American Journal of Surgical Pathology最新文献

{"title":"SALL4 as a Useful Marker for the Distinction of Various Gestational Trophoblastic Disease Subtypes: Choriocarcinoma From Other Trophoblastic Lesions and Early Complete Hydatidiform Mole From Partial Mole and NonMolar Villi.","authors":"Alexis Trecourt, Marie Donzel, Lucie Gaillot-Durand, Pierre A Bolze, François Golfier, Pierre Descargues, Touria Hajri, Claire Mauduit, Mojgan Devouassoux-Shisheboran, Fabienne Allias","doi":"10.1097/PAS.0000000000002358","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002358","url":null,"abstract":"<p><p>The distinction between choriocarcinoma and residual trophoblastic cell proliferation from a complete hydatidiform mole/invasive mole (CHM/IM) without villi is challenging on curettage materials. We investigated whether SALL4 immunostaining could help differentiate various gestational trophoblastic diseases. Placental site nodules (PSN; n=10), atypical PSN (APSN; n=8), placental site trophoblastic tumors (PSTT; n=9), epithelioid trophoblastic tumors (ETT; n=5), gestational choriocarcinomas (n=31), partial hydatidiform moles (PHM; n=13), CHM/IM (n=47), and nonmolar products of conception (POC) (n=26) were included. SALL4 immunostaining was quantified (0 [1% to 10%], [11% to 100%]) and characterized (scattered single-cell or clustered nuclear positivity) in 2 locations: cytotrophoblast/intermediate trophoblast and villous stromal fibroblasts. A diffuse (11% to 100%) and clustered pattern of SALL4 immunostaining in cytotrophoblast/intermediate trophoblast was statistically associated with choriocarcinomas (74.2%, 23/31) as compared with PSN (0/10; P<0.0001), APSN (0/8; P=0.0002), PSTT (0/9; P<0.0001), ETT (0/5; P=0.0034), PHM (0/13; P<0.0001), CHM/IM (0/47; P<0.0001), and nonmolar POC (0/26; P<0.0001). Most nonchoriocarcinoma samples showed no SALL4 expression; when present, it was of low level (1% to 10%) and with a scattered single-cell staining in 3/9 PSTT (33%), 1/13 PHM (7.7%), 19/47 CHM/IM (40%), and 1/26 nonmolar POC (1.7%). These results were confirmed using a validation cohort. In addition, 66% (31/47) of CHM/IM villous stromal fibroblasts showed SALL4 expression (11% to 100%) (all before 14 gestational weeks), whereas this level of expression was never observed in PHM (0/13), nor in nonmolar POC (0/26; P<0.0001). Finally, a clustered and >10% SALL4 immunostaining in cytotrophoblast/intermediate trophoblast favors choriocarcinoma diagnosis. SALL4 expression in >10% villous stromal fibroblasts before 14 gestational weeks favors CHM/IM rather than PHM and nonmolar POC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057791","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":"Prospective Fumarate Hydratase Tumor Predisposition Syndrome Screening in Patients With Uterine Smooth Muscle Tumors: Age, Morphology, Fumarate Hydratase/S-(2-succino) Cysteine Immunohistochemistry, and Germline Testing.","authors":"Austin McHenry, Ashley Monsrud, Jennifer Pors, Ann Folkins, Teri Longacre, Rachel Hodan","doi":"10.1097/PAS.0000000000002362","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002362","url":null,"abstract":"<p><p>Fumarate hydratase tumor predisposition syndrome (FHTPS) is caused by germline fumarate hydratase (FH) pathogenic variants (PVs). Most women with FHTPS develop FH-deficient (FHD) uterine leiomyomas (ULs), which arise 10 to 15 years earlier than aggressive FHD-renal cell carcinoma. We evaluate a previously proposed FHTPS screening strategy for women with ULs. This 5-year, prospective and retrospective study performed FH and later S-(2-succino) cysteine immunohistochemistry (IHC) on all uterine smooth muscle (USM) tumors in patients 40 (later ≤30) years or younger and on all USM tumors with suggestive FHD morphology regardless of age. Patients with FHD tumors by IHC were referred to genetic counseling. Of 840 USM tumors, 112 FHD-tumors by IHC (13%) were identified, all with suggestive FHD-morphology; 44 patients (39%) underwent germline testing, and 15 harbored germline FH PVs (34.1% of germline tested, 13.4% of all FHD-tumors). While FHD tumors were seen across a wide age range (24 to 73 y), those with germline FH PVs were significantly younger (median 33 vs 44 years wild-type, P = 0.0032). Few (12.5%) patients ≥40 and no patients ≥50 had a germline FH PV, whereas a majority (60%) of patients <40 (86% of those <30) had a germline FH PV. We demonstrate that previously proposed resource-conscious screening involving morphology and IHC is effective for identifying women with FHTPS. We provide prospective data confirming patients presenting with FHD-ULs over age 50 are unlikely to harbor germline FH PVs and argue that for germline testing without consideration of other factors, a threshold of younger than 50 years may be appropriate.