Papillary renal cell carcinoma revisited: a comprehensive histomorphologic study with outcome correlations

Abstract

Papillary renal cell carcinoma (P-RCC) is the second most common type of malignant renal epithelial tumor and can be subclassified into type 1, which demonstrates simple cuboidal low-grade epithelium and type 2, which demonstrates pseudostratified high-grade epithelium with abundant eosinophilic cytoplasm. Despite this clinically useful subclassification, P-RCCs exhibit considerable histomorphologic diversity, with many cases having features differing from classically described type 1 and type 2 tumors. To our knowledge, there has been no recent study that has methodically evaluated the histomorphologic features of a series of P-RCCs. To address this, we evaluated a cohort of P-RCCs diagnosed between 1997 and 2004 with long-term clinical follow-up data (n = 56). Histomorphologic features previously described in the spectrum of type 1 and type 2 P-RCCs were recorded for each tumor, including nuclear grade, complete tumor capsule, and cytoplasmic eosinophilia as well as several other features. The current TNM staging (American Joint Committee on Cancer, seventh edition) was assigned to all cases. Histomorphologic features were diverse, demonstrating classic type 1 P-RCC and classic type 2 P-RCC morphology and several tumors with nonclassic features. Four patients in this cohort had distant metastasis. The primary tumor was equally divided between type 1 (2 cases) and type 2 (2 cases) morphology in the cases with metastasis. All P-RCC cases with metastases demonstrated presence of high nuclear grade and high tumor stage in the primary tumor. Cluster analysis using staging parameters and histomorphologic features divided tumors into 2 primary clusters. All primary tumors associated with metastasis were in the same cluster.

Keywords: Nuclear grade; Papillary renal cell carcinoma; Tumor stage.

Figure 1:

Microphotographs - larger photographs 200× magnification, smaller inset photographs 400× magnification of the same tumor. A – Classic type 1 papillary renal cell carcinoma with low grade (Fuhrman grade 2) nuclei, amphophilic cytoplasm, papillary architecture, and foamy macrophages within papillae. B – Type 1 papillary renal cell carcinoma with low grade (Fuhrman grade 2) nuclei and abundant eosinophilic cytoplasm. C – Type 1 papillary renal cell carcinoma with Fuhrman grade 2 nuclei and optically clear cytoplasm. D – Type 1 papillary renal cell carcinoma with Fuhrman grade 2 nuclei and glomerulations. E – Type 1 papillary renal cell carcinoma with higher grade (Fuhrman grade 3) nuclei. F – Type 1 papillary renal cell carcinoma with higher grade (Fuhrman grade 3) nuclei and abundant eosinophilic cytoplasm. G – Classic type 2 papillary renal cell carcinoma with higher grade (Fuhrman grade 3) nuclei, true pseudostratification, and abundant eosinophilic cytoplasm. H – Representative image from a Type 2 papillary renal cell carcinoma which demonstrated papillary areas with cells with eosinophilic cytoplasm (not shown in H) intermixed with other areas where the cytoplasm was more optically clear (which are demonstrated here).

Figure 2:

Heatmap including histomorphological features of papillary renal cell carcinomas and pathologic staging variables. For binary variables, red indicates the feature was present, and blue indicates the feature was absent. For percentage variables, red indicates 100%, blue indicates 0%, and varying shades of blue, red, and purple indicate percentage per the color key. For ordinal variables, red indicates the highest category, and blue indicates the lowest category, with varying color shades indicating higher category per the color key. For numeric variables, red indicates the highest value, blue indicates the lowest value, and varying shades indicate higher values per the color key. For gender, red indicates female and blue male. White indicates data for the variable was not available.