Human pathology最新文献

{"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}

{"title":"Acquired cystic disease associated renal cell carcinoma: A clinicopathologic and molecular study of 31 tumors","authors":"Ejas Palathingal Bava ,&nbsp;Joseph M. Sanfrancesco ,&nbsp;Ahmed Alkashash ,&nbsp;Laura Favazza ,&nbsp;Akram Aldilami ,&nbsp;Sean R. Williamson ,&nbsp;Liang Cheng ,&nbsp;Mohammed T. Idrees ,&nbsp;Khaleel I. Al-Obaidy","doi":"10.1016/j.humpath.2024.06.002","DOIUrl":"10.1016/j.humpath.2024.06.002","url":null,"abstract":"<div><p>Acquired cystic disease associated renal cell carcinomas (ACD-RCC) are rare and their molecular and histopathological characteristics are still being explored. We therefore investigated the clinicopathologic and molecular characteristics of 31 tumors. The patients were predominantly male (n = 30), with tumors mainly left-sided (n = 17), unifocal (n = 19), and unilateral (n = 29) and a mean tumor size of 25 mm (range, 3–65 mm). Microscopically, several histologic patterns were present, including pure classic sieve-like (n = 4), and varied proportions of mixed classic sieve-like with papillary (n = 23), tubulocystic (n = 9), compact tubular (n = 4) and solid (n = 1) patterns. Calcium-oxalate crystals were seen in all tumors. Molecular analysis of 9 tumors using next generation sequencing showed alterations in <em>SMARCB1</em> in 3 tumors (1 with frameshift deletion and 2 with copy number loss in chromosome 22 involving <em>SMARCB1</em> region), however, INI1 stain was retained in all. Nonrecurrent genetic alterations in <em>SETD2, NF1, NOTCH4</em>, <em>BRCA2</em> and <em>CANT1</em> genes were also seen. Additionally, <em>MTOR</em> p.Pro351Ser was identified in one tumor. Copy number analysis showed gains in chromosome 16 (n = 5), 17 (n = 2) and 8 (n = 2) as well as loss in chromosome 22 (n = 2). In summary, ACD-RCC is a recognized subtype of kidney tumors, with several histological architectural patterns. Our molecular data identifies genetic alterations in chromatin modifying genes (<em>SMARCB1</em> and <em>SETD2</em>), which may suggest a role of such genes in ACD-RCC development.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 48-54"},"PeriodicalIF":3.3,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305814","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":"Comparison of genomic profiling of patient-matched primary colorectal and surgical resected distant metastatic (stage IV) colorectal carcinoma for drug actionability","authors":"Yi-Hua Jan ,&nbsp;Cu tai Lu ,&nbsp;Alfred King-yin Lam","doi":"10.1016/j.humpath.2024.06.001","DOIUrl":"10.1016/j.humpath.2024.06.001","url":null,"abstract":"<div><p>It is often difficult to obtain adequate tissue for genomic study from distant metastases for assessment of targeted therapy in colorectal carcinomas. The study aims to explore the genomic differences between matched distant metastatic colorectal carcinomas (mCRC) and primary carcinoma using surgical specimens of both with adequate tissue. Thirty-four paired primary and distant metastatic colorectal carcinoma samples (liver, ovary, and lung) were obtained from surgical excisions (not small biopsies) and are microsatellite stable. They were subjected to DNA sequencing using comprehensive next-generation sequencing. This included mutation concordance analysis and mutational signature analysis. The mutation concordance analysis showed 49.6% shared mutations between primary and metastatic tumours, with 23.0% mutations exclusive to primary tumours and 27.4% mutations exclusive to distant metastases. While many patients with <em>KRAS</em>/<em>BRAF</em> mutations had shared mutations, two cases had unique <em>KRAS</em> mutations in the primary tumours only. Additionally, TMB (tumour mutational burden) analysis revealed that half of the TMB-high (≥7.5 mutations/Mb) metastatic colorectal carcinomas had a low TMB (&lt;7.5 mutations/Mb) in the primary tumours. The mutational signature analysis identified de novo signatures consistent with known single base substitution patterns such as SBS11 (alkylation agents) and SBS30 (base excision repair deficiency) post-chemotherapy. To conclude, this study demonstrates significant genomic variations in resected distant metastasis when compared to primary colorectal carcinomas when adequate tissue is available. This finding underscores the importance of considering these differences and selecting tissue for mutation analysis in planning targeted and effective treatment strategies for mCRC.