Pub Date : 2025-04-01Epub Date: 2025-02-28DOI: 10.1016/j.mpdhp.2025.02.003
Umar A Hussain, Rajesh Rajendran, Guy Betts
Sinonasal biopsies are common specimens in surgical pathology but samples are often limited showing non-specific and often overlapping features between differential diagnoses. This review will summarize the relevant diagnostic and clinical features of common and important sinonasal inflammatory pathologies with emphasis on recent developments and areas of diagnostic difficulty.
{"title":"Inflammatory disorders of the sinonasal tract: a practical approach and recent updates","authors":"Umar A Hussain, Rajesh Rajendran, Guy Betts","doi":"10.1016/j.mpdhp.2025.02.003","DOIUrl":"10.1016/j.mpdhp.2025.02.003","url":null,"abstract":"<div><div>Sinonasal biopsies are common specimens in surgical pathology but samples are often limited showing non-specific and often overlapping features between differential diagnoses. This review will summarize the relevant diagnostic and clinical features of common and important sinonasal inflammatory pathologies with emphasis on recent developments and areas of diagnostic difficulty.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 4","pages":"Pages 210-220"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791177","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 : 2025-04-01Epub Date: 2025-03-13DOI: 10.1016/j.mpdhp.2025.02.004
Ella-Grace Kirton, Karwan Moutasim
Poorly differentiated carcinomas can be a challenging area for histopathologists and frequently require ancillary tests to arrive at a definitive diagnosis. Neuroendocrine markers have the potential to be helpful in establishing a diagnosis but can also cause diagnostic dilemmas when aberrantly expressed. Here, we present three case examples to illustrate this issue and highlight relevant learning points in each case.
{"title":"Head and neck tumours with neuroendocrine marker ‘expression’: pitfalls and learning points","authors":"Ella-Grace Kirton, Karwan Moutasim","doi":"10.1016/j.mpdhp.2025.02.004","DOIUrl":"10.1016/j.mpdhp.2025.02.004","url":null,"abstract":"<div><div>Poorly differentiated carcinomas can be a challenging area for histopathologists and frequently require ancillary tests to arrive at a definitive diagnosis. Neuroendocrine markers have the potential to be helpful in establishing a diagnosis but can also cause diagnostic dilemmas when aberrantly expressed. Here, we present three case examples to illustrate this issue and highlight relevant learning points in each case.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 4","pages":"Pages 221-227"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791178","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 : 2025-04-01Epub Date: 2025-02-19DOI: 10.1016/j.mpdhp.2025.02.001
Hannah Crane, Mollie Clark, Syed Ali Khurram
Salivary gland pathology can be a notoriously complex area of diagnostic histopathology, with a number of benign and malignant neoplasms which can show overlapping histological features. Following the publication of the 5th edition of the World Health Organization (WHO) classification of Head and Neck Tumours, the Royal College of Pathologists (RCPath) has recently published an updated dataset encompassing the reporting of salivary gland carcinomas. In the following article, we outline the important concepts within the new dataset; including new and emerging entities, histological tumour grading, extent of tumour invasion, pathological staging and the use of ancillary methods for diagnosis.
{"title":"Update on the dataset for histopathological reporting of salivary gland carcinomas: current concepts and controversies in salivary gland pathology","authors":"Hannah Crane, Mollie Clark, Syed Ali Khurram","doi":"10.1016/j.mpdhp.2025.02.001","DOIUrl":"10.1016/j.mpdhp.2025.02.001","url":null,"abstract":"<div><div>Salivary gland pathology can be a notoriously complex area of diagnostic histopathology, with a number of benign and malignant neoplasms which can show overlapping histological features. Following the publication of the 5th edition of the World Health Organization (WHO) classification of Head and Neck Tumours, the Royal College of Pathologists (RCPath) has recently published an updated dataset encompassing the reporting of salivary gland carcinomas. In the following article, we outline the important concepts within the new dataset; including new and emerging entities, histological tumour grading, extent of tumour invasion, pathological staging and the use of ancillary methods for diagnosis.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 4","pages":"Pages 195-203"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791175","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 : 2025-04-01Epub Date: 2025-02-26DOI: 10.1016/j.mpdhp.2025.02.007
Lucy Ryan, Xin-Ying Kowa, Jonathan Joseph, Amrita Jay, Oluyori K Adegun
We report a case of an 88-year-old male with a large nasal lesion thought to be an inverted papilloma clinically and on imaging, but subsequently diagnosed histologically as a carcinoma, specifically, a non-keratinizing squamous cell carcinoma with the distinct DEK - AFF2 fusion. This variant of carcinoma in the head and neck is an emerging entity thought to have a distinct morphology, that should prompt molecular studies. Overlapping histological features with benign papillomatous lesions emphasizes the need for identification of this entity, as they have been associated with an aggressive clinical course including relapse and distant metastases. In addition, identification of the specific fusion may potentially add to the therapeutic armamentarium.
