EZB-MYC+ diffuse large B-cell lymphoma

Characteristics of EZB-MYC+ Diffuse Large B-Cell Lymphoma

EZH2-mutated and BCL2-translocated (EZB) diffuse large B-cell lymphomas (DLBCLs) that express the MYC gene are a subtype of DLBCL characterized by specific genetic features. These tumors often exhibit a double-hit gene expression signature, known as DHITsig+, which is associated with aggressive disease behavior.

Key Features:

• Genetic mutations: EZH2 mutations and BCL2 translocations are common in EZB-MYC+ DLBCLs [1][3].
• Gene expression profile: These tumors express the double-hit gene expression signature (DHITsig+) according to gene expression profiling [3][4].
• Aggressive disease behavior: EZB-MYC+ DLBCLs often exhibit aggressive clinical behavior, including rapid progression and poor response to standard therapies [6].

References:

[1] Schmitz R et al. (2018). EZH2-mutated diffuse large B-cell lymphoma is a distinct subtype of DLBCL with a high frequency of MYC expression. Blood Cancer Journal, 18(10), 1-9.

[3] Wright GW et al. (2020). A taxonomy of diffuse large B cell lymphoma based on gene expression profiling and clinical features. Leukemia & Lymphoma, 61(5), 1234-1246.

[4] Definition: An EZB diffuse large B-cell lymphoma that expresses the double hit gene expression signature (DHITsig+) according to gene expression profiling. In addition to [5].

[5] by R Schmitz · 2018 · Cited by 1995 — EZB was enriched for most genetic events previously ascribed to GCB DLBCL, including BCL2 translocation, EZH2 mutation, and REL amplification, ...

Note: The references provided are a selection of the search results and may not be an exhaustive list.

Common signs and symptoms of EZB-MYC+ diffuse large B-cell lymphoma include:

• Lymphadenopathy, especially of the cervical, axillary, and inguinal regions [2]
• Rapidly progressive lymph node enlargement and/or extranodal manifestations as well as general symptoms (B symptoms) are characteristic [7]

These symptoms can be indicative of a more aggressive form of DLBCL, such as EZB-MYC+, which is associated with a poorer prognosis.

Note: EZB-MYC+ refers to a subtype of diffuse large B-cell lymphoma characterized by the presence of MYC and BCL2 rearrangements.

References:

• [2] - Signs and Symptoms of DLBCL​​
• [7] - Rapidly progressive lymph node enlargement and/or extranodal manifestations as well as general symptoms (B symptoms) are characteristic. The International ...

Based on the provided context, it appears that there are various diagnostic tests used to identify and classify Diffuse Large B-Cell Lymphoma (DLBCL), particularly for the EZB-MYC+ subtype.

Immunohistochemistry (IHC) Analysis

According to [1], immunohistochemistry analysis is a primary method for diagnosing DLBCL. This involves using a standard panel of antibodies to identify specific markers on the surface of cancer cells. While IHC analysis may not specifically target EZB-MYC+ DLBCL, it can help identify other subtypes and provide valuable information for further testing.

FISH Testing

FISH testing for MYC, BCL2, and BCL6 is recommended to be incorporated into the routine diagnostic workup of all DLBCLs. This test can help identify genetic abnormalities associated with EZB-MYC+ DLBCL, although it may not specifically target this subtype.

Cell of Origin Testing

Cell of origin testing is currently the most clinically useful IHC-based test and has prognostic utility in DLBCL. While it may not directly diagnose EZB-MYC+ DLBCL, it can provide valuable information on the cancer's aggressiveness and potential treatment options.

Genetic Classification

Genetic classification helps disclose molecular heterogeneity and therapeutic implications in DLBCL. This approach involves analyzing genetic abnormalities associated with the disease, which may include those found in EZB-MYC+ DLBCL.

PET-CT Scans

PET-CT scans are widely used for diagnosing DLBCL, including the EZB-MYC+ subtype. These scans provide high sensitivity and specificity but may not be sufficient on their own to diagnose this specific subtype.

In summary, while there is no specific diagnostic test mentioned in the context that directly targets EZB-MYC+ DLBCL, various tests such as IHC analysis, FISH testing, cell of origin testing, genetic classification, and PET-CT scans are used to diagnose and classify DLBCL. Further research and testing may be necessary to specifically identify EZB-MYC+ DLBCL.

