American Journal of Surgical Pathology最新文献

{"title":"Dual TRBC1-CD3 Immunohistochemistry Shows High Diagnostic Utility in Differentiating Mycosis Fungoides/Sezary Syndrome From Reactive Inflammatory Dermatoses in Skin Biopsies.","authors":"Natasha E Lewis, David J DiCaudo, Jiehao Zhou, Dragan Jevremovic, Matthew T Howard, Mark E Law, Aaron R Mangold, Allison C Rosenthal, Sarah E Gibson","doi":"10.1097/PAS.0000000000002474","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002474","url":null,"abstract":"<p><p>Evaluation of T-cell receptor (TCR) β-chain constant region 1 (TRBC1) expression is an alternative T-cell clonality assessment method. However, evaluation of TRBC1 immunohistochemistry (IHC) for distinguishing mycosis fungoides (MF)/Sezary syndrome (SS) from reactive inflammatory infiltrates in skin is incomplete. We evaluated the utility of a novel dual TRBC1-CD3 IHC stain in skin biopsies with MF/SS (n=40), reactive (n=24), or atypical T-cell infiltrates indeterminant for MF/SS (n=9). Twenty of 24 reactive cases showed clear polytypic TRBC1 expression (median percent TRBC1 positivity among CD3-positive T cells [%TRBC1+] 50% in dermis, 42.5% in epidermis among all cases), while 34/40 MF/SS were clearly monotypic (%TRBC1+ either ≤20% or ≥85%) (sensitivity 85.0%, specificity 91.7%, positive predictive value 94.4%, negative predictive value 78.6%). Discordance between TRBC1 expression and diagnosis was associated with few neoplastic/monotypic T cells and/or lack of physical separation between neoplastic and non-neoplastic populations. Among patch/plaque MF/SS, TRBC1 showed similar diagnostic sensitivity (80.0% vs. 86.7%) and high categorical correlation (monotypic vs. not monotypic, 80%) with TCR gene rearrangement results. TRBC1 interpretation was reproducible, with ≥2/3 and 3/3 pathologists rendering identical interpretations in 100% and 86% of cases, respectively, after independent review and 100% agreement following collective review. Digital image analysis confirmed visual %TRBC1+ accuracy (r=0.9749, P<0.0001). On the basis of these results, we propose %TRBC1+ cutoffs of <25% or >75% for establishing T-cell monotypia in skin. Considering such thresholds, TRBC1-CD3 evaluation facilitated diagnostic refinement in 7/9 (78%) atypical cases. Overall, TRBC1-CD3 IHC clearly and rapidly aids diagnosis of cutaneous T-cell proliferations.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211375","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":"Anaplastic Juvenile Granulosa Cell Tumor: A Report of 10 Cases of an Unemphasized Variant With Adverse Prognostic Features Characterized by TP53 Inactivation With MYC Family Amplifications.","authors":"Baris Boyraz, Robert H Young, Esther Oliva, Kyle M Devins, Jaclyn C Watkins, Rishikesh Haridas, Pankhuri Wanjari, Zehra Ordulu, Jennifer A Bennett","doi":"10.1097/PAS.0000000000002469","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002469","url":null,"abstract":"<p><p>Ten anaplastic juvenile granulosa cell tumors (JGCT) with architectural and cytologic features that differ from those seen in conventional JGCTs were identified from patients who ranged from 7 to 44 (median 13) years. The tumors measured from 8.3 to 28 (median 21) cm. FIGO stage was IA (n=3), IC3 (n=2), II (n=1), IIIA (n=3), or unknown (n=1). All tumors had conventional areas with solid/nodular growth usually punctuated by follicles. However, all demonstrated areas (median 50%, range: 10% to 90%) with effacement of this architecture, characterized by diffuse growth, marked cytologic atypia, and brisk mitoses (up to 40/10 HPFs). In contrast, the conventional component exhibited significantly less atypia and mitoses. Next-generation sequencing was performed in 7 tumors and all harbored TP53 mutations; the remaining 3 showed aberrant p53 expression by immunohistochemistry. MYC family (MYC and MYCN) amplifications were identified in 4 tumors, while other alterations included AKT1 in-frame duplications (n=4) and DICER1 mutations (n=2). Follow-up was available for 9 patients (median 22 mo); 4 died of disease (all stage II/III with MYC/MYCN amplifications), one was alive with disease (stage IA), and 4 were alive and well (stages IA/IC). Anaplastic JGCTs have a distinct morphologic appearance and consistently demonstrate TP53 inactivation, with MYC family amplification evident in advanced-stage tumors. Although it cannot be determined whether MYC family amplifications are an independent predictor of behavior, they are important to recognize as such patients may benefit from MYC inhibitors. Tumors with the features described herein should be distinguished from conventional JGCTs because of the prognostic implications. In addition, the architectural deviations from that usually encountered and pleomorphism further add to diagnostic challenges in evaluating JGCTs.