Pub Date : 2025-12-11DOI: 10.1016/j.semdp.2025.150978
John M. Gross , Karen J. Fritchie
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently described benign matrix-forming soft tissue tumor with a predilection for the distal extremities and the temporomandibular joint (TMJ) of adults which frequently harbors FN1 fusions. Since its initial description in 2021, nearly 100 CCMNs have been reported thus broadening its clinicopathologic and molecular genetic spectrum in recent years. This manuscript will discuss, in detail, our current understanding of CCMN including a historical review of morphologically similar entities, as well as provide pertinent differential diagnoses of CCMN with a specific focus on tumors arising within the head and neck region.
{"title":"Calcified chondroid mesenchymal neoplasm","authors":"John M. Gross , Karen J. Fritchie","doi":"10.1016/j.semdp.2025.150978","DOIUrl":"10.1016/j.semdp.2025.150978","url":null,"abstract":"<div><div>Calcified chondroid mesenchymal neoplasm (CCMN) is a recently described benign matrix-forming soft tissue tumor with a predilection for the distal extremities and the temporomandibular joint (TMJ) of adults which frequently harbors FN1 fusions. Since its initial description in 2021, nearly 100 CCMNs have been reported thus broadening its clinicopathologic and molecular genetic spectrum in recent years. This manuscript will discuss, in detail, our current understanding of CCMN including a historical review of morphologically similar entities, as well as provide pertinent differential diagnoses of CCMN with a specific focus on tumors arising within the head and neck region.</div></div>","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"43 1","pages":"Article 150978"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.semdp.2025.150979
Giorgia Arcovito , Alessandro Franchi
Thyroid angiosarcoma (TAS) is an aggressive vascular tumor, accounting for 20 % of thyroid mesenchymal neoplasms and affecting elderly patients with frequent extra-thyroidal local extension and distant spread. It usually arises in the context of a long-standing goiter with higher incidence in iodine-deficient Alpine districts of Italy, Austria and Switzerland. Nevertheless, a relevant proportion of cases have been documented in iodine sufficient areas, being unrelated to goitrogen etiology and possibly associated with other risk factors. Histological features consist of large epithelioid cells with severe pleomorphism, arranged in a solid growth pattern with formation of vascular spaces, and set in a fibrotic stroma admixed with hemosiderin deposits and necrosis. Immunohistochemistry reveals positive staining for CD31, ERG and factor VIII, frequently accompanied by cytokeratin expression. Such findings may raise concern for the diagnosis of angiomatoid anaplastic carcinoma, which can be ruled out by the absence of thyroidal differentiation markers (including PAX8 and TTF-1). Cytological findings are rather non-specific and fine needle aspiration frequently yields inconclusive results. The genetic background of angiosarcoma is dominated by the impairment of genes deeply involved in angiogenesis, proliferation and survival (including MYC, KDR, FLT4, PTPRB and PLCG1) along with the dysregulation of crucial pathways like PIK3CA/AKT/mTOR and MAP kinase, with a relevant impact on possible novel therapeutic strategies. However, little is known about the molecular features of TAS and more investigations are needed to improve the characterization of this entity.
{"title":"Thyroid angiosarcoma: a comprehensive review","authors":"Giorgia Arcovito , Alessandro Franchi","doi":"10.1016/j.semdp.2025.150979","DOIUrl":"10.1016/j.semdp.2025.150979","url":null,"abstract":"<div><div>Thyroid angiosarcoma (TAS) is an aggressive vascular tumor, accounting for 20 % of thyroid mesenchymal neoplasms and affecting elderly patients with frequent extra-thyroidal local extension and distant spread. It usually arises in the context of a long-standing goiter with higher incidence in iodine-deficient Alpine districts of Italy, Austria and Switzerland. Nevertheless, a relevant proportion of cases have been documented in iodine sufficient areas, being unrelated to goitrogen etiology and possibly associated with other risk factors. Histological features consist of large epithelioid cells with severe pleomorphism, arranged in a solid growth pattern with formation of vascular spaces, and set in a fibrotic stroma admixed with hemosiderin deposits and necrosis. Immunohistochemistry reveals positive staining for CD31, ERG and factor VIII, frequently accompanied by cytokeratin expression. Such findings may raise concern for the diagnosis of angiomatoid anaplastic carcinoma, which can be ruled out by the absence of thyroidal differentiation markers (including PAX8 and TTF-1). Cytological findings are rather non-specific and fine needle aspiration frequently yields inconclusive results. The genetic background of angiosarcoma is dominated by the impairment of genes deeply involved in angiogenesis, proliferation and survival (including <em>MYC, KDR, FLT4, PTPRB</em> and <em>PLCG1</em>) along with the dysregulation of crucial pathways like PIK3CA/AKT/mTOR and MAP kinase, with a relevant impact on possible novel therapeutic strategies. However, little is known about the molecular features of TAS and more investigations are needed to improve the characterization of this entity.</div></div>","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"43 1","pages":"Article 150979"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.semdp.2025.150976
Sharon Koorse Germans , Bo Zhang , Olga Weinberg
Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow, leading to significant end-organ damage. Recent therapeutic advancements, including immunomodulatory drugs (IMiDs), proteasome inhibitors, autologous stem cell transplant (ASCT), and chimeric antigen receptor T-cell (CAR-T) therapy, have significantly improved survival outcomes. However, with prolonged survival, there is an emerging concern regarding therapy-related secondary malignancies (SM), particularly therapy-related myeloid neoplasms (tMN) and secondary lymphoid neoplasms. This article reviews the incidence, contributing factors, clinicopathological features, and outcomes associated with secondary malignancies in MM patients, including recent observations on therapy-related B-lymphoblastic leukemia and lymphomas.
