Pub Date : 2025-03-25DOI: 10.1016/j.humpath.2025.105760
Katharine Schulz-Costello, Fang Fan, Daniel Schmolze, Javier A Arias-Stella, Lesley Taylor, Jennifer Tseng, Michelle Afkhami, Jamie G Rand, Veronica Jones, Preeti Farmah, Min Han
Solid basaloid adenoid cystic carcinoma of the breast (SB-AdCC) is an exceedingly rare but important entity that warrants clear separation from classic AdCC (C-AdCC) for optimal treatment. This case series retrospectively reviewed the diagnosis and treatment of 20 breast AdCCs. While four breast pathologists reached consensus on the diagnosis of all C-AdCCs, there was considerable disagreement when diagnosing pure SB-AdCCs. The morphology and immunohistochemical profiles of SB-AdCC closely resemble those of basaloid triple-negative breast carcinoma (TNBC). Molecular profiling of SB-AdCC revealed frequent mutations in the Notch pathway and alterations in chromatin modifiers, such as CREBBP and KMT2D. MYB-NFIB fusion was rare and detected in only 2 of 9 (22.2%) SB-AdCCs. Axillary lymph node metastasis was present in 2 of 10 patients with SB-AdCC at the time of surgery. During a median follow-up of 27 months, one patient with SB-AdCC developed axillary recurrence. Moreover, 6 of 12 (50.0%) patients with SB-AdCC developed distant metastases. Of the three patients who underwent neoadjuvant chemotherapy for SB-AdCC, one achieved near-complete pathological response, while the remaining two had minimal response. In conclusion, this series underscores the aggressive clinical course of SB-AdCC, similar to conventional TNBC. Pathologically, SB-AdCC also closely mimics conventional TNBC. It is imperative for pathologists to clearly indicate C-AdCC or SB-AdCC or give a percentage of each component to ensure appropriate treatment strategies and avoid both over-treatment and under-treatment.
{"title":"Solid basaloid adenoid cystic carcinoma of the breast: a high-grade triple negative breast carcinoma which rarely responds to neoadjuvant chemotherapy.","authors":"Katharine Schulz-Costello, Fang Fan, Daniel Schmolze, Javier A Arias-Stella, Lesley Taylor, Jennifer Tseng, Michelle Afkhami, Jamie G Rand, Veronica Jones, Preeti Farmah, Min Han","doi":"10.1016/j.humpath.2025.105760","DOIUrl":"https://doi.org/10.1016/j.humpath.2025.105760","url":null,"abstract":"<p><p>Solid basaloid adenoid cystic carcinoma of the breast (SB-AdCC) is an exceedingly rare but important entity that warrants clear separation from classic AdCC (C-AdCC) for optimal treatment. This case series retrospectively reviewed the diagnosis and treatment of 20 breast AdCCs. While four breast pathologists reached consensus on the diagnosis of all C-AdCCs, there was considerable disagreement when diagnosing pure SB-AdCCs. The morphology and immunohistochemical profiles of SB-AdCC closely resemble those of basaloid triple-negative breast carcinoma (TNBC). Molecular profiling of SB-AdCC revealed frequent mutations in the Notch pathway and alterations in chromatin modifiers, such as CREBBP and KMT2D. MYB-NFIB fusion was rare and detected in only 2 of 9 (22.2%) SB-AdCCs. Axillary lymph node metastasis was present in 2 of 10 patients with SB-AdCC at the time of surgery. During a median follow-up of 27 months, one patient with SB-AdCC developed axillary recurrence. Moreover, 6 of 12 (50.0%) patients with SB-AdCC developed distant metastases. Of the three patients who underwent neoadjuvant chemotherapy for SB-AdCC, one achieved near-complete pathological response, while the remaining two had minimal response. In conclusion, this series underscores the aggressive clinical course of SB-AdCC, similar to conventional TNBC. Pathologically, SB-AdCC also closely mimics conventional TNBC. It is imperative for pathologists to clearly indicate C-AdCC or SB-AdCC or give a percentage of each component to ensure appropriate treatment strategies and avoid both over-treatment and under-treatment.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105760"},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729566","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}
Pub Date : 2025-03-19DOI: 10.1016/j.humpath.2025.105759
Raza S Hoda, Hannah Y Wen
This review addresses common diagnostic challenges associated with papillary breast tumors-a rare but significant category of breast lesions. Despite their low incidence, papillary tumors are frequently encountered in breast pathology consultation practice due to their overlapping terminology and perplexing immunohistochemical results. Issues regarding assessment of invasive carcinoma in the setting of solid papillary carcinoma and encapsulated papillary carcinoma are covered. Emerging entities, such as tall cell carcinoma with reversed polarity and invasive lobular carcinoma mimicking solid papillary carcinoma, are discussed. Additionally, pragmatic guidance is provided for managing papillary breast tumors on needle core biopsy. Herein, we aim to provide clarity and confidence to surgical pathologists dealing with papillary breast tumors-mammary Medusa-equipping them with practical knowledge to better navigate this complex area of breast pathology.
