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Giant inflammatory polyposis in Crohn's disease mimicking recurrent obstructing colon cancer 模仿复发性梗阻性结肠癌的克罗恩病巨型炎性息肉病
IF 2.2 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-10 DOI: 10.1111/pin.13479
Christopher Holt, David E. Elliott, Yiqin Xiong
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引用次数: 0
Standardization of CD30 immunohistochemistry staining among three automated immunostaining platforms. 三种自动免疫染色平台的 CD30 免疫组化染色标准化。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-22 DOI: 10.1111/pin.13472
Masafumi Seki, Akira Satou, Renji Funato, Tomoko Tamaki, Naoki Wada, Norihiro Nakada, Hirofumi Matsumoto, Iwao Nakazato, Eriko Wada, Kaneko Sakurai, Toyonori Tsuzuki, Kennosuke Karube

The identification of CD30 expression by immunohistochemistry is essential for the treatment of lymphomas using an antibody-drug conjugate targeting CD30. However, no standardized protocol for CD30 staining has been available. In this study, we compared three common automated immunostaining platforms {Bond III (B III), Dako Omnis (DO) and Ventana BenchMark ULTRA (VBMU)}. A primary antibody for CD30, the Ber-H2 clone, was diluted 50- to 400-fold for B III and DO, and ready-to-use antibody was used for VBMU. An enhancement step using a linker was introduced in all protocols. First, several candidate dilutions were selected for each platform by staining six cases. These candidate conditions were then confirmed with 60 cases of various types of peripheral T-cell lymphomas (PTCLs). The concordance rates of CD30 expression among platforms differed depending on cutoff values and antibody dilutions, except for anaplastic large cell lymphoma. The concordance rates among three platforms in the evaluation of "positive" or "negative" were 100% and 97% when the cutoff values were 1% and 10% respectively, if using 400-diluted antibody in B III and 100-diluted antibody in DO. This study demonstrated the feasibility of equalizing CD30 staining of PTCLs among different platforms by adjusting protocols.

通过免疫组化鉴定 CD30 的表达对于使用 CD30 靶向抗体-药物共轭物治疗淋巴瘤至关重要。然而,目前还没有标准化的 CD30 染色方案。在这项研究中,我们比较了三种常见的自动免疫染色平台{Bond III (B III)、Dako Omnis (DO) 和 Ventana BenchMark ULTRA (VBMU)}。B III 和 DO 使用的是稀释 50-400 倍的 CD30 一抗(Ber-H2 克隆),VBMU 使用的是即用型抗体。所有方案中都引入了使用连接剂的增强步骤。首先,通过对六个病例进行染色,为每个平台挑选出几个候选稀释度。然后用 60 例各种类型的外周 T 细胞淋巴瘤(PTCL)来确认这些候选条件。除无性大细胞淋巴瘤外,不同平台的 CD30 表达一致性因截断值和抗体稀释度的不同而不同。如果在 B III 中使用 400 稀释的抗体,在 DO 中使用 100 稀释的抗体,那么当临界值分别为 1%和 10%时,三个平台评价 "阳性 "或 "阴性 "的一致率分别为 100%和 97%。该研究证明了通过调整方案在不同平台间实现 PTCL CD30 染色均等化的可行性。
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引用次数: 0
Non-calcifying Langerhans cell-rich myxoid squamous odontogenic neoplasm without amyloid: A seemingly amyloid-negative calcifying epithelial odontogenic tumor. 不含淀粉样蛋白的非钙化朗格汉斯细胞丰富肌样鳞状牙源性肿瘤:一种看似淀粉样蛋白阴性的钙化上皮性牙源性肿瘤。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-31 DOI: 10.1111/pin.13470
Fumio Ide, Shinnichi Sakamoto, Yoko Tateishi, Hiroyuki Hayashi, Takayuki Ohsawa, Yumi Ito, Kentaro Kikuchi
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引用次数: 0
FHL1: A novel diagnostic marker for papillary thyroid carcinoma. FHL1:甲状腺乳头状癌的新型诊断标记物。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-09 DOI: 10.1111/pin.13467
Yeting Zeng, Dehua Zeng, Xingfeng Qi, Hanxi Wang, Xuzhou Wang, Xiaodong Dai, Lijuan Qu

