Translocation Renal Carcinoma Research Articles

Towards a new WHO classification of renal cell tumor: what the clinician needs to know-a narrative review.

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.

ASO Author Reflections: The Oncologic Efficacy and Feasibility of Nephron-Sparing Surgery for Adult Xp11.2 Translocation Renal Cell Carcinoma.

Since the description of Xp11.2 translocation renal cell carcinoma as a clinicopathologic entity in 2001, it has attracted increasing attention. This study focused on the oncologic efficacy and feasibility of nephron-sparing surgery (NSS)in this rare tumor. The findings showed that NSS is not recommended for adult Xp11.2 translocation renal carcinoma atcT1bstage due to the possibility of increased risk for postoperative recurrence and metastasis. The results warrant large-scale studies and long-term follow-up evaluation.

Xp 11.2 translocation renal carcinoma in young adults; recently classified distinct subtype.

BackgroundXP11.2 renal translocation carcinomas are often encountered in paediatric group of patients where they are believed to be rather indolent. They are rare but more aggressive in young adults. They are slow growing, sometimes without characteristic symptoms and their biologic behaviour is uncertain.Case reportWe report two cases of this type of tumour in Slovenian young adult males with long and unusual history. Tumours were confirmed imunohistologically by positive reaction for CD10, P504S and TFE3.ConclusionsAccording to the indications in the literature prognosis of these tumours in young adults depends upon the stage. It seems that cysts, haematomas and necrosis around the kidney are often encountered in these tumours. In advanced stage with lymph nodes involvement or distant metastases, the prognosis is poor. Surgery seems to be basic mode of therapy.

Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions

Cathepsin K is a protease whose expression is driven by microphthalmia transcription factor (MITF) in osteoclasts. TFE3 and TFEB are members of the same transcription factor subfamily as MITF and all three have overlapping transcriptional targets. We have shown that all t(6;11) renal cell carcinomas, which harbor an Alpha-TFEB gene fusion, as well as a subset of the Xp11 translocation renal carcinomas, which harbor various TFE3 gene fusions, express cathepsin K, while no other common renal carcinoma does. We have hypothesized that overexpression of TFEB or certain TFE3 fusion proteins function like MITF in these neoplasms, and thus activate cathepsin K expression. However, the expression of cathepsin K in specific genetic subtypes of Xp11 translocation carcinomas, as well as alveolar soft part sarcoma, which harbors the same ASPSCR1-TFE3 gene fusion as some Xp11 translocation carcinomas, has not been addressed. We performed immunohistochemistry for cathepsin K on 14 genetically confirmed t(X;1)(p11;q21) carcinomas, harboring the PRCC-TFE3 gene fusion; eight genetically confirmed t(X;17)(p11;q25) carcinomas, harboring the ASPSCR1-TFE3 gene fusion; and 18 alveolar soft part sarcomas (12 genetically confirmed), harboring the identical ASPSCR1-TFE3 gene fusion. All 18 alveolar soft part sarcomas expressed cathepsin K. In contrast, all eight ASPSCR1-TFE3 carcinomas were completely negative for cathepsin K. However, 12 of 14 PRCC-TFE3 carcinomas expressed cathepsin K. Expression of cathepsin K distinguishes alveolar soft part sarcoma from the ASPSCR1-TFE3 carcinoma, harboring the same gene fusion. The latter can be useful diagnostically, especially when alveolar soft part sarcoma presents in an unusual site (such as bone) or with clear cell morphology, which raises the differential diagnosis of metastatic ASPSCR1-TFE3 renal cell carcinoma. The difference in expression of cathepsin K between the PRCC-TFE3 and ASPSCR1-TFE3 carcinomas, together with the observed clinical differences between these subtypes of Xp11 translocation carcinomas, suggests the possibility of functional differences between these two related fusion proteins.

