Main epidemiologic characteristics, disease distribution, and prognosis of T- and NK-cell neoplasms
| ICC-20224 . | WHO5-20225 . | Epidemiology . | Sites of involvement . | Prognosis . |
|---|---|---|---|---|
| Leukemic diseases | ||||
| T-lymphoblastic leukemia/lymphoma | T-lymphoblastic leukemia/lymphoma | 15% of childhood ALL and 25% of adult ALL Adolescents and adults M > F | Mediastinum, cervical lymph nodes, bone marrow, and blood | Favorable in children, intermediate in adults |
| T-cell prolymphocytic leukemia | T-prolymphocytic leukemia | 2% of mature leukemias Older adults, younger adults with AT or NBS, M > F | Peripheral blood and bone marrow, spleen, lymph nodes | Very poor |
| Sezary syndrome | Sezary syndrome | Rare leukemia associated with skin involvement accounting for ∼5% of cutaneous T-cell lymphomas Older adults, M > F | Blood, bone marrow, skin, lymph nodes | Poor |
| Adult T-cell leukemia/lymphoma | Adult T-cell leukemia/lymphoma | Affects ∼2.5% HTLV-1 carriers Endemic in south-western Japan, the Caribbean Basin, and parts of central Africa Various clinical presentations (acute, lymphomatous, chronic, and smoldering) Adults, M > F | Blood, lymph nodes, skin, lung, liver, gastrointestinal tract, and CNS | Very poor in lymphomatous and acute types, poor to intermediate in chronic and smoldering subtypes |
| Aggressive NK-cell leukemia | Aggressive NK-cell leukemia | Very rare Most cases reported in Asia, occasional cases in White people or African people Young to middle-aged adults, M = F | Bone marrow, blood, liver, spleen, lymph nodes, any other organ | Very poor |
| T-cell large granular lymphocytic leukemia | T- large granular lymphocytic leukemia | T-cell and NK-cell types account for 2%-5% of chronic (mature) leukemias Association with rheumatoid arthritis, autoimmune disorders, and other hematologic neoplasms Older adults, M = F | Peripheral blood and bone marrow, spleen, and liver | Favorable |
| Chronic lymphoproliferative disorder of NK cells | NK- large granular lymphocytic leukemia | |||
| Nodal lymphomas | ||||
| Anaplastic large cell lymphoma, ALK+ | ALK+ anaplastic large cell lymphoma | Accounts for 16%, 6%, and 3% of PTCLs in North America, Europe, and Asia, respectively Children and young adults, M > F | Lymph nodes, mediastinum, spleen, bone, skin | Favorable |
| Anaplastic large cell lymphoma, ALK− | ALK− anaplastic large cell lymphoma | Accounts for 8%-9% of PTCLs in North America and Europe, and 3% in Asia Adults and elderly, M>F | Peripheral lymph nodes or less commonly (20%) skin, lung, liver, gastrointestinal tract | Intermediate |
| Follicular helper T-cell lymphoma, including 3 subtypes: angioimmunoblastic, follicular, and NOS | Nodal T follicular helper cell lymphoma (nTFHL), angioimmunoblastic type nTFHL, follicular type nTFHL, NOS | Most common nodal PTCL, representing 35%-40%, 27%, and 25% of PTCLs in Europe, North America, and Asia, respectively More common in elderly adults, can occur at any age, very rare in children, M > F | Lymph nodes, spleen, bone marrow, skin, Waldeyer’s ring | Poor |
| Primary nodal EBV+ T-cell/NK-cell lymphoma | EBV+ nodal T- and NK-cell lymphoma | Very rare, more frequent in Asia than in Western countries Association with HIV and other immunodeficiency conditions Adults and elderly, M > F | Lymph nodes, liver and spleen, bone marrow, no nasal involvement | Very poor |
| Peripheral T-cell lymphoma, NOS | Peripheral T-cell lymphoma, NOS | Second most common nodal PTCL, representing 26%-27% of PTCL in North America and Europe, and 20% in Asia Adults and elderly adults, very rare in children, M>F | Lymph nodes, spleen, any organ, leukemic dissemination rare | Poor |
| Extranodal lymphomas and lymphoproliferative disorders | ||||
| Extranodal NK/Tcell lymphoma, nasal type | Extranodal NK/T-cell lymphoma | Most common extranodal noncutaneous PTCL, accounting for 10%, 6%, and 28% of PTCLs in North America, Europe, and Asia, respectively; also frequent in Latin America Adults, M > F | Nasal region more commonly than extranasal sites (skin, gastrointestinal tract, lung, testis, central nervous system), secondary lymph node involvement can occur | Intermediate to poor according to staging |