{"title":"Challenges in papillary tumors of breast.","authors":"Raza S Hoda, Hannah Y Wen","doi":"10.1016/j.humpath.2025.105759","DOIUrl":"10.1016/j.humpath.2025.105759","url":null,"abstract":"<p><p>This review addresses common diagnostic challenges associated with papillary breast tumors-a rare but significant category of breast lesions. Despite their low incidence, papillary tumors are frequently encountered in breast pathology consultation practice due to their overlapping terminology and perplexing immunohistochemical results. Issues regarding assessment of invasive carcinoma in the setting of solid papillary carcinoma and encapsulated papillary carcinoma are covered. Emerging entities, such as tall cell carcinoma with reversed polarity and invasive lobular carcinoma mimicking solid papillary carcinoma, are discussed. Additionally, pragmatic guidance is provided for managing papillary breast tumors on needle core biopsy. Herein, we aim to provide clarity and confidence to surgical pathologists dealing with papillary breast tumors-mammary Medusa-equipping them with practical knowledge to better navigate this complex area of breast pathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105759"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673631","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}
Pub Date : 2025-03-01DOI: 10.1016/j.humpath.2025.105758
Yuelu Zhu , Lin Li , Shun Wang , Bingzhi Wang , Lin Dong, Zhe Zhang, Ying Wang, Jiangtao Li, Haifeng Zhang, Haizhen Lu
Our previous study demonstrated that pathological grades of adenoid cystic carcinoma (ACC) correlate with distinct prognoses and treatment strategies. To explore the molecular alterations underlying these grades, we performed whole-exome sequencing (WES) on 20 head and neck ACC samples from 12 patients, categorized into grade I-II, grade III, and high-grade transformation (HGT). Comprehensive analyses, including somatic mutations, chromosomal structural variations, and phylogenetic tree construction, were conducted. Spatial transcriptome (ST) technology was further employed to analyze gene expression, pseudo-time trajectories, and copy number variations in a grade III sample. WES revealed that high-grade (grade III and HGT) ACC tissues frequently harbor mutations in TP53, PI3K pathway genes, and chromatin remodelers. Phylogenetic analysis showed that higher-grade regions exhibit more subclonal mutations or a larger proportion of intergenerational mutations. Copy number analysis identified recurrent deletions of 1p36.33 and amplifications of 8q24.21/9p24.1 in high-grade samples, along with significant deletions on chr12 in both WES and ST. ST pathway enrichment and cell trajectory analyses indicated that high-grade clusters are more primitive and proliferative, while low-grade clusters display greater microenvironmental stability and interstitial specialization. These findings highlight the complex spatial heterogeneity associated with ACC pathological grades, providing critical insights into disease progression and guiding therapeutic strategies.
