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Mycosis Fungoides

  • Amrita Goyal
  • Kavita Goyal
  • Joi B. Carter
  • Jeffrey A. Barnes
  • Rosalynn M. Nazarian
  • Mai P. Hoang
  • Adriano Piris
  • Thomas Kupper
  • Lyn McDivitt DuncanEmail author

Abstract

Mycosis fungoides (MF) is a CD4+ primary cutaneous T-cell lymphoma with a good prognosis. Patients with MF classicly present with pink-to-erythematous patches, well-demarcated plaques, and/or tumors on sun-protected areas, including the flanks, breasts, inner thighs, groin, and buttocks. Cutaneous biopsies of classic MF demonstrate characteristic epidermotropism, “tagging” of atypical T cells along the dermoepidermal junction, and Pautrier microabscesses. There are a number of subtypes of MF with varied presentations, including folliculotropic MF, pagetoid reticulosis, granulomatous slack skin, poikilodermatous MF, and hypopigmented MF. This chapter will discuss the clinical presentation, prognosis, treatment, histopathology, immunohistochemistry, and molecular biology of several of the subtypes of MF. It closes with five clinical cases, each representing a different subtype of MF.

Keywords

Mycosis fungoides (MF) Patch Plaque Tumor Tagging Large cell transformation Pautrier’s microabscesses Folliculotropic MF Pagetoid reticulosis Woringer-Kolopp Ketron-Goodman Granulomatous slack skin Poikilodermatous MF Hypopigmented MF Syringotropic MF CD4+ T-cell lymphoma Sézary syndrome Follicular mucinosis Psoriasis Pilotropic Folliculocentric Bexarotene Psoralen UVA PUVA Interferon alpha Extracorporeal photophoresis Nitrogen mustard Retinoids Lichenoid Cerebriform Epidermotropism Dermatopathic STAT3 CDKN2A/p16INK4a PTEN Microsatellite instability Pruritus Alopecia Mucinorrhea Follicular keratosis 

