Endocrine Pathology最新文献

{"title":"Roadmap to Challenges in Limited Cellularity Specimens from Pancreatic Neuroendocrine Neoplasms: Diagnostic Tools for the Most Appropriate Management of Limited Material.","authors":"Stefano La Rosa, Roberta Maragliano, Deborah Marchiori","doi":"10.1007/s12022-025-09870-3","DOIUrl":"https://doi.org/10.1007/s12022-025-09870-3","url":null,"abstract":"<p><p>Fine needle aspiration (FNA) and fine needle biopsy (FNB) procedures are increasingly employed in the diagnostic work-up of pancreatic masses. These procedures represent a challenge for pathologists who have to adapt to handling specimens of limited cellularity. In several cases, FNA and FNB specimens are the only available material, as many pancreatic neoplasms are surgically unresectable at the time of the initial diagnosis. In the present review paper, the diagnosis of pancreatic neuroendocrine neoplasms in limited cellularity specimens is presented using a morphology-based approach. The aim is to provide a practical guide for pathologists to select the most appropriate ancillary techniques to be used for the diagnostic work-up, while conserving precious material. The integration of morphology, immunohistochemistry, and molecular biology will be discussed to provide the reader with practical tools to solve the main differential diagnostic problems encountered in routine practice when working with cytological samples or small biopsies.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"25"},"PeriodicalIF":11.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644191","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":"Prognostic Features in Surgically Resected Well-Differentiated Pancreatic Neuroendocrine Tumors: an Analysis of 904 Patients with 7882 Person-Years of Follow-Up.","authors":"Ashley L Kiemen, Eric D Young, Amanda L Blackford, Pengfei Wu, Richard A Burkhart, William R Burns, John L Cameron, Kelly Lafaro, Christopher Shubert, Zoe Gaillard, Uwakmfon-Abasi Ebong, Ian Reucroft, Yu Shen, Lucie Dequiedt, Valentina Matos, Günter Klöppel, Atsuko Kasajima, Jin He, Ralph H Hruban","doi":"10.1007/s12022-025-09866-z","DOIUrl":"10.1007/s12022-025-09866-z","url":null,"abstract":"<p><p>The clinical behavior of well-differentiated pancreatic neuroendocrine tumors (PanNETs) is difficult to predict. In order to define, more accurately, prognosticators for patients with a surgically resected PanNET, the pathologic features and Ki-67 immunolabeling indexes of PanNETs resected from 904 consecutive patients at an academic tertiary care hospital were correlated with patient outcome. The mean patient age at surgery was 56.6 years (SD 14.0), 477 were male (52.8%), and 7882 person-years of follow-up were obtained (mean 8.8 years, SD 6.5). The 10-year survival was 81% (95% CI: 77,86%) for patients with G1 PanNETs (Ki-67 <3%), 68% (95% CI: 61,76%) for patients with G2a PanNETs (Ki-67 3 - <10%), 44% (95% CI: 29,66%) for patients with G2b PanNETs (Ki-67 of 10%- ≤20%), and 23% (95% CI: 8,61%) for patients with G3 PanNETs. Vascular invasion (HR 3.0, p <0.0001), tumor size ≥ 2 cm (HR 2.88, p <0.0001), perineural invasion (HR 2.42, p<0.0001), and positive margins (HR 2.18, p <0.0001) were associated with worse overall survival. Insulinoma (HR 0.34, p=3e-04), sclerosing variant (HR 0.47, p=0.05), and cystic variant (HR 0.61, p=0.05) were associated with improved overall survival. T, N and M stages were all statistically significant classifiers of overall survival. Similar associations were found with respect to disease relapse. There was a significant (P<0.001) increase in the proportion of patients diagnosed with stage I vs stage IV disease over time. This study supports the classification of PanNETs into four grades (G1, G2a, G2b, and G3) based on Ki-67 labeling, which allows a more accurate prognostic assessments of patients.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"24"},"PeriodicalIF":11.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509530","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":"Extended Hormone Profiling Identifies a Wider Network of Duodenal Neuroendocrine Tumor Subtypes.","authors":"Luvy Delfin, Shereen Ezzat, Sylvia L Asa","doi":"10.1007/s12022-025-09868-x","DOIUrl":"10.1007/s12022-025-09868-x","url":null,"abstract":"<p><p>We studied transcription factors and hormones expressed by duodenal neuroendocrine cells in a consecutively diagnosed series of 53 patients with well-differentiated duodenal NETs. There were 30 men; the mean age was 65 years (33 to 81). The study included biopsies (n = 18), endoscopic mucosal resections (n = 19), and surgical resections (n = 16). Three patients had multifocal disease; two had MEN1. Two patients had neurofibromatosis. Metastases were identified in 15/23 patients with biopsied lymph nodes. PAX6 was expressed in 85%, followed by CDX2 in 65%; ARX was expressed in 33%, and no tumors expressed