{"title":"Secondary neoplasms following treatment for multiple myeloma","authors":"Sharon Koorse Germans , Bo Zhang , Olga Weinberg","doi":"10.1016/j.semdp.2025.150976","DOIUrl":"10.1016/j.semdp.2025.150976","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow, leading to significant end-organ damage. Recent therapeutic advancements, including immunomodulatory drugs (IMiDs), proteasome inhibitors, autologous stem cell transplant (ASCT), and chimeric antigen receptor T-cell (CAR-T) therapy, have significantly improved survival outcomes. However, with prolonged survival, there is an emerging concern regarding therapy-related secondary malignancies (SM), particularly therapy-related myeloid neoplasms (tMN) and secondary lymphoid neoplasms. This article reviews the incidence, contributing factors, clinicopathological features, and outcomes associated with secondary malignancies in MM patients, including recent observations on therapy-related B-lymphoblastic leukemia and lymphomas.</div></div>","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"43 1","pages":"Article 150976"},"PeriodicalIF":3.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.semdp.2025.150974
Katrina Collins, Andres M. Acosta, Muhammad T. Idrees, Thomas M. Ulbright
Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimens from patients with testicular germ cell tumors (TGCTs) often reveal a complex mix of residual tumor components and treatment-related changes. This review focuses on the morphologic spectrum of yolk sac tumor (YST) variants, trophoblastic tumors, and somatic-type malignancies in PC-RPLNDs, which continue to pose significant diagnostic and clinical challenges. Accurate identification of these entities is critical, as they carry distinct prognostic implications and influence management decisions. A multidisciplinary approach—integrating histopathology, immunohistochemistry, clinical history, and imaging—is essential for navigating these complex specimens. Emerging insights into chemotherapy resistance and tumor evolution are refining our understanding of TGCT biology and informing future diagnostic and therapeutic strategies. Herein, we highlight the increased frequency in postchemotherapy resections of glandular, hepatoid, parietal, and sarcomatoid differentiation in YSTs, as well as cystic, epithelioid, and placental site trophoblastic tumors, sarcomas, adenocarcinomas, and embryonic-type neuroectodermal tumors.
{"title":"Postchemotherapy phenotypes of GCNIS-derived testicular germ cell tumors, focusing on yolk sac tumor variants, trophoblastic tumors, and somatic-type malignancies","authors":"Katrina Collins, Andres M. Acosta, Muhammad T. Idrees, Thomas M. Ulbright","doi":"10.1016/j.semdp.2025.150974","DOIUrl":"10.1016/j.semdp.2025.150974","url":null,"abstract":"<div><div>Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimens from patients with testicular germ cell tumors (TGCTs) often reveal a complex mix of residual tumor components and treatment-related changes. This review focuses on the morphologic spectrum of yolk sac tumor (YST) variants, trophoblastic tumors, and somatic-type malignancies in PC-RPLNDs, which continue to pose significant diagnostic and clinical challenges. Accurate identification of these entities is critical, as they carry distinct prognostic implications and influence management decisions. A multidisciplinary approach—integrating histopathology, immunohistochemistry, clinical history, and imaging—is essential for navigating these complex specimens. Emerging insights into chemotherapy resistance and tumor evolution are refining our understanding of TGCT biology and informing future diagnostic and therapeutic strategies. Herein, we highlight the increased frequency in postchemotherapy resections of glandular, hepatoid, parietal, and sarcomatoid differentiation in YSTs, as well as cystic, epithelioid, and placental site trophoblastic tumors, sarcomas, adenocarcinomas, and embryonic-type neuroectodermal tumors.</div></div>","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"43 1","pages":"Article 150974"},"PeriodicalIF":3.5,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.semdp.2025.150946
Grace J Kwon, Chanjuan Shi
Pancreatic neuroendocrine neoplasms (PanNENs) are broadly divided into well-differentiated pancreatic neuroendocrine tumors (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). Grading is based on the mitotic count and Ki-67 proliferation index. PanNETs demonstrate typical neuroendocrine morphology, including nested and trabecular growth patterns, and “salt-and-pepper” coarse, clumped chromatin, whereas PanNECs can look like any poorly differentiated carcinoma. Differentiation of PanNETs from PanNECs and other hypercellular pancreatic neoplasms may sometimes be challenging but is crucial for patient management. Immunohistochemistry will demonstrate positivity for neuroendocrine markers. The advent of sequencing technology has elucidated critical signaling pathways potentially involved in the development of PanNENs, while also highlighting potential predispositions due to previously known and newly identified germline mutations.
