Pub Date : 2025-02-01Epub Date: 2024-10-28DOI: 10.1097/PAS.0000000000002328
Ying Wan, Ping Zhou, Yuqing Miao, Lili Jiang
Pulmonary sclerosing pneumocytoma (PSP) is a rare neoplasm with indolent clinical behavior and usually presents as a solitary nodule, while only a few cases involving multiple nodules. Recent studies have revealed frequent AKT1 mutations in PSP; however, the molecular genetics of multiple PSPs remain unclear. To better understand the genetic background, eleven patients (4.2%, 11/260) with multiple PSP nodules were identified, and whole-exome sequencing (WES) was performed on 6 patients. Among 5 patients with 2 or 3 PSP nodules, AKT1 alterations were the most common (50%, 7/14), and the predominant alteration was p.E17K (21.4%, 3/14). Novel ARID1A mutations were the second most common driver (14.3%, 2/14), and we first identified these mutations cooccurred with AKT1 p.E17K mutation. Moreover, we observed limited concordance in the mutation spectra and few comutated genes among different lesions from these 5 patients, indicating that PSP with 2 or 3 nodules were independent arising tumors. No AKT1 mutations were identified in 3 PSP samples from a patient with multiple diffuse nodules. However, there were 17 shared genetic alterations among the 3 lesions, but none were typical driver mutations. The findings on multiple diffuse PSP nodules may also have independent origins, but the potential that some of these nodules are metastatic nodules cannot be excluded. In conclusion, this retrospective study is the largest series of multiple PSP cases and provides new insights into the genomic underpinning of PSP. This work has a potential to broaden our understanding of the pathogenesis and development of these lesions and warrants analysis in larger cohorts.
{"title":"Multiple Pulmonary Sclerosing Pneumocytomas (PSPs): A Comprehensive Analysis of Clinicopathological Characteristics and Whole-exome Sequencing (WES) Results.","authors":"Ying Wan, Ping Zhou, Yuqing Miao, Lili Jiang","doi":"10.1097/PAS.0000000000002328","DOIUrl":"10.1097/PAS.0000000000002328","url":null,"abstract":"<p><p>Pulmonary sclerosing pneumocytoma (PSP) is a rare neoplasm with indolent clinical behavior and usually presents as a solitary nodule, while only a few cases involving multiple nodules. Recent studies have revealed frequent AKT1 mutations in PSP; however, the molecular genetics of multiple PSPs remain unclear. To better understand the genetic background, eleven patients (4.2%, 11/260) with multiple PSP nodules were identified, and whole-exome sequencing (WES) was performed on 6 patients. Among 5 patients with 2 or 3 PSP nodules, AKT1 alterations were the most common (50%, 7/14), and the predominant alteration was p.E17K (21.4%, 3/14). Novel ARID1A mutations were the second most common driver (14.3%, 2/14), and we first identified these mutations cooccurred with AKT1 p.E17K mutation. Moreover, we observed limited concordance in the mutation spectra and few comutated genes among different lesions from these 5 patients, indicating that PSP with 2 or 3 nodules were independent arising tumors. No AKT1 mutations were identified in 3 PSP samples from a patient with multiple diffuse nodules. However, there were 17 shared genetic alterations among the 3 lesions, but none were typical driver mutations. The findings on multiple diffuse PSP nodules may also have independent origins, but the potential that some of these nodules are metastatic nodules cannot be excluded. In conclusion, this retrospective study is the largest series of multiple PSP cases and provides new insights into the genomic underpinning of PSP. This work has a potential to broaden our understanding of the pathogenesis and development of these lesions and warrants analysis in larger cohorts.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"138-149"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-09-26DOI: 10.1097/PAS.0000000000002314
Burak Tekin, Ruifeng Guo, Lori A Erickson, John C Cheville, Sounak Gupta
{"title":"Re: p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis.","authors":"Burak Tekin, Ruifeng Guo, Lori A Erickson, John C Cheville, Sounak Gupta","doi":"10.1097/PAS.0000000000002314","DOIUrl":"10.1097/PAS.0000000000002314","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"189-190"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-11-14DOI: 10.1097/PAS.0000000000002331
Miranda E Machacek, Hanzhang Wang, Kyle Devins, Peter M Sadow, Chin-Lee Wu, Esther Oliva, Philip J Saylor, Kristine M Cornejo