PAX4. The commonest hormone expressed was gastrin; 23 (43%) had diffuse expression, and 12 (23%) had focal reactivity. Pancreatic polypeptide was diffuse and strong in 17 tumors (32%) classified as PP cell NETs; another 3 tumors had focal staining (total n = 20, 38%). Serotonin was identified only focally in 14 tumors (26%). Somatostatin was positive in 13 tumors (25%), 3 classical D cell tumors and 10 tumors with focal positivity. PYY was expressed in 10 tumors (19%), diffusely in 1 and focally in 9. CCK was identified in 6 tumors (11%), diffusely in 1 and focally in 5. Staining for glucagon/GLPs, insulin, and motilin was completely negative in all tumors. Thirty tumors (57%) expressed more than one hormone; gastrin was the most frequent. In 2 composite gangliocytoma/NETs (CoGNETs), the NET component expressed PP, and both NET and ganglion cells expressed ARX. These data identify a broad spectrum of duodenal NETs including novel cell types and a high incidence of plurihormonality.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"23"},"PeriodicalIF":11.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477963","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":"A Novel Three-Stage AI-Assisted Approach for Accurate Differential Diagnosis and Classification of NIFTP and Thyroid Neoplasms.","authors":"Shweta Birla, Nimisha Tiwari, Pragati Shyamal, Abhishek Khatri, Divya Bandaru, Arundhati Sharma, Dinesh Gupta, Shipra Agarwal","doi":"10.1007/s12022-025-09865-0","DOIUrl":"https://doi.org/10.1007/s12022-025-09865-0","url":null,"abstract":"<p><p>The recent introduction of the term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) marked a pivotal shift in the classification of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) lacking invasive features. While its reclassification from the \"malignant\" to \"low-risk neoplasm\" category significantly reduced overtreatment, its histopathological diagnosis remains challenging due to overlapping features with other thyroid lesions and inter-observer variability. Artificial intelligence (AI) overcomes such key limitations of histopathological evaluation, ensuring a robust and efficient diagnostic process. While preliminary studies are promising, AI models capable of efficiently distinguishing NIFTP from other benign and malignant thyroid entities are yet to be developed. We devised an innovative AI-based three-stage hierarchical pipeline that systematically evaluates architectural patterns and nuclear features. The prioritized models were trained using 154,498 patches, derived from 134 sections prepared from 125 thyroid nodules, representing follicular nodular disease (FND), follicular adenoma, dominant nodule in FND, invasive EFVPTC (IEFVPTC), and classic and infiltrative follicular subtypes of PTC. External validation revealed good accuracy at the overall, patient-wise, and class-wise levels. However, it showed limitations in the differential diagnosis of NIFTP from IEFVPTC-an expected challenge due to overlapping nuclear features and the absence of incorporating the assessment of the tumor capsule for invasive characteristics. While the novel approach and the algorithm show promise in transforming histopathological NIFTP diagnostics, further improvements and rigorous validations are necessary before considering its application in real-world clinical settings.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"22"},"PeriodicalIF":11.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327827","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":"Reticulin Framework Assessment in Neoplastic Endocrine Pathology.","authors":"Umberto Mortara, Giulia Orlando, Marco Volante, Mauro Papotti, Eleonora Duregon","doi":"10.1007/s12022-025-09867-y","DOIUrl":"https://doi.org/10.1007/s12022-025-09867-y","url":null,"abstract":"<p><p>The reticulin framework, composed mainly of type III collagen, is an essential structural component of biological tissues. Reticulin stains, particularly silver-based methods, enable detailed visualization of reticulin framework alterations, which have been proven to be quick, low-cost, and reliable solutions for highlighting quantitative and qualitative changes of reticulin framework and have been variably associated with neoplastic and non-neoplastic conditions. This review provides an updated overview of reticulin stain applications and reticulin framework assessment in endocrine and neuroendocrine neoplasms, including those of the pituitary, parathyroid, adrenal, and other neuroendocrine systems. In pituitary neuroendocrine tumors, reticulin framework loss serves as a distinguishing feature between normal and neoplastic adenohypophysis. Parathyroid neoplasms, including adenomas, atypical tumors, and carcinomas, exhibit varying degrees of reticulin framework disruption, which may aid in differential diagnosis. Similarly, in adrenocortical neoplasms, reticulin