UROLOGICAL SURVEY   ( Download pdf )

 

PATHOLOGY

Xp11.2 Translocation Renal Cell Carcinoma with Very Aggressive Course in Five Adult Patients
Meyer PN, Clark JI, Flanigan RC, Picken MM
Loyola University Medical Center, Maywood, IL, USA
Mod Pathol Suppl. 1 2006; 19: 150A

  • Background: Renal cell carcinomas (RCC) associated with Xp11.2 translocations (TFE3 gene fusions) are rare tumors occurring predominantly in children and young adults. Although, thus far, only limited data is available, these tumors are believed to be rather indolent even when diagnosed at advanced stages.
  • Design: Five cases of TFE3-RCC were evaluated in patients aged 18 or older (mean age 31). Diagnosis was confirmed by IHC detection of increased TFE3 fusion protein. Morphology was examined by HE, IHC and electron microscopy (EM) and correlated with clinical picture.
  • Results: HE showed clear cells, arranged in a pseudopapillary architecture, with retention of morphology in the metastatic tumor deposits. By IHC there was strong nuclear positivity for TFE3 in all cases and focal stain for AE3 and vimentin; stains for HMB45, calretinin, pankeratin and AE1 were all negative. By EM (2/5 cases examined) there were junctional complexes and rudimentary microvilli. In one case there were abundant lipid droplets and glycogen; in a second case, rare rhomboid crystals, similar to those seen in alveolar soft part sarcoma, were present. All patients (3 Caucasian, 2 Hispanic) presented with innocuous complaints, abdominal/flank pain and hematuria, and lacked any significant prior history. All but one patient presented with distant metastases at the time of diagnosis, and all patients were diagnosed with additional metastases or tumor recurrence within 5 months of presentation. Treatments included tumor resection, interleukin-2 therapy, combination chemotherapy, and radiation therapy, all with minimal success. Patients followed a rapidly terminal course, with a mean survival of 15 months post-diagnosis (range 10-20 months). One patient is currently undergoing chemotherapy at 13 months post-diagnosis (with brain metastasis), and another patient is alive at 6 months post-diagnosis, with metastases.
  • Conclusions: The patients presented here were older than typically described for TFE3-RCC. Although tumor morphology was similar to pediatric patients, these adult patients had a very aggressive clinical course compared to pediatric TFE3-RCC and even to conventional, adult-type RCC. Consistent use of antibodies against TFE3 in all tumors, regardless of patient age, may expand the spectrum of Xp11.2 translocation RCC with respect to age, clinical behavior and molecular abnormalities.

  • Editorial Comment
    These carcinomas are defined by several different translocations involving chromosome Xp11.2. The t(X; 1) (p11.2; q21) translocation results in the fusion of TFE3 gene in chromosome X to PRCC gene in chromosome 1; the t(X; 17) (p11.2; q25) translocation results in the fusion of TFE3 gene in chromosome X with the ASPL gene in chromosome 17. This latter translocation is also seen in the alveolar soft part sarcoma.
    These carcinomas predominantly affect children and adolescents and are believed to be rather indolent even when diagnosed at advanced stages. The most distinctive histopathologic appearance is that of a carcinoma with papillary architecture comprised of voluminous clear to eosinophilic cytoplasm, discrete cell borders, vesicular chromatin and prominent nucleoli. Scattered hyaline nodules and psammomatous bodies can be seen. The most distinctive immunohistochemical feature of these tumors is nuclear immunoreactivity for the chimerical (mutant) TFE3 protein (1).
    The present study by Meyer et al. reported 5 patients of TFE3 renal cell carcinoma aged 18 or older (mean age 31). All but one patient presented with distant metastases at the time of diagnosis, and all patients were diagnosed with additional metastases or tumor recurrence within 5 months of presentation. The authors emphasize the fact that although tumor morphology was similar to children and adolescents, these adult patients had a very aggressive course. It is noteworthy a Brazilian female 58-year old recently reported with renal cell carcinoma associated with Xp11.2 translocation TFE3 (ASPL-TFE3) gene fusion (2). Metastases were seen in 3 of the 6 dissected lymph nodes, thus determining a final staging (TNM, 2002) pT1b, pN2, pMX (stage IV). After approximately 6 months of follow-up, the patient showed favorable outcome, without manifesting disease or any other signs or symptoms.

References
1. Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter M, Hutchinson B, Reuter VE, Boccon-Gibod L, Timmons C, Hafez N, Ladanyi M: PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). Am J Surg Pathol. 2002; 26: 1553-66.
2. Salles PG, Soto M Jr. M. Kidney carcinoma associated with Xp11.2 translocation/TFE3 (ASPL-TFE3) gene fusion. Int Braz J Urol 2005; 31: 251-5.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, Sao Paulo, Brazil