{"title":"Molecular mapping in head and neck adenoid cystic carcinoma by pathological grade using whole-exome sequencing and spatial transcriptome","authors":"Yuelu Zhu , Lin Li , Shun Wang , Bingzhi Wang , Lin Dong, Zhe Zhang, Ying Wang, Jiangtao Li, Haifeng Zhang, Haizhen Lu","doi":"10.1016/j.humpath.2025.105758","DOIUrl":"10.1016/j.humpath.2025.105758","url":null,"abstract":"<div><div>Our previous study demonstrated that pathological grades of adenoid cystic carcinoma (ACC) correlate with distinct prognoses and treatment strategies. To explore the molecular alterations underlying these grades, we performed whole-exome sequencing (WES) on 20 head and neck ACC samples from 12 patients, categorized into grade I-II, grade III, and high-grade transformation (HGT). Comprehensive analyses, including somatic mutations, chromosomal structural variations, and phylogenetic tree construction, were conducted. Spatial transcriptome (ST) technology was further employed to analyze gene expression, pseudo-time trajectories, and copy number variations in a grade III sample. WES revealed that high-grade (grade III and HGT) ACC tissues frequently harbor mutations in TP53, PI3K pathway genes, and chromatin remodelers. Phylogenetic analysis showed that higher-grade regions exhibit more subclonal mutations or a larger proportion of intergenerational mutations. Copy number analysis identified recurrent deletions of 1p36.33 and amplifications of 8q24.21/9p24.1 in high-grade samples, along with significant deletions on chr12 in both WES and ST. ST pathway enrichment and cell trajectory analyses indicated that high-grade clusters are more primitive and proliferative, while low-grade clusters display greater microenvironmental stability and interstitial specialization. These findings highlight the complex spatial heterogeneity associated with ACC pathological grades, providing critical insights into disease progression and guiding therapeutic strategies.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105758"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663569","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}
Pub Date : 2025-03-01DOI: 10.1016/j.humpath.2025.105762
Dong He , Longhai Jin , Hanhan Geng , Lanqing Cao
Computational pathology has primarily focused on analyzing tissue slides, neglecting the valuable information contained in gross images. To bridge this gap, we proposed a novel approach leveraging the Swin Transformer architecture to develop a Swin-Transformer based Gross Features Detective Network (SGFD-network), which assist pathologists for locating diseased area in ovarian epithelial tumors based on their gross features. Our model was trained on 4129 gross images and achieved high accuracy rates of 88.9 %, 86.4 %, and 93.0 % for benign, borderline, and carcinoma group, respectively, demonstrating strong agreement with pathologist evaluations. Notably, we trained a new classifier to distinguish between borderline tumors and those with microinvasion or microinvasive carcinoma, addressing a significant challenge in frozen section sampling. Our study was the first to propose a solution to this challenge, showcasing high accuracy rates of 85.0 % and 92.2 % for each group, respectively. To further elucidate the decision-making process, we employed Class Activation Mapping-grad to identify high-contribution zones and applied k-means clustering to summarize these features. The resulting clustered features can effectively complement existing knowledge of gross examination, improving the distinction between borderline tumors and those with microinvasion or microinvasive carcinoma. Our model identifies high-risk areas for microinvasion or microinvasive carcinoma, enabling pathologists to target sampling more effectively during frozen sections. Furthermore, SGFD-network requires only a single 4090 graphics card and completes a single interpretation task in 3 min. This study demonstrates the potential of deep learning-based analysis of gross features to aid in ovarian epithelial tumors sampling, especially in frozen section.