Staging of renal pelvic urothelial carcinoma can be challenging due to anatomic variation at the renal pelvis compared with ureter and bladder and calls into question the prognostic accuracy of the current TNM staging. In this study, we determined staging and cancer-specific survival (CSS) in 141 patients undergoing nephroureterectomy for renal pelvic urothelial carcinoma (pTa=50, pT1=29, pT2=10, pT3=36, and pT4=16). Under current staging criteria, we found no significant difference in CSS between adjacent staging categories step-wise across pTa, pT1, pT2, and pT3 tumors. When pT3 tumors were subcategorized into renal medulla, peripelvic adipose, or renal cortex invasion with or without peripelvic adipose invasion, we found that cortical invasion was associated with significantly worse CSS compared with medulla or peripelvic adipose invasion only. We next revised staging criteria such that pT1 correlated with invasion of lamina or muscularis propria (n=37), T2 with invasion of medulla or peripelvic adipose only (n=26), and pT3 with cortical invasion (n=12). Under the new criteria, better separation of survival curves was achieved; however, pT1 and pT2 remained statistically insignificant. When further redefining pT3 as invasive of cortex only (n=12) and combining medulla with lamina and muscularis propria invasion as a lower stage (pT1, n=63), there was further improvement in the prognostic stratification. Therefore, our data show that consideration of revised and simplified T staging criteria at the renal pelvis is warranted, wherein invasion of any anatomic structure up to the cortex shows a similar prognosis (combined pT1 category) and invasion of cortex showing significantly worse prognosis (pT3).
{"title":"A Proposal for Revised and Simplified Renal Pelvic Urothelial Carcinoma Staging Criteria: A Clinicopathologic Study of 141 Tumors.","authors":"Miranda E Machacek, Hanzhang Wang, Kyle Devins, Peter M Sadow, Chin-Lee Wu, Esther Oliva, Philip J Saylor, Kristine M Cornejo","doi":"10.1097/PAS.0000000000002331","DOIUrl":"10.1097/PAS.0000000000002331","url":null,"abstract":"<p><p>Staging of renal pelvic urothelial carcinoma can be challenging due to anatomic variation at the renal pelvis compared with ureter and bladder and calls into question the prognostic accuracy of the current TNM staging. In this study, we determined staging and cancer-specific survival (CSS) in 141 patients undergoing nephroureterectomy for renal pelvic urothelial carcinoma (pTa=50, pT1=29, pT2=10, pT3=36, and pT4=16). Under current staging criteria, we found no significant difference in CSS between adjacent staging categories step-wise across pTa, pT1, pT2, and pT3 tumors. When pT3 tumors were subcategorized into renal medulla, peripelvic adipose, or renal cortex invasion with or without peripelvic adipose invasion, we found that cortical invasion was associated with significantly worse CSS compared with medulla or peripelvic adipose invasion only. We next revised staging criteria such that pT1 correlated with invasion of lamina or muscularis propria (n=37), T2 with invasion of medulla or peripelvic adipose only (n=26), and pT3 with cortical invasion (n=12). Under the new criteria, better separation of survival curves was achieved; however, pT1 and pT2 remained statistically insignificant. When further redefining pT3 as invasive of cortex only (n=12) and combining medulla with lamina and muscularis propria invasion as a lower stage (pT1, n=63), there was further improvement in the prognostic stratification. Therefore, our data show that consideration of revised and simplified T staging criteria at the renal pelvis is warranted, wherein invasion of any anatomic structure up to the cortex shows a similar prognosis (combined pT1 category) and invasion of cortex showing significantly worse prognosis (pT3).</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"113-120"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-12-24DOI: 10.1097/PAS.0000000000002337
Manal Kordahi, Andréanne Gagné, Hanie Abolfathi, Michèle Orain, Christian Couture, Patrice Desmeules, Sylvain Trahan, Sylvain Pagé, Jonathan Vaucher, Frederic Nicodème, Massimo Conti, Paula Ugalde Figueroa, Anne-Sophie Laliberté, Fabien C Lamaze, Yohan Bossé, Philippe Joubert
Intraoperative frozen section (FS) examination of oncologic surgical specimens is frequently performed to ensure complete surgical resection. Data on the gross evaluation of surgical margins are limited. We recently published a study suggesting the use of a macroscopic 2.0 cm tumor-margin cutoff during intraoperative evaluation to decrease the number of unnecessary FS. This study aimed to validate the safety and the clinical impacts of implementing a 2.0 cm tumor-margin threshold for FS diagnosis in evaluating surgical margins during oncologic lung surgery. This retrospective analysis included patients who underwent lung resection for primary or metastatic neoplasms between 2018 and 2022 at the Institut Universitaire de Cardiologie et de Pneumologie de Québec, following the implementation of this practice. Clinicopathological data were retrieved from the medical files. Univariate and multivariate analyses were used to identify the variables associated with positive margins. This study included 1575 tumors in 1299 patients. FS evaluations were performed in 24.4% of patients. No positive margins were observed when the tumor-margin distance was >2.0 cm. The incidence rate of positive margins was 2.95%, with parenchymal margins being the most affected. Multivariate analysis identified the tumor-margin distance as a significant predictor of positive margin status. This practice led to a 79.9% reduction in FS evaluations without compromising the margin assessment accuracy or patient safety. A 2.0 cm tumor-margin distance threshold for intraoperative FS evaluation in oncologic lung surgery is safe and effective in reducing unnecessary FS evaluations while maintaining accurate margin assessments.
