Primary Cutaneous CD30+ Lymphoproliferative Disorders: a Comprehensive Review

Abstract

Purpose of Review

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPDs) are the second most common cutaneous lymphomas after mycosis fungoides and Sezary syndrome. They include primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP), and borderline lesions. The purpose of this literature review is to consolidate the available evidence on the primary cutaneous CD30+ LPD in order to define the tools for correct diagnosis and appropriate treatment.

Recent Findings

The current body of knowledge regarding the clinical features, histopathologic changes, recently described genetic alterations, and therapeutic options will be covered in this comprehensive review.

Summary

Primary cutaneous CD30+ LPD represent rare cutaneous lymphomas that have significant histologic overlap within the defined group as well as with other neoplastic and reactive entities. The importance of differentiating these entities is crucial, as each one has a different clinical course and prognosis.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.

    Fujii K. New therapies and immunological findings in cutaneous T-cell lymphoma. Front Oncol. 2018;8(198):1–17.

    Google Scholar 

  2. 2.

    Sauder MB, O'Malley JT, LeBoeuf NR. CD30(+) lymphoproliferative disorders of the skin. Hematol Oncol Clin North Am. 2017;31(2):317–34.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Kempf W, Pfaltz K, Vermeer MH, Cozzio A, Ortiz-Romero PL, Bagot M, 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;118(15):4024–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Willemze R et al. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018: 29(4): iv30-iv40.

  5. 5.

    Chen C, Gu YD, Geskin LJ. A review of primary cutaneous CD30(+) lymphoproliferative disorders. Hematol Oncol Clin North Am. 2019;33(1):121–34.

    PubMed  Google Scholar 

  6. 6.

    •Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90 The WHO defines the entities of note, primary cutaneous CD30+ lymphoproliferative disorders, as well as the neoplastic entities that have clinical and histologic overlap.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Bekkenk MW, Geelen F̧AMJ, Vader PCV, Heule F, Geerts ML, van Vloten WA, et al. Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch cutaneous lymphoma group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment. Blood. 2000;95(12):3653–61.

    CAS  PubMed  Google Scholar 

  8. 8.

    Horie R, Watanabe T. CD30: expression and function in health and disease. Semin Immunol. 1998;10(6):457–70.

    CAS  PubMed  Google Scholar 

  9. 9.

    Durkop H, et al. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin’s disease. Cell. 1992;68(3):421–7.

    CAS  PubMed  Google Scholar 

  10. 10.

    Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000;96(12):3681–95.

    CAS  PubMed  Google Scholar 

  11. 11.

    Del Prete G, et al. CD30-mediated signaling promotes the development of human T helper type 2-like T cells. J Exp Med. 1995;182(6):1655–61.

    PubMed  Google Scholar 

  12. 12.

    Schneider C, Hubinger G. Pleiotropic signal transduction mediated by human CD30: a member of the tumor necrosis factor receptor (TNFR) family. Leuk Lymphoma. 2002;43(7):1355–66.

    CAS  PubMed  Google Scholar 

  13. 13.

    Krysov SV, Rowley TF, Al-Shamkhani A. Inhibition of p38 mitogen-activated protein kinase unmasks a CD30-triggered apoptotic pathway in anaplastic large cell lymphoma cells. Mol Cancer Ther. 2007;6(2):703–11.

    CAS  PubMed  Google Scholar 

  14. 14.

    Zheng B, Fiumara P, Li YV, Georgakis G, Snell V, Younes M, et al. MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survival. Blood. 2003;102(3):1019–27.

    CAS  PubMed  Google Scholar 

  15. 15.

    Watanabe M, Nakano K, Togano T, Nakashima M, Higashihara M, Kadin ME, et al. Targeted repression of overexpressed CD30 downregulates NF-kappaB and ERK1/2 pathway in Hodgkin lymphoma cell lines. Oncol Res. 2011;19(10–11):463–9.

    PubMed  Google Scholar 

  16. 16.

    Gruss HJ, DaSilva N, Hu ZB, Uphoff CC, Goodwin RG, Drexler HG. Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. Leukemia. 1994;8(12):2083–94.

    CAS  PubMed  Google Scholar 

  17. 17.

    Durkop H, et al. Expression of the CD30 antigen in non-lymphoid tissues and cells. J Pathol. 2000;190(5):613–8.