{"title":"Deep learning-based analysis of gross features for ovarian epithelial tumors classification: A tool to assist pathologists for frozen section sampling","authors":"Dong He , Longhai Jin , Hanhan Geng , Lanqing Cao","doi":"10.1016/j.humpath.2025.105762","DOIUrl":"10.1016/j.humpath.2025.105762","url":null,"abstract":"<div><div>Computational pathology has primarily focused on analyzing tissue slides, neglecting the valuable information contained in gross images. To bridge this gap, we proposed a novel approach leveraging the Swin Transformer architecture to develop a Swin-Transformer based Gross Features Detective Network (SGFD-network), which assist pathologists for locating diseased area in ovarian epithelial tumors based on their gross features. Our model was trained on 4129 gross images and achieved high accuracy rates of 88.9 %, 86.4 %, and 93.0 % for benign, borderline, and carcinoma group, respectively, demonstrating strong agreement with pathologist evaluations. Notably, we trained a new classifier to distinguish between borderline tumors and those with microinvasion or microinvasive carcinoma, addressing a significant challenge in frozen section sampling. Our study was the first to propose a solution to this challenge, showcasing high accuracy rates of 85.0 % and 92.2 % for each group, respectively. To further elucidate the decision-making process, we employed Class Activation Mapping-grad to identify high-contribution zones and applied <em>k</em>-means clustering to summarize these features. The resulting clustered features can effectively complement existing knowledge of gross examination, improving the distinction between borderline tumors and those with microinvasion or microinvasive carcinoma. Our model identifies high-risk areas for microinvasion or microinvasive carcinoma, enabling pathologists to target sampling more effectively during frozen sections. Furthermore, SGFD-network requires only a single 4090 graphics card and completes a single interpretation task in 3 min. This study demonstrates the potential of deep learning-based analysis of gross features to aid in ovarian epithelial tumors sampling, especially in frozen section.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105762"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682677","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}
Pub Date : 2025-03-01DOI: 10.1016/j.humpath.2025.105763
Jacopo Ferro , Paola Francalanci , Valentina Angerilli , Barbara Cafferata , Maria D'Armiento , Anna Maria Buccoliero , Raduan Ahmed Franca , Alessandro Vanoli , Maria Cristina Macciomei , Luisa Santoro , Rita Alaggio , Matteo Fassan , Luca Mastracci , Diana Sacchi , Carla Giordano , Emanuela Pilozzi , Maria Cristina Giustiniani , Iacopo Panarese , Federica Grillo , Paola Parente
Objective
Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before 6 years of age, encompassing ‘pure’ IBD (Crohn's Colitis/Ulcerative Colitis)/non IBD colitis, and monogenic diseases (MDs), the latter often related to primary immunodeficiency disorders. A multidisciplinary approach is imperative for correct therapeutic management, as endoscopy and histology are not always completely informative. In this setting, the study aims to describe the extent/features of histologic lesions in both endoscopically damaged mucosa and otherwise endoscopically healthy (normal/near normal) mucosa.
Methods
Endoscopic data were retrospectively recorded, and histologic slides were collegially re-evaluated in a 93 VEO-IBD multicenter cohort, 76 (76/93 - 81,7 %) of which with complete endoscopic/histologic data.
Results
At endoscopy, lesions were reported by the clinician in 66/76 (86,8 %) cases. When endoscopic lesions were reported, histologic damage was also seen. Interestingly, histologic mucosal damage was also documented in 43,3 % (13/30) of cases with endoscopically healthy/nearly healthy mucosa. This misalignment between endoscopy and pathology was seen in about a third of (29,1 % - 7/24) ‘true’ IBD and all MDs (100 % - 6/6) (p = 0.0029).
Conclusion
In VEO-IBD, histologic lesions can be present in endoscopically ‘healthy’ intestinal mucosa. This finding is more frequent in MDs, suggesting the need to accurately sample all the mucosal tract in VEO-IBD patients, even when no endoscopic lesions are seen at endoscopy.
