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Overview

Xp11 translocation renal cell carcinoma (Xp11 tRCC)
is a rare subtype of kidney cancer characterized by genetic translocations involving the Xp11.2 chromosome region, which result in the fusion of the TFE3 gene with various partners (e.g., PRCC, ASPSCR1, SFPQ).
This fusion drives abnormal TFE3 protein expression, promoting tumor growth.
Xp11 tRCC occurs in children, adolescents, and young adults, but can also appear in older patients, sometimes after prior chemotherapy. It is considered part of the MiT family translocation renal cell carcinomas

Symptoms

  • Blood in urine (hematuria)
  • Flank or abdominal pain
  • Palpable abdominal mass
  • Fatigue, weight loss, or fever (systemic symptoms)
  • Occasionally discovered incidentally on imaging
  • Advanced cases may show metastases to lungs, lymph nodes, or bones

Causes & Risk Factors

  • Chromosomal translocation involving 2 (TFE3 gene)
  • Mostly sporadic, not inherited
  • History of prior chemotherapy (especially in childhood cancer survivors) increases risk
  • Slight female predominance due to X-linked location
  • Younger age groups more affected than other RCC subtypes

Diagnosis

  • Imaging: CT or MRI of abdomen/pelvis reveals a solid renal mass
  • Histopathology: Papillary or nested architecture with clear/eosinophilic cytoplasm
  • Immunohistochemistry: Strong TFE3 nuclear positivity
  • Molecular confirmation: FISH or next-generation sequencing for TFE3 gene fusion
  • Metastatic workup: Chest CT, bone scan, PET-CT if indicated

Treatment Options

  • Surgical resection: Partial or radical nephrectomy is the primary treatment
  • Targeted therapy: VEGF inhibitors (e.g., sunitinib, pazopanib) and mTOR inhibitors may offer benefit in advanced disease
  • Immunotherapy: Checkpoint inhibitors (nivolumab, pembrolizumab) are being investigated
  • Chemotherapy: Generally limited effectiveness
  • Clinical trials: Ongoing studies exploring novel targeted and TFE3-specific therapies

Prognosis

  • Children: Often favorable outcomes after complete resection
  • Adults: More aggressive behavior and higher risk of metastasis
  • Stage at diagnosis strongly influences survival
  • TFE3 fusion type may impact prognosis (e.g., ASPSCR1-TFE3 fusions often more aggressive)
  • Regular imaging surveillance recommended post-surgery

Living with this Cancer Type

  • Lifelong follow-up with imaging and kidney function monitoring
  • Supportive care for fatigue, pain, and emotional well-being
  • Multidisciplinary management: urology, oncology, radiology, pathology, and genetics
  • Nutrition and exercise programs to maintain general health
  • Counseling for fertility and long-term medication side effects

Prevention & Screening

  • No specific prevention due to genetic origin
  • Early evaluation of hematuria or kidney pain is critical
  • Survivors of childhood cancers (especially those treated with chemotherapy) should undergo periodic renal imaging
  • Genetic testing for TFE3 rearrangements in atypical RCC presentations

FAQs

Q: What does “Xp11 translocation” mean?
A: It refers to a chromosomal rearrangement involving the Xp11.2 region, leading to fusion of the TFE3 gene with another gene, which drives cancer growth.

Q: Is Xp11 tRCC hereditary?
A: No, it is usually sporadic and not passed through families.

Q: How is it different from other kidney cancers?
A: It occurs in younger patients, shows TFE3 gene fusion, and can behave more aggressively.

Q: Can targeted therapy or immunotherapy cure it?
A: They can help control disease, especially in advanced cases, but surgery remains the main curative approach.

Resources

  • National Cancer Institute (NCI)cancer.gov
  • American Urological Association (AUA)auanet.org
  • Kidney Cancer Associationkidneycancer.org
  • gov – Search “Xp11 translocation renal cell carcinoma”
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