Pub Date : 2025-11-24DOI: 10.1016/j.mpdhp.2025.10.005
Eleanor McTaggart, Sophie Stenton
The placenta has long been one of the most misunderstood and neglected areas in surgical pathology. Whilst some groups have at times questioned the importance of the placenta in the medical management of pregnancy, it is now generally accepted that a fully functioning placenta is required for successful pregnancy and there has been an uptick in interest for placental examination. This article shall not only evaluate the pathological findings of some of the more common placental disorders, but it shall provide an overview of the most up to date understanding of disease processes and offer some practical advice on sampling and grading these lesions. Herein we focus on the following common entities: maternal vascular malperfusion, fetal vascular malperfusion, acute chorioamnionitis and chronic villitis of unknown aetiology. The article shall also address the placental lesion chronic histiocytic intervillositis (CHI), as, whilst rare, it can have particularly devastating consequences. CHI is present in first trimester products of conception and may be encountered by general pathologists inexperienced in placental pathology.
{"title":"Placental pathology: what not to miss","authors":"Eleanor McTaggart, Sophie Stenton","doi":"10.1016/j.mpdhp.2025.10.005","DOIUrl":"10.1016/j.mpdhp.2025.10.005","url":null,"abstract":"<div><div>The placenta has long been one of the most misunderstood and neglected areas in surgical pathology. Whilst some groups have at times questioned the importance of the placenta in the medical management of pregnancy, it is now generally accepted that a fully functioning placenta is required for successful pregnancy and there has been an uptick in interest for placental examination. This article shall not only evaluate the pathological findings of some of the more common placental disorders, but it shall provide an overview of the most up to date understanding of disease processes and offer some practical advice on sampling and grading these lesions. Herein we focus on the following common entities: maternal vascular malperfusion, fetal vascular malperfusion, acute chorioamnionitis and chronic villitis of unknown aetiology. The article shall also address the placental lesion chronic histiocytic intervillositis (CHI), as, whilst rare, it can have particularly devastating consequences. CHI is present in first trimester products of conception and may be encountered by general pathologists inexperienced in placental pathology.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 1","pages":"Pages 1-11"},"PeriodicalIF":0.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-22DOI: 10.1016/j.mpdhp.2025.10.006
Lesley Christie, Lesley M McMahon
Sporadic miscarriages occur in 10–20% of all pregnancies and affect one in four women. Products of conception (POC) are one of the commonest specimens submitted to the histopathology laboratory. The pathologist's role is to adequately sample, confirm a pregnancy and identify or exclude a molar pregnancy. This review summarises the genetic basis of the disease, key diagnostic features and ancillary investigations that can be employed to classify a gestation. Accurate and timely diagnosis of molar pregnancy ensures appropriate follow up and favourable outcomes.
{"title":"Hydatidiform moles and mimics: an up-to-date review on morphology and immunocytochemistry to aid the diagnosis","authors":"Lesley Christie, Lesley M McMahon","doi":"10.1016/j.mpdhp.2025.10.006","DOIUrl":"10.1016/j.mpdhp.2025.10.006","url":null,"abstract":"<div><div>Sporadic miscarriages occur in 10–20% of all pregnancies and affect one in four women. Products of conception (POC) are one of the commonest specimens submitted to the histopathology laboratory. The pathologist's role is to adequately sample, confirm a pregnancy and identify or exclude a molar pregnancy. This review summarises the genetic basis of the disease, key diagnostic features and ancillary investigations that can be employed to classify a gestation. Accurate and timely diagnosis of molar pregnancy ensures appropriate follow up and favourable outcomes.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 1","pages":"Pages 12-25"},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.mpdhp.2025.10.011
Anjana Kalladathil Sreenivasan, Limi Mohandas, David Milliken, Surabhi Agrawal
Atypical polypoid adenomyoma (APA) represents a rare benign endometrial lesion characterized by proliferative, atypical glands interspersed within smooth muscle bundles. It usually affects perimenopausal women and may manifest with abnormal uterine bleeding. Although most APAs behave benignly, malignant transformation – most commonly endometrioid carcinoma – has been reported in a small proportion of cases. Clear cell carcinoma arising in APA is exceptionally rare, with only isolated cases described in the literature. Cowden syndrome, an autosomal dominant disorder caused by germline mutations in the PTEN gene, confers increased lifetime risks of breast (25–50%), thyroid (3–10%), endometrial (5–10%) and colon cancer (13%). The coexistence of APA, clear cell carcinoma and Cowden syndrome is extremely rare.