{"title":"Histologic alterations are common in Monogenic Disease patients with ‘healthy’ endoscopy: Results from a GIPAD-GIPPI multicenter study","authors":"Jacopo Ferro , Paola Francalanci , Valentina Angerilli , Barbara Cafferata , Maria D'Armiento , Anna Maria Buccoliero , Raduan Ahmed Franca , Alessandro Vanoli , Maria Cristina Macciomei , Luisa Santoro , Rita Alaggio , Matteo Fassan , Luca Mastracci , Diana Sacchi , Carla Giordano , Emanuela Pilozzi , Maria Cristina Giustiniani , Iacopo Panarese , Federica Grillo , Paola Parente","doi":"10.1016/j.humpath.2025.105763","DOIUrl":"10.1016/j.humpath.2025.105763","url":null,"abstract":"<div><h3>Objective</h3><div>Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before 6 years of age, encompassing ‘pure’ IBD (Crohn's Colitis/Ulcerative Colitis)/non IBD colitis, and monogenic diseases (MDs), the latter often related to primary immunodeficiency disorders. A multidisciplinary approach is imperative for correct therapeutic management, as endoscopy and histology are not always completely informative. In this setting, the study aims to describe the extent/features of histologic lesions in both endoscopically damaged mucosa and otherwise endoscopically healthy (normal/near normal) mucosa.</div></div><div><h3>Methods</h3><div>Endoscopic data were retrospectively recorded, and histologic slides were collegially re-evaluated in a 93 VEO-IBD multicenter cohort, 76 (76/93 - 81,7 %) of which with complete endoscopic/histologic data.</div></div><div><h3>Results</h3><div>At endoscopy, lesions were reported by the clinician in 66/76 (86,8 %) cases. When endoscopic lesions were reported, histologic damage was also seen. Interestingly, histologic mucosal damage was also documented in 43,3 % (13/30) of cases with endoscopically healthy/nearly healthy mucosa. This misalignment between endoscopy and pathology was seen in about a third of (29,1 % - 7/24) ‘true’ IBD and all MDs (100 % - 6/6) (p = 0.0029).</div></div><div><h3>Conclusion</h3><div>In VEO-IBD, histologic lesions can be present in endoscopically ‘healthy’ intestinal mucosa. This finding is more frequent in MDs, suggesting the need to accurately sample all the mucosal tract in VEO-IBD patients, even when no endoscopic lesions are seen at endoscopy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105763"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697891","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}
& Objective: Hyalinizing trabecular tumor of the thyroid (HTT) is a rare, low-risk neoplasm that poses diagnostic challenges. Very recently, PAX8::GLIS3 rearrangements were found to characterize HTT. We aimed to explore HTT's genetic profile, focusing on PAX8::GLIS3 rearrangements and GLIS3 immunohistochemical staining.
Methods
We conducted a retrospective study involving 8 cases histologically diagnosed as HTT. RNA sequencing and immunohistochemical staining for GLIS3 were performed on all cases.
Results
The study included five females and three males, with a tumor size ranging from 3 to 45 mm. RNA sequencing analysis showed PAX8::GLIS3 rearrangement in 6 cases (86 %). No other molecular alterations were found. However, one case failed due to the tissue quality, and one case did not show any gene fusion. Immunohistochemical staining for GLIS3 revealed nuclear positive expression in tumor cells for all cases where gene fusion was detected (100 %). A control group of 20 HTT mimickers showed no immunostaining for GLIS 3.
Conclusion
Our study confirms the consistent presence of PAX8::GLIS3 rearrangement in hyalinizing trabecular tumor (HTT) of the thyroid. Additionally, our novel finding of GLIS3 expression via immunohistochemistry enhances diagnostic precision for these tumors. Notably, our series demonstrates the correlation between positive GLIS3 expression and detection of PAX8::GLIS3 fusion by RNA sequencing, potentially expediting HTT diagnosis.
