American Journal of Surgical Pathology最新文献

{"title":"Pilomatrix-like High-grade Endometrial Carcinoma: An Underdiagnosed Entity With Aggressive Clinicopathologic Features.","authors":"Feng Zhou, Lei Qin, Suming Huang, Wanrun Lin, Huijuan Zhang, Vinita Parkash, Wenxin Zheng","doi":"10.1097/PAS.0000000000002402","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002402","url":null,"abstract":"<p><p>Pilomatrix-like high-grade endometrial carcinoma (PiMHEC) is a rare and aggressive variant of endometrial carcinoma often misdiagnosed due to overlapping features with other high-grade malignancies. This study characterizes its clinicopathologic, immunophenotypic, and molecular features to establish key diagnostic criteria and propose a standardized terminology. Ten tumors were analyzed using histopathologic examination, immunohistochemistry, and next-generation sequencing. All but 1 tumor exhibited both low-grade endometrioid and high-grade basaloid components, the latter characterized by either geographic or comedo-type necrosis and shadow cells. Although shadow cells are a hallmark feature, they may be focal or absent, necessitating careful evaluation. High-grade areas consistently showed ER and PR negativity with diffuse nuclear β-catenin staining, correlating with CTNNB1 exon 3 mutations in all tumors. Identical CTNNB1 mutations in spatially distinct tumor components suggest a clonal progression from a low-grade precursor. Additional mutations in ARID1A, PTEN, and PIK3CA were identified. Clinically, PiMHEC exhibited aggressive behavior, with 7 patients experiencing recurrence and 1 succumbing to the disease within 9 months. Metastatic sites included the lungs, liver, lymph nodes, and abdominal wall. PD-L1 expression in 4 tumors suggests potential responsiveness to immune checkpoint inhibitors, whereas low-level HER2 expression (1+ to 2+) in 5 tumors raises the possibility of HER2-targeted therapies. Folate receptor alpha was not expressed in any tumor. In conclusion, PiMHEC is a distinct and highly aggressive endometrial carcinoma with unique histopathologic and molecular features that differentiate it from high-grade endometrioid and other high-grade endometrial cancers including squamous cell carcinoma in rare situations. Its key diagnostic features include high-grade basaloid tumor cells associated with shadow cells, tumor necrosis, and diffuse nuclear β-catenin staining. To improve diagnostic accuracy and reduce ambiguity, we propose adopting \"pilomatrix-like high-grade endometrial carcinoma\" as a standardized term.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810344","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 Malignant Neoplasms With Yolk Sac Tumor Differentiation in Women 40 Years of Age and Older.","authors":"Tricia A Numan, Brigitte M Ronnett, Lisa Haley, Aparna Pallavajjala, Jaclyn B Murry, Jaden Kohn, Phillip M Galbo, Russell Vang, Fausto J Rodriguez, Harsimar Kaur, Kimberly Levinson, Jeffrey Lin, Doreen N Palsgrove","doi":"10.1097/PAS.0000000000002389","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002389","url":null,"abstract":"<p><p>Gynecologic yolk sac tumors (YSTs) are more commonly encountered in children and young women as pure or mixed germ cell tumors and are rarely observed in older women. YSTs in older women are sometimes accompanied by a Müllerian-type carcinoma component, indicating a likely somatic rather than germ-cell origin. Studies of YSTs of germ cell and somatic types in this age group are limited. Analysis of additional pure and mixed tumors with YST differentiation could elucidate differences between these tumor subtypes and the relationship between components in mixed tumors. Clinicopathologic features of 32 malignant neoplasms with YST differentiation in women aged 40+ were analyzed. There were 11 pure YSTs, 7 mixed germ cell tumors, and 14 YSTs with a malignant non-germ cell tumor component (somatically derived yolk sac tumor [SDYST]). Targeted next-generation sequencing (NGS) was performed in 4/11 pure YSTs, 0/7 mixed germ cell tumors, and 4/14 SDYSTs. For the pure YSTs, alterations in DICER1 (1/4), PIK3R1 and PTPRT (1/4), PMS1 (1/4), and TP53 (2/4) were identified. One other pure YST had alterations in PTEN, ARID1A, ARID1B, FGFR2, and CTNNB1 (alterations common in endometrioid carcinoma). SDYSTs demonstrated shared alterations between both components including TP53, KRAS, FBXW7, and KMT2C, suggesting a common origin. The findings in the pure YSTs in older women suggest that for some, the origin could be germ cell as they harbor similar alterations as those described in pure YSTs in young women, whereas in other \"pure\" YSTs, the molecular profile aligns with previously described SDYSTs, which suggests a SDYST with an unsampled Müllerian carcinoma component rather than a germ cell origin. In SDYSTs, shared alterations are consistent with prior studies and suggest a somatic rather than germ-cell origin.