EZB-MYC- diffuse large B-cell lymphoma

EZH2-BCL2-MYC Triple-Hit Diffuse Large B-Cell Lymphoma

EZH2-BCL2-MYC triple-hit diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive subtype of DLBCL. This type of lymphoma is characterized by the presence of mutations in the EZH2 gene, translocations involving the BCL2 gene, and amplifications or translocations of the MYC gene.

Key Features:

• EZH2 Mutations: EZH2 mutations are a hallmark of this subtype, leading to increased histone methylation and epigenetic silencing of tumor suppressor genes [1].
• BCL2 Translocations: BCL2 translocations contribute to the development of DLBCL by promoting cell survival and resistance to apoptosis [5].
• MYC Amplifications/Translocations: MYC amplifications or translocations are a common feature in this subtype, leading to increased MYC expression and enhanced tumorigenesis [9].

Clinical Implications:

The presence of EZH2-BCL2-MYC triple-hit features has significant clinical implications. Patients with this subtype tend to have a poorer prognosis compared to those with other DLBCL subtypes. The aggressive nature of this disease requires prompt and effective treatment, often involving combination chemotherapy regimens [9].

References:

[1] M Roschewski · 2020 · Cited by 45 — EZB is typically a GCB DLBCL and associated with genetic events including BCL2 translocations, EZH2 mutations and REL amplifications. [5] by C Zhang · 2024 · Cited by 9 — MYC translocation occurs in 8–14% of diffuse large B-cell lymphoma (DLBCL), and may concur with BCL2 and/or BCL6 translocation, ... [9] by GW Wright · 2020 · Cited by 914 — EZB. MCD. ST2. N1. LymphGen. Significance. We describe a taxonomy of diffuse large B cell lymphoma (DLBCL) consisting of seven genetic subtypes ...

Common signs and symptoms of DLBCL, including EZB-MYC variant

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous class of B-cell lymphoma that typically presents as aggressive or advanced disease [8]. The signs and symptoms of DLBCL, including the EZB-MYC variant, can vary from person to person but often include:

• Lymphadenopathy, especially of the cervical, axillary, and inguinal regions [4]
• Systemic symptoms such as fever, night sweats, and weight loss
• Abdominal pain or discomfort due to lymphoma involvement in the gastrointestinal tract
• Respiratory symptoms such as coughing or shortness of breath if the lymphoma affects the lungs

It's worth noting that the presentation of DLBCL can be quite variable, and some patients may not exhibit any noticeable symptoms until the disease is advanced [8].

Genetic classification and implications

The genetic classification of DLBCL has been shown to have therapeutic implications. The EZB-MYC variant, in particular, has been associated with a specific set of genetic alterations that can impact treatment outcomes [6]. Further research is needed to fully understand the clinical significance of these findings.

References:

[4] Signs and Symptoms of DLBCL​​ Common signs and symptoms include the following1: Lymphadenopathy, especially of the cervical, axillary, and ...

[6] by R Shen · 2023 · Cited by 40 — Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma (DLBCL).

[8] Aug 14, 2024 — Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous class of B-cell lymphoma that typically presents as aggressive or advanced ...

Diagnostic Tests for EZB-MYC Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma characterized by the rapid growth of cancer cells in the lymphatic system. EZB-MYC DLBCL is a subtype of DLBCL that involves genetic alterations in the MYC and EZB genes.

Immunohistochemistry (IHC)

The diagnosis of EZB-MYC DLBCL primarily relies on immunohistochemistry (IHC) analysis, which uses a standard panel of antibodies to detect specific proteins expressed by cancer cells [1]. IHC can help identify the presence of MYC and EZB protein expression in tumor cells.

Molecular Testing

Genetic classification is also essential for disclosing molecular heterogeneity and therapeutic implications in DLBCL, including EZB-MYC subtype [3]. Molecular testing can help identify specific genetic alterations, such as MYC rearrangements, which are present in a significant proportion of EZB-MYC DLBCL cases.

Bone Marrow Biopsy

In some selected circumstances, bone marrow biopsy (BMB) remains an important diagnostic method for DLBCL, including EZB-MYC subtype [6]. BMB can help assess the extent of lymphoma involvement and identify any potential bone marrow involvement.

Other Diagnostic Tests

While not specifically mentioned in the context provided, other diagnostic tests such as flow cytometry, molecular diagnostics (e.g., PCR, FISH), and imaging studies (e.g., PET-CT) may also be used to support the diagnosis of EZB-MYC DLBCL.

References:

[1] by R Ta · 2022 · Cited by 11 — The current diagnosis of DLBCL was primarily accomplished by utilizing immunohistochemistry (IHC) analysis, using a standard panel of antibodies ...

[3] by R Shen · 2023 · Cited by 40 — Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma (DLBCL).

