CASE OF THE WEEK
2020-26 / June 29
(Contributors: Xiaotun Zhang and Maria Tretiakova)
A 30 year-old male presented with long history of back pain and pain with ejaculation, which led to imaging studies that revealed left renal (3.5cm) and large retroperitoneal mass (6.5cm). He has a history of left undescended testicle as a child. Grossly, the kidney tumor exhibits solid and cystic cut surface on partial nephrectomy. Immunohistochemical stains show positive PAX8, GATA3 and AMACR expression in tumor cells, and negative immunoreactivity for CK7.
Quiz
1. What is the appropriate next step for definitive diagnosis of this case?
a. Immunohistochemical stain of SALL4, PLAP, OCT3/4 and AFP
b. Immunohistochemical and molecular testing for Fumarate Hydratase deficiency
c. Immunohistochemical stains of TFE3, TFEB and SDHB
d. FISH study for ETV6-NTRK3 gene fusion
1. b
1. Immunohistochemical and molecular testing for Fumarate Hydratase deficiency (Fumarate Hydratase-deficient renal cell carcinoma)
Grossly, the renal mass demonstrates solid and cystic appearance. Histologic sections reveal mixed architectural features including papillary, tubulocystic, sieve-like and micropapillary patterns. The tumor cells exhibit abundant granular and eosinophilic cytoplasm with occasional vacuoles, centrally located round nuclei and large eosinophilic nucleoli. Focally, viral inclusion-like macronucleoli with perinucleolar clearing are present. Mitotic figures are frequently seen. Another feature of this tumor is fibrovascular cores with hyalinization. Immunohistochemical stains are negative for CK7 and positive for PAX8, AMACR and GATA3. These morphologic and immunophenotypic features are highly suggestive of the Fumarate Hydratase-deficient renal cell carcinoma. Although FH and 2SC immunostains can help with establish diagnosis, genetic testing is required for confirmation of definitive diagnosis.
Although this patient has history of undescended testicle, the positivity of PAX8 and tumor morphology helps to rule out a germ cell tumor. ETV6-NTRK3 gene fusion is reported in association with cellular congenital mesoblastic nephroma (CMN), but not FH-deficient RCC. TFE3 translocation RCC usually exhibits a high-grade renal cell carcinoma with voluminous clear cytoplasm and forming papillary architecture. Psammoma bodies are frequently seen in this entity. SDH-deficient RCC, on the other hand, is classified as WHO/ISUP low-grade RCC, with solid growth pattern and characteristic eosinophilic and vacuolated cytoplasm.
Molecular testing was performed confirming morphologic impression of FH-deficient RCC.
1. Lau HD, Chan E, Fan AC et al. A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-deficient Renal Cell Carcinoma in 32 Patients. Am J Surg Pathol 2020;44:98-110 [PMID: 31524643].
2. Chen YB, Brannon AR, Toubaji A et al. Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. Am J Surg Pathol. 2014;38:627-37 [PMID:24441663]
Xiaotun Zhang, MD
Maria Tretiakova, MD, PhD
University of Washington
Department of Pathology
Seattle, WA
Kidney
Kidney, Fumarate Hydratase-deficient renal cell carcinoma