    CAS  PubMed  Google Scholar 

  18. 18.

    Schwarting R, Gerdes J, Durkop H, Falini B, Pileri S, Stein H. BER-H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood. 1989;74(5):1678–89.

    CAS  PubMed  Google Scholar 

  19. 19.

    de los Fayos Alonso IG, Liang HC, Turner SD, Lagger S, Merkel O, Kenner L. The role of activator protein-1 (AP-1) family members in CD30-positive lymphomas. Cancers 2018: 10(4): 93.

  20. 20.

    Boddicker R, et al. The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma. Blood. 2015;125(20):3118–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Diaz-Cascajo C. Strong immunoexpression of the monoclonal antibody CD-30 in lymphocytic infiltrates of the skin not by itself evidence for diagnosing malignant lymphoma. Am J Dermatopathol. 2001;23(1):79–80.

    CAS  PubMed  Google Scholar 

  22. 22.

    Gallardo F, Barranco C, Toll A, Pujol RM. CD30 antigen expression in cutaneous inflammatory infiltrates of scabies: a dynamic immunophenotypic pattern that should be distinguished from lymphomatoid papulosis. J Cutan Pathol. 2002;29(6):368–73.

    PubMed  Google Scholar 

  23. 23.

    Dummer W, Rose C, Brocker EB. Expression of CD30 on T helper cells in the inflammatory infiltrate of acute atopic dermatitis but not of allergic contact dermatitis. Arch Dermatol Res. 1998;290(11):598–602.

    CAS  PubMed  Google Scholar 

  24. 24.

    Del Prete G, et al. CD30, Th2 cytokines and HIV infection: a complex and fascinating link. Immunol Today. 1995;16(2):76–80.

    PubMed  Google Scholar 

  25. 25.

    Rose C, Starostik P, Brocker EB. Infection with parapoxvirus induces CD30-positive cutaneous infiltrates in humans. J Cutan Pathol. 1999;26(10):520–2.

    CAS  PubMed  Google Scholar 

  26. 26.

    McCalmont TH, LeBoit PE. A lymphomatoid papule, but not lymphomatoid papulosis! Am J Dermatopathol. 2000;22(2):188–90.

    CAS  PubMed  Google Scholar 

  27. 27.

    Werner B, Massone C, Kerl H, Cerroni L. Large CD30-positive cells in benign, atypical lymphoid infiltrates of the skin. J Cutan Pathol. 2008;35(12):1100–7.

    PubMed  Google Scholar 

  28. 28.

    Deroo-Berger MC, Skowron F, Ronger S, Balme B, Berard F, Causeret AS, et al. Lymphomatoid papulosis: a localized form with acral pustular involvement. Dermatology. 2002;205(1):60–2.

    CAS  PubMed  Google Scholar 

  29. 29.

    Ross NA, Truong H, Keller MS, Mulholland JK, Lee JB, Sahu J. Follicular lymphomatoid papulosis: an Eosinophilic-rich follicular subtype masquerading as folliculitis clinically and histologically. Am J Dermatopathol. 2016;38(1):e1–10.

    PubMed  Google Scholar 

  30. 30.

    Chimenti S, Fargnoli MC, Pacifico A, Peris K. Mucosal involvement in a patient with lymphomatoid papulosis. J Am Acad Dermatol. 2001;44(2):339–41.

    CAS  PubMed  Google Scholar 

  31. 31.

    Romero-Mate A, et al. Persistent agmination of lymphomatoid papulosis evolving to classical lesions of lymphomatoid papulosis. J Am Acad Dermatol. 2009;61(6):1087–8.

    PubMed  Google Scholar 

  32. 32.

    Greisser J, Palmedo G, Sander C, Kutzner H, Kazakov DV, Roos M, et al. Detection of clonal rearrangement of T-cell receptor genes in the diagnosis of primary cutaneous CD30 lymphoproliferative disorders. J Cutan Pathol. 2006;33(11):711–5.

    PubMed  Google Scholar 

  33. 33.

    Humme D, Lukowsky A, Steinhoff M, Beyer M, Walden P, Sterry W, et al. Dominance of nonmalignant T-cell clones and distortion of the TCR repertoire in the peripheral blood of patients with cutaneous CD30+ lymphoproliferative disorders. J Invest Dermatol. 2009;129(1):89–98.