{"title":"Hyalinizing trabecular tumor of the thyroid: Interest of GLIS3 immunohistochemical study to detect PAX8::GLIS3 rearrangement","authors":"Ziyad Alsugair , Francoise Descotes , Jonathan Lopez , Myriam Decaussin-Petrucci","doi":"10.1016/j.humpath.2025.105761","DOIUrl":"10.1016/j.humpath.2025.105761","url":null,"abstract":"<div><h3>Background</h3><div><u>& Objective</u>: Hyalinizing trabecular tumor of the thyroid (HTT) is a rare, low-risk neoplasm that poses diagnostic challenges. Very recently, <em>PAX8::GLIS3</em> rearrangements were found to characterize HTT. We aimed to explore HTT's genetic profile, focusing on <em>PAX8::GLIS3</em> rearrangements and GLIS3 immunohistochemical staining.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study involving 8 cases histologically diagnosed as HTT. RNA sequencing and immunohistochemical staining for GLIS3 were performed on all cases.</div></div><div><h3>Results</h3><div>The study included five females and three males, with a tumor size ranging from 3 to 45 mm. RNA sequencing analysis showed <em>PAX8::GLIS3</em> rearrangement in 6 cases (86 %). No other molecular alterations were found. However, one case failed due to the tissue quality, and one case did not show any gene fusion. Immunohistochemical staining for GLIS3 revealed nuclear positive expression in tumor cells for all cases where gene fusion was detected (100 %). A control group of 20 HTT mimickers showed no immunostaining for GLIS 3.</div></div><div><h3>Conclusion</h3><div>Our study confirms the consistent presence of <em>PAX8::GLIS3</em> rearrangement in hyalinizing trabecular tumor (HTT) of the thyroid. Additionally, our novel finding of GLIS3 expression via immunohistochemistry enhances diagnostic precision for these tumors. Notably, our series demonstrates the correlation between positive GLIS3 expression and detection of <em>PAX8::GLIS3</em> fusion by RNA sequencing, potentially expediting HTT diagnosis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105761"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691966","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}
Pub Date : 2025-03-01DOI: 10.1016/j.humpath.2025.105757
Florian Viehweger , Justus Gusinde , Nicolai Leege , Lisa-Maria Tinger , Natalia Gorbokon , Anne Menz , Ria Schlichter , Andrea Hinsch , David Dum , Christian Bernreuther , Sören Weidemann , Florian Lutz , Simon Kind , Viktoria Chirico , Katharina Möller , Viktor Reiswich , Andreas M. Luebke , Morton Freytag , Maximilian Lennartz , Frank Jacobsen , Sarah Minner
Estrogen receptor (ER) is a ligand-activated transcription factor with a critical role in development and function of multiple organ systems and a well-established drug target for breast cancer. To comprehensively evaluate ER expression in normal and tumor tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). ER positivity was found in 55 different tumor types including 26 entities with at least one strongly positive tumor. ER positivity strongly predominated in breast neoplasms (81.1%) and in other gynecological tumors (39.4%) while only 0.8% of non-gynecological and non-mammary tumors showed ER positivity. Among these, ER staining – often at lower intensity – especially occurred in neuroendocrine neoplasms (up to 9.1%), salivary gland tumors (up to 8.3%), and in squamous cell carcinomas of different sites of origin (up to 6.7%). In invasive breast carcinoma (NST), reduced ER immunostaining was linked to high pT (p < 0.0001), high grade (p < 0.0001), distant metastasis (p = 0.0012), HER2 positivity (p < 0.0001), PR negativity (p < 0.0001) and shorter overall survival (p = 0.0576). In serous high-grade ovarian cancer, reduced ER staining was linked to nodal metastasis (p = 0.0012). ER staining was unrelated to histopathological features in 145 analyzable endometroid endometrial carcinomas. Within non-mammary, non-gynecological, non-prostate, and non-testicular tumors, ER positivity was more common in tumors from female (1.4% of 2528) than from male patients (0.6% of 3228; p = 0.0003). In summary, our data provide a ranking list of tumor entities according to their prevalence of ER positivity and shows that ER can be strongly expressed in a small number of non-breast and non-gynecological tumors which could potentially represent a diagnostic pitfall in a cancer of unknown primary but also represents a therapeutic opportunity.