术中冷冻切片(FS)检查肿瘤手术标本经常进行,以确保手术完全切除。关于手术切缘大体评估的数据是有限的。我们最近发表了一项研究,建议在术中评估时使用宏观2.0 cm肿瘤边缘切除来减少不必要的FS数量。本研究旨在验证2.0 cm肿瘤边缘阈值在肺肿瘤手术中诊断FS的安全性和临床影响。这项回顾性分析纳入了2018年至2022年期间在心血管和肺部研究所(Institut Universitaire de Cardiologie et de Pneumologie de qubec)因原发性或转移性肿瘤接受肺切除术的患者。从医学档案中检索临床病理资料。采用单变量和多变量分析来确定与正边际相关的变量。这项研究包括1299名患者的1575个肿瘤。24.4%的患者进行了FS评估。当肿瘤与边缘距离为> ~ 2.0 cm时,未见阳性边缘。阳性切缘发生率为2.95%,以实质切缘发生率最高。多变量分析发现肿瘤边缘距离是肿瘤边缘阳性状态的重要预测因子。这种做法导致FS评估减少79.9%,而不影响差值评估的准确性和患者安全。在肺肿瘤性手术中,术中FS评估2.0 cm肿瘤边缘距离阈值是安全有效的,可以减少不必要的FS评估,同时保持准确的边缘评估。
{"title":"Impact of Implementing a Grossing Tumor-margin Distance Threshold for Frozen Section in Oncologic Lung Surgery.","authors":"Manal Kordahi, Andréanne Gagné, Hanie Abolfathi, Michèle Orain, Christian Couture, Patrice Desmeules, Sylvain Trahan, Sylvain Pagé, Jonathan Vaucher, Frederic Nicodème, Massimo Conti, Paula Ugalde Figueroa, Anne-Sophie Laliberté, Fabien C Lamaze, Yohan Bossé, Philippe Joubert","doi":"10.1097/PAS.0000000000002337","DOIUrl":"10.1097/PAS.0000000000002337","url":null,"abstract":"<p><p>Intraoperative frozen section (FS) examination of oncologic surgical specimens is frequently performed to ensure complete surgical resection. Data on the gross evaluation of surgical margins are limited. We recently published a study suggesting the use of a macroscopic 2.0 cm tumor-margin cutoff during intraoperative evaluation to decrease the number of unnecessary FS. This study aimed to validate the safety and the clinical impacts of implementing a 2.0 cm tumor-margin threshold for FS diagnosis in evaluating surgical margins during oncologic lung surgery. This retrospective analysis included patients who underwent lung resection for primary or metastatic neoplasms between 2018 and 2022 at the Institut Universitaire de Cardiologie et de Pneumologie de Québec, following the implementation of this practice. Clinicopathological data were retrieved from the medical files. Univariate and multivariate analyses were used to identify the variables associated with positive margins. This study included 1575 tumors in 1299 patients. FS evaluations were performed in 24.4% of patients. No positive margins were observed when the tumor-margin distance was >2.0 cm. The incidence rate of positive margins was 2.95%, with parenchymal margins being the most affected. Multivariate analysis identified the tumor-margin distance as a significant predictor of positive margin status. This practice led to a 79.9% reduction in FS evaluations without compromising the margin assessment accuracy or patient safety. A 2.0 cm tumor-margin distance threshold for intraoperative FS evaluation in oncologic lung surgery is safe and effective in reducing unnecessary FS evaluations while maintaining accurate margin assessments.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"169-175"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-12-06DOI: 10.1097/PAS.0000000000002336
Susanne K Jeffus, Jacob T Wooldridge, Lynn Hoang, Carlos Parra-Herran, Mugahed Hamza, Miki Lindsey, Meredith Verret, Nicholas Zoumberos, Bradley Fogel, Autumn Wyeth, João Gama, Charles M Quick
Squamous cell carcinoma of the vulva (vSCC) is currently categorized either as human papillomavirus (HPV) associated or independent. Immunohistochemical stains, p16 INK4a (p16) and p53 are helpful biomarkers to support the designation of vSCC into 1 of the 3 tumor pathways: (1) HPV-associated, (2) HPV-independent, TP53 mutant, or (3) HPV-independent, TP53 wild type. Recently, a framework of p53 expression patterns in vSCC was proposed. In this international and multi-institutional study, we evaluated the interrater agreement for p53 and p16 and tumor pathway classification in a cohort of 50 invasive vSCC across a variety of practice settings (private practice, academic medicine) and levels of expertise (trainees, gynecologic pathologists, dermatopathologists, private practice pathologists). Our study shows that the overall interrater agreement for the interpretation of p16 in vSCC is strong to near perfect, while the agreement for p53 and tumor pathway assignment is overall moderate. Interrater agreement for p53 and tumor pathway is higher (strong) in the academic practice setting. Pathologists without gynecologic subspecialty expertise benefited the most from a brief educational module, which fostered a better understanding and improved comfort level with the p16/p53 stain interpretation and tumor pathway designation in the diagnosis of vSCC. Some interpretative challenges remain, particularly in regard to select p53 patterns and high-risk HPV-in situ hybridization utilization, warranting additional research.
