Applied immunohistochemistry & molecular morphology : AIMM最新文献

{"title":"Renal Cell Carcinoma With Concurrent Loss of SMARCB1/INI-1 and Fumarate Hydratase By Immunohistochemistry: A Case Report With Review of the Literature.","authors":"Huili Li, Ezra Baraban, Pedram Argani, Andres Matoso","doi":"10.1097/PAI.0000000000001325","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001325","url":null,"abstract":"<p><p>Both SMARCB1(INI-1)-deficient and FH (fumarate hydratase)-deficient renal cell carcinoma (RCC) have a male predominance, potentially overlapping high-grade histologic features, and typically poor clinical outcomes. SMARCB1(INI-1) deficiency is the characteristic pathogenic alteration in medullary (or medullary-like) RCC, which is aggressively treated with chemotherapy, primarily platinum-based. In contrast, a distinct set of agents, such as the combination of bevacizumab and erlotinib, is the principal systemic therapy consideration for FH-deficient RCC. SMARCB1 (INI-1) is a core subunit of the SWI/SNF complex, regulating chromatin remodeling and gene transcription through epigenetics. The accumulation of fumarate, resulting from the loss of FH, can alter DNA methylation and promote a CpG island methylator phenotype (CIMP), silencing tumor suppressor genes. Rare case reports of FH-deficient RCC with concurrent loss of SMARCB1 (INI-1) have been reported, which is likely due to secondary epigenetic silencing of SMARCB1 . Herein, we report a unique RCC case with concurrent loss of SMARCB1 (INI-1) and FH expression by immunohistochemistry. Molecular studies demonstrated a SMARCB1 mutation, but no FH mutation was identified. Relatively low FH transcription was detected in the case, which raises the possibility of a pathogenic loss of SMARCB1 (INI-1), accompanied by a potential secondary, epigenetic loss of FH expression. Therefore, FH loss by IHC does not necessarily always indicate a pathogenic FH mutation. Further molecular studies are critical in determining the underlying pathogenic mutation.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPS1 Expression Across the Spectrum of Paget Disease and Morphologic Mimics.","authors":"Cooper D Rutland, Aihui Wang, Sabrina Zdravkovic, Rebekah Wieland, Ryanne A Brown, Gabrielle M Baker, Megan L Troxell, Gregor Krings, Gregory R Bean","doi":"10.1097/PAI.0000000000001313","DOIUrl":"10.1097/PAI.0000000000001313","url":null,"abstract":"<p><p>Paget disease (PD) is histologically characterized by malignant glandular epithelial cells singly or in clusters within the epidermis. PD most commonly involves the nipple, though it may also occur at extramammary sites. Immunohistochemistry is helpful in highlighting PD and its extent. Differentiating PD from histologic mimics with overlapping immunophenotypes can be challenging. TRPS1, a GATA family transcription factor, has emerged as a breast origin marker with greater sensitivity than GATA3. In this study, we comprehensively examined the immunohistochemical expression of TRPS1 in mammary PD (n=29) with different biomarker profiles, including ER - /HER2 + (n=12), ER + /HER2 + (n=7), ER + /HER2 - (n=6), and ER - /HER2 - (n=4) cases, as well as benign and malignant histologic mimics and extramammary PD (EMPD). TRPS1 demonstrated strong to moderate nuclear staining of PD tumor cells across all ER/HER2 subgroups. Toker cells/Toker cell hyperplasia (n=11) also exhibited strong TRPS1 immunoreactivity, while melanoma in situ (n=10) and cutaneous sebaceous carcinoma (n=9) were essentially negative. Squamous cell carcinoma in situ (n=13) showed predominantly weak staining for TRPS1. Two cases of presumed intraepidermal metastases in patients with breast cancer demonstrated strong TRPS1 expression. Notably, TRPS1 highlighted PD tumor cells from background keratinocytes more distinctly compared with GATA3. Among EMPD cases, perivulvar (n=10) and periscrotal (n=5) cases were consistently positive, whereas perianal lesions (n=10) showed no/weak expression. In summary, TRPS1 demonstrates universal expression in mammary PD of all ER/HER2 subgroups and in Toker cells, and corroborates recent reports regarding the utility of TRPS1 in site-of-origin studies.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"155-165"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC Class I and PD-L1 Expression May Predict Treatment Response to Anti-PD-1/PD-L1 Therapy in Metastatic Triple-negative Breast Cancer Patients.","authors":"Joseph L Maniaci, Hijun Ryu, Anne M Mills, Patrick Dillon, Elizabeth M Gaughan, Taylor M Jenkins","doi":"10.1097/PAI.0000000000001319","DOIUrl":"10.1097/PAI.0000000000001319","url":null,"abstract":"<p><p>Although immune checkpoint inhibition has proven to be efficacious in a subset of breast cancer patients, there remains a heterogeneity in clinical responses. Major histocompatibility complex class I (MHC I) expression has been touted as a possible predictor of response to immune checkpoint inhibition given its role in the adaptive immune system. Loss of tumoral MHC I expression in