Primary cutaneous lymphomas are the second most common extranodal non-Hodgkin Lymphomas. They may be of either T cell, B cell, or NK cell origin. Cutaneous T Cell lymphomas (CTCL) comprise a group of heterogeneous lymphomas which clinically differ from systemic lymphomas, even though they might show similar histology. 
Mycosis fungoides is the most common type of CTCL. It is a cutaneous lymphoma that originates in the peripheral epidermotropic T-cells, specifically the memory T-cells (CD45RO+), which express the T-cell receptor (TCR) and CD4+ immunophenotype.
The cause of mycosis fungoides is unclear. The following are various hypotheses proposed:
Mycosis fungoides has an incidence of around 6 cases per million per year in Europe and the United States. This accounts for 4% of all non-Hodgkin lymphoma cases. It is more common in adults over 50 years of age, with a male:female ratio between 1.6 and 2. The disease is more common amongst Blacks than Caucasians or Asians.
Among the cutaneous lymphomas, nearly two-thirds are of the T cell type. The most common immunophenotype is CD4 positive. In mycosis fungoides, there is a clonal expansion of CD4 cells that often lack the normal T cell antigens like CD7, CD5 or CD 2. These cells are attracted towards the skin by keratinocytes. As the cells accumulate in the dermis, they cluster around the langerhan cells- which is known as Pautrier microabscesses. Some of the malignant cells travel to the local lymph nodes and then pass into the bloodstream where they circulate with other CLA-positive T cells.
Histopathology of mycosis fungoides varies within stages of the disease. Superficial lymphoid infiltrate, epidermotropism with absent or rare spongiosis spongiosis, and lymphoid atypia are the predominant features.
Mycosis fungoides tumor cells are characterized by epidermotropic peripheral T lymphocytes whose phenotype is CD2+, CD3+, CD4+, and CD5+. In a minority of patients with mycosis fungoides, T lymphocytes may be CD4- and CD8+, CD4- and CD8-, or CD4+ and CD8+.
The loss of CD7 expression can be observed even in the early phases of the disease. However, isolated negativity for CD7 is not a sufficient criterion for diagnosis as it can be shown in inflammatory dermatoses. The loss of CD26 expression seems to be specific to mycosis fungoides neoplastic cells.
The immunohistochemical pattern of Sezary syndrome is CD3+, CD4+, CD7-, and CD8- cells, which is identical to mycosis fungoides. Immunostaining for MUM-1 (multiple myeloma oncogene) might be used to differentiate these as it is positive in Sezary syndrome and negative in mycosis fungoides.
The clinical presentation of mycosis fungoides varies with the stage of the disease.
The frequency of lymph nodal or visceral dissemination increases as the lesions progress from the patch stage to the plaque stage and finally the tumor stage.
Less Common or Rare Clinical Variants
Clinical Variants (as described in the WHO-EORTC Classification for Cutaneous Lymphomas)
Sezary syndrome constitutes 3% of all cutaneous lymphomas and is characterized by a triad of manifestations: erythroderma with pruritus, lymphadenopathy, and atypical circulating lymphocytes (referred to as Sezary or Lutzner cells). The syndrome is understood as a leukemic phase of T-cell cutaneous lymphomas and bone marrow compromise is rarely found in advanced forms of the disease only. Associated clinical manifestations include lagophthalmos, alopecia, palmoplantar hyperkeratosis and onycodystrophy. Sezary Syndrome must be differentiated from erythroderma in mycosis fungoides progression. In the WHO-EORTC classification, MF and SS are listed as seperate diseases.
Complete Physical Examination
Lymph Node Biopsy
It is easy to confuse mycosis fungoides for common skin disorders such as eczema, psoriasis, parapsoriasis, photodermatitis, or drug reactions. The important differentials to keep in mind include:
The standard staging system for mycosis fungoides was the TNMB system, which was the strongest prognostic indicator for mycosis fungoides. Olsen et al. (2007) published the staging norms of mycosis fungoides and SS as a result of the ISCL-EORTC discussions, and modified the existing TNMB staging system in view of advances in cellular and molecular biology in diagnostic methods, as given below.
