KIDNEY
CARCINOMA ASSOCIATED WITH Xp11.2 TRANSLOCATION / TFE3 (ASPL-TFE3) GENE
FUSION
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PAULO G. O. SALLES,
MARIO SOTO JR
Biocor Hospital,
Belo Horizonte, Minas Gerais, Brazil
ABSTRACT
We
report the case of a 58-year old patient, showing a solid image in the
right kidney, who underwent radical nephrectomy that revealed neoplasia,
whose pathological study led to the diagnosis of kidney carcinoma associated
with Xp11.2 translocation / TFE3 (ASPL-TFE3) gene fusion. The authors
discuss aspects related to this lesion, such as frequency, pathogenesis,
clinical presentation, histopathology and outcome, as observed in the
literature.
Key
words: kidney neoplasms; renal cell; nephrectomy; TFE3 protein,
human
Int Braz J Urol. 2005; 31: 251-5
INTRODUCTION
Kidney
carcinomas associated with Xp11.2 translocations / TFE3 gene fusions are
present in the new version of the WHO classification of kidney tumors
(2004) (1). They are defined by a number of different translocations involving
the Xp11.2 chromosome, all of them resulting from genic fusions involving
the TFE3 gene. It is an uncommon tumor, with approximately 30 reports
in international literature, with no Brazilian publications, whose morphology
and biological behavior are not widely recognized as yet (1-3).
CASE REPORT
Female
58-year old patent reported infrequent episodes of nephritic colic during
the past 6 months. The physical examination revealed no significant changes,
as well as the exam of urinary sediment and urine culture. Imaging examinations
(Figure-1) showed a nodule in the middle third of right kidney. Considering
this finding, after a discussion on surgical approach and management with
the patient, we opted for a right radical nephrectomy. The surgical procedure
was performed without any intercurrence, and immediate post-operative
outcome was satisfactory.
The pathological examination showed right
kidney measuring 12.5 x 7.5 x 5.5 cm, weighting 242 g, and presenting
in its middle portion, in subcapsular position, a circumscribed nodular
lesion measuring 4.8 x 4.5 x 3.5 cm. When observing the sections, the
lesion was well delimited, with brownish-yellowish color, containing areas
of necrosis and hemorrhage. It presented a varying aspect, in a combination
of cystic, solid and papilliferous areas (Figure-1). The renal pelvis
was not affected, and renal artery and vein, as well as the ureter, showed
no signs of neoplastic infiltration. The tumor did not pass over the renal
capsule. Six lymph nodes from the perirenal fibroadipous tissue were dissected,
with sizes ranging from 0.6 to 2 cm in the longest axis. On microscopy,
the tumor showed either papillary or solid architecture (forming well
defined cell nests), hyaline nodules and cells with clear or slightly
eosinophilic and granular cytoplasm, limited by quite distinctive edges
(Figure-2). Metastases were seen in 3 of the 6 dissected lymph nodes,
thus determining a final staging (TNM 2002) pT1b pN2 pMX (stage IV). Based
on the aforementioned morphological findings, immunohistochemical analysis
was performed in order to search for the TFE3 protein, with positive result.
The set of morphological and immunohistochemical findings confirmed the
diagnosis of renal cell carcinoma associated with Xp11.2 translocation
/ TFE3 (ASPL-TFE3) gene fusion. After approximately 6 months of follow-up,
the patient shows favorable outcome, without manifesting disease or any
other signs or symptoms.
COMMENTS
These
tumors are characterized by translocations involving the Xp11.2 chromosome,
all of them resulting in genic fusions involving the TFE3 gene. Those
include t(X;1)(p11.2;q21) translocation, with fusion of the TFE3 and PRCC
genes, a t(X;1)(p11.2;p34) translocation, with fusion between PSF and
TFE3, inv(X)(p11;q12) translocation, with fusion of NonO (p54nrb) and
TFE3 genes, and t(X;17)(p11.2;q25) translocation, with fusion of the ASPL
(also known as RCC17 or ASPSCR1) and TFE3 genes. The latter is also present,
though in a cytogenetically unbalanced form, in alveolar soft part sarcomas
(1-3). A chromosome translocation is an aberration associated with a change
in the chromosomal structure: a segment from one chromosome is transferred
to another one. This kind of change allows the recombination of unrelated
sequences from different chromosomes, with the formation of hybrid genes.
