SMARCB1-deficient renal medullary carcinoma

SMARCB1-deficient Renal Medullary Carcinoma: A Rare and Aggressive Cancer

SMARCB1-deficient renal medullary carcinoma (RMC) is a rare and highly aggressive type of kidney cancer. It is characterized by the loss of SMARCB1 protein expression, which is a tumor suppressor gene.

Key Features:

• Rare: RMC is a rare subtype of kidney cancer, accounting for only a small percentage of all renal cancers.
• Aggressive: RMC is highly aggressive and has a poor prognosis, with most patients experiencing rapid progression and metastasis.
• Associated with Sickle Cell Trait: RMC is often associated with sickle cell trait (HbAS), which increases the risk of developing this cancer.
• Symptoms: Common symptoms include hematuria (blood in urine), abdominal/flank pain, weight loss, and fatigue.

Causes and Risk Factors:

• SMARCB1 Loss: The loss of SMARCB1 protein expression is a key driver of RMC development.
• Sickle Cell Trait: Individuals with sickle cell trait are at increased risk of developing RMC.
• Genetic Predisposition: Some individuals may have a genetic predisposition to develop RMC due to inherited mutations in the SMARCB1 gene.

References:

• [1] SMARCB1-deficient renal medullary carcinoma is a rare, highly aggressive, typically medulla centered carcinoma with SMARCB1 (INI1) loss. [1]
• [3] SMARCB1-deficient RMC is a rare kidney cancer associated with sickle cell hemoglobinopathies with poor outcomes. [3]
• [5] SMARCB1-deficient renal medullary carcinoma is a rare malignant kidney tumour associated with sickle cell trait and a poor prognosis. [5]
• [7] It is characterized by a large, white or tan, firm tumor in the renal medulla, often leading to symptoms such as hematuria, abdominal/flank pain, weight loss, ... [7]

Note: The above information is based on the search results provided and may not be an exhaustive list of all relevant features and causes.

Common symptoms of SMARCB1-deficient renal medullary carcinoma (RMC) include:

• Blood in the urine, which is often reported as the first symptom by patients with RMC [2].
• Pain on the kidney side, which can be a significant symptom for many patients [1].
• A large, white or tan, firm tumor in the renal medulla, which can lead to symptoms such as hematuria (blood in the urine), abdominal/flank pain, weight loss, and others [3].

Other possible symptoms:

• Abdominal/flank pain due to the tumor's presence in the medullary region [4].
• Weight loss, which can occur as a result of the tumor's growth and impact on overall health.

It is essential to note that SMARCB1-deficient RMC is a rare and aggressive form of cancer, often associated with sickle cell trait. Early detection and treatment are crucial for improving patient outcomes.

References: [1] - Search result 1 [2] - Search result 2 [3] - Search result 3 [4] - Search result 4

Diagnostic Tests for SMARCB1-deficient Renal Medullary Carcinoma

SMARCB1-deficient renal medullary carcinoma (RMC) is a rare and aggressive form of kidney cancer. Diagnosing this condition requires a combination of clinical evaluation, imaging studies, and molecular testing.

• Immunohistochemistry: This test detects the loss of SMARCB1 protein expression in tumor cells. A negative result for SMARCB1 protein can help confirm the diagnosis of RMC [3][4].
• Fluorescence In Situ Hybridization (FISH): FISH can detect alterations in the SMARCB1/INI1 gene, including inactivating translocations that lead to loss of function. This test is particularly useful for confirming the diagnosis of RMC in patients without sickle cell trait [10].
• Imaging Studies: Imaging studies such as CT or MRI scans are used to evaluate the extent of tumor spread and involvement of surrounding tissues.
• Clinical Evaluation: A thorough clinical evaluation, including physical examination and medical history, is essential for diagnosing RMC. Patients may present with symptoms such as hematuria (blood in urine), flank pain, or a palpable mass [8].

Key Diagnostic Features

• Loss of SMARCB1 protein expression
• Inactivating translocations of the SMARCB1/INI1 gene
• Presence of tumor cells in the renal medulla

These diagnostic tests and features are crucial for accurate diagnosis and management of SMARCB1-deficient RMC.