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 21-28"},"PeriodicalIF":3.3,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001023/pdfft?md5=a503fc4534fc6dbcb93b777f967200df&pid=1-s2.0-S0046817724001023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305815","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":"A comparison of the histopathologic features of thyroid carcinomas with NTRK fusions to those with other malignant fusions","authors":"I. Tondi Resta ,&nbsp;A. Rind ,&nbsp;K.T. Montone ,&nbsp;V.A. Livolsi ,&nbsp;Z.W. Baloch","doi":"10.1016/j.humpath.2024.06.004","DOIUrl":"10.1016/j.humpath.2024.06.004","url":null,"abstract":"<div><h3>Background</h3><p>Chromosomal rearrangements involving one of the <em>NTRK</em> genes result in oncogenic driver mutations in thyroid carcinoma (TC) and serve as a target for therapy. We compared the clinicopathologic features of thyroid carcinomas with <em>NTRK</em> fusions vs. thyroid neoplasms with other malignancy associated gene fusions within our institution.</p></div><div><h3>Materials and methods</h3><p>Our pathology archives were searched from 2013 to 2023 for thyroid neoplasms with gene fusions, excluding <em>THADA</em> fusions and medullary thyroid carcinomas.</p></div><div><h3>Results</h3><p>55 thyroid lesions were identified: 22 with <em>NTRK</em> fusions (<em>NTRK</em> cohort) and 33 with other fusions (non-<em>NTRK</em> cohort). On fine needle aspiration (FNA), 54% of the <em>NTRK</em> cohort were classified as Category V as per Bethesda System for Reporting Thyroid Cytology (TBSRTC) and 51.5% of non-<em>NTRK</em> cohort as TBSRTC Category III. In the <em>NTRK</em> cohort, the most common reported fusion was <em>ETV6::NTRK3</em> and the most common reported fusion in the non-<em>NTRK</em> cohort was <em>PAX8::PPAR-gamma</em>. On histologic examination both cohorts were most commonly diagnosed as PTC follicular variant. Invasive features were more common in the <em>NTRK</em> cohort in comparison to the non-<em>NTRK</em> cohort. Locoregional recurrence occurred in 2/22 NTRK cases and 2/33 non-<em>NTRK</em> cases, with average time from surgery to recurrence being 5.5 months and 21 months, respectively. The majority of patients in both groups are alive with no evidence of disease.</p></div><div><h3>Conclusions</h3><p>Thyroid neoplasms with a malignancy associated gene fusion are likely to be diagnosed as subtype/variant of PTC. Patients whose thyroid lesions harbor <em>NTRK</em> fusions present with a PTC-FV that on presentation has more aggressive clinicopathologic findings and are likely to have earlier disease recurrence.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 29-38"},"PeriodicalIF":3.3,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300567","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":"Inside front cover - Masthead","authors":"","doi":"10.1016/S0046-8177(24)00095-9","DOIUrl":"https://doi.org/10.1016/S0046-8177(24)00095-9","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Page IFC"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294447","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":"Prevalence and detection methodology for preliminary exploration of NTRK fusion in gastric cancer from a single-center retrospective cohort","authors":"Kun Dong ,&nbsp;Lisha Yin ,&nbsp;Yu Wang ,&nbsp;Ling Jia ,&nbsp;Xinting Diao ,&nbsp;Xiaozheng Huang ,&nbsp;Lixin Zhou ,&nbsp;Dongmei Lin ,&nbsp;Yu Sun","doi":"10.1016/j.humpath.2024.04.011","DOIUrl":"10.1016/j.humpath.2024.04.011","url":null,"abstract":"<div><p>The fusion of neurotrophic tyrosine receptor kinase (<em>NTRK</em>) is a novel target for cancer therapy and offers hope for patients with gastric cancer (GC). However, there are few studies on the prevalence and detection methods of <em>NTRK</em> fusions in GC. In this study, we used immunohistochemistry (IHC) as a screening method to select cases for molecular testing and evaluated the effectiveness of IHC, fluorescence <em>in situ</em> hybridization (FISH), and next-generation sequencing (NGS). We retrospectively collected 1970 patients with GC. Pan-TRK IHC was conducted in all cases, and three cases were positive: one with strong and diffuse cytoplasmic staining, while two with weak cytoplasmic staining. All three cases were validated using <em>NTRK</em>1/2/3 FISH. FISH results revealed a single 3′ signal of <em>NTRK</em>1 in 95% of the tumor cells in the first case, while the remaining two cases were negative. NGS confirmed LMNA-<em>NTRK1</em> fusion in the first case, with no gene fusion detected in the other two cases. Out of 46 negative controls, one had a non-functional fusion of <em>IGR-NTRK</em>1, and four had point mutations. The case with <em>LMNA-NTRK</em>1 fusion were negative for pMMR, EBV, HER2, and AFP. The pan-TRK IHC showed a 33.33% (1/3) concordance rate with RNA-based NGS. If the criterion for positivity was 3+ cytoplasmic staining, the agreement between IHC and RNA-based NGS was 100% (1/1). In conclusion, the incidence of NTRK fusion in GC is extremely low (0.05%). If the criteria are strict, pan-TRK IHC is highly effective for screening NTRK fusions. FISH could complement NGS detection, particularly when <em>NTRK</em> fusion is detected by DNA sequencing. <em>NTRK</em> fusion in GC may not be limited to specific subtypes.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Pages 87-92"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759894","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}