Table 1.

Salient Clinicopathological and Biological Features of The Major Types of Mature T/NK Cell Lymphomas.

Entity	Pathological Features	Clinical Features
T-cell Prolymphocytic Leukemia (t-PLL)	Small to medium size lymphocytes, non-granular basophilic cytoplasm, usually CD4-negative, Inv(14)(q11;q32) with TCL-1 gene, trisomy 8, del(11)(q22.3-23.1) with ATM gene	Hepatosplenomegaly, generalized lymphadenopathy, anemia, thrombocytopenia. Progressive clinical course.
T-cell Large Granular Lymphocyte (LGL) Leukemia	Circulating LGL, may have atypia or immaturity; usually CD8-positive with variable expression of CD57 and CD16.	Lymphocytosis and neutropenia, often asymptomatic, rheumatoid arthritis, autoantibodies; bone marrow involved, usually indolent, non-progressive
NK-cell Leukemia	Circulating LGL, with atypia and immaturity, typically sCD3-negative, CD56-positive, TIA/Granzyme/Perforin-positive, often EBV-positive.	More prevalent among Asians and younger adults; fever, hepatosplenomegaly, variable lymphoadenopathy, circulating atypical lymphocytes, highly aggressive, multiorgan failure.
Adult T-cell Leukemia/Lymphoma (ATLL)	Histology variable; usually CD7-negative, CD4/CD25 positive, clonally integrated HTLV-I.	Endemic in Japan, Caribbean, Brazil; four clinical types: acute leukemic, lymphomatous, chronic and smoldering. Frequent cutaneous lesions, hypercalcemia, lytic bone lesions; rapid progressive course.
Angioimmunoblastic T-cell Lymphoma (AITL)	Polymorphic T-cells, often clear cells, arborizing vessels, eosinophils and plasma cells, increased FDC outside of the GC; usually CD4-positive but often CD8-positive cells present, typically CD10-positive; many EBV-positive B-cells, often oligoclonal or monoclonal; trisomy 3, 8, X with frequent unrelated clones.	Lymphadenopathy, hepatosplenomegaly, advanced stage, B-symptoms, skin rash, hypergammaglobulinemia, Coombs-positive hemolytic anemia; prognosis poor. Risk of developing B-cell lymphomas.
Peripheral T-cell Lymphoma NOS (PTCL)	Histology variable. Usually CD4-positive; extranodal forms often TIA/Granzyme/Perforin-positive, complex chromosomal aberrations.	Wastebasket category; clinical course variable but generally aggressive; advanced stage; lymphadenopathy, cure rate low (25%).
Anaplastic Large Cell Lymphoma, CD30-positive, T/Null-cell, Systemic (CD30+ ALCL)	Large cells with eccentric nuclei and Golgi-like inclusions, wreath-like nuclei, abundant cytoplasm, not all tumor cells are very large or pleomorphic, some are small and monomorphic (variants); common sinusoidal infiltration; CD30-positive, EMA-positive, often CD45-negative, CD15-negative, T-cell markers variable, often TIA/Granzyme/Perforin-positive; t(2;5)-positive subset with overexpression of ALK (ALK-1) has best prognosis.	Used to be called Ki1-lymphoma; Ki1 antigen now known as CD30; lymphadenopathy, extranodal sites (skin), bimodal age distribution, advanced disease, B-symptoms, aggressive course; responds well to therapy and cure rate high (75-80%) for the ALK-1-positive subset (younger patients).
Mycosis Fungoides (MF)	Epidermotropic CD4-positive, CLA-positive, CD7-negative, CD26-negative cells, cerebriform nucleus	Adults, multiple skin lesions in patch, plaque and tumor stage; indolent but progressive.
Sezary Syndrome (SS)	Circulating small lymphoid cells with cerebriform nucleus, ocasionally large cells; CD4-positive, CD7-negative, CD26-negative.	Adults, erythroderma, often generalized lymphadenopathy, blood and bone marrow involvement; unfavorable prognosis (about 3 years MS).
Primary Cutaneous CD30-positive T/Null-cell lymphomas	Large CD30-positive lymphoid cells, variable T-cell markers, usually anaplastic features but may be typical large cell; cytology has no prognostic significance; lack t(2;5) and is ALK-1-negative.	Adults, usually solitary lesions, nodular, may be ulcerated; no systemic disease on staging, highly favorable prognosis, progression to systemic disease rare; need to distinguish from LyP.
Subcutaneous, Panniculitis-like T-cell Lymphoma	Subcutaneous lace-like lymphoid infiltrate with predominant small cells, rimming around fat cells common; usually CD8-positive, TIA/Granzyme/Perforin-positive; most cases are derived from αβ cells, some TCR; EBV negative	Subcutaneous nodules especially in the extremities, systemic/nodal dissemination rare, clinically variable, may have chronic course but can be aggressive, particularly when hemophagocytic syndrome develops.
NK/T-cell Lymphoma, Nasal and Nasal-type	Variable cytology, angioinvasive and angiodestructive (originally called angiocentric lymphomas), common necrosis and apoptosis; typically CD2-positive, TIA/Granzyme/Perforin-positive, sCD3-negative, CD5-negative, CD56-positive; almost always EBV-positive; TCR not rearranged.	More common in Asia, Central (Mexico), and South America; mostly adults, nodal involvement rare. Nasal form presents with destructive lesion in the nose, sinuses, upper palate; usually early stage but aggressive and prognosis poor. Nasal-type involves the skin, soft tissues, GI tract, and testis.
T-cell Lymphoma, α/β vs γ/δ -type, hepatosplenic and non-hepatosplenic	Monotonous, medium-size cells infiltration in liver, spleen red-pulp, marrow, sinusoidal pattern; typically CD3-positive, CD56 variable, TIA-positive, Granzyme/Perforin variable; mostly TCRδ1+, occasionally α/β type.	Young adults, male predominance, marked hepatosplenomegaly, no lymphoadenopathy, bone marrow usually involved, occasional leukemic involvement; aggressive course; relapse the rule, non curable.
Enteropathy-associated T-cell lymphoma (EATL)	Broad cytological spectrum, epitheliotropism common, ulceration common, adjacent mucosa shows features of enteropathy, with villous atrophy, increased intraepithelial small lymphocytes, CD103-positive (integrin); typically TIA/Granzyme/Perforin-positive	Most patients have adult-onset celiac disease (CD) or are diagnosed with CD at the time of EATL presentation; abdominal pain, diarrhea, often small bowel perforation; prognosis poor.