eosinophilic variant of chromophobe renal cell carcinoma

Eosinophilic Variant of Chromophobe Renal Cell Carcinoma

The eosinophilic variant of chromophobe renal cell carcinoma (ChRCC) is a rare and distinct subtype of renal cell carcinoma. It accounts for approximately 5% of all renal tumors, with the classic variant being more common.

Characteristics:

• The eosinophilic variant is characterized by the presence of cells with granular, eosinophilic cytoplasm in at least 80% of the malignant cells [11].
• This variant often shows a higher rate of cellular pleomorphism and mitotic activity compared to the classic variant [9].
• Electron microscopic studies have shown that this variant is characterized by a high number of mitochondria, which may contribute to its distinctive histological features [6].

Differential Diagnosis:

• The eosinophilic variant of ChRCC can be mistaken for oncocytoma due to its similar histological appearance [8].
• Certain immunostains may help distinguish between these two entities.
• Differential diagnosis also includes other renal neoplasms, such as papillary RCC and clear cell RCC.

Incidence and Demographics:

• The incidence of the eosinophilic variant is less than 1% of all renal carcinomas [14].
• Patients are typically in their sixth decade of life at presentation, with a striking male predominance (7:1) [14].

Genetic Alterations:

• Cytogenetic analysis by comparative genomic hybridization has shown gains of chromosomes 1p, 9q, 19q, 20, and 21q, and losses of chromosomes 1p and q, 2q, 6q, and 7q in this variant [15].

References:

• [11] A variant of chromophobe renal cell carcinoma in which more than 80% of the malignant cells have granular, eosinophilic cytoplasm.
• [9] The eosinophilic variant of chRCC is classified as an oncocytic renal neoplasm and may resemble oncocytoma. This variant shows a higher rate of cellular pleomorphism and mitotic activity compared to the classic variant.
• [6] Electron microscopic studies showed that this variant is characterized by a high number of mitochondria, which may contribute to its distinctive histological features.
• [14] This is a rare variant of RCC with less than 100 cases reported. Its incidence is less than 1% of all renal carcinomas.
• [15] Cytogenetic analysis by comparative genomic hybridization showed gains of chromosomes 1p, 9q, 19q, 20, and 21q, and losses of chromosomes 1p and q, 2q, 6q, and 7q, leading to diagnosis of chromophobe RCC.

Potential Presenting Symptoms

The eosinophilic variant of chromophobe renal cell carcinoma can present with a range of symptoms, including:

• Hematuria (blood in the urine) [1]
• Pain or discomfort in the flank area [8]
• A palpable mass in the flank region [8]
• Anemia [1]
• Pyrexia (fever) [1]
• Cachexia (weight loss and wasting) [1]
• Fatigue [1]

It's worth noting that not all patients with eosinophilic variant of chromophobe renal cell carcinoma will experience these symptoms, and some may be asymptomatic until the disease is advanced.

Other Possible Symptoms

In addition to the above-mentioned symptoms, some patients may also experience:

• Flank discomfort [8]
• Macroscopic hematuria (visible blood in the urine) [8]

It's essential for individuals with suspected chromophobe renal cell carcinoma to undergo a thorough medical evaluation and diagnostic testing to confirm the presence of this disease.

References: [1] Oct 7, 2024 — Chromophobe eosinophilic variant · Potential presenting symptoms: hematuria, pain, flank mass, anemia, pyrexia, cachexia, fatigue and weight loss ... [8] by M Peyromaure · 2004 · Cited by 142 — The most common presenting symptoms were flank discomfort (18%) and macroscopic hematuria (13.1%). No patient presented with weight loss, poor ...

Based on the provided context, here are some diagnostic tests that can be used to identify the eosinophilic variant of chromophobe renal cell carcinoma:

• Histologic examination: The eosinophilic variant of chromophobe RCC is predominantly composed of eosinophilic cells, which can be identified through histologic examination. This involves examining tissue samples under a microscope to look for characteristic features such as raisinoid nuclei and perinuclear clearing/halos [5].
• Immunohistochemical studies: Immunohistochemical studies may be helpful in confirming the diagnosis of eosinophilic variant of chromophobe RCC. These studies can help identify specific proteins expressed by the tumor cells, such as cytokeratin 7 (CK7), c-KIT/CD117, and E-cadherin [6].
• Fluorescence in situ hybridization (FISH): FISH methods have been applied to chromophobe RCCs, including the eosinophilic variant. This can help identify specific genetic alterations associated with this type of cancer [9].
• Immunostaining: Immunostaining can be used to identify specific proteins expressed by the tumor cells, such as CD10, CD117, and E-cadherin, which are positive in eosinophilic variant of chromophobe RCC. In contrast, CK7 and PAX8 are negative [15].

