Biphasic squamoid alveolar papillary renal cell carcinoma: A unique papillary renal cell carcinoma with distinctive morphology, immunophenotype and molecular genetic features

Biphasic squamoid alveolar papillary renal cell carcinoma (BSARCC) is a recently described renal tumor, considered as a unique rare morphological pattern of PRCC in the 2022 WHO classification. We aimed to further explore the clinicopathological, immunophenotypic, and molecular genetic characteristics of BSARCC in a Chinese cohort. The clinicopathological data of 8 patients with BSARCC were collected for morphology observation and immunohistochemical staining. QRT-PCR was performed to detect BRAF gene mutation. The abnormalities of chromosomes 7, 17 and Y, and CCND1 gene were investigated by fluorescence in situ hybridization (FISH). Among the 8 cases, 5 were males and 3 were females. 6 cases were revealed by physical examination incidentally, and 2 cases were presented with low back pain and hematuria. Microscopically, the tumors were mainly composed of small cells with different proportions of large cells. The small cells were arranged in acinar, compact and long narrow tubular, solid sheet or papillary structures. Single or clustered large cells were arranged in glomerular structures in the acinar cavity formed by small cells. Among the 8 cases, 2 cases had a small amount of typical type I papillary renal cell carcinoma without large cells at the edge of the tumor. And 5 cases presented the swallowing phenomenon of lymphocytes or neutrophils in the cytoplasm of a few large cells. Immunohistochemical staining showed both large and small cells were diffusely and strongly positive for CK7, P504s, EMA, and vimentin. MET was expressed in most tumors (6/8), and large cells (70–90%) exhibited a prominent higher positive rate than small cells (20–90%). CD57 was positive in both large and small cells in 5 cases. Notably, CyclinD1 was exclusively expressed in large cells, while RCC marker was mainly expressed in small cells. Large cells showed a higher ki67 index than small cells. BRAF V600E mutation was negative in all cases. FISH showed 4 cases had chromosome 7 trisomy, 2 cases had chromosome 17 trisomy, and 4 of 5 male patients had Y chromosome deletion. CCND1 gene amplification or rearrangement was not revealed in any case. Follow-up data were available in 8 cases ranging from 3 to 66 months, and there was no recurrence or metastasis of the tumor. BSARCC is a rare unique morphological pattern of papillary renal cell carcinoma, featured by the presence of two cell populations of different morphology and immunophenotype. Distinctive CyclinD1 and RCC immunostainings are essential in diagnosing this type of renal tumor. Large and small cells may be tumor cells in different stages of proliferation and differentiation, and large cells immunoreactive to CyclinD1 and presenting higher ki67 index might be more aggressive than small cells. The anomalous expression of CyclinD1 in large cells is not due to the aberrance of CCND1 gene itself. Most BSARCC is low-stage and inert with a favorable prognosis. Our study not only validates previously described clinicopathological features, but also supplements the clinicopathological features and expands the potential genetic alterations and available clinical outcome data of BSARCC.