Human pathology最新文献

{"title":"DDR2 expression in breast cancer is associated with blood vessel invasion, basal-like tumors, tumor associated macrophages, regulatory T cells, detection mode and prognosis","authors":"Tor Audun Klingen MD, PhD (Senoir physician) ,&nbsp;Ying Chen MD, PhD (Senoir physician) ,&nbsp;Hans Aas MD (Senior physician) ,&nbsp;Lars A. Akslen MD, PhD (Professor, Senior physician)","doi":"10.1016/j.humpath.2024.06.009","DOIUrl":"10.1016/j.humpath.2024.06.009","url":null,"abstract":"<div><p>Discoidin Domain Receptor 2 (DDR2) is a receptor tyrosine kinase for collagen, stimulating epithelial-mesenchymal transition and stiffness in breast cancer. Here, we investigated levels of DDR2 in breast tumor cells in relation to vascular invasion, TIL subsets, macrophages, molecular tumor subtypes, modes of detection and prognosis. This retrospective, population-based series of invasive breast carcinomas from the Norwegian Screening Program in Vestfold County (Norway), period 2004–2009, included 200 screening patients and 82 cases detected in screening intervals. DDR2 was examined on core needle biopsies using a semi-quantitative, immunohistochemical staining index and dichotomized as low or high DDR2 expression. Counts of macrophages and TIL subsets were dichotomized based on immunohistochemistry using TMA. We also recorded blood or lymphatic vessel invasion (BVI or LVI) as present or absent by immunohistochemistry. High expression of DDR2 in tumor cells showed significant relation with high counts of CD163+ macrophages (p &lt; 0.001) and FOXP3 TILs (p = 0.011), presence of BVI (p = 0.028), high tumor cell proliferation by Ki67 (p = 0.033), ER negativity (p = 0.001), triple-negative cases (p = 0.038), basal-like features (p &lt; 0.001) as well as interval detection (p &lt; 0.001). By multivariate analysis, high DDR2 expression was related to reduced recurrence-free survival (HR, 2.3, p = 0.017), when examined together with histologic grading, lymph node assessment, tumor diameter, BVI, and molecular tumor subtype. This study supports a link between high DDR2 expression, high counts of macrophages by CD163 (tumor associated) and regulatory T cells by FOXP3 together with the presence of <span>BVI</span>, possibly indicating increased tumor motility and intravasation in aggressive breast tumors.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 29-35"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of micronest in cancer stroma in resected lung squamous cell carcinoma","authors":"Yasunori Kaminuma ,&nbsp;Tokiko Nakai ,&nbsp;Keiju Aokage ,&nbsp;Tetsuro Taki ,&nbsp;Tomohiro Miyoshi ,&nbsp;Kenta Tane ,&nbsp;Joji Samejima ,&nbsp;Saori Miyazaki ,&nbsp;Naoya Sakamoto ,&nbsp;Shingo Sakashita ,&nbsp;Motohiro Kojima ,&nbsp;Reiko Watanabe ,&nbsp;Masahiro Tsuboi ,&nbsp;Genichiro Ishii","doi":"10.1016/j.humpath.2024.06.010","DOIUrl":"10.1016/j.humpath.2024.06.010","url":null,"abstract":"<div><p>Tumor budding in the cancer stroma has been reported to be a prognostic factor in non-small cell lung cancer. Micronest in cancer stroma (MICS) is often observed as a formation that is larger and more conspicuous than budding, but its clinicopathologic significance is unclear. In this study, we aimed to examine the clinicopathological significance of MICS in lung squamous cell carcinoma (LSqCC).</p><p>A total of 198 consecutive patients with pathologically diagnosed LSqCC (anyT N0-1M0) were enrolled in this study. MICS were defined as those that met the following criteria: (1) consisting of 5–200 tumor cells or less than 200 μm in diameter and (2) more than 200 μm away from the adjacent main lesion. The prognostic impact of the presence or absence of MICS and the characteristics of MICS-forming cancer cells were evaluated by immunohistochemistry (IHC).