Inadequate specimen quality or quantity hinders comprehensive genomic profiling in identifying actionable mutations and guiding treatment strategies. We investigated the optimal conditions for pancreatic cancer specimen selection for comprehensive genomic profiling. We retrospectively analyzed 213 pancreatic cancer cases ordered for comprehensive genomic profiling and compared results from pancreatic biopsy, liver biopsy of pancreatic cancer metastases, pancreatectomy, liquid, and nonliver metastatic organ specimens. We examined preanalytical conditions, including cellularity (tumor cell count/size). The successfully tested cases were those that underwent comprehensive genomic profiling tests without any issues. The successfully tested case ratio was 72.8%. Pancreatic biopsy had the highest successfully tested case ratio (87%), with a high tumor cell percentage, despite the small number of cells (median, 3425). Pancreatic biopsy, liver biopsy of pancreatic cancer metastases, and non-liver metastatic organ had higher successfully tested case ratios than that for pancreatectomy. Liver biopsy of pancreatic cancer metastases and pancreatectomy cases with tumor size (mm2) × tumor ratio (%) > 150 and >3000, respectively, had high successfully tested case ratios. The success of comprehensive genomic profiling is significantly influenced by the tumor cell ratio, and pancreatic biopsy is a potentially suitable specimen for comprehensive genomic profiling.
{"title":"Evaluation of pancreatic cancer specimens for comprehensive genomic profiling.","authors":"Kota Washimi, Yukihiko Hiroshima, Shinya Sato, Makoto Ueno, Satoshi Kobayashi, Naoto Yamamoto, Chie Hasegawa, Emi Yoshioka, Kyoko Ono, Yoichiro Okubo, Tomoyuki Yokose, Yohei Miyagi","doi":"10.1111/pin.13416","DOIUrl":"10.1111/pin.13416","url":null,"abstract":"<p><p>Inadequate specimen quality or quantity hinders comprehensive genomic profiling in identifying actionable mutations and guiding treatment strategies. We investigated the optimal conditions for pancreatic cancer specimen selection for comprehensive genomic profiling. We retrospectively analyzed 213 pancreatic cancer cases ordered for comprehensive genomic profiling and compared results from pancreatic biopsy, liver biopsy of pancreatic cancer metastases, pancreatectomy, liquid, and nonliver metastatic organ specimens. We examined preanalytical conditions, including cellularity (tumor cell count/size). The successfully tested cases were those that underwent comprehensive genomic profiling tests without any issues. The successfully tested case ratio was 72.8%. Pancreatic biopsy had the highest successfully tested case ratio (87%), with a high tumor cell percentage, despite the small number of cells (median, 3425). Pancreatic biopsy, liver biopsy of pancreatic cancer metastases, and non-liver metastatic organ had higher successfully tested case ratios than that for pancreatectomy. Liver biopsy of pancreatic cancer metastases and pancreatectomy cases with tumor size (mm<sup>2</sup>) × tumor ratio (%) > 150 and >3000, respectively, had high successfully tested case ratios. The success of comprehensive genomic profiling is significantly influenced by the tumor cell ratio, and pancreatic biopsy is a potentially suitable specimen for comprehensive genomic profiling.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kei Ito, N. Honma, Hideaki Ogata, Akimitsu Yamada, Mika Miyashita, Tomio Arai, E. Sasaki, Kazutoshi Shibuya, Tetuo Mikami, Masataka Sawaki
Appropriate biomarkers are required to predict the clinical outcome of triple-negative breast cancer (TNBC). In this study, we focused on the clinical importance of two representative tumor-associated proteins, Bcl-2 and p53. Bcl-2 expression is usually related to estrogen receptor expression and a favorable outcome in breast cancer. TNBC has been reported to show a high frequency of p53 positivity suggesting TP53 mutations. The expressions of Bcl-2 and p53 were immunohistochemically examined in TNBC involving two age groups of postmenopausal women (≥75 y/o, n = 75; 55-64 y/o, n = 47), who underwent surgery without neoadjuvant therapy. We examined their associations with each other, or with clinicopathological factors including the outcome. Bcl-2 expression was inversely correlated with androgen receptor, apocrine morphology, and p53 expressions, and was an independent predictor of a poor outcome in total or in younger women. p53 positivity was associated with a more favorable outcome than p53 negativity in the younger group. In combined analyzes, none of the twenty Bcl-2-negative/p53-positive cases in the younger group exhibited recurrence, resulting in the independent favorable predictive value of Bcl-2-negative/p53-positive. The anti-apoptotic nature of Bcl-2 may be apparent in TNBC. The excellent outcome of Bcl-2-negative/p53-positive cases in the younger group warrants further combined investigation of Bcl-2/p53 in TNBC.
