An Xp11.2 translocation renal cell carcinoma with SMARCB1 (INI1) inactivation in adult end-stage renal disease: a case report

Abstract

Background: Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data.

Case presentation: Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity. In some areas, non-adhesive tumor cells with eccentric nuclei were observed. Immunohistochemically (IHC), the tumor cells are positive for TFE3 and the renal tubular markers (PAX2 and PAX8), and completely negative for SMARCB1, an oncosuppressor protein. Break-apart florescence in situ hybridization and reverse transcription polymerase chain reaction confirmed TFE3 rearrangement on Xp11.2 and the presence of ASPSCR1-TFE3 fusion gene. DNA sequencing revealed a frameshift mutation in exon 4 of SMARCB1 gene.

Conclusion: It is important to recognize this rare RCC with both TFE3 rearrangement and SMARCB1 inactivation, as the prognosis and therapeutic strategies, particularly targeted therapies for such tumors, might be different.

Keywords: Kidney; Renal cell carcinoma; SMARCB1; TFE3; Xp11.2.

Fig. 1

Magnetic Resonance Image (MRI) of the abdomen in a 40-year-old man with Xp11.2 translocation RCC. a, b, Axial T2WI (a) and plain T1WI (b) showed a large, well-defined, irregular mass (T2, high-low heterogeneous signal intensity; T1, iso-signal intensity) with patchy hemorrhage and necrosis in the mass and enlargement of abdominal lymph nodes

Fig. 2

Histopathological and immunohistochemical features of the renal tumor. a, b Nested eosinophilic tumor cells (a) and non-cohesive tumor cells (b) with abundant pink cytoplasm and eosinophilic intracytoplasmic inclusions (H&E staining, 400X magnification). c, d, e, f Neoplastic cells in both organoid and non-adhesive areas demonstrated strong nuclear staining of TFE3 (c, d) and negative staining of INI1 (e, f) (400X magnification). g, h, i, j All tumor cells showed strong positive staining for vimentin (g, h) and pan-CK (i, j) with prominent perinuclear and cytoplasmic staining in non-adhesive area (400X magnification)

Fig. 3

Molecular genetic analyses for the renal tumor. a The TFE3 break-apart probe assay identified split signals (white arrow) and increased TFE3 copy numbers (yellow arrow, 4 signals in one nucleus including one split signal). b Reverse transcription polymerase chain reaction detected an ASPSCR1-TFE3 fusion gene product. c Sequence analysis of SMARCB1 gene (exon 1–9) demonstrated c.147InsT in exon 4, causing a frameshift alteration