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CC BY 4.0 · Indian J Med Paediatr Oncol
DOI: 10.1055/s-0043-1775804
Original Article

Fumarate Hydratase-Deficient Renal Cell Carcinoma—A Clinicopathological Study of a Series of 11 Cases

Aswathy A. Menon 
1   Department of Pathology, Neuberg Anand Reference Laboratory, Bengaluru, Karnataka, India
,
Swapnil Rane 
2   Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Uma Sakhadeo
2   Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Gagan Prakash 
3   Department of Urology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Amit Joshi
4   Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Mahendra Pal
3   Department of Urology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Amandeep Arora
3   Department of Urology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Nilesh Sable
5   Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Aparna Katdare
5   Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Palak Popat
5   Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Priyamvada Maitre
6   Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Archi Agarwal
7   Department of Nuclear Medicine, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Vedang Murthy
6   Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Sangeetha B. Desai 
2   Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
,
Santosh Menon 
2   Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
› Author Affiliations Financial Support or Sponsorship None.
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Abstract

Introduction Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare, molecularly defined renal tumor with aggressive behavior. The diagnosis of these tumors is challenging because of varied morphology and limited access to molecular testing and immunohistochemistry (IHC) for FH and 2-succinocysteine. We aim to elucidate the histomorphology, clinical presentation, and follow-up of this tumor in this first series of cases of FH-deficient RCCs from India.

Objectives This article aims to understand and elucidate the clinical presentation, pathologic findings, treatment options, and outcomes of FH-deficient RCC.

Materials and Methods Diagnosed cases of FH-deficient RCC between January 2021 and January 2023 including clinical details were retrieved from the electronic medical record database. Histopathological and immunohistochemical slides were reviewed.

Results Out of 11 cases of FH-deficient RCC, 36% had been referred with a diagnosis of type 2 papillary RCC. One patient presented with metastatic disease. All had mixed histologic patterns with the predominant pattern being papillary and showed FH loss on IHC. The classically described inclusion like nucleoli was present only focally in most cases. A subset of tumors had low-grade solid-nested morphology and these patients presented at an earlier stage (T2a). Two patients on multikinase inhibitors are alive with disease at 14 months' follow-up.

Conclusion FH-deficient RCCs can have varied histologic patterns within the same tumor and show loss of FH expression by IHC. A subset has low grade morphology and tends to have a more indolent course. It is important to have a high index of suspicion for this diagnosis due to its varied histological appearance and aggressive behavior.

Keywords

fumarate hydratase-deficient renal cell carcinoma - fumarate hydratase - RCC - FH IHC - HLRCC

Patient Consent

Waiver of consent was obtained since this was a retrospective study with less than minimal risk and participants are de-identified or cannot be contacted.

Ethics clearance letter stating the same has been provided during manuscript submission and also the ethics project approval number is provided within the manuscript.


Department(s) and institution(s) where the work was carried out: Department of Pathology, Tata Memorial Hospital, Mumbai.




Publication History

Article published online:
07 May 2024

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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