Endocrine Pathology最新文献

{"title":"Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms.","authors":"Jiri Soukup, Monika Manethova, Vaclav Stejskal, Marie Novakova, Jaroslava Duskova, Helena Hornychova, Maria Hacova, Iva Staniczkova-Zambo, Tomas Zelinka, Mikulas Kosak, Tomas Cesak, David Netuka, Ales Ryska, Filip Gabalec","doi":"10.1007/s12022-024-09803-6","DOIUrl":"10.1007/s12022-024-09803-6","url":null,"abstract":"<p><p>Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"14-24"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms.","authors":"Sule Canberk, João Gonçalves, Elisabete Rios, Antónia A Povoa, Ebru Tastekin, Manuel Sobrinho-Simões, Aysun Uguz, Ozlem Aydin, Umit Ince, Paula Soares, Valdemar Máximo","doi":"10.1007/s12022-024-09800-9","DOIUrl":"10.1007/s12022-024-09800-9","url":null,"abstract":"<p><p>Cytosine modifications at the 5-carbon position play a critical role in gene expression regulation and have been implicated in cancer development. 5-Hydroxymethylcytosine (5hmC), arising from 5-methylcytosine (5-mC) oxidation, has shown promise as a potential malignancy marker due to its depletion in various human cancers. However, its significance in thyroid tumors remains underexplored, primarily due to limited data. In our study, we evaluated 5hmC expression levels by immunohistochemistry in a cohort of 318 thyroid tumors. Our analysis revealed significant correlations between 5hmC staining extension scores and nodule size, vascular invasion, and oncocytic morphology. Nuclear 5hmC staining intensity demonstrated associations with focality, capsule status, extrathyroidal extension, vascular invasion, and oncocytic morphology. Follicular/oncocytic adenomas exhibited higher 5hmC expression than uncertain malignant potential (UMP) or noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as malignant neoplasms, including papillary thyroid carcinomas (PTCs), oncocytic carcinomas (OCAs), follicular thyroid carcinomas (FTCs), and invasive encapsulated follicular variants of PTC (IEFV-PTC). TERT promoter mutation cases showed notably lower values for the 5hmC expression, while RAS (H, N, or K) mutations, particularly HRAS mutations, were associated with higher 5hmC expression. Additionally, we identified, for the first time, a significant link between 5hmC expression and oncocytic morphology. However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"25-39"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Multiglandular Parathyroid Disease in the Setting of Pompe Disease.","authors":"Meryl Nath, Rumeal D Whaley, William Sukov, Lori A Erickson","doi":"10.1007/s12022-024-09805-4","DOIUrl":"10.1007/s12022-024-09805-4","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"88-90"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More.","authors":"Merve Bagıs, Nuray Can, Necdet Sut, Ebru Tastekin, Ezgi Genc Erdogan, Buket Yilmaz Bulbul, Yavuz Atakan Sezer, Osman Kula, Elif Mercan Demirtas, Inci Usta","doi":"10.1007/s12022-024-09797-1","DOIUrl":"10.1007/s12022-024-09797-1","url":null,"abstract":"<p><p>Significant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS \"nuclear\" and AUS \"other\" is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely \"high-risk group\" than the group including other subcategories, namely \"low-risk group\" (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"51-76"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not All Parafibromin Deficiency Relates to Parathyroid Carcinoma: The Role of Morphological Assessment.","authors":"C Christofer Juhlin","doi":"10.1007/s12022-024-09804-5","DOIUrl":"10.1007/s12022-024-09804-5","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"84-87"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence Detected the Relationship Between Nuclear Morphological Features and Molecular Abnormalities of Papillary Thyroid Carcinoma","authors":"Toui Nishikawa, Ibu Matsuzaki, Ayata Takahashi, Iwamoto Ryuta, Fidele Yambayamba Musangile, Kanako Sagan, Mizuki Nishikawa, Yurina Mikasa, Yuichi Takahashi, Fumiyoshi Kojima, Shin-ichi Murata","doi":"10.1007/s12022-023-09796-8","DOIUrl":"https://doi.org/10.1007/s12022-023-09796-8","url":null,"abstract":"<p>Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma and has characteristic nuclear features. Genetic abnormalities of PTC affect recent molecular target therapeutic strategy towards <i>RET</i>-altered cases, and they affect clinical prognosis and progression. However, there has been insufficient objective analysis of the correlation between genetic abnormalities and nuclear features. Using our newly developed methods, we studied the correlation between nuclear morphology and molecular abnormalities of PTC with the aim of predicting genetic abnormalities of PTC. We studied 72 cases of PTC and performed genetic analysis to detect <i>BRAF p.V600E</i> mutation and <i>RET</i> fusions. Nuclear features of PTC, such as nuclear grooves, pseudo-nuclear inclusions, and glassy nuclei, were also automatically detected by deep learning models. After analyzing the correlation between genetic abnormalities and nuclear features of PTC, logistic regression models could be used to predict gene abnormalities. Nuclear features were accurately detected with over 0.90 of AUCs in every class. The ratio of glassy nuclei to nuclear groove and the ratio of pseudo-nuclear inclusion to glassy nuclei were significantly higher in cases that were positive for <i>RET</i> fusions (<i>p</i> = 0.027, <i>p</i> = 0.043, respectively) than in cases that were negative for <i>RET</i> fusions. <i>RET</i> fusions were significantly predicted by glassy nuclei/nuclear grooves, pseudo-nuclear inclusions/glassy nuclei, and age (<i>p</i> = 0.023). Our deep learning models could accurately detect nuclear features. Genetic abnormalities had a correlation with nuclear features of PTC. Furthermore, our artificial intelligence model could significantly predict <i>RET</i> fusions of classic PTC.