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810329","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 Characteristics of Immune Checkpoint Inhibitor-related Pancreatitis.","authors":"Feidi Chen, Monika Vyas, Matthew Gosse, Vikram Deshpande, Matthew W Rosenbaum","doi":"10.1097/PAS.0000000000002398","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002398","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibitors (ICIs), although associated with adverse events, has heralded a new era in cancer therapy. ICI-related pancreatitis is a rare adverse effect of ICIs. The nonspecific clinical manifestations have posed diagnostic challenges, and the detailed histologic features remain largely unknown. This study aims to characterize the clinical and histopathologic features of ICI-related pancreatitis to increase awareness and improve diagnostic accuracy. We retrospectively identified 5 specimens from 4 patients from our database and consultation practice. We reviewed demographic, clinical, serological, and radiologic data and examined each specimen's histologic features. Patients (2 female, 2 male) were all prescribed anti-PD-1 monoclonal antibodies (1 on Nivolumab and 3 on Pembrolizumab) for metastatic melanoma, unresectable colon cancer, metastatic pancreatic adenocarcinoma, and urothelial carcinoma. The onset of ICI-related pancreatitis ranged from 28 to 473 days after ICI initiation. All 4 patients showed elevated amylase and/or lipase. Two patients presented with the chief complaint of abdominal pain. The other 2 initially asymptomatic patients showed hypointense mass lesions on imaging resembling malignant processes. The most common histologic findings were acinar-centric mixed inflammatory infiltrate (5/5 specimens) followed by atrophy (4/5 specimens) and fibrosis (4/5 specimens). Storiform fibrosis was identified in one patient who was biopsied twice. Other findings included edema (3/5 specimens) and acinar-to-ductal metaplasia (3/5 specimens). Granulocytic epithelial lesion was identified in 2 specimens. No obliterative phlebitis or granulomas were identified. By immunohistochemistry, the inflammatory infiltrates were predominately composed of CD3+ T cells with a variable CD4 to CD8 ratio. Neutrophils and eosinophils were readily identifiable with rare plasma cells. Management included stopping the ICI and starting steroids. Whereas 1 patient lacked follow-up information, 2 patients showed marked improvement. One patient succumbed to severe ICI-related myocarditis. In conclusion, ICI-related pancreatitis shows overlapping clinical-radiologic features with malignancy and autoimmune pancreatitis with the potential for chronic injury. Although ICI-related pancreatitis lacks the classic histologic features of autoimmune pancreatitis, there is considerable histologic overlap, particularly on small biopsies. Therefore, correlation with the patient's medications is critical when evaluating pancreatic specimens with nonspecific chronic pancreatitis histologic patterns.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794449","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 FCGR2B Expression Can Identify Low-tumor-burden Follicular Lymphoma Patients Who Do Not Require Any Antilymphoma Therapy for a Long Term.","authors":"Shotaro Watanabe, Hiroki Kato, Tohru Fujiwara, Shunsuke Hatta, Yasuo Tomiya, Koichi Onodera, Satoshi Ichikawa, Yasushi Onishi, Hisayuki Yokoyama, Fumiyoshi Fujishima, Ryo Ichinohasama, Hideo Harigae, Noriko Fukuhara","doi":"10.1097/PAS.0000000000002397","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002397","url":null,"abstract":"<p><p>Spontaneous regression or a long-term lack of obvious progression is often observed in patients with low-tumor-burden (LTB) follicular lymphoma (FL). However, conventional prognostic risk models are unable to precisely identify the patients who will not require any antilymphoma treatment for a long term, especially at diagnosis. In this study, we identified genes whose expression levels were associated with the clinical outcome of LTB FL and verified their prognostic value using immunohistochemistry. Because the tumor microenvironment may influence FL pathogenesis, we used digital expression profiling to quantify the expression of 730 immune-related genes extracted from tumor tissue specimens collected from 55 untreated patients with LTB FL. Five genes were identified as potential transcriptomic predictive markers. Among these, FCGR2B, an inhibitory FC gamma receptor, was immunohistochemically stainable and identified as a reliable immunohistochemical prognostic marker mainly expressed in tumor cells but not in the surrounding reactive cells. Our findings could help identify patients with LTB FL who do not require any antilymphoma treatment for the long term.