Although there are clear morphologic criteria for the diagnosis of papillary thyroid carcinoma (PTC), when the morphology is untypical or overlaps, accurate diagnostic indicators are necessary. Since few studies investigated the role of down-regulated genes in PTC, this article aims to further explore the molecular markers associated with PTC. We conducted bioinformatics analysis of gene microarrays of PTC and normal adjacent tissues. Besides, quantitative real-time quantitative polymerase chain reaction array and immunohistochemical staining were used to investigate the expression of the major down-regulated genes. The results indicated that several important down-regulated genes, including TLE1, BCL2, FHL1, GHR, KIT, and PPARGC1A were involved in the process of PTC. Compared to normal adjacent tissues, the mRNA expression of the major genes was down-regulated in PTC (p<0.05). Immunohistochemically, FHL1 shows negative or low expression in PTC tissues (p<0.05). BCL2 did not show a significant difference between PTC and normal thyroid tissues (p > 0.05). TLE1, KIT, PPARGC1A and GHR showed negative expression in both tumor and normal tissues. These results suggested that FHL1 could serve as a novel tumor marker for precise diagnosis of PTC.

尽管甲状腺乳头状癌(PTC)的诊断有明确的形态学标准,但当形态不典型或重叠时,准确的诊断指标就显得十分必要。由于很少有研究调查下调基因在 PTC 中的作用,本文旨在进一步探讨与 PTC 相关的分子标记物。我们对 PTC 和正常邻近组织的基因芯片进行了生物信息学分析。此外,我们还利用实时定量聚合酶链反应阵列和免疫组化染色来研究主要下调基因的表达。结果表明,TLE1、BCL2、FHL1、GHR、KIT和PPARGC1A等几个重要的下调基因参与了PTC的发病过程。与正常邻近组织相比,PTC 中主要基因的 mRNA 表达均呈下调趋势(p<0.05)。免疫组化结果显示,FHL1在PTC组织中呈阴性或低表达(p<0.05)。BCL2在PTC和正常甲状腺组织中无明显差异(P>0.05)。TLE1、KIT、PPARGC1A和GHR在肿瘤和正常组织中均呈阴性表达。这些结果表明,FHL1可作为一种新型肿瘤标志物用于PTC的精确诊断。
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引用次数: 0
New insights into cancer pathology learned from the dynamics of cancer-associated fibroblasts. 从癌症相关成纤维细胞的动态中了解癌症病理学的新见解。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-25 DOI: 10.1111/pin.13461
Genichiro Ishii

Paget's "Seed and Soil" theory, proposed in 1889, emphasizes the importance of the microenvironment where cancer cells grow in metastatic sites. Over a century later, this concept remains a cornerstone in comprehending cancer biology and devising treatment strategies. The "Seed and Soil" theory, which initially explained how cancer spreads to distant organs, now also applies to the tumor microenvironment (TME) within primary tumors. This theory emphasizes the critical interaction between cancer cells ("seeds") and their surrounding environment ("soil") and how this interaction affects both tumor progression within the primary site and at metastatic sites. An important point to note is that the characteristics of the TME are not static but dynamic, undergoing substantial changes during tumor progression and after treatment with therapeutic drugs. Cancer-associated fibroblasts (CAFs), recognized as the principal noncancerous cellular component within the TME, play multifaceted roles in tumor progression including promoting angiogenesis, remodeling the extracellular matrix, and regulating immune responses. In this comprehensive review, we focus on the findings regarding how the dynamics of CAFs contribute to cancer progression and drug sensitivity. Understanding the dynamics of CAFs could provide new insights into cancer pathology and lead to important advancements in cancer research and treatment.

佩吉特的 "种子与土壤 "理论于 1889 年提出,强调了癌细胞在转移部位生长的微环境的重要性。一个多世纪过去了,这一概念仍然是理解癌症生物学和制定治疗策略的基石。种子与土壤 "理论最初解释了癌症如何向远处器官扩散,现在也适用于原发性肿瘤内的肿瘤微环境(TME)。该理论强调了癌细胞("种子")与其周围环境("土壤")之间的重要相互作用,以及这种相互作用如何影响原发部位和转移部位的肿瘤进展。值得注意的一点是,TME 的特征不是静态的,而是动态的,在肿瘤进展过程中和接受治疗药物治疗后会发生重大变化。癌症相关成纤维细胞(CAFs)被认为是TME内主要的非癌细胞成分,在肿瘤进展过程中发挥着多方面的作用,包括促进血管生成、重塑细胞外基质和调节免疫反应。在这篇综述中,我们将重点关注有关 CAFs 的动态如何促进癌症进展和药物敏感性的研究结果。了解 CAFs 的动态可为癌症病理学提供新的见解,并为癌症研究和治疗带来重要进展。
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引用次数: 0
A case of hepatoid adenocarcinoma of the lung harboring KRAS G12C responded favorably to sotorasib. 一例携带 KRAS G12C 的肺肝样腺癌患者对索托拉西布治疗反应良好。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1111/pin.13464
Hironori Uruga, Atsushi Miyamoto, Takeshi Fujii, Takashi Okuma, Takahiro Mitsumura, Meiyo Tamaoka, Yutaka Takazawa

