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Review Article| Volume 41, ISSUE 1, P209-229, January 2023

A Practical Guide to the Diagnosis, Evaluation, and Treatment of Cutaneous T-Cell Lymphoma

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      References

        • Olsen E.A.
        Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma.
        Dermatol Clin. 2015; 33: 643-654https://doi.org/10.1016/j.det.2015.06.001
        • National Comprehensive Cancer Network
        NCCN Guidelines, Primary Cutaneous Lymphomas.
        (Available at:) (Accessed February 2, 2022)
        • Willemze R.
        • Cerroni L.
        • Kempf W.
        • et al.
        The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas.
        Blood. 2019; 133https://doi.org/10.1182/blood-2018-11-881268
        • National Cancer Institute
        SEER Database on Mycosis Fungoides.
        (Available at:) (Accessed February 2, 2022)
        • Martínez-Escala M.E.
        • González B.R.
        • Guitart J.
        Mycosis Fungoides Variants.
        Surg Pathol Clin. 2014; 7: 169-189https://doi.org/10.1016/j.path.2014.02.003
        • Pulitzer M.
        • Myskowski P.L.
        • Horwitz S.M.
        • et al.
        Mycosis fungoides with large cell transformation: clinicopathological features and prognostic factors.
        Pathology. 2014; 46https://doi.org/10.1097/PAT.0000000000000166
        • Thurber S.E.
        • Zhang B.
        • Kim Y.H.
        • et al.
        T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides.
        J Am Acad Dermatol. 2007; 57: 782-790https://doi.org/10.1016/j.jaad.2007.06.004
        • Hristov A.C.
        • Tejasvi T.
        • Wilcox R.A.
        Mycosis fungoides and Sézary syndrome: 2019 update on diagnosis, risk-stratification, and management.
        Am J Hematol. 2019; 94: 1027-1041https://doi.org/10.1002/ajh.25577
        • Brumfiel C.M.
        • Patel M.H.
        • Puri P.
        • et al.
        How to Sequence Therapies in Mycosis Fungoides.
        Curr Treat Options Oncol. 2021; 22: 101https://doi.org/10.1007/s11864-021-00899-0
        • Kamijo H.
        • Miyagaki T.
        Mycosis Fungoides and Sézary Syndrome: Updates and Review of Current Therapy.
        Curr Treat Options Oncol. 2021; 22: 10https://doi.org/10.1007/s11864-020-00809-w
        • Olsen E.A.
        • Hodak E.
        • Anderson T.
        • et al.
        Guidelines for phototherapy of mycosis fungoides and Sézary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium.
        J Am Acad Dermatol. 2016; 74: 27-58https://doi.org/10.1016/j.jaad.2015.09.033
        • King B.J.
        • Lester S.C.
        • Tolkachjov S.N.
        • et al.
        Skin-directed radiation therapy for cutaneous lymphoma: The Mayo Clinic experience.
        J Am Acad Dermatol. 2020; 82: 634-641https://doi.org/10.1016/j.jaad.2019.07.040
        • Song A.
        • Gochoco A.
        • Zhan T.
        • et al.
        A prospective cohort study of condensed low-dose total skin electron beam therapy for mycosis fungoides: Reduction of disease burden and improvement in quality of life.
        J Am Acad Dermatol. 2020; 83: 78-85https://doi.org/10.1016/j.jaad.2020.01.046
        • Photiou L.
        • van der Weyden C.
        • McCormack C.
        • et al.
        Systemic Treatment Options for Advanced-Stage Mycosis Fungoides and Sézary Syndrome.
        Curr Oncol Rep. 2018; 20: 32https://doi.org/10.1007/s11912-018-0678-x
        • Talpur R.
        • Alberti-Violetti S.
        • Schilti M.
        • et al.
        Prognostic Factors, Staging and Treatments in Advanced Stage Mycosis Fungoides and Sézary Syndrome.
        Blood. 2014; 124: 1673https://doi.org/10.1182/blood.V124.21.1673.1673
        • Su C.
        • Nguyen K.A.
        • Bai H.X.
        • et al.
        Racial disparity in mycosis fungoides: An analysis of 4495 cases from the US National Cancer Database.
