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Evaluation of pancreatic cancer specimens for comprehensive genomic profiling. 评估胰腺癌标本以进行全面基因组分析。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2024-03-13 DOI: 10.1111/pin.13416
Kota Washimi, Yukihiko Hiroshima, Shinya Sato, Makoto Ueno, Satoshi Kobayashi, Naoto Yamamoto, Chie Hasegawa, Emi Yoshioka, Kyoko Ono, Yoichiro Okubo, Tomoyuki Yokose, Yohei Miyagi

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.

标本的质量或数量不足会妨碍全面基因组图谱分析确定可操作的突变和指导治疗策略。我们研究了选择胰腺癌标本进行全面基因组图谱分析的最佳条件。我们回顾性分析了213例胰腺癌病例,并比较了胰腺活检、胰腺癌转移肝活检、胰腺切除术、液体和非肝转移器官标本的结果。我们检查了分析前的条件,包括细胞度(肿瘤细胞数量/大小)。成功检测的病例是指在没有任何问题的情况下进行了全面基因组分析测试的病例。成功检测的病例比例为 72.8%。胰腺活检的成功检测率最高(87%),尽管细胞数量较少(中位数为 3425 个),但肿瘤细胞比例较高。与胰腺切除术相比,胰腺活检、胰腺癌转移的肝活检和非肝转移器官的成功检测率更高。胰腺癌转移肝活检和胰腺切除术病例的肿瘤大小(平方毫米)×肿瘤比率(%)分别大于 150 和大于 3000,其成功检测病例比率较高。综合基因组图谱分析的成功率受肿瘤细胞比例的显著影响,而胰腺活检是一种潜在的适合进行综合基因组图谱分析的标本。
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引用次数: 0
Low-grade carcinoma with acinic cell carcinoma-like features of the parotid gland with CRTC3::IQGAP1 fusion. 伴有 CRTC3::IQGAP1 融合的腮腺低分化癌,具有尖细胞癌样特征。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2024-04-02 DOI: 10.1111/pin.13423
Masami Iwamoto, Taisuke Mori, Eijitsu Ryo, Shoko Handa, Yuuki Nishimura, Masato Nagaoka, Masayuki Shimoda
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引用次数: 0
Clinicopathological importance of Bcl-2 and p53 in postmenopausal triple-negative breast carcinoma and association with age. 绝经后三阴性乳腺癌中 Bcl-2 和 p53 的临床病理学重要性以及与年龄的关系。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-24 DOI: 10.1111/pin.13429
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.
预测三阴性乳腺癌(TNBC)的临床结果需要适当的生物标志物。在本研究中,我们重点研究了两种具有代表性的肿瘤相关蛋白--Bcl-2 和 p53 的临床重要性。Bcl-2 的表达通常与雌激素受体的表达和乳腺癌的良好预后有关。有报道称,TNBC的p53阳性率很高,这表明TP53发生了突变。我们用免疫组化方法检测了两个年龄组绝经后妇女(≥75 岁/o,n = 75;55-64 岁/o,n = 47)TNBC 中 Bcl-2 和 p53 的表达,这些妇女接受了手术,但没有接受新辅助治疗。我们研究了它们之间的关系,或与临床病理因素(包括预后)之间的关系。Bcl-2的表达与雄激素受体、腺体形态和p53的表达成反比,是预测所有女性或年轻女性不良预后的独立指标。在综合分析中,年轻组的 20 例 Bcl-2 阴性/p53 阳性病例中没有一例出现复发,因此 Bcl-2 阴性/p53 阳性具有独立的有利预测价值。Bcl-2的抗凋亡特性在TNBC中可能很明显。年轻组中Bcl-2阴性/p53阳性病例的良好预后值得进一步对TNBC中的Bcl-2/p53进行联合研究。
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引用次数: 0
Composite ALK-negative anaplastic large cell lymphoma and follicular lymphoma involving jejunum and mesenteric lymph nodes. ALK阴性的非典型大细胞淋巴瘤和滤泡性淋巴瘤复合体,累及空肠和肠系膜淋巴结。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-24 DOI: 10.1111/pin.13433
Qiongzhi Yang, Tianming Zhang, Na Fang, Wenjia Sun
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引用次数: 0
Retinal gliosis with osseous metaplasia in an infant. 婴儿视网膜胶质细胞病变并伴有骨化。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-23 DOI: 10.1111/pin.13431
Daichi Morii, T. Matsui, Taisuke Mori, Y. Yatabe, Eiichi Morii
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引用次数: 0
Molecular classification and intratumoral heterogeneity of gastric adenocarcinoma. 胃腺癌的分子分类和瘤内异质性。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-23 DOI: 10.1111/pin.13427
Takeshi Kuwata
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.