Hepatoid adenocarcinoma of the lung is a rare variant of adenocarcinoma. We describe a case of hepatoid adenocarcinoma of the lung that harbored KRAS G12C and responded favorably to sotorasib. A man in his 70s was found to have an abnormality on his chest X-ray. He underwent right middle lobectomy, and a pathological examination of the surgical specimen showed conventional invasive adenocarcinoma with highly focal hepatoid adenocarcinoma. He received chemoradiotherapy and concurrent radiation, followed by durvalumab for postoperative recurrence. After three doses of durvalumab, he reported feeling short of breath. A computed tomography scan showed emerging broad consolidation in the right lower lobe. Transbronchial lung biopsy specimens from the consolidation showed hepatoid adenocarcinoma harboring KRAS G12C mutation. Therefore, he was started on sotorasib 960 mg daily. Eight days later, a computed tomography scan showed that the area of consolidation had reduced in size. Progressive disease was detected after 42 days of treatment with sotorasib. The patient died 1 month after cessation of sotorasib and 3 months after postoperative recurrence. We have encountered what we believe to be the first case of hepatoid adenocarcinoma of the lung with KRAS G12C mutation that responded favorably to treatment with sotorasib.

肺肝样腺癌是腺癌的一种罕见变体。我们描述了一例携带 KRAS G12C 并对索托拉西布反应良好的肺肝样腺癌。一名 70 多岁的男子在胸部 X 光片上发现异常。他接受了右侧中叶切除术,手术标本的病理检查显示为传统的浸润性腺癌,伴有高灶性肝样腺癌。他接受了化疗和同期放疗,术后复发时又接受了杜伐单抗治疗。在服用了三剂杜瓦鲁单抗后,他报告说感觉气短。计算机断层扫描显示,他的右下叶出现了广泛的合并症。经支气管肺活检标本显示,肝样腺癌携带 KRAS G12C 突变。因此,他开始每天服用索托拉西布(sotorasib)960 毫克。八天后,计算机断层扫描显示,合并区的面积缩小了。使用索托拉西布治疗42天后,发现病情有所进展。患者在停止索托拉西布治疗 1 个月后死亡,术后复发 3 个月后死亡。我们相信这是首例对索托拉西布治疗反应良好的 KRAS G12C 突变的肺肝样腺癌患者。
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引用次数: 0
Digital whole-slide imaging of changes in amyloid after peripheral blood stem cell transplantation in patients with amyloid light-chain amyloidosis. 淀粉样轻链淀粉样变性病患者外周血干细胞移植后淀粉样蛋白变化的数字全切片成像。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1111/pin.13466
Kei Kono, Naoki Sawa, Atsushi Wake, Yukako Shintani-Domoto, Takeshi Fujii, Yutaka Takazawa, Yoshifumi Ubara, Kenichi Ohashi

Peripheral blood stem cell transplantation (PBSCT) has made amyloid light-chain (AL) amyloidosis treatable. After PBSCT, hematological complete remission (HCR) can be achieved, leading to improved renal prognosis. The purpose of this study was to evaluate whether whole slide imaging of biopsy samples shows a post-treatment reduction in amyloid deposits in patients with AL amyloidosis. Patients were divided into three groups: Group A (n = 8), not eligible for PBSCT and treated with other therapies; Group B (n = 11), treated with PBSCT and achieved HCR; and Group C (n = 5), treated with PBSCT but did not achieve HCR. Clinical findings and amyloid deposition in glomeruli, interstitium, and blood vessels were compared before and after treatment using digital whole-slide imaging. Proteinuria and hypoalbuminemia improved more in Group B than in the other groups, and in Group B, amyloid deposition improved more in the glomeruli than in the interstitium and blood vessels. The long-term renal and survival prognosis was better in Group B than in the other groups. PBSCT can be expected to improve long-term clinical and renal histological prognosis in patients with AL amyloidosis who achieve HCR. Amyloid disappearance from renal tissue may take a long time even after clinical HCR.