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204982","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":"PRRX1-rearranged Fibroblastic Tumors: A Clinicopathologic and Molecular Study of 18 Cases Including a Novel PRRX1::EP300 Fusion.","authors":"Carina A Dehner, Jorge Torres-Mora, Judith Jebastin Thangaiah, Andre Oliveira, Michael Michal, Faizan Malik, Nasir Ud Din, Usman Hassan, Hina Maqbool, Farres Obeidin, Mara Caragea, Cheng-Han Lee, Christian Schubart, Abbas Agaimy, Bo Grundtmann, Linea Melchior, Maj-Lis Talman, John Gross, Alison L Cheah, Khin Thway, Cyril Fisher, Cristina R Antonescu, Konstantinos Linos","doi":"10.1097/PAS.0000000000002472","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002472","url":null,"abstract":"<p><p>With the first series of PRRX1-rearranged tumors published in 2019, the spectrum of these so-called fibroblastic tumors has been expanded. Since then, several smaller case series have been published; however, our understanding of them continues to be quite limited given their rarity. We herein studied 18 additional cases, the largest series to date. Eighteen tumors present in 9 male, 8 female, and 1 nonbinary patient with a median age of 35 years (range: 11 to 70 y) and involved the neck (5), the chest region (4), thigh (3), back (1), shoulder (1), forehead (1), lower leg (1), axilla (1), and the parapharyngeal region (1). Clinical follow-up (9/18 tumors; 50%; median: 10 mo; range: 4 to 40 mo) showed consistent indolent behavior without local recurrences or distant metastases. On morphology, these tumors were characterized by well-circumscription and distinctive peripheral crescent-shaped vessels. They were composed of uniform spindle and round cells growing in short fascicles within often densely hyalinized collagen lacking significant mitotic activity, necrosis, or cytologic atypia. Immunohistochemically, about half of the tested tumors expressed focal to rarely diffuse S100 with occasional co-expression of SOX10. Interestingly, almost half of the tested cases also showed complete loss of RB expression. All but 1 tumor harbored a PRRX1::NCOA1 fusion, while 1 case harbored a novel PRRX1::EP300 fusion. We herein provide additional data on these exceptionally uncommon tumors, expand their molecular spectrum, and compare them to their close morphologic mimics to aid in accurate diagnosis and avoid confusion with potentially more aggressive neoplasms.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204923","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":"Low-Grade Endometrial Stromal Sarcoma: Clinicopathologic and Prognostic Features in a Cohort of 102 Tumors.","authors":"Kyle M Devins, Rachelle P Mendoza, Maryam Shahi, Mariachristina Ghioni, Rofieda Alwaqfi, Sabrina Croce, Anna Pesci, Joana Ferreira, Ana Felix, Iñigo Espinosa, Damiano Arciuolo, Gian F Zannoni, Esther Oliva","doi":"10.1097/PAS.0000000000002428","DOIUrl":"10.1097/PAS.0000000000002428","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Low-grade endometrial stromal sarcomas (LG-ESS) are the second most common malignant uterine mesenchymal tumors, but in contrast to the more common leiomyosarcomas, they are often characterized by a prolonged and relatively indolent course. However, a subset of patients experience significant morbidity or die of disease, and it is difficult to predict which tumors will behave aggressively, with most published studies limited in either the number of tumors or the depth of pathologic parameters evaluated. Thus, we studied the clinicopathologic features of LG-ESS in 102 patients ranging from 21 to 74 (median: 47) years. All were treated with hysterectomy and staged according to both the FIGO 2018 system (stage IA=22, IB=36, I-not otherwise specified=5, II=16, III=13, IV=10) and the FIGO 1988 system (stage I=62, II=1, III=17, IV=22). Tumors measured 1.2-49 (median: 7) cm. Microscopically, 69 involved the endometrium while 33 were centered in the myometrium. Thirteen showed only minimal infiltration of the myometrium while the rest displayed the typical extensive myometrial permeation. The cervical stroma was involved in 18, the uterine serosa in 27, and the parametrium in 22. Conventional morphology resembling proliferative endometrial stroma was seen in 95, fibroblastic appearance in 35, smooth muscle differentiation in 23, sex cord-like differentiation in 21, stromal hyalinization in 21, and myxoid stroma in 9. Less common features