N0: No clinically abnormal peripheral lymph nodes; biopsy not required
N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2
N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3
N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3 to 4 or NCI LN4; clone positive or negative
Nx: Clinically abnormal peripheral lymph nodes; no histologic confirmation
M0: No visceral organ involvement
M1: Visceral involvement (must have pathology confirmation and organ involved should be specified)
B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary) cells
B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary) cells but does not meet the criteria of B2
B2: High blood tumor burden: 1000/microL or more Sezary cells with positive clone
The prognosis of mycosis fungoides and Sezary syndrome is variable. The TNMB staging is the strongest prognostic factor. The following factors may be associated with a poor prognosis:
The management of mycosis fungoides is best done with an interprofessional team of healthcare workers that includes an oncologist, internist, dermatologist, nurses, pharmacists, and social workers. The disorder has no cure, and the aim is to improve the quality of life. The patient should be encouraged to use ample moisturizer to prevent skin dryness and pruritus. The patient should be told to avoid the sun and wear long-sleeved garments when going out. A cool humidified environment is highly recommended. The patient should also be educated about the other treatment options like irradiation, Photodynamic therapy and UV light treatment enhanced with psoralen. Finally, the patient should be seen by a dietitian as many people develop moderate nausea from the treatment and lose significant weight. A high-calorie diet with regular exercise is recommended. (Level V)
Mycosis fungoides is an incurable disorder unless the patient has very early stage disease. The mortality and morbidity increase as the tumor advances. While early-stage patients have a 95% survival over ten years, those who advanced cancer only have a 3-4 year survival. Those with the advanced extra-cutaneous disease only have a survival of fewer than 18 months. Poor prognostic factors include male gender, advanced age, and elevated LDH. (Level V)
|||Scarisbrick JJ,Quaglino P,Prince HM,Papadavid E,Hodak E,Bagot M,Servitje O,Berti E,Ortiz-Romero P,Stadler R,Patsatsi A,Knobler R,Guenova E,Nikolaou V,Tomasini C,Amitay I,Prag Naveh H,Ram-Wolff C,Battistella M,Alberti-Violetti S,Stranzenbach R,Gargallo V,Muniesa C,Koletsa T,Jonak C,Porkert S,Mitteldorf C,Estrach T,Combalia A,Marschalko M,Csomor J,Szepesi A,Cozzio A,Dummer R,Pimpinelli N,Grandi V,Beylot-Barry M,Pham-Ledard A,Wobser M,Geissinger E,Wehkamp U,Weichenthal M,Cowan R,Parry E,Harris J,Wachsmuth R,Turner D,Bates A,Healy E,Trautinger F,Latzka J,Yoo J,Vydianath B,Amel-Kashipaz R,Marinos L,Oikonomidi A,Stratigos A,Vignon-Pennamen MD,Battistella M,Climent F,Gonzalez-Barca E,Georgiou E,Senetta R,Zinzani P,Vakeva L,Ranki A,Busschots AM,Hauben E,Bervoets A,Sherida Woei-A-Jin FJ,Matin R,Collins G,Weatherhead S,Frew J,Bayne M,Dunnill G,McKay P,Arumainathan A,Azurdia R,Benstead K,Twigger R,Rieger K,Brown R,Sanchez JA,Miyashiro D,Akilov O,McCann S,Sahi H,Damasco FM,Querfeld C,Folkes A,Bur C,Klemke CD,Enz P,Pujol R,Quint K,Geskin L,Hong E,Evison F,Vermeer M,Cerroni L,Kempf W,Kim Y,Willemze R, The PROCLIPI international registry of early stage Mycosis Fungoides identifies substantial diagnostic delay in most patients. The British journal of dermatology. 2018 Sep 29 [PubMed PMID: 30267549]|
|||Su C,Tang R,Bai HX,Girardi M,Karakousis G,Zhang PJ,Xiao R,Zhang G, Disease site as a prognostic factor for mycosis fungoides: an analysis of 2428 cases from the US National Cancer Database. British journal of haematology. 2018 Sep 14 [PubMed PMID: 30216417]|
|||Prince HM,Querfeld C, Integrating novel systemic therapies for the treatment of mycosis fungoides and Sézary syndrome. Best practice [PubMed PMID: 30213403]|
