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

Lipoadenoma of the Parathyroid Gland: Characterization of an Institutional Series Spanning 28  Years
AbstractParathyroid lipoadenomas (PLAs) are rare tumors, and case descriptions are limited,  50% fat on histologic examination with preoperative evidence of primary hyperparathyroidism (PHPT). A total of 8 bona fide PLA cases and 2 equivocal PLAs (close to 50% fat) were included. As approximately 4000 conventional parathyroid adenomas were diagnosed at our department during the same time interval, the prevalence of PLA was 0.20%. PLA patients were predominately female (63%) and presented with classical PHPT-related symptoms. Majority of cases were successfully located preoperatively and had an average tumor weight o...
Source: Endocrine Pathology - March 18, 2020 Category: Pathology Source Type: research

Utility of GATA-3 Expression in the Analysis of Pituitary Neuroendocrine Tumour (PitNET) Transcription Factors
AbstractWith the introduction of the WHO 2017 classification of endocrine neoplasms, the use of the pituitary transcription factors PIT-1, Tpit and SF-1 has become the standard of care. However, immunohistochemistry for these transcription factors is not available in all institutions, and their reliability has been questioned. We read with interest the findings of Mete et al. that GATA-3 expression was detected in some pituitary neuroendocrine tumours (PitNET). We therefore sort to validate this in our large cohort of PitNETs. We searched the database of Royal North Shore Hospital for PitNETs between 1998 and 2012, constru...
Source: Endocrine Pathology - March 18, 2020 Category: Pathology Source Type: research

Book Review on “The Survival Guide to Endocrine Pathology (Pathology Survival Guides Series 1, Volume 4) by Sylvia L. Asa, MD, PhD”
(Source: Endocrine Pathology)
Source: Endocrine Pathology - March 18, 2020 Category: Pathology Source Type: research

Frequency and Role of CDKN2A Deletion in High-Risk Pituitary Neuroendocrine Tumors
AbstractThe underlying mechanisms of aggressive pituitary neuroendocrine tumors (pitNETs) are still unclear. The p16 protein, encoded by theCDKN2A tumor suppressor gene on chromosome 9p21, is commonly reported to be lost in numerous types of cancer. For this reason, this study examined to examine the status of homozygous deletion ofCDKN2A in high-risk pitNETs. Thirty-eight high-risk pitNETs (30 male, 8 female) were analyzed forCDKN2A deletion by fluorescent in situ hybridization (FISH). Demographic characteristics such as sex, patient age at operation, and sellar magnetic resonance imaging findings including tumor size and...
Source: Endocrine Pathology - March 8, 2020 Category: Pathology Source Type: research

Practice Paradigms Before and After Introduction of the Diagnosis-Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): an Institutional Experience
AbstractThe recently adopted terminology of “Noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) reflects the indolent behavior of these tumors. In contrast to conventional papillary thyroid carcinomas, NIFTP can be managed conservatively. The purpose of this study was to investigate changes in surgical a nd pathologic practice patterns at our institution since the introduction of the NIFTP diagnosis in 2016. A retrospective analysis of all thyroid specimens received in our laboratory between January 2015 and April 2017 was performed. The final cohort consisted of 1508 thyroide...
Source: Endocrine Pathology - March 6, 2020 Category: Pathology Source Type: research

Images in Endocrine Pathology: High-Grade Intrathyroidal Parathyroid Carcinoma with Crooke ’s Hyalinization
(Source: Endocrine Pathology)
Source: Endocrine Pathology - March 6, 2020 Category: Pathology Source Type: research

Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas
AbstractNeuroendocrine neoplasms comprise a heterogeneous group of tumors, categorized into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) depending on tumor differentiation. NECs and high-grade NETs (G3) confer a poor prognosis, demanding novel treatment strategies such as immune checkpoint inhibition in tumors with microsatellite instability (MSI). To study any possible intratumoral heterogeneity of MSI, a tissue microarray (TMA) containing 199 NETs and 40 NECs was constructed to screen for MSI using immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Four case...
Source: Endocrine Pathology - March 5, 2020 Category: Pathology Source Type: research

Immunohistochemical Profile and 47-Gene Next-Generation Sequencing (NGS) Solid Tumor Panel Analysis of a Series of 13 Strumal Carcinoids
AbstractStrumal carcinoid is an extraordinary rare tumor of the ovary consisting of thyroid tissue intermixed with neuroendocrine tumor component. The cellular origin of strumal carcinoids has been an area of debate. There is also little data on detailed immunohistochemical and molecular characteristics of these neoplasms. For this reason, this series investigated the characteristics of a series of 13 strumal carcinoids using immunohistochemical markers and a 47-gene next-generation sequencing (NGS) solid tumor panel analysis. Both cellular components showed thyroglobulin expression in all tumors. TTF-1 expression was note...
Source: Endocrine Pathology - March 1, 2020 Category: Pathology Source Type: research