{"title":"Interpretation of p16 and p53 in the Classification of Squamous Cell Carcinoma of the Vulva-An Interobserver Agreement Study.","authors":"Susanne K Jeffus, Jacob T Wooldridge, Lynn Hoang, Carlos Parra-Herran, Mugahed Hamza, Miki Lindsey, Meredith Verret, Nicholas Zoumberos, Bradley Fogel, Autumn Wyeth, João Gama, Charles M Quick","doi":"10.1097/PAS.0000000000002336","DOIUrl":"10.1097/PAS.0000000000002336","url":null,"abstract":"<p><p>Squamous cell carcinoma of the vulva (vSCC) is currently categorized either as human papillomavirus (HPV) associated or independent. Immunohistochemical stains, p16 INK4a (p16) and p53 are helpful biomarkers to support the designation of vSCC into 1 of the 3 tumor pathways: (1) HPV-associated, (2) HPV-independent, TP53 mutant, or (3) HPV-independent, TP53 wild type. Recently, a framework of p53 expression patterns in vSCC was proposed. In this international and multi-institutional study, we evaluated the interrater agreement for p53 and p16 and tumor pathway classification in a cohort of 50 invasive vSCC across a variety of practice settings (private practice, academic medicine) and levels of expertise (trainees, gynecologic pathologists, dermatopathologists, private practice pathologists). Our study shows that the overall interrater agreement for the interpretation of p16 in vSCC is strong to near perfect, while the agreement for p53 and tumor pathway assignment is overall moderate. Interrater agreement for p53 and tumor pathway is higher (strong) in the academic practice setting. Pathologists without gynecologic subspecialty expertise benefited the most from a brief educational module, which fostered a better understanding and improved comfort level with the p16/p53 stain interpretation and tumor pathway designation in the diagnosis of vSCC. Some interpretative challenges remain, particularly in regard to select p53 patterns and high-risk HPV-in situ hybridization utilization, warranting additional research.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"176-187"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
While the skin is a common target organ for sarcoidosis, cutaneous granulomatous vasculitis is rare among patients with sarcoidosis. Due to the lack of detailed studies on cutaneous sarcoid vasculitis, both dermatologists and pathologists remain unfamiliar with this rare but important vasculitic disorder. We clinicopathologically evaluated eight cases with biopsy-proven cutaneous vasculitis and cutaneous sarcoidosis and analyzed morphologic changes in the process of vasculitis for both small vessels and muscular vessels in detail. The various skin lesions ranged from papulonodular erythema, annular erythema, maculopapular erythema, livedo reticularis-like eruptions, erythema nodosum-like lesions, subcutaneous nodules to ulcerative lesions. The extremities were the most frequently affected sites. Bilateral hilar lymphadenopathy with pulmonary sarcoidosis was the most common extracutaneous comorbidity. Skin-limited sarcoidosis was identified in 3 cases. All cases demonstrated a common histopathologic feature with sarcoid granulomas impinging on the target vessels with resultant vessel destruction. Perivascular infiltration of sarcoid granulomas resulted in compression and destruction of small vessels. In muscular arteries and veins, sarcoid granulomas closely attached to the muscular vessel wall, infiltrated the muscular layers and either occupied or penetrated the vessel walls, eventually invading the vascular lumen and replacing the entire muscular layers. The intimal infiltration of sarcoid granulomas resulted in a marked luminal narrowing. The scarcity of reports on cutaneous sarcoid vasculitis may be due to the overlooking or misinterpretation of vascular destruction caused by sarcoid granuloma infiltration as a feature of sarcoid granuloma masses.