</p><p>MICS was observed in 57 patients (28.8%), and overall survival (OS) and recurrence-free survival (RFS) were significantly shorter in the MICS-positive group (OS: 44.4% vs. 84.4%, p &lt; 0.001; RFS: 30.0% vs. 82.6%, p &lt; 0.001). Univariate and multivariate analyses revealed that the presence of MICS was an independent poor prognostic factor for OS (hazard ratio [HR] 3.54, p &lt; 0.001) and RFS (HR 4.99, p &lt; 0.001). Immunohistochemistry showed that the expression levels of the cell-cell adhesion molecule E-cadherin and hypoxia-induced protein GLUT-1 were significantly decreased in cancer cells forming MICS lesions compared to the tumor component excluding MICS within the same tumor (non-MICS lesions).</p><p>Our data show that MICS is a distinct morphological feature with important biological and prognostic significance.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 20-28"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and morphologic characterization of intraductal tubulopapillary neoplasms of pancreas with novel potentially targetable fusions","authors":"Irena Manukyan,&nbsp;Susan J. Hsiao,&nbsp;Ladan Fazlollahi,&nbsp;Helen Remotti,&nbsp;Mahesh M. Mansukhani","doi":"10.1016/j.humpath.2024.06.014","DOIUrl":"10.1016/j.humpath.2024.06.014","url":null,"abstract":"<div><p>Intraductal tubulopapillary neoplasms (ITPNs) are rare pancreatic tumors with distinct histological and molecular features. Distinction of ITPN from other pancreatic neoplasms is crucial given the known favorable prognosis and the high frequency and diversity of potentially targetable fusions in ITPN. While the histological features of ITPN are well documented, there are few reports on the cytological features, and molecular characterization of ITPN. The authors reported three cases diagnosed in their laboratory between 2016 and 2021. Clinical data, cytomorphological and histological features, with immunophenotypic and molecular characterizations of these cases are described and compared with those reported in the literature. All 3 cases were diagnosed as ITPN based on the microscopic presence of intraductal nodules composed of tightly packed small tubular glands lined by cuboidal cells lacking apparent mucin. On molecular profiling <em>KRAS</em> and <em>TP53</em> variants were found in Case 1, FGFR2-INA fusion in Case 2, and STARD3NL-BRAF fusion was detected in Case 3. Immunohistochemistry (IHC) revealed that the neoplastic cells in Case 1 were MUC2 positive and MUC6 negative, but in Cases 2 and 3, were negative for MUC2 and positive for MUC6. These results demonstrate the immunophenotypic and molecular variabilities of histologically similar pancreatic neoplasms. The absence of alterations characteristic of more common pancreatic neoplasms should prompt the consideration of fusion studies in morphologically relevant cases. The combination of morphological, IHC, and molecular analyses is important for reliable identification of ITPN given its potential clinical management implications.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 36-41"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VHL-mutated papillary cystadenoma of the mesosalpinx with omental tumor deposits and immunophenotypic overlap with mesothelioma","authors":"","doi":"10.1016/j.humpath.2024.06.011","DOIUrl":"10.1016/j.humpath.2024.06.011","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105617"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of ATRX and DAXX in pancreatic neuroendocrine tumors: Association with recurrence risk, cellular phenotype, and heterogeneity","authors":"Yoichi Yasunaga ,&nbsp;Mariko Tanaka ,&nbsp;Junichi Arita ,&nbsp;Kiyoshi Hasegawa ,&nbsp;Tetsuo Ushiku","doi":"10.1016/j.humpath.2024.06.015","DOIUrl":"10.1016/j.humpath.2024.06.015","url":null,"abstract":"<div><p>Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of neoplasms in terms of biological behavior. This study aims