        J Am Acad Dermatol. 2017; 77: 497-502.e2https://doi.org/10.1016/j.jaad.2017.04.1137
        • Ahern K.
        • Gilmore E.S.
        • Poligone B.
        Pruritus in cutaneous T-cell lymphoma: A review.
        J Am Acad Dermatol. 2012; 67: 760-768https://doi.org/10.1016/j.jaad.2011.12.021
        • Willemze R.
        WHO-EORTC classification for cutaneous lymphomas.
        Blood. 2005; 105https://doi.org/10.1182/blood-2004-09-3502
        • Macaulay W.L.
        Lymphomatoid papulosis. A continuing self-healing eruption, clinically benign--histologically malignant.
        Arch Dermatol. 1968; 97https://doi.org/10.1001/archderm.97.1.23
        • Martinez-Cabriales S.A.
        • Walsh S.
        • Sade S.
        • et al.
        Lymphomatoid papulosis: an update and review.
        J Eur Acad Dermatol Venereol. 2020; 34https://doi.org/10.1111/jdv.15931
        • Moy A.
        • Sun J.
        • Ma S.
        • et al.
        Lymphomatoid Papulosis and Other Lymphoma-Like Diseases.
        Dermatol Clin. 2019; 37https://doi.org/10.1016/j.det.2019.05.005
        • Wieser I.
        • Wohlmuth C.
        • Nunez C.A.
        • et al.
        Lymphomatoid Papulosis in Children and Adolescents: A Systematic Review.
        Am J Clin Dermatol. 2016; 17: 319-327https://doi.org/10.1007/s40257-016-0192-6
        • Cordel N.
        • Tressières B.
        • D’Incan M.
        • et al.
        Frequency and Risk Factors for Associated Lymphomas in Patients With Lymphomatoid Papulosis.
        Oncologist. 2016; 21: 76-83https://doi.org/10.1634/theoncologist.2015-0242
        • Melchers R.C.
        • Willemze R.
        • Bekkenk M.W.
        • et al.
        Frequency and prognosis of associated malignancies in 504 patients with lymphomatoid papulosis.
        J Eur Acad Dermatol Venereol. 2020; 34: 260-266https://doi.org/10.1111/jdv.16065
        • Oh Y.
        • Stoll J.R.
        • Moskowitz A.
        • et al.
        Primary cutaneous T-cell lymphomas other than Mycosis Fungoides and Sezary Syndrome – Part II: Prognosis and Management.
        J Am Acad Dermatol. 2021; (Published online)https://doi.org/10.1016/j.jaad.2021.04.081
        • Pulitzer M.
        • Ogunrinade O.
        • Lin O.
        • et al.
        ALK-positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient.
        J Cutan Pathol. 2015; 42https://doi.org/10.1111/cup.12446
        • Brown R.A.
        • Fernandez-Pol S.
        • Kim J.
        Primary cutaneous anaplastic large cell lymphoma.
        J Cutan Pathol. 2017; 44https://doi.org/10.1111/cup.12937
        • Kempf W.
        • Pfaltz K.
        • Vermeer M.H.
        • et al.
        EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.
        Blood. 2011; 118https://doi.org/10.1182/blood-2011-05-351346
        • Fernández-de-Misa R.
        • Hernández-Machín B.
        • Combalía A.
        • et al.
        Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.
        J Eur Acad Dermatol Venereol. 2020; 34: 762-768https://doi.org/10.1111/jdv.16006
        • Eberle F.C.
        • Song J.Y.
        • Xi L.
        • et al.
        Nodal involvement by cutaneous CD30-positive T-cell lymphoma mimicking classical Hodgkin lymphoma.
        Am J Surg Pathol. 2012; 36https://doi.org/10.1097/PAS.0b013e3182487158
        • Wada D.A.
        • Law M.E.
        • Hsi E.D.
        • et al.
        Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies.
        Mod Pathol. 2011; 24: 596-605https://doi.org/10.1038/modpathol.2010.225
        • Parrilla Castellar E.R.
        • Jaffe E.S.
        • Said J.W.
        • et al.
        ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes.
        Blood. 2014; 124: 1473-1480https://doi.org/10.1182/blood-2014-04-571091
        • Pham-Ledard A.
        • Prochazkova-Carlotti M.