{"title":"Sarcoid Vasculitis in the Skin: A Clinicopathologic Study of 8 Cases With Various Skin Lesions but the Common Unique Cannonball-like Vessel Destruction by Sarcoid Granulomas.","authors":"Ko-Ron Chen, Keiko Miura, Toyoko Inazumi, Yoshio Nakamura, Hideki Nakajima, Hayato Takahashi, Toshiyuki Yamamoto","doi":"10.1097/PAS.0000000000002333","DOIUrl":"10.1097/PAS.0000000000002333","url":null,"abstract":"<p><p>While the skin is a common target organ for sarcoidosis, cutaneous granulomatous vasculitis is rare among patients with sarcoidosis. Due to the lack of detailed studies on cutaneous sarcoid vasculitis, both dermatologists and pathologists remain unfamiliar with this rare but important vasculitic disorder. We clinicopathologically evaluated eight cases with biopsy-proven cutaneous vasculitis and cutaneous sarcoidosis and analyzed morphologic changes in the process of vasculitis for both small vessels and muscular vessels in detail. The various skin lesions ranged from papulonodular erythema, annular erythema, maculopapular erythema, livedo reticularis-like eruptions, erythema nodosum-like lesions, subcutaneous nodules to ulcerative lesions. The extremities were the most frequently affected sites. Bilateral hilar lymphadenopathy with pulmonary sarcoidosis was the most common extracutaneous comorbidity. Skin-limited sarcoidosis was identified in 3 cases. All cases demonstrated a common histopathologic feature with sarcoid granulomas impinging on the target vessels with resultant vessel destruction. Perivascular infiltration of sarcoid granulomas resulted in compression and destruction of small vessels. In muscular arteries and veins, sarcoid granulomas closely attached to the muscular vessel wall, infiltrated the muscular layers and either occupied or penetrated the vessel walls, eventually invading the vascular lumen and replacing the entire muscular layers. The intimal infiltration of sarcoid granulomas resulted in a marked luminal narrowing. The scarcity of reports on cutaneous sarcoid vasculitis may be due to the overlooking or misinterpretation of vascular destruction caused by sarcoid granuloma infiltration as a feature of sarcoid granuloma masses.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"150-158"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1097/PAS.0000000000002367
Guy A Williams, Annie A Wu, Henrietta C Eugene, Ya-Chea Tsai, Margaret Wong, Hiro Nonogaki, Richard B S Roden, Chien-Fu Hung, Tzyy-Choou Wu, Russell Vang, Deyin Xing
Despite being designated as "noncarcinogenic" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.