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997836","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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","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}

{"title":"Aberrant E-cadherin Expression in Lobular Carcinoma In Situ: A Comprehensive Immunohistochemical Evaluation of N-terminal, Extracellular, and C-terminal E-cadherin Domains.","authors":"Rita Canas-Marques, Ana Blanca, Raquel Graça-Lopes, Inês Carvalho, David G Pinto, Maria Antónia Vasconcelos, Antonio Lopez-Beltran, Isabel Fonseca","doi":"10.1097/PAS.0000000000002361","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002361","url":null,"abstract":"<p><p>E-cadherin (E-cad) immunohistochemistry is commonly used to distinguish lobular carcinoma in situ (LCIS) from ductal carcinoma in situ in histologically uncertain or ambiguous cases. Although most LCIS cases show an absence of E-cad expression on the neoplastic cell membranes, some show aberrant E-cad expression which can lead to diagnostic confusion. Awareness and understanding of the frequency, patterns, and distribution of aberrant E-cad staining in LCIS is crucial to achieving a correct diagnosis. We studied 55 LCIS cases diagnosed on core needle biopsy, classified each case by WHO subtype (classic, pleomorphic, or florid), and evaluated the frequency and patterns of aberrant E-cad expression using 3 different E-cad antibodies targeting the N-terminal (N), extracellular (EC), and C-terminal domains (C). Aberrant E-cad expression in one or more of the E-cad domains was identified in 17 cases (31%) and was significantly more frequent among LCIS variants (10/19, 56%) than among classic cases (7/36, 19.4%) (P=0.02). Among these 17 cases, aberrant E-cad expression was seen for all 3 domains in 10 cases, for EC+C in 4, for EC+N in 2, and for N only in 1. These results indicate that about one-third of cases of LCIS can show aberrant E-cad expression, that this is more common in variants than classic types of LCIS, and that this may be seen in different E-cad domains, most often in combination. These different patterns of aberrant E-cad expression may reflect different mechanisms of E-cad alterations in LCIS, the underlying nature of which merits further studies.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977068","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":"Ovarian Carcinomas: Clinicopathologic and Molecular Features With Comments on 2014 FIGO Staging.","authors":"Jaime Prat, Emanuela D'Angelo, Iñigo Espinosa","doi":"10.1097/PAS.0000000000002352","DOIUrl":"10.1097/PAS.0000000000002352","url":null,"abstract":"<p><p>According to histopathology and molecular genetics, there are 5 major subtypes of ovarian carcinomas: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3% to 4%), and low-grade serous (<5%) carcinomas. These tumors, which constitute over 95% of cases, represent distinct diseases with different prognoses and therapy. This review outlines contemporary advances in molecular pathology, which have expanded our knowledge of the biology of epithelial ovarian cancer and are also important to patient management. We also comment on some controversial points of the FIGO staging classification that we proposed in 2014.