        • Laharanne E.
        • et al.
        IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases.
        J Invest Dermatol. 2010; 130https://doi.org/10.1038/jid.2009.314
        • Gonzalez C.L.
        • Medeiros L.J.
        • Braziel R.M.
        • et al.
        T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome.
        Am J Surg Pathol. 1991; 15: 17-27https://doi.org/10.1097/00000478-199101000-00002
        • Goyal A.
        • Goyal K.
        • Bohjanen K.
        • et al.
        Epidemiology of primary cutaneous γδ T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma in the U.S.A. from 2006 to 2015: a Surveillance, Epidemiology, and End Results-18 analysis.
        Br J Dermatol. 2019; 181: 848-850https://doi.org/10.1111/bjd.17985
        • Willemze R.
        • Jansen P.M.
        • Cerroni L.
        • et al.
        Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases.
        Blood. 2008; 111https://doi.org/10.1182/blood-2007-04-087288
        • López-Lerma I.
        • Peñate Y.
        • Gallardo F.
        • et al.
        Subcutaneous panniculitis-like T-cell lymphoma: Clinical features, therapeutic approach, and outcome in a case series of 16 patients.
        J Am Acad Dermatol. 2018; 79https://doi.org/10.1016/j.jaad.2018.05.1243
        • Swerdlow S.
        • Campo E.
        • Lee Harris N.
        • et al.
        WHO classification of tumours of haematopoietic and lymphoid tissues.
        WHO Press, 2008
        • Takahashi Y.
        • Takata K.
        • Kato S.
        • et al.
        Clinicopathological analysis of 17 primary cutaneous T-cell lymphoma of the γδ phenotype from Japan.
        Cancer Sci. 2014; 105https://doi.org/10.1111/cas.12439
        • Rodríguez-Pinilla S.M.
        • Ortiz-Romero P.L.
        • Monsalvez V.
        • et al.
        TCR-γ expression in primary cutaneous T-cell lymphomas.
        Am J Surg Pathol. 2013; 37https://doi.org/10.1097/PAS.0b013e318275d1a2
        • Foppoli M.
        • Ferreri A.J.M.
        Gamma-delta t-cell lymphomas.
        Eur J Haematol. 2015; 94https://doi.org/10.1111/ejh.12439
        • Daniels J.
        • Doukas P.G.
        • Escala M.E.M.
        • et al.
        Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas.
        Nat Commun. 2020; 11: 1806https://doi.org/10.1038/s41467-020-15572-7
        • Goyal A.
        • O’Leary D.
        • Duncan L.M.
        The significance of epidermal involvement in primary cutaneous gamma/delta (γδ) T-cell lymphoma: A systematic review and meta-analysis.
        J Cutan Pathol. 2021; 48: 1449-1454https://doi.org/10.1111/cup.14082
        • Toro J.R.
        • Liewehr D.J.
        • Pabby N.
        • et al.
        Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma.
        Blood. 2003; 101: 3407-3412https://doi.org/10.1182/blood-2002-05-1597
        • Küçük C.
        • Jiang B.
        • Hu X.
        • et al.
        Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.
        Nat Commun. 2015; 6https://doi.org/10.1038/ncomms7025
        • Merrill E.D.
        • Agbay R.
        • Miranda R.N.
        • et al.
        Primary Cutaneous T-Cell Lymphomas Showing Gamma-Delta (γδ) Phenotype and Predominantly Epidermotropic Pattern are Clinicopathologically Distinct From Classic Primary Cutaneous γδ T-Cell Lymphomas.
        Am J Surg Pathol. 2017; 41: 204-215https://doi.org/10.1097/PAS.0000000000000768
        • Yamaguchi M.
        • Suzuki R.
        • Oguchi M.
        Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type.
        Blood. 2018; 131https://doi.org/10.1182/blood-2017-12-791418
        • Allen P.B.
        • Lechowicz M.J.
        Management of NK/T-Cell Lymphoma, Nasal Type.
        J Oncol Pract. 2019; 15https://doi.org/10.1200/JOP.18.00719
        • Haverkos B.M.
        • Pan Z.
        • Gru A.A.
        • et al.
        Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases.
        Curr Hematol Malig Rep. 2016; 11https://doi.org/10.1007/s11899-016-0355-9
        • Tse E.