breast cancer as an evasion of immune checkpoint inhibition has been described; however, outcome data are limited. We herein evaluate the relationship between PD-L1 and MHC I expression and response to PD-1/PD-L1 inhibitors in a cohort of treated metastatic triple-negative breast cancer (TNBC) patients. Best treatment response was assessed in 46 metastatic TNBC patients treated with anti-PD-1/PD-L1 immune checkpoint inhibition with or without chemotherapy. Primary tumors were evaluated by immunohistochemistry (IHC) for expression of PD-L1 and MHC I. PD-L1 was scored via the combined positive score (CPS). MHC I was evaluated for retention, partial loss (≥10%), or complete loss within the tumor cells. Models using logistic ordinal regression were constructed to determine the ability of PD-L1 and MHC I by IHC to predict treatment response. The best responses by RECIST 1.1 were 16 (34%) with complete response (CR), 15 (33%) with partial response (PR), and 15 (33%) with stable or progressive disease (no response; NR). Of the patients with CR, 13 (87%) had retained MHC, and of those, 12 (92%) were positive for PD-L1. Of the patients with PR, 7 (47%) had retained MHC, and of those, 4 (57%) were positive for PD-L1. Of the patients with NR, 8 had partial or complete loss of MHC (53%), and of those, all (100%) expressed PD-L1. We found that MHC I status is independently and significantly associated with treatment response ( P =0.024), with intact MHC I more common in complete responders and partial or complete loss of MHC I more common in partial responders and nonresponders. We found no association between PD-L1 expression alone with treatment response in our cohort of TNBC patients. Loss of tumoral MHC I expression is more frequently seen in patients without treatment response, despite most of these tumors having some PD-L1 expression (CPS ≥1). Using a logistical ordinal regression model, we found that both MHC I and binary PD-L1 (bPD-L1) status play significant roles in the prediction of grouped treatment response (MHC I P =0.002 and bPD-L1 P =0.03). Additional studies evaluating MHC I loss as a potential barrier to successful immune checkpoint inhibition are needed to ascertain the potential use of MHC I as a predictive biomarker in combination with PD-L1.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"172-177"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IHC p53 Performance in NordiQC: Recalibration of IHC Assays is Needed.","authors":"Kristi Bøgh Anderson, Søren Nielsen, Rasmus Røge","doi":"10.1097/PAI.0000000000001314","DOIUrl":"10.1097/PAI.0000000000001314","url":null,"abstract":"<p><p>The TP53 gene is the most frequently mutated gene in human cancers, with alterations occurring in ∼50% of all malignancies. When properly optimized, p53 immunohistochemistry (IHC) can serve as a reliable surrogate for detecting TP53 mutations. However, many laboratories struggle to identify p53 IHC reaction patterns beyond overexpression, particularly the absence, cytoplasmic, and wild-type patterns. As the clinical relevance of these additional patterns became recognized, NordiQC updated its assessment in 2021 to include wild-type and absence patterns, thereby increasing the complexity of p53 IHC and revealing widespread difficulties across laboratories. In this study, we analyze data from 6 consecutive NordiQC external quality assessment rounds from 2007 to 2024, covering 1,796 submitted p53 IHC assays. Our findings show that while most laboratories can reliably detect high antigen expression of overexpression, many protocols fail to adequately demonstrate low-level p53 expression, limiting the validity of the IHC assay. Ready-To-Use products, particularly when used according to manufacturer recommendations, performed suboptimally. These kits are calibrated exclusively to detect overexpression, leading to false-negative or too-weak results for other mutation-associated patterns. Our data represents the most comprehensive evaluation of p53 IHC assay performance to date. The findings underscore an urgent need to recalibrate p53 IHC protocols, with a special focus on improving analytical sensitivity and ensuring consistent use of both internal and external controls. Aligning IHC assays calibrated to identify the full spectrum of TP53 mutations, including those that result in absent and wild-type patterns, can significantly enhance the diagnostic accuracy of p53 IHC.