| Enteropathy-associated T-cell lymphoma | Enteropathy-associated T-cell lymphoma | Accounts for <2% of PTCLs Most prevalent in Northern Europe, followed by North America, very rare in Asia Adults and elderly adults, M > F | Small intestine, colon, stomach, mesenteric LN, rarely extraintestinal localizations (skin, spleen, central nervous system, lung, etc) | Very poor |
| Type II refractory celiac disease | Not listed | Type II refractory celiac disease develops in 1% of individuals with celiac disease Adults and elderly adults, M > F | Small intestine, occasionally peripheral blood, distant organs | Poor |
| Monomorphic epitheliotropic intestinal T-cell lymphoma | Monomorphic epitheliotropic intestinal T-cell lymphoma | Accounts for <2% of PTCLs Most common in Asia, but seen worldwide Adults and elderly adults M = F | Small intestine, colon, stomach, mesenteric LN, extraintestinal dissemination | Very poor |
| Intestinal T-cell lymphoma, NOS | Intestinal T-cell lymphoma, NOS | Very rare Adults and elderly adults M > F | Small intestine, colon | Very poor |
| Indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract | Indolent T-cell lymphoma of the gastrointestinal tract | Very rare Adults, M > F | Gastrointestinal tract, small intestine and colon more commonly than stomach and duodenum | Favorable |
| Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract | Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract | Very rare First described in Asia, also reported in North America and Europe Older adults, rarely young adults, F > M | Gastrointestinal tract, stomach and duodenum more commonly than small intestine and colon | Favorable |
| Hepatosplenic T-cell lymphoma | Hepatosplenic T-cell lymphoma | 1%-2% of PTCLs Adolescents and young adults, M > F | Spleen, liver, bone marrow, blood | Very poor |
| Breast implant-associated anaplastic large cell lymphoma | Breast implant-associated anaplastic large cell lymphoma | Rare, occurs in 1/1000 to 1/30 000 individuals with textured breast implants Adults, F > M | Breast implant capsule or pericapsular fluid, regional lymph nodes | Favorable |
| Cutaneous lymphomas and lymphoproliferative disorders | ||||
| Mycosis fungoides | Mycosis fungoides | Most common primary cutaneous lymphoma (CTCL∗) accounting for ≥65% CTCLs Individuals of any age but usually middle-aged to older adults, M > F except in Black populations | Unique or multiple erythematous skin lesions (plaques, patches, or nodules), with possible dissemination to lymph nodes or other sites | Favorable to poor depending on staging; large cell transformation associated with poor prognosis |
| Lymphomatoid papulosis | Lymphomatoid papulosis | Lymphoproliferative disorder representing ∼9% of CTCL Adults or children, M > F | Multiple skin papules (trunk, extremities), may also occur in head and neck mucosa | Favorable |
| Primary cutaneous anaplastic large cell lymphoma | Primary cutaneous anaplastic large cell lymphoma | Second most cutaneous lymphoma, accounting for 7% of cases Usually older adults but can occur in children, M > F | Single cutaneous nodule or papule, often ulcerated, with no predilection site, or mucosae | Favorable |
| Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder | Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder | Accounts for 6%-8% of CTCLs Adults, M = F | Single cutaneous nodule or papule, most common in head and neck | Favorable |
| Subcutaneous panniculitis-like T-cell lymphoma | Subcutaneous panniculitis-like T-cell lymphoma | Rare (<1% of all lymphomas) More common in Asia than in Western countries Young adults and children, F > M | Subcutaneous nodules or plaques in extremities and trunk | Favorable |
| Primary cutaneous gamma-delta T-cell lymphoma | Primary cutaneous gamma-delta T-cell lymphoma | Very rare, <1% of CTCLs Adults and elderly adults, rarely children, M = F | Skin (plaques, nodules, or tumors) | Very poor |
| Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder | Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder | Very rare, <1% of CTCLs Adults or rarely children, M > F | Skin (papule, nodule, or plaque) of acral sites (ear, nose, hands, and feet) | Favorable |
| Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma | Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma | Very rare, <1% of CTCLs Adults or any age, M > F | Skin with predilection for acral sites, localized or generalized lesions | Very poor |
| Not listed | Primary cutaneous peripheral T-cell lymphoma, NOS | Unknown | Multiple or less commonly single skin tumors or papules | Unknown |
| EBV-associated lymphoproliferative disorders and lymphomas of childhood | ||||
| Hydroa vacciniforme lymphoproliferative disorder, classic type and systemic type | Hydroa vacciniforme lymphoproliferative disorder | Very rare The classic type affects White populations, the systemic type is seen in Asia and Latin America Children and adolescents, M > F | Classic type: skin Systemic type: skin, lymph nodes, liver, spleen, lung | Favorable (classic type), intermediate to poor (systemic type) |
| Severe mosquito bite allergy | Severe mosquito bite allergy | Very rare Japan and other Asian countries, Latin America Children and adolescents, M = F | Skin, can progress to systemic disease | Intermediate |
| Chronic active EBV disease, systemic (T-cell and NK-cell phenotype) | Systemic chronic active EBV disease | Asia and Latin America, rare in Western countries Children to young adults, rarely adults, M = F | Lymph node, bone marrow and any nonhematopoietic organ | Intermediate to poor |
| Systemic EBV+ T-cell lymphoma of childhood | Systemic EBV+ T-cell lymphoma of childhood | Very rare More common in Asia than in Causasian populations Children to young adults, M = F | Spleen and liver, bone marrow, lymph nodes, skin, and lungs | Very poor |
| ICC-20224 . | WHO5-20225 . | Epidemiology . | Sites of involvement . | Prognosis . |
|---|---|---|---|---|
| Leukemic diseases | ||||
| T-lymphoblastic leukemia/lymphoma | T-lymphoblastic leukemia/lymphoma | 15% of childhood ALL and 25% of adult ALL Adolescents and adults M > F | Mediastinum, cervical lymph nodes, bone marrow, and blood | Favorable in children, intermediate in adults |
| T-cell prolymphocytic leukemia | T-prolymphocytic leukemia | 2% of mature leukemias Older adults, younger adults with AT or NBS, M > F | Peripheral blood and bone marrow, spleen, lymph nodes | Very poor |
| Sezary syndrome | Sezary syndrome | Rare leukemia associated with skin involvement accounting for ∼5% of cutaneous T-cell lymphomas Older adults, M > F | Blood, bone marrow, skin, lymph nodes | Poor |
| Adult T-cell leukemia/lymphoma | Adult T-cell leukemia/lymphoma | Affects ∼2.5% HTLV-1 carriers Endemic in south-western Japan, the Caribbean Basin, and parts of central Africa Various clinical presentations (acute, lymphomatous, chronic, and smoldering) Adults, M > F | Blood, lymph nodes, skin, lung, liver, gastrointestinal tract, and CNS | Very poor in lymphomatous and acute types, poor to intermediate in chronic and smoldering subtypes |
| Aggressive NK-cell leukemia | Aggressive NK-cell leukemia | Very rare Most cases reported in Asia, occasional cases in White people or African people Young to middle-aged adults, M = F | Bone marrow, blood, liver, spleen, lymph nodes, any other organ | Very poor |
| T-cell large granular lymphocytic leukemia | T- large granular lymphocytic leukemia | T-cell and NK-cell types account for 2%-5% of chronic (mature) leukemias Association with rheumatoid arthritis, autoimmune disorders, and other hematologic neoplasms Older adults, M = F | Peripheral blood and bone marrow, spleen, and liver | Favorable |
| Chronic lymphoproliferative disorder of NK cells | NK- large granular lymphocytic leukemia | |||
| Nodal lymphomas | ||||
| Anaplastic large cell lymphoma, ALK+ | ALK+ anaplastic large cell lymphoma | Accounts for 16%, 6%, and 3% of PTCLs in North America, Europe, and Asia, respectively Children and young adults, M > F | Lymph nodes, mediastinum, spleen, bone, skin | Favorable |
| Anaplastic large cell lymphoma, ALK− | ALK− anaplastic large cell lymphoma | Accounts for 8%-9% of PTCLs in North America and Europe, and 3% in Asia Adults and elderly, M>F | Peripheral lymph nodes or less commonly (20%) skin, lung, liver, gastrointestinal tract | Intermediate |