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794456","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":"Comparative Molecular Profiling of \"Mixed Endometrioid Adenocarcinoma and Adenosarcoma\" of the Uterus and Ovary: A Multi-institutional Series of 14 Cases.","authors":"Lucy X Ma, Jennifer A Bennett, Melissa Y Tjota, Amir Momeni-Boroujeni, Zehra Ordulu, Emily Meserve, Stephanie L Skala, Tao Huang, David B Chapel","doi":"10.1097/PAS.0000000000002399","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002399","url":null,"abstract":"<p><p>\"Mixed endometrioid adenocarcinoma and adenosarcoma\" is a recently described malignancy of the uterus and ovary characterized by discrete components of Mullerian adenosarcoma and typically low-grade endometrioid adenocarcinoma. Its molecular biology, natural history, and proper classification remain uncertain. We analyzed clinicopathologic data and performed comparative molecular analysis on the adenocarcinomatous and adenosarcomatous components of 14 tumors using a 168-gene next-generation sequencing panel (n=11) and the MSK-IMPACT assay (n=3). Thirteen tumors were stage I, and 1 stage II. The epithelial component was endometrioid carcinoma in 12 (86%), endometrioid intraepithelial neoplasia in 1 (7%), and mesonephric-like adenocarcinoma in 1. The adenosarcomatous component showed sarcomatous overgrowth in 8 (57%), high-grade atypia in 4 (29%), heterologous differentiation in 10 (71%), and lymphovascular invasion in 3 (21%). The adenocarcinomatous and adenosarcomatous components shared molecular alterations in all cases, including mutations in ARID1A (10, 71%), KRAS (8, 57%), DICER1 (7, 50%), PIK3CA (7, 50%), PTEN (6, 43%), and PIK3R1 (4, 29%). Twelve tumors were of no specific molecular profile and 2 were microsatellite instability-high. Four (31%) patients recurred, and 3 (23%) died of disease 7, 8, and 18 months after hysterectomy. Prognosis correlated with high-risk morphologic features in the adenosarcomatous component, including sarcomatous overgrowth, extensive rhabdomyosarcomatous differentiation, vascular invasion, and high-grade nuclear atypia. \"Mixed endometrioid adenocarcinoma and adenosarcoma\" is a clonal biphasic malignant neoplasm of uncertain histogenesis, with a high frequency of DICER1 mutations.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794398","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":"CPZ: A Highly Sensitive Diagnostic Biomarker for the Differentiation Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma, Particularly in Poorly Differentiated Hepatocellular Carcinoma.","authors":"Minying Deng, Rongkui Luo, Lingli Chen, Huimei Wang, Wen Huang, Qi Song, Dongxian Jiang, Lei Xu, Jieakesu Su, Chen Xu, Yingyong Hou","doi":"10.1097/PAS.0000000000002393","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002393","url":null,"abstract":"<p><p>Carboxypeptidase Z (CPZ) is a newly identified member of the metallopeptidase family, primarily reported in rats; however, its distribution in normal human tissues and expression characteristics in tumor tissues remain unclear. This study uses high-throughput and mass production technology for tissue microarray (TMA) to perform immunohistochemical staining of CPZ, for the first time delineating its distribution and expression in normal tissues and various tumors throughout the body, to discuss its potential pathologic value. CPZ exhibited varying degrees of cytoplasmic positive expression in the normal hepatocytes, pancreatic islets, and gallbladder epithelium, with no expression observed in other normal tissues. The positive expression rates of CPZ in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic liver tumors, and normal liver tissue were 90.8% (109/120), 27.7% (13/47), 0% (0/22), and 100% (81/81), respectively. The sensitivity and specificity for diagnosing HCC with any of the 3 markers (CPZ, arginase-1 (Arg-1), and hepatocyte paraffin antigen-1 (Hep Par-1)) positive were 96.7% (116/120) and 65.2% (45/69), respectively. The sensitivity and specificity for diagnosing HCC with all 3 markers positive were 70.8% (85/120) and 100% (69/69), respectively. The sensitivity and specificity for diagnosing HCC with both CPZ and Arg-1 positive were 79.2% (95/120) and 95.7% (66/69), respectively. The sensitivity and specificity for diagnosing HCC with both CPZ and Hep Par-1 positive