American Journal of Surgical Pathology最新文献

{"title":"DEK :: AFF2 Fusion Sinonasal and Skull Base Nonkeratinizing Squamous Cell Carcinoma : A Clinical Outcome Study Compared With Conventional Sinonasal Squamous Cell Carcinoma.","authors":"Stephanie A Hart, Jen-Fan Hang, Rebecca D Chernock, Michael W Mikula, Lisa Rooper, Sara E Amin, Karan Saluja, Justin A Bishop, Yu Hsiu Chen, Nicole A Cipriani, Stephanie N David, William D Dupont, W Dale Plummer, Karen T Ferrer, Ariana Geromes, Min-Shu Hsieh, Juan C Hernandez-Prera, Ying-Ju Kuo, Eiichi Sasaki, Qiuying Shi, Tra Truong, Jaylou M Velez Torres, James S Lewis","doi":"10.1097/PAS.0000000000002335","DOIUrl":"10.1097/PAS.0000000000002335","url":null,"abstract":"<p><p>DEK :: AFF2 fusion nonkeratinizing squamous cell carcinoma (NKSCC) is an emerging entity in the sinonasal tract, temporal bone, and skull base. However, the clinical behavior of these tumors has not been well studied. Here, we report the largest cohort of DEK :: AFF2 carcinomas to determine if morphology, mitotic rate, and/or Ki-67 IHC are associated with patient outcomes, including a comparison with high-risk human papillomavirus (HPV)-associated and independent patients. We solicited cases of molecularly or AFF2 immunohistochemistry (IHC) proven DEK :: AFF2 SCC from surgical pathologists to collect patient demographic, clinical, and outcome data. Using representative H&E slides, we characterized the morphology and counted mitoses. Ki-67 immunohistochemistry was performed. We also compared the DEK :: AFF2 survival rates to those in a cohort of AFF2 IHC-negative HPV-associated and HPV-independent SCC. DEK :: AFF2 carcinomas most commonly arose in the nasal cavity (13/30, 43%), and the average number of recurrences was 1.8 (range: 0 to 10). At the last follow-up, most patients were disease free (19/30, 63%) or were alive with disease (9/30, 30%). There was an average mitotic rate of 2 per 2 mm 2 (range: 0 to 9) and Ki-67 proliferation rate of 26% (range: 3% to 60%). Local recurrence was common, but morphology, mitotic activity, and Ki-67 index were not associated with recurrence or survival. On Kaplan-Meier survival analysis, DEK :: AFF2 patients had lower disease-free survival but otherwise had similar outcomes to conventional SCC patients. Our multi-institutional study shows that local recurrence is common in DEK :: AFF2 fusion nonkeratinizing SCC patients, but patients have survival rates similar to conventional SCC. Despite showing a range of different features and proliferation rates, traditional grading by morphology, mitotic rate, and/or Ki-67 activity does not seem to be predictive of outcome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"130-137"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885088","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":"Time Marches On.","authors":"Stacey E Mills","doi":"10.1097/PAS.0000000000002348","DOIUrl":"10.1097/PAS.0000000000002348","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"97"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885091","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":"High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma : Identification of an MCD-like Subtype.","authors":"Fangli Peng, Takuro Igawa, Tomohiro Urata, Hiroki Kobayashi, Tetsuya Isoda, Sawako Ono, Takehiro Tanaka, Daisuke Ennisshi, Yoshinobu Maeda, Hidetaka Yamamoto","doi":"10.1097/PAS.0000000000002329","DOIUrl":"10.1097/PAS.0000000000002329","url":null,"abstract":"<p><p>Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2 / BCL6 / c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B , was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P <0.01) and double-expressor cases (20/32, 62.5%; P =0.01) compared with the MYD88 / CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type ( P =0.03), showing poorer outcomes in overall survival ( P =0.02) and progression-free survival ( P =0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"159-168"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556969","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":"TFE3 -rearranged Head and Neck Neoplasms : Twenty-two Cases Spanning the Morphologic Continuum Between Alveolar Soft Part Sarcoma and PEComa and Highlighting Genotypic Diversity.","authors":"Abbas Agaimy, Michael Michal, Ali Abdelsatir, Azza A Abdelsatir, Sawsan Abdulrahim, Jan Laco, Stephan Ihrler, Lars Tögel, Robert Stoehr, Justin A Bishop, Nasir Ud Din, Michal Michal","doi":"10.1097/PAS.0000000000002334","DOIUrl":"10.1097/PAS.0000000000002334","url":null,"abstract":"<p><p>TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3 -related neoplasms are rare in the head and neck and may pose diagnostic challenges. We herein describe 22 TFE3 fusion neoplasms affecting 11 males and 11 females aged 4 to 79 years (median, 25) and involving different head and neck sites: sinonasal cavities (n = 8), tongue (n = 4), oral cavity/oropharynx (n = 3), salivary glands (n = 2), orbit (n = 2), and soft tissue or unspecified sites (n = 3). Based on morphology and myomelanocytic immunophenotype, 10 tumors qualified as ASPS, 7 as PEComas (3 melanotic; all sinonasal), and 5 showed intermediate (indeterminate) histology overlapping with ASPS and PEComa. Immunohistochemistry for TFE3 was homogeneously strongly positive in all cases. Targeted RNA sequencing/FISH testing confirmed TFE3 fusions in 14 of 16 successfully tested cases (88%). ASPSCR1 was the most frequent fusion partner in ASPS (4 of 5 cases); one ASPS had a rare VCP::TFE3 fusion. The 6 successfully tested PEComas had known fusion partners as reported in renal cell carcinoma and PEComas ( NONO, PRCC, SFPQ , and PSPC1 ). The indeterminate tumors harbored ASPSCR1::TFE3 (n = 2) and U2AF2::TFE3 (n = 1) fusions, respectively. This large series devoted to TFE3-positive head and neck tumors illustrates the recently proposed morphologic overlap in the spectrum of TFE3 -associated mesenchymal neoplasms. While all PEComas were sinonasal, ASPS was never sinonasal and occurred in diverse head and neck sites with a predilection for the tongue. The indeterminate (PEComa-like) category is molecularly more akin to ASPS but shows different age, sex, and anatomic distribution compared with classic ASPS. We report VCP as a novel fusion partner in ASPS and PSPC1 as a novel TFE3 fusion partner in PEComa (detected in one PEComa). Future studies should shed light on the most appropriate terminological subtyping of these highly overlapping tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"104-112"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724727","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":"OTP Expression in Pulmonary and Thymic Neuroendocrine Neoplasms.","authors":"Paige H Parrack, Lynette M Sholl","doi":"10.1097/PAS.0000000000002263","DOIUrl":"10.1097/PAS.0000000000002263","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"188-189"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417345","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":"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}

{"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}

{"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}

{"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}