    CAS  PubMed  Google Scholar 

  34. 34.

    Kaudewitz P, Stein H, Plewig G, Schwarting R, Gerdes J, Burg G, et al. Hodgkin’s disease followed by lymphomatoid papulosis. Immunophenotypic evidence for a close relationship between lymphomatoid papulosis and Hodgkin’s disease. J Am Acad Dermatol. 1990;22:999–1006.

    CAS  PubMed  Google Scholar 

  35. 35.

    Wood GS, Crooks CF, Uluer AZ. Lymphomatoid papulosis and associated cutaneous lymphoproliferative disorders exhibit a common clonal origin. J Invest Dermatol. 1995;105(1):51–5.

    CAS  PubMed  Google Scholar 

  36. 36.

    Chott A. The dominant T cell clone is present in multiple regressing skin lesions and associated T cell lymphomas of patients with lymphomatoid papulosis. J Invest Dermatol. 1996;106(4):696–700.

    CAS  PubMed  Google Scholar 

  37. 37.

    Kadin ME, Carpenter C. Systemic and primary cutaneous anaplastic large cell lymphomas. Semin Hematol. 2003;40(3):244–56.

    CAS  PubMed  Google Scholar 

  38. 38.

    Kempf W, Kerl K, Mitteldorf C. Cutaneous CD30-positive T-cell lymphoproliferative disorders-clinical and histopathologic features, differential diagnosis, and treatment. Semin Cutan Med Surg. 2018;37(1):24–9.

    PubMed  Google Scholar 

  39. 39.

    Benner MF, Willemze R. Applicability and prognostic value of the new TNM classification system in 135 patients with primary cutaneous anaplastic large cell lymphoma. Arch Dermatol. 2009;145(12):1399–404.

    PubMed  Google Scholar 

  40. 40.

    Shehan JM, Kalaaji AN, Markovic SN, Ahmed I. Management of multifocal primary cutaneous CD30 anaplastic large cell lymphoma. J Am Acad Dermatol. 2004;51(1):103–10.

    PubMed  Google Scholar 

  41. 41.

    Vu K, Ai W. Update on the treatment of anaplastic large cell lymphoma. Curr Hematol Malig Rep. 2018;13(2):135–41.

    PubMed  Google Scholar 

  42. 42.

    Kim YH. Primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) with worse outcome: presentation with extensive limb disease (ELD). The Internet Journal of Dermatology. 2008;7:3.

    Google Scholar 

  43. 43.

    Melchers RC, Willemze R, Bekkenk MW, de Haas ERM, Horvath B, van Rossum MM, et al. Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: report of the Dutch cutaneous lymphoma group. Br J Dermatol. 2018;179:724–31.

    CAS  PubMed  Google Scholar 

  44. 44.

    Bertolotti A, Pham-Ledard AL, Vergier B, Parrens M, Bedane C, Beylot-Barry M. Lymphomatoid papulosis type D: an aggressive histology for an indolent disease. Br J Dermatol. 2013;169(5):1157–9.

    CAS  PubMed  Google Scholar 

  45. 45.

    Saggini A, Gulia A, Argenyi Z, Fink-Puches R, Lissia A, Magaña M, et al. A variant of lymphomatoid papulosis simulating primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Description of 9 cases. Am J Surg Pathol. 2010;34(8):1168–75.

    PubMed  Google Scholar 

  46. 46.

    Kempf W, Kazakov DV, Schärer L, Rütten A, Mentzel T, Paredes BE, et al. Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas. Am J Surg Pathol. 2013;37(1):1–13.

    PubMed  Google Scholar 

  47. 47.

    •Karai LJ, Kadin ME, Hsi ED, Sluzevich JC, Ketterling RP, Knudson RA, et al. Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis. Am J Surg Pathol. 2013;37(8):1173–81 Primary Cutaneous CD30+ disorders are defined by clinical-pathologic correlation. This paper is the first to define a subtype of lymphomatoid papulosis by a chromosomal rearranagement.

    PubMed  Google Scholar 

  48. 48.

    Kempf W, Kazakov DV, Baumgartner HP, Kutzner H. Follicular lymphomatoid papulosis revisited: a study of 11 cases, with new histopathological findings. J Am Acad Dermatol. 2013;68(5):809–16.

