Highlights of changes in the International Consensus Classification of aggressive B-cell lymphomas
| Diffuse large B-cell lymphoma, NOS | The cell-of-origin designation in diffuse large B-cell lymphoma, NOS should be maintained, but it is considered insufficient to fully capture the biological complexity of these tumors. Molecular profiling studies have identified 5 to 7 new functional genetic subgroups of diffuse large B-cell lymphoma that may provide more precise patient stratification in the future. |
| Large B-cell lymphoma with 11q aberration | This term replaces Burkitt-like lymphoma with 11q aberration, and the entity is still considered provisional. Molecular studies indicate that it is closer to diffuse large B-cell lymphoma than to Burkitt lymphoma. |
| Nodular lymphocyte predominant B-cell lymphoma | This term replaces nodular lymphocyte-predominant Hodgkin lymphoma, recognizing major biological and clinical differences from classic Hodgkin lymphoma. Close relationship to T-cell/histiocyte-rich large B-cell lymphoma is emphasized. |
| Primary diffuse large B-cell lymphoma of the testis | Now recognized as a specific entity closely related to primary diffuse large B-cell lymphoma of the central nervous system. Most patients share molecular and cytogenetic features of the MCD/C5131-134 subgroup of diffuse large B-cell lymphoma, similar to some other primary extranodal large B-cell lymphomas of the activated B-cell–like subtype. |
| HHV-8 and Epstein-Barr virus–negative primary effusion-based lymphoma | Recognized as a provisional entity frequently associated with fluid overload. Patients who conform to other well-defined lymphomas should not be included. |
| Epstein-Barr virus–positive mucocutaneous ulcer | Now recognized as a definite entity, and diagnostic criteria have been refined. |
| Epstein-Barr virus–positive diffuse large B-cell lymphoma, NOS | Tumors are morphologically heterogeneous, but the distinction between polymorphic and monomorphic does not have prognostic significance in the elderly. The T-cell/histiocyte-rich large B-cell lymphoma–like pattern, more common in younger patients (younger than age 45 years), is distinct from what has been termed polymorphic. |
| Lymphomatoid granulomatosis | Generally diagnosed in the absence of known immunodeficiency and, per definition, requires pulmonary involvement. Isolated central nervous system or gastrointestinal tract involvement by an Epstein-Barr virus–positive lesion resembling lymphomatoid granulomatosis is usually associated with immunodeficiency and Epstein-Barr virus latency III. These patients should be classified as Epstein-Barr virus–positive B-cell lymphoproliferative disorder or Epstein-Barr virus–positive diffuse large B-cell lymphoma, NOS and not as lymphomatoid granulomatosis. |
| Epstein-Barr virus–positive polymorphic B-cell lymphoproliferative disorder, NOS | A term used for B-cell proliferations with or without known immunodeficiency when the morphologic changes do not fulfill the criteria of a well-defined Epstein-Barr virus–positive lymphoma. In patients with focal Epstein-Barr virus–positive B cells and preserved lymph node architecture, the term “EBV reactivation” is preferred. |
| Primary effusion lymphoma and extracavitary primary effusion lymphoma | In patients with Epstein-Barr virus–negative extracavitary lymphoma, a diagnosis of HHV-8–positive diffuse large B-cell lymphoma, NOS is preferred, particularly if the tumor is IgM lambda positive. |
| Burkitt lymphoma | Neoplasms with a precursor B-cell phenotype and MYC rearrangement will be called B-lymphoblastic leukemia/lymphoma with MYC rearrangement rather than Burkitt leukemia or lymphoma. |
| High-grade B-cell lymphoma with MYC and BCL2 rearrangement | The category is redefined to exclude patients with only MYC and BCL6 rearrangements. Some neoplasms may express terminal deoxynucleotide transferase without being considered a B-lymphoblastic neoplasm. |
| High-grade B-cell lymphoma with MYC and BCL6 rearrangements | With the change in the definition of high-grade B-cell lymphoma with MYC and BCL2 rearrangements, this provisional category was added. |
| Mediastinal gray-zone lymphoma | Criteria for distinction from classic Hodgkin lymphoma have been refined. Clinical and genomic data indicate that most non-mediastinal gray-zone lymphomas are distinct from mediastinal gray-zone lymphoma; thus, patients with extra-mediastinal disease should be diagnosed as having diffuse large B-cell lymphoma, NOS. |
