Peripheral T-Cell Lymphoma (PTCL)

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of aggressive non-Hodgkin lymphomas derived from post-thymic mature T-cells and natural killer (NK) cells, comprising approximately 10-15% of all non-Hodgkin lymphomas in Western populations and 20-25% in Asian populations. The 2017/2022 WHO classification recognizes more than 30 distinct PTCL entities grouped by primary clinical presentation: nodal-predominant (PTCL-NOS, AITL/follicular helper T-cell origin lymphomas, ALCL), extranodal (extranodal NK/T-cell lymphoma nasal type, hepatosplenic T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, breast implant-associated ALCL), leukemic (T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma), and cutaneous (mycosis fungoides, Sezary syndrome, primary cutaneous CD30+ disorders, primary cutaneous gamma-delta T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma).

Epidemiology: incidence approximately 1.5-2 per 100,000 per year, increasing globally, slight male predominance, median age 60-65 years for systemic types. Geographic and ethnic variations: ATLL endemic in HTLV-1 areas (Japan, Caribbean, parts of Africa and South America), extranodal NK/T-cell lymphoma higher in East Asia and Latin America, EATL associated with celiac disease in Northern Europe. Clinical presentation: B-symptoms (60-75%), advanced stage III/IV disease (75-85%), extranodal involvement (skin, bone marrow, liver, spleen, gastrointestinal), elevated LDH, hemophagocytic lymphohistiocytosis (especially in NK/T-cell and ATLL), hypereosinophilia, polyclonal hypergammaglobulinemia (AITL), autoimmune phenomena (AITL — Coombs+ hemolytic anemia, ITP). PTCL-NOS is a diagnosis of exclusion after ruling out other specific entities.

Diagnosis requires excisional or core needle biopsy with comprehensive immunophenotyping (CD2, CD3, CD4, CD5, CD7, CD8, CD30, CD56, CD25, CD20, BCL2, BCL6, PD1, ICOS, CXCL13, EBER), TCR gene rearrangement (clonality), specific molecular tests (ALK, DUSP22, TP63 for ALCL; RHOA G17V, IDH2 R172, TET2, DNMT3A for AITL; STAT3, STAT5B for LGL leukemia; HTLV-1 serology for ATLL). Staging: PET-CT, CT chest/abdomen/pelvis, bone marrow biopsy, CSF analysis if indicated, GI endoscopy if EATL suspected. Treatment: first-line CHOP-based regimens (CHOEP for younger fit patients) for 6 cycles, with consolidation autologous stem cell transplantation in first complete remission for transplant-eligible patients (improves PFS); BV-CHP (brentuximab vedotin + CHP) for CD30+ PTCL (ECHELON-2); SMILE or asparaginase-based regimens for extranodal NK/T-cell lymphoma; involved-site radiation for early-stage extranodal NK/T-cell lymphoma nasal type. Relapsed/refractory disease: brentuximab vedotin, romidepsin (HDAC inhibitor), belinostat (HDAC inhibitor), pralatrexate (antifolate), bendamustine, chidamide (China), allogeneic stem cell transplantation for fit patients. Novel therapies in development: PI3K inhibitors (duvelisib), CAR-T cell therapy, anti-CD30 ADCs, EZH2 inhibitors (tazemetostat), JAK inhibitors. Prognosis varies by subtype: 5-year overall survival 30-40% for PTCL-NOS, 30-40% for AITL, 70-80% for ALK+ ALCL, 30-50% for ALK- ALCL, 40-50% for nasal NK/T-cell lymphoma.