{"title":"Clinicopathological importance of Bcl-2 and p53 in postmenopausal triple-negative breast carcinoma and association with age.","authors":"Kei Ito, N. Honma, Hideaki Ogata, Akimitsu Yamada, Mika Miyashita, Tomio Arai, E. Sasaki, Kazutoshi Shibuya, Tetuo Mikami, Masataka Sawaki","doi":"10.1111/pin.13429","DOIUrl":"https://doi.org/10.1111/pin.13429","url":null,"abstract":"Appropriate biomarkers are required to predict the clinical outcome of triple-negative breast cancer (TNBC). In this study, we focused on the clinical importance of two representative tumor-associated proteins, Bcl-2 and p53. Bcl-2 expression is usually related to estrogen receptor expression and a favorable outcome in breast cancer. TNBC has been reported to show a high frequency of p53 positivity suggesting TP53 mutations. The expressions of Bcl-2 and p53 were immunohistochemically examined in TNBC involving two age groups of postmenopausal women (≥75 y/o, n = 75; 55-64 y/o, n = 47), who underwent surgery without neoadjuvant therapy. We examined their associations with each other, or with clinicopathological factors including the outcome. Bcl-2 expression was inversely correlated with androgen receptor, apocrine morphology, and p53 expressions, and was an independent predictor of a poor outcome in total or in younger women. p53 positivity was associated with a more favorable outcome than p53 negativity in the younger group. In combined analyzes, none of the twenty Bcl-2-negative/p53-positive cases in the younger group exhibited recurrence, resulting in the independent favorable predictive value of Bcl-2-negative/p53-positive. The anti-apoptotic nature of Bcl-2 may be apparent in TNBC. The excellent outcome of Bcl-2-negative/p53-positive cases in the younger group warrants further combined investigation of Bcl-2/p53 in TNBC.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daichi Morii, T. Matsui, Taisuke Mori, Y. Yatabe, Eiichi Morii
{"title":"Retinal gliosis with osseous metaplasia in an infant.","authors":"Daichi Morii, T. Matsui, Taisuke Mori, Y. Yatabe, Eiichi Morii","doi":"10.1111/pin.13431","DOIUrl":"https://doi.org/10.1111/pin.13431","url":null,"abstract":"","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastric cancers frequently harbor striking histological complexity and diversity between lesions as well as within single lesions, known as inter- and intratumoral heterogeneity, respectively. The latest World Health Organization Classification of Tumors designated more than 30 histological subtypes for gastric epithelial tumors, assigning 12 subtypes for gastric adenocarcinoma (GAD). Meanwhile, recent advances in genome-wide analyses have provided molecular aspects to the histological classification of GAD, and consequently revealed different molecular traits underlying these histological subtypes. Moreover, accumulating knowledge of comprehensive molecular profiles has led to establishing molecular classifications of GAD, which are often associated with clinical biomarkers for therapeutics and prognosis. However, most of our knowledge of GAD molecular profiles is based on inter-tumoral heterogeneity, and the molecular profiles underlying intratumoral heterogeneity are yet to be determined. In this review, recently established molecular classifications of GAD are introduced in the aspect of pathological diagnosis and are discussed in the context of intratumoral heterogeneity.