| Follicular helper T-cell lymphoma, including 3 subtypes: angioimmunoblastic, follicular, and NOS | Nodal T follicular helper cell lymphoma (nTFHL), angioimmunoblastic type nTFHL, follicular type nTFHL, NOS | Most common nodal PTCL, representing 35%-40%, 27%, and 25% of PTCLs in Europe, North America, and Asia, respectively More common in elderly adults, can occur at any age, very rare in children, M > F | Lymph nodes, spleen, bone marrow, skin, Waldeyer’s ring | Poor |
| Primary nodal EBV+ T-cell/NK-cell lymphoma | EBV+ nodal T- and NK-cell lymphoma | Very rare, more frequent in Asia than in Western countries Association with HIV and other immunodeficiency conditions Adults and elderly, M > F | Lymph nodes, liver and spleen, bone marrow, no nasal involvement | Very poor |
| Peripheral T-cell lymphoma, NOS | Peripheral T-cell lymphoma, NOS | Second most common nodal PTCL, representing 26%-27% of PTCL in North America and Europe, and 20% in Asia Adults and elderly adults, very rare in children, M>F | Lymph nodes, spleen, any organ, leukemic dissemination rare | Poor |
| Extranodal lymphomas and lymphoproliferative disorders | ||||
| Extranodal NK/Tcell lymphoma, nasal type | Extranodal NK/T-cell lymphoma | Most common extranodal noncutaneous PTCL, accounting for 10%, 6%, and 28% of PTCLs in North America, Europe, and Asia, respectively; also frequent in Latin America Adults, M > F | Nasal region more commonly than extranasal sites (skin, gastrointestinal tract, lung, testis, central nervous system), secondary lymph node involvement can occur | Intermediate to poor according to staging |
| Enteropathy-associated T-cell lymphoma | Enteropathy-associated T-cell lymphoma | Accounts for <2% of PTCLs Most prevalent in Northern Europe, followed by North America, very rare in Asia Adults and elderly adults, M > F | Small intestine, colon, stomach, mesenteric LN, rarely extraintestinal localizations (skin, spleen, central nervous system, lung, etc) | Very poor |
| Type II refractory celiac disease | Not listed | Type II refractory celiac disease develops in 1% of individuals with celiac disease Adults and elderly adults, M > F | Small intestine, occasionally peripheral blood, distant organs | Poor |
| Monomorphic epitheliotropic intestinal T-cell lymphoma | Monomorphic epitheliotropic intestinal T-cell lymphoma | Accounts for <2% of PTCLs Most common in Asia, but seen worldwide Adults and elderly adults M = F | Small intestine, colon, stomach, mesenteric LN, extraintestinal dissemination | Very poor |
| Intestinal T-cell lymphoma, NOS | Intestinal T-cell lymphoma, NOS | Very rare Adults and elderly adults M > F | Small intestine, colon | Very poor |
| Indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract | Indolent T-cell lymphoma of the gastrointestinal tract | Very rare Adults, M > F | Gastrointestinal tract, small intestine and colon more commonly than stomach and duodenum | Favorable |
| Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract | Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract | Very rare First described in Asia, also reported in North America and Europe Older adults, rarely young adults, F > M | Gastrointestinal tract, stomach and duodenum more commonly than small intestine and colon | Favorable |
| Hepatosplenic T-cell lymphoma | Hepatosplenic T-cell lymphoma | 1%-2% of PTCLs Adolescents and young adults, M > F | Spleen, liver, bone marrow, blood | Very poor |
| Breast implant-associated anaplastic large cell lymphoma | Breast implant-associated anaplastic large cell lymphoma | Rare, occurs in 1/1000 to 1/30 000 individuals with textured breast implants Adults, F > M | Breast implant capsule or pericapsular fluid, regional lymph nodes | Favorable |
| Cutaneous lymphomas and lymphoproliferative disorders | ||||