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"166-171"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISIMM Page.","authors":"","doi":"10.1097/PAI.0000000000001327","DOIUrl":"10.1097/PAI.0000000000001327","url":null,"abstract":"","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":"34 3","pages":"135-142"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing HER2 IHC: Pan-HER2 and Low-HER2.","authors":"Megan L Troxell","doi":"10.1097/PAI.0000000000001316","DOIUrl":"10.1097/PAI.0000000000001316","url":null,"abstract":"<p><p>The recent clinical trials and regulatory approval of new antibody drug conjugates targeting HER2 protein (trastuzumab deruxtecan, T-DXd) has moved the bar in terms of therapy for breast cancer and other solid tumors. With new drugs and expanding indications comes a need for refined companion diagnostics. Pathologists are asked to adapt IHC and other assays (mutation testing, circulating tumor DNA) accordingly. This brings attention to lower HER2 expression levels in breast cancer (\"low\" and even \"ultralow\"), and a tumor agnostic approval for cancers with high HER2 expression (3+ according to gastric scoring). This new landscape raises many questions concerning HER2 immunohistochemistry assay comparability, applicability (sensitivity, limit of detection), readout reproducibility, and clinical reporting, among many others. With a myriad of clinical trials still underway, this will remain a rapidly evolving field.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"135-142"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Characterization of Biphasic Follicular Dendritic Cell Sarcoma.","authors":"Farhan Hassan, Theresa Boyle, Justin Palma, Julie Li, Mohammad Hussaini","doi":"10.1097/PAI.0000000000001318","DOIUrl":"10.1097/PAI.0000000000001318","url":null,"abstract":"<p><p>Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm commonly found in extranodal sites with unclear pathogenesis. Tumor cells typically exhibit a spindled morphology, whereas epithelioid morphology is rarely reported. Here, we have presented a rare biphasic FDCS with distinct immunophenotypic and molecular characteristics. A 63-year-old female presented with constipation and rectal bleeding. Imaging revealed an 11.4 cm lobulated enhancing soft tissue mass in the posterior pelvis. H&E sections revealed 2 sharply demarcated biphasic neoplastic populations: one population comprised spindled cells expressing CD21, CD23, CD35, clusterin, EMA, and D2-40; the other population consisted of epithelioid cells lacking CD21 and other FDC-associated markers except for focal weak clusterin expression. Both populations tested negative for CD163, CD68, S-100, langerin, CD1a, ALK-1, CD30, CD117, HMB45, Pan-CK, and EBER. The tumor was initially misdiagnosed as a collision (FDCS and perivascular epithelioid cell tumor) tumor. Molecular studies revealed a nearly identical mutational profile in both components confirming clonal identity and ruling out a composite tumor. In addition, low-level pathogenic mutations (variant allele frequency <10%) were found in GABRA6 , ICOSLG , and VEGFA , alongside altered transcript expression in PDGFRB in both populations. Although no RNA fusions were detected, we demonstrated a significant increase in PDGFRB expression using the RNA Salah Targeted Expression panel, with a log 2 ratio > 2, indicating a more than 4-fold increase compared with a pooled normal control. Here, we have provided molecular characterization of biphasic FDCS. Prior such characterization seems to be unavailable in the literature.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"209-217"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Assays for TROP2 Measurement in Breast Cancer and Comparison to H-Score.","authors":"Mengni He, Nay N N Chan, Matthew Liu, Charles J Robbins, Katherine Bates, Julia Benanto, Lorraine Colón-Cartagena, Mohamed Kahila, Haiying Zhan, Uma Krishnamurti, Myrto Moutafi, Vesal Yaghoobi, Daniel C Liebler, Regan Fulton, David L Rimm","doi":"10.1097/PAI.0000000000001311","DOIUrl":"10.1097/PAI.0000000000001311","url":null,"abstract":"<p><p>Trophoblast cell surface antigen 2 (TROP2) is a popular current antibody-drug conjugate target due to its high expression in various solid tumor types. With the recent FDA-approval of sacituzumab govitecan and datopotamab deruxtecan in breast cancer, TROP2-targeting therapies showed promising clinical outcomes. Despite the prevalent expression of TROP2 in breast cancer (about 90%), the objective response rates from clinical trials are around 30% with nonsignificant hazard ratios for benefit from sacituzumab govitecan in low TROP2-expressing tumors. This suggests that there may be value in a companion diagnostic assay to measure TROP2 protein expression in tumor samples, but H-score assessment is not required. Here, we develop a quantitative immunofluorescence (QIF) assay and a quantitative hematoxylin-DAB (QH-DAB) assay for potential use as a future companion diagnostic test. TROP2 peptide concentrations were measured in cell lines using mass spectrometry to convert fluorescent signal or chromogen optical density to protein concentrations in amol/mm 2 . Coupled with QuPath-based image analysis tool Qymia, our QIF and QH-DAB assays have limits of detection of 90 amol/mm 2 and 667 amol/mm 2 , and limits of quantifications of 272 amol/mm 2 and 2021 amol/mm 2 , respectively. Using these assays, we measured the TROP2 expression in a breast cancer serial cohort (N=264) and a triple-negative breast cancer cohort (N=100) from Yale New Haven Hospital, identifying a broad dynamic range of TROP2 expression in breast cancer samples. Since the H-score method is the current standard of practice in the clinics, we selected 68 breast cancer biopsies and compared the measurements from our assays to H-scores evaluated by 5 certified pathologists. There is an overall agreement between our QIF and QH-DAB measurements and pathologists' readings. However, the quantitative assay has better sensitivity and less subjectivity. In summary, these assays allow for an accurate and reproducible TROP2 protein measurement that could be incorporated into a clinical workflow. This work represents only analytic validation, but work on clinical validation has begun. In the future, this assay may help identify patients who are more likely to benefit from TROP2-targeted therapies.