{"title":"Molecular classification and intratumoral heterogeneity of gastric adenocarcinoma.","authors":"Takeshi Kuwata","doi":"10.1111/pin.13427","DOIUrl":"https://doi.org/10.1111/pin.13427","url":null,"abstract":"Gastric cancers frequently harbor striking histological complexity and diversity between lesions as well as within single lesions, known as inter- and intratumoral heterogeneity, respectively. The latest World Health Organization Classification of Tumors designated more than 30 histological subtypes for gastric epithelial tumors, assigning 12 subtypes for gastric adenocarcinoma (GAD). Meanwhile, recent advances in genome-wide analyses have provided molecular aspects to the histological classification of GAD, and consequently revealed different molecular traits underlying these histological subtypes. Moreover, accumulating knowledge of comprehensive molecular profiles has led to establishing molecular classifications of GAD, which are often associated with clinical biomarkers for therapeutics and prognosis. However, most of our knowledge of GAD molecular profiles is based on inter-tumoral heterogeneity, and the molecular profiles underlying intratumoral heterogeneity are yet to be determined. In this review, recently established molecular classifications of GAD are introduced in the aspect of pathological diagnosis and are discussed in the context of intratumoral heterogeneity.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune‐related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative pathological feature of renal irAEs. However, the clinicopathological entity and underlying pathogenesis of ICI‐induced TIN are unclear. Therefore, we compared the clinical and histological features of this condition with those of non‐ICI drug‐induced TIN. Age and C‐reactive protein levels were significantly higher in ICI‐induced TIN, but there were no significant differences in renal function. Immunophenotyping of ICI‐induced TIN showed massive T cell and macrophage infiltration with fewer B cells, plasma cells, neutrophils, and eosinophils. Compared with those in non‐ICI drug‐induced TIN, CD4+ cell numbers were significantly lower in ICI‐induced TIN but CD8+ cell numbers were not significantly different. However, CD8/CD3 and CD8/CD4 ratios were higher in ICI‐induced TIN. Moreover, CD25+ and FOXP3+ cells, namely regulatory T cells, were less abundant in ICI‐induced TIN. In conclusion, T cell, B cell, plasma cell, neutrophil, and eosinophil numbers proved useful for differentiating ICI‐induced and non‐ICI drug‐induced TIN. Furthermore, the predominant distribution of CD8+ cells and low accumulation of regulatory T cells might be associated with ICI‐induced TIN development.
免疫检查点抑制剂(ICIs)可为癌症患者带来生存益处,但有时也会导致肾脏免疫相关不良事件(irAEs)的发生。肾小管间质性肾炎(TIN)是肾脏免疫相关不良事件中最具代表性的病理特征。然而,ICI 诱导的 TIN 的临床病理实体和潜在发病机制尚不清楚。因此,我们比较了该病症与非 ICI 药物诱导的 TIN 的临床和组织学特征。ICI诱发的TIN患者年龄和C反应蛋白水平明显升高,但肾功能无明显差异。ICI 诱导的 TIN 的免疫分型显示大量 T 细胞和巨噬细胞浸润,B 细胞、浆细胞、中性粒细胞和嗜酸性粒细胞较少。与非ICI药物诱导的TIN相比,ICI诱导的TIN中CD4+细胞数量明显减少,但CD8+细胞数量无明显差异。但是,在 ICI 诱导的 TIN 中,CD8/CD3 和 CD8/CD4 比率较高。此外,在 ICI 诱导的 TIN 中,CD25+ 和 FOXP3+ 细胞(即调节性 T 细胞)的数量较少。总之,T细胞、B细胞、浆细胞、中性粒细胞和嗜酸性粒细胞的数量证明有助于区分ICI诱导的TIN和非ICI药物诱导的TIN。此外,CD8+细胞的主要分布和调节性T细胞的低积累可能与ICI诱导的TIN发展有关。
{"title":"Predominant CD8+ cell infiltration and low accumulation of regulatory T cells in immune checkpoint inhibitor‐induced tubulointerstitial nephritis","authors":"Kenta Tominaga, Etsuko Toda, Kazuhiro Takeuchi, Shoichiro Takakuma, Emi Sakamoto, Hideaki Kuno, Yusuke Kajimoto, Yasuhiro Terasaki, Shinobu Kunugi, Akiko Mii, Yukinao Sakai, Mika Terasaki, Akira Shimizu","doi":"10.1111/pin.13428","DOIUrl":"https://doi.org/10.1111/pin.13428","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune‐related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative pathological feature of renal irAEs. However, the clinicopathological entity and underlying pathogenesis of ICI‐induced TIN are unclear. Therefore, we compared the clinical and histological features of this condition with those of non‐ICI drug‐induced TIN. Age and C‐reactive protein levels were significantly higher in ICI‐induced TIN, but there were no significant differences in renal function. Immunophenotyping of ICI‐induced TIN showed massive T cell and macrophage infiltration with fewer B cells, plasma cells, neutrophils, and eosinophils. Compared with those in non‐ICI drug‐induced TIN, CD4<jats:sup>+</jats:sup> cell numbers were significantly lower in ICI‐induced TIN but CD8<jats:sup>+</jats:sup> cell numbers were not significantly different. However, CD8/CD3 and CD8/CD4 ratios were higher in ICI‐induced TIN. Moreover, CD25<jats:sup>+</jats:sup> and FOXP3<jats:sup>+</jats:sup> cells, namely regulatory T cells, were less abundant in ICI‐induced TIN. In conclusion, T cell, B cell, plasma cell, neutrophil, and eosinophil numbers proved useful for differentiating ICI‐induced and non‐ICI drug‐induced TIN. Furthermore, the predominant distribution of CD8<jats:sup>+</jats:sup> cells and low accumulation of regulatory T cells might be associated with ICI‐induced TIN development.