Renal carcinoma with (6;11)(p21;q12) translocation: Report of an adult case

An extremely rare adult example of renal carcinoma with t(6;11)(p21;q12 or q13) is presented here. The tumor of a 45-year-old Japanese male, excised under the diagnosis of renal cell carcinoma, was a well circumscribed 7 cm mass with light brown sectioned surfaces. Histologically, it was composed of a major population of large polygonal epithelioid cells in a nested alveolar growth and a subpopulation of smaller cells clustering around hyaline basement membrane material. The former cells possessed ample, clear to eosinophilic granular cytoplasm with well-defined cell borders and the latter was frequently accompanied by psammomatous calcification. These tumor cells exhibited immunoreactivity for melanoma markers, transcription factor EB and cathepsin K, but were not reactive for epithelial markers and transcription factor E3. While pulmonary metastatic foci that were noted preoperatively progressed rapidly following interferon-based therapy, subsequent sunitinib malate yielded a partial response and stabilized the lung metastasis for 6 months after surgery. We could trace 20 cases of 6p21 translocation renal carcinoma, among which only four were in individuals older than 40 years. Description of a new case like this is important since little is known about the prognosis and treatment of adult patients with this condition.

Abstract 3922: TFEB translocation renal carcinoma: Two cases of novel isoforms with unique clinicopathological features

Abstract Renal cell carcinoma (RCC) with t(6;11) translocation, involving the transcription factor EB (TFEB), is an extremely rare neoplasm with only 20 cases reported to date. According to the available clinical histories, TFEB translocation renal carcinoma (TFEB RC) is predominantly seen in children and young adults and generally indolent. So far, only two TFEB RC cases have been reported to result in metastases and patient death. We herein present two cases of novel isoforms of TFEB RC with unique clinicopathological features, involving a 37-year-old man and a 47-year-old man. Whereas the former case had an aggressive course, the latter case had the borderline features between TFEB RC and chromophobe type RCC histologically and immunohistochemically except for the nuclear staining of TFEB. Genetically, the former case had two variants of mRNA in RT-PCR analysis, one of which directly connected to the exon 3 of TFEB in sequencing analysis. The latter case had the fusion point of TFEB downstream of the wild-type ATG in exon 3, although the nuclear staining of TFEB was detected. Our data including the molecular characterization contribute to clarify this tumor entity genetically and clinicopathologically. Further investigations with additional new cases are required. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3922. doi:10.1158/1538-7445.AM2011-3922

11. Xp11.2 translocation renal cell carcinoma in an adult: a case report

We present a case of Xp11.2 translocation carcinoma in a 52-year-old woman who presented with haematuria and right upper quadrant pain. She was found on imaging to have a right renal mass. Histologically this was a tumour demonstrating well-demarcated areas of clear cell and papillary renal cell carcinoma, with cells having abundant clear cytoplasm and distinct cell borders. Immunohistochemical stains showed weak cytokeratin staining and membranous CD10 positivity. Interphase/nuclear <i>in situ</i> hybridisation studies showed an abnormal signal pattern consistent with an Xp11 translocation/TFE3 gene rearrangement. The patient had rapid progression of her disease postoperatively with widespread nodal and extranodal metastases, and died of disease 6 months after diagnosis. Xp11.2 translocation renal carcinomas are a recent addition to the World Health Organization classification of renal tumours. They are intimately associated with defined chromosomal translocations involving the TFE3 gene resulting in gene fusions proposed to interfere with gene expression and cell cycle regulation. These tumours are predominantly paediatric, however cases are increasingly being recognised in adults. Nevertheless they are rare in all ages. Histologically they show distinct features including sharply demarcated nested and papillary architecture composed of cells with voluminous clear to eosinophilic cytoplasm and discrete cell borders. Classically there is strong TFE3 nuclear immunoreactivity and weak cytokeratin staining. These tumours provide insight into gene fusion products and their role in tumourigenesis and we discuss the expanding cytogenetic knowledge regarding this tumour. The clinical behaviour of these tumours is yet to be fully elucidated. They generally follow an indolent course, however rarely aggressive behaviour is reported, hence the prognosis remains guarded.

