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北京大学学报（医学版） ›› 2021, Vol. 53 ›› Issue (4): 640-646. doi: 10.19723/j.issn.1671-167X.2021.04.003

• 论著 • 上一篇    下一篇

延胡索酸水合酶缺陷型肾细胞癌的临床病理特征及预后

于妍斐,何世明,吴宇财,熊盛炜,沈棋,李妍妍,杨风,何群(),李学松()   

  1. 北京大学第一医院泌尿外科,北京大学泌尿外科研究所,国家泌尿、男性生殖系肿瘤研究中心,北京 100034
  • 收稿日期:2021-01-11 出版日期:2021-08-18 发布日期:2021-08-25
  • 通讯作者: 何群,李学松 E-mail:bdyyqhe@sina.com;pineneedle@sina.com
  • 基金资助:
    北京大学第一医院科研种子基金(2020SF36)

Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma

YU Yan-fei,HE Shi-ming,WU Yu-cai,XIONG Sheng-wei,SHEN Qi,LI Yan-yan,YANG Feng,HE Qun(),LI Xue-song()   

  1. National Urological Cancer Center, Beijing 100034, China
  • Received:2021-01-11 Online:2021-08-18 Published:2021-08-25
  • Contact: Qun HE,Xue-song LI E-mail:bdyyqhe@sina.com;pineneedle@sina.com
  • Supported by:
    Scientific Research Seed Fund of Peking University First Hospital(2020SF36)

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摘要：

目的: 探讨延胡索酸水合酶缺陷型肾细胞癌(fumarate hydratase-deficient renal cell carcinoma,FH-RCC)的临床病理特征及预后。方法: 应用免疫组织化学染色的方法检测北京大学第一医院泌尿外科2013年1月至2019年12月收治的109例60岁及以下不同类型肾细胞癌患者肿瘤组织中延胡索酸水合酶(fumarate hydratase,FH)的表达情况,分析FH-RCC的临床病理特征及预后。结果: 筛选出11例FH-RCC患者,其中男性7例,女性4例,发病年龄16~53岁(平均36.7岁)。4名女性患者均有子宫肌瘤病史,仅1例患者的一级亲属有肾癌家族史,所有患者均无皮肤平滑肌肿瘤的病史及家族史。肾细胞癌的肿瘤直径2.1~12.0 cm(平均8.83 cm), 9例患者有肾窦或肾周脂肪侵犯,6例有肾静脉或下腔静脉内瘤栓形成,7例有淋巴结转移,4例侵犯肾上腺,1例侵犯脾脏被膜。11例患者中7例(7/49例,14.3%)原诊断为Ⅱ型乳头状肾细胞癌,2例(2/9例,22.2%)原诊断为集合管癌,2例(2/51例,3.9%)原诊断为未分类型肾细胞癌。肿瘤组织病理学大多表现为乳头状、管囊状、实性片状等不同结构的混合,最常见的组织结构为乳头状(9/11例,81.8%)及管状(8/11例,72.7%)结构,3例伴有肉瘤样分化。肿瘤细胞均可见灶状分布大而明显的嗜酸性核仁(WHO/国际泌尿病理协会Ⅲ~Ⅳ级)及核周空晕。免疫组织化学检测显示,癌组织CA9、CD10、CK7染色大多阴性,2例TFE3阳性表达的病例经荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测,结果显示TFE3基因均未发生易位或扩增。11例患者均获得随访资料,随访时间11~82个月,确诊后患者平均生存期为24个月,其中5例于术后9~31个月(平均19个月)因肿瘤远处转移而死亡,6例存活患者中已有5例发生了远处转移。结论: FH-RCC在组织形态学上与多种肾细胞癌有重叠,乳头状及管囊状排列方式的混合存在是FH-RCC最常见的生长方式,癌细胞中灶状出现大而明显的嗜酸性核仁是该类型肾细胞癌的重要组织学特征,FH免疫组织化学染色有助于明确诊断。对于患有平滑肌瘤的年轻女性肾细胞癌患者,需警惕FH-RCC的可能。部分FH-RCC的诊断缺少临床证据,应根据组织病理学特征进一步行基因检测以确诊。

关键词: 肾细胞癌, 延胡索酸水合酶, 免疫组织化学, 预后

Abstract:

Objective: To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC). Methods: Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed. Results: There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic. Conclusion: Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Key words: Renal cell carcinoma, Fumarate hydratase, Immunohistochemistry, Prognosis

中图分类号: 

  • R737.11

表1

延胡索酸水合酶缺陷型肾细胞癌的临床特征"

Patient
No.		 Gender Age/
years		 Presentation Personal history Family history Tumor
location		 Distant metastasis OS/month
1 M 39 Flank pain - Uterine leiomyomas Right Liver, thoracic
vertebrae		 11.3
2 F 35 Physical examination Uterine leiomyomas,
adrenal cortical hyperplasia		 Uterine leiomyomas Left Omentum 12.5
3 F 26 Flank pain Uterine leiomyomas RCC Right Bone 13.2
4 M 34 Physical examination - - Left Bone, diaphragm 20.0
5 M 16 Flank pain - Uterine leiomyomas Left - 9.2 (DOD)
6 M 53 Physical examination - - Right Bone 16.6 (DOD)
7 M 37 Physical examination - Uterine leiomyomas Left Rectum 32.8
8 F 40 Physical examination Multiple uterine leiomyomas Uterine leiomyomas Left - 17.2 (DOD)
9 M 48 Hematuria - - Left Unkown 17.2 (DOD)
10 F 28 Flank pain Uterine leiomyomas Uterine leiomyomas,
colorectal carcinoma		 Right - 31.5 (DOD)
11 M 48 Hematuria Cystic nephroma - Right - 82.7

表2

延胡索酸水合酶缺陷型肾细胞癌的病理特征"

Patient No. Size/cm Initial histological type Fuhrman grade pTNM stage Histological structures
Solid Papillary Tubulocystic Cribriform
1 12.0 PRCC Ⅱ G3 pT3aN1 - Yes Yes Yes
2 6.5 PRCC Ⅱ G3 pT3aN1 - Yes Yes -
3 11.0 PRCC Ⅱ G3 pT2b - Yes Yes -
4 6.5 PRCC Ⅱ G3 pT4N1 Yes Yes - -
5 8.5 PRCC Ⅱ G3 pT4N1 - Yes - -
6 10.5 CDC G3 pT4N1 Yes Yes Yes -
7 12.0 U-RCC G4 pT4N1 Yes Yes Yes Yes
8 9.0 U-RCC G3 pT3aN1 - Yes Yes Yes
9 8.0 PRCC Ⅱ G3 pT3bN2 Yes Yes Yes -
10 11.0 PRCC Ⅱ G3 T3a - Yes Yes -
11 2.1 CDC G3 pT1a - - Yes -

图1

延胡索酸水合酶缺陷型肾细胞癌的组织病理学特点(HE ×40)"

图2

免疫组织化学染色(×40)"

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CN 11-4691/R
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