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pulmonary neuroendocrine (NE) cells are rare airway epithelial cells. The balance between Achaete‐scute complex homolog 1 (ASCL1) and hairy and enhancer of split 1, one of the target molecules of the Notch signaling pathway, is crucial for NE differentiation. Small cell lung cancer (SCLC) is a highly aggressive lung tumor, characterized by rapid cell proliferation, a high metastatic potential, and the acquisition of resistance to treatment. The subtypes of SCLC are defined by the expression status of NE cell‐lineage transcription factors, such as ASCL1, which roles are supported by SRY‐box 2, insulinoma‐associated protein 1, NK2 homeobox 1, and wingless‐related integration site signaling. This network reinforces NE differentiation and may induce the characteristic morphology and chemosensitivity of SCLC. Notch signaling mediates cell‐fate decisions, resulting in an NE to non‐NE fate switch. The suppression of NE differentiation may change the histological type of SCLC to a non‐SCLC morphology. In SCLC with NE differentiation, Notch signaling is typically inactive and genetically or epigenetically regulated. However, Notch signaling may be activated after chemotherapy, and, in concert with Yes‐associated protein signaling and RE1‐silencing transcription factor, suppresses NE differentiation, producing intratumor heterogeneity and chemoresistance. Accumulated information on the molecular mechanisms of SCLC will contribute to further advances in the control of this recalcitrant cancer.
{"title":"Molecular pathology of small cell lung cancer: Overview from studies on neuroendocrine differentiation regulated by ASCL1 and Notch signaling","authors":"Takaaki Ito","doi":"10.1111/pin.13426","DOIUrl":"https://doi.org/10.1111/pin.13426","url":null,"abstract":"Pulmonary neuroendocrine (NE) cells are rare airway epithelial cells. The balance between Achaete‐scute complex homolog 1 (ASCL1) and hairy and enhancer of split 1, one of the target molecules of the Notch signaling pathway, is crucial for NE differentiation. Small cell lung cancer (SCLC) is a highly aggressive lung tumor, characterized by rapid cell proliferation, a high metastatic potential, and the acquisition of resistance to treatment. The subtypes of SCLC are defined by the expression status of NE cell‐lineage transcription factors, such as ASCL1, which roles are supported by SRY‐box 2, insulinoma‐associated protein 1, NK2 homeobox 1, and wingless‐related integration site signaling. This network reinforces NE differentiation and may induce the characteristic morphology and chemosensitivity of SCLC. Notch signaling mediates cell‐fate decisions, resulting in an NE to non‐NE fate switch. The suppression of NE differentiation may change the histological type of SCLC to a non‐SCLC morphology. In SCLC with NE differentiation, Notch signaling is typically inactive and genetically or epigenetically regulated. However, Notch signaling may be activated after chemotherapy, and, in concert with Yes‐associated protein signaling and RE1‐silencing transcription factor, suppresses NE differentiation, producing intratumor heterogeneity and chemoresistance. Accumulated information on the molecular mechanisms of SCLC will contribute to further advances in the control of this recalcitrant cancer.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nodal T‐follicular helper cell lymphoma (TFHL) is a subset of T‐cell lymphoma and frequently co‐occurs with Epstein–Barr virus (EBV)‐positive B‐cell lymphoma but not with T/NK‐cell lymphoma. Recently, a new entity with a worse prognosis, called EBV‐positive nodal T/NK‐cell lymphoma (NTNKL) has been established. Here, we report an autopsy case of synchronous multiple lymphomas, including TFHL and NTNKL. The patient was a 78‐year‐old female admitted with pneumonia. Although pneumonic symptoms were improved, fever, pancytopenia, and disseminated intravascular coagulation emerged, implicating lymphoma. She died on the 21st hospital day without a definitive diagnosis. The autopsy revealed the enlargement of multiple lymph nodes throughout her body. Histological analysis revealed three distinct regions in the left inguinal lymph node. The first region consists of small‐sized lymphocytes with T‐follicular helper phenotype and extended follicular dendritic cell meshwork, indicating TFHL. The second region included EBV‐positive large B cells. The third region comprised EBV‐positive large cells with cytotoxic T/NK cell phenotype, indicating NTNKL. Clonality analysis of the first and the third regions showed different patterns. Since various hematopoietic malignancies progress from common clonal hematopoiesis according to existing literature, this case may help to understand TFHL and NTNKL.
