Fumaratehydratase-deficient renal cell carcinoma: a clinicopathological and molecular study of 13 cases
Fumaratehydratase-deficient renal cell carcinoma: a clinicopathological and molecular study of 13 cases
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富马酸水合酶缺陷型肾细胞癌13例临床病理及分子生物学研究
DOI：
10.1136/jclinpath-2019-205924
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发表时间：
2019-11-01
影响因子：
3.4
通讯作者：
Chen, Ni
中科院分区：
文献类型：
--
作者：
Pan, Xiuyi;Zhang, Mengni;Chen, Ni
目的遗传性平滑肌瘤病和肾细胞癌（HLRCC）是WHO 2016分类中新认识的实体，定义为FH基因的种系突变。富马酸水合酶缺陷型肾细胞癌（FH缺陷型RCC）被推荐用于FH缺陷但缺乏FH种系突变遗传证据的肿瘤。在这项研究中，我们描述了13例FH缺陷型RCC的临床病理和分子变化。方法和结果收集每例患者的组织学特征、临床病理资料、放射学表现和结局。对FH基因进行下一代测序和DNA测序，以检测FH突变。患者组包括5名女性和8名男性。不同形态的间质有乳头状、巢状、腺样、泡沫腺样、筛状、管状、管状囊状、囊状和疏松水肿。除典型的大核伴或不伴嗜酸性核仁和核仁周晕外，还可见到葡萄干样、针钉样甚至低级别核。11例高级别细胞核的病例显示疾病进展或死亡，但2例低级别细胞核和嗜酸性细胞质的病例未检测到疾病进展。除病例11外，肿瘤细胞中不存在FH表达。下一代测序和DNA测序证实了13例病例中的7个FH种系突变和4个体细胞突变。结论FH缺陷型肾细胞癌是一种少见的肾肿瘤，形态多样。大多数肿瘤具有高级别的细胞核，并且具有侵袭性。然而，我们观察到一种形态学亚型的FH-缺陷型肾细胞癌，细胞核低级别，胞浆嗜酸性，这可能主要发生在年轻女性，并显示出相对良好的预后。
Aims Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a newly recognised entity in the WHO 2016 classification defined as the germline mutation of FH gene. Fumaratehydratase-deficient renal cell carcinoma (FH-deficient RCC) is recommended for tumours with FH deficiency but lacking of genetic evidences of FH germline mutation. In this study, we described the clinicopathological and molecular changes of 13 FH-deficient RCCs. Methods and results Histology features, clinicopathological data, radiology performance and outcomes were collected for each patient. Next-generation sequencing and DNA sequencing of FH gene were performed to examine FH mutations. The patient group included five females and eight males. Different morphological patterns of papillary, nested, adenoid, foam adenoid, cribriform, tubular, tubulocystic, cystic and loose oedema stroma were observed. Except typical big nuclei with or without eosinophilic nucleoli and perinucleolar halos, raisin-like, hobnail-like and even low-grade nuclei were also observed in these tumours. Eleven cases with high-grade nuclei showed disease progression or death, but no disease progression was detected in two cases with low-grade nuclei and eosinophilic cytoplasm. FH expression was absent in tumour cells except for case 11. Next-generation sequencing and DNA sequencing verified seven FH germline mutations and four somatic mutations out of 13 cases. Conclusions FH-deficient RCC is a rare renal tumour and has a wide morphological spectrum. Most of the tumours had high-grade nuclei and were aggressive. However, we observed a morphological subtype of FH-deficient RCC with low-grade nuclei and eosinophilic cytoplasm, which might mainly occur in young women and show a relatively good prognosis.