Clinicopathological analysis of fumarate hydratase-deficient renal cell carcinoma and literature review

Yali YANG; Youli WU; Yang LAN; Xiaochu YAN; Guangjie DUAN

doi:10.16016/j.1000-5404.202103180

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Clinicopathological analysis of fumarate hydratase-deficient renal cell carcinoma and literature review

Basic Medicine | 更新时间：2026-01-09

- Clinicopathological analysis of fumarate hydratase-deficient renal cell carcinoma and literature review
- Journal of Third Military Medical University Vol. 43, Issue 18, Pages: 1743-1750(2021)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院病理研究所
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202103180
  CLC： R730.21;R737.11
- Received：22 March 2021，
  
  Revised：2021-06-16，
  
  Published：30 September 2021
- 稿件说明：
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Yali YANG, Youli WU, Yang LAN, et al. Clinicopathological analysis of fumarate hydratase-deficient renal cell carcinoma and literature review[J]. Journal of Third Military Medical University, 2021, 43(18): 1743-1750.
DOI：

Yali YANG, Youli WU, Yang LAN, et al. Clinicopathological analysis of fumarate hydratase-deficient renal cell carcinoma and literature review[J]. Journal of Third Military Medical University, 2021, 43(18): 1743-1750. DOI： 10.16016/j.1000-5404.202103180.

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-d RCC)的临床病理学特征，加强对该罕见肿瘤的认识。

方法

收集2010－2020年陆军军医大学第一附属医院诊断的2例FH-d RCC患者资料，包括组织病理形态、免疫组织化学染色、荧光原位杂交(FISH)和下一代测序(NGS)，并复习相关文献。

结果

2例患者均为男性，年龄分别为34和35岁。例1为双肾肿瘤伴肾门淋巴结转移，瘤细胞核级高，呈乳头状、腺管状排列。例2肿瘤位于肾脏上极并累及肾上腺，大部分区域瘤细胞分化好，呈大小不等的管状、囊状排列，周围伴局灶低分化区域。2例部分瘤细胞核内均可见到嗜酸性病毒包涵体样的大核仁及核仁周空晕。免疫组织化学染色显示两例瘤细胞除表达上皮和肾源性标记外，均呈现CK7阴性/CA9灶性阳性；FH的表达例1缺失、例2无缺失，但2例NGS均检测到FH基因的体细胞突变。FISH检测未发现TFE3基因重排。

结论

FH-d RCC是一种具有FH基因突变的高级别肾细胞癌，侵袭性强、预后差。肿瘤细胞呈乳头状排列伴有明显的嗜酸性病毒包涵体样大核仁及核仁周空晕是其典型病理形态特征。

Abstract

Objective

To investigate the clinicopathological characteristics of fumarate hydratase-deficient renal cell carcinoma (FH-d RCC) so as to further understand this rare tumor.

Methods

Two cases with FH-d RCC diagnosed in our hospital from 2010 to 2020 were studied by histopathological observation

immunohistochemical staining (IHC)

fluorescence

in situ

hybridization (FISH) and next generation sequencing (NGS)

respectively. A literature review was also performed.

Results

Both patients were males and aged 34 and 35 years respectively. In case 1

the tumor affected bilateral kidneys with renal hilar lymph node metastasis

whose tumor cells displayed papillary and glandular patterns with high-grade morphology. In case 2

the tumor was located in the upper pole of the kidney and afflicted the adrenal gland; the tumor cells in most areas were well differentiated

presenting tubular and cystic arrangement in varying sizes

and were surrounded by focal areas of low differentiation. Eosinophilic viral inclusion-like macronucleoli and perinucleolar halos are observed in some tumor nuclei of both cases. Besides positive staining for epithelial and renal markers by IHC

both tumors showed negative for CK7 and focal positive for CA9 (CK7

/CA9

). FH expression was absent in case 1 while retained in case 2

but somatic FH gene mutations were detected in both cases by NGS. Moreover

no rearrangement of TFE3 gene was found by FISH.

Conclusion

FH-d RCC is a rare high-grade renal cell carcinoma with FH gene mutation

often showing highly aggressive behavior and poor prognosis

whose typical histopathologic features include the papillary arrangement of tumor cells

eosinophilic viral inclusion-like macronucleoli and perinucleolar halos.

关键词

Keywords

references

MOCH H, CUBILLAA L, HUMPHREY P A, et al . The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours[J ] . Eur Urol, 2016, 70(1): 93-105. DOI: 10.1016/j.eururo.2016.02.029.

TRPKOV K, HES O, AGAIMY A, et al . Fumarate hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome[J ] . Am J Surg Pathol, 2016, 40(7): 865-875. DOI: 10.1097/PAS.0000000000000617.

SMITHS C, TRPKOV K, CHEN Y B, et al . Tubulocystic carcinoma of the kidney with poorly differentiated foci: a frequent morphologic pattern of fumarate hydratase-deficient renal cell carcinoma[J ] . Am J Surg Pathol, 2016, 40(11): 1457-1472. DOI: 10.1097/PAS.0000000000000719.

SMITHS C, SIROHI D, OHE C, et al . A distinctiv e, low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase-deficient renal cell carcinoma[J ] . Histopathology, 2017, 71(1): 42-52. DOI: 10.1111/his.13183.

