PAPILLARY RENAL CELL CARCINOMA, BIPHASIC VARIANT.
Biphasic papillary renal cell carcinoma (BPRCC) is a rare and distinct morphological variant of papillary RCC, with a slight male predominance and frequent occurrence as multifocal or bilateral tumors (1, 2). Multiple tumors was also described in a family harboring a MET mutation (3). Association with other neoplasms such as papillary adenomas, clear cell renal cell carcinoma or low grade urothelial carcinoma has been documented (1). Case series show that the great majority of Biphasic papillary RCC exhibit indolent behavior. However, malignant potential and aggressive behavior has been documented in up to 15% of cases including recurrence, metastasis or death (1, 4, 5).
Grossly, the tumor appears homogeneous and solid with pale, tan-white, yellow or slight brown cut surface, occasionally with areas of hemorrhage and necrosis. On microscopic examination, BPRCC shows a distinct dual-cell population with large eosinophilic squamoid cells, often forming alveolar, glomeruloid or micronodular aggregates closely intermixed with a population of smaller basophilic cells with scant amphophilic cytoplasm, resembling those seen in papillary RCC type I. BPRCC often shows diffuse solid growth without discrete papillary formation. Although the larger eosinophilic cells are designated as squamoid owing to their morphologic resemblance to squamous cells, no evidence of squamous differentiation such as intercellular bridges, keratin pearl formation (on light microscopy), or positivity for squamous cell markers (p63 or CK5/6) has been documented. The presence of emperipolesis exclusively within the large squamoid cells is a very distinct and represents one of the hallmarks of this entity (1, 2, 4).
By immunohistochemistry, BPRCC is immunoreactive for PAX-8, CK7, P504S, epithelial membrane antigen (EMA), and vimentin. Cyclin D1 positivity exclusively seen in the larger eosinophilic squamoid cells. CAIX, CD117, GATA3, WT1, CK5/6 and CK20 all show negative staining (2).
The chromosomal profile of BPRCC matches that of papillary RCC, with gains of chromosome 7 and 17 and loss of chromosome Y in males described in most cases (4).
The differential diagnosis of biphasic squamoid papillary RCC primarily involves metanephric adenoma (MA) and mucinous tubular and spindle cell carcinoma (MTSC) of the kidney. MA may also show papillary and solid growth, but lack the biphasic morphology and has different immunohistochemical profile (negative for CK7, P504S, and EMA; and positive for WT1 and CD57), and lacks gains of chromosome 7 and/or 17. MTSC may also show some morphological similarity to biphasic papillary RCC, but usually lack the biphasic morphology and exhibit low-grade spindle cell areas and mucinous stroma. By immunohistochemistry, MTSC shows an overlapping profile with biphasic squamoid papillary RCC, but only rare MTSC cases showed gains of chromosomes 7 and/or 17, whereas high-grade MTSC typically showed multiple chromosomal losses (2).
Contributed by Fawaz Almutairi, MD, Shikha Malhotra, MD and Gabriela Quiroga-Garza, MD