American Journal of Surgical Pathology最新文献

{"title":"Neuroendocrine Carcinoma of the Gallbladder: Clinicopathologic and Immunohistochemical Analysis of 31 Cases.","authors":"Michelle D Reid, Burcin Pehlivanoglu, Bahar Memis, Juan C Roa, Takashi Muraki, Jill Koshiol, Giancarlo Licitra, Michael Goodman, Juan C Araya, Miguel Villaseca, Hector Losada, Juan M Sarmiento, Nevra Dursun, Olca Basturk, Volkan Adsay","doi":"10.1097/PAS.0000000000002580","DOIUrl":"10.1097/PAS.0000000000002580","url":null,"abstract":"<p><p>Neuroendocrine carcinomas of the gallbladder (GBNECs) have been very poorly characterized. In this study, 31 NECs were identified through an analysis of 636 GB cancers and contrasted with the ordinary GBCs (O-GBCs) in the same cohort. Seven were pure small cell NECs, 2 pure large cell, and 22 had mixed adenocarcinoma component (with NEC component being small cell in 6 and large cell in 16). High-grade glandular dysplasia was evident in 15 (6 as intracholecystic neoplasms; vs. 6% in O-GBC), F:M ratio was 5.2:1, and median age was 58 (vs. 65 in O-GBC). The average neuroendocrine component constituted 80% of the tumor; the median Ki-67 was 70%; lymph-vascular invasion was seen in 74%, and perineural invasion in 56%. GBNECs presented with more advanced tumors; 72% were pT3/T4 (vs. 26% in O-GBC, P =0.001). Lymph node metastasis was in 5/10 (with lymph nodes available in the specimen), and 5 had distant metastases. Tumor cells were positive for neuroendocrine markers (synaptophysin 95%, chromogranin 75%, CD56 90%), keratins (AE1/3 90%, Cam5.2 88%), with upper-GI profile (CK7 65%; CK20 0%); TTF-1 expression in 25%. pRB loss was detected in 67%, positive p16 83%, mutant p53 88.8%, and SMAD4 loss in 24%. Overall, the pRB/p16 pathway was inactivated in 83% (12 [67%] as pRB loss/p16 + , and 3 [17%] as pRB + /p16 - ). DAXX was retained in all. Loss of pRB and p16 was also detected in about a third of the adenocarcinoma and preinvasive components. ATRX loss was noted in 1 large-cell NEC. The median survival was 6.1 months, significantly shorter than O-GBCs, although a few survived unexpectedly longer. Factors associated with shorter survival included pT3 versus pT2 stage, and a trend for lower synaptophysin and CD56 expression. In conclusion, NECs constitute <5% of GBCs, and two-thirds are admixed with an adenocarcinoma component. A fifth arises in intracholecystic neoplasms. Inactivation of the pRB/p16 pathway is common, with 2/3 showing pRB loss. They present as advanced tumors and behave aggressively.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1152-1165"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300715","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":"EVALI and Beyond: An Update on the Spectrum of Vaping-Associated Lung Pathology.","authors":"Peter J Manchen, Brandon T Larsen, Maxwell L Smith, Henry D Tazelaar, Yasmeen M Butt","doi":"10.1097/PAS.0000000000002585","DOIUrl":"10.1097/PAS.0000000000002585","url":null,"abstract":"<p><p>E-cigarette or vaping-associated lung injury (EVALI) was initially recognized as a public health problem in 2019, but pathologic changes from vaping (if any) outside the context of EVALI remain unknown. We aimed to further characterize the pathology of EVALI and vaping-associated changes in otherwise healthy patients without EVALI, including those presenting with spontaneous pneumothorax. Archives were searched for lung specimens from these patient groups (2019 to 2025). Previously reported cases were excluded. Clinical history and pathology slides were reviewed. Sixty-three patients (43 men; mean age: 36.0±15.2 y) were enrolled, including 47 wedge resections, 15 transbronchial biopsies, and 1 core biopsy. All reported current or recent vaping, and 24 reported prior or concurrent cigarette smoking. Thirty-six met criteria for EVALI and showed characteristic histologic features; novel findings included 12 (35%) with coarse lipid vacuolization and 6 (18%) with grungy proteinosis-like deposits. Eleven patients with prior suspected EVALI had chronic respiratory symptoms with airway-centered macrophages and variable airway-centered fibrosis. The