新一代测序通过标准组织病理学方法证实了两种不同的肺癌和肝癌之间的克隆关系

Tian Li, John Diks, Snow Trinh Nguyen, Jianying Zeng, Neil Chen, S. Vignesh
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引用次数: 0

摘要

两个肿瘤在解剖学上不同的部位具有不同的组织病理学,给出了双重原发性恶性肿瘤的图像。我们在此报告一个可能有两个原发肿瘤和一个继发肿块的病例。病例报告:74岁女性,活跃吸烟者,无个人或家族癌症病史,表现为早饱腹和虚弱两个月。系统检查显示胃有“生涩”的感觉,用抗酸剂缓解。生命体征稳定,腹部检查呈阴性。实验室显示白细胞增多24.8 K/uL (3.5-10.8 K/uL)左移,小细胞贫血血红蛋白6.1 g/dL (12.0-16.0 g/dL),反应性血小板增多477 K/uL (130-400 K/uL)。CT增强扫描显示右上肺叶坏死性空化灶伴纵隔反应性淋巴结及右肺门淋巴结病变,胰头尾2个不规则低密度灶,无导管扩张,肝脏2个不规则低密度灶。内镜超声(EUS)对肺和胰腺病变进行免疫组化检查,结果与低分化鳞状细胞癌(SCC)伴广泛坏死一致,提示胰腺肿块可能从肺转移。肝组织活检显示高级别神经内分泌肿瘤伴局灶性坏死。接下来进行基因测序。由于功能状况不佳,提供姑息性免疫治疗;然而,病人死于呼吸衰竭。结论:考虑到形态学和免疫特征,鉴别诊断应包括双原发癌合并一转移或原发SCC合并神经内分泌分化。尽管具有不同的组织病理学和免疫表型,但肺和肝肿瘤具有相同的分子谱,即使在未知意义的变异中也表现出相同的突变。因此,它们是直接相关的。TP53、RB1、MYCL1和MEK1突变在SCC中比NET更普遍。肿瘤突变负担值可能随着肿瘤克隆结构在原发位点和转移位点之间的差异而变化,由于克隆选择,转移中记录的单克隆结构率更高,导致整体遗传多样性降低(“瓶颈”)。这引起了肝肿瘤为神经内分泌分化的SCC的怀疑。标本的缺乏和快速的临床过程限制了进一步的研究。生殖系测试对于确定这些发现是体细胞还是生殖系是有用的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Next-generation sequencing proves clonal relationship between two distinguished lung and liver carcinomas by standard histopathology approach
Introduction: Two tumors having different histopathologies at anatomically distinct sites giving the picture of dual primary malignancies. Here we presented a case of two possible primary tumors and one secondary mass. Case Report: A 74-year-old female, active smoker, without personal or family cancer history presented with early satiety and weakness for two months. Systems review was positive for a “raw” feeling in stomach, alleviated with antacids. Vital signs were stable with a negative abdominal exam. Lab showed leukocytosis 24.8 K/uL (3.5–10.8 K/uL) with left shift, microcytic anemia with hemoglobin 6.1 g/dL (12.0–16.0 g/dL), and reactive thrombocytosis 477 K/uL (130–400 K/uL). Contrast-enhanced computed tomography (CT) showed right upper lobe necrotizing cavitating lesion with reactive mediastinal and right hilar lymphadenopathy, two irregular hypodense lesions in pancreatic head and tail without ductal dilation with two irregular hypodense liver lesions. Immunohistochemistry of lung and pancreatic lesions were biopsied through endoscopic ultrasound (EUS), consistent with poorly differentiated squamous cell carcinoma (SCC) with extensive necrosis, which indicates pancreatic masses are likely metastases from the lung. Liver lesion biopsy exhibited high-grade neuroendocrine tumor (NET) with focal necrosis. Next gene sequencing was pursued. Given poor functional status, palliative immunotherapy was offered; however, the patient succumbed to respiratory failure. Conclusion: Given the morphology and immunoprofile, differential diagnosis includes dual primary cancers with one metastasis, or primary SCC with metastasis with neuroendocrine differentiation. Despite having different histopathology and immunophenotype, both lung and liver tumors harbor the same molecular profile even at the variants of unknown significance that show identical mutations. As a result, they are directly related. TP53, RB1, MYCL1, and MEK1 mutations are more prevalent in SCC than NET. Tumor mutation burden values may vary as the tumor clonal structure varies between primary and metastatic sites, with higher rates of monoclonal structure recorded in metastases due to clonal selection, leading to a reduction in overall genetic diversity (“bottlenecking”). This raises the suspicion that the liver tumor is a SCC with neuroendocrine differentiation. The paucity of the specimen and rapid clinical course limited further investigation. Germline testing would have been useful to determine whether these findings are somatic or germline.
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