included glandular differentiation resembling adenomyosis (n=5), pseudopapillary pattern (n=1), deciduoid appearance (n=2), adipocytic differentiation (n=2), multinucleated cells (n=2), and rhabdomyoblastic differentiation (n=1). Mitoses ranged from &lt;1 to 20 per 10 high-power fields (median=3). Lymphovascular invasion and infarct-type necrosis were present in 64 and 23, respectively. Follow-up was available in all patients ranging from 16 to 358 (median: 79) months. Forty-six received adjuvant treatment as hormonal therapy (n=34), radiation (n=4), radiation and hormonal therapy (n=4), chemotherapy (n=3), or chemotherapy and radiation (n=1). Three patients had persistent unresected tumor following surgery, and an additional 34 had recurrences at intervals of 3 to 272 (median: 79) months, including 2 tumors with minimal infiltration. At last follow-up, 75 patients were alive with no evidence of disease, 14 were alive with disease, and 9 died of disease at intervals of 16 to 167 (median=70) months. Four died of unrelated causes without recurrence. Five-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 80% and 94%, while 10-year RFS and DSS were 51% and 87%, respectively. On statistical analysis, cervical stromal involvement ( P =0.018) and myxoid stroma ( P &lt;0.001) were associated with shorter recurrence-free survival. Tumors lacking a conventional component had worse disease-specific survival ( P =0.048). All other clinical and morphologic features, including stage, were not significantly a","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"977-991"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155568","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":"Primary Ewing Sarcoma of the Kidney: Clinicopathologic and Molecular Study of 24 Patients Including a Rare EWSR1::ETV4 Fusion.","authors":"João Lobo, Huiying He, Raheel Ahmed, Bassel Zein-Sabatto, Thomas Winokur, Shi Wei, Shuko Harada, Jesse K McKenney, Jonathan L Myles, Jane K Nguyen, Christopher G Przybycin, Sean R Williamson, Cristina Magi-Galluzzi, Reza Alaghehbandan","doi":"10.1097/PAS.0000000000002427","DOIUrl":"10.1097/PAS.0000000000002427","url":null,"abstract":"<p><p>Primary Ewing sarcoma (ES) of the kidney is rare. We describe the clinicopathologic features of primary renal ES with emphasis on gene fusion partners. A multi-institutional study was conducted to obtain clinicopathologic data on primary ES of the kidney. All tumors with available tissue underwent NGS to determine fusion partners. Twenty-four patients (8 male, 16 female) were identified. Mean age was 33.2 (±12.3). Mean tumor size was 10.5 cm (±4.2). Clinical presentation was available in 21 patients: flank/abdominal pain (13, 61.9%), hematuria (4, 19%), mass (2, 9.5%), hypertension (1, 4.8%), and incidental (1, 4.8%). For 23 nephrectomies, 2 (8.7%) were ypT0 (post-neoadjuvant therapy), 3 (13%) pT1, 15 (65.2%) pT2, 1 (4.4%) pT3, and 2 (8.7%) pT4. Four (16.7%) had metastatic disease at presentation. Of 18 patients with available follow-up, 9 (50%) were alive with disease, 7 (38.9%) alive with no disease, and 2 (11.1%) died of disease (mean follow-up 34 mo). Metastatic disease was documented in 9/18 patients, including lung (3), adrenal (2), bone (2), retroperitoneum (2), liver (2), lymph node (1), and ureter (1). FISH was performed in 14 tumors and real-time quantitative PCR in 1, confirming EWSR1 rearrangements. NGS was performed in 17 tumors, showing EWSR1::FLI1 in 16 (94.1%) and EWSR1::ETV4 in 1. Primary renal ES is a rare neoplasm occurring in a wide age range. Most tumors invaded adjacent tissues. Although they share similar histologic and molecular features with their counterpart in the bone/soft tissue, we document the first case of a rare EWSR1::ETV4 fusion in the kidney.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1078-1089"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155570","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":"Clinicopathological, Genomic, and Transcriptomic Feature Analysis of Primary Adrenal Large B-cell Lymphoma: Insights Into Immune-privileged Sites.","authors":"Shijie Deng, Anqi Li, Zhongyu Wang, Xuejing Wang, Binshen Ouyang, Lingyan Zhu, Teng Yu, Li Jiang, Yue Fan, Xia Shen, Haimin Xu, Miao Ruan, Qian Da, Jing Wang, Lei Dong, Zebing Liu, Hongmei Yi, Chaofu Wang","doi":"10.1097/PAS.0000000000002426","DOIUrl":"10.1097/PAS.0000000000002426","url":null,"abstract":"<p><p>Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is a newly categorized disease entity in the 5th WHO Classification of Tumors. Through an analysis of 53 primary adrenal large B-cell lymphoma (PA-LBCL) cases, we unraveled