Such genes (then considered as oncogenes), in turn, can eventually encode
chimeric (mutant) proteins that would act as mediators related to cell
growth and motility, potential for invasion and cellular morphogenetic
differentiation. Thus, recognizing and studying such chromosomal change
could have a fundamental role for understanding carcinogenesis, as well
as for diagnosing and determining prognostic factors associated with kidney
carcinomas (2,3).
These tumors usually occur in children and
young adults (on the second and third decades of life), though some cases
have been described in older patients as well; apparently there is no
difference in the distribution by gender. Morphologically, they are generally
characterized by their varied aspect, with predominantly papillary areas,
eventually with solid or cystic portions. Cells have a somewhat voluminous,
clear or slightly eosinophilic cytoplasm, with well-defined limits, and
nuclei containing vesicular chromatin and prominent nucleoli. Scattered
hyaline nodules and psammomatous bodies can be seen. Such findings can
vary according to the different variants (ASPL-TFE3 tumors have cells
with less abundant cytoplasm, more hyaline nodules and psammomatous bodies,
and are less solid than PRCC-TFE3 tumors). The immunohistochemical analysis
reveals the nuclear labeling for the chimeric protein TFE3, which is produced
by the fusion of genes that encode chimeric proteins composed by the C-terminal
portion of TFE3 and by N-terminal portions of other translocated segments,
which constitutes the most distinctive feature in these neoplasias; expression
of CD10 and RCC (renal cell carcinoma marker antigen) has been described,
but only 50% express epithelial markers (EMA and cytokeratin, for example)
(1-4). Differential diagnosis includes papillary and conventional (clear
cell) renal cell carcinomas. In relation to outcome, little is known about
the clinical behavior of these carcinomas: the literature reports that
tumors ASPL-TFE3, despite their advanced stage, usually presented slow
progression (1-2). In summary, it is a rare renal tumor, with peculiar
morphogenetic characteristics and biological behavior, which must be recognized
by specialists.
____________________________
Dr. Pedram Argani, Johns Hopkins
University Hospital,Baltimore, MD, USA,
performed the immunohistochemical analysis.
REFERENCES
- Tumours of the Kidney. In: Eble JN, Sauter G, Epstein JI, Sesterhenn
I (eds.). WHO Classification of Tumours: Tumours of the Urinary System
and Male Genital Organs. Lyon, IARC Press. 2004, pp. 9-88.
- Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R,
et al.: Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar
soft part sarcoma: a distinctive tumor entity previously included among
renal cell carcinomas of children and adolescents. Am J Pathol. 2001;
159: 179-92.
- Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter
M, et al.: 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.
- Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M. Aberrant
nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions:
a sensitive and specific immunohistochemical assay. Am J Surg Pathol.
2003; 27: 750-61.
_______________________
Received: January 11, 2005
Accepted after revision: April 29, 2005
_______________________
Correspondence address:
Dr. Paulo G. de Oliveira Salles
Rua Pitangueiras 554
Belo Horizonte, MG, 30350-200, Brazil
Phone.: + 55 31 3296-9851
E-mail: paulogsalles@yahoo.com
EDITORIAL COMMENT
The
WHO has recently presented a new classification for renal cell carcinomas
in 2004. This classification included renal carcinomas with fusion of
the ASPL gene, which is present in alveolar soft part sarcoma alveolar,
and the PRCC gene, found in papillary renal cell carcinoma. Jointly, theses
tumors have been denominated as carcinomas with translocation of TFE3
gene in Xp 11.2 (PRCC-TFE3 and ASPL-TFE3).
Recent
information from European pathologists and from the John Hopkins University
show that a large percentage of renal carcinomas occurring in the first
decades of life present TFE3 translocations, thus suggesting that this
group of tumors that are currently described, under a pathological perspective,
as typical renal cell carcinomas, are in fact genetically and phenotypically
different from conventional tumors.
The
case described in this paper is interesting; furthermore, it reports an
adult patient, which is an uncommon fact. The real clinical significance
of this gene fusion is still unknown, but it could possibly indicate tumors
that are sensitive to different chemotherapy agents.
Dr. Marcus V Sadi
Section of Urology
University of Santo Amaro
Sao Paulo, SP, Brazil
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