remaining 16 patients presented with spontaneous pneumothoraces without EVALI and had rare foamy or lightly pigmented macrophages in airspaces but no other abnormalities beyond secondary changes from the pneumothorax. To our knowledge, this is the largest pathologic study of EVALI and the first to review histologic findings in the lungs of otherwise healthy vapers. EVALI is less common than in 2019 but is still encountered. Outside the context of EVALI, patients who vape and develop spontaneous pneumothorax have minimal histologic changes. The role (if any) of vaping in the development of pneumothorax remains unknown.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1231-1239"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429675","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":"Metastatic High-Grade Endometrioid Carcinoma to the Lung With Pilomatrix Carcinoma-Like Morphology: Potential for Misdiagnosis as Non-Small Cell Carcinoma.","authors":"Timothy A Dinh, Mary M Torrez, Kristine E Konopka, William R Perry, Heather I Chen-Yost, David B Chapel, Amir Dehghani, Douglas Rottmann, Stephanie L Skala, Tao Huang","doi":"10.1097/PAS.0000000000002591","DOIUrl":"10.1097/PAS.0000000000002591","url":null,"abstract":"<p><p>Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a recently described aggressive variant of endometrioid carcinoma characterized by solid nests of basaloid cells with abrupt keratinization, geographic necrosis, and anucleated ghost cells. PiMHEC shows aberrant nuclear and cytoplasmic β-catenin staining, loss of PAX8 and hormone receptor expression, and aberrant expression of CDX2 and neuroendocrine markers. As a result, when presenting as metastatic disease, particularly in the lung, PiMHEC can be misdiagnosed as primary pulmonary non-small cell carcinoma or metastatic carcinoma of nongynecologic origin. We identified 7 cases of metastatic PiMHEC to the lung through our institution's thoracic consultation service. None, including those with a known history, were initially diagnosed with metastatic endometrial carcinoma. All cases demonstrated aberrant β-catenin staining and loss of PAX8, ER, and PR. Radiographically, all cases presented with multiple to innumerable bilateral lung masses. In conclusion, in female patients presenting with multiple lung masses, morphologic features resembling pilomatrix carcinoma, and aberrant β-catenin staining, metastatic PiMHEC should remain high on differential diagnosis even without Mullerian marker immunoreactivity or a history of Mullerian malignancy. Our case series further confirms the aggressive nature of PiMHEC: 3 patients developed lung metastases within 3 months of their initial diagnosis of endometrial carcinoma, 2 presented with postmenopausal bleeding or endometrial thickening and simultaneous lung metastases, and in 1 case, a lung biopsy led to endometrial sampling without clinical suspicion of endometrial carcinoma. Recognizing the morphologic and immunophenotypic features of pulmonary metastases of PiMHEC is crucial to avoid misdiagnosis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1252-1261"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597802","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":"Papillary Hyperplasia in Autosomal Dominant Polycystic Kidney Disease: A Multi-Institutional Study With Immunohistochemical and Molecular Characterization.","authors":"Kara S Tanaka, Sean R Williamson, Nicole Zalles, Douglas J Wu, Mahmut Akgul, Khaleel Al-Obaidy, Emily Chan, Ankur R Sangoi","doi":"10.1097/PAS.0000000000002592","DOIUrl":"10.1097/PAS.0000000000002592","url":null,"abstract":"<p><p>Renal cysts in autosomal dominant polycystic kidney disease (ADPKD) frequently harbor small intracystic epithelial proliferations that arise in continuity with the cyst lining and are distinct from other recognized proliferative lesions or well-defined renal tumors and lack a formal designation. We aim to provide the histomorphologic, immunohistochemical (IHC), and molecular characteristics of these lesions, determine their incidence, and employ the term papillary hyperplasia (PH), consistent with the