        • Kwong Y.L.
        NK/T-cell lymphomas.
        Best Pract Res Clin Haematol. 2019; 32: 253-261https://doi.org/10.1016/j.beha.2019.06.005
        • Rodríguez-Pinilla S.M.
        • Barrionuevo C.
        • Garcia J.
        • et al.
        EBV-associated cutaneous NK/T-cell lymphoma: review of a series of 14 cases from peru in children and young adults.
        Am J Surg Pathol. 2010; 34https://doi.org/10.1097/PAS.0b013e3181fbb4fd
        • Chan J.K.
        • Quintanilla-Martinez L.
        • Ferry J.A.
        Extranodal NK/T cell lymphoma, nasal type WHO classification of tumours of haematopoietic and lymphoid Tissues.
        International Agency for Research on Cancer, 2017: 368-371
        • Horwitz S.M.
        • Ansell S.M.
        • Ai W.Z.
        • et al.
        NCCN Guidelines Insights: T-Cell Lymphomas, Version 2.2018.
        J Natl Compr Canc Netw. 2018; 16: 123-135https://doi.org/10.6004/jnccn.2018.0007
        • Tse E.
        • Chan T.S.Y.
        • Koh L.P.
        • et al.
        Allogeneic haematopoietic SCT for natural killer/T-cell lymphoma: a multicentre analysis from the Asia Lymphoma Study Group.
        Bone Marrow Transpl. 2014; 49: 902-906https://doi.org/10.1038/bmt.2014.65
        • Goyal N.
        • O’Leary D.
        • Rubin N.
        • et al.
        Localization patterns and survival of extranodal natural killer/T-cell lymphomas in the United States: A population-based study of 945 cases.
        J Am Acad Dermatol. 2021; 85: 1318-1321https://doi.org/10.1016/j.jaad.2020.08.109
        • Tolkachjov S.N.
        • Weenig R.H.
        • Comfere N.I.
        Cutaneous peripheral T-cell lymphoma, not otherwise specified: A single-center prognostic analysis.
        J Am Acad Dermatol. 2016; 75https://doi.org/10.1016/j.jaad.2016.06.011
        • Kempf W.
        • Mitteldorf C.
        • Battistella M.
        • et al.
        Primary cutaneous peripheral T-cell lymphoma, not otherwise specified: results of a multicentre European Organization for Research and Treatment of Cancer (EORTC) cutaneous lymphoma taskforce study on the clinico-pathological and prognostic features.
        J Eur Acad Dermatol Venereol. 2021; 35https://doi.org/10.1111/jdv.16969
        • Cardwell L.A.
        • Majerowski J.
        • Chiu Y.E.
        • et al.
        Post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified in a pediatric patient.
        J Cutan Pathol. 2021; 48https://doi.org/10.1111/cup.13967
        • Peterson E.
        • Weed J.
        • lo Sicco K.
        • et al.
        Cutaneous T Cell Lymphoma: A Difficult Diagnosis Demystified.
        Dermatol Clin. 2019; 37https://doi.org/10.1016/j.det.2019.05.007
        • le Tourneau A.
        • Audouin J.
        • Molina T.
        • et al.
        Primary cutaneous follicular variant of peripheral T-cell lymphoma NOS. A report of two cases.
        Histopathology. 2010; 56https://doi.org/10.1111/j.1365-2559.2010.03498.x
        • Uchiyama T.
        • Yodoi J.
        • Sagawa K.
        • et al.
        Adult T-cell leukemia: clinical and hematologic features of 16 cases.
        Blood. 1977; 50: 481-492
        • Jain M.
        • Goyal K.
        • O’Leary D.
        • et al.
        Improved survival for skin-primary presentation of adult T-cell leukemia/lymphoma (ATLL).
        J Am Acad Dermatol. 2020; 83https://doi.org/10.1016/j.jaad.2019.11.034
        • Sawada Y.
        • Hino R.
        • Hama K.
        • et al.
        Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia/lymphoma.
        Blood. 2011; 117https://doi.org/10.1182/blood-2010-11-316794
        • Miyashiro D.
        • Sanches J.A.
        Cutaneous manifestations of adult T-cell leukemia/lymphoma.