    PubMed  Google Scholar 

  49. 49.

    Ba W, Yang Y, Zhang Z, Wei X, Wang W, Zhao Z, et al. Lymphomatoid papulosis with folliculotropism, eccrinotropism and neurotropism. J Cutan Pathol. 2018;45(7):530–4.

    PubMed  Google Scholar 

  50. 50.

    Dore E, Swick BL, Link BK, Ghahramani GK, Liu V. Follicular lymphomatoid papulosis with follicular mucinosis: a clinicopathologic study of 3 cases with literature review and conceptual reappraisal. J Cutan Pathol. 2017;44(4):360–6.

    PubMed  Google Scholar 

  51. 51.

    Macgrogan G et al. CD30-positive cutaneous large cell lymphomas. A comparative study of clinicopathologic and molecular features of 16 cases. Am J Clin Pathol 199: 105(4): 440–50.

  52. 52.

    Ferrara G, Ena L, Cota C, Cerroni L. Intralymphatic spread is a common finding in cutaneous CD30+ lymphoproliferative disorders. Am J Surg Pathol. 2015;39(11):1511–7.

    PubMed  Google Scholar 

  53. 53.

    Guitart J, Martinez-Escala ME, Deonizio JMD, Gerami P, Kadin ME. CD30(+) cutaneous lymphoproliferative disorders with pseudocarcinomatous hyperplasia are associated with a T-helper-17 cytokine profile and infiltrating granulocytes. J Am Acad Dermatol. 2015;72(3):508–15.

    CAS  PubMed  Google Scholar 

  54. 54.

    Kempf W, Kazakov DV, Paredes BE, Laeng HR, Palmedo G, Kutzner H. Primary cutaneous anaplastic large cell lymphoma with angioinvasive features and cytotoxic phenotype: a rare lymphoma variant within the spectrum of CD30+ lymphoproliferative disorders. Dermatology. 2013;227(4):346–52.

    PubMed  Google Scholar 

  55. 55.

    Resnik KS, Kutzner H. Of lymphocytes and cutaneous epithelium: keratoacanthomatous hyperplasia in CD30+ lymphoproliferative disorders and CD30+ cells associated with keratoacanthoma. Am J Dermatopathol. 2010;32(3):314–5.

    PubMed  Google Scholar 

  56. 56.

    Wang J, Sun NCJ, Nozawa Y, Arber DA, Chu P, Chang KL, et al. Histological and immunohistochemical characterization of extranodal diffuse large-cell lymphomas with prominent spindle cell features. Histopathology. 2001;39(5):476–81.

    CAS  PubMed  Google Scholar 

  57. 57.

    Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME. A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma. Am J Surg Pathol. 1993;17(9):859–68.

    CAS  PubMed  Google Scholar 

  58. 58.

    Droc C, Cualing HD, Kadin ME. Need for an improved molecular/genetic classification for CD30+ lymphomas involving the skin. Cancer Control. 2007;14(2):124–32.

    PubMed  Google Scholar 

  59. 59.

    Tokura Y, Sugita K, Yagi H, Shimauchi T, Kabashima K, Takigawa M. Primary cutaneous anaplastic large cell lymphoma with fatal leukemic outcome in association with CLA and CCR4-negative conversion. J Am Acad Dermatol. 2007;57:S92–6.

    PubMed  Google Scholar 

  60. 60.

    Mitteldorf C, Robson A, Tronnier M, Pfaltz MC, Kempf W. Galectin-3 expression in primary cutaneous CD30-positive lymphoproliferative disorders and transformed mycosis fungoides. Dermatology. 2015;231:164–70.

    CAS  PubMed  Google Scholar 

  61. 61.

    Schrader AM, Jansen PM, Willemze R. TOX expression in cutaneous T-cell lymphomas: an adjunctive diagnostic marker that is not tumour specific and not restricted to the CD4(+) CD8(−) phenotype. Br J Dermatol. 2016;175(2):382–6.

    CAS  PubMed  Google Scholar 

  62. 62.

    Benoit BM, Jariwala N, O’Connor G, Oetjen LK, Whelan TM, Werth A, et al. CD164 identifies CD4(+) T cells highly expressing genes associated with malignancy in Sezary syndrome: the Sezary signature genes, FCRL3, Tox, and miR-214. Arch Dermatol Res. 2017;309(1):11–9.