framework evaluation plays a crucial role in malignancy assessment, as defined in the reticulin algorithm, which incorporates reticulin framework alterations alongside three Weiss criteria: necrosis, high mitotic count (> 5/10 mm²), and venous invasion. Moreover, specific reticulin framework patterns help to distinguish the different morphological subtypes of bilateral macronodular adrenocortical disease. Pheochromocytomas and paragangliomas display a range of reticulin framework patterns which might be related to the genetic background of the tumor. Finally, different neuroendocrine neoplasms exhibit variable reticulin framework integrity, with a more significant disruption observed in high-grade carcinomas. Advancements in digital pathology and artificial intelligence offer promising avenues for automated reticulin framework quantification, enhancing diagnostic precision and prognostic assessments. The integration of computational approaches may further improve the clinical utility of reticulin framework evaluation in endocrine pathology.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"21"},"PeriodicalIF":11.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217631","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":"Focal High-Grade Areas with a Tumor-in-Tumor Pattern: Another Feature of Pediatric DICER1-Associated Thyroid Carcinoma?","authors":"Marco Schiavo Lena, María Sánchez-Ares, Emanuela Brunetto, Ihab Abdulkader-Nallib, Riccardo Maggiore, Diego Barbieri, Maria Cristina Vigone, Francesca Perticone, Roberto Lanzi, Silvia Presi, Paola Carrera, Maria Giulia Cangi, Gianluigi Arrigoni, Claudio Doglioni, José Manuel Cameselle-Teijeiro","doi":"10.1007/s12022-025-09863-2","DOIUrl":"10.1007/s12022-025-09863-2","url":null,"abstract":"<p><p>In the thyroid gland, during childhood or adolescence, DICER1-driven tumors include differentiated follicular thyroid carcinoma and, more rarely, poorly differentiated carcinoma. Herein, we describe the features of DICER1-associated thyroid carcinoma with the presence of high-grade areas within a differentiated tumor in four patients (median age 12.5 years, range 6-15 years), three of them carrying germline pathogenic variants of DICER1. A new tumor-in-tumor pattern characterized by intratumoral nodules with a higher histological grade (increased mitotic activity/Ki-67 and solid/trabecular/insular and/or microfollicular architecture) was detected in these DICER1-associated tumors. In two patients, the high-grade component also demonstrated the presence of CHEK2 p.(Tyr390Cys) likely pathogenic variants, suggesting a role for this gene and more generally for the ATM-CHECK2-TP53 pathway as a mechanism of malignant progression of DICER1-associated thyroid carcinomas. One of these two patients presented lymph node recurrence 8 months after surgery. An immunohistochemical study was also performed to explore the possible contribution of anti-DICER1 antibodies as well as thyroglobulin, Ki-67, p53, and PRAME in characterizing these tumors. DICER1 proved to be strongly expressed in mutated tumors compared to a control cohort (p < 0.001), deserving further validation to define its possible diagnostic role. Finally, well-demarcated ischemic-like areas with ghost cells embedded in a thick hyaline stroma (atrophic changes) were found within four tumors, whereas bunches of ectatic macrofollicles lined by flattened epithelium (involutional changes) were only detected in the background thyroid parenchyma of patients with germline DICER1 variants. These morphological features may alert pathologists to suspect a somatic and/or germline DICER1 alteration.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"20"},"PeriodicalIF":11.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192562","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":"Three Synchronous Pituitary Neuroendocrine Tumors-Epigenomics Confirm an Exceptional Triple PitNET.","authors":"Temor Rafiq, Jakob Matschke, Jörg Flitsch, Matthias Dottermusch","doi":"10.1007/s12022-025-09864-1","DOIUrl":"10.1007/s12022-025-09864-1","url":null,"abstract":"","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"19"},"PeriodicalIF":11.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082212","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":"Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases.","authors":"Alessandro Vanoli, Nestor Piva, Frediano Socrate Inzani, Federica Grillo, Catherine Klersy, Silvia Uccella, Paola Spaggiari, Luca Albarello, Marco Schiavo Lena, Massimo Milione, Caterina Antoniacomi, Anna Caterina Milanetto, Alessandro Zerbi, Antonio Di Sabatino, Massimo Falconi, Andrea Anderloni, Paola Mattiolo, Claudio Luchini, Aldo Scarpa, Matteo Fassan, Paola Parente, Ombretta Luinetti, Guido Rindi, Marco Paulli, Stefano La Rosa","doi":"10.1007/s12022-025-09861-4","DOIUrl":"10.1007/s12022-025-09861-4","url":null,"abstract":"<p><p>Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"18"},"PeriodicalIF":11.