References

  1. 1.
    Ralfkiaer E, Cerroni L, Sander CA, Smoller BR, Willemze R. Mycosis fungoides. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. p. 296–8.Google Scholar
  2. 2.
    Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009;113:5064–73.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Willenze R, Jaffees, Burg G, Cerroni L, Berti E, Swerdlow Sh et al. WHO/EORTC classification for Cutaneous Lymphomas. Blood 2005;105:3768–85.Google Scholar
  4. 4.
    Yazganoglu KD, Topkarci Z, Buyukbabani N, Baykal C. Childhood mycosis fungoides: a report of 20 cases from Turkey. J Eur Acad Dermatol Venereol. 2013;27:295–300.PubMedCrossRefGoogle Scholar
  5. 5.
    Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol. 2003;139:857–66.PubMedGoogle Scholar
  6. 6.
    Marks JG, Miller JJ. In: Marks JG, Miller JJ, editors. Scaling papules, plaques and patches. Lookingbill and Marks’ principles of dermatology. 4th ed. Philadelphia: Saunders Elsevier. p. 134–5.Google Scholar
  7. 7.
    Pimpinelli N, Olsen EA, Santucci M, Vonderheid E, Haeffner AC, Stevens S, et al. Defining early mycosis fungoides. J Am Acad Dermatol. 2005;53:1053–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Ralfkiaer E, Willemze R, Whittaker SJ, et al. Sezary syndrome. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. p. 299.Google Scholar
  9. 9.
    Vergier B, De Muret A, Beylot-barry M, Vaillant L, Ekouevi D, Chene G, et al. Transformation of mycosis fungoides: clinicopathological and prognostic features of 45 cases. Blood. 2000;95:2212–8.PubMedGoogle Scholar
  10. 10.
    Agar NS, Wedgeworth E, Crichton S, Mitchell TJ, Cox M, Ferreira S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol. 2010;28:4730–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Hwang S, Janik J, Jaffe E, Wilson W. Mycosis fungoides and Sézary syndrome. Lancet. 2008;371:945–57.PubMedCrossRefGoogle Scholar
  12. 12.
    Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Ca. Blood. 2007;110:1713–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Benner MF, Jansen PM, Vermeer MH, Willemze R. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood. 2012;119:1643–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Molina A, Zain J, Arber DA, Angelopolou M, O’Donnell M, Murata-Collins J, et al. Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol. 2005;23:6163–71.PubMedCrossRefGoogle Scholar
  15. 15.
    Abbott RA, Whittaker SJ, Morris SL, Russell-Jones R, Hung T, Bashir SJ, et al. Bexarotene therapy for mycosis fungoides and Sézary syndrome. Br J Dermatol. 2009;160:1299–307.PubMedCrossRefGoogle Scholar
  16. 16.
    Talpur R, Singh L, Daulat S, Liu P, Seyfer S, Trynosky T, et al. Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res. 2012;18:5051–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Kazakov DV, Burg G, Kempf W. Clinicopathological spectrum of mycosis fungoides. J Eur Acad Dermatol Venereol. 2004;18:397–415.PubMedCrossRefGoogle Scholar
  18. 18.
    Vega F, Luthra R, Medeiros LJ, Dunmire V, Lee S-J, Duvic M, et al. Clonal heterogeneity in mycosis fungoides and its relationship to clinical course. Blood. 2002;100:3369–73.PubMedCrossRefGoogle Scholar
  19. 19.
    Van Doorn R, van Kester MS, Dijkman R, Vermeer MH, Mulder AA, Szuhai K, et al. Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome. Blood. 2009;113:127–36.PubMedCrossRefGoogle Scholar
  20. 20.
    Carbone A, Bernardini L, Valenzano F, Bottillo I, De Simone C, Capizzi R, et al. Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF. Genes Chromosomes Cancer. 2008;47:1067–75.PubMedCrossRefGoogle Scholar
  21. 21.
    Fischer TC, Gellrich S, Muche JM, Sherev T, Audring H, Neitzel H, et al. Genomic aberrations and survival in cutaneous T cell lymphomas. J Invest Dermatol. 2004;122:579–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Gallardo F, Esteller M, Pujol RM, Costa C, Estrach T, Servitje O. Methylation status of the p15, p16 and MGMT promoter genes in primary cutaneous T-cell lymphomas. Haematologica. 2004;89:1401–3.PubMedGoogle Scholar
  23. 23.
    Mao X, Lillington D, Scarisbrick JJ, Mitchell T, Czepulkowski B, Russell-Jones R, et al. Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides. Br J Dermatol. 2002;147:464–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Navas IC, Ortiz-Romero PL, Villuendas R, Martínez P, García C, Gómez E, et al. p16(INK4a) gene alterations are frequent in lesions of mycosis fungoides. Am J Pathol. 2000;156:1565–72.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Prochazkova M, Chevret E, Mainhaguiet G, Sobotka J, Vergier B, Belaud-Rotureau M-A, et al. Common chromosomal abnormalities in mycosis fungoides transformation. Genes Chromosomes Cancer. 2007;46:828–38.PubMedCrossRefGoogle Scholar
  26. 26.
    Scarisbrick JJ, Mitchell TJ, Calonje E, Orchard G, Russell-Jones R, Whittaker SJ. Microsatellite instability is associated with hypermethylation of the hMLH1 gene and reduced gene expression in mycosis fungoides. J Invest Dermatol. 2003;121:894–901.PubMedCrossRefGoogle Scholar
  27. 27.
    Van Doorn R, Scheffer E, Willemze R. Follicular mycosis fungoides, a distinct disease entity with or without associated follicular mucinosis. Arch Dermatol. 2002;138:191–8.PubMedGoogle Scholar
  28. 28.
    Lehman J, Cook-Norris RH, Weed BR, Weenig RH, Gibson LE, Weaver AL, et al. Folliculotropic mycosis fungoides: single-center study and systematic review. Arch Dermatol. 2010;146:607–13.PubMedGoogle Scholar
  29. 29.
    Tannous Z, Baldassano MF, Li VW, Kvedar J, Duncan LM. Syringolymphoid hyperplasia and follicular mucinosis in a patient with cutaneous T-cell lymphoma. J Am Acad Dermatol. 1999;41:303–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Haghighi B, Smoller BR, LeBoit PE, Warnke RA, Sander CA, Kohler S. Pagetoid reticulosis (Woringer-Kolopp disease): an immunophenotypic, molecular, and clinicopathologic study. Mod Pathol. 2000;13:502–10.PubMedCrossRefGoogle Scholar
