Pranav P Patwardhan, Nathanael G Bailey, Sara A Monaghan, Aatur D Singhi, Nidhi Aggarwal, Miroslav Djokic, Erika M Moore, Bryan Rea
{"title":"IRF8 Demonstrates Positivity in a Significant Subset of Histiocytic and Dendritic Cell Neoplasms.","authors":"Pranav P Patwardhan, Nathanael G Bailey, Sara A Monaghan, Aatur D Singhi, Nidhi Aggarwal, Miroslav Djokic, Erika M Moore, Bryan Rea","doi":"10.1097/PAS.0000000000002332","DOIUrl":"10.1097/PAS.0000000000002332","url":null,"abstract":"<p><p>Histiocytic and dendritic cell neoplasms, especially histiocytic sarcoma, can show morphologic and phenotypic overlap with immature monocytic neoplasms. IRF8 immunohistochemical staining has been demonstrated to be useful in identifying monoblasts, but it has not been extensively studied in histiocytic and dendritic cell neoplasms. IRF8 immunohistochemistry was performed on cases of histiocytic sarcoma (HS, n=6), Langerhans cell histiocytosis (LCH, n=25), Rosai Dorfman disease (RDD, n=17), follicular dendritic cell sarcoma (FDCS, n=3), and Erdheim Chester disease (ECD, n=5), along with a control group that included a subset of myeloid neoplasms with monocytic differentiation. Of 89 total cases, IRF8 was positive in 3/6 cases of HS, 3/5 cases of ECD, 12/17 cases of RDD, 7/25 cases of LCH, and 0/3 cases of FDCS. Control cases were stained similarly to previous reports, with IRF8 expression roughly correlating to monoblast count and normal staining in other control groups. We demonstrate that IRF8 is expressed in a significant subset of tested neoplasms of histiocytic and dendritic cell lineage. While we confirmed that IRF8 is useful to identify monoblasts, these results highlight that IRF8 cannot be reliably used to distinguish histiocytic sarcomas from myeloid neoplasms of monocytic lineages, and caution is advised interpreting IRF8 staining in that setting.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"98-103"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680086","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}
Isabel Trias, Ferran Algaba, Inés de Torres, Adela Saco, Lorena Marimon, Núria Peñuelas, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Alba Morató, Marta Del Pino, Carla Ferrándiz-Pulido, María José Ribal, Tarek Ajami, Juan Manuel Corral, Josep Maria Gaya, Oscar Reig, Oriol Ordi, Inmaculada Ribera-Cortada, Adriana García-Herrera, Natalia Rakislova
{"title":"p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-independent Penile Squamous Cell Carcinomas With Adverse Prognosis.","authors":"Isabel Trias, Ferran Algaba, Inés de Torres, Adela Saco, Lorena Marimon, Núria Peñuelas, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Alba Morató, Marta Del Pino, Carla Ferrándiz-Pulido, María José Ribal, Tarek Ajami, Juan Manuel Corral, Josep Maria Gaya, Oscar Reig, Oriol Ordi, Inmaculada Ribera-Cortada, Adriana García-Herrera, Natalia Rakislova","doi":"10.1097/PAS.0000000000002341","DOIUrl":"10.1097/PAS.0000000000002341","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"190-193"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799105","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}
Ryan Sappenfield, Felipe Camacho-Cordovez, Tatianna Larman, Deyin Xing, Elizabeth A Montgomery, Brigitte M Ronnett, Lysandra Voltaggio
{"title":"Stratified Mucin-producing Lesions of the Anus: Insights into an Emerging Histologic Type of HPV-driven Anal Neoplasia.","authors":"Ryan Sappenfield, Felipe Camacho-Cordovez, Tatianna Larman, Deyin Xing, Elizabeth A Montgomery, Brigitte M Ronnett, Lysandra Voltaggio","doi":"10.1097/PAS.0000000000002312","DOIUrl":"10.1097/PAS.0000000000002312","url":null,"abstract":"<p><p>Primary anal cancers are rare and typically driven by high-risk human papillomavirus (HPV) infection. Though squamous cell carcinoma is most common, a spectrum of HPV-related nonsquamous anogenital neoplasms with similarities to cervical stratified mucin-producing carcinoma has been reported. In this study, we mined our institutional archives to characterize the clinicopathologic features of this emerging entity. Six cases were identified from the files at 2 institutions, including 4 cases of invasive stratified mucin-producing carcinoma and 2 stratified mucin-producing intraepithelial lesions (SMILE). Four patients were women, and the mean age was 70 years. Patients presented with rectal/anal mass or polyp, rectal bleeding or pain, weight loss, or at the time of screening colonoscopy. Tumors displayed histologic features as described in the gynecologic tract. Cases of invasive stratified mucinous carcinoma showed infiltrative tumor nests with variable intracytoplasmic mucin, peripheral palisading, prominent apoptosis, and neutrophilic infiltrate. One invasive stratified mucinous carcinoma associated with high grade glandular dysplasia, whereas 1 SMILE was next to conventional low-grade squamous intraepithelial lesion. All lesions stained with p16 showed block-like p16 expression. HPV in situ hybridization was performed in 5 cases, 4 of which were positive; one was interpreted as equivocal. Follow-up information, available in 4 patients, revealed 1 local recurrence followed by death due to unrelated causes in a patient with invasive stratified mucin-producing carcinoma. We report the first series of HPV-associated primary anal stratified mucin-producing neoplasms analogous to those seen in the gynecologic tract, further broadening the spectrum of HPV-related anal neoplasia.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"121-129"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279301","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}
{"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}
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}
Miranda E Machacek, Hanzhang Wang, Kyle Devins, Peter M Sadow, Chin-Lee Wu, Esther Oliva, Philip J Saylor, Kristine M Cornejo
{"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}
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
{"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}
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
{"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}
{"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}
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
{"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}