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060574","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":"ABCC3 Is a Differential Marker of CYP11B2-Negative Zona Glomerulosa Cells in Human Adrenal Cortex.","authors":"Yingxian Pang, Sanas Mir-Bashiri, Zhuolun Sun, Yuhong Yang, Isabella Castellano, Thomas Knösel, Martin Reincke, Tracy Ann Williams","doi":"10.1007/s12022-025-09862-3","DOIUrl":"https://doi.org/10.1007/s12022-025-09862-3","url":null,"abstract":"<p><p>ATP Binding Cassette Subfamily C Member 3 (ABCC3) is a membrane transporter that exports diverse compounds, influencing drug resistance in cancers and impacting metabolic and malignant diseases. We previously reported ABCC3 upregulation in human adrenal cells under lipid peroxidation-induced oxidative stress. We investigated ABCC3 expression and function in the human adrenal cortex in the context of primary aldosteronism, focusing on its relationship to CYP11B2 (aldosterone synthase) in zona glomerulosa (ZG) cells and aldosterone-producing lesions. ABCC3 expression in aldosterone-producing adenomas (APAs) was markedly reduced compared to the adjacent adrenal cortex, cortisol-producing adenomas, and non-functioning adenomas. The reduction in APAs showed genotypic variability: in APAs harboring KCNJ5 mutations-known drivers of autonomous aldosterone production via altered potassium channel function-ABCC3 mRNA/protein levels were significantly higher than in wild-type KCNJ5 APAs. Spatial transcriptomics and immunofluorescence colocalization revealed an inverse expression pattern between ABCC3 and CYP11B2 (aldosterone synthase) in APAs and aldosterone-producing micronodules (APMs). Notably, high ABCC3 expression was exclusively observed in adrenal ZG cells that lacked CYP11B2 expression. This expression pattern distinguishes ABCC3 from common ZG markers such as KCNJ5 and DAB2, which are expressed across adrenal ZG cells, APMs, and APA tumor cells. In cultured human adrenocortical cells, both angiotensin II stimulation and induced expression of the KCNJ5-L168R mutation resulted in upregulation of CYP11B2 transcription while concomitantly suppressing ABCC3 expression. In conclusion, ABCC3 serves as a novel marker of CYP11B2-negative ZG cells, providing a histopathological tool to differentiate normal adrenal zonation from aldosterone-producing lesions in primary aldosteronism, as well as from cortisol-producing and nonfunctional adenomas.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"17"},"PeriodicalIF":11.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043009","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":"Is Ectopic Cushing Syndrome Commonly Associated with Small Cell Lung Cancer (SCLC)? Critical Review of the Literature and ACTH Expression in Resected SCLC.","authors":"Ayako Ura, Elisa Moser, Matthias Evert, Katja Evert, Bruno Märkl, Eva Sipos, Marcus Kremer, Hironobu Sasano, Yoshinori Okada, Katja Steiger, Carolin Mogler, Hans Hoffmann, Alexander von Werder, Daniel Kaemmerer, Silvia Uccella, Stefano La Rosa, Günter Klöppel, Atsuko Kasajima","doi":"10.1007/s12022-025-09860-5","DOIUrl":"10.1007/s12022-025-09860-5","url":null,"abstract":"<p><p>The literature emphasizes that pulmonary ectopic Cushing syndrome (ECS) is associated not only with neuroendocrine tumors (NETs), but also with small cell lung carcinomas (SCLCs). This statement is debatable, because extrapulmonary ECS is associated with NETs in the vast majority of cases and very rarely with neuroendocrine carcinomas (NECs). Therefore, we critically reviewed the literature on SCLCs associated with ECS (ECS-SCLC) and performed immunohistochemical analysis of ACTH expression in 155 resected SCLCs and 158 pulmonary NETs. The literature search revealed that 90% of the 205 ECS-SCLC patients identified between 1952 and 2023 had no or poor-quality histologic images, so the diagnosis of SCLC could not be confirmed. Review of the 20 reports (10%) with histologic images revealed that 18/20 (90%) had to be reclassified as \"probable NET\", of which 5/18 (28%) showed spindle cell morphology, while only 2 cases were qualified as \"SCLC compatible\" due to their pleomorphic cell features. Immunohistochemically, 5/155 (3%) resected SCLCs, all without ECS, showed weak single cell ACTH expression, whereas in the NET cohort, 61/158 (39%) tumors expressed ACTH, of which 4 (3%) were associated with ECS. Both observations, the literature review, which casts doubt on previously reported data regarding the frequency of SCLC in ECS, and the immunohistochemical study, suggest that there is limited evidence that SCLC is the cause of ECS.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":"36 1","pages":"16"},"PeriodicalIF":11.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057584","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}