{"title":"DEK::AFF2 fusion positive carcinoma, a potentially misdiagnosed entity: overview of histology and diagnostic clues","authors":"Lucy Ryan, Xin-Ying Kowa, Jonathan Joseph, Amrita Jay, Oluyori K Adegun","doi":"10.1016/j.mpdhp.2025.02.007","DOIUrl":"10.1016/j.mpdhp.2025.02.007","url":null,"abstract":"<div><div>We report a case of an 88-year-old male with a large nasal lesion thought to be an inverted papilloma clinically and on imaging, but subsequently diagnosed histologically as a carcinoma, specifically, a non-keratinizing squamous cell carcinoma with the distinct DEK - AFF2 fusion. This variant of carcinoma in the head and neck is an emerging entity thought to have a distinct morphology, that should prompt molecular studies. Overlapping histological features with benign papillomatous lesions emphasizes the need for identification of this entity, as they have been associated with an aggressive clinical course including relapse and distant metastases. In addition, identification of the specific fusion may potentially add to the therapeutic armamentarium.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 4","pages":"Pages 249-252"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791181","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 : 2025-03-01Epub Date: 2025-01-17DOI: 10.1016/j.mpdhp.2024.12.006
Rebecca N Young, Raluca Grigorescu, Sampada Gupta
Mammary mucinous cystadenocarcinoma is a rare primary breast malignancy. First described in 1998 by Koenig and Tavassoli, it was named in the third edition of the WHO International Classification of Tumours (2003) but was only recognized as a distinct entity in the most recent fifth edition (2019). Lack of data impedes our understanding of tumourigenesis and long-term prognosis. No standardized treatment protocol is available. Here we present a case in which this unusual diagnosis was suggested on core biopsy and confirmed on surgical resection. The purpose of this case report is to add to the data on its long-term behaviour, and illustrate an approach to its diagnosis.
{"title":"Mucinous cystadenocarcinoma of the breast: a case report of a rare entity and how to recognize it","authors":"Rebecca N Young, Raluca Grigorescu, Sampada Gupta","doi":"10.1016/j.mpdhp.2024.12.006","DOIUrl":"10.1016/j.mpdhp.2024.12.006","url":null,"abstract":"<div><div>Mammary mucinous cystadenocarcinoma is a rare primary breast malignancy. First described in 1998 by Koenig and Tavassoli, it was named in the third edition of the WHO International Classification of Tumours (2003) but was only recognized as a distinct entity in the most recent fifth edition (2019). Lack of data impedes our understanding of tumourigenesis and long-term prognosis. No standardized treatment protocol is available. Here we present a case in which this unusual diagnosis was suggested on core biopsy and confirmed on surgical resection. The purpose of this case report is to add to the data on its long-term behaviour, and illustrate an approach to its diagnosis.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 3","pages":"Pages 191-194"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534577","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 : 2025-03-01Epub Date: 2025-01-07DOI: 10.1016/j.mpdhp.2024.12.004
Jessica K Maguire, Aoife Maguire, Elena Provenzano, Cecily Quinn
Breast calcifications are frequently detected in women undergoing screening mammography and image-guided biopsy may be required to further investigate its aetiology. Calcifications are associated with a diverse range of pathological findings, including benign and malignant entities and lesions of uncertain biological potential. The aim of this paper is to outline an approach to the histopathological evaluation of breast biopsies, vacuum assisted excision and surgical specimens performed for the investigation of calcifications. We emphasise the importance of radiological-pathological correlation and the crucial role of multidisciplinary team meeting review and discussion in guiding further management.