the similarity to IP-LBCL in clinical presentation, pathologic features, and genetic landscape. Our findings reveal a predominant immunophenotype of CD10-/BCL6+/MUM1+ in PA-LBCL, mirroring that observed in IP-LBCL, and a shared mutation spectrum characterized by the notable presence of PIM1, MYD88 L265P, and CD79B mutations. In addition, the results of RNA sequencing showed that there are significant differences in the expression profiles of PA-LBCL and SA-LBCL. The top 5 RNAs with the most significant expression differences were RPL23AP82, IGSF21, CMKLR, PTPRG, and PRKCA. Moreover, PA-LBCL exhibited a more favorable prognosis than DLBCL-NOS with secondary adrenal involvement. The results of this study indicate that PA-LBCL shares similar clinical features, immunophenotypes, and molecular genetic profiles with IP-LBCL, suggesting that it may belong to a subtype of IP-LBCL. This research has improved our understanding of lymphoma, especially those occurring in atypical sites, and reshaped our concept of lymphoma classification and management. We suggest considering incorporating PA-LBCL into IP-LBCL in the future classification of lymphoma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1028-1035"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245951","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}

{"title":"Psammomatous Calcifications Identified in Targeted Needle Biopsies and Radical Prostatectomy From IDH1 Mutant Prostatic Adenocarcinoma : Case Report and Literature Review.","authors":"Yang Zong, Mark Sharobim, Edward M Lawrence, Rong Hu, Wei Huang, Daniel D Shapiro","doi":"10.1097/PAS.0000000000002461","DOIUrl":"10.1097/PAS.0000000000002461","url":null,"abstract":"<p><p>IDH1 mutant prostatic adenocarcinoma represents a small fraction of prostate cancer with distinct epigenetic changes, characterized by genome-wide DNA hypermethylation. Recently, prostatic adenocarcinoma with intratumoral psammomatous calcifications was found to frequently harbors IDH1 R132 mutations. However, the association with IDH1 hotspot mutations and psammomatous calcifications in prostate cancer remains controversial. Here we report another rare case of IDH1 R132H mutant prostatic adenocarcinoma, showing intratumoral psammomatous calcifications identified in targeted needle biopsies as well as subsequent radical prostatectomy specimen. This case provides independent evidence for identification of IDH1 mutant prostate cancer by combined histologic features, including intratumoral psammomatous calcifications, anterior tumor location, and high Gleason score. In addition, to our knowledge, this is the first case of multifocal prostate cancer reported in the literature, with the co-existence of spatially disparate and genetically distinct tumor foci harboring IDH1 R132H mutation or TMPRSS2 - ERG gene fusion in the same prostate.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1090-1096"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726554","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":"A Brief Guide to Interpreting Transbronchial Cryobiopsies for Diffuse Parenchymal Lung Disease.","authors":"Andrew Churg, Joanne L Wright, Peter Manchen, Michelle Garlin Politis, Yasmeen Butt, Brandon T Larsen, Maxwell L Smith, Kenneth Sakata, Laszlo Vaszar, Henry D Tazelaar","doi":"10.1097/PAS.0000000000002424","DOIUrl":"10.1097/PAS.0000000000002424","url":null,"abstract":"<p><p>Transbronchial cryobiopsies (CB) are increasingly replacing surgical biopsies (video-assisted thoracoscopic/VATS biopsies) for diagnosing diffuse parenchymal lung disease (interstitial lung disease, ILD), but there is very little guidance for pathologists on CB interpretation. Here we propose a fairly simple approach. First, if the diagnosis can be made on a traditional forceps biopsy, it can be made on a cryobiopsy. Many diseases with specific features will fall into this category (eg, sarcoidosis or Langerhans cell histiocytosis). More problematic are patterns such as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP), in which low-power architecture is the key to diagnosis. In this circumstance, an adequate sample is crucial to look for features such as fibroblast foci, because a combination of fibroblast foci plus any patchy old fibrosis, fibrotic architectural remodeling, or honeycombing, allows a diagnosis of a UIP pattern. However, in most instances, CB will not separate the UIP patterns seen in idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis, or connective tissue disease-interstitial lung disease (CTD-ILD), although giant cells/granulomas (uncommon findings) in this setting favor fibrotic hypersensitivity pneumonitis. Fibroblast foci can be difficult to differentiate from organizing pneumonia (OP), but granulation tissue plugs clearly in airspaces favor OP. Absent fibroblast foci, patchy old fibrosis, architectural distortion, and honeycombing by themselves do not allow a specific diagnosis. NSIP in CB microscopically looks like NSIP in VATS biopsies, and the presence of an NSIP or an NSIP+OP pattern is typical of CTD-ILD. All the above diagnoses require correlation with clinical and radiologic findings.