|||Hossain C,Jennings T,Duffy R,Knoblauch K,Gochoco A,Chervoneva I,Shi W,Alpdogan SO,Porcu P,Pro B,Sahu J, The histological prevalence and clinical implications of folliculotropism and syringotropism in mycosis fungoides. Chinese clinical oncology. 2019 Feb; [PubMed PMID: 30818957]|
|||Lim HLJ,Tan STE,Tee SI,Ho ZY,Boey JJJ,Tan WP,Tang MBY,Shen L,Chan YH,Tan SH, Epidemiology and prognostic factors for mycosis fungoides and Sézary syndrome in a multi-ethnic Asian cohort: A 12-year review. Journal of the European Academy of Dermatology and Venereology : JEADV. 2019 Feb 23; [PubMed PMID: 30801779]|
|||Bergallo M,Daprà V,Fava P,Ponti R,Calvi C,Montanari P,Novelli M,Quaglino P,Galliano I,Fierro MT, DNA from Human Polyomaviruses, MWPyV, HPyV6, HPyV7, HPyV9 and HPyV12 in Cutaneous T-cell Lymphomas. Anticancer research. 2018 Jul [PubMed PMID: 29970537]|
|||Väisänen E,Fu Y,Koskenmies S,Fyhrquist N,Wang Y,Keinonen A,Mäkisalo H,Väkevä L,Pitkänen S,Ranki A,Hedman K,Söderlund-Venermo M, Cutavirus DNA in malignant and non-malignant skin of cutaneous T-cell lymphoma and organ transplant patients but not of healthy adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 Sep 20 [PubMed PMID: 30239652]|
|||Slodownik D,Moshe S,Sprecher E,Goldberg I, Occupational mycosis fungoides - a case series. International journal of dermatology. 2017 Jul [PubMed PMID: 28255994]|
|||Blaizot R,Ouattara E,Fauconneau A,Beylot-Barry M,Pham-Ledard A, Infectious events and associated risk factors in mycosis fungoides/Sézary syndrome: a retrospective cohort study. The British journal of dermatology. 2018 Dec [PubMed PMID: 30098016]|
|||Fujii K, New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma. Frontiers in oncology. 2018 [PubMed PMID: 29915722]|
|||Amorim GM,Niemeyer-Corbellini JP,Quintella DC,Cuzzi T,Ramos-E-Silva M, Clinical and epidemiological profile of patients with early stage mycosis fungoides. Anais brasileiros de dermatologia. 2018 Jul-Aug [PubMed PMID: 30066762]|
|||Amorim GM,Niemeyer-Corbellini JP,Quintella DC,Cuzzi T,Ramos-E-Silva M, Hypopigmented mycosis fungoides: a 20-case retrospective series. International journal of dermatology. 2018 Mar [PubMed PMID: 29318586]|
|||Eder J,Rogojanu R,Jerney W,Erhart F,Dohnal A,Kitzwögerer M,Steiner G,Moser J,Trautinger F, Mast Cells Are Abundant in Primary Cutaneous T-Cell Lymphomas: Results from a Computer-Aided Quantitative Immunohistological Study. PloS one. 2016 [PubMed PMID: 27893746]|
|||Tardío JC,Arias D,Khedaoui R, Indeterminate Cell Histiocytosis and Mycosis Fungoides. A Hitherto Unreported Association. The American Journal of dermatopathology. 2018 Jul 17 [PubMed PMID: 30024412]|
|||Yamashita T,Abbade LP,Marques ME,Marques SA, Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update. Anais brasileiros de dermatologia. 2012 Nov-Dec; [PubMed PMID: 23197199]|
|||Pimpinelli N,Olsen EA,Santucci M,Vonderheid E,Haeffner AC,Stevens S,Burg G,Cerroni L,Dreno B,Glusac E,Guitart J,Heald PW,Kempf W,Knobler R,Lessin S,Sander C,Smoller BS,Telang G,Whittaker S,Iwatsuki K,Obitz E,Takigawa M,Turner ML,Wood GS, Defining early mycosis fungoides. Journal of the American Academy of Dermatology. 2005 Dec; [PubMed PMID: 16310068]|
|||Robson A, Immunocytochemistry and the diagnosis of cutaneous lymphoma. Histopathology. 2010 Jan; [PubMed PMID: 20055906]|
|||Burg G,Dummer R,Nestle FO,Doebbeling U,Haeffner A, Cutaneous lymphomas consist of a spectrum of nosologically different entities including mycosis fungoides and small plaque parapsoriasis. Archives of dermatology. 1996 May; [PubMed PMID: 8624155]|
|||Keehn CA,Belongie IP,Shistik G,Fenske NA,Glass LF, The diagnosis, staging, and treatment options for mycosis fungoides. Cancer control : journal of the Moffitt Cancer Center. 2007 Apr; [PubMed PMID: 17387295]|
|||Bowman PH,Hogan DJ,Sanusi ID, Mycosis fungoides bullosa: report of a case and review of the literature. Journal of the American Academy of Dermatology. 2001 Dec; [PubMed PMID: 11712043]|
|||Georgala S,Katoulis AC,Symeonidou S,Georgala C,Vayopoulos G, Persistent pigmented purpuric eruption associated with mycosis fungoides: a case report and review of the literature. Journal of the European Academy of Dermatology and Venereology : JEADV. 2001 Jan; [PubMed PMID: 11451328]|