{"title":"Pancreatic neuroendocrine neoplasms: current paradigms and diagnostic challenges","authors":"Grace J Kwon, Chanjuan Shi","doi":"10.1016/j.semdp.2025.150946","DOIUrl":"10.1016/j.semdp.2025.150946","url":null,"abstract":"<div><div>Pancreatic neuroendocrine neoplasms (PanNENs) are broadly divided into well-differentiated pancreatic neuroendocrine tumors (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). Grading is based on the mitotic count and Ki-67 proliferation index. PanNETs demonstrate typical neuroendocrine morphology, including nested and trabecular growth patterns, and “salt-and-pepper” coarse, clumped chromatin, whereas PanNECs can look like any poorly differentiated carcinoma. Differentiation of PanNETs from PanNECs and other hypercellular pancreatic neoplasms may sometimes be challenging but is crucial for patient management. Immunohistochemistry will demonstrate positivity for neuroendocrine markers. The advent of sequencing technology has elucidated critical signaling pathways potentially involved in the development of PanNENs, while also highlighting potential predispositions due to previously known and newly identified germline mutations.</div></div>","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"42 6","pages":"Article 150946"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1053/S0740-2570(25)00103-0
{"title":"TABLE OF CONTENTS (p/u from previous issue w/updates)","authors":"","doi":"10.1053/S0740-2570(25)00103-0","DOIUrl":"10.1053/S0740-2570(25)00103-0","url":null,"abstract":"","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"42 6","pages":"Article 150967"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.semdp.2025.150961
Wei Zheng , Yue Xue
Biliary epithelial precursor lesions represent key initiating steps in the multistep pathogenesis of cholangiocarcinoma. The three commonly recognized entities—biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), and intraductal tubulopapillary neoplasm of the bile duct (ITPN-B) —include both flat and mass-forming lesions and span a broad spectrum of morphologic, immunophenotypic, and molecular profiles. While their classification partially parallels that of pancreatic precursor lesions, biliary lesions exhibit unique architectural patterns, molecular alterations, and phenotypic variability. Accurate diagnosis is often complicated by overlapping histologic features, limited or fragmented sampling, and under-recognition of critical diagnostic criteria. This review synthesizes contemporary pathologic insights into biliary precursor lesions and provides a practical diagnostic framework based on detailed histologic evaluation, supported by ancillary immunohistochemical and molecular testing, differential diagnostic considerations, and integration of clinico-radiologic context. A nuanced understanding of the defining features and biological behavior of these lesions is essential to reduce diagnostic ambiguity, guide appropriate clinical decision-making, and enable effective risk stratification.
{"title":"Epithelial precursor lesions of the bile duct","authors":"Wei Zheng , Yue Xue","doi":"10.1016/j.semdp.2025.150961","DOIUrl":"10.1016/j.semdp.2025.150961","url":null,"abstract":"<div><div>Biliary epithelial precursor lesions represent key initiating steps in the multistep pathogenesis of cholangiocarcinoma. The three commonly recognized entities—biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), and intraductal tubulopapillary neoplasm of the bile duct (ITPN-B) —include both flat and mass-forming lesions and span a broad spectrum of morphologic, immunophenotypic, and molecular profiles. While their classification partially parallels that of pancreatic precursor lesions, biliary lesions exhibit unique architectural patterns, molecular alterations, and phenotypic variability. Accurate diagnosis is often complicated by overlapping histologic features, limited or fragmented sampling, and under-recognition of critical diagnostic criteria. This review synthesizes contemporary pathologic insights into biliary precursor lesions and provides a practical diagnostic framework based on detailed histologic evaluation, supported by ancillary immunohistochemical and molecular testing, differential diagnostic considerations, and integration of clinico-radiologic context. A nuanced understanding of the defining features and biological behavior of these lesions is essential to reduce diagnostic ambiguity, guide appropriate clinical decision-making, and enable effective risk stratification.</div></div>","PeriodicalId":49548,"journal":{"name":"Seminars in Diagnostic Pathology","volume":"42 6","pages":"Article 150961"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号