Highlights of changes in the International Consensus Classification of mature T-cell and NK-cell neoplasms and histiocytic tumors
| Hydroa vacciniforme lymphoproliferative disorder | This term replaces the previous hydroa vacciniforme-like lymphoproliferative disorder; 2 forms are recognized: classic and systemic. The classic form is indolent, self-limited, and more common in whites. The systemic form is severe and includes fever, lymphadenopathy, and often liver involvement, and it is more common in Asians and Latin Americans. Treatment is similar to that for chronic active Epstein-Barr virus disease. |
| Chronic active Epstein-Barr virus disease | This term replaces chronic active Epstein-Barr virus infection and is restricted to patients who have the T-cell and NK-cell phenotype; B-cell patients are excluded. Mutations in DDX3X and KMT2D indicate the neoplastic nature of the disease. |
| Primarynodal Epstein-Barr virus–positive T-cell/NK-cell lymphoma | Introduced in the 2017 WHO classification as a variant of peripheral T-cell lymphoma, NOS; it is now considered a provisional entity. |
| Type II refractory celiac disease* | Accepted as a precursor of enteropathy-associated T-cell lymphoma and has therefore been added to the classification. |
| Indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract | Considered a definite entity. The name was changed to acknowledge its monoclonal nature. It may have neoplastic-type gene mutations and rearrangements and may progress to more aggressive disease. |
| Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract | Mutational studies provide evidence for the neoplastic origin. The term replaces both NK-cell enteropathy and lymphomatoid gastropathy. |
| Subcutaneous panniculitis-like T-cell lymphomas | Molecular studies have recognized germline HAVCR2 mutations in a subset of patients. |
| Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder | Now considered a lymphoproliferative disorder rather than an overt lymphoma. |
| Follicular helper T-cell lymphoma (TFH lymphoma) | Considered a single entity that encompasses 3 subtypes: angioimmunoblastic-type (angioimmunoblastic T-cell lymphoma), follicular-type, and NOS. |
| ALK-negative anaplastic large cell lymphoma | DUSP22-R ALK anaplastic large cell lymphoma is now defined as a genetic subtype of systemic ALK-negative anaplastic large cell lymphoma. JAK2 rearrangements or coexisting TP63 and DUSP22 rearrangements are rarely seen; understanding their significance requires further study. |
| Breast implant–associated anaplastic large cell lymphoma | Upgraded from a provisional to a definite entity. Use of tumor-node-metastasis staging criteria is recommended to facilitate clinical management. |
| Histiocytic and dendritic cell neoplasms | ALK-positive histiocytosis is accepted as an entity in the classification. A subset of Rosai-Dorfman-Destombes disease is identified as neoplastic based on clonal genetic alterations. |
| Epstein-Barr virus–positive inflammatory follicular dendritic cell/fibroblastic reticular cell tumor | The name of this entity has been changed. “Tumor” is preferred over “sarcoma” because of the indolent nature of these lesions. Heterogeneity in lineage is recognized. |
| Hydroa vacciniforme lymphoproliferative disorder | This term replaces the previous hydroa vacciniforme-like lymphoproliferative disorder; 2 forms are recognized: classic and systemic. The classic form is indolent, self-limited, and more common in whites. The systemic form is severe and includes fever, lymphadenopathy, and often liver involvement, and it is more common in Asians and Latin Americans. Treatment is similar to that for chronic active Epstein-Barr virus disease. |
| Chronic active Epstein-Barr virus disease | This term replaces chronic active Epstein-Barr virus infection and is restricted to patients who have the T-cell and NK-cell phenotype; B-cell patients are excluded. Mutations in DDX3X and KMT2D indicate the neoplastic nature of the disease. |
| Primarynodal Epstein-Barr virus–positive T-cell/NK-cell lymphoma | Introduced in the 2017 WHO classification as a variant of peripheral T-cell lymphoma, NOS; it is now considered a provisional entity. |
| Type II refractory celiac disease* | Accepted as a precursor of enteropathy-associated T-cell lymphoma and has therefore been added to the classification. |
| Indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract | Considered a definite entity. The name was changed to acknowledge its monoclonal nature. It may have neoplastic-type gene mutations and rearrangements and may progress to more aggressive disease. |
| Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract | Mutational studies provide evidence for the neoplastic origin. The term replaces both NK-cell enteropathy and lymphomatoid gastropathy. |
| Subcutaneous panniculitis-like T-cell lymphomas | Molecular studies have recognized germline HAVCR2 mutations in a subset of patients. |
| Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder | Now considered a lymphoproliferative disorder rather than an overt lymphoma. |
| Follicular helper T-cell lymphoma (TFH lymphoma) | Considered a single entity that encompasses 3 subtypes: angioimmunoblastic-type (angioimmunoblastic T-cell lymphoma), follicular-type, and NOS. |
| ALK-negative anaplastic large cell lymphoma | DUSP22-R ALK anaplastic large cell lymphoma is now defined as a genetic subtype of systemic ALK-negative anaplastic large cell lymphoma. JAK2 rearrangements or coexisting TP63 and DUSP22 rearrangements are rarely seen; understanding their significance requires further study. |
| Breast implant–associated anaplastic large cell lymphoma | Upgraded from a provisional to a definite entity. Use of tumor-node-metastasis staging criteria is recommended to facilitate clinical management. |
| Histiocytic and dendritic cell neoplasms | ALK-positive histiocytosis is accepted as an entity in the classification. A subset of Rosai-Dorfman-Destombes disease is identified as neoplastic based on clonal genetic alterations. |
| Epstein-Barr virus–positive inflammatory follicular dendritic cell/fibroblastic reticular cell tumor | The name of this entity has been changed. “Tumor” is preferred over “sarcoma” because of the indolent nature of these lesions. Heterogeneity in lineage is recognized. |
Italic font indicates provisional tumor entity.