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977128","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":"Quantifying Tumor Budding: Implications for Prognosis in Gastric Adenocarcinoma.","authors":"Jie Lian, Wenwen Zhang, Chunbao Wang, Yun Zhang, Luyang Wang, Pengfei Nan, Xuqi Li","doi":"10.1097/PAS.0000000000002360","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002360","url":null,"abstract":"<p><p>The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6-10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977132","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":"Sialoblastomas With Solid Pattern Have FGFR2 Mutations and an Unfavorable Prognosis.","authors":"Xiaoli Jia, NanNan Leng, Min Wang, Xiaohong Zhan, Jiang Li","doi":"10.1097/PAS.0000000000002356","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002356","url":null,"abstract":"<p><p>Although sialoblastoma (SBL) is defined as a low-grade malignant salivary gland anlage neoplasm in the 2022 World Health Organization (WHO) Classification of Head and Neck Tumors, its histology, genetics, and behavior remain controversial due to the rarity of the tumor. Here, we performed the first comprehensive clinical, histologic, and molecular analyses of 8 SBLs to better understand their pathogenesis and prognosis. This cohort consisted of 5 boys and 3 girls, with ages ranging from birth to 9 years at diagnosis. Tumors occurred in the parotid (4), cheek (3), and submandibular glands (1). Histologically, 5 tumors primarily presented as a solid pattern consisting of primitive basaloid epithelial cells, often with necrosis. Three tumors exhibited a non-solid pattern, with 1 tumor mainly showing epithelial-myoepithelial carcinoma (EMC)-like histology, whereas the other 2 tumors exhibited basal cell adenoma (BCA)-like histology. All 5 solid SBLs harbored FGFR2 mutations, and 1 also harbored mutations in PALB2, AR, and MAP2K1. In contrast, non-solid pattern tumors were characterized by HRAS mutations or significant β-catenin nuclear positivity. All 5 solid tumors recurred, 3 of them developed distant metastases, and 2 died 40 and 44 months after diagnosis. Three non-solid tumors showed no evidence of disease recurrence at 49, 144, and 132 months, suggesting a relatively favorable prognosis. Overall, SBLs can be stratified into solid and non-solid patterns, with solid pattern tumors usually having FGFR2 mutations, increasing the risk of recurrence and metastasis. This stratification underscores the importance of genetic and morphologic profiling for predicting the prognosis of SBLs.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977135","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":"Increased SOX10, p16, and Cyclin D1 Immunoreactivity Differentiates MAP Kinase-activated Low-grade Gliomas From Piloid Gliosis.","authors":"Vivian Tang, Kevin Y Zhang, Kanish Mirchia, Rufei Lu, Ekin Guney, Merryl Terry, Azra H Ligon, Keith L Ligon, Charles G Eberhart, Arie Perry, Calixto-Hope G Lucas","doi":"10.1097/PAS.0000000000002353","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002353","url":null,"abstract":"<p><p>Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis. Reviewers blinded to clinical and pathologic data reviewed and quantified immunohistochemical expression patterns across 20 cases of piloid gliosis and 37 cases of MAP kinase-activated low-grade gliomas, including pilocytic astrocytoma and ganglioglioma. The majority of MAP kinase-activated low-grade glioma cases demonstrated extensive immunoreactivity for at least 2 of the 3 immunohistochemical markers, whereas none of the gliosis cases demonstrated significant immunoreactivity for more than one individual immunohistochemical marker. SOX10 and p16 demonstrated the highest individual sensitivity whereas cyclin D1 demonstrated the highest individual specificity to discriminate neoplastic from nonneoplastic cases in this cohort. A composite panel score based on significant immunoreactivity of at least 2 of the 3 markers provided specificity and a positive predictive value of 100% in differentiating MAP kinase-activated low-grade glioma from gliosis, as 0/20 (0%) of gliosis cases were scored positive compared with 24/37 (65%) of MAP kinase-activated low-grade glioma cases. We conclude that while the immunoreactivity of these markers may be suggestive of a low-grade glioma diagnosis, SOX10, p16, and cyclin D1 should be applied in combination to maximize diagnostic value.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977125","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}