recent International Society of Urological Pathology (ISUP) consensus meeting report on precursor lesions of the kidney. A multi-institutional retrospective study of nephrectomies affected by ADPKD was reviewed for PH, histomorphologic features, and clinicopathologic data. PH was defined by intracystic tufted or papillary epithelial proliferations composed of a single layer of bland cuboidal epithelial cells with minimal amphophilic to eosinophilic cytoplasm. IHC stains and molecular analysis using whole-genome sequencing were performed on a subset of cases. Eighty-five nephrectomies from 48 patients demonstrated PH in 88% (75/85) of kidneys. Predominant architectural patterns were tufting (97%), papillary (72%), hobnail (72%), and micropapillary (51%). All PH exhibited low-grade nuclei without atypia, with amphophilic (95%) and/or eosinophilic cytoplasm (63%). The most well-developed PH per case measured 0.3 by 3.1 mm (mean height by width) and occurred within small cysts with an average diameter of 3 mm. PH were positive for KRT7, GATA3, L1CAM, variably positive for AMACR, and negative for CA9 and showed no definitive molecular alterations. PH are common microscopic findings in kidneys affected by ADPKD. PH show a distinct combined histomorphologic, IHC, and molecular profile.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1262-1268"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668254","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":"Histiocyte-Rich Renal Epithelial Neoplasm: A Morphology Associated With Folliculin Mutations and Birt-Hogg-Dubé Syndrome.","authors":"Pedram Argani, Ezra Baraban, Angela Sanguino, Derek Allison, Cristina Magi-Galuzzi, Oksana Yaskiv, Betina Katz, Doreen N Palsgrove","doi":"10.1097/PAS.0000000000002587","DOIUrl":"10.1097/PAS.0000000000002587","url":null,"abstract":"<p><p>So-called hybrid oncocytic tumor (HOT) is the renal neoplasm most commonly associated with the germline folliculin ( FLCN ) mutations that define Birt-Hogg-Dubé syndrome. However, the spectrum of renal epithelial neoplasms associated with FLCN gene mutations has recently expanded to include neoplasms with somatic FLCN mutations and those with variant morphology. Some of these FLCN -mutated neoplasms overlap morphologically and immunohistochemically with TSC/MTOR -mutated and TFE3/TFEB fusion renal cell carcinomas, which makes sense given their overlapping genetic pathways. One morphology that has been reported in 1 to 2 cases each across multiple studies is that of a \"histiocyte-rich\" renal epithelial neoplasm, characterized by acinar spaces lined by neoplastic oncocytic epithelial cells variably distended by luminal histiocytes. An unanswered question is how frequently this morphology is associated with FLCN mutations. We identified 11 previously unreported cases of histiocyte-rich renal epithelial neoplasms and performed immunohistochemistry and next-generation sequencing. Five out of 11 cases (45%) demonstrated FLCN mutations, including at least 3 cases with evidence supporting occult Birt-Hogg-Dubé syndrome. All FLCN- mutated neoplasms were diffusely immunoreactive for glycoprotein nonmetastatic B (GPNMB), but so were 3 of the 6 morphologically similar cases in which FLCN mutations were not detected. The 2 syndromic cases with adequate surrounding kidney for evaluation demonstrated GPNMB-positive cysts lined by cells with similar cytology to that of the neoplasms, possibly representing precursor lesions. In summary, histiocyte-rich renal epithelial neoplasm is a morphologic pattern that is strongly but not invariably associated with FLCN mutations. Recognition of this pattern is helpful in that it may provide the first clue to the presence of occult Birt-Hogg-Dubé syndrome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1139-1151"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410148","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":"Proteomic Analysis Identifies Potential Biomarkers of ELOC -Mutated Renal Cell Carcinoma.","authors":"Akihiko Fukagawa, Yasuhito Arai, Akiko Maeshima, Natsuko Hama, Yasushi Totoki, Hiromi Nakamura, Mihoko Saito-Adachi, Yukio