{"title":"Clear cell carcinoma arising in the background of atypical polypoid adenomyoma","authors":"Anjana Kalladathil Sreenivasan, Limi Mohandas, David Milliken, Surabhi Agrawal","doi":"10.1016/j.mpdhp.2025.10.011","DOIUrl":"10.1016/j.mpdhp.2025.10.011","url":null,"abstract":"<div><div>Atypical polypoid adenomyoma (APA) represents a rare benign endometrial lesion characterized by proliferative, atypical glands interspersed within smooth muscle bundles. It usually affects perimenopausal women and may manifest with abnormal uterine bleeding. Although most APAs behave benignly, malignant transformation – most commonly endometrioid carcinoma – has been reported in a small proportion of cases. Clear cell carcinoma arising in APA is exceptionally rare, with only isolated cases described in the literature. Cowden syndrome, an autosomal dominant disorder caused by germline mutations in the PTEN gene, confers increased lifetime risks of breast (25–50%), thyroid (3–10%), endometrial (5–10%) and colon cancer (13%). The coexistence of APA, clear cell carcinoma and Cowden syndrome is extremely rare.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 1","pages":"Pages 64-66"},"PeriodicalIF":0.0,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.mpdhp.2025.10.009
Fabienne Allias, Lucie Gaillot-Durand
Gestational trophoblastic disease encompasses a range of pregnancy-related disorders including premalignant hydatidiform mole (HM), non-neoplastic tumor-like lesion and gestational trophoblastic neoplasia. Hydatidiform moles are characterized by specific morphological, immunohistochemical and genetic features. Extensive histopathological and genetic studies over the past decades have led to the description of new entities in the differential diagnosis of HM. Androgenetic/biparental mosaic/chimera (ABMC) is an abnormal pregnancy product containing a mixture of two genetically different lineages, one androgenetic and the other biparental, within individual villi. Placental mesenchymal dysplasia (PMD) is a rare placental disorder characterized by a specific association of macroscopic and microscopic findings, and its pathogenesis is complex and heterogeneous, implying epigenetic or genetic alterations in two imprinted domains on chromosome 11p15.5. ABMC is most often an incidental finding discovered during pathological examination of molar specimen but can also be demonstrated in some placentas in the context of PMD. Although ABMC and PMD can have the same ultrasound appearance, morphologic features and discordant p57 expression, they differ in definition, pathogenesis, histopathological assessment, and clinical management.
An increasing number of pathologists are now familiar with HM, but few are aware of ABMC and PMD as separate diagnoses. This review of recent findings provides a practical approach to diagnosing ABMC and PMD.