were 76.7% (92/120) and 97.1% (67/69), respectively. The sensitivity and specificity for diagnosing HCC with both Arg-1 and Hep Par-1 positive were 72.5% (87/120) and 98.6% (68/69), respectively. The ROC curve indicated that the combined detection of CPZ, Arg-1, and Hep Par-1 had the best diagnostic value for HCC (AUC=0.939, P<0.001). However, for individual detection, CPZ had the highest AUC value among the 3 markers (AUC=0.908, P<0.001). CPZ was not observed to be positive in the majority of 897 cases of solid tumors. Utilizing the TMA repository, we propose for the first time that CPZ may serve as a useful adjunctive tool for the diagnosis or differential diagnosis of HCC in routine surgical pathology practice. CPZ shows a trend of superiority over Arg-1 and Hep Par-1, particularly in poorly differentiated HCC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794400","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":"Molecular Analysis of Cutaneous Sarcomatoid Neoplasms Frequently Identifies Melanoma Driver Variants.","authors":"Louise A Jackett, Catherine Mitchell, Cameron Snell, Chelsee Hewitt, Shravan Yellenki, Hayden Snow, David Speakman, Chris Angel, Christine Khoo, Jia-Min Pang, Serigne N Lo, Richard A Scolyer, Stephen Fox, David Gyorki","doi":"10.1097/PAS.0000000000002390","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002390","url":null,"abstract":"<p><p>Primary cutaneous neoplasms that lack definitive histologic and immunophenotypic evidence of differentiation are a heterogeneous group of tumors with diverse prognoses and management options. These include undifferentiated and dedifferentiated melanoma (UM/DM), atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), and sarcomatoid squamous cell carcinoma. Diagnosis requires careful correlation between the clinicopathologic and molecular features, and the finding of a MAPK pathway variant commonly associated with melanoma may support the diagnosis of melanoma over other tumors in this group. To examine the frequency of typical melanoma-associated MAPK pathway-related variants (BRAF, NRAS, KIT, GNAQ, GNA11) among a cohort of primary cutaneous sarcomatoid neoplasms, we conducted a retrospective analysis of 37 cases of immunohistologically unclassifiable primary cutaneous neoplasms, submitted for targeted NGS analysis. All cases lacked a history of a prior relevant tumor, were negative for melanocytic markers (S100, SOX10, HMB45, and Melan-A), or showed <5% staining with 1 or 2 of these markers. Other lineage markers were negative. We identified typical melanoma driver variants in 7 cases (7/37, 19%), including NRAS (5/37, 14%), KIT (1/37, 3%), and GNAQ (1/37, 3%). There were no significant differences in age, sex, tumor site, or mitotic rate between patients with and without a melanoma driver variant. Melanoma cases were thicker (16.3 vs. 9.25 mm, P=0.041) and more likely to show epithelioid cell phenotype (P=0.008). In our cohort, nearly 20% of patients with immunohistologically unclassifiable cutaneous tumors could be reclassified as having primary UM/DM after molecular testing, thereby opening alternative management pathways.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778920","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":"Cholangioblastic Cholangiocarcinoma ( NIPBL :: NACC1 Cholangiocarcinoma) : Expanded Morphologic Spectrum and Further Genetic Characterization.","authors":"Pedram Argani, Kiyoko Oshima, Robert A Anders, Raul S Gonzalez, Osman Yilmaz, Munita Bal, Lisa Rooper, Jessica Hicks, Angelo De Marzo, Jeffrey Gagan, Chengsong Zhu, Doreen N Palsgrove","doi":"10.1097/PAS.0000000000002365","DOIUrl":"10.1097/PAS.0000000000002365","url":null,"abstract":"<p><p>The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature. We report 2 additional cases, both of which caused diagnostic challenges. The first was previously published as a \"biliary adenofibroma with malignant features\" which we now show recurred as a high-grade adenocarcinoma. Re-review of the original lesion demonstrated the morphologic and immunohistochemical features of highly cystic cholangioblastic cholangiocarcinoma, whereas the high-grade recurrence lacked many of these features. In addition to the characteristic NIPBL::NACC1 gene fusion, the recurrence demonstrated loss of the RB1 and PTEN genes which were found in the highly cystic, bland areas of the original tumor, suggesting that the recurrence was derived from this bland component. The second case was originally misclassified as metastatic well-differentiated neuroendocrine neoplasm and only focally demonstrated the characteristic biphasic small cell-large cell cytology. In addition, a review of 7 cholangioblastic cholangiocarcinomas in our files demonstrates that loss of chromosome 13q14.2 (where the RB1 gene resides) and loss of chromosome 6q15-q16.3 are recurrent secondary changes in these neoplasms. Expression profiling demonstrated alterations in the transforming growth factor receptor beta superfamily, and overexpression of MYC which was validated by immunohistochemistry. Our findings expand the morphologic and genetic spectrum of this neoplasm and provide insight into secondary genetic changes associated with progression.