|||Lindae ML,Abel EA,Hoppe RT,Wood GS, Poikilodermatous mycosis fungoides and atrophic large-plaque parapsoriasis exhibit similar abnormalities of T-cell antigen expression. Archives of dermatology. 1988 Mar; [PubMed PMID: 3257858]|
|||Zelger B,Sepp N,Weyrer K,Grünewald K,Zelger B, Syringotropic cutaneous T-cell lymphoma: a variant of mycosis fungoides? The British journal of dermatology. 1994 Jun; [PubMed PMID: 8011503]|
|||El-Shabrawi-Caelen L,Cerroni L,Medeiros LJ,McCalmont TH, Hypopigmented mycosis fungoides: frequent expression of a CD8 T-cell phenotype. The American journal of surgical pathology. 2002 Apr; [PubMed PMID: 11914622]|
|||Willemze R,Jaffe ES,Burg G,Cerroni L,Berti E,Swerdlow SH,Ralfkiaer E,Chimenti S,Diaz-Perez JL,Duncan LM,Grange F,Harris NL,Kempf W,Kerl H,Kurrer M,Knobler R,Pimpinelli N,Sander C,Santucci M,Sterry W,Vermeer MH,Wechsler J,Whittaker S,Meijer CJ, WHO-EORTC classification for cutaneous lymphomas. Blood. 2005 May 15; [PubMed PMID: 15692063]|
|||Lopez AT,Bates S,Geskin L, Current Status of HDAC Inhibitors in Cutaneous T-cell Lymphoma. American journal of clinical dermatology. 2018 Sep 1 [PubMed PMID: 30173294]|
|||Mycosis Fungoides (Including Sézary Syndrome) Treatment (PDQ®): Health Professional Version null. 2002 [PubMed PMID: 26389288]|
|||Wain T,Venning VL,Consuegra G,Fernandez-Peñas P,Wells J, Management of cutaneous T-cell lymphomas: Established and emergent therapies. The Australasian journal of dermatology. 2019 Feb 26; [PubMed PMID: 30809800]|
|||Dairi M,Dadban A,Arnault JP,Lok C,Chaby G, Localized mycosis fungoides treated with laser-assisted photodynamic therapy: a case series. Clinical and experimental dermatology. 2019 Mar 1; [PubMed PMID: 30825216]|
|||Cho A,Jantschitsch C,Knobler R, Extracorporeal Photopheresis-An Overview. Frontiers in medicine. 2018 [PubMed PMID: 30211164]|
|||Brazzelli V,Bernacca C,Segal A,Barruscotti S,Bolcato V,Michelerio A,Tomasini CF, Photo-photochemotherapy in Juvenile-onset Mycosis Fungoides: A Retrospective Study on 9 Patients. Journal of pediatric hematology/oncology. 2018 Aug 20 [PubMed PMID: 30130275]|
|||Photiou L,van der Weyden C,McCormack C,Miles Prince H, Systemic Treatment Options for Advanced-Stage Mycosis Fungoides and Sézary Syndrome. Current oncology reports. 2018 Mar 23 [PubMed PMID: 29572582]|
|||Jang BS,Kim E,Kim IH,Kang HC,Ye SJ, Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution. Radiation oncology journal. 2018 Jun [PubMed PMID: 29983036]|
|||Alpdogan O,Kartan S,Johnson W,Sokol K,Porcu P, Systemic therapy of cutaneous T-cell lymphoma (CTCL). Chinese clinical oncology. 2019 Feb; [PubMed PMID: 30818958]|
|||Berg S,Villasenor-Park J,Haun P,Kim EJ, Multidisciplinary Management of Mycosis Fungoides/Sézary Syndrome. Current hematologic malignancy reports. 2017 Jun [PubMed PMID: 28540671]|
|||Olisova OY,Grekova EV,Varshavsky VA,Gorenkova LG,Alekseeva EA,Zaletaev DV,Sydikov AA, [Current possibilities of the differential diagnosis of plaque parapsoriasis and the early stages of mycosis fungoides]. Arkhiv patologii. 2019; [PubMed PMID: 30830099]|
|||Olsen E,Vonderheid E,Pimpinelli N,Willemze R,Kim Y,Knobler R,Zackheim H,Duvic M,Estrach T,Lamberg S,Wood G,Dummer R,Ranki A,Burg G,Heald P,Pittelkow M,Bernengo MG,Sterry W,Laroche L,Trautinger F,Whittaker S, 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 Cancer (EORTC). Blood. 2007 Sep 15; [PubMed PMID: 17540844]|
|||O'Brien JS,Manning T,Perera M,Prince HM,Lawrentschuk N, Blueprint unknown: a case for multidisciplinary management of advanced penile mycosis fungoides. The Canadian journal of urology. 2017 Dec [PubMed PMID: 29260643]|
|||Lebowitz E,Geller S,Flores E,Pulitzer M,Horwitz S,Moskowitz A,Kheterpal M,Myskowski PL, Survival, disease progression and prognostic factors in elderly patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of 174 patients. Journal of the European Academy of Dermatology and Venereology : JEADV. 2018 Sep 3 [PubMed PMID: 30176169]|