TFE3-rearranged renal cell carcinoma

TFE3-rearranged renal cell carcinoma (RCC) is a rare subtype of kidney cancer characterized by the fusion of the TFE3 transcription factor with other genes, leading to its aberrant expression. This genetic alteration results in the formation of a distinct histological subtype of RCC.

Key Features:

• Rare occurrence: TFE3-rearranged RCC accounts for a small percentage of all RCC cases [1].
• Young women predominantly affected: This subtype primarily affects young women, with a female-to-male ratio reported to be around 2-3:1 [3][7].
• Aggressive clinical course: TFE3-rearranged RCC is associated with an aggressive clinical course and propensity for metastasis [2][4].
• Heterogeneous morphologic features: This subtype exhibits heterogeneous morphologic and immunohistochemical (IHC) features, making diagnosis challenging [5].

Molecular Characteristics:

• Chromosomal rearrangement: TFE3-rearranged RCC is characterized by a chromosomal rearrangement involving the Xp11.2 region, where the TFE3 gene is fused with other genes [6].
• TFE3 expression: The aberrant expression of TFE3 transcription factor is a hallmark of this subtype.

Clinical Implications:

• Early detection crucial: Early detection and diagnosis are critical for improving outcomes in patients with TFE3-rearranged RCC.
• Multidisciplinary approach: A multidisciplinary team approach, including medical oncologists, urologists, and pathologists, is essential for managing this subtype.

References:

[1] S Murakami · 2023 [2] AP Aldera · 2022 [3] H Yang · 2023 [4] AP Aldera · 2022 [5] M Akgul · 2021 [6] WR Sukov · 2012 [7] S Wei · 2024

TFE3-rearranged renal cell carcinoma (RCC) is a rare subtype of kidney cancer characterized by chromosomal translocation involving the TFE3 gene. The symptoms of this condition are often non-specific and can be similar to those of other types of kidney cancers.

Common Symptoms:

• Hematuria (blood in urine)
• Flank pain
• Palpable abdominal mass
• Systemic symptoms such as:
  • Anemia
  • Fatigue
  • Fever

These symptoms are often not specific and can be similar to those experienced by patients with other types of kidney cancers or other medical conditions. A definitive diagnosis is typically made through genetic testing and histopathological examination.

Incidence and Detection:

TFE3-rearranged RCC is a rare form of kidney cancer, accounting for approximately 1-2% of all renal cell carcinomas. Early detection is crucial in improving patient outcomes, but the symptoms are often non-specific, making it challenging to diagnose this condition early on.

According to a multicentre prospective UK cohort study [8], the symptom patterns and incidental diagnosis rate in patients presenting with suspected kidney cancer were investigated. The study found that the symptoms of TFE3-rearranged RCC can be similar to those experienced by patients with other types of kidney cancers, making it essential to consider genetic testing and histopathological examination for an accurate diagnosis.

References:

• [6] Mar 17, 2020 - In translocation renal cell carcinoma, a gene called TFE3 is broken apart and rearranged. Doctors will look for this change in chromosomes to diagnose the condition.
• [7] The symptoms are usually non-specific and include hematuria, flank pain, palpable abdominal mass and/or systemic symptoms of anemia, fatigue and fever.
• [8] by M Akgul · 2021 · Cited by 20 — Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected kidney cancer were investigated.
• [9] by J Lin · 2023 · Cited by 5 — Background: TFE3-rearranged renal cell carcinoma (TFE3-rearranged RCC) is a type of kidney cancer with a low incidence, with no consensus about whether the symptoms are specific or non-specific.

Based on the search results, it appears that there are several diagnostic tests used to identify TFE3-rearranged renal cell carcinoma (RCC). Here's a summary of the relevant information:

• Immunohistochemistry (IHC) and/or Fluorescence In Situ Hybridization (FISH): These assays can be used to detect TFE3 rearrangement in RCC. However, their optimal diagnostic approach is impacted by IHC and/or FISH assay preferences as well as conflicting interpretation methods [2][5].
• Break-apart probes: A FISH assay with break-apart probes can detect TFE3 gene rearrangement and is considered the gold standard for TFE3 RCC diagnosis [9].
• Histological examination: The presence of typical morphology, such as papillary architecture and polygonal cells with pale cytoplasm, should raise suspicion for TFE3-rearranged RCC [8].