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"303-314"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997741","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 Novel Case of Pulmonary Sclerosing Diffuse PEComatosis With Neuroendocrine Cell Hyperplasia.","authors":"Kristine E Konopka, Ella A Kazerooni, MeiLan K Han, Jeffrey L Myers","doi":"10.1097/PAS.0000000000002354","DOIUrl":"10.1097/PAS.0000000000002354","url":null,"abstract":"<p><p>Proliferations of neoplastic perivascular epithelioid cells (PECs) may occur within the lung and extrathoracic sites. The term \"PEComatosis\" is applied to multiple or diffuse microscopic proliferations of neoplastic PECs. Pulmonary diffuse PEComatosis is extremely rare, with only one case documented in the literature to date. We herein report a novel sclerosing variant of diffuse PEComatosis in a 68-year-old woman with clinical tuberous sclerosis complex (TSC), who underwent lung resection for evaluation of persistent, bilateral ground glass opacities. The patient had no respiratory complaints or ventilatory defects in pulmonary function tests. The morphologic features resembled the previous description of pulmonary diffuse PEComatosis, showing interstitial nodular and diffuse proliferation of predominantly clear epithelioid cells with PEC differentiation by immunohistochemistry. The PEComatous proliferation was accompanied by a pattern of sclerosis that overlapped with the sclerosing variant of PEComa. There was no evidence of lymphangioleiomyomatosis. The changes were complicated by neuroendocrine cell hyperplasia, which has not previously been reported in the lungs of patients with TSC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"411-415"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998776","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 Characterization of Basal Cell Carcinoma Arising at Sun-protected Sites.","authors":"Elizabeth Draper, Yvonne Y Li, Navin R Mahadevan, Alvaro C Laga, John Hanna, Eleanor Russell-Goldman","doi":"10.1097/PAS.0000000000002366","DOIUrl":"10.1097/PAS.0000000000002366","url":null,"abstract":"<p><p>Basal cell carcinomas (BCC) are driven primarily by cumulative ultraviolet (UV) radiation exposure resulting in activation of the Hedgehog (Hh) signaling pathway, often as a result of UV-mediated Patched-1 ( PTCH1) gene inactivation. Accordingly, BCCs most commonly arise at sun-exposed sites such as the head and neck. Very rarely, BCCs can arise at sun-protected sites such as the genital skin and perianal area. This can pose significant diagnostic challenges not only due to the rarity of BCC at these sites but also due to the potential morphologic overlap with other entities such as basaloid squamous cell carcinoma, trichoblastic carcinoma, and even benign neoplasms such as trichoblastomas. Hh pathway alterations have not yet been described in BCCs arising at genital and perianal sites, and the role of UV radiation is uncertain at these anatomic locations. To address this ambiguity, we report the clinicopathologic features of a cohort of 14 BCCs arising at sun-protected sites (perianal n=7, vulva n=4, scrotum n=3). Furthermore, we use a next-generation DNA sequencing platform to investigate their pathogenesis and compare it to that of a cohort of 8 BCCs arising on sun-exposed skin. We find that BCCs arising on sun-protected sites display a spectrum of morphologic patterns, rarely recur, and do not metastasize. Both sun-protected and sun-exposed BCCs are characterized by recurrent PTCH1 alterations (93% and 100% of cases, respectively), supporting the classification of the tumors arising at sun-protected sites as bona fide BCCs. Notably, in contrast to conventional BCCs, none of the sun-protected BCCs harbored a UV mutation signature, suggesting an alternative mechanism of mutagenesis. Furthermore, the presence of upstream Hh pathway alterations in sun-protected BCCs supports their susceptibility to Hh pathway inhibitors such as vismodegib and sonidegib.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"328-335"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977092","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}