Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases

Abstract

Aims To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC. Methods and results We identified 28 tumours from multiple institutions. They typically showed two cell populations—larger cells with eosinophilic cytoplasm and higher‐grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5–100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39–86 years). The median tumour size was 20 mm (range 9–65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low‐grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt–Hogg–Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α‐methylacyl‐CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA‐3, WT1, CK5/6, and CK20; CD10 and 34βE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow‐up was available for 23 patients (median 24 months, range 1–244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes). Conclusions Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal.

New and emerging renal entities: a perspective post‐WHO 2016 classification

“…Marked cyclin D1 positivity has been noted only in the larger eosinophilic cells. CA9, CD117, GATA3, WT1, CK5/6 and CK20 all showed negative staining …”

“…Additionally, a substantial proportion of biphasic squamoid papillary RCCs show at least focal papillary morphology, as seen in papillary RCC, type 1. To date, ~100 cases of biphasic squamoid papillary RCC have been reported in the English‐language literature, including two examples arising in renal allografts …”

“…Multiple tumours occurring in a mother and son of a family harbouring a MET mutation were also recently reported . Biphasic squamoid papillary RCC has malignant potential, and evidence of aggressive behaviour, including metastasis, recurrence, or death due to the disease, has been documented in up to 15% of patients …”

“…Many biphasic squamoid papillary RCCs also show diffuse solid growth, without recognisable or very rare papillary formations. Although the larger eosinophilic cells were designated ‘squamoid’ (squamous cell‐like), owing to their morphological resemblance to squamous cells, no definitive evidence of squamous differentiation was found on light microscopy, such as intercellular bridges, keratin pearl formation, and p63 or CK5/6 positivity . The presence of emperipolesis exclusively within the large squamoid cells is a very distinct and peculiar phenomenon observed in all documented cases, and represents one of the hallmarks of this entity.…”

Biphasic squamoid alveolar renal carcinoma with positive CD57 expression: A clinicopathologic study of three cases

“…In some instances, there are visible foam‐like histiocytic deposits and grit between acini . The large squamoid cells often show evidence of emperipolesis, with neutrophils, cell fragments, and debris being visible within these larger cells …”