Hokazono, Eijiro Nakamura, Yoshiyuki Matsui, Shungo Adachi, Ryuji Hamamoto, Tetsuo Ushiku, Shinichi Yachida, Tatsuhiro Shibata","doi":"10.1097/PAS.0000000000002583","DOIUrl":"10.1097/PAS.0000000000002583","url":null,"abstract":"<p><p>ELOC -mutated renal cell carcinoma (RCC) is a rare tumor with only ∼40 cases reported to date; it shares a molecular background with clear cell RCC (ccRCC) in terms of hypoxia-inducible factor-alpha (HIF-α) protein accumulation. ELOC -mutated RCC is characterized by prominent leiomyomatous stromal growth and a more indolent clinical course compared with ccRCC. In our previous study, whole-genome sequencing of 102 ccRCC cases identified 5 cases of ELOC -mutated RCC. In the present study, we conducted proteomic and immunohistochemical analyses on up to 13 Japanese ELOC -mutated RCCs, including 8 previously reported cases, to elucidate its distinct molecular mechanisms and identify biomarkers that may be useful in distinguishing ELOC -mutated RCC from ccRCC. Proteomic profiling revealed that molecules, including cytokeratin 7, scinderin (SCIN), and sortilin 1 (SORT1), were significantly overexpressed in ELOC -mutated RCC compared with ccRCC. Notably, SCIN and SORT1 emerged as novel potential diagnostic biomarkers for distinguishing ELOC -mutated RCC from ccRCC. The analysis further suggested that ELOC -mutated RCC relies more on oxidative phosphorylation and less on glycolysis than ccRCC. This metabolic shift may be linked to the relative depletion of NAD+ due to the low expression of NAPRT and QPRT. In addition, we observed geographic variation in the disease frequency among different cohorts, with a higher frequency in Japan. Our findings provide novel insights into the pathogenesis of ELOC -mutated RCC and highlight SCIN and SORT1 as potential supportive biomarkers.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1205-1216"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429625","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":"NF2/Merlin Immunohistochemistry Helps Distinguish Collecting Duct Carcinoma From Upper Tract Urothelial Carcinoma.","authors":"Ezra Baraban, Doreen N Palsgrove, Cansu Yol, Hikmat Al-Ahmadie, Pedram Argani","doi":"10.1097/PAS.0000000000002584","DOIUrl":"10.1097/PAS.0000000000002584","url":null,"abstract":"<p><p>Collecting duct carcinoma (CDC) and upper tract urothelial carcinoma (UTUC) can exhibit overlapping morphologic features, particularly in limited biopsies, creating diagnostic challenges with significant therapeutic implications. Recent molecular studies have identified recurrent NF2 alterations in CDC, whereas pathogenic NF2 alterations are uncommon in UTUC. We evaluated the utility of NF2/Merlin immunohistochemistry (IHC) as a diagnostic tool in this differential diagnosis. NF2/Merlin IHC was performed on 16 cases of CDC and 35 UTUCs. Next-generation sequencing was performed on 13/16 CDC cases. NF2/Merlin loss by IHC was observed in 10/16 CDC cases (63%) compared with 0/35 UTUC cases (0%, P <0.000001). Among 13 CDC cases with available molecular data, 6 harbored NF2 mutations. Of these, 6/6 showed NF2/Merlin protein loss by IHC, while among 7 CDC cases lacking NF2 genetic alterations, 5 retained NF2/Merlin expression and 2 showed protein loss by IHC. Thus, overall NF2/Merlin loss by IHC demonstrates imperfect correlation with molecular studies but high specificity for CDC in the differential diagnosis with UTUC. While not present in all CDC cases, NF2/Merlin loss provides valuable diagnostic support for CDC, particularly in morphologically challenging cases where traditional urothelial markers are negative. While NF2/Merlin loss can be seen in a variety of renal cell carcinoma subtypes, consistent retention of NF2/Merlin expression in our UTUC cohort indicates that NF2/Merlin loss can be a useful adjunct that favors CDC in the challenging differential diagnosis with UTUC. This marker represents a useful addition to the immunohistochemical panel for evaluating infiltrative renal carcinomas with tubular architecture, offering objective support for the diagnosis of CDC in the appropriate morphologic and immunohistochemical context.