The Squamoid Cells in Biphasic Squamoid Alveolar Renal Carcinoma Present Cytophagocytosis (Not Emperipolesis) of Apoptotic Neutrophilic Granulocytes

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To the Editor:
Recently, Hes et al1 described 21 cases of biphasic squamoid alveolar variants of papillary renal cell carcinoma (BSARC). This is a little known neoplasm of which there are few references in the literature.1–7 Characteristically, in most cases, emperipolesis within the squamoid cells is reported.1,2,5–7 Nevertheless, the type of cell or cellular component inside the squamoid cells is not determined in any of these works.1,2,5–7
We describe a new case of BSARC. On the basis of our histologic and immnunohistochemical findings, we think that the name “emperipolesis” used in BSARC is not exact inasmuch as what is really found in this tumor is cytophagocytosis of apoptotic neutrophils. This phenomenon of cytophagocytosis or cellular cannibalism of apoptotic neutrophils has been described in other extrarenal tumors and can transfer fragments of DNA to the tumor cells.8–10
Our case corresponds to a 54-year-old woman with a cortical tumor 2 cm in size located in the left kidney. A laparoscopic partial nephrectomy was performed (January 2017). Histologically, the neoplasm showed typical features of BSARC1–7 and was composed of small cells that formed alveolar structures, which were filled by bigger cells with squamoid appearance (Fig. 1A). Some of these squamoid cells displayed dense intracytoplasmic globules measuring between 4 and 6 μm in diameter. Some of them seemed to be inside cytoplasmic vacuoles (phagosomes) and others in tumor cells with a degenerative aspect that presented dense cytoplasm without nuclei (Fig. 1B). The immunohistochemical results were also similar to those described in BSARC but with some peculiar findings. Both cell types were positive for 34βE12 cytokeratin, P16, carbonic anhydrase IX, E-cadherin, and β-catenin but with a heterogeneous and scattered distribution. The 2 latter antibodies showed different patterns depending on the cellular component being positive on the cellular membrane of the small cells and predominantly cytoplasmic in the large cells (Fig. 1C). Other antibodies selectively marked each of the cellular components: renal cell carcinoma marker, napsin A, and BCL2 in the small cells, and cyclin-D1, P21, CD15, and GATA3 (cytoplasmic) in the large cells. Some isolated large cells stained for CD10 and P53. On using Ki-67 antibody, the proliferation index was 1% among the large cells and <1% among the small cells. The intracellular globular material was positive for vimentin, CD15, myeloperoxidase, lysozyme, and caspase-3 (Figs. 1D–F). The study for cytokeratin 5/6, cytokeratin 20, WT-1, C-MYC, P27, P63, CD31, CD57, CD68, CD117, DOG1, and S-100 protein gave negative results in both cellular components and in the intracellular material.
Both histologic and immunohistochemical findings in our case are those described in BSARC.1–7 This is a very uncommon tumor, with only around 50 cases described, most of them in abstracts.3,6 The definitive classification of this rare neoplasm is not clear, although, on the basis of immunohistochemical and genetic findings, it seems to correspond to a variant of papillary renal cell carcinoma.1–7 A phenomenon called emperipolesis has been described in large squamoid cells in most reported cases of BSARC1,2,5–7; nevertheless, the images of the different works showed intracytoplasmic cellular fragments of diverse sizes, similar to those described in our case, but well-preserved cells, as those described in emperipolesis, which were not identified within the squamoid cells. This finding is identical to that found in other extrarenal tumors.8–10 In contrast, the true cellular origin of this material internalized in the tumor cells is not determined. In our study we demonstrate that the intracellular fragments are in reality apoptotic bodies composed of dense chromatin aggregates and retracted cytoplasmic components (Fig. 1B). These apoptotic bodies are strongly positive for caspase-3 (Fig. 1F), which is an essential and specific mediator in the apoptotic process.

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