{"title":"Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva.","authors":"Guy A Williams, Annie A Wu, Henrietta C Eugene, Ya-Chea Tsai, Margaret Wong, Hiro Nonogaki, Richard B S Roden, Chien-Fu Hung, Tzyy-Choou Wu, Russell Vang, Deyin Xing","doi":"10.1097/PAS.0000000000002367","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002367","url":null,"abstract":"<p><p>Despite being designated as \"noncarcinogenic\" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-29DOI: 10.1097/PAS.0000000000002358
Alexis Trecourt, Marie Donzel, Lucie Gaillot-Durand, Pierre A Bolze, François Golfier, Pierre Descargues, Touria Hajri, Claire Mauduit, Mojgan Devouassoux-Shisheboran, Fabienne Allias
The distinction between choriocarcinoma and residual trophoblastic cell proliferation from a complete hydatidiform mole/invasive mole (CHM/IM) without villi is challenging on curettage materials. We investigated whether SALL4 immunostaining could help differentiate various gestational trophoblastic diseases. Placental site nodules (PSN; n=10), atypical PSN (APSN; n=8), placental site trophoblastic tumors (PSTT; n=9), epithelioid trophoblastic tumors (ETT; n=5), gestational choriocarcinomas (n=31), partial hydatidiform moles (PHM; n=13), CHM/IM (n=47), and nonmolar products of conception (POC) (n=26) were included. SALL4 immunostaining was quantified (0 [1% to 10%], [11% to 100%]) and characterized (scattered single-cell or clustered nuclear positivity) in 2 locations: cytotrophoblast/intermediate trophoblast and villous stromal fibroblasts. A diffuse (11% to 100%) and clustered pattern of SALL4 immunostaining in cytotrophoblast/intermediate trophoblast was statistically associated with choriocarcinomas (74.2%, 23/31) as compared with PSN (0/10; P<0.0001), APSN (0/8; P=0.0002), PSTT (0/9; P<0.0001), ETT (0/5; P=0.0034), PHM (0/13; P<0.0001), CHM/IM (0/47; P<0.0001), and nonmolar POC (0/26; P<0.0001). Most nonchoriocarcinoma samples showed no SALL4 expression; when present, it was of low level (1% to 10%) and with a scattered single-cell staining in 3/9 PSTT (33%), 1/13 PHM (7.7%), 19/47 CHM/IM (40%), and 1/26 nonmolar POC (1.7%). These results were confirmed using a validation cohort. In addition, 66% (31/47) of CHM/IM villous stromal fibroblasts showed SALL4 expression (11% to 100%) (all before 14 gestational weeks), whereas this level of expression was never observed in PHM (0/13), nor in nonmolar POC (0/26; P<0.0001). Finally, a clustered and >10% SALL4 immunostaining in cytotrophoblast/intermediate trophoblast favors choriocarcinoma diagnosis. SALL4 expression in >10% villous stromal fibroblasts before 14 gestational weeks favors CHM/IM rather than PHM and nonmolar POC.
{"title":"SALL4 as a Useful Marker for the Distinction of Various Gestational Trophoblastic Disease Subtypes: Choriocarcinoma From Other Trophoblastic Lesions and Early Complete Hydatidiform Mole From Partial Mole and NonMolar Villi.","authors":"Alexis Trecourt, Marie Donzel, Lucie Gaillot-Durand, Pierre A Bolze, François Golfier, Pierre Descargues, Touria Hajri, Claire Mauduit, Mojgan Devouassoux-Shisheboran, Fabienne Allias","doi":"10.1097/PAS.0000000000002358","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002358","url":null,"abstract":"<p><p>The distinction between choriocarcinoma and residual trophoblastic cell proliferation from a complete hydatidiform mole/invasive mole (CHM/IM) without villi is challenging on curettage materials. We investigated whether SALL4 immunostaining could help differentiate various gestational trophoblastic diseases. Placental site nodules (PSN; n=10), atypical PSN (APSN; n=8), placental site trophoblastic tumors (PSTT; n=9), epithelioid trophoblastic tumors (ETT; n=5), gestational choriocarcinomas (n=31), partial hydatidiform moles (PHM; n=13), CHM/IM (n=47), and nonmolar products of conception (POC) (n=26) were included. SALL4 immunostaining was quantified (0 [1% to 10%], [11% to 100%]) and characterized (scattered single-cell or clustered nuclear positivity) in 2 locations: cytotrophoblast/intermediate trophoblast and villous stromal fibroblasts. A diffuse (11% to 100%) and clustered pattern of SALL4 immunostaining in cytotrophoblast/intermediate trophoblast was statistically associated with choriocarcinomas (74.2%, 23/31) as compared with PSN (0/10; P<0.0001), APSN (0/8; P=0.0002), PSTT (0/9; P<0.0001), ETT (0/5; P=0.0034), PHM (0/13; P<0.0001), CHM/IM (0/47; P<0.0001), and nonmolar POC (0/26; P<0.0001). Most nonchoriocarcinoma samples showed no SALL4 expression; when present, it was of low level (1% to 10%) and with a scattered single-cell staining in 3/9 PSTT (33%), 