohistochemistry in greater than 94% of pulmonary NENs, indicating that it is a highly sensitive marker of pulmonary NENs and is useful to detect poorly differentiated pulmonary NECs. Although there are well-established morphological and immunohistologic criteria to diagnose pulmonary NENs, there is no universal consensus regarding prognostic markers of pulmonary NENs. Studies have shown that non –small cell lung cancers express long non-coding RNAs (lncRNAs), which regulate gene expression, epithelial-to-mesenchymal transition, and carcinogenesis. We characterized ...
Source: Endocrine Pathology - May 8, 2020 Category: Pathology Source Type: research

Long Survival and Prolonged Remission after Surgery and Chemotherapy in a Metastatic Mismatch Repair Deficient Pancreatic Neuroendocrine Carcinoma with MLH1/PMS2 Immunodeficiency and Minimal Microsatellite Shift
We describe a 62-year-old patient who underwent pancreaticoduodenectomy for a NEC located in the pancreatic head, with peripancreatic lymph node metastases. Tumor necrosis was prominent and the Ki67 proliferative index was 60%. One year after the diagnosis, the patient experienced recurrence with a left supraclavicular lymph node metastasis, which was surgically removed, followed by standard cisplatin-etoposide chemotherapy. Neoplastic cells showed combined loss of expression of MLH1 and PMS2 in both primary tumor and lymph node metastasis. Microsatellite instability (MSI) test using a mononucleotide repeats pentaplex PCR ...
Source: Endocrine Pathology - May 8, 2020 Category: Pathology Source Type: research

Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma
AbstractMetabolic reprogramming is a cellular process contributing to carcinogenesis. However, it remains poorly understood in adrenal cortical carcinoma (ACC), an aggressive malignancy with overall poor prognosis and limited therapeutic options. We characterized the metabolic phenotype of ACC, by examining the immunoprofile of key proteins involved in glucose metabolism, hexokinase (HK1), pyruvate kinase (PKM1, PKM2), succinate dehydrogenase (SDHB), and phospho-S6 ribosomal protein (pS6), in a tissue microarray of 137 adrenal cortical tissue samples. Protein expression was compared between ACC (n = 42), adrena...
Source: Endocrine Pathology - May 3, 2020 Category: Pathology Source Type: research

Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT)
AbstractPeptide Receptor Radionuclide Therapy (PRRT) is an emerging therapeutic option for pancreatic neuroendocrine tumors (PanNETs). A possible role for PRRT as a neoadjuvant agent is still largely undetermined, explored only in case reports or small case series. Likewise, the histopathological and immunophenotypic changes induced by PRRT are poorly characterized. In the present study, 24 patients who underwent neoadjuvant PRRT on the basis of their disease ’s characteristics were retrospectively matched with 24 patients who underwent upfront surgery. A comprehensive morphological and immunohistochemical evaluation...
Source: Endocrine Pathology - May 1, 2020 Category: Pathology Source Type: research

The Diagnostic Dilemma of GATA3 Immunohistochemistry in Pheochromocytoma and Paraganglioma
In conclusions, immunohistochemistry for GATA3 in PCCs/PGLs requires stronger antigen retrieval than that in mammary and urinary carcinomas. This finding is especially important to consider if GATA3 is applied for the differential diagnosis of PGLs in unusual sites as supplemental data to the expression of catecholamine-synthesizing enzymes. (Source: Endocrine Pathology)
Source: Endocrine Pathology - April 16, 2020 Category: Pathology Source Type: research

Did Introducing a New Category of Thyroid Tumors (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Decrease the Risk of Malignancy for the Diagnostic Categories in the Bethesda System for Reporting Thyroid Cytopathology?
AbstractIn 2016, Nikiforov et al. (JAMA Oncol 2:1023 –1029, 2016) proposed replacing the term “non-invasive encapsulated follicular variant of papillary thyroid carcinoma” (FVPTC) with the term “non-invasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP). In 2018, to avoid the misdiagnosis of papillary thyroid canc er as NIFTP, the authors proposed changes to the criteria for NIFTP classification. Some previous studies evaluated the impact of NIFTP on the risk of malignancy (ROM) in the fine-needle aspiration cytology (FNAC) diagnostic categories according to the Bet...
Source: Endocrine Pathology - March 30, 2020 Category: Pathology Source Type: research

Histopathologic Assessment of Capsular Invasion in Follicular Thyroid Neoplasms —an Observer Variation Study
In conclusion, this study revealed considerable interobserver variation in the evaluation of capsular invasion, especially in follicular neoplasms with questionable invasion. (Source: Endocrine Pathology)
Source: Endocrine Pathology - March 30, 2020 Category: Pathology Source Type: research

Thyroid Tumor Capsular Invasion: the Bottom Line or Much Ado About Nothing?
(Source: Endocrine Pathology)
Source: Endocrine Pathology - March 23, 2020 Category: Pathology Source Type: research