  31. 31.
    Steffen C. Ketron-Goodman disease, Woringer-Kolopp disease, and pagetoid reticulosis. Am J Dermatopathol. 2005;27:68–85.PubMedCrossRefGoogle Scholar
  32. 32.
    Kempf W, Ostheeren-michaelis S, Paulli M, Lucioni M, Wechsler J, Audring H, et al. Granulomatous mycosis fungoides and granulomatous slack skin. Arch Dermatol. 2008;144:1609–17.PubMedCrossRefGoogle Scholar
  33. 33.
    Kempf W, Kazakov DV, Palmedo G, Fraitag S, Schaerer L, Kutzner H. Pityriasis lichenoides et varioliformis acuta with numerous CD30(+) cells: a variant mimicking lymphomatoid papulosis and other cutaneous lymphomas. A clinicopathologic, immunohistochemical, and molecular biological study of 13 cases. Am J Surg Pathol. 2012;36:1021–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Ardigó M, Borroni G, Muscardin L, Kerl H, Cerroni L. Hypopigmented mycosis fungoides in Caucasian patients: a clinicopathologic study of 7 cases. J Am Acad Dermatol. 2003;49:264–70.PubMedCrossRefGoogle Scholar
  35. 35.
    Pavlovsky L, Mimouni D, Amitay-Laish I, Feinmesser M, David M, Hodak E. Hyperpigmented mycosis fungoides: an unusual variant of cutaneous T-cell lymphoma with a frequent CD8+ phenotype. J Am Acad Dermatol. 2012;67:69–75. Elsevier Inc.PubMedCrossRefGoogle Scholar
  36. 36.
    Pileri A, Facchetti F, Rütten A, Zumiani G, Boi S, Fink-Puches R, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Scarabello A, Leinweber B. Cutaneous lymphomas with prominent granulomatous reaction: a potential pitfall in the histopathologic diagnosis of cutaneous T-and B-cell lymphomas. Am J Surg Pathol. 2002;26:1259–68.PubMedCrossRefGoogle Scholar
  38. 38.
    Nashan D, Faulhaber D, Ständer S, Luger TA, Stadler R. Mycosis fungoides: a dermatological masquerader. Br J Dermatol. 2007;156:1–10.PubMedCrossRefGoogle Scholar
  39. 39.
    Johnson MAN, Armstrong AW. Clinical and histologic diagnostic guidelines for psoriasis: a critical review. Clin Rev Allergy Immunol. 2013;44:166–72.PubMedCrossRefGoogle Scholar
  40. 40.
    Griffiths C, Barker J. Pathogenesis and clinical features of psoriasis. Lancet. 2007;270:263–71.CrossRefGoogle Scholar
  41. 41.
    Fung MA. “Epidermotropism” vs. “exocytosis” of lymphocytes 101: definition of terms. J Cutan Pathol. 2010;37:525–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Brady SP, Magro CM, Diaz-Cano SJ, Wolfe HJ. Analysis of clonality of atypical cutaneous lymphoid infiltrates associated with drug therapy by PCR/DGGE. Hum Pathol. 1999;30:130–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Guitart J, Magro C. Cutaneous T-cell lymphoid dyscrasia. Arch Dermatol. 2014;143:921–32.Google Scholar
  44. 44.
    Matutes E. Adult T-cell leukaemia/lymphoma. J Clin Pathol. 2007;60:1373–7.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Yamaguchi T, Ohshima K, Karube K, Tutiya T, Kawano R, Suefuji H, et al. Clinicopathological features of cutaneous lesions of adult T-cell leukaemia/lymphoma. Br J Dermatol. 2005;152:76–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Jaffe E, Cossman J, Blattner W, Robert-Guroff M, Blayney D, Gallo RC, et al. The pathologic spectrum of adult T-cell leukemia/lymphoma in the United States. Am J Surg Pathol. 1984;8:263–75.PubMedCrossRefGoogle Scholar
  47. 47.
    Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009;27:453–9.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Kunishige JH, McDonald H, Alvarez G, Johnson M, Prieto V, Duvic M. Lymphomatoid papulosis and associated lymphomas: a retrospective case series of 84 patients. Clin Exp Dermatol. 2009;34:576–81.PubMedCrossRefGoogle Scholar
  49. 49.
    Cerroni L, Fink-Puches R, Back B, Kerl H. Follicular mucinosis: a critical reappraisal of clinicopathologic features and associated with mycosis fungoides and Sezary syndrome. Arch Dermatol. 2002;138:182–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol. 2000;42:549–66.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhang J-A, Yu J-B. Hypopigmented mycosis fungoides in a Chinese woman. Indian J Dermatol. 2013;58:161.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Mendez-Tovar LJ. Pathogenesis of dermatophytosis and tinea versicolor. Clin Dermatol. 2010;28:185–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Blessmann Weber M, Sponchiado de Avila LG, Albaneze R, Magalhães de Oliveira OL, Sudhaus BD, Cestari TF. Pityriasis alba: a study of pathogenic factors. J Eur Acad Dermatol Venereol. 2002;16:463–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Vargas-Ocampo F. Pityriasis alba: a histologic study. Int J Dermatol. 1993;32:870–3.PubMedCrossRefGoogle Scholar
  55. 55.
    Nofal A, Salah E. Acquired poikiloderma: proposed classification and diagnostic approach. J Am Acad Dermatol. 2013;69:e129–40.PubMedCrossRefGoogle Scholar
  56. 56.
    Magro CM, Schaefer JT, Crowson AN, Li J, Morrison C. Pigmented purpuric dermatosis: classification by phenotypic and molecular profiles. Am J Clin Pathol. 2007;128:218–29.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Amrita Goyal
    • 1
  • Kavita Goyal
    • 2
  • Joi B. Carter
    • 3
  • Jeffrey A. Barnes
    • 4
  • Rosalynn M. Nazarian
    • 5
  • Mai P. Hoang
    • 6
  • Adriano Piris
    • 7
  • Thomas Kupper
    • 7
  • Lyn McDivitt Duncan
    • 6
    Email author
  1. 1.Harvard-MIT Division of Health Sciences and TechnologyHarvard Medical SchoolBostonUSA
  2. 2.Drexel University College of MedicinePhiladelphiaUSA
  3. 3.Department of DermatologyMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  4. 4.Comprehensive Cutaneous Lymphoma ProgramMassachusetts General Hospital Cancer CenterBostonUSA
  5. 5.Dermatopathology Unit, Pathology ServiceMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  6. 6.Dermatopathology Service, Department of PathologyMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  7. 7.Department of DermatologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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