COW-2020-13

CASE OF THE WEEK

2020-13 / MARCH 31
(CONTRIBUTOR: DANIEL H. RUSSELL)

A 29-year-old man presented with symptoms of lithiasis and was found to have a heavily calcified 1.9 cm renal mass, interpreted radiographically as a benign process. IHC was performed for CK7 (diffuse positive), and CA-IX (diffuse positive, picture shown) and CD10 (negative).

Quiz

1. What is the correct diagnosis?

a. Multilocular cystic renal neoplasm of low malignant potential

b. Clear cell papillary renal cell carcinoma

c. Clear cell renal cell carcinoma with regression

d. Renal cell carcinoma with leiomyomatous stroma

e. Unclassified renal cell carcinoma

1. Clear cell renal cell carcinoma with regression

This case consists of a heavily scarred and calcified lesion with renal cysts lined by clear to eosinophilic cells. Within the scar, rare foci of nests of clear cells with inconspicuous nucleoli at 400x (WHO/ISUP nucleolar grade 1) were identified. Immunohistochemical stains (IHC) were strongly and diffusely positive for CK7, showed strong diffuse circumferential positivity for CA-IX and were completely negative for CD10.

Some tumors previously classified as clear cell renal cell carcinoma (ccRCC) or renal cell carcinoma NOS, have recently been re-classified as clear cell papillary renal cell carcinoma (ccPRCC), multilocular cystic renal cell neoplasm of low malignant potential (LMP), and renal cell carcinoma with leiomyomatous stroma (RCC-LM), to name a few. Characteristic IHC expression profiles with CD10, CK7, and CA-IX, among others, have aided in accurate classification.

The current case does not fit neatly into World Health Organization (WHO) nomenclature, and challenges the relative emphasis placed on morphology and IHC in interpretation. Co-expression of CK7 and CA-IX with negative CD10 typically argues against ccRCC, while full circumferential CA-IX, as opposed to “cup-shaped” staining, and lack of reverse polarity nuclei casts doubt on the diagnosis of ccPRCC. Stroma of RCC-LM was not identified, while LMP is excluded by the presence of tumor nests.

The presence of nests of clear cells within scar support the diagnosis of ccRCC with regression. Loss of CD10 and expression of CK7 has been described ccRCC with regression. Although morphologically some have considered these lesions along a spectrum between ccRCC and ccPRCC, until more definitive characterization exists, most authorities recommend strict criteria for ccPRCC and LMP.

Dhakal HP, McKenney JK, Khor LY, Reynolds JP, Magi-Galluzi C, Pryzbycin CG. Renal neoplasms with overlapping features of clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. A clinicopathologic study of 37 cases from a single institution. Am J Surg Pathol 2016; 40:141-154.

Williamson SR, Gupta NS, Eble JN, Rogers CG, Michalowski S, Zhang S, et al. Clear cell renal cell carcinoma with borderline features of clear cell papillary renal cell carcinoma. Combined morphologic, immunohistochemical, and cytogenetic analysis. Am J Surg Pathol 2015; 39:1502-1510.

Williamson SR, Halat S, Eble JN, Grignon DJ, Lopez-Beltran A, Montironi R, et al. Multilocular cystic renal cell carcinoma: similarities and differences in immunoprofile compared with clear cell renal cell carcinoma. Am J Surg Pathol 2012; 36:1425-1433.

Daniel H. Russell, M.D.
Tripler Army Medical Center
russdanny22@gmail.com

Kidney

kidney; clear cell RCC; regression; low-malignant potential