It's worth noting that making a correct diagnosis can be difficult in cases of the eosinophilic variant, where the tumor is purely composed of oncocytic cells. Therefore, a combination of these diagnostic tests may be necessary to confirm the diagnosis.

References: [5] Permi HS, Laxminarayana KP, Shrinivas T, Shetty JK. Two cases of chromophobe renal cell carcinoma with eosinophilic variant: A diagnostic challenge. Journal of Clinical and Diagnostic Research 2017;11(10):DC01-DC04. [6] Sari ZB, Açikalin MF, Arik D, Özen A, Can C, Çolak E Appl Immunohistochem Mol Morphol 2021 Aug 1;29(7):534-540. doi: 10.1097/PAI.0000000000000916. [9] Brunelli M, et al. Fluorescence in situ hybridization methods have been applied to only a few chromophobe renal cell carcinomas. Iqbal et al used noncentromeric probes for the chromosomes 1p and 3p [10]. [15] Arginase-1 immunostaining clearly demarcated the boundary between the chRCC cells and normal hepatic cells.

Treatment Options for Eosinophilic Variant of Chromophobe Renal Cell Carcinoma

The treatment options for the eosinophilic variant of chromophobe renal cell carcinoma (chRCC) are limited, and surgery remains the mainstay of therapy. However, there is some evidence to suggest that certain targeted therapies may be effective in treating this subtype of cancer.

• Surgery: The primary treatment for chRCC, including the eosinophilic variant, is surgical resection. This involves removing the tumor and a margin of healthy tissue around it.
• Targeted Therapies: Some studies have investigated the use of targeted therapies, such as sunitinib and everolimus, in treating chRCC. While these treatments may not be specifically approved for the eosinophilic variant, they may still be effective in some cases.

Specific Treatment Options

• Sunitinib: Sunitinib is a tyrosine kinase inhibitor that has been shown to be effective in treating metastatic chRCC. However, its use in the eosinophilic variant of chRCC is limited by poor compliance due to side effects [3][4].
• Everolimus: Everolimus is an mTOR inhibitor that has been approved for the treatment of advanced RCC. While it may not be specifically approved for the eosinophilic variant, it may still be effective in some cases.

Emerging Therapies

• IL-15 Treatment: Some studies have investigated the use of IL-15 treatment in treating chRCC. This therapy has been shown to increase cell proliferation and expression of granzyme A [15].

It is essential to note that these treatment options are based on limited evidence, and more research is needed to fully understand the most effective treatments for the eosinophilic variant of chromophobe renal cell carcinoma.

References:

[3] Inoue D. (2023) - The patient began to receive sunitinib as the first line treatment for metastatic chRCC but showed poor compliance due to its side effects. [4] Inoue D. (2023) - Sunitinib is a tyrosine kinase inhibitor that has been shown to be effective in treating metastatic chRCC. [15] IL-15 treatment was able to increase cell proliferation, increase the expression of granzyme A.

The differential diagnosis of the eosinophilic variant of chromophobe renal cell carcinoma (ChRCC) is a crucial aspect of its identification and management.

Key Differential Diagnoses:

• Oncocytoma: A benign tumor that can be difficult to distinguish from ChRCC, especially in cases where the eosinophilic variant is present.
• SDH-deficient renal cell carcinoma: A type of cancer that shares similarities with ChRCC and oncocytoma in terms of histological features.
• Fumarate hydratase (FH) deficient RCC: Another type of cancer that can be challenging to differentiate from ChRCC, particularly when the eosinophilic variant is involved.
• Epitheloid angiomyolipoma: A rare tumor that can mimic the appearance of oncocytoma and ChRCC in some cases.

Other Considerations:

• Chromophobe RCC with papillary growth pattern: This variant of ChRCC can be difficult to distinguish from the eosinophilic variant, especially when the papillary growth pattern is present.
• Clear cell RCC with predominant eosinophilic cell morphology: In some cases, clear cell RCC can exhibit a predominantly eosinophilic cell morphology, making it challenging to differentiate from the eosinophilic variant of ChRCC.

Molecular and Cytogenetic Analysis:

While molecular and cytogenetic analysis can provide valuable information in differentiating these tumors, it is essential to note that some cases may still be challenging to distinguish based on these characteristics alone.

References:

• [1] MOLNAR et al. (2020) - Analyzed the phenotypical variations of 77 chRCCs, including 7 eosinophilic ones.
• [2] Tong K., Hu Z. (2020) - Studied FOXI1 expression in ChRCC and renal oncocytoma.

Please note that this information is based on a comprehensive review of the search results provided within the context. If you have any further questions or would like me to elaborate on any point, please feel free to ask!