[6] by Y Shi · 2024 — In some selected circumstances, bone marrow biopsy (BMB) remains an important diagnostic method for DLBCL. The clinical manifestation, organ ...

Note: The above answer is based on the information provided in the context and may not be comprehensive or up-to-date. It's always best to consult with a medical professional for accurate diagnosis and treatment.

Treatment Options for EZB-MYC+ Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma that can be aggressive and rapidly progressing. The treatment options for DLBCL, including the EZB-MYC+ subtype, have evolved over time to improve patient outcomes.

Standard Therapy: R-CHOP

The current standard therapy for patients with advanced-stage DLBCL, including those with the EZB-MYC+ subtype, is six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) [2]. This regimen has been shown to be effective in curing more than 60% of patients with DLBCL [3].

Intensified Therapy

However, some patients may not respond adequately to R-CHOP or may experience relapse. In such cases, intensified therapy using a combination of four drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been explored [7]. Additionally, trials have used other regimens, including polatuzumab vedotin, which was granted approval for treatment in several countries based on the results of these studies [8].

Bromodomain Inhibition

Recent research has also focused on bromodomain inhibition as a potential therapeutic strategy for DLBCL. A study published by G Shimkus et al. in 2023 explored the use of bromodomain inhibitors in treating patients with EZB-MYC+ diffuse large B-cell lymphoma [9].

Conclusion

In conclusion, while R-CHOP remains the standard therapy for DLBCL, including the EZB-MYC+ subtype, other treatment options and intensified therapies are being explored to improve patient outcomes. Further research is needed to determine the most effective treatment strategies for this aggressive form of lymphoma.

References:

[1] Not applicable

[2] Sehn LH et al. (2021) [2]

[3] Jan 20, 2022 [3]

[7] Vodicka P et al. (2022) [7]

[8] Ghione P et al. (2020) [8]

[9] Shimkus G et al. (2023) [9]

Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma characterized by the rapid growth and spread of cancerous white blood cells in the body. EZB-MYC-DLBCL, also known as MYC/BCL2 double-positive DLBCL, is a specific subtype of DLBCL that is associated with a poor prognosis.

To determine the differential diagnosis for EZB-MYC-DLBCL, it's essential to consider other types of lymphomas and cancers that may present similarly. Here are some possible differential diagnoses:

• Double-hit lymphoma (DHL): DHL is characterized by the presence of two or more translocations involving MYC, BCL2, or BCL6 genes. Like EZB-MYC-DLBCL, DHL has a poor prognosis and requires aggressive treatment.
• MYC/BCL2 protein double-positive DLBCL: This subtype of DLBCL is characterized by the co-expression of MYC and BCL2 proteins, which can lead to a more aggressive disease course.
• Burkitt lymphoma: Burkitt lymphoma is a type of high-grade B-cell lymphoma that can present with similar clinical features to EZB-MYC-DLBCL. However, it typically involves the translocation of MYC and IGH genes.
• Diffuse large B-cell lymphoma with MYC rearrangement: This subtype of DLBCL is characterized by the presence of a MYC rearrangement, which can lead to overexpression of the MYC protein.

The differential diagnosis for EZB-MYC-DLBCL also includes other types of cancers and lymphomas that may present with similar clinical features. These include:

• Hodgkin lymphoma: Hodgkin lymphoma is a type of lymphoma that can present with similar symptoms to DLBCL, including fever, night sweats, and weight loss.
• T-cell lymphoma: T-cell lymphoma is a type of non-Hodgkin lymphoma that can involve the skin, lymph nodes, or other organs.

To accurately diagnose EZB-MYC-DLBCL, it's essential to perform a thorough clinical evaluation, including imaging studies, laboratory tests, and biopsy. The diagnosis is typically made based on histopathological examination of tissue samples, which may show characteristic features such as:

• Large B cells: EZB-MYC-DLBCL is characterized by the presence of large B cells with irregular nuclei.
• MYC/BCL2 protein expression: Immunohistochemical staining can be used to detect the expression of MYC and BCL2 proteins in tumor cells.

The prognosis for patients with EZB-MYC-DLBCL is generally poor, especially if left untreated. Aggressive treatment strategies, including chemotherapy and targeted therapy, may improve outcomes but require careful consideration of individual patient factors.

References:

• [1] by C Zhang · 2024 · Cited by 11 — For routine diagnosis and prognostication of DLBCL, only MYC, BCL2 and BCL6 translocations are investigated along with international prognostic ...
• [5] by R Schmitz · 2018 · Cited by 2001 — We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2 (based on ...
• [7] by A Künstner · 2022 · Cited by 29 — MYC cytogenetic status correlates with expression and has prognostic significance in patients with MYC/BCL2 protein double-positive diffuse large B-cell ...