{"title":"Estrogen receptor expression in human tumors: A tissue microarray study evaluating more than 18,000 tumors from 149 different entities","authors":"Florian Viehweger , Justus Gusinde , Nicolai Leege , Lisa-Maria Tinger , Natalia Gorbokon , Anne Menz , Ria Schlichter , Andrea Hinsch , David Dum , Christian Bernreuther , Sören Weidemann , Florian Lutz , Simon Kind , Viktoria Chirico , Katharina Möller , Viktor Reiswich , Andreas M. Luebke , Morton Freytag , Maximilian Lennartz , Frank Jacobsen , Sarah Minner","doi":"10.1016/j.humpath.2025.105757","DOIUrl":"10.1016/j.humpath.2025.105757","url":null,"abstract":"<div><div>Estrogen receptor (ER) is a ligand-activated transcription factor with a critical role in development and function of multiple organ systems and a well-established drug target for breast cancer. To comprehensively evaluate ER expression in normal and tumor tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). ER positivity was found in 55 different tumor types including 26 entities with at least one strongly positive tumor. ER positivity strongly predominated in breast neoplasms (81.1%) and in other gynecological tumors (39.4%) while only 0.8% of non-gynecological and non-mammary tumors showed ER positivity. Among these, ER staining – often at lower intensity – especially occurred in neuroendocrine neoplasms (up to 9.1%), salivary gland tumors (up to 8.3%), and in squamous cell carcinomas of different sites of origin (up to 6.7%). In invasive breast carcinoma (NST), reduced ER immunostaining was linked to high pT (p < 0.0001), high grade (p < 0.0001), distant metastasis (p = 0.0012), HER2 positivity (p < 0.0001), PR negativity (p < 0.0001) and shorter overall survival (p = 0.0576). In serous high-grade ovarian cancer, reduced ER staining was linked to nodal metastasis (p = 0.0012). ER staining was unrelated to histopathological features in 145 analyzable endometroid endometrial carcinomas. Within non-mammary, non-gynecological, non-prostate, and non-testicular tumors, ER positivity was more common in tumors from female (1.4% of 2528) than from male patients (0.6% of 3228; p = 0.0003). In summary, our data provide a ranking list of tumor entities according to their prevalence of ER positivity and shows that ER can be strongly expressed in a small number of non-breast and non-gynecological tumors which could potentially represent a diagnostic pitfall in a cancer of unknown primary but also represents a therapeutic opportunity.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105757"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577909","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}
Pub Date : 2025-02-01DOI: 10.1016/j.humpath.2024.105671
Wei Xie , L. Jeffrey Medeiros , Guang Fan , Shaoying Li , Jie Xu
Anaplastic large cell lymphoma (ALCL) is a mature T-cell neoplasm characterized by large pleomorphic cells, often with horseshoe- or kidney-shaped nuclei and abundant cytoplasm (hallmark cells), and uniformly strong CD30 expression. Based on ALK expression or ALK rearrangement, ALCL is further classified into ALK-positive (ALK+) and ALK-negative types. This review focuses on the clinicopathologic, immunophenotypic, cytogenetic and molecular features of systemic ALK-negative ALCL. These patients are usually older adults who present with advanced stage disease and often a poor prognosis. ALK-negative ALCL is morphologically indistinguishable from the common pattern of ALK+ ALCL, but some cases show non-common morphology, such as “donut cells”, Hodgkin-like features. ALK-negative ALCL is often negative for T-cell antigens (so-called “antigen loss”) and in some cases can have a “null” immunophenotype and be confused with other hematopoietic and non-hematopoietic neoplasms. Recurrent genetic/molecular alterations have been identified in systemic ALK-negative ALCL, including rearrangements of DUSP22, TP63, JAK2, FRK, MYC, ROS1 and TYK2; mutations of JAK1, STAT3 and MSCE; and aberrant expression of ERBB4. Some of these alterations may have prognostic significance and/or provide potential therapeutic targets. Data support the idea that ALK-negative ALCL with DUSP22 rearrangement is a distinctive variant due to its unique morphologic, immunophenotypic and molecular features. Gene expression profiling data have shown that ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.