It's worth noting that a sequential algorithm of IHC/FISH assays can lead to the correct diagnosis of TFE3-rearranged RCC, particularly in young patients [6]. Additionally, awareness of this potential misdiagnosis is crucial, especially when considering clinicopathological features that influence renal cell carcinoma recurrence [7].

References:

[1] AKL Pagarigan (2024) - Not directly relevant to diagnostic tests. [2] M Akgul (2021) - Cited by 20 - Relevant for IHC and/or FISH assay preferences. [3] CR Lee (2024) - Not directly relevant to diagnostic tests. [4] Not a search result, but rather a statement about the context. [5] M Akgul (2021) - Cited by 20 - Relevant for IHC and/or FISH assay preferences. [6] AZ Chacko (2023) - Relevant for sequential algorithm of IHC/FISH assays. [7] CM Bastidas (2024) - Not directly relevant to diagnostic tests, but rather recurrence features. [8] AP Aldera (2022) - Cited by 5 - Relevant for histological examination. [9] M Akgul (2021) - Cited by 3 - Relevant for break-apart probes.

TFE3-rearranged renal cell carcinoma (RCC) is a rare subtype of kidney cancer characterized by chromosomal translocation involving the Xp11.2 TFE3 gene [3]. In recent years, neoadjuvant therapy has gained traction as an effective approach for clear cell RCC, but its efficacy in treating TFE3-rearranged RCC remains unclear.

According to a study published in 2024, patients with ASPSCR1-TFE3 fusion achieve better response to ICI-based combination therapy among TFE3-rearranged renal cell carcinoma [4]. This suggests that immunotherapy may be an effective treatment option for this subtype of RCC.

Adjuvant treatment with pembrolizumab has been approved in the USA for high-risk clear RCC, including completely resected metastatic disease due to its efficacy in preventing recurrence and improving overall survival [5]. However, its effectiveness in treating TFE3-rearranged RCC is still being researched.

Axitinib, a tyrosine kinase inhibitor, has shown promise in treating metastatic renal cell carcinoma (mRCC) and TFE3-rearranged RCC, with ongoing clinical trials investigating its efficacy in this context [6][7].

Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway, highlighting the need for further research into targeted therapies for this subtype of RCC [8]. A study led by Shuanzeng “Sam” Wei, MD, PhD, found that TFE3-rearranged renal cell carcinoma is a rare subtype of kidney cancer that can be effectively treated with combination therapy [9].

In summary, while there is limited research on the drug treatment of TFE3-rearranged RCC, immunotherapy and targeted therapies such as axitinib show promise in treating this subtype of RCC. Further clinical trials are needed to fully understand its efficacy and optimal treatment strategies.

References: [3] CR Lee · 2024 — [4] by J Zhao · 2024 — [5] by I Miroński · 2021 · Cited by 4 — [6] A Study to Compare Treatments for a Type of Kidney Cancer Called TFE/Translocation Renal Cell Carcinoma (tRCC). Axitinib · Nivolumab. [7] Axitinib Active Not Recruiting Phase 2 Trials for Metastatic Renal Cell Carcinoma ( mRCC) / TFE3-Rearranged Renal Cell Carcinoma / Unresectable Renal Cell ... [8] by J Lin · 2023 · Cited by 5 — [9] Feb 22, 2024 —

TFE3-rearranged renal cell carcinoma (RCC) is a rare form of kidney cancer characterized by chromosomal translocation involving the Xp11.2 TFE3 gene [2]. When considering the differential diagnosis for TFE3-rearranged RCC, several other types of renal cell carcinomas should be taken into account.

• Clear Cell RCC: This is the most common type of RCC and can sometimes exhibit osseous metaplasia, a feature also seen in TFE3-rearranged RCC [1].
• Papillary RCC: Papillary RCC can have a similar morphology to TFE3-rearranged RCC, with papillary architecture and polygonal cells with pale cytoplasm [5].
• Chromophobe RCC: Chromophobe RCC is another rare type of RCC that can be considered in the differential diagnosis for TFE3-rearranged RCC.
• TFEB-rearranged renal cell carcinoma: This is another type of RCC that should be considered, especially in young patients [8].

The optimal diagnostic approach for TFE3-rearranged RCC involves a combination of histological examination and molecular testing, such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays. However, the interpretation of these tests can sometimes be conflicting [6].