外周血干细胞移植(PBSCT)使淀粉样轻链(AL)淀粉样变性病变得可以治疗。PBSCT后,可实现血液学完全缓解(HCR),从而改善肾脏预后。本研究旨在评估活检样本的全切片成像是否显示AL淀粉样变性患者治疗后淀粉样沉积物减少。患者分为三组:A组(n = 8),不符合PBSCT条件,接受其他疗法治疗;B组(n = 11),接受PBSCT治疗并获得HCR;C组(n = 5),接受PBSCT治疗但未获得HCR。采用数字全切片成像技术比较了治疗前后的临床表现以及肾小球、间质和血管中的淀粉样蛋白沉积情况。与其他组相比,B 组的蛋白尿和低白蛋白血症得到了改善,B 组的肾小球淀粉样蛋白沉积改善程度高于肾间质和血管。B 组的长期肾脏和生存预后优于其他组。PBSCT有望改善达到HCR的AL淀粉样变性患者的长期临床和肾组织学预后。即使在临床HCR后,肾组织中淀粉样蛋白的消失也可能需要很长时间。
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引用次数: 0
Autopsy case of linear nevus sebaceous syndrome with KRAS (G12D) mutation. KRAS(G12D)突变的线性皮脂腺痣综合征尸检病例。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-12 DOI: 10.1111/pin.13463
Akira Ohishi, Yasunori Enomoto, Hideto Iwafuchi, Shiori Meguro, Isao Kosugi, Satoshi Baba, Toshihide Iwashita, Yuki Segawa, Daizo Ueno, Shigeo Iijima

Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous syndrome associated with systemic complications that involve multiple organs, including the skin, central nervous system, eyes, and skeleton. LNSS is considered to be caused by mosaic RAS gene mutation. In this report, we present an autopsy case of LNSS in a Japanese boy. The affected neonate had hydrops fetalis and was born at 28 weeks and 4 days of gestation, weighing 2104 g. He had bilateral inverted eyelids, verrucous linear nevus separated along Blaschko's line, myocardial hypertrophy, and pharyngeal constriction, and underwent intensive treatment in NICU for arrhythmia, hydrocephalus, and respiratory distress. The hydrocephalus progressed gradually and he died at the age of 181 days, 12 days after a sudden cardiac arrest and recovery. KRAS G12D mutation was found in a skin biopsy specimen but not in blood cells, suggesting a postzygotic mosaicism. Autopsy revealed novel pathological findings related to LNSS, including intracranial lipomatous hamartoma and mesenteric lymphangioma, in addition to previously reported findings such as multicystic dysplastic kidney. There was the limited expression of mutated KRAS protein in kidneys.

线性皮脂腺痣综合征(LNSS)是一种神经皮肤综合征,伴有全身并发症,涉及多个器官,包括皮肤、中枢神经系统、眼睛和骨骼。LNSS 被认为是由镶嵌型 RAS 基因突变引起的。在本报告中,我们对一名日本男童的 LNSS 病例进行了尸检。受影响的新生儿患有胎儿水肿,出生时妊娠 28 周零 4 天,体重 2104 克。他患有双侧倒睫、沿布拉氏线分隔的疣状线形痣、心肌肥厚和咽部狭窄,并因心律失常、脑积水和呼吸窘迫在新生儿重症监护室接受了强化治疗。脑积水逐渐加重,在心脏骤停并恢复 12 天后死亡,享年 181 天。在皮肤活检标本中发现了 KRAS G12D 突变,但在血细胞中没有发现,这表明是后染色体嵌合。尸检发现了与LNSS相关的新病理结果,除了之前报道的多囊性发育不良肾脏等病理结果外,还包括颅内脂肪瘤和肠系膜淋巴管瘤。肾脏中突变的 KRAS 蛋白表达有限。
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引用次数: 0
Pathological evaluation of the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy. 对糖尿病和糖尿病周围神经病变发病机制的病理学评估。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-18 DOI: 10.1111/pin.13458
Hiroki Mizukami

Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications leading to its cure is becoming increasingly urgent. Pathological examination of pancreatic tissues from patients with type 2 diabetes reveals a decrease in the volume of beta cells because of a combination of various stresses. In human type 2 diabetes, islet amyloid deposition is a unique pathological change characterized by proinflammatory macrophage (M1) infiltration into the islets. The pathological changes in the pancreas with islet amyloid were different according to clinical factors, which suggests that type 2 diabetes can be further subclassified based on islet pathology. On the other hand, diabetic peripheral neuropathy is the most frequent diabetic complication. In early diabetic peripheral neuropathy, M1 infiltration in the sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated by in vitro live imaging. Furthermore, islet parasympathetic nerve density and beta cell volume were inversely correlated in type 2 diabetic Goto-Kakizaki rats, suggesting that diabetic peripheral neuropathy itself may contribute to the decrease in beta cell volume. These findings suggest that the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy may be interrelated.