to develop a practical algorithm based on emerging biomarkers, including chromatin-remodeling molecules DAXX/ATRX/H3K36me3, in conjunction with established prognostic factors, such as WHO grade and size. In immunohistochemical analyses, 18 of the 111 (16.2%) primary PanNETs showed DAXX or ATRX loss in a mutually exclusive manner. DAXX/ATRX loss was significantly correlated with higher recurrence risk and better predicted postoperative recurrence than WHO grade. We proposed a novel algorithm for stratifying patients with resectable PanNET into three groups according to recurrence risk: (A) WHO Grade 1 and ≤2 cm (very low-risk); for the others, (B) retained DAXX/ATRX (low-risk) and (C) DAXX/ATRX complete/heterogeneous loss (high-risk). Furthermore, we elucidated the intratumoral heterogeneities of PanNETs. Among cases with DAXX or ATRX loss, nine cases demonstrated heterogeneous loss of expression of DAXX/ATRX/H3K36me3. The majority of cases with DAXX/ATRX loss, either homogeneous or heterogeneous loss, showed uniform α-cell-like phenotype (ARX1+/PDX1−). In cases of metastatic or recurrent tumors, the expression pattern was identical to that observed in at least part of the primary tumor. In some instances, the expression pattern differed among different metastatic or recurrent tumors of the same patient. In summary, we propose a clinically useful and practical algorithm for postoperative recurrence risk stratification in PanNETs, by combining DAXX/ATRX status with WHO grade and size. Moreover, our findings highlighted the frequent spatiotemporal heterogeneity of chromatin-remodeling molecule expression in PanNETs with an α-cell phenotype, offering insights into tumorigenesis.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 51-57"},"PeriodicalIF":2.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001230/pdfft?md5=2900c1437649f16b77683703d88bd24d&pid=1-s2.0-S0046817724001230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application and pitfalls of immunophenotyping in challenging plasma cell neoplasms: A case series","authors":"","doi":"10.1016/j.humpath.2024.06.012","DOIUrl":"10.1016/j.humpath.2024.06.012","url":null,"abstract":"<div><p>Multiple myeloma (MM) is an incurable malignant plasma cell neoplasm, representing the second most common hematopoietic cancer. As plasma cell neoplasms are clonal and often secrete a monoclonal protein (M-spike), laboratory diagnosis is usually straightforward, especially when ancillary studies such as immunohistochemistry, flow cytometry, and protein electrophoresis are available in addition to microscopic examination. Despite the repertoire of diagnostic tools, rare cases pose diagnostic dilemmas, especially when reagent antibodies do not react as expected, extent of disease is patchy, or when disease occurs in unique age groups. In this retrospective study, we report a series of challenging diagnostic cases, discussing aberrant findings and comparing them to more classic counterparts. Twelve cases collected during routine clinical sign-out were reanalyzed and include examples of MGUS, classic multiple myeloma, t(11; 14) rearranged myeloma, minimal residual disease, AA and AL amyloidosis, truncated light chain, non-secretory and non-producer myeloma, biphenotypic myeloma, oligoclonal expansion after bone marrow transplant, and plasma cell leukemia in a young adult. This cohort showcases the diversity of atypical presentations of plasma cell neoplasms, and we highlight standardized approaches to workup to avoid diagnostic pitfalls.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 86-96"},"PeriodicalIF":2.