OHE C, SMITHS C, SIROHI D, et al . Reappraisal of morphologic differences between renal medullary carcinoma, collecting duct carcinoma, and fumarate hydratase-deficient renal cell carcinoma[J ] . Am J Surg Pathol, 2018, 42(3): 279-292. DOI: 10.1097/pas.0000000000001000.

张伟, 褚菁, 邹玉玮, 等. 延胡索酸水合酶缺陷型肾细胞癌的临床病理学特征[J]. 中华病理学杂志, 2019, 48(2): 120-126. DOI: 10.3760/cma.j.issn.0529-5807.2019.02.009.

ZHANG W, CHU J, ZOU Y W, et al . Clinicopathological characteristics of fumarate hydratase-deficient renal cell carcinoma[J ] . Chin J Pathol, 2019, 48(2): 120-126. DOI: 10.3760/cma.j.issn.0529-5807.2019.02.009.

KURODA N, TSUTSUI M, IGUCHI M, et al . Fumarate hydratase-deficient renal cell carcinoma: a clinicopathological study of seven cases including hereditary and sporadic forms[J ] . Ann Diagn Pathol, 2020, 49: 151599. DOI: 10.1016/j.anndiagpath.2020.151599.

LAUH D, CHAN E, FAN A C, et al . A clinicopathologic and molecular analysis of fumarate hydratase-deficient renal cell car cinoma in 32 patients[J ] . Am J Surg Pathol, 2020, 44(1): 98-110. DOI: 10.1097/PAS.0000000000001372.

GLEESON J P, NIKOLOVSKI I, DINATALE R G, et al . Comprehensive molecular characterization and response to therapy in FH-deficient renal cell carcinoma[J ] . Clin Cancer Res, 2021, 27(10): 2910-2919. clincanres. 4367.2020. DOI: 10.1158/1078-0432.CCR-20-4367.

TRPKOV K, HES O. New and emerging renal entities: a perspective post-WHO 2016 classification[J]. Histopathology, 2019, 74(1): 31-59. DOI: 10.1111/his.13727.

WU Y L, LANG L, MA Q, et al . Perivascular epithelioid cell tumor of urinary bladder[J ] . Am J Clin Pathol, 2020. [published online ahead of print ] . DOI: 10.1093/ajcp/aqaa204.

GUNNALA V, PEREIRA N, IRANI M, et al . Novelfumarate hydratase mutation in siblings with early onset uterine leiomyomas and hereditary leiomyomatosis and renal cell cancer syndrome[J ] . Int J Gynecol Pathol, 2018, 37(3): 256-261. DOI: 10.1097/PGP.0000000000000423.

KOSKIT A, LEHTONEN H J, JEE K J, et al . Array comparative genomic hybridization identifies a distinct DNA copy number profile in renal cell cancer associated with hereditary leiomyomatosis and renal cell cancer[J ] . Genes Chromosomes Cancer, 2009, 48(7): 544-551. DOI: 10.1002/gcc.20663.

BANIAK N, TSAI H, HIRSCHM S. The differential diagnosis of medullary-based renal masses[J]. Arch Pathol Lab Med, 2021. [published online ahead of print]. DOI: 10.5858/arpa.2020-0464-ra.

PAN X Y, ZHANG M N, YAO J, et al . Fumaratehydratase-deficient renal cell carcinoma: a clinicopathological and molecular study of 13 cases[J ] . J Clin Pathol, 2019, 72(11): 748-754. DOI: 10.1136/jclinpath-2019-205924.

WYVEKENS N, VALTCHEVA N, MISCHO A, et al . Novel morphological and genetic features of fumarate hydratase deficient renal cell carcinoma in HLRCC syndrome patients with a tailored therapeutic approach[J ] . Genes Chromosomes Cancer, 2020, 59(11): 611-619. DOI: 10.1002/gcc.22878.

GUPTA S, SWANSONA A, CHEN Y B, et al . Incidence of succinate dehydrogenase and fumarate hydratase-deficient renal cell carcinoma based on immunohistochemical screening with SDHA/SDHB and FH/2SC[J ] . Hum Pathol, 2019, 91: 114-122. DOI: 10.1016/j.humpath.2019.07.004.

BANIAK N, FLOOD T A, BUCHANAN M, et al . Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes[J ] . Histopathology, 2020, 77(4): 659-666. DOI: 10.1111/his.14204.

PARK I, SHIMY S, GO H, et al . Long-term response of metastatic hereditary leiomyomatosis and renal cell carcinoma syndrome associated renal cell carcinoma to bevacizumab plus erlotinib after temsirolimus and axitinib treatment failures[J ] . BMC Urol, 2019, 19(1): 51. DOI: 10.1186/s12894-019-0484-2.

CHOI Y, KEAM B, KIM M, et al . Bevacizumab plus erlotinib combination therapy for advanced hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma: a multicenter retrospective analysis in Korean patients[J ] . Cancer Res Treat, 2019, 51(4): 1549-1556. DOI: 10.4143/crt.2019.086.

ALAGHEHBANDAN R, STEHLIK J, TRPKOV K, et al . Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) expression in fumarate hydratase-deficient renal cell carcinoma[J ] . Ann Diagn Pathol, 2017, 29: 17-22. DOI: 10.1016/j.anndiagpath.2017.04.007.

SUN G X, ZHANG X M, LIANG J Y, et al . Integrated molecular characterization of fumarate hydratase-deficient renal cell carcinoma[J ] . Clin Cancer Res, 2021, 27(6): 1734-1743. DOI: 10.1158/1078-0432.CCR-20-3788.

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