{"title":"The overlapping spectra of androgenetic/biparental mosaic/chimera and placental mesenchymal dysplasia","authors":"Fabienne Allias, Lucie Gaillot-Durand","doi":"10.1016/j.mpdhp.2025.10.009","DOIUrl":"10.1016/j.mpdhp.2025.10.009","url":null,"abstract":"<div><div>Gestational trophoblastic disease encompasses a range of pregnancy-related disorders including premalignant hydatidiform mole (HM), non-neoplastic tumor-like lesion and gestational trophoblastic neoplasia. Hydatidiform moles are characterized by specific morphological, immunohistochemical and genetic features. Extensive histopathological and genetic studies over the past decades have led to the description of new entities in the differential diagnosis of HM. Androgenetic/biparental mosaic/chimera (ABMC) is an abnormal pregnancy product containing a mixture of two genetically different lineages, one androgenetic and the other biparental, within individual villi. Placental mesenchymal dysplasia (PMD) is a rare placental disorder characterized by a specific association of macroscopic and microscopic findings, and its pathogenesis is complex and heterogeneous, implying epigenetic or genetic alterations in two imprinted domains on chromosome 11p15.5. ABMC is most often an incidental finding discovered during pathological examination of molar specimen but can also be demonstrated in some placentas in the context of PMD. Although ABMC and PMD can have the same ultrasound appearance, morphologic features and discordant p57 expression, they differ in definition, pathogenesis, histopathological assessment, and clinical management.</div><div>An increasing number of pathologists are now familiar with HM, but few are aware of ABMC and PMD as separate diagnoses. This review of recent findings provides a practical approach to diagnosing ABMC and PMD.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 1","pages":"Pages 47-60"},"PeriodicalIF":0.0,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-15DOI: 10.1016/j.mpdhp.2025.10.008
Geoffrey J Maher
Gestational trophoblastic disease (GTD) comprises molar pregnancies, abnormal pregnancies that are genetically distinct from other pregnancies, and gestational trophoblastic neoplasms (GTN) that are genetically different from non-gestational tumours. A variety of ancillary assays are available to support the diagnosis of gestational trophoblastic disease. Genotyping, a molecular assay that analyses genetic variation, is the most versatile assay for diagnosing gestational trophoblastic disease as it is informative for all types of molar pregnancy and trophoblastic tumours. This article highlights clinical contexts where genotyping, most commonly short tandem repeat (STR) genotyping, is particularly informative including determining the parental origin of DNA in triploid products of conception, diagnosing recurrent molar pregnancies and identifying the gestational origin and causative pregnancy for trophoblastic tumours. While certain pitfalls are associated with STR genotyping, these can be mitigated through careful integration of relevant clinical and pathological data and, when necessary, the application of complementary ancillary techniques.
{"title":"Diagnoses where genotyping is critical in gestational trophoblastic disease and five important pitfalls","authors":"Geoffrey J Maher","doi":"10.1016/j.mpdhp.2025.10.008","DOIUrl":"10.1016/j.mpdhp.2025.10.008","url":null,"abstract":"<div><div>Gestational trophoblastic disease (GTD) comprises molar pregnancies, abnormal pregnancies that are genetically distinct from other pregnancies, and gestational trophoblastic neoplasms (GTN) that are genetically different from non-gestational tumours. A variety of ancillary assays are available to support the diagnosis of gestational trophoblastic disease. Genotyping, a molecular assay that analyses genetic variation, is the most versatile assay for diagnosing gestational trophoblastic disease as it is informative for all types of molar pregnancy and trophoblastic tumours. This article highlights clinical contexts where genotyping, most commonly short tandem repeat (STR) genotyping, is particularly informative including determining the parental origin of DNA in triploid products of conception, diagnosing recurrent molar pregnancies and identifying the gestational origin and causative pregnancy for trophoblastic tumours. While certain pitfalls are associated with STR genotyping, these can be mitigated through careful integration of relevant clinical and pathological data and, when necessary, the application of complementary ancillary techniques.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 1","pages":"Pages 40-46"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.mpdhp.2025.10.010
Brodie Crooks, Daniel T Field, Yasin Dhonye, Katherine Quiohilag
A case of uterine mesonephric-like carcinosarcoma is reported with particular emphasis on morphology, immunohistochemistry and possible diagnostic pitfalls with other entities demonstrating mesonephric morphology in the female genital tract.
