A distinctive, low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase-deficient renal cell carcinoma.
OBJECTIVE
Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a high-grade, aggressive tubulopapillary carcinoma, arising predominantly in the setting of the hereditary leiomyomatosis-RCC syndrome of familial uterocutaneous leiomyomatosis and deficiency of FH. In contrast, succinate dehydrogenase (SDH)-deficient RCC is a lower-grade oncocytic carcinoma with cytoplasmic flocculence/vacuolation and inclusions, arising mostly in individuals harbouring germline mutations of subunit B of the SDH complex (SDHB). Herein we aim to report the clinicopathologic features of a novel form of FH-deficient RCC showing a low grade oncocytic morphology, reminiscent of SDH-deficient RCC.


RESULTS
These distinctive, low-grade oncocytic neoplasms, with solid, nested and focally tubular architecture (2-90 mm), arose in four males (aged 11-41 years). Uniform cytology of polygonal cells, with flocculent, vacuolated eosinophilic cytoplasm with scattered inclusions, fine chromatin, and inconspicuous nucleoli, was apparent. Despite these features suggestive of SDH-deficient RCC, each tumour was confirmed as an FH-deficient carcinoma with retained SDHB expression. One case showed a synchronous, anatomically separate, typical high-grade FH-deficient RCC; one other showed such a tumour at nephrectomy 4 years later. No progression has been noted at 3 and 7 years in the cases with only the SDH-like lesions; the two cases with separate, typical FH-deficient RCCs progressed.


CONCLUSIONS
In summary, we characterize a novel oncocytic type of FH-deficient RCC with a striking resemblance to SDH-deficient RCC, posing a diagnostic challenge and raising concerns about sampling and multifocality for syndrome-associated cases under surveillance protocols.
Departments of Pathology and Urology, VCU School of Medicine, Richmond, VA, USA.
Steven C
http://orcid.org/0000-0003-0982-4607
SC
Smith
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Deepika
D
Sirohi
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Chisato
C
Ohe
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jonathan B
JB
McHugh
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Jason L
JL
Hornick
BT Savani Kidney Hospital, Rajkot, India.
Jigna
J
Kalariya
BT Savani Kidney Hospital, Rajkot, India.
Sushil
S
Karia
St Georges Hospital, London, UK.
Katie
K
Snape
St Georges Hospital, London, UK.
Shirley V
SV
Hodgson
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Andi K
AK
Cani
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Daniel
D
Hovelson
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Daniel J
DJ
Luthringer
Department of Pathology and Public Health, University of Verona, Verona, Italy.|Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy.
Guido
G
Martignoni
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ying-Bei
YB
Chen
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Michigan Center for Translational Pathology, Department of Urology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Scott A
SA
Tomlins
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Michigan Center for Translational Pathology, Department of Urology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Rohit
R
Mehra
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.|Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Mahul B
MB
Amin
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000473:pathology*; D002648:Child; D005649:Fumarate Hydratase / Q000172:deficiency*; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D013385:Succinate Dehydrogenase
D013385:Succinate Dehydrogenase; D005649:Fumarate Hydratase
fumarate hydratase-deficient renal cell carcinoma; hereditary leiomyomatosis-renal cell carcinoma syndrome; oncocytic carcinoma; renal cell carcinoma; succinate dehydrogenase-deficient renal cell carcinoma