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"143-154"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesothelin Expression in Acute Leukemia: Correlations With Immunophenotype, Cytogenetics, and Mutational Status.","authors":"Dua'a N Ashour, Manal A Abbas, Maher A Sughayer","doi":"10.1097/PAI.0000000000001302","DOIUrl":"10.1097/PAI.0000000000001302","url":null,"abstract":"<p><p>Mesothelin is a surface glycoprotein overexpressed in several solid tumors and a known immunotherapy target. While present on blast cells in acute myeloid leukemia (AML), its role in acute lymphoblastic leukemia (ALL) remains unclear. This study evaluated mesothelin expression in 181 newly diagnosed acute leukemia cases using immunohistochemistry (IHC) on bone marrow biopsies and ELISA on plasma samples. Mesothelin was expressed in 31% of pediatric and 15% of adult AML cases (n=65), with no significant differences among AML subtypes. It was absent or rare in ALL (n=51) and undetectable in normal bone marrow. In AML, mesothelin was detected in 49% of CD38⁺, 60% of CD64⁺, 62.5% of KMT2A-rearranged, and 69% of core binding factor AML [83% with inv(16)/ t(16;16) , 57% with t(8;21) ]. It was largely absent in cases with NPM1 (87.5%), GATA2, and DNMT3A mutations. Expression correlated significantly with age, CD38, CD64, and mutations in NPM1, GATA2, DNMT3A, and KDM6A. No significant association was found between mesothelin expression and 5-year overall or event-free survival, measurable residual disease, remission, or relapse. In ALL, 83.3% of T-ALL and 85% of B-ALL cases showed no expression. However, mesothelin correlated with CD11c, PHF6, and CBLC mutations in ALL. Soluble mesothelin was present in 17.6% of AML and 2.7% of ALL cases (all adults), but not in healthy individuals. In AML, it correlated with CD33 expression and inv(16)/ t(16;16) . In conclusion, mesothelin is rare in ALL but enriched in specific AML subtypes and not prognostic for survival.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"184-194"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Utility of T-PIT, PIT-1, and SF-1 in Differentiating Pituitary Neuroendocrine Tumors From Sinonasal and Skull Base Tumors.","authors":"Hebatullah Elsafy, Nelli S Lakis, Mohammad Haeri, Devin L Shrock, Justin A Bishop, Lisa M Rooper, Todd M Stevens","doi":"10.1097/PAI.0000000000001317","DOIUrl":"10.1097/PAI.0000000000001317","url":null,"abstract":"<p><p>Pituitary adenoma (pituitary neuroendocrine tumor) can present a diagnostic pitfall when it involves the sinonasal tract ectopically or by direct extension due to morphologic and immunohistochemical overlap with sinonasal small round blue cell tumors. T-box transcription factor (T-PIT), pituitary-specific transcription factor (PIT-1), and steroidogenic factor 1 (SF-1) have emerged as lineage-specific markers for corticotroph, somatotroph, and gonadotroph-type adenomas, respectively, but have not been extensively tested in sinonasal tumors. We examined T-PIT, PIT-1, and SF-1 expression across sinonasal and skull base tumors to assess their specificity in this differential diagnosis. Staining for T-PIT, PIT-1, and SF-1 was performed on tissue microarrays including 199 sinonasal tumors and 12 nonsinonasal head and neck neuroendocrine carcinomas. Whole tissue sections from 20 adenomas, 2 olfactory carcinomas, and 1 Merkel cell carcinoma of nasal skin also underwent staining for all 3 markers, while 9 other sinonasal or skull base tumors underwent staining for T-PIT and PIT-1 only. All 223 sinonasal tumors and neuroendocrine carcinomas of the head and neck were negative for T-PIT and PIT-1. Only 7 of 214 nonpituitary tumors (3.3%) showed SF-1 expression, including 2 of 43 HPV-positive squamous cell carcinomas, 1 of 75 HPV-negative squamous cell carcinomas, 2 of 8 SMARCB1-deficient sinonasal carcinomas, 1 of 4 salivary neuroendocrine carcinomas, and 1 of 5 NUT carcinomas. All pituitary tumors stained as expected. These findings demonstrate that T-PIT and PIT-1 are highly specific for pituitary origin, while SF-1 shows limited off-target expression in certain high-grade sinonasal tumors with chromatin remodeling (e.g., NUT carcinoma and SMARCB1-deficient carcinoma).</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"178-183"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}