结节性T滤泡辅助细胞淋巴瘤(TFHL)是T细胞淋巴瘤的一个亚型,经常与Epstein-Barr病毒(EBV)阳性B细胞淋巴瘤并发,但不与T/NK细胞淋巴瘤并发。最近,一种预后较差的新类型淋巴瘤--EBV 阳性结节性 T/NK 细胞淋巴瘤(NTNKL)被发现。在此,我们报告了一例同步多发性淋巴瘤(包括TFHL和NTNKL)的尸检病例。患者是一名因肺炎入院的 78 岁女性。虽然肺炎症状有所改善,但出现了发热、全血细胞减少和弥散性血管内凝血,这与淋巴瘤有关。她在住院第 21 天死亡,但没有得到明确诊断。尸检显示她全身多处淋巴结肿大。组织学分析显示,左腹股沟淋巴结有三个不同的区域。第一个区域由具有 T 滤泡辅助表型和扩展的滤泡树突状细胞网状结构的小体积淋巴细胞组成,显示为 TFHL。第二个区域包括 EBV 阳性的大 B 细胞。第三个区域包括具有细胞毒性 T/NK 细胞表型的 EBV 阳性大细胞,表明是 NTNKL。第一和第三区域的克隆分析显示出不同的模式。根据现有文献,各种造血恶性肿瘤都是从常见的克隆造血发展而来,因此本病例可能有助于理解TFHL和NTNKL。
{"title":"Co‐occurrence of Epstein–Barr virus‐positive nodal T/NK‐cell lymphoma and nodal T‐follicular helper cell lymphoma of different clonal origins: An autopsy case report","authors":"Daisuke Hoshi, Nami Migita, Shin Ishizawa, Yasuharu Sato, Koichi Yamamura, Etsuko Kiyokawa","doi":"10.1111/pin.13425","DOIUrl":"https://doi.org/10.1111/pin.13425","url":null,"abstract":"Nodal T‐follicular helper cell lymphoma (TFHL) is a subset of T‐cell lymphoma and frequently co‐occurs with Epstein–Barr virus (EBV)‐positive B‐cell lymphoma but not with T/NK‐cell lymphoma. Recently, a new entity with a worse prognosis, called EBV‐positive nodal T/NK‐cell lymphoma (NTNKL) has been established. Here, we report an autopsy case of synchronous multiple lymphomas, including TFHL and NTNKL. The patient was a 78‐year‐old female admitted with pneumonia. Although pneumonic symptoms were improved, fever, pancytopenia, and disseminated intravascular coagulation emerged, implicating lymphoma. She died on the 21st hospital day without a definitive diagnosis. The autopsy revealed the enlargement of multiple lymph nodes throughout her body. Histological analysis revealed three distinct regions in the left inguinal lymph node. The first region consists of small‐sized lymphocytes with T‐follicular helper phenotype and extended follicular dendritic cell meshwork, indicating TFHL. The second region included EBV‐positive large B cells. The third region comprised EBV‐positive large cells with cytotoxic T/NK cell phenotype, indicating NTNKL. Clonality analysis of the first and the third regions showed different patterns. Since various hematopoietic malignancies progress from common clonal hematopoiesis according to existing literature, this case may help to understand TFHL and NTNKL.","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}