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"17 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139077525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphometric Analysis of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Using Digital Pathology","authors":"Chae A Kim, Hyeong Rok An, Jungmin Yoo, Yu-Mi Lee, Tae-Yon Sung, Won Gu Kim, Dong Eun Song","doi":"10.1007/s12022-023-09790-0","DOIUrl":"https://doi.org/10.1007/s12022-023-09790-0","url":null,"abstract":"<p>Digital pathology uses digitized images for cancer research. We aimed to assess morphometric parameters using digital pathology for predicting recurrence in patients with papillary thyroid carcinoma (PTC) and lateral cervical lymph node (LN) metastasis. We analyzed 316 PTC patients and assessed the longest diameter and largest area of metastatic focus in LNs using a whole slide imaging scanner. In digital pathology assessment, the longest diameters and largest areas of metastatic foci in LNs were positively correlated with traditional optically measured diameters (<i>R</i> = 0.928 and <i>R</i>² = 0.727, <i>p</i> &lt; 0.001 and <i>p</i> &lt; 0.001, respectively). The optimal cutoff diameter was 8.0 mm in both traditional microscopic (<i>p</i> = 0.009) and digital pathology (<i>p</i> = 0.016) evaluations, with significant differences in progression-free survival (PFS) observed at this cutoff (<i>p</i> = 0.006 and <i>p</i> = 0.002, respectively). The predictive area’s cutoff was 35.6 mm² (<i>p</i> = 0.005), which significantly affected PFS (<i>p</i> = 0.015). Using an 8.0-mm cutoff in traditional microscopic evaluation and a 35.6-mm² cutoff in digital pathology showed comparable predictive results using the proportion of variation explained (PVE) methods (2.6% vs. 2.4%). Excluding cases with predominant cystic changes in LNs, the largest metastatic areas by digital pathology had the highest PVE at 3.9%. Furthermore, high volume of LN metastasis (<i>p</i> = 0.001), extranodal extension (<i>p</i> = 0.047), and high ratio of metastatic LNs (<i>p</i> = 0.006) were associated with poor prognosis. Both traditional microscopic and digital pathology evaluations effectively measured the longest diameter of metastatic foci in LNs. Moreover, digital pathology offers limited advantages in predicting PFS of patients with lateral cervical LN metastasis of PTC, especially those without predominant cystic changes in LNs.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"78 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Critical Assessment of Diagnostic Criteria for the Tall Cell Subtype of Papillary Thyroid Carcinoma-How Much? How Tall? And When Is It Relevant?","authors":"John Turchini, Talia L Fuchs, Angela Chou, Loretta Sioson, Adele Clarkson, Amy Sheen, Leigh Delbridge, Anthony Glover, Mark Sywak, Stan Sidhu, Anthony J Gill","doi":"10.1007/s12022-023-09788-8","DOIUrl":"10.1007/s12022-023-09788-8","url":null,"abstract":"<p><p>Tall cell papillary thyroid carcinoma (TC-PTC) is considered adverse histology. However, previous studies are confounded by inconsistent criteria and strong associations with other adverse features. It is therefore still unclear if TC-PTC represents an independent prognostic factor in multivariate analysis and, if it does, what criteria should be employed for the diagnosis. We retrospectively reviewed 487 PTCs from our institution (where we have historically avoided the prospective diagnosis of TC-PTC) for both the height of tall cells (that is if the cells were two, or three, times as tall as wide) and the percentage of tall cells. On univariate analysis, there was significantly better disease free survival (DFS) in PTCs with no significant tall cell component (< 30%) compared to PTCs with cells two times tall as wide (p = 0.005). The proportion of tall cells (30-50% and > 50%) was significantly associated with DFS (p = 0.012). In a multivariate model including age, size, vascular space invasion, and lymph node metastasis, the current WHO tall cell criteria, met by 7.8% of PTCs, lacked statistical significance for DFS (p = 0.519). However, in the subset of tumours otherwise similar to the American Thyroid Association (ATA) guidelines low-risk category, WHO TC-PTC demonstrated a highly significant reduction in DFS (p = 0.004). In contrast, in intermediate to high-risk tumours, TC-PTC by WHO criteria lacked statistical significance (p = 0.384). We conclude that it may be simplistic to think of tall cell features as being present or absent, as both the height of the cells (two times versus three times) and the percentage of cells that are tall have different clinical significances in different contexts. Most importantly, the primary clinical significance of TC-PTC is restricted to PTCs that are otherwise low risk by ATA guidelines.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"461-470"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fundamentals of Endocrine Pathology: Part I.","authors":"Ozgur Mete","doi":"10.1007/s12022-023-09793-x","DOIUrl":"10.1007/s12022-023-09793-x","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"365"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memory of Kalman Kovacs and Eva Horvath.","authors":"Sylvia L Asa, Shozo Yamada, George Kontogeorgos, Ricardo V Lloyd","doi":"10.1007/s12022-023-09783-z","DOIUrl":"10.1007/s12022-023-09783-z","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"366-367"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10003099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}