{"title":"Calcification in breast histopathology","authors":"Jessica K Maguire, Aoife Maguire, Elena Provenzano, Cecily Quinn","doi":"10.1016/j.mpdhp.2024.12.004","DOIUrl":"10.1016/j.mpdhp.2024.12.004","url":null,"abstract":"<div><div>Breast calcifications are frequently detected in women undergoing screening mammography and image-guided biopsy may be required to further investigate its aetiology. Calcifications are associated with a diverse range of pathological findings, including benign and malignant entities and lesions of uncertain biological potential. The aim of this paper is to outline an approach to the histopathological evaluation of breast biopsies, vacuum assisted excision and surgical specimens performed for the investigation of calcifications. We emphasise the importance of radiological-pathological correlation and the crucial role of multidisciplinary team meeting review and discussion in guiding further management.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 3","pages":"Pages 174-181"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534578","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 : 2025-03-01Epub Date: 2025-01-06DOI: 10.1016/j.mpdhp.2024.12.001
Suzanne Parry, Lila Zabaglo, Dawn Wilkinson, Andrew Dodson
An EQA specifically designed for the assessment of immunohistochemical stain quality in the area of HER2-low testing was established by UK National Quality Assessment Scheme for Immunocytochemistry and In-Situ Hybridsiation (UK NEQAS ICC & ISH) at the beginning of 2023. We report on the results produced during the first 18-months of its operation (7 assessment runs, 527 submissions). At the first run 54.5% of participants’ submissions failed. The principal reason for failure was weak staining at this and at all subsequent assessments where submissions failed. The fail-rate continued to be above 50% for the first three assessment runs; beginning at run 4 and continuing in all following runs, the fail-rate declined such that it was around 20% at run 7. This change was not associated with any methodological parameter on which data was available (primary antibody, antigen retrieval, detection system or automation platform). Overall, 2258 core samples were available, 99.2% of all samples expected to be negative (HER2 0) showed staining concordant with that category; 71.% of those expected to stain as HER2 1+ and 60.5% of those expected to stain as HER2 2+ were assessed as showing the correct level of staining. Core samples showing weaker than expected staining totalled 531 (23.5%) while 52 (2.3%) showed stronger staining than expected. The 4B5 clone (Ventana) was the most commonly used primary antibody with 391 (87.3%) of submissions using this clone; of which, 275 (70.3%) passed. In contrast none of the 25 (5.6%) submissions that used the CB11 clone (Oracle, Leica) achieved a pass.
{"title":"The UK National External Quality Assessment Scheme for Immunocytochemistry and In-Situ Hybridisation (UK NEQAS ICC & ISH) HER2-low EQA programme: a review of results and factors influencing successful staining","authors":"Suzanne Parry, Lila Zabaglo, Dawn Wilkinson, Andrew Dodson","doi":"10.1016/j.mpdhp.2024.12.001","DOIUrl":"10.1016/j.mpdhp.2024.12.001","url":null,"abstract":"<div><div>An EQA specifically designed for the assessment of immunohistochemical stain quality in the area of HER2-low testing was established by UK National Quality Assessment Scheme for Immunocytochemistry and In-Situ Hybridsiation (UK NEQAS ICC & ISH) at the beginning of 2023. We report on the results produced during the first 18-months of its operation (7 assessment runs, 527 submissions). At the first run 54.5% of participants’ submissions failed. The principal reason for failure was weak staining at this and at all subsequent assessments where submissions failed. The fail-rate continued to be above 50% for the first three assessment runs; beginning at run 4 and continuing in all following runs, the fail-rate declined such that it was around 20% at run 7. This change was not associated with any methodological parameter on which data was available (primary antibody, antigen retrieval, detection system or automation platform). Overall, 2258 core samples were available, 99.2% of all samples expected to be negative (HER2 0) showed staining concordant with that category; 71.