    CAS  PubMed  Google Scholar 

  63. 63.

    De Souza A, et al. Characterization of the tumor microenvironment in primary cutaneous CD30-positive lymphoproliferative disorders: a predominance of CD163-positive M2 macrophages. J Cutan Pathol. 2016;43(7):579–88.

    PubMed  Google Scholar 

  64. 64.

    Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol. 1999;155:483–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Massone C, Chott A, Metze D, Kerl K, Citarella L, Vale E, et al. Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients. Am J Surg Pathol. 2004;28:719–35.

    PubMed  Google Scholar 

  66. 66.

    Santucci M, Pimpinelli N, Massi D, Kadin ME, Meijer CJ, Müller-Hermelink HK, et al. EORTC cutaneous lymphoma task force. Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC cutaneous lymphoma task force workshop. Cancer. 2003;97:610–27.

    PubMed  Google Scholar 

  67. 67.

    Nofal A, Abdel-Mawla MY, Assaf M, Salah E. Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: proposed diagnostic criteria and therapeutic evaluation. J Am Acad Dermatol. 2012;67:748–59.

    PubMed  Google Scholar 

  68. 68.

    Gormley RH, Hess SD, Anand D, Junkins-Hopkins J, Rook AH, Kim EJ. Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. J Am Acad Dermatol. 2010;62:300–7.

    PubMed  Google Scholar 

  69. 69.

    Diwan H, Ivan D. CD8-positive mycosis fungoides and primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma. J Cutan Pathol. 2009;36:390–2.

    PubMed  Google Scholar 

  70. 70.

    Fujiwara Y, Abe Y, Kuyama M, Arata J, Yoshino T, Akagi T, et al. CD8+ cutaneous T-cell lymphoma with pagetoid epidermotropism and angiocentric and angiodestructive infiltration. Arch Dermatol. 1990;126:801–4.

    CAS  PubMed  Google Scholar 

  71. 71.

    Benetatos L, Dova L, Baxevanos G, Kolaitis NI, Bourantas KL, Vartholomatos G. Peripheral blood flow cytometry based diagnosis in primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: implications for more extensive use. Cytometry B Clin Cytom. 2009;76:102–6.

    PubMed  Google Scholar 

  72. 72.

    Robson A, Assaf C, Bagot M, Burg G, Calonje E, Castillo C, et al. Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC cutaneous lymphoma task force workshop. Histopathology. 2015;67:425–41.

    PubMed  Google Scholar 

  73. 73.

    Pham-Ledard A, Prochazkova-Carlotti M, Laharanne E, Vergier B, Jouary T, Beylot-Barry M, et al. IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases. J Invest Dermatol. 2010;130(3):816–25.

    CAS  PubMed  Google Scholar 

  74. 74.

    Olson LC, Cheng E, Mathew S, Torres-Quinones M, Magro C. Primary cutaneous anaplastic large-cell lymphoma with 6p25.3 rearrangement in a cardiac transplant recipient: a case report and review of the literature. Am J Dermatopathol. 2016;38(6):461–5.

    PubMed  Google Scholar 

  75. 75.

    Cerroni L. Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment. Semin Cutan Med Surg. 2018;37(1):2–10.

    PubMed  Google Scholar 

  76. 76.

    Fauconneau A, Pham-Ledard A, Cappellen D, Frison E, Prochazkova-Carlotti M, Parrens M, et al. Assessment of diagnostic criteria between primary cutaneous anaplastic large-cell lymphoma and CD30-rich transformed mycosis fungoides; a study of 66 cases. Br J Dermatol. 2015;172(6):1547–54.

    CAS  PubMed  Google Scholar 

  77. 77.

    Velusamy T, Kiel MJ, Sahasrabuddhe AA, Rolland D, Dixon CA, Bailey NG, et al. A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders. Blood. 2014;124(25):3768–71.

    CAS  PubMed  Google Scholar 

  78. 78.

    Querfeld C, Khan I, Mahon B, Nelson BP, Rosen ST, Evens AM. Primary cutaneous and systemic anaplastic large cell lymphoma: clinicopathologic aspects and therapeutic options. Oncology (Williston Park). 2010;24(7):574–87.