| Diffuse large B-cell lymphoma, NOS | The cell-of-origin designation in diffuse large B-cell lymphoma, NOS should be maintained, but it is considered insufficient to fully capture the biological complexity of these tumors. Molecular profiling studies have identified 5 to 7 new functional genetic subgroups of diffuse large B-cell lymphoma that may provide more precise patient stratification in the future. |
| Large B-cell lymphoma with 11q aberration | This term replaces Burkitt-like lymphoma with 11q aberration, and the entity is still considered provisional. Molecular studies indicate that it is closer to diffuse large B-cell lymphoma than to Burkitt lymphoma. |
| Nodular lymphocyte predominant B-cell lymphoma | This term replaces nodular lymphocyte-predominant Hodgkin lymphoma, recognizing major biological and clinical differences from classic Hodgkin lymphoma. Close relationship to T-cell/histiocyte-rich large B-cell lymphoma is emphasized. |
| Primary diffuse large B-cell lymphoma of the testis | Now recognized as a specific entity closely related to primary diffuse large B-cell lymphoma of the central nervous system. Most patients share molecular and cytogenetic features of the MCD/C5131-134 subgroup of diffuse large B-cell lymphoma, similar to some other primary extranodal large B-cell lymphomas of the activated B-cell–like subtype. |
| HHV-8 and Epstein-Barr virus–negative primary effusion-based lymphoma | Recognized as a provisional entity frequently associated with fluid overload. Patients who conform to other well-defined lymphomas should not be included. |
| Epstein-Barr virus–positive mucocutaneous ulcer | Now recognized as a definite entity, and diagnostic criteria have been refined. |
| Epstein-Barr virus–positive diffuse large B-cell lymphoma, NOS | Tumors are morphologically heterogeneous, but the distinction between polymorphic and monomorphic does not have prognostic significance in the elderly. The T-cell/histiocyte-rich large B-cell lymphoma–like pattern, more common in younger patients (younger than age 45 years), is distinct from what has been termed polymorphic. |
| Lymphomatoid granulomatosis | Generally diagnosed in the absence of known immunodeficiency and, per definition, requires pulmonary involvement. Isolated central nervous system or gastrointestinal tract involvement by an Epstein-Barr virus–positive lesion resembling lymphomatoid granulomatosis is usually associated with immunodeficiency and Epstein-Barr virus latency III. These patients should be classified as Epstein-Barr virus–positive B-cell lymphoproliferative disorder or Epstein-Barr virus–positive diffuse large B-cell lymphoma, NOS and not as lymphomatoid granulomatosis. |
| Epstein-Barr virus–positive polymorphic B-cell lymphoproliferative disorder, NOS | A term used for B-cell proliferations with or without known immunodeficiency when the morphologic changes do not fulfill the criteria of a well-defined Epstein-Barr virus–positive lymphoma. In patients with focal Epstein-Barr virus–positive B cells and preserved lymph node architecture, the term “EBV reactivation” is preferred. |
| Primary effusion lymphoma and extracavitary primary effusion lymphoma | In patients with Epstein-Barr virus–negative extracavitary lymphoma, a diagnosis of HHV-8–positive diffuse large B-cell lymphoma, NOS is preferred, particularly if the tumor is IgM lambda positive. |
| Burkitt lymphoma | Neoplasms with a precursor B-cell phenotype and MYC rearrangement will be called B-lymphoblastic leukemia/lymphoma with MYC rearrangement rather than Burkitt leukemia or lymphoma. |
| High-grade B-cell lymphoma with MYC and BCL2 rearrangement | The category is redefined to exclude patients with only MYC and BCL6 rearrangements. Some neoplasms may express terminal deoxynucleotide transferase without being considered a B-lymphoblastic neoplasm. |
| High-grade B-cell lymphoma with MYC and BCL6 rearrangements | With the change in the definition of high-grade B-cell lymphoma with MYC and BCL2 rearrangements, this provisional category was added. |
| Mediastinal gray-zone lymphoma | Criteria for distinction from classic Hodgkin lymphoma have been refined. Clinical and genomic data indicate that most non-mediastinal gray-zone lymphomas are distinct from mediastinal gray-zone lymphoma; thus, patients with extra-mediastinal disease should be diagnosed as having diffuse large B-cell lymphoma, NOS. |
Italic font indicates provisional tumor entities.