Renal medullary carcinoma: molecular, immunohistochemistry, and morphologic correlation

Abstract

Renal medullary carcinoma, a highly aggressive tumor mainly occurring in patients with sickle cell hemoglobinopathy, is characterized by advanced stage at the time of presentation and poor response to treatment. Currently, the pathogenesis of this tumor is not well understood. In this study, the clinicopathologic features and molecular changes of 15 renal medullary carcinoma cases were evaluated. These cases demonstrated male predominance (M:F=2:1) with a median age of 26 years. The tumors occurred predominantly in the right kidney with an average size of 5.9 cm. Immunohistochemistry analysis showed that the neoplastic cells were positive for CEA (7/8), AE1/3 (8/8), CAM5.2 (7/7), CK7 (5/5), CK20 (4/6), and vimentin (6/6). Absence of SMARCB1 protein expression in tumor cells was demonstrated in all of the 7 cases analyzed. By polymerase chain reaction-based microsatellite analysis, loss of heterozygosity of SMARCB1 was identified in 9 of 10 cases. These data suggest that inactivation of SMARCB1 may play a role in the pathogenesis of renal medullary carcinoma.

FIGURE 1.

Histopathologic features of renal medullary carcinoma. Renal medullary carcinoma displays various morphologic features (A). The tumor cells often form a reticular pattern or sheets with large, prominent nucleoli, some displaying rhabdoid features (D). Desmoplastic stroma (B) and mucin in the background are not uncommon (D). Neutrophilic and lymphocytic infiltrates are also often admixed with tumor cells (C).

FIGURE 2.

Immunohistochemistry of CAM5.2 and CEA of renal medullary carcinoma (case #4). CAM5.2 shows diffuse and strong positivity in tumor cells (A);CEA polyclonal antibody staining shows cytoplasmic positivity in tumor cells (B).

FIGURE 3.

LOH analysis of renal medullary carcinoma. A representative example of PCR-based microsatellite LOH analysis from case #2 using primer set D22S257 is shown here. The upper panel shows the 2 alleles from normal renal tissue, and the lower panel shows the 2 alleles from tumor cells. LOH is calculated using the formulation as indicated in the Materials and methods section. The ratio of allelic peaks between tumor and normal tissue indicates LOH in this region.

FIGURE 4.

Immunohistochemistry of SMARCB1 (INI1) in renal medullary carcinoma. Immunohistochemical staining of SMARCB1 (INI1) in case #4 (A, B) and case #7 (C, D) are shown here. Tumor cells are negative for SMARCB1 (INI1) nuclear staining. In contrast, lymphocytes in the background show positive nuclear staining of SMARCB1 (INI1).