目前,日本有 1 000 多万糖尿病患者。因此,探索糖尿病的发病机理和导致糖尿病并发症的治疗方法变得越来越迫切。对 2 型糖尿病患者的胰腺组织进行病理学检查发现,由于各种压力的综合作用,β 细胞的体积减少。在人类 2 型糖尿病患者中,胰岛淀粉样蛋白沉积是一种独特的病理变化,其特点是促炎性巨噬细胞(M1)浸润胰岛。胰岛淀粉样蛋白在胰腺中的病理变化因临床因素而异,这表明 2 型糖尿病可根据胰岛病理进一步细分。另一方面,糖尿病周围神经病变是最常见的糖尿病并发症。体外活体成像清楚地表明,在早期糖尿病周围神经病变中,坐骨神经中的M1浸润会诱发氧化应激或减弱轴突逆行运输。此外,2 型糖尿病 Goto-Kakizaki 大鼠的胰岛副交感神经密度与β细胞体积成反比,这表明糖尿病周围神经病变本身可能导致β细胞体积减少。这些研究结果表明,糖尿病和糖尿病周围神经病变的发病机制可能是相互关联的。
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引用次数: 0
Clear cell hidradenoma of the breast with MAML2 gene rearrangement. 伴有 MAML2 基因重排的乳腺透明细胞色素痣。
IF 2.5 4区 医学 Q2 PATHOLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-31 DOI: 10.1111/pin.13455
Li Luo, Yanping Hu

Clear cell hidradenoma is a rare benign tumor of the breast, its origin and pathogenesis are controversial. We have experienced a case of breast clear cell hidradenoma with mastermind like transcriptional coactivator 2 (MAML2) gene rearrangement. The patient found a painless mass with a hard texture in the left breast areola without nipple discharge. Microscopically, the tumor was cystic and solid, locally arranged in a glandular structure, covered by single cuboidal cells; it was composed of clear cells, epidermoid cells, and basaloid cells; there were no necrosis or mitotic figures. Immunohistochemical staining showed that the tumor cells positively expressed low-molecular cytokeratin 7, low-molecular cytokeratins (Cam5.2), high-molecular cytokeratin 5/6, cytokeratin 14, CD117, and p63; and did not express calponin, and smooth muscle myosin heavy chain. The cuboidal cells were positive for SOX10 but negative for p63. Additionally, periodic acid-Schiff reaction showed purple-red granules in the tumor cytoplasm, but Alcian blue staining showed no blue mucus in the cytoplasm. The split signals of MAML2 gene were detected by fluorescence in situ hybridization. Subtle histological and immunophenotypical differences may help to distinguish breast clear cell hidradenoma from common breast tumors. Furthermore, the MAML2 gene rearrangement may be a molecular genetic characteristic of breast clear cell hidradenoma.

透明细胞乳头状瘤是一种罕见的乳腺良性肿瘤,其起源和发病机制尚存在争议。我们曾接诊过一例乳腺透明细胞坐落细胞瘤,其主谋样转录辅激活剂 2(MAML2)基因重排。患者发现左侧乳晕有一质地较硬的无痛性肿块,无乳头溢液。显微镜下,肿瘤呈囊实性,局部排列成腺体结构,由单个立方体细胞覆盖,由透明细胞、表皮细胞和基底细胞组成,无坏死和有丝分裂。免疫组化染色显示,肿瘤细胞阳性表达低分子细胞角蛋白7、低分子细胞角蛋白(Cam5.2)、高分子细胞角蛋白5/6、细胞角蛋白14、CD117和p63,不表达钙蛋白和平滑肌肌球蛋白重链。立方体细胞的 SOX10 呈阳性,但 p63 呈阴性。此外,周期性酸-希夫反应显示肿瘤细胞质中有紫红色颗粒,但阿尔新蓝染色显示细胞质中没有蓝色粘液。荧光原位杂交检测到 MAML2 基因的分裂信号。组织学和免疫表型上的细微差别可能有助于区分乳腺透明细胞坐落细胞瘤和普通乳腺肿瘤。此外,MAML2基因重排可能是乳腺透明细胞坐落细胞瘤的分子遗传特征。
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引用次数: 0
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