胃癌经常具有惊人的组织学复杂性和多样性,病灶之间以及单个病灶内部的组织学复杂性和多样性分别被称为瘤间异质性和瘤内异质性。世界卫生组织最新的肿瘤分类为胃上皮肿瘤指定了 30 多个组织学亚型,为胃腺癌(GAD)指定了 12 个亚型。与此同时,全基因组分析的最新进展为 GAD 的组织学分类提供了分子方面的依据,从而揭示了这些组织学亚型背后的不同分子特征。此外,综合分子图谱知识的不断积累也促成了 GAD 分子分类的建立,这些分类通常与治疗和预后的临床生物标志物相关联。然而,我们对 GAD 分子图谱的了解大多基于肿瘤间的异质性,而肿瘤内异质性的分子图谱尚待确定。本综述从病理诊断的角度介绍了最近确立的 GAD 分子分类,并结合瘤内异质性进行了讨论。
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引用次数: 0
The first lichen planus case coexisting bronchiolitis obliterans without malignant tumors. 首例扁平苔藓与无恶性肿瘤的闭塞性支气管炎并存的病例。
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-23 DOI: 10.1111/pin.13432
T. Nikaido, Y. Tanino, Yuki Sato, R. Togawa, N. Watanabe, Xintao Wang, Naoko Fukuhara, Rina Harigane, Koshi Saito, Kentaro Kazama, Ryuki Yamada, Riko Sato, H. Tomita, Mami Rikimaru, Yasuhito Suzuki, H. Minemura, J. Saito, Kenya Kanazawa, Toshiyuki Yamamoto, Yuko Hashimoto, Akira Hebisawa, Yoko Shibata
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引用次数: 0
Predominant CD8+ cell infiltration and low accumulation of regulatory T cells in immune checkpoint inhibitor‐induced tubulointerstitial nephritis 在免疫检查点抑制剂诱导的肾小管间质性肾炎中,CD8+细胞浸润占主导地位,而调节性T细胞积累较少
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-18 DOI: 10.1111/pin.13428
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
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。
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引用次数: 0
Molecular pathology of small cell lung cancer: Overview from studies on neuroendocrine differentiation regulated by ASCL1 and Notch signaling 小细胞肺癌的分子病理学:受 ASCL1 和 Notch 信号调控的神经内分泌分化研究综述
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-12 DOI: 10.1111/pin.13426
Takaaki Ito
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.
肺神经内分泌(NE)细胞是罕见的气道上皮细胞。Achaete-scute复合体同源物1(ASCL1)与Notch信号通路的靶分子之一毛发和分裂增强子1之间的平衡对NE的分化至关重要。小细胞肺癌(SCLC)是一种侵袭性很强的肺部肿瘤,其特点是细胞增殖快、转移潜力大、耐药性强。SCLC的亚型是根据NE细胞系转录因子(如ASCL1)的表达状态确定的,SRY-box 2、胰岛素瘤相关蛋白1、NK2 homeobox 1和无翼鸟相关整合位点信号支持这些转录因子的作用。这一网络加强了NE的分化,并可能诱发SCLC的特征性形态和化学敏感性。Notch信号介导细胞命运决定,导致NE向非NE命运转换。抑制NE分化可能会使SCLC的组织学类型变为非SCLC形态。在NE分化的SCLC中,Notch信号通常不活跃,并受遗传或表观遗传调控。然而,化疗后Notch信号可能被激活,并与Yes相关蛋白信号和RE1沉默转录因子共同抑制NE分化,从而产生瘤内异质性和化疗耐药性。有关 SCLC 分子机制的信息积累将有助于进一步推动对这种顽固癌症的控制。
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引用次数: 0
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 Epstein-Barr病毒阳性结节性T/NK细胞淋巴瘤和不同克隆起源的结节性T滤泡辅助细胞淋巴瘤同时存在:尸检病例报告
IF 2.2 4区 医学 Q2 Medicine Pub Date : 2024-04-05 DOI: 10.1111/pin.13425
Daisuke Hoshi, Nami Migita, Shin Ishizawa, Yasuharu Sato, Koichi Yamamura, Etsuko Kiyokawa
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。
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