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1068-1077"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109198","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":"HPV42: A Common Low-Risk HPV Type Associated With Distinctive Cervicovaginal and Cutaneous Neoplasia.","authors":"Karen L Talia, David Hawkes, Gloria Zhang, Jackie Jamison, Jennifer Shanks, Bin Yang, Robert Soslow, W Glenn McCluggage","doi":"10.1097/PAS.0000000000002420","DOIUrl":"10.1097/PAS.0000000000002420","url":null,"abstract":"<p><p>Seborrheic keratosis-like lesion (SKLL) is an extremely rare, morphologically distinct lesion occurring in the cervix and vagina that differs histologically from other squamous intraepithelial lesions in these sites due to its unique morphology, including close resemblance to cutaneous seborrheic keratosis and lack of viral cytopathic effect (koilocytosis). We report a series of 17 cases, describe in detail the morphology and add to the evidence linking SKLL with low-risk human papillomavirus (LRHPV), specifically HPV42, which was detected in 13 cases; in 3 cases, an additional single HPV type (HPV6, 16, 61) was detected. In 2 of the SKLLs, a component of high-grade morphology and block-type p16 immunoreactivity were observed, prompting speculation as to the oncogenic potential of HPV42. Nineteen cases of papillary immature metaplasia, another distinctive LRHPV-associated lesion with some morphologic overlap with SKLL, were HPV42 negative. Independently, HPV42 has recently been implicated as the cause of a rare, aggressive cutaneous tumour, digital papillary adenocarcinoma (DPA), with experimental molecular data supporting the transforming capacity of this virus. These findings, along with the observation that rare anogenital squamous cell carcinomas are associated with HPV42, demonstrate the rare carcinogenic potential of this LRHPV. The association of HPV42 with these 2 unique and distinctive tumours (SKLL and DPA) also illustrates the incompletely understood diversity of HPV genotype-phenotype associations and virus-host interactions and highlights the importance of HPV typing of novel genital and cutaneous tumours.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"992-1003"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092684","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":"Dedifferentiated Solitary Fibrous Tumor: A Clinicopathologic, Immunohistochemical, and Molecular Characterization of 25 Cases.","authors":"Adrian Georg Simon, Adrian Mariño-Enríquez, Jason L Hornick, Christopher D M Fletcher, William J Anderson","doi":"10.1097/PAS.0000000000002417","DOIUrl":"10.1097/PAS.0000000000002417","url":null,"abstract":"<p><p>Dedifferentiated solitary fibrous tumor (DDSFT) is a rare and clinically aggressive malignancy with a poor prognosis. It represents the progression of solitary fibrous tumor to a high-grade, morphologically nondistinctive sarcoma. This study characterizes the clinicopathologic and molecular features of 25 DDSFT. The study cohort comprised 13 males and 12 females with a median age of 63 years (range 31 to 84). Tumors were most common in the pelvic cavity (8/25), thoracic cavity (6/25), and trunk (4/25). Histologically, DDSFT demonstrated remarkably variable morphology, including pleomorphic, epithelioid, spindle cell, and round cell features. Heterologous elements were present in 4/25 (16%). Immunohistochemical expression of STAT6 was completely lost in 8/22 (36%) tumors. Targeted DNA sequencing demonstrated that in most tumors (10/13; 77%), the NAB2 :: STAT6 fusion variant resulted in a truncated STAT6 (STAT6-TAD) in the fusion protein. Recurrent secondary alterations involved TP53 (10/14; 71%), TERT (8/14; 57%), and RB1 (3/14; 21%). Statistical analysis of the study cohort and 55 cases reported in the literature demonstrated that complete loss of STAT6 in DDSFT is associated with shorter disease-specific survival (HR 12.69, P =0.023).</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1015-1027"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148911","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}