    Google Scholar 

  79. 79.

    Vergier B, Beylot-Barry M, Pulford K, Michel P, Bosq J, de Muret A, et al. Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases. Am J Surg Pathol. 1998;22(10):1192–202.

    CAS  PubMed  Google Scholar 

  80. 80.

    DeCoteau JF, Butmarc JR, Kinney MC, Kadin ME. The t(2;5) chromosomal translocation is not a common feature of primary cutaneous CD30+ lymphoproliferative disorders: comparison with anaplastic large-cell lymphoma of nodal origin. Blood. 1996;87(8):3437–41.

    CAS  PubMed  Google Scholar 

  81. 81.

    Su LD, Schnitzer B, Ross CW, Vasef M, Mori S, Shiota M, et al. The t(2;5)-associated p80 NPM/ALK fusion protein in nodal and cutaneous CD30+ lymphoproliferative disorders. J Cutan Pathol. 1997;24(10):597–603.

    CAS  PubMed  Google Scholar 

  82. 82.

    Oschlies I, Lisfeld J, Lamant L, Nakazawa A, d'Amore ESG, Hansson U, et al. ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study. Haematologica. 2013;98(1):50–6.

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    Pulitzer M, Ogunrinade O, Lin O, Steinherz P. ALK-positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient. J Cutan Pathol. 2015;42(3):182–7.

    PubMed  PubMed Central  Google Scholar 

  84. 84.

    Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X, et al. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin’s lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK). Oncogene. 1997;14(18):2175–88.

    CAS  PubMed  Google Scholar 

  85. 85.

    Palmer RH, Vernersson E, Grabbe C, Hallberg B. Anaplastic lymphoma kinase: signalling in development and disease. Biochem J. 2009;420(3):345–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Pulford K, Lamant L, Morris SW, Butler LH, Wood KM, Stroud D, et al. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood. 1997;89(4):1394–404.

    CAS  PubMed  Google Scholar 

  87. 87.

    Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124(9):1473–80.

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Chavan RN, Bridges AG, Knudson RA, Ketterling RP, Comfere N, Wada DA, et al. Somatic rearrangement of the TP63 gene preceding development of mycosis fungoides with aggressive clinical course. Blood Cancer J. 2014;4:e253.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Schrader AM, et al. No TP63 rearrangements in a selected group of primary cutaneous CD30+ lymphoproliferative disorders with aggressive clinical course. Blood. 2016;128(1):141–3.

    CAS  PubMed  Google Scholar 

  90. 90.

    Poglio S, Merlio JP. SATB1 is a pivotal epigenetic biomarker in cutaneous T-cell lymphomas. J Invest Dermatol. 2018;138(8):1694–6.

    CAS  PubMed  Google Scholar 

  91. 91.

    Sun J, Yi S, Qiu L, Fu W, Wang A, Liu F, et al. SATB1 defines a subtype of cutaneous CD30(+) lymphoproliferative disorders associated with a T-helper 17 cytokine profile. J Invest Dermatol. 2018;138(8):1795–804.

    CAS  PubMed  Google Scholar 

  92. 92.

    De Souza A, et al. Loss of expression of 5-hydroxymethylcytosine in CD30-positive cutaneous lymphoproliferative disorders. J Cutan Pathol. 2014;41(12):901–6.

    PubMed  Google Scholar 

  93. 93.

    Assaf C, Hirsch B, Wagner F, Lucka L, Grünbaum M, Gellrich S, et al. Differential expression of TRAF1 aids in the distinction of cutaneous CD30-positive lymphoproliferations. J Invest Dermatol. 2007;127(8):1898–904.

    CAS  PubMed  Google Scholar 

  94. 94.

    Kamstrup MR, Ralfkiaer E, Skovgaard GL, Gniadecki R. Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders. Br J Dermatol. 2008;158(4):747–53.

    CAS  PubMed  Google Scholar 

  95. 95.

    Wieser I, Oh CW, Talpur R, Duvic M. Lymphomatoid papulosis: treatment response and associated lymphomas in a study of 180 patients. J Am Acad Dermatol. 2016;74(1):59–67.

    PubMed  Google Scholar 

  96. 96.

