Endocrine PathologyPub Date : 2024-03-01Epub Date: 2023-12-14DOI: 10.1007/s12022-023-09794-w
Francesca Carbonara, Tiziana Feola, Francesca Gianno, Michela Anna Polidoro, Rosa Maria Di Crescenzo, Antonietta Arcella, Michelangelo De Angelis, Roberta Morace, Dario de Alcubierre, Vincenzo Esposito, Felice Giangaspero, Marie-Lise Jaffrain-Rea
{"title":"Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification.","authors":"Francesca Carbonara, Tiziana Feola, Francesca Gianno, Michela Anna Polidoro, Rosa Maria Di Crescenzo, Antonietta Arcella, Michelangelo De Angelis, Roberta Morace, Dario de Alcubierre, Vincenzo Esposito, Felice Giangaspero, Marie-Lise Jaffrain-Rea","doi":"10.1007/s12022-023-09794-w","DOIUrl":"10.1007/s12022-023-09794-w","url":null,"abstract":"<p><p>Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1, βFSH, βLH, CCNA2, CCNB1, CCND1, caspase 3, D2R, and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases. Overall, patients were significantly younger in group 1 (P = 0.040 vs group 2), with a similar trend excluding recurrent cases (P = 0.078), and no significant difference in gender, tumor size, invasion or Ki67. SF1 expression was similar in both groups but negatively correlated with the patient's age (P = 0.013) and positively correlated with βLH (P < 0.001) expression. Beta-FSH and AIP were significantly higher in group 1 (P = 0.042 and P = 0.024, respectively). Ki67 was unrelated to gonadotroph markers but positively correlated with CCNB1 (P = 0.001) and negatively correlated with CCND1 (P = 0.008). D2R and AIP were strongly correlated with each other (P < 0.001), and both positively correlated with SF1, βFSH, βLH, and CCND1. AIP immunopositivity was frequently observed in both groups, with a similar median score, and unrelated to Ki67. D2R immunostaining was best detected with a polyclonal antibody and mostly cytoplasmic. This study indicates that hormone-negative GnPT tend to occur in older patients but do not significantly differ from other GnPT in terms of invasion or proliferation. It also points out the current limits of D2R immunostaining in such tumors.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"1-13"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813701","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}
Endocrine PathologyPub Date : 2024-03-01Epub Date: 2024-01-22DOI: 10.1007/s12022-024-09799-z
Rumeal D Whaley, Lori A Erickson
{"title":"Thyroid Gland Blastomycosis.","authors":"Rumeal D Whaley, Lori A Erickson","doi":"10.1007/s12022-024-09799-z","DOIUrl":"10.1007/s12022-024-09799-z","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"82-83"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514303","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}
Endocrine PathologyPub Date : 2024-03-01Epub Date: 2023-11-30DOI: 10.1007/s12022-023-09795-9
C Christofer Juhlin, Zubair W Baloch
{"title":"The 3<sup>rd</sup> Edition of Bethesda System for Reporting Thyroid Cytopathology: Highlights and Comments.","authors":"C Christofer Juhlin, Zubair W Baloch","doi":"10.1007/s12022-023-09795-9","DOIUrl":"10.1007/s12022-023-09795-9","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":" ","pages":"77-79"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464554","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}
Endocrine PathologyPub Date : 2024-03-01Epub Date: 2024-02-28DOI: 10.1007/s12022-024-09803-6
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
{"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}
Endocrine PathologyPub Date : 2024-03-01Epub Date: 2024-01-29DOI: 10.1007/s12022-024-09800-9
Sule Canberk, João Gonçalves, Elisabete Rios, Antónia A Povoa, Ebru Tastekin, Manuel Sobrinho-Simões, Aysun Uguz, Ozlem Aydin, Umit Ince, Paula Soares, Valdemar Máximo
{"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}
Endocrine PathologyPub Date : 2024-03-01Epub Date: 2024-03-02DOI: 10.1007/s12022-024-09805-4
Meryl Nath, Rumeal D Whaley, William Sukov, Lori A Erickson
{"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}
Endocrine PathologyPub Date : 2024-03-01Epub Date: 2024-02-16DOI: 10.1007/s12022-024-09804-5
C Christofer Juhlin
{"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}