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience","authors":"Burak Tekin ,&nbsp;Antonio L. Cubilla ,&nbsp;John C. Cheville ,&nbsp;Carin Y. Smith ,&nbsp;Sarah M. Jenkins ,&nbsp;Surendra Dasari ,&nbsp;Elizabeth Ann L. Enninga ,&nbsp;Andrew P. Norgan ,&nbsp;Santosh Menon ,&nbsp;Rumeal D. Whaley ,&nbsp;Loren Herrera Hernandez ,&nbsp;Rafael E. Jimenez ,&nbsp;Joaquin J. Garcia ,&nbsp;R. Houston Thompson ,&nbsp;Bradley C. Leibovich ,&nbsp;R. Jeffrey Karnes ,&nbsp;Stephen A. Boorjian ,&nbsp;Lance C. Pagliaro ,&nbsp;Lori A. Erickson ,&nbsp;Ruifeng Guo ,&nbsp;Sounak Gupta","doi":"10.1016/j.humpath.2024.06.013","DOIUrl":"10.1016/j.humpath.2024.06.013","url":null,"abstract":"<div><h3>Objectives</h3><p>There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV–positivity, and evaluate the prognostic impact of relevant clinicopathologic variables.</p></div><div><h3>Methods</h3><p>Patients with pSCC (<em>n</em> = 121) consecutively treated with partial/total penectomy (2000–2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression.</p></div><div><h3>Results</h3><p>The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV–positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2–99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV–negative compared to high-risk HPV–positive patients (HR 2.74, CI 1.12–8.23, <em>P</em> = 0.03). Moreover, among high-risk HPV–negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1–48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV–positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0–33.1).</p></div><div><h3>Conclusions</h3><p>We demonstrate high-risk HPV–positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV–negative, and basaloid subtype in high-risk HPV–positive pSCC) may have prognostic value.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 9-19"},"PeriodicalIF":2.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis","authors":"Amanda J. Nguyen ,&nbsp;Emma Johnson ,&nbsp;Michael Camilleri ,&nbsp;Carilyn Wieland ,&nbsp;Julia S. Lehman ,&nbsp;Shruti Agrawal ,&nbsp;Nneka Comfere ,&nbsp;Numrah Fadra ,&nbsp;Ryan A. Knudson ,&nbsp;Patricia Greipp ,&nbsp;Kevin Halling ,&nbsp;Ruifeng (Ray) Guo","doi":"10.1016/j.humpath.2024.06.006","DOIUrl":"10.1016/j.humpath.2024.06.006","url":null,"abstract":"<div><p>Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored <em>YAP1</em>::<em>NUTM1</em> fusion gene by RNA sequencing. <em>MAML2</em> fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 1-8"},"PeriodicalIF":2.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal neoplasms of the tongue: A clinicopathologic study of 93 cases","authors":"Domenika Ortiz Requena ,&nbsp;Jaylou M. Velez-Torres ,&nbsp;Julio A. Diaz-Perez ,&nbsp;Carmen Gomez-Fernandez ,&nbsp;Elizabeth A. Montgomery ,&nbsp;Andrew E. Rosenberg","doi":"10.1016/j.humpath.2024.06.005","DOIUrl":"10.1016/j.humpath.2024.06.005","url":null,"abstract":"<div><p>Neoplasms of the tongue are relatively common, and the vast majority are epithelial in phenotype. Although uncommon, a diverse and distinctive array of mesenchymal neoplasms arises in this anatomic site. To increase our understanding of these lesions, we reviewed our experience of MNs of the tongue and described their clinicopathologic features. The pathology archives from 2005 to 2021 and the consultation files of one of the authors were queried for all MNs of the tongue. We reviewed the histologic slides and ancillary studies and obtained clinical data from the available medical records. Ninety-three cases were identified, and they form the study cohort - to our knowledge, this is the largest series of mesenchymal neoplasms of the tongue. Forty-eight patients were female, and forty-five were male, with a mean age of 51 years (range: 1–94 years). The tumors included 43 (46.2%) hemangiomas, 14 (15%) granular cell tumors, 8 (9%) lipomas, 4 (4.3%) schwannomas, 4 (4.3%) solitary fibrous tumors - all with low risk of progression based on risk stratification criteria, 2 (2.2%) lymphangiomas, 3 (3.2%) Kaposi sarcomas, 2 (2.2%) chondromas, 2 (2.2%) myofibromas, 1 (1.1%) solitary circumscribed