Alternative Lengthening of Telomeres and Differential Expression of Endocrine Transcription Factors Distinguish Metastatic and Non-metastatic Insulinomas
AbstractInsulin-producing pancreatic neuroendocrine tumors (PanNETs)/insulinomas are generally considered to be indolent tumors with an excellent prognosis after complete resection. However, some insulinomas have a poor prognosis due to relapses and metastatic disease. Recently, studies in non-functional PanNETs indicated that behavior can be stratified according to alpha- and beta-cell differentiation, as defined by expression of the transcription factors ARX and PDX1, respectively. It is unknown whether similar mechanisms play a role in insulinomas. Therefore, we determined ARX and PDX1 expression in a cohort of 35 spora...
Source: Endocrine Pathology - February 25, 2020 Category: Pathology Source Type: research

Message from the New Editor-in-Chief of Endocrine Pathology
(Source: Endocrine Pathology)
Source: Endocrine Pathology - February 14, 2020 Category: Pathology Source Type: research

Germline Mutations in Familial Papillary Thyroid Cancer
In this study, the genetic basis of hereditary PTC in three Brazilian families was investigated. Whole exom e sequencing (WES) was carried out for probands in each family, and validated, pathogenic/likely pathogenic sequence variants (P/LPSVs) were genotyped in additional family members to establish their putative pathogenic role. Overall, seven P/LPSVs in seven novel genes were detected: p.D283N*ANXA3, p.Y157S*NTN4, p.G172W*SERPINA1, p.G188S*FKBP10, p.R937C*PLEKHG5, p.L32Q*P2RX5, and p.Q76*SAPCD1. These results indicate that these novel genes are seemingly associated with hereditary PTC, but extension and validation in ot...
Source: Endocrine Pathology - February 7, 2020 Category: Pathology Source Type: research

Metastatic Anaplastic Thyroid Carcinoma in Complete Remission: Morphological, Molecular, and Clinical Work-Up of a Rare Case
We describe a 64-year-old male who developed a rapidly growing mass in the left thyroid lobe. A fine-needle aspiration biopsy (FNAB) was consistent with ATC, and the patient underwent preoperative combined chemo- and radiotherapy followed by a hemithyroidectomy. The ensuing histopathological investigation was consistent with ATC adjoined by an oxyphilic well-differentiated lesion, likely a H ürthle cell carcinoma. Tumor margins were negative, and no extrathyroidal extension was noted. Focused next-generation sequencing analysis of the primary tumor tissue identified aTP53 gene mutation but could not identify any poten...
Source: Endocrine Pathology - February 2, 2020 Category: Pathology Source Type: research

Gallbladder Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN) Arising in Intracholecystic Papillary Neoplasm: Clinicopathologic and Molecular Analysis of a Case and Review of the Literature
We describe the clinicopathologic and molecular features of a MiNEN composed of ICPN, adenocarcinoma, and NEC. A 66-year-old woman presented with severe abdominal pain. She underwent radical cholecystectomy and an intracholecystic mass was found. Histologically, it was composed of ICPN associated with adenocarcinoma and large cell neuroendocrine carcinoma (LCNEC). The three components were positive for DNA repair proteins and p53. EMA was positive in the ICPN and adenocarcinoma components, while it was negative in the LCNEC. Heterogeneous expression of Muc5AC, cytokeratin 20, and CDX2 was only observed in the ICPN componen...
Source: Endocrine Pathology - January 23, 2020 Category: Pathology Source Type: research

Testing for Afirma in Thyroid Nodules with High-Risk Indeterminate Cytology (TIR3B): First Italian Experience
We described the first Italian experience with Afirma tests in a single Italian institution and assessed the performance of the Afirma test in TIR3B. Moreover, this is a preliminary study to assess the patient response to the offer of Afirma testing. The Afirma test was proposed to 67 patients with thyroid nodules that had yielded TIR3B cytology. Fifty-one patients (76.1%) chose the Afirma test, 25/51 underwent the test but the remaining 26 did not because of cost. A total of 41/67 (61.2%) patients underwent surgery, and 22/41 (53.7%) nodules were carcinomas. Of the 25 tested by Afirma, 9 (36%) were classified as Afirma-su...
Source: Endocrine Pathology - January 19, 2020 Category: Pathology Source Type: research

Do You Know the Details of Your PAX8 Antibody? Monoclonal PAX8 (MRQ-50) Is Not Expressed in a Series of 45 Medullary Thyroid Carcinomas
AbstractMedullary thyroid carcinomas display cytologic and architectural features that can simulate various primary and metastatic neoplasms. PAX8 immunoexpression in neuroendocrine neoplasms yielded antibody-dependent findings. Since the data regarding the expression profile of monoclonal PAX8 (MRQ-50) antibody is limited in large series of medullary thyroid carcinomas, this study investigated the expression profile of PAX8 (MRQ-50) in a series of 45 medullary thyroid carcinomas. PAX8 (MRQ-50) expression was noted in the thyroid follicular epithelial cells surrounding the tumor and was negative in all medullary thyroid ca...
Source: Endocrine Pathology - January 6, 2020 Category: Pathology Source Type: research

Risk of Malignancy (ROM) of Thyroid FNA Diagnosed as Suspicious for Malignancy or Malignant: an Institutional Experience with Systematic Review and Meta-Analysis of Literature
In conclusion, these new findings should prompt the guidelines board to fully revise the estimated ROM of SFM category. Clinical thyroidologists and thyroid surgeons should be aware of these data and the patients with SFM should be informed of their ROM. (Source: Endocrine Pathology)
Source: Endocrine Pathology - January 1, 2020 Category: Pathology Source Type: research