| Mycosis fungoides | Mycosis fungoides | Most common primary cutaneous lymphoma (CTCL∗) accounting for ≥65% CTCLs Individuals of any age but usually middle-aged to older adults, M > F except in Black populations | Unique or multiple erythematous skin lesions (plaques, patches, or nodules), with possible dissemination to lymph nodes or other sites | Favorable to poor depending on staging; large cell transformation associated with poor prognosis |
| Lymphomatoid papulosis | Lymphomatoid papulosis | Lymphoproliferative disorder representing ∼9% of CTCL Adults or children, M > F | Multiple skin papules (trunk, extremities), may also occur in head and neck mucosa | Favorable |
| Primary cutaneous anaplastic large cell lymphoma | Primary cutaneous anaplastic large cell lymphoma | Second most cutaneous lymphoma, accounting for 7% of cases Usually older adults but can occur in children, M > F | Single cutaneous nodule or papule, often ulcerated, with no predilection site, or mucosae | Favorable |
| Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder | Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder | Accounts for 6%-8% of CTCLs Adults, M = F | Single cutaneous nodule or papule, most common in head and neck | Favorable |
| Subcutaneous panniculitis-like T-cell lymphoma | Subcutaneous panniculitis-like T-cell lymphoma | Rare (<1% of all lymphomas) More common in Asia than in Western countries Young adults and children, F > M | Subcutaneous nodules or plaques in extremities and trunk | Favorable |
| Primary cutaneous gamma-delta T-cell lymphoma | Primary cutaneous gamma-delta T-cell lymphoma | Very rare, <1% of CTCLs Adults and elderly adults, rarely children, M = F | Skin (plaques, nodules, or tumors) | Very poor |
| Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder | Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder | Very rare, <1% of CTCLs Adults or rarely children, M > F | Skin (papule, nodule, or plaque) of acral sites (ear, nose, hands, and feet) | Favorable |
| Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma | Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma | Very rare, <1% of CTCLs Adults or any age, M > F | Skin with predilection for acral sites, localized or generalized lesions | Very poor |
| Not listed | Primary cutaneous peripheral T-cell lymphoma, NOS | Unknown | Multiple or less commonly single skin tumors or papules | Unknown |
| EBV-associated lymphoproliferative disorders and lymphomas of childhood | ||||
| Hydroa vacciniforme lymphoproliferative disorder, classic type and systemic type | Hydroa vacciniforme lymphoproliferative disorder | Very rare The classic type affects White populations, the systemic type is seen in Asia and Latin America Children and adolescents, M > F | Classic type: skin Systemic type: skin, lymph nodes, liver, spleen, lung | Favorable (classic type), intermediate to poor (systemic type) |
| Severe mosquito bite allergy | Severe mosquito bite allergy | Very rare Japan and other Asian countries, Latin America Children and adolescents, M = F | Skin, can progress to systemic disease | Intermediate |
| Chronic active EBV disease, systemic (T-cell and NK-cell phenotype) | Systemic chronic active EBV disease | Asia and Latin America, rare in Western countries Children to young adults, rarely adults, M = F | Lymph node, bone marrow and any nonhematopoietic organ | Intermediate to poor |
| Systemic EBV+ T-cell lymphoma of childhood | Systemic EBV+ T-cell lymphoma of childhood | Very rare More common in Asia than in Causasian populations Children to young adults, M = F | Spleen and liver, bone marrow, lymph nodes, skin, and lungs | Very poor |
Italics indicate the entities provisional in the ICC. Prognosis is indicated according to 5-year overall survival estimates: favorable, >75%; intermediate, >50% to 75%; poor, 30% to 50%; very poor: <30%.
ALK, anaplastic lymphoma kinase; ALL, acute lymphoblastic leukemia; AT, ataxia telangiectasia; CNS, central nervous system; CTCL, cutaneous T-cell lymphoma; F, female; ICC, International Consensus Classification of lymphoid tumors; M, male; NBS, Nijmegen breakage syndrome; NOS, not otherwise specified; WHO5, The fifth Edition of the WHO classification of hematolymphoid tumors.
CTCL, “cutaneous T-cell lymphoma” is a generic term encompassing both lymphomas and LPDs primarily occurring in the skin.