    Sokolowska-Wojdylo M, Olek-Hrab K, Ruckemann-Dziurdzinska K. Primary cutaneous lymphomas: diagnosis and treatment. Postepy Dermatol Alergol. 2015;32(5):368–83.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Hughes PS. Treatment of lymphomatoid papulosis with imiquimod 5% cream. J Am Acad Dermatol. 2006;54(3):546–7.

    PubMed  Google Scholar 

  98. 98.

    Calista D, Riccioni L, Bagli L, Valenzano F. Long-term remission of primary cutaneous neutrophil-rich CD30+ anaplastic large cell lymphoma treated with topical imiquimod. A case report. J Eur Acad Dermatol Venereol. 2016;30(5):899–901.

    CAS  PubMed  Google Scholar 

  99. 99.

    Ehst BD, Dreno B, Vonderheid EC. Primary cutaneous CD30+ anaplastic large cell lymphoma responds to imiquimod cream. Eur J Dermatol. 2008;18(4):467–8.

    PubMed  Google Scholar 

  100. 100.

    Yagi H, Tokura Y, Furukawa F, Takigawa M. Th2 cytokine mRNA expression in primary cutaneous CD30-positive lymphoproliferative disorders: successful treatment with recombinant interferon-gamma. J Invest Dermatol. 1996;107(6):827–32.

    CAS  PubMed  Google Scholar 

  101. 101.

    Shang SX, Chen H, Sun JF, Xu XL. Regional lymphomatoid papulosis successfully controlled by interferon alpha-2b and nitrogen mustard solution. Chin Med J. 2013;126(16):3194–5.

    PubMed  Google Scholar 

  102. 102.

    French LE, Shapiro M, Junkins-Hopkins JM, Vittorio CC, Rook AH. Regression of multifocal, skin-restricted, CD30-positive large T-cell lymphoma with interferon alfa and bexarotene therapy. J Am Acad Dermatol. 2001;45(6):914–8.

    CAS  PubMed  Google Scholar 

  103. 103.

    Vonderheid EC, Sajjadian A, Kadin ME. Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders. J Am Acad Dermatol. 1996;34:470–81.

    CAS  PubMed  Google Scholar 

  104. 104.

    Fujita H, Nagatani T, Miyazawa M, Wada H, Koiwa K, Komatsu H, et al. Primary cutaneous anaplastic large cell lymphoma successfully treated with low-dose oral methotrexate. Eur J Dermatol. 2008;18:360–1.

    PubMed  Google Scholar 

  105. 105.

    Nandini A, Mysore V, Sacchidanand S, Chandra S. Primarycutaneous anaplastic large cell lymphoma arising from lymphomatoid papulosis, responding to low dose methotrexate.J Cutan Aesthet Surg 2009; 2: 97–100.

  106. 106.

    Krathen RA, Ward S, Duvic M. Bexarotene is a new treatment option for lymphomatoid papulosis. Dermatology. 2003;206(2):142–7.

    CAS  PubMed  Google Scholar 

  107. 107.

    Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S, et al. Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sezary syndrome with variable CD30 expression level: a multi-institution collaborative project. J Clin Oncol. 2015;33(32):3750–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R. Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis. J Clin Oncol. 2015;33(32):3759–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. 109.

    •Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, et al. Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017;390:555–66 The treatment options offered in primary cutaneous CD30+ lymphoproliferative disorders are based on expert recommendations and case series. This is one of the first recommendations based on trial experience.

    CAS  PubMed  Google Scholar 

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Correspondence to Farah R. Abdulla.

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Dr. Querfeld, Dr. Martinez, Dr. Song, and Dr. Di Raimondo declare no conflicts of interest. Dr. Parekh reports personal fees from Genentech/Roche, outside of the submitted work. Dr. Abdulla reports personal fees from Jonshon & Johnson, Elorac, and Mallinckrodt, as well as other fees from Bionz, Trillium, Stemline, and MiRagen outside of the submitted work.

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Di Raimondo, C., Parekh, V., Song, J.Y. et al. Primary Cutaneous CD30+ Lymphoproliferative Disorders: a Comprehensive Review. Curr Hematol Malig Rep 15, 333–342 (2020). https://doi.org/10.1007/s11899-020-00583-4

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Keywords

  • CD30+ lymphoproliferative disorders
  • Cutaneous lymphoma
  • Lymphomatoid papulosis
  • Primary cutaneous anaplastic large cell lymphoma