References:

[3] by Y Su · 2022 · Cited by 7 — The key biological and diagnostic feature of RMC is the loss of SMARCB1 protein expression. [4] Jan 24, 2023 — All RMC and RCCU-MP tumors characteristically do not express a protein called INI1, also known as SMARCB1, hSNF5 or BAF47. [8] by BO Severseike · 2023 · Cited by 2 — The tumor develops in the medulla of the kidney. The first sign is often blood in the urine (hematuria). [10] by M Valeri · 2022 · Cited by 2 — Fluorescence in situ Hybridization (FISH) can detect alterations in SMARCB1/INI1 consisting mostly in inactivating translocation of one allele.

Current Treatment Options for SMARCB1-deficient Renal Medullary Carcinoma

SMARCB1-deficient renal medullary carcinoma (RMC) is a rare and aggressive form of cancer. The current recommended management for this disease involves first-line systemic therapy using platinum-based cytotoxic chemotherapy [2]. This treatment approach has shown some effectiveness in managing the condition.

Platinum-Based Chemotherapy

Platinum-based chemotherapy, which includes drugs such as cisplatin and carboplatin, is currently the standard of care for SMARCB1-deficient RMC. These medications work by interfering with the cancer cells' ability to divide and grow [1].

Other Treatment Options

In addition to platinum-based chemotherapy, other treatment options are being explored for SMARCB1-deficient RMC. For example, a phase 2 trial is currently assessing the efficacy of ubamatamab in patients with MUC16-expressing SMARCB1-deficient renal medullary carcinoma and epithelioid sarcoma [4]. Another study is investigating the use of cemiplimab in combination with ubamatamab for this condition [6].

Immune Checkpoint Inhibitors

Research has also shown that immune checkpoint inhibitors may be effective in treating SMARCB1-deficient medullary renal cell carcinoma. Tertiary lymphoid structures, which are thought to promote an anti-tumor immune response, have been found to potentially enhance the effectiveness of these medications [8].

Conclusion

While there is no cure for SMARCB1-deficient RMC, current treatment options such as platinum-based chemotherapy and other emerging therapies offer hope for managing this aggressive form of cancer.

References:

[1] by W McCamy · 2024

[2] Sep 17, 2024

[3] Oct 8, 2024 (Note: This search result is not directly relevant to the question but provides context on a related clinical trial)

[4] Jul 27, 2024

[5] Jan 24, 2023 (Note: This search result is not directly relevant to the question but provides general information on RMC)

[6] This phase II trial studies how well ubamatamab works alone or in combination with cemiplimab for patients with renal medullary carcinoma or epithelioid sarcoma.

[7] by AL Hong · 2019 (Note: This search result is not directly relevant to the question but provides context on proteasome inhibitors)

[8] by Y Tang · 2024

The differential diagnosis of SMARCB1-deficient renal medullary carcinoma (RMC) can be organized based on age, location, cytologic features, and loss of nuclear SMARCB1/INI1 expression [2]. This is a crucial step in accurately diagnosing the condition.

Factors to Consider:

• Age: RMC typically affects young people, often with African ancestry [5].
• Location: The tumor develops in the medulla of the kidney.
• Cytologic features: The cancer cells may exhibit specific characteristics that can aid in diagnosis.
• Loss of nuclear SMARCB1/INI1 expression: This is a key feature of RMC, as most patients with this condition do not express the SMARCB1 protein [8].

Other Conditions to Rule Out:

• Rhabdoid tumor of the kidney (RTK) and other rare childhood cancers may also be driven by loss of SMARCB1 [3].
• Biallelic inactivation of SMARCB1 has been observed in some cases, which can lead to different molecular mechanisms underlying the loss of SMARCB1 expression in RMC [9].

Key Takeaways:

• Accurate diagnosis of SMARCB1-deficient RMC requires consideration of age, location, cytologic features, and loss of nuclear SMARCB1/INI1 expression.
• Other conditions, such as RTK and rare childhood cancers, should be ruled out based on specific characteristics.

References:

[2] Severseike BO (2023) - Cited by 2 [3] Su Y (2022) - Cited by 7 [5] Search result 5 [8] Search result 8 [9] Search result 9