{"title":"A case of uterine mesonephric-like carcinosarcoma","authors":"Brodie Crooks, Daniel T Field, Yasin Dhonye, Katherine Quiohilag","doi":"10.1016/j.mpdhp.2025.10.010","DOIUrl":"10.1016/j.mpdhp.2025.10.010","url":null,"abstract":"<div><div>A case of uterine mesonephric-like carcinosarcoma is reported with particular emphasis on morphology, immunohistochemistry and possible diagnostic pitfalls with other entities demonstrating mesonephric morphology in the female genital tract.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 1","pages":"Pages 61-63"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.mpdhp.2025.10.003
Abeer M Shaaban
Breast core biopsies are a standard component of the triple approach that includes clinical examination, imaging and tissue sampling. Conventional cores, diagnostic vacuum assisted biopsy and vacuum assisted excisions are established methods for sampling and managing breast lesions. It is important to be aware of the potential pitfalls in the technical handling and interpretation of the limited core biopsy samples. Here, we present a clinically oriented, well-illustrated update of the common diagnostic pitfalls based on the author's diagnostic and second opinion practice, emphasize the value of clinicopathological correlation and provide histological tips and clues with useful immunohistochemistry to aid the reporting pathologists in their daily interpretation of breast core biopsies. We also include an overview of potential pitfalls in the interpretation using digital pathology and artificial intelligence.
{"title":"Diagnostic pitfalls in needle core biopsy of the breast: an update","authors":"Abeer M Shaaban","doi":"10.1016/j.mpdhp.2025.10.003","DOIUrl":"10.1016/j.mpdhp.2025.10.003","url":null,"abstract":"<div><div>Breast core biopsies are a standard component of the triple approach that includes clinical examination, imaging and tissue sampling. Conventional cores, diagnostic vacuum assisted biopsy and vacuum assisted excisions are established methods for sampling and managing breast lesions. It is important to be aware of the potential pitfalls in the technical handling and interpretation of the limited core biopsy samples. Here, we present a clinically oriented, well-illustrated update of the common diagnostic pitfalls based on the author's diagnostic and second opinion practice, emphasize the value of clinicopathological correlation and provide histological tips and clues with useful immunohistochemistry to aid the reporting pathologists in their daily interpretation of breast core biopsies. We also include an overview of potential pitfalls in the interpretation using digital pathology and artificial intelligence.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 12","pages":"Pages 701-706"},"PeriodicalIF":0.0,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.mpdhp.2025.10.002
Helen Turner, Matthew Theodosiou, Elizabeth Crawford, Mona Jain, Kate Macdougall, Scarlet Brockmoeller
This is the case of a 30-year-old male patient with an oncocytic renal neoplasm that was difficult to classify. There are range of lesions to consider in the differential diagnosis of unusual oncocytic renal tumours including molecular defined renal cell carcinomas. Histology from a partial nephrectomy revealed an extensively degenerative tumour, which was composed of solid nodules and small clusters/nests with some prominent tubulocystic architecture. The tumour cells had moderately well-defined cell borders and abundant vacuolated to densely eosinophilic cytoplasm. Flocculent cytoplasmic inclusions were conspicuous. The nuclei showed up to moderate pleomorphism and were slightly irregular to rounded, with finely granular staining chromatin and occasional eosinophilic nucleoli. Entrapped native renal structures were seen peripherally. Immunohistochemical stains showed positive staining for PAX8, CD10 (patchy), racemase and EMA. PanCK, AE1/3, CAIX, HMB45, CK20, vimentin, S100, RCC, CK7, CD117 and MelanA were all negative. FH expression was retained and TFE-3 showed no strong nuclear expression. There was loss of SDHB expression with positive non-neoplastic internal control. These characteristics are therefore most in keeping with a succinate dehydrogenase-deficient (SDH) renal cell carcinoma. Identification of these rare SDH-deficient renal cell carcinomas (1–3) is important as they are strongly hereditary and most commonly present in young adulthood (mean age 35 years). Long term follow-up and surveillance for other SDH-deficient neoplasms (3), like for example paraganglioma, GIST, pituitary adenoma are indicated, following referral for genetic counselling/germline mutation testing. Further, if SDH germline mutation is found, genetic screening may be considered in first- and second-degree relatives.