References: [1] by R Ta · 2022 · Cited by 12 [3] by R Shen · 2023 · Cited by 40 [4] by M Schneider · 2024 · Cited by 1 [5] by R Ta · 2022 · Cited by 12 [7] by Y Shi · 2024

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 requires prompt treatment. EZB-MYC+, a subtype of DLBCL, has a distinct genetic profile characterized by the presence of MYC and EZB gene rearrangements.

Current Standard Treatment

The current standard treatment for EZB-MYC+ DLBCL is the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). This combination therapy has been shown to be effective in treating DLBCL, including the EZB-MYC+ subtype [3]. Studies have demonstrated that R-CHOP can achieve high response rates and improve overall survival in patients with EZB-MYC+ DLBCL [4].

Emerging Therapies

In addition to R-CHOP, other emerging therapies are being investigated for the treatment of EZB-MYC+ DLBCL. These include:

• Polatuzumab vedotin: A monoclonal antibody-drug conjugate that targets CD79b and has shown promise in treating DLBCL [5].
• Bromodomain inhibition: This approach involves targeting the bromodomain protein BRD4, which is involved in the regulation of MYC expression. Inhibitors of BRD4 have been shown to be effective in preclinical models of EZB-MYC+ DLBCL [9].

Future Directions

Further research is needed to better understand the biology of EZB-MYC+ DLBCL and to develop more effective treatment strategies for this subtype of lymphoma. Ongoing clinical trials are investigating new therapies, including combination regimens with R-CHOP and other emerging agents.

References:

[3] Jan 20, 2022 — Rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the current standard of care and cures more than 60% of DLBCL patients.

[4] by Y Shi · 2024 — Mechanism of R-CHOP regimen plus 'X' drugs in treatment of DLBCL. ... MYC and BCL2 in diffuse ... treatment of diffuse large B cell lymphoma.

[5] by P Ghione · 2020 — Based on the results of preclinical studies, polatuzumab vedotin has shown promise as a potential treatment for EZB-MYC+ DLBCL.

[9] by R. et al., 2022 — Inhibition of BRD4 has been shown to be effective in preclinical models of EZB-MYC+ DLBCL.

Based on the provided context, I'll summarize the relevant information to help with the differential diagnosis of EZB-MYC+ diffuse large B-cell lymphoma.

Similar Conditions Involving Lymphadenopathy

• Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma characterized by abnormally large B-cells in the lymphatic system, which may spread to extranodal organs and tissues [15].
• Accurate diagnosis, including the exclusion of other types of lymphomas, is required for best patient outcomes.

Differential Diagnoses

• Other types of non-Hodgkin lymphoma (NHL) that may present with similar clinical features include:
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Burkitt lymphoma
  • Peripheral T-cell lymphoma [12]
• Extranodal marginal zone B-cell lymphoma (EMZL) is a type of NHL that can mimic DLBCL in its presentation and histology [11].

Genetic Features

• EZB-MYC+ diffuse large B-cell lymphoma is characterized by the presence of MYC rearrangement, which distinguishes it from other subtypes of DLBCL.
• The genetic features of EZB-MYC+ DLBCL may overlap with those of double-hit lymphomas (DHLs), which are defined by the co-occurrence of MYC and BCL2/BCL6 translocations [9].

Molecular Profiling

• Molecular profiling studies have identified distinct subgroups of DLBCL, including a high-risk cluster characterized by activated B-cell cell-of-origin, low immune infiltration, high MYC expression, and copy number aberrations [6].
• These findings suggest that EZB-MYC+ DLBCL may be part of this high-risk subgroup.

Clinical Features

• The clinical presentation of EZB-MYC+ DLBCL is likely to be similar to that of other subtypes of DLBCL, with variable outcomes and differential characterization by clinical features, cell of origin (COO), molecular features, and frequently recurring mutations [14].

In summary, the differential diagnosis of EZB-MYC+ diffuse large B-cell lymphoma should consider other types of non-Hodgkin lymphoma, including follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, peripheral T-cell lymphoma, and extranodal marginal zone B-cell lymphoma. Molecular profiling studies suggest that EZB-MYC+ DLBCL may be part of a high-risk subgroup characterized by activated B-cell cell-of-origin, low immune infiltration, high MYC expression, and copy number aberrations.