        Semin Diagn Pathol. 2020; 37https://doi.org/10.1053/j.semdp.2019.07.010
        • AbdullGaffar B.
        • Abdulrahman S.
        Adult T-cell leukemia/lymphoma clinically confused with viral/drug skin eruptions and pathologically misinterpreted as mycosis fungoides/Sézary syndrome.
        J Cutan Pathol. 2021; 48https://doi.org/10.1111/cup.13789
        • Bangham C.R.M.
        • Ratner L.
        How does HTLV-1 cause adult T-cell leukaemia/lymphoma (ATL)?.
        Curr Opin Virol. 2015; 14: 93-100https://doi.org/10.1016/j.coviro.2015.09.004
        • Marchetti M.A.
        • Pulitzer M.P.
        • Myskowski P.L.
        • et al.
        Cutaneous manifestations of human T-cell lymphotrophic virus type-1-associated adult T-cell leukemia/lymphoma: a single-center, retrospective study.
        J Am Acad Dermatol. 2015; 72: 293-301https://doi.org/10.1016/j.jaad.2014.10.006
        • Ishida T.
        • Fujiwara H.
        • Nosaka K.
        • et al.
        Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002.
        J Clin Oncol. 2016; 34https://doi.org/10.1200/JCO.2016.67.7732
        • Kchour G.
        • Tarhini M.
        • Kooshyar M.M.
        • et al.
        Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL).
        Blood. 2009; 113https://doi.org/10.1182/blood-2009-03-211821
        • Cook L.B.
        • Fuji S.
        • Hermine O.
        • et al.
        Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report.
        J Clin Oncol. 2019; 37: 677-687https://doi.org/10.1200/JCO.18.00501
        • Walia R.
        • Yeung C.C.S.
        An Update on Molecular Biology of Cutaneous T Cell Lymphoma.
        Front Oncol. 2019; 9: 1558https://doi.org/10.3389/fonc.2019.01558
        • Choi J.
        • Goh G.
        • Walradt T.
        • et al.
        Genomic landscape of cutaneous T cell lymphoma.
        Nat Genet. 2015; 47: 1011-1019https://doi.org/10.1038/ng.3356
        • Ungewickell A.
        • Bhaduri A.
        • Rios E.
        • et al.
        Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2.
        Nat Genet. 2015; 47: 1056-1060https://doi.org/10.1038/ng.3370
        • Pérez C.
        • González-Rincón J.
        • Onaindia A.
        • et al.
        Mutated JAK kinases and deregulated STAT activity are potential therapeutic targets in cutaneous T-cell lymphoma.
        Haematologica. 2015; 100: e450-e453https://doi.org/10.3324/haematol.2015.132837
        • Mirza A.S.
        • Horna P.
        • Teer J.K.
        • et al.
        New Insights Into the Complex Mutational Landscape of Sézary Syndrome.
        Front Oncol. 2020; 10https://doi.org/10.3389/fonc.2020.00514
        • Phyo Z.H.
        • Shanbhag S.
        • Rozati S.
        Update on Biology of Cutaneous T-Cell Lymphoma.
        Front Oncol. 2020; 10https://doi.org/10.3389/fonc.2020.00765
        • Machan S.
        • Rodríguez M.
        • Alonso-Alonso R.
        • et al.
        Subcutaneous panniculitis-like T-cell lymphoma, lupus erythematosus profundus, and overlapping cases: molecular characterization through the study of 208 genes.
        Leuk Lymphoma. 2021; 62: 2130-2140https://doi.org/10.1080/10428194.2021.1901098
        • Gayden T.
        • Sepulveda F.E.
        • Khuong-Quang D.A.
        • et al.
        Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome.
        Nat Genet. 2018; 50: 1650-1657https://doi.org/10.1038/s41588-018-0251-4
        • Polprasert C.
        • Takeuchi Y.
        • Kakiuchi N.
        • et al.
        Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma.
        Blood Adv. 2019; 3: 588-595https://doi.org/10.1182/bloodadvances.2018028340
        • Sonigo G.
        • Battistella M.
        • Beylot-Barry M.
        • et al.
        HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma.
        Blood. 2020; 135: 1058-1061https://doi.org/10.1182/blood.2019003811