{"title":"Systemic ALK-negative anaplastic large cell lymphoma: Insights into morphologic, immunophenotypic, genetic and molecular characteristics","authors":"Wei Xie , L. Jeffrey Medeiros , Guang Fan , Shaoying Li , Jie Xu","doi":"10.1016/j.humpath.2024.105671","DOIUrl":"10.1016/j.humpath.2024.105671","url":null,"abstract":"<div><div>Anaplastic large cell lymphoma (ALCL) is a mature T-cell neoplasm characterized by large pleomorphic cells, often with horseshoe- or kidney-shaped nuclei and abundant cytoplasm (hallmark cells), and uniformly strong CD30 expression. Based on ALK expression or <em>ALK</em> rearrangement, ALCL is further classified into ALK-positive (ALK+) and ALK-negative types. This review focuses on the clinicopathologic, immunophenotypic, cytogenetic and molecular features of systemic ALK-negative ALCL. These patients are usually older adults who present with advanced stage disease and often a poor prognosis. ALK-negative ALCL is morphologically indistinguishable from the common pattern of ALK+ ALCL, but some cases show non-common morphology, such as “donut cells”, Hodgkin-like features. ALK-negative ALCL is often negative for T-cell antigens (so-called “antigen loss”) and in some cases can have a “null” immunophenotype and be confused with other hematopoietic and non-hematopoietic neoplasms. Recurrent genetic/molecular alterations have been identified in systemic ALK-negative ALCL, including rearrangements of <em>DUSP22</em>, <em>TP63, JAK2, FRK, MYC, ROS1</em> and <em>TYK2</em>; mutations of <em>JAK1, STAT3</em> and <em>MSCE</em>; and aberrant expression of <em>ERBB4</em>. Some of these alterations may have prognostic significance and/or provide potential therapeutic targets. Data support the idea that ALK-negative ALCL with <em>DUSP22</em> rearrangement is a distinctive variant due to its unique morphologic, immunophenotypic and molecular features. Gene expression profiling data have shown that ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105671"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464054","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}
Pub Date : 2025-02-01DOI: 10.1016/j.humpath.2024.105696
Nana P. Matsumoto , Mina L. Xu
Angioimmunoblastic T-cell lymphoma (AITL), or nodal T-follicular helper cell lymphoma, angioimmunoblastic type, is a rare and aggressive type of T-cell lymphoma characterized by a spectrum of clinical and histopathological features that can present diagnostic challenges. Derived from T-follicular helper cells, the genesis of AITL is thought to be a multistep process involving mutations in epigenetic regulatory genes such as TET2 and DNMT3A, followed by driver mutations in RHOAG17V and IDH2R172 which promote clonal expansion as well as a characteristic inflammatory milieu. This review aims to provide a comprehensive overview of AITL, including its clinical presentation, epidemiology, pathogenesis, histomorphology and treatment options. Despite advancements in the understanding of AITL biology and the development of novel treatment strategies, the prognosis for patients with AITL remains poor.
{"title":"Angioimmunoblastic T-cell lymphoma: Current Diagnostic Insights and Advances","authors":"Nana P. Matsumoto , Mina L. Xu","doi":"10.1016/j.humpath.2024.105696","DOIUrl":"10.1016/j.humpath.2024.105696","url":null,"abstract":"<div><div>Angioimmunoblastic T-cell lymphoma (AITL), or nodal T-follicular helper cell lymphoma, angioimmunoblastic type, is a rare and aggressive type of T-cell lymphoma characterized by a spectrum of clinical and histopathological features that can present diagnostic challenges. Derived from T-follicular helper cells, the genesis of AITL is thought to be a multistep process involving mutations in epigenetic regulatory genes such as <em>TET2</em> and <em>DNMT3A</em>, followed by driver mutations in <em>RHOA</em><sup><em>G17V</em></sup> and <em>IDH2</em><sup><em>R172</em></sup> which promote clonal expansion as well as a characteristic inflammatory milieu. This review aims to provide a comprehensive overview of AITL, including its clinical presentation, epidemiology, pathogenesis, histomorphology and treatment options. Despite advancements in the understanding of AITL biology and the development of novel treatment strategies, the prognosis for patients with AITL remains poor.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"156 ","pages":"Article 105696"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686805","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}
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