2019-16 / JUNE 3

40 year old male with a 9.5 cm cystic and solid renal mass. All images are from the radical nephrectomy specimen.


1- What is the correct diagnosis?

a. Papillary renal cell carcinoma

b. Dedifferentiated tubulocystic renal cell carcinoma

c. FH deficient renal cell carcinoma

d. SDH deficient renal cell carcinoma

e. Unclassified renal cell carcinoma


2- What is the prognosis of this tumor?

a. Benign

b. Mostly indolent, very rare metastases

c. Locally aggressive, but usually not metastatic

d. Locally aggressive with frequent metastatic disease

1. c
2. d

1. FH deficient Renal Cell Carcinoma
2. Locally aggressive with frequent metastatic disease

Fumarate Hydratase deficient renal cell carcinoma (FH-deficient RCC) is characterized by aggressive behavior and frequent metastatic disease. FH-deficient RCC typically present with advanced stage and involvement of the perinephric adipose tissues, renal sinus, renal vein, as well as metastatic disease in the regional nodes and at distant sites. The morphology comprises variable and often mixed architectural patterns, including papillary, tubulocystic, solid/sarcomatoid, and cystic. The cells show round to oval nuclei with markedly enlarged, viral-like nucleoli.
FH-deficient RCC demonstrate germline and rarely somatic mutation of the FH gene, located at 1q42.3–q43. Patients with renal tumors with confirmed FH mutation can be referred to as ‘FH-deficient RCC’, as well as ‘Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC) associated RCC’, if the patient syndromic setting is known. In fact, FH-deficient RCC is closely related to the renal cancers found in the HLRCC syndrome, an autosomal dominant hereditary disease characterized by multiple uterine and cutaneous leiomyomas and RCCs. ‘FH-deficient RCC’ is however a term that refers to RCCs in patients with: compatible morphology; negative immunostaining for FH, and/or positive staining for S-(2-succino)-cysteine (2SC); uncertain clinical and family history of skin and uterine leiomyomas and RCC; and unknown genetic status at the time of the case sign-out.

Fumarate Hydratase–deficient Renal Cell Carcinoma Is Strongly Correlated with Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome. Trpkov K, Hes O, Agaimy A, et al.
Am J Surg Pathol. 2016;40(7): 865–875.

Tubulocystic carcinoma of the kidney with dedifferentiation: A frequent morphologic pattern of Fumarate Hydratase-deficient renal cell carcinoma. Smith SC, Trpkov K, Chen Y-B, et al.
Am J Surg Pathol. 2016;40(11): 1457-1472.

Kiril Trpkov, Yuan Gao
University of Calgary


FH, Fumarate Hydratase, FH-deficient RCC, Hereditary Leiomyomatosis Renal Cell Carcinoma; HLRCC