1/13 PHM (7.7%), 19/47 CHM/IM (40%), and 1/26 nonmolar POC (1.7%). These results were confirmed using a validation cohort. In addition, 66% (31/47) of CHM/IM villous stromal fibroblasts showed SALL4 expression (11% to 100%) (all before 14 gestational weeks), whereas this level of expression was never observed in PHM (0/13), nor in nonmolar POC (0/26; P<0.0001). Finally, a clustered and >10% SALL4 immunostaining in cytotrophoblast/intermediate trophoblast favors choriocarcinoma diagnosis. SALL4 expression in >10% villous stromal fibroblasts before 14 gestational weeks favors CHM/IM rather than PHM and nonmolar POC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-10-30DOI: 10.1097/PAS.0000000000002325
Elan Hahn, Ilan Weinreb, Raja R Seethala, Esther O'Regan, Daniel Baumhoer, Elizabeth Ann Bilodeau, Jeffrey Gagan, Peter J B Sabatini, Yen Chen Kevin Ko, Nada Binmadi, R John McComb, Iona T Leong, Justin A Bishop
Sialadenoma papilliferum is a tumor characterized by surface papillary projections and glandular/microcystic proliferation at the lesion base. Cases in which surface involvement is absent have been termed "sialadenoma papilliferum-like intraductal papillary tumor." Similar tumors that are present in the mandible have been termed "tubulopapillary hidradenoma-like tumor of the mandible." While previously considered benign, these tumors demonstrate variable clinical behavior and likely exist on a spectrum, rather than as discrete entities. In this study, we present a detailed clinicopathologic and molecular analysis of these lesions and propose a unifying diagnostic term: sialadenopapillary ductal tumor (SDT). Twenty-two cases with similar histologic features were reviewed, with special attention being paid to the clinicopathologic features. Immunohistochemistry for BRAF V600E and molecular testing were performed where material was available. The cases had varying diagnoses, ranging from benign to malignant. Six cases involved bone, 1 of which metastasized to a local lymph node. Of the 20 cases tested for BRAF V600E by immunohistochemistry, 18 were positive. Molecular testing was performed in 5 cases, where BRAF, PTPN11, and PIK3CA mutations were identified, predominantly members of the RAS-RAF-MEK-ERK pathway. In addition, 1 case was reclassified as an intraductal carcinoma after the identification of an NCOA4::RET gene fusion. Tumors on the SDT spectrum all share morphologic and molecular commonalities with unreliable distinguishing features. These tumors demonstrate the potential for aggressive local growth and regional metastasis. We propose a unifying diagnostic term for these lesions to reflect their common morphologic and molecular features and, most importantly, low malignant potential.
{"title":"Sialadenopapillary Ductal Tumors: Unifying the Spectrum of Sialadenoma Papilliferum-like Tumors With Low Malignant Potential.","authors":"Elan Hahn, Ilan Weinreb, Raja R Seethala, Esther O'Regan, Daniel Baumhoer, Elizabeth Ann Bilodeau, Jeffrey Gagan, Peter J B Sabatini, Yen Chen Kevin Ko, Nada Binmadi, R John McComb, Iona T Leong, Justin A Bishop","doi":"10.1097/PAS.0000000000002325","DOIUrl":"10.1097/PAS.0000000000002325","url":null,"abstract":"<p><p>Sialadenoma papilliferum is a tumor characterized by surface papillary projections and glandular/microcystic proliferation at the lesion base. Cases in which surface involvement is absent have been termed \"sialadenoma papilliferum-like intraductal papillary tumor.\" Similar tumors that are present in the mandible have been termed \"tubulopapillary hidradenoma-like tumor of the mandible.\" While previously considered benign, these tumors demonstrate variable clinical behavior and likely exist on a spectrum, rather than as discrete entities. In this study, we present a detailed clinicopathologic and molecular analysis of these lesions and propose a unifying diagnostic term: sialadenopapillary ductal tumor (SDT). Twenty-two cases with similar histologic features were reviewed, with special attention being paid to the clinicopathologic features. Immunohistochemistry for BRAF V600E and molecular testing were performed where material was available. The cases had varying diagnoses, ranging from benign to malignant. Six cases involved bone, 1 of which metastasized to a local lymph node. Of the 20 cases tested for BRAF V600E by immunohistochemistry, 18 were positive. Molecular testing was performed in 5 cases, where BRAF, PTPN11, and PIK3CA mutations were identified, predominantly members of the RAS-RAF-MEK-ERK pathway. In addition, 1 case was reclassified as an intraductal carcinoma after the identification of an NCOA4::RET gene fusion. Tumors on the SDT spectrum all share morphologic and molecular commonalities with unreliable distinguishing features. These tumors demonstrate the potential for aggressive local growth and regional metastasis. We propose a unifying diagnostic term for these lesions to reflect their common morphologic and molecular features and, most importantly, low malignant potential.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"45-50"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-08DOI: 10.1097/PAS.0000000000002324