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1224-1230"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306779","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":"Clinicopathologic and Molecular Analysis of Traditional Serrated Adenoma and Its Possible Precursor Lesions With Special Reference to RSPO Fusion Status : A Large Case Series From Single Institution.","authors":"Yuichiro Kadomatsu, Tsuyoshi Saito, Eiji Kamba, Takashi Murakami, Takashi Yao","doi":"10.1097/PAS.0000000000002586","DOIUrl":"10.1097/PAS.0000000000002586","url":null,"abstract":"<p><p>Colorectal serrated lesions are divided into hyperplastic polyps (HP), sessile serrated lesions (SSL), and traditional serrated adenomas (TSA) in the sixth edition of the WHO classification. In 2018, superficially serrated adenoma (SuSA) was proposed as a new subtype of colorectal serrated lesions and a possible precursor of traditional serrated adenoma (TSA). However, tumorigenesis in the serrated pathway remains uncertain. In this study, 271 colorectal serrated lesions (13 SuSAs and 258 TSAs) were collected, and the clinicopathologic features, including the coexistence of possible precursor components (SuSA/SSL/HP), and molecular features ( RSPO fusion and KRAS/BRAF mutation status) were investigated. In 13 SuSAs, RSPO fusion was detected in 13 cases, and KRAS mutations were detected in 9 cases. Among the 258 TSAs, RSPO fusion and KRAS and BRAF mutations were detected in 103, 92, and 102 cases, respectively. RSPO fusion-positive TSAs harbored KRAS and BRAF mutations in 62 (60%) and 18 (17%) cases, respectively, and were accompanied by SuSA/SSL/HP in 31/4/4 cases, respectively. KRAS -mutated TSAs exhibited RSPO fusion in 62 cases (67%), accompanied by SuSA/SSL/HP in 29/1/1 cases, respectively. BRAF -mutated TSAs exhibited RSPO fusion in 18 (18%) cases and SuSA/SSL/HP in 2/20/12 cases, respectively. These findings indicate that SuSA could be a possible precursor of TSA with KRAS mutation and RSPO fusion, whereas SSL and HP (microvesicular hyperplastic polyp) are possible precursors of TSA with BRAF mutation. RSPO fusions are more strongly associated with KRAS mutation and SuSA than with BRAF mutation and SSL/HP in serrated pathway tumorigenesis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1217-1223"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374180","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":"Uterine Leiomyomas Presenting During Pregnancy and Delivery: Comprehensive Characterization of Features Helpful in the Distinction From Malignant Mimics.","authors":"Ekaterina Olkhov-Mitsel, Yutaka Amemiya, Arun Seth, Carlos Parra-Herran, Jelena Mirkovic","doi":"10.1097/PAS.0000000000002589","DOIUrl":"10.1097/PAS.0000000000002589","url":null,"abstract":"<p><p>A subset of uterine leiomyomas becomes clinically apparent during pregnancy/delivery and is typically excised during Cesarean section. Although benign, these leiomyomas excised during pregnancy and/or delivery (LEPs) can pose diagnostic challenges due to morphologic changes that mimic malignant mesenchymal neoplasms, such as leiomyosarcoma. This study analyzed 97 LEPs to characterize their histopathologic and immunohistochemical features. Histologic examination revealed predominantly low mitotic activity (mean: 0.5 mitoses/10 HPFs) and mild (87.6% of tumors) to at most focal moderate (9.3% of tumors) nuclear atypia. Ischemic necrosis occurred in 57.7% of tumors. Features attributed to coagulative necrosis were common, including sharp viable-nonviable transition (22.7%), perivascular tumor preservation (9.3%), and ghost outlines of tumor cell nuclei (50.5%). Focal myxoid changes, affecting ≤30% of tumor volume, were seen in 42.3% of tumors. Rare, bizarre cells were identified in 48.5% of tumors. Immunohistochemistry demonstrated the absence of estrogen receptor staining in 65% of tumors, with focal staining in 35.2%, and progesterone receptor expression in 97.7%. Caldesmon (98.9%) and desmin (100%) were positive, with the majority diffuse. CD10 (100%) showed variable staining intensity. Wild-type p53 expression was seen in all