neuroma, 1 (1.1%) perineurioma, 1 (1.1%) neurofibroma, 1 (1.1%) ectomesenchymal chondromyxoid tumor, 1 (1.1%) atypical glomus tumor with a <em>NOTCH2</em> rearrangement and <em>TLL2</em> mutation, 1 (1.1%) spindle cell rhabdomyosarcoma, 1 (1.1%) pleomorphic fibroblastic sarcoma, 1 (1.1%) malignant rhabdoid tumor, 1 (1.1%) leiomyosarcoma, 1 (1.1%) angiosarcoma, and 1 (1.1%) alveolar soft part sarcoma. Most of the patients underwent surgical excision, and 1 patient (with hemangioma) underwent embolization. On follow-up, the patient with spindle cell rhabdomyosarcoma developed postoperative numbness at the surgical site and was disease-free through 17 months of follow-up. The patient with leiomyosarcoma declined adjuvant radiation and developed metastasis to the lung at 22 months. The patient with alveolar soft part sarcoma had metastases to the lung at the time of diagnosis and received adjuvant chemotherapy. The remaining patients had no local or distant recurrence. MNs of the tongue are usually benign and characterized by either endothelial, adipocytic, or schwannian differentiation. The mainstay of treatment is surgical excision with the extent of excision determined by tumor type. Adjuvant therapy is reserved for high-grade sarcomas.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 42-50"},"PeriodicalIF":2.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of two-step approach for screening NTRK fusion in two major subtypes of non-small cell lung cancer within a large cohort","authors":"Kun Dong,&nbsp;Yanli Zhu,&nbsp;Xinying Liu,&nbsp;Wei Sun,&nbsp;Xin Yang,&nbsp;Kaiwen Chi,&nbsp;Ling Jia,&nbsp;Xinting Diao,&nbsp;Xiaozheng Huang,&nbsp;Lixin Zhou,&nbsp;Dongmei Lin","doi":"10.1016/j.humpath.2024.06.003","DOIUrl":"10.1016/j.humpath.2024.06.003","url":null,"abstract":"<div><p>Our objective is to investigate a cost-effective approach to screen for <em>NTRK</em> fusion in the major subtypes of non-small cell lung cancer (NSCLC). Evaluate the concordance between immunohistochemistry (IHC) and next-generation sequencing (NGS), as well as between fluorescence in situ hybridization (FISH) and NGS, to detect any discrepancies in methodological consistency between lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). Analyze the factors influencing IHC results. A cohort of 1654 patients with NSCLC underwent screening for <em>NTRK</em> fusion using whole slide IHC. The positive cases were analyzed by both FISH and NGS. Totally, 57 tested positive for pan-TRK, with positivity rates of 0.68% (10/1467) for LADC and 29.01% (47/162) for LSCC. FISH showed separate <em>NTRK1</em> and <em>NTRK3</em> rearrangements in two pan-TRK-positive LADCs, while all LSCCs tested negative. NGS confirmed functional <em>NTRK</em> fusion in two FISH-positive cases: one involving <em>TPM3-NTRK1</em> and the other involving <em>SQSTM1-NTRK3</em>. A non-functional fusion of <em>NTRK2-XRCC1</em> was detected in LSCC, while FISH was negative. According to our approach, the prevalence of <em>NTRK</em> fusion in NSCLC is 0.12%. The concordance rate between IHC and RNA-based NGS was 20% (2/10) in LADC and 0% (0/162) in LSCC. When the positive criteria increased over 50% of tumor cells showing strong staining, the concordance would be 100% (2/2). A concordance rate of 100% (2/2) was observed between FISH and RNA-based NGS in LADC. The expression of pan-TRK was significantly correlated with the tumor proportion score (TPS) of PD-L1 (p &lt; 0.05) and transcript per million (TPM) values of <em>NTRK2</em> (p &lt; 0.05). We recommend using IHC with strict criteria to screen NTRK fusion in LADC rather than LSCC, confirmed by RNA-based NGS directly. When the NGS results are inconclusive, FISH validation is necessary.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 39-47"},"PeriodicalIF":3.3,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}