Lucas Vial, Françoise Descotes, Jonathan Lopez, Ziyad Alsugair, Philippe Céruse, Pierre Philouze, Maxime Fieux, Michel Wassef, Anne-Catherine Baglin, Mihaela Onea, Claire Castain, Philippe Delvenne, Gaelle Fromont-Hankard, Hugot Gilles, Franck Monnien, Olivier Mauvais, Charles Lépine, Francois Le Gall, Marie-Christine Rousselet, Anne Sudaka, Emmanuelle Uro-Coste, Odile Casiraghi, Valérie Costes-Martineau, Nazim Benzerdjeb
Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS and emerging entities" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification. It is becoming essential to clarify the complex spectrum of potential diagnoses surrounding oncocytic tumors. The objective of this study was to explore the histologic features, as well as the immunohistochemical and molecular profiles, of cases previously diagnosed as OC or OMEC of the salivary glands. This study involved 28 cases of carcinomas with a predominantly oncocytic component. The sex distribution was equal. The median age was 59 years (range 10 to 89). Most of these cases originated from the parotid gland (25/28). The mean tumor size was 2.4 cm (range 0.5 to 6.5). Primary immuno-morphological and mutation/gene fusion profiles reclassified mainly (64.3%, 18/28). Most of them were reclassified in descending order as OSDC (8/18), OMEC (5/18), and OC (2/18). But 3 cases remained unclassified (3/18). The transcriptomic analysis found a proximity of their transcriptomic profile with the OMEC group and a distance from the OSDCs. These findings imply that OC is not distinct but represents oncocytic variants of other salivary carcinomas. It underscores the importance of thorough morphologic, immunohistochemical, and molecular examinations to accurately diagnose carcinomas with predominant oncocytic components in the salivary glands.
{"title":"Reappraisal of Oncocytic Adenocarcinoma: Unveiling Its Connection to Oncocytic Variants of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma Through ImmunoHisto-Molecular Perspectives.","authors":"Lucas Vial, Françoise Descotes, Jonathan Lopez, Ziyad Alsugair, Philippe Céruse, Pierre Philouze, Maxime Fieux, Michel Wassef, Anne-Catherine Baglin, Mihaela Onea, Claire Castain, Philippe Delvenne, Gaelle Fromont-Hankard, Hugot Gilles, Franck Monnien, Olivier Mauvais, Charles Lépine, Francois Le Gall, Marie-Christine Rousselet, Anne Sudaka, Emmanuelle Uro-Coste, Odile Casiraghi, Valérie Costes-Martineau, Nazim Benzerdjeb","doi":"10.1097/PAS.0000000000002324","DOIUrl":"10.1097/PAS.0000000000002324","url":null,"abstract":"<p><p>Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as \"salivary carcinoma NOS and emerging entities\" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification. It is becoming essential to clarify the complex spectrum of potential diagnoses surrounding oncocytic tumors. The objective of this study was to explore the histologic features, as well as the immunohistochemical and molecular profiles, of cases previously diagnosed as OC or OMEC of the salivary glands. This study involved 28 cases of carcinomas with a predominantly oncocytic component. The sex distribution was equal. The median age was 59 years (range 10 to 89). Most of these cases originated from the parotid gland (25/28). The mean tumor size was 2.4 cm (range 0.5 to 6.5). Primary immuno-morphological and mutation/gene fusion profiles reclassified mainly (64.3%, 18/28). Most of them were reclassified in descending order as OSDC (8/18), OMEC (5/18), and OC (2/18). But 3 cases remained unclassified (3/18). The transcriptomic analysis found a proximity of their transcriptomic profile with the OMEC group and a distance from the OSDCs. These findings imply that OC is not distinct but represents oncocytic variants of other salivary carcinomas. It underscores the importance of thorough morphologic, immunohistochemical, and molecular examinations to accurately diagnose carcinomas with predominant oncocytic components in the salivary glands.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"73-82"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}