CASE OF THE WEEK
Editor: Mahmut Akgul (akgulm@amc.edu)
2022-14/April 4
Contributors: Sai Tun Hein Aung; Soe Htet Arker; Mahmut Akgul
A male in his 40s with the incidental finding of a right renal mass on CT angiography of the abdomen during cardiac surgery work up. He underwent right open partial nephrectomy which showed a 2.2 cm, well-circumscribed, solid, tan-white to yellow tumor.
Quiz
1. What would be the most appropriate diagnosis?
a) Clear cell renal cell carcinoma
b) Clear cell papillary renal tumor (formerly known as clear cell papillary renal cell carcinoma)
c) Papillary renal cell carcinoma, clear cell variant
d) Renal cell carcinoma with fibromatous stroma
e) ELOC/TCEB1 mutated renal cell carcinoma
2. What should be the next step for definitive diagnosis?
a) No additional studies needed for definitive diagnosis.
b) Additional immunohistochemical studies are needed.
c) Special stains are required.
d) Sequencing is needed for definitive diagnosis
1. d; 2.d
1. renal cell carcinoma with fibromatous stroma; 2. sequencing is needed for definitive diagnosis.
Microscopic examination showed the tumor cells with voluminous clear cytoplasm grow in small nested and tubular patterns. They are embedded in a cellular stroma resembling smooth muscle. No evidence of mitotic activity or tumor necrosis are found. Immunohistochemical assays show that the neoplastic cells are diffusely and strongly positive for CA9, KRT7, CD10, CA9, and racemase. These findings are consistent with the diagnosis of renal cell carcinoma with fibromatous stroma (RCCFS)
RCCFS is a rare neoplasm which has been included as an “emerging/provisional” entity of “RCC with (angio) leiomyomatous stroma” in the 2016 World Health Organization (WHO) classification of tumours. Patients usually present in the age range of 31 to 79 years. There is no gender predilection. Small nests or nodules of elongated tubules lined by tumor cells having abundant clear cytoplasm are characteristic. Diffuse co-expression of CA9 and KRT7 are seen in RCCFS with frequent CD10 and racemase expression. Recent studies that have utilized targeted next-generation sequencing have found that the majority of sporadically occurring RCCFS exhibit recurrent mutations involving TSC1, TSC2 or mTOR. The importance of this morphology and immunophenotype is that there are multiple entities including clear cell RCC and TCEB1/ELOC mutated RCC with overlapping features. These findings may fail to identify the exact RCC subtype, but RCCFS, clear cell RCC, and ELOC/TCEB1 mutated RCC have distinct molecular features, hereditary associations, and behavior as demonstrated in the table (last image).
In short, clear cell RCC has aggressive features with significant metastatic potential as opposed to indolent clinical courses of RCCFS and ELOC mutated RCC. Therefore, it is advised to do further molecular testing for possible VHL gene abnormalities, as well as ELOC and TSC/MTOR in order to distinguish between these malignancies.
Shah RB. Renal Cell Carcinoma With Fibromyomatous Stroma-The Whole Story. Adv Anat Pathol. 2022 Mar 7. doi: 10.1097/PAP.0000000000000337. Epub ahead of print. PMID: 35249990.
Cimadamore A, Cheng L, Scarpelli M, Massari F, Mollica V, Santoni M, Lopez-Beltran A, Montironi R, Moch H. Towards a new WHO classification of renal cell tumor: what the clinician needs to know-a narrative review. Transl Androl Urol. 2021 Mar;10(3):1506-1520. doi: 10.21037/tau-20-1150. PMID: 33850785; PMCID: PMC8039604.
Yeh YA, Constantinescu M, Chaudoir C, Tanner A, Serkin F, Yu X, Fazili T, Lurie AA. Renal cell carcinoma with leiomyomatous stroma: a review of an emerging entity distinct from clear cell conventional renal cell carcinoma. Am J Clin Exp Urol. 2019 Oct 15;7(5):321-326. PMID: 31763363; PMCID: PMC6872474.
Sai Tun Hein Aung; Soe Htet Arker; Mahmut Akgul
Department of Pathology and Laboratory Medicine
Albany Medical Center
Albany, NY
Kidney
renal cell carcinoma with fibromatous stroma, clear cell RCC, ELOC/TCEB1 mutated RCC