Case 1 -
Xp11.2 Translocation Renal Cell Carcinoma
Loyola University Medical Center
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An 82-year-old man presented with severe dyspnea on exertion and severe pain between his scapulae. He had a significant past medical history of adenocarcinoma of the colon, and a recent history of prostatic carcinoma with a TRUS prostatic biopsy revealing prostatic adenocarcinoma, Gleason score 4+4=8. In an effort to evaluate the dyspnea, a chest X-ray was taken, followed by CT of the abdomen, thorax, and pelvis. Imaging showed enlarged mediastinal, retroperitoneal, and retrocrural lymph nodes, numerous lung nodules < 5 mm, bilateral pleural effusions, ascitis and a heterogenous 6.0 x 6.1 x 5.3 cm. mass occupying most of the right kidney. An FNA of the renal mass was performed.
Case 1 - Slide 1
Case 1 - Slide 2
Diagnosis: Xp11.2 Translocation Renal Cell Carcinoma
Renal cell carcinoma associated with Xp11.2
There is no corresponding histologic diagnosis for
the renal mass. The patient passed away before a definitive procedure could be undertaken, and an
autopsy was denied. Final diagnosis was confirmed by strong (nuclear) immunohistochemical positivity for
TFE 3 on the cell block section.
The smears are highly cellular showing large three dimensional clusters, papillary structures, and cells
associated with extracellular matrix-like material. The cells have a finely vacuolated cytoplasm, low N:
C ratio, and prominent nucleoli. Some cells have intracytoplasmic hemosiderin pigment. There is
occasional nuclear hyperchromasia and pleomorphism, and there are rare mitotic figures. The differential
diagnosis (based on morphology alone) includes renal cell carcinoma, clear cell type and papillary type.
In cases in which tumor cells have a clear vacuolated cytoplasm and widespread papillary structures the
differential diagnosis of translocation type renal cell carcinoma should be considered and an
immunohistochemical stain for TFE 3 should be performed to rule in/out this diagnosis. The table shows
immunohistochemical differentiation between renal cell carcinoma clear cell type, papillary type and
| ||CD 10 ||RCC ma ||Vimentin ||AE1/AE3 ||CK 7 ||AMACR ||TFE 3|
|Clear cell carcinoma ||+ ||+ ||+ ||+ ||- ||- ||-|
|Papillary carcinoma ||+ ||+ ||+ ||+ ||+ ||+ ||-|
|Translocation type carcinoma ||+ ||+ ||+/- ||+/- ||- ||- ||+|
Translocation (Xp11.2) renal cell carcinomas are relatively rare tumors and have predominantly been
diagnosed in children. It is estimated that approximately one third of pediatric renal cell carcinomas
are TFE3-related translocation carcinomas. Unlike in children, although clear cell carcinomas make up
70% of renal cell carcinomas in adults and 53% in young adults, the exact incidence of TFE3 translocation
carcinomas in these age groups is not known. Although in the pediatric age group most tumors present at
an advanced stage, the clinical course is thought to be indolent. However, recent studies have shown
that the tumor follows a very aggressive clinical course in young adults.
The Xp11.2 translocation carcinomas are characterized by various chromosomal translocations, all of
which may involve a breakpoint at Xp11.2, and all of which result in fusion involving the TFE3 transcription factor gene that maps to this locus. Five distinct gene
fusions involving TFE3 have been characterized and include the following:
|PSF-TFE3 || t(X;1)(p11.2;p34)|
|NoNo-TFE3 || inv(X)(p11;q12)|
|CLTC-TFE3 || t(X;17)(p11.2;q23)|
Of note, the ASPL-TFE3 fusion renal cell carcinoma has identical
breakpoints to alveolar soft part sarcoma, a rare pediatric soft tissue neoplasm of uncertain
The gross appearance of these tumors can closely resemble conventional clear cell carcinoma; they
usually are tan-yellow with areas of hemorrhage and necrosis. Cytologically tumor cells are arranged in
papillary formations and nests. The cells have well defined cell borders and predominantly clear, and
occasionally granular, eosinophilic cytoplasm. Especially in the tumors with ASPL-TFE3 gene fusions (voluminous cell variant) microscopically cells with
voluminous clear to eosinophilic cytoplasm; vesicular nuclear chromatin, and prominent nucleoli are seen.
Psammoma bodies are also frequently observed.
Strong nuclear immunoreactivity for TFE3 proves to be highly sensitive and specific for
tumors with TFE3 fusion proteins. These tumors usually underexpress epithelial markers (EMA and
cytokeratin) and vimentin whereas they show strong CD10 positivity, as seen in our case.
The optimal therapy for Xp11 translocation carcinomas remains to be determined. Given
that immunotherapy has been the standard treatment for patients with advanced stage renal cell
carcinomas, some patients with Xp11 translocation carcinoma have also received this therapy without
associated significant response. Additional gene expression profiling studies have suggested a novel
therapeutic target in Xp11 translocation carcinomas. In vitro studies have demonstrated that ASPL-TFE3
fusion protein common to ASPS and Xp11 translocation carcinomas transactivate the MET promoter,
increasing MET mRNA expression. High levels of MET protein have also been shown by Immunohistochemistry
and Western Blotting. In addition, the ASPL-TFE3 cell lines have shown diminished growth in response to
either a selective inhibitor of MET tyrosine kinase or RNA interference mediated knockdown of MET.
Therefore MET tyrosine kinase inhibitors could be potentially used as a targeted therapy modality to
treat these translocation carcinomas.
- Argani P, Olgac S, Tickoo S, Ladanyi M et al. Xp11 Translocation Renal Cell Carcinoma in Adults: Expanded Clinical, Pathologic and Genetic Spectrum. Am J Surg Pathol. 2007;31(8):1149-1160.
- Mansouri D, Dimet S, Vielh P et al. Diagn Cytopathol.2006;34(11);757-760.
- Meyer P, Picken M et al. Xp11.2 Translocation renal cell carcinoma with very aggressive course in five adults. Am J Clin Pathol 2007;128:70-79.
- Argani et al. Translocation carcinomas of the kidney. Clin Lab Med 2005;25:363-378.