An adult Xp11.2 translocation renal carcinoma showing response to treatment with sunitinib

A rare variant of renal cell carcinoma (RCC) with a translocation involving Xp11.2 has become increasingly recognized as a separate entity in the 2004 World Health Organization (WHO) kidney carcinoma classification. These tumors predominantly affect children and young adults and tend to present with advanced stage disease. Although reported to be indolent in children, adult cases run a more aggressive course. Little is known about their natural history, prognosis and response to therapy. We report a case of Xp11 translocation renal cancer in a 33-year-old male patient who presented with widespread rapidly progressive metastatic disease involving extensive intra-thoracic lymph nodes, supra-clavicular, retroperitoneal lymph nodes, lung nodules, and peritoneal mass. He had failed to respond to treatment with high dose interleukin 2, but showed a significant clinical response to treatment with the multikinase inhibitor sunitinib. CT scan performed after 3 cycles (18 weeks) of therapy revealed more than 65% reduction of measurable disease by response evaluation criteria in solid tumors (RECIST) criteria, resolution of other assessable lesions, and a clinical benefit that lasted for over 13 months. But unfortunately, this was subsequently followed by a rapidly progressive course. The well-recognized clinical efficacy of multikinase inhibitors such as sunitinib and sorafenib is based on the outcomes in patients with clear cell histology. There is limited data on efficacy in non-clear cell RCC, but activity in translocation RCC has not been reported. To our knowledge, this is the first documented case of Xp11 translocation carcinoma to have demonstrated an objective durable response to sunitinib. It remains unclear how resistance to sunitinib develops, but the results to date support further evaluation of sunitinib in cases of translocation RCC.

XpII.2 Translocation Renal Carcinoma With Placental Metastasis: A Case Report

Renal cell carcinomas with sporadic Xp11.2 translocations are uncommon malignancies in children and young adults associated with several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Placental metastases are extremely rare, with only a handful of cases reported. This study reports the case of a 20-year-old woman with an Xp11.2 translocation renal carcinoma that metastasized to the placenta. This is the first reported case of a renal cell carcinoma metastatic to the placenta and highlights the aggressive behavior of Xp11 translocation renal cell carcinomas.

Tumores renales de la infancia y adolescencia asociados a anomalías cromosómicas

The pediatric kidney is a common site for tumors carrying specific chomosomal alterations. The most common of these is the nephroblastoma or Wilms tumor (WT), which is associated with anomalies in two loci: 11p13 and 11p15, the latter also linked to Beckwith-Wiedemann syndrome. Two other genes that seem to be implicated are WT3 and WT4. In addition, 1q gains or 22 deletions have been shown to independently be associated with a worst prognosis in WTs. Other neoplasms with chromosomal rearrangements, such as Renal Cell carcinomas (CRs) are much less frequent in children (between 1.8 and 6.3 % of all malignant renal tumors). Among these, the “translocation renal carcinomas” have been identified involving the locus Xp11 with two main types of translocations: t(X;1), and t(X;17). Congenital mesoblastic nephroma (NMC) is a renal tumor affecting newborns and young infants. NMCs of the cellular type feature a specific translocation t(12;15)(p13;q25), which is also present in congenital fibrosarcomas outside of the kidney. These findings have led to conclude that these two tumors (NMC and congenital fibrosarcoma) are genetically equivalent. Rhabdoid tumors (TRs) of the kidney are very rare and aggressive neoplasms that appear with a mean age of 11 months. At least 50% of these TRs carry abnormalities in the hSNF5/INI1 gene, at 22q11.2. This gene is probably involved in transcriptional modulation of other genes such as the oncogene c-Myc, and also of the retinoblastoma protein RB signaling pathway.

Aggressive Metastatic Translocation Renal Carcinoma in a 23-year-old Man

Aggressive Metastatic Translocation Renal Carcinoma in a 23-year-old Man