{"title":"Case report of a succinate dehydrogenase-deficient renal cell carcinoma","authors":"Helen Turner, Matthew Theodosiou, Elizabeth Crawford, Mona Jain, Kate Macdougall, Scarlet Brockmoeller","doi":"10.1016/j.mpdhp.2025.10.002","DOIUrl":"10.1016/j.mpdhp.2025.10.002","url":null,"abstract":"<div><div>This is the case of a 30-year-old male patient with an oncocytic renal neoplasm that was difficult to classify. There are range of lesions to consider in the differential diagnosis of unusual oncocytic renal tumours including molecular defined renal cell carcinomas. Histology from a partial nephrectomy revealed an extensively degenerative tumour, which was composed of solid nodules and small clusters/nests with some prominent tubulocystic architecture. The tumour cells had moderately well-defined cell borders and abundant vacuolated to densely eosinophilic cytoplasm. Flocculent cytoplasmic inclusions were conspicuous. The nuclei showed up to moderate pleomorphism and were slightly irregular to rounded, with finely granular staining chromatin and occasional eosinophilic nucleoli. Entrapped native renal structures were seen peripherally. Immunohistochemical stains showed positive staining for PAX8, CD10 (patchy), racemase and EMA. PanCK, AE1/3, CAIX, HMB45, CK20, vimentin, S100, RCC, CK7, CD117 and MelanA were all negative. FH expression was retained and TFE-3 showed no strong nuclear expression. There was loss of SDHB expression with positive non-neoplastic internal control. These characteristics are therefore most in keeping with a succinate dehydrogenase-deficient (SDH) renal cell carcinoma. Identification of these rare SDH-deficient renal cell carcinomas (1–3) is important as they are strongly hereditary and most commonly present in young adulthood (mean age 35 years). Long term follow-up and surveillance for other SDH-deficient neoplasms (3), like for example paraganglioma, GIST, pituitary adenoma are indicated, following referral for genetic counselling/germline mutation testing. Further, if SDH germline mutation is found, genetic screening may be considered in first- and second-degree relatives.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 12","pages":"Pages 736-739"},"PeriodicalIF":0.0,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.mpdhp.2025.10.004
Shirley K Jamidi, Gary M Tse
Breast papillary lesions encompass a wide spectrum of entities characterized by a papillary architecture with arborizing fibrovascular cores. Clinical examination and imaging lack sufficient specificity to distinguish these lesions, making histopathologic analysis essential for accurate diagnosis. Classification hinges on the nature of proliferating epithelial cells and the presence or absence of basal myoepithelial cells. Benign lesions include intraductal papilloma, which may be accompanied by epithelial metaplasia, hyperplasia, or atypical ductal hyperplasia/ductal carcinoma in situ (DCIS). Malignant papillary lesions comprise papillary ductal carcinoma in situ, encapsulated papillary carcinoma, solid papillary carcinoma (in situ and invasive), and invasive papillary carcinoma. Their overlapping morphologic features and immunohistochemical (IHC) profiles pose diagnostic challenges, particularly on core needle biopsy, where underdiagnosis is more common than overdiagnosis. Distinguishing noninvasive from invasive malignant papillary tumors is critical for management and is supported by the presence of irregular clusters, tongues, and nests of tumor cells extending into the stroma beyond a well-defined boundary. Genetically, papillary carcinomas predominantly align with luminal subtypes, underscoring their generally low-grade biology.
