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 criteri...
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. Immunohistochemistry...
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
In conclusion, PanNETs display various morphologic patterns that are not only challenging and important diagnostically but appear to have biologic significance. Tumors with more diffuse growth of cells with nucleoli and abundant cytoplasm and/or discohesion (oncocytic, hepatoid, lipid-rich, plasmacytoid PanNETs), provisionally termed “metabolic cell phenotype,” show aggressive characteristics and are an independent determinant of adverse outcome and thus may require closer post-surgical follow-up, whereas variants with more degenerative or mature features (ductuloinsular, pleomorphic, paraganglioma-like) appear to be m...
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
In conclusion, the difference in overall survival between ATC groups in our cohort was not significant; however, this could be due to the small cohort size or due to characteristics of our group with a minor ATC component; that is, no tumors in this group were limited to the thyroid (stage IVA), resectability with negative margins was infrequent, and 38% of this group had distant metastases at diagnosis (stage IVC). (Source: Endocrine Pathology)
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 synaptop...
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 expr...
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), adrenal cortica...
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 was...
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