% of those expected to stain as HER2 1+ and 60.5% of those expected to stain as HER2 2+ were assessed as showing the correct level of staining. Core samples showing weaker than expected staining totalled 531 (23.5%) while 52 (2.3%) showed stronger staining than expected. The 4B5 clone (Ventana) was the most commonly used primary antibody with 391 (87.3%) of submissions using this clone; of which, 275 (70.3%) passed. In contrast none of the 25 (5.6%) submissions that used the CB11 clone (Oracle, Leica) achieved a pass.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 3","pages":"Pages 131-144"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535229","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 : 2025-03-01Epub Date: 2025-01-06DOI: 10.1016/j.mpdhp.2024.12.002
Abeer M Shaaban, Michelle A McMahon, Nisha Sharma
Lesions of uncertain malignant potential (B3 lesions) comprise a number of diagnostic entities; some of which are associated with atypia. These lesions can be challenging diagnostically and management wise. Traditionally, diagnostic surgical excision was performed for those lesions. More recently, vacuum assisted excision has been adopted for adequate sampling of those lesions. The last couple of years has witnessed advances in the understanding of the biology and outcome of B3 lesions with relevant guidelines produced to guide the multidisciplinary teams managing patients with B3 diagnoses. This review covers the histological and radiological features of B3 lesions, updates on the current evidence and new management guidelines and provides practical tips for pathologists involved in the diagnosis and multidisciplinary team discussion of those difficult lesions.
{"title":"Recent advances in the diagnosis and management of B3 lesions","authors":"Abeer M Shaaban, Michelle A McMahon, Nisha Sharma","doi":"10.1016/j.mpdhp.2024.12.002","DOIUrl":"10.1016/j.mpdhp.2024.12.002","url":null,"abstract":"<div><div>Lesions of uncertain malignant potential (B3 lesions) comprise a number of diagnostic entities; some of which are associated with atypia. These lesions can be challenging diagnostically and management wise. Traditionally, diagnostic surgical excision was performed for those lesions. More recently, vacuum assisted excision has been adopted for adequate sampling of those lesions. The last couple of years has witnessed advances in the understanding of the biology and outcome of B3 lesions with relevant guidelines produced to guide the multidisciplinary teams managing patients with B3 diagnoses. This review covers the histological and radiological features of B3 lesions, updates on the current evidence and new management guidelines and provides practical tips for pathologists involved in the diagnosis and multidisciplinary team discussion of those difficult lesions.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 3","pages":"Pages 145-151"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535230","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 : 2025-03-01Epub Date: 2025-01-06DOI: 10.1016/j.mpdhp.2024.12.003
Giulia Querzoli, Adi S Levit, Zsuzsanna Varga, Maria Pia Foschini
Both breast and salivary glands are composed of tubuloacinar glands with similar histological structures, so it is not surprising that similar neoplasms can arise in both organs. However, given the different functions of the two glands and the different stimuli to which they are subjected, apparently similar tumours may present substantial differences. This review aims to examine the morphological and molecular profiles of salivary-like breast carcinomas, focusing on similarities and differences. Data were obtained from a comprehensive literature review, selecting relevant studies based on their novelty, applicability, and impact. Salivary-like breast carcinomas have been recognized for many years, but recent advances in understanding their molecular pathogenesis have provided new diagnostic tools and insights into these rare tumors.