{"title":"Papillary lesions of the breast","authors":"Shirley K Jamidi, Gary M Tse","doi":"10.1016/j.mpdhp.2025.10.004","DOIUrl":"10.1016/j.mpdhp.2025.10.004","url":null,"abstract":"<div><div>Breast papillary lesions encompass a wide spectrum of entities characterized by a papillary architecture with arborizing fibrovascular cores. Clinical examination and imaging lack sufficient specificity to distinguish these lesions, making histopathologic analysis essential for accurate diagnosis. Classification hinges on the nature of proliferating epithelial cells and the presence or absence of basal myoepithelial cells. Benign lesions include intraductal papilloma, which may be accompanied by epithelial metaplasia, hyperplasia, or atypical ductal hyperplasia/ductal carcinoma <em>in situ</em> (DCIS). Malignant papillary lesions comprise papillary ductal carcinoma <em>in situ</em>, encapsulated papillary carcinoma, solid papillary carcinoma (<em>in situ</em> and invasive), and invasive papillary carcinoma. Their overlapping morphologic features and immunohistochemical (IHC) profiles pose diagnostic challenges, particularly on core needle biopsy, where underdiagnosis is more common than overdiagnosis. Distinguishing noninvasive from invasive malignant papillary tumors is critical for management and is supported by the presence of irregular clusters, tongues, and nests of tumor cells extending into the stroma beyond a well-defined boundary. Genetically, papillary carcinomas predominantly align with luminal subtypes, underscoring their generally low-grade biology.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 12","pages":"Pages 707-714"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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.mpdhp.2025.08.006
Vikram Deshpande, Osman Yilmaz, Monika Vyas, Yaileen D Guzman, Vanda F Torous
Anal squamous intraepithelial lesions (SILs) are a growing public health concern, particularly in high-risk populations such as men who have sex with men and individuals living with HIV. This review synthesizes current histopathologic, cytologic, and immunohistochemical approaches to the detection and classification of anal squamous intraepithelial lesions (SILs), with an emphasis on standardization and diagnostic precision. The adoption of the Lower Anogenital Squamous Terminology (LAST) Project's two-tiered system, distinguishing low-grade (LSIL) from high-grade squamous intraepithelial lesions (HSIL), has improved reproducibility and clinical relevance. Adjunctive biomarkers, such as p16, are valuable in equivocal cases but must be interpreted in conjunction with morphology. Anal cytology remains the cornerstone of screening, demonstrating moderate sensitivity and specificity, with performance varying significantly across different risk groups. Human papillomavirus (HPV) DNA testing offers higher sensitivity but lower specificity, necessitating the use of triage strategies that incorporate cytology, genotyping, and dual-stain biomarkers. Emerging machine learning tools, particularly AI-assisted digital cytology and automated p16/Ki-67 interpretation, show promise in enhancing diagnostic accuracy and reducing observer variability. Despite the absence of universally endorsed screening guidelines, the ANCHOR trial has validated the clinical benefit of treating HSIL to prevent anal cancer.
{"title":"Anal squamous intraepithelial lesions: a contemporary guide to histology, cytology, and diagnostic standardization","authors":"Vikram Deshpande, Osman Yilmaz, Monika Vyas, Yaileen D Guzman, Vanda F Torous","doi":"10.1016/j.mpdhp.2025.08.006","DOIUrl":"10.1016/j.mpdhp.2025.08.006","url":null,"abstract":"<div><div>Anal squamous intraepithelial lesions (SILs) are a growing public health concern, particularly in high-risk populations such as men who have sex with men and individuals living with HIV. This review synthesizes current histopathologic, cytologic, and immunohistochemical approaches to the detection and classification of anal squamous intraepithelial lesions (SILs), with an emphasis on standardization and diagnostic precision. The adoption of the Lower Anogenital Squamous Terminology (LAST) Project's two-tiered system, distinguishing low-grade (LSIL) from high-grade squamous intraepithelial lesions (HSIL), has improved reproducibility and clinical relevance. Adjunctive biomarkers, such as p16, are valuable in equivocal cases but must be interpreted in conjunction with morphology. Anal cytology remains the cornerstone of screening, demonstrating moderate sensitivity and specificity, with performance varying significantly across different risk groups. Human papillomavirus (HPV) DNA testing offers higher sensitivity but lower specificity, necessitating the use of triage strategies that incorporate cytology, genotyping, and dual-stain biomarkers. Emerging machine learning tools, particularly AI-assisted digital cytology and automated p16/Ki-67 interpretation, show promise in enhancing diagnostic accuracy and reducing observer variability. Despite the absence of universally endorsed screening guidelines, the ANCHOR trial has validated the clinical benefit of treating HSIL to prevent anal cancer.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 11","pages":"Pages 689-697"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145448679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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