tumors tested. Expression of ATRX, MTAP, RB1, and PTEN was predominantly retained with equivocal staining in 35.3% (ATRX) and 3.4% (RB1) of tumors. Although Cyclin D1 expression was common (97.4%), it was always focal, with no diffuse (≥70%) strong nuclear staining. FH loss occurred in 3.2% of tumors. All tumors were negative for MelanA, and 92.4% were negative for HMB45. Calretinin expression was observed in 39% of tumors, typically focal and strong, while only 1 tumor showed positive inhibin staining in <5% of cells. ALK expression was focally positive or equivocal in 9.6% of cases, but no gene rearrangements were identified by in situ hybridization. Follow-up data were available for 71 patients (mean: 56 mo), with no malignant transformation or recurrence. These findings confirm that LEPs exhibit distinct morphologic and immunophenotypic alterations, including features typically attributed to coagulative tumor cell necrosis. However, given benign clinical outcomes, low mitotic activity, and lack of significant atypia, such a finding does not warrant designation as leiomyosarcoma or smooth muscle tumor of uncertain malignant potential in the context of concurrent pregnancy.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1240-1251"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444090","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":"Does Positive Margin in Secondary Tumors at Radical Prostatectomy Predict Biochemical Recurrence in Multifocal Prostate Cancer?","authors":"Nikunj B Shah, Angelica Menendez, Sanoj Punnen, Adam D Williams, Radka Stoyanova, Alan Pollack, Bruno Nahar, Dipen J Parekh, Mark L Gonzalgo, Oleksandr N Kryvenko","doi":"10.1097/PAS.0000000000002622","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002622","url":null,"abstract":"<p><p>Positive surgical margin (M+), higher-grade group (GG), extraprostatic extension (EPE), seminal vesicle invasion (SV+), and tumor volume (TV) are among the factors at radical prostatectomy (RP) demonstrating strong independent correlations with subsequent biochemical recurrence (BCR). However, the prognostic significance of M+ in secondary tumors on BCR when a dominant tumor is excised with a clear margin has not been studied. A review of 1,687 RPs with multifocal prostate cancer was performed to assess GG, margin status, EPE, SV+, and TV for each individual tumor. The final analytical cohort consisted of 1,449 RPs, as patients without follow-up were excluded. The highest GG determined the dominant tumor. In tumors with equal GG, higher stage tumors were considered dominant. In tumors with equal GG and stage, a tumor with a larger TV was considered dominant. In all cases, the dominant tumor was excised with clear margins. Associations between secondary tumor margin status and BCR were evaluated using multivariable logistic regression analysis. The dominant tumors were GG1 (n=195 [13.5%]), GG2 (n=551 [38.0%]), GG3 (n=308 [21.2%]), GG4 (n=72 [5.0%]), and GG5 (n=323 [22.3%]). The median TV of the dominant tumor was 0.73 mL (range: 0.03 to 22). EPE was seen in 481 (33.2%) cases and SV+ in 77 (5.3%). In 74 (5.1%) RPs, a secondary tumor showed M+, composed of GG1 32 (43.2%), GG2 33 (44.6%), GG3 4 (5.4%), GG4 3 (4.1%), and GG5 2 (2.7%). BCR was observed in 137 (9.4%) patients, and 62 (4.3%) had persistent PSA. The median follow-up for patients with BCR was 855 days (range: 395 to 1,575) and for those without, 729 (range: 236 to 1,582), P=0.045. In the Cox proportional hazards model, after adjusting for GG, TV, EPE, and SV+, M+ in secondary tumors predicted BCR (HR: 3.14; P=0.0002). Except for GG2 and EPE, all other RP findings correlated statistically significantly with BCR: GG3 (HR: 9.53; P=0.0002), GG4 (HR: 16.4; P<0.0001), GG5 (HR: 14.2; P<0.0001), TV (HR: 1.16; P<0.0001), and SV+ (HR: 3.03; P=0.0001). While published literature indicates that M+ in the dominant tumor is one of the strongest predictors of BCR, M+ in secondary tumors appears to have a lesser effect on BCR than dominant tumor characteristics.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069084","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}