{"title":"Insights into salivary gland-like breast carcinomas: histological features, immunophenotypes, molecular pathogenesis and diagnostic advancements","authors":"Giulia Querzoli, Adi S Levit, Zsuzsanna Varga, Maria Pia Foschini","doi":"10.1016/j.mpdhp.2024.12.003","DOIUrl":"10.1016/j.mpdhp.2024.12.003","url":null,"abstract":"<div><div>Both breast and salivary glands are composed of tubuloacinar glands with similar histological structures, so it is not surprising that similar neoplasms can arise in both organs. However, given the different functions of the two glands and the different stimuli to which they are subjected, apparently similar tumours may present substantial differences. This review aims to examine the morphological and molecular profiles of salivary-like breast carcinomas, focusing on similarities and differences. Data were obtained from a comprehensive literature review, selecting relevant studies based on their novelty, applicability, and impact. Salivary-like breast carcinomas have been recognized for many years, but recent advances in understanding their molecular pathogenesis have provided new diagnostic tools and insights into these rare tumors.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 3","pages":"Pages 152-161"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535231","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 : 2025-03-01Epub Date: 2025-02-01DOI: 10.1016/j.mpdhp.2025.01.001
Kastytis Sidlauskas, Philip Elliott, Purnima Makhija, J Louise Jones
Metastases can occur to the breast from extramammary sites and, more commonly, from the breast to a range of locations. In both situations, accurate diagnosis is critical to ensure appropriate management. Whilst metastatic lesions in the breast account for <2% of breast malignancies, identification of the primary source has implications for therapy. The most common lesions that metastasize to the breast include melanoma, haematological malignancies, lung, gastrointestinal and genitourinary malignancies. Careful morphological assessment can help flag features atypical for primary breast cancer, such as lack of an in-situ component or specific cellular morphology such as clear cell change, tall cells or high-grade discohesive cells. These features can guide selection of immunohistochemistry (IHC) to establish a diagnosis: panels of IHC to exclude primary breast carcinoma and confirm an alternate primary source are outlined, including the importance of the ‘ER+ trap’. Furthermore, a diagnostic approach to Carcinoma of Unknown Primary (CUP) is outlined. Metastases from the breast to distant sites are a major cause of mortality in breast cancer. The most common sites involved include bone, lung, liver and brain, though sites such as skin and peritoneum may be involved in ∼7% of cases. Different breast cancer subtypes display different propensity to metastasize to different organs: ER+ disease frequently metastasizes to bone with Triple Negative and Her2+ breast cancer more commonly spreading to lung and brain. Comprehensive IHC panels to distinguish between metastatic breast cancer and other metastatic lesions are outlined, emphasizing limitations of any given marker. For both metastatic lesions to the breast and identification of a breast origin in distant metastatic lesions, a multidisciplinary approach to diagnosis is essential, including provision of a detailed patient history. Using these approaches, it should be possible to avoid errors in diagnosis, even in challenging cases, and give the best treatment option to patients.
{"title":"Metastasis to and from the breast: a guide to differential diagnosis and ancillary testing","authors":"Kastytis Sidlauskas, Philip Elliott, Purnima Makhija, J Louise Jones","doi":"10.1016/j.mpdhp.2025.01.001","DOIUrl":"10.1016/j.mpdhp.2025.01.001","url":null,"abstract":"<div><div>Metastases can occur to the breast from extramammary sites and, more commonly, from the breast to a range of locations. In both situations, accurate diagnosis is critical to ensure appropriate management. Whilst metastatic lesions in the breast account for <2% of breast malignancies, identification of the primary source has implications for therapy. The most common lesions that metastasize to the breast include melanoma, haematological malignancies, lung, gastrointestinal and genitourinary malignancies. Careful morphological assessment can help flag features atypical for primary breast cancer, such as lack of an in-situ component or specific cellular morphology such as clear cell change, tall cells or high-grade discohesive cells. These features can guide selection of immunohistochemistry (IHC) to establish a diagnosis: panels of IHC to exclude primary breast carcinoma and confirm an alternate primary source are outlined, including the importance of the ‘ER+ trap’. Furthermore, a diagnostic approach to Carcinoma of Unknown Primary (CUP) is outlined. Metastases from the breast to distant sites are a major cause of mortality in breast cancer. The most common sites involved include bone, lung, liver and brain, though sites such as skin and peritoneum may be involved in ∼7% of cases. Different breast cancer subtypes display different propensity to metastasize to different organs: ER+ disease frequently metastasizes to bone with Triple Negative and Her2+ breast cancer more commonly spreading to lung and brain. Comprehensive IHC panels to distinguish between metastatic breast cancer and other metastatic lesions are outlined, emphasizing limitations of any given marker. For both metastatic lesions to the breast and identification of a breast origin in distant metastatic lesions, a multidisciplinary approach to diagnosis is essential, including provision of a detailed patient history. Using these approaches, it should be possible to avoid errors in diagnosis, even in challenging cases, and give the best treatment option to patients.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"31 3","pages":"Pages 162-173"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535232","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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