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Xp11.2 translocation/ TFE3 rearrangement-associated renal cell carcinoma (RCC) and Xp11 translocation renal mesenchymal tumor are distinct tumor entity. To broaden the spectrum of Xp11 neoplasms, we investigated a novel tumor exhibiting morphologies overlapping Xp11.2 translocation/ TFE3 rearrangement-associated RCC and the mesenchymal counterpart with melanocytic differentiation by immunohistochemistry, fluorescence in situ hybridization (FISH) and RNA sequencing, as well as literature review. Histologically, the tumor was composed of three different types of tumor cells, including a large proportion of clear cells, small round cells, and a few spindle cells, presenting a relatively clear border in the majority area. The nuclei of all tumor cells showed extensively and strong positive expressions of TFE3. Whereas, the clear cells positively expressed the RCC-related markers including PAX8, RCC marker and CD10, and negatively expressed HMB45; On the contrary, the small round cells and spindle cells positively expressed melanocytic marker HMB45, and negatively expressed PAX8, RCC marker and CD10. The ki67 index was higher in the small round cells and spindle cells than that in the clear cells. FISH revealed the rearrangement of TFE3 gene in all the three types of cells. The NONO-TFE3 fusion gene was detected in all tumor cells by RNA sequencing. This unique Xp11 translocation-associated neoplasm might represent a distinct entity overlapping Xp11 translocation RCC and the mesenchymal counterpart with melanocytic differentiation, broadening the spectrum of Xp11 neoplasms. The patient died of tumor recurrence and lung metastasis after seven months after the surgery suggesting those tumors have an unfavorable prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Papillary renal cell carcinoma (PRCC) includes two different morphological subtypes. The differences of genetics and ultrastructure of the two subtypes have been rarely reported. Also, new biomarkers related to the diagnosis and prognosis of PRCC have still not been well elucidated. Immunohistochemistry, fluorescence in situ hybridization (FISH) and transmission electron microscopy were used systematically to determine the characteristics of 56 cases of PRCC and to reveal new diagnostic and prognostic information. Type 1 PRCC presented higher expression rates of EMA and CK7, whereas type 2 presented a higher expression rate of CD10. New immunohistochemical markers, including: p504s, PAX-2, PAX-8 and CA-IX showed extensive immunostaining in PRCC. We first revealed a distinct immunostaining pattern of CA-IX, which was located in multiple foci in PRCC. All tumors had at least one chromosomal aberration including loss of Y, gains of 7 or 17. Gain of chromosome 17 was common in type 1; losses of chromosome 18, 11 and 8 appeared in type 2. Ultrastructurally, glycogen granules and secondary lysosomes were seen in type 1, mitochondria and smooth endoplasmic reticulum were scattered in type 2. Tumor subtype, nuclear grade, TNM stage, clear cell renal cell carcinoma (CCRCC) component and sarcomatoid elements, metastasis, CAIX expression, losses of chromosome 18 and 8 were related to poor outcome of PRCC. We conclude that the two subtypes of PRCC originate from different renal cells, and arise from partially common genetic pathways. EMA, CK7, CD10, p504s, PAX-2, PAX-8 and CA-IX are helpful markers in the differential diagnosis of PRCC. CA-IX expression, losses of chromosome 18 and 8 are new prognostic factors of PRCC. [Copyright &y& Elsevier]