Mycosis fungoides (overview) C84.0

Authors: Prof. Dr. med. Peter Altmeyer, Dr. med. Antje Polensky

Co-Autor: Hadrian Tran

All authors of this article

Last updated on: 27.11.2021

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CTCL of the mycosis fungoides type; Cutaneous T-cell lymphoma of the mycosis fungoides type; Granuloma fungoides; MF; mycosis fungoides

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Most common (about 50% of all CTCL), chronic progressive, phased, primarily cutaneous T-cell lymphoma (low malignant T-cell lymphoma), which originates from CD4-positive, small to medium-sized T-cells (T-helper lymphocytes).

Functionally, the neoplastic T-helper cells can be assigned to a TH2 pattern characterized by a corresponding cytokine profile (IL-4, IL-5, IL-10) with possible consecutive eosinophilia and a potential increase in immunoglobulin (IgE, IgA).

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See clinical picture.

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Incidence: 0.4-0.5/100,000/inhabitant/year.

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Unknown. Excessive proliferation mostly of T-helper cells. While in the context of immunological homeostasis there is a constant migration of lymphocytes into and out of the skin organ, this balance is disturbed in MF. There is a pathological accumulation of CD4-positive T lymphocytes, a "skin-homing" in the uppermost layer of the skin. In some cases, patients show an increased allergic reaction of type IV, which suggests an increased activity of T-helper cells. Here, the production of chemokines by keratinocytes plays a decisive role. In the early phase of the disease, T-lymphocytes accumulate around the epidermal Langerhans cells and form abscess-like clusters, which appear as Pautrier's microabscesses under the light microscope. In addition to the "skin-homing" properties, activated T cells can also become secretorially active and thus intervene immunomodulatory in the inflammatory process. Furthermore, neoplastic T cells show a reduction of apoptosis, which delays their degradation.

An increased colonization rate with Staphylococcus aureus also appears to be of pathogenetic significance (see also atopic eczema). Their toxins belonging to the superantigens are able to stimulate T-cells in a special way. Eradication is recommended.

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Beginning in the 5th-7th decade of life (mean age of illness 55-60 years), rarely in childhood (age range 20-90 years). Course over several years (decades). Men are 1.5-2 times more frequently affected than women.

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Torso and flexor-sided thighs, flexor-sided upper arms, especially proximal third. In late stages, the entire integument is affected.

Clinical features
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Clinically varied and variable picture (mean time interval from first symptoms to diagnosis: 4.2 years!). Skin symptoms are initially in the foreground, systemic involvement is only detectable after a longer clinical course. The clinical course of mycosis fungoides is divided into 3 stages according to a rough scheme, which generally follow one another, but can also occur side by side:

  • Initial stage (premycotic stage) ("patch-stage"):
    • Usually few (< 10), rarely solitary, stationary spots occurring on non-sun-exposed sites (chest, flexor side of upper arms and thighs, other trunk areas e.g. flanks). Rarely the face is affected in the early stages!
    • Sharply demarcated, extensive (length > 5.0 cm; width < 3.0 cm), aligned in the cleavage lines of the skin, either homogeneously red or red-brown spots with a crumpled surface (like cigarette paper). A variegated surface pattern (poikilodermic) with intralesional, alternating brown, brown-red, and white patches and telangiectasias is also possible.
    • Clinically uncharacteristic, eczema-like picture, moderate or absent pruritus. Little to no scaling, usually small spots. Significant improvement with sun exposure and local glucocorticoid therapy, but no healing.
  • plaque stage:
    • Suspicious sign of an imminent progression of the lymphoma is an increasing, stronger "inflammation" of the spots and accentuated poikilodermic aspect as well as an increasing increase in consistency.
    • Increasing itching.
    • Scaling increasing.
    • Large plaques, markedly increased in consistency. The previously eczematous foci, which are more prominent in untanned skin and may disappear altogether in summer, increasingly increase their clinical presence with constant local fidelity. They spread, with a tendency to confluence and increasing planar consistency.
    • Colour: Vivid red.
    • Lymphadenopathy is possible and usually nonspecific.

At this stage of the disease, mycosis fungoides is increasingly perceived by the patient as a disease.

  • tumor stage:
    • Nodules in lesional skin; tendency to ulceration.
    • Strong itching in affected skin.
    • Specific lymph node involvement.
    • Infestation of internal organs (liver, spleen) is possible.
    • Increasing marked disturbance of general condition.
    • Tendency to septic bacterial and viral infections.
  • Concomitant symptoms in mycosis fungoides:
    • Mucosal involvement: Possible at any stage; especially of oral mucosa, tongue, tonsils, nasal cavities, pharynx.
    • Organ involvement: Involvement of spleen, liver, lungs, gastrointestinal tract or CNS in later phases of the disease.

Variants of mycosis fungoides:

  • Pagetoid reticulosis: Misnomer for a localized, low-malignant cutaneous T-cell lymphoma with unusually marked epidermotropy. Clinically, a localized and a disseminated type are distinguished.
  • Folliculotropic mycosis fungoides: Rare variant oft mycosis fungoides with folliculotropic accentuated, rubbing iron-like surface texture.
  • Syringotropic mycosis fungoides: Rare variant with preferential infiltration of the eccrine sweat glands.
  • Granulomatous slack skin: Very rare variant (about 50 cases in the world literature) of a usually CD4-positive cutaneous T-cell lymphoma characterized by granulomatous tissue formations and loss of elastic fibers.
  • Hypopigmented mycosis fungoides: Rare variant with good prognosis, observed mainly in children (skin type IV-VI according to Fitzpatrick).

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Blood count: Lymphocytosis, eosinophilia, atypical T-lymphocytes (= Lutzner cells), flow cytometrically clear T-lymphocytosis (especially CD4-positive cells) with increasing immaturity of the lymphocytes. Occasional IgE increase.

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  • It is important for a histopathological evaluation to discontinue local or systemic glucocorticoid therapy!
  • Initial or patch stage: Varying density, band or lichenoid, subepidermal infiltrate of small, epidermotropic, neoplastic CD4+ lymphocytes, a mixture of non-neoplastic CD4 and CD8+ lymphocytes and dendritic cells. Eosinophilic granulocytes and histiocytes are present in varying densities. Plasma cells are usually missing! Typical: Pearl-like accumulation of lymphocytes at the dermo-epidermal junction zone(lining-up phenomenon). Moderate epidermotropy of atypical lymphoid and monocytoid cells into the epidermis. The invaded cells often appear enlarged in the epidermis and are surrounded by an optically empty halo (halo cells). A typical spongiosis is missing; likewise a pronounced parakeratosis (delimitation to eczema). Pauterian microabscesses are detectable, but are rather rare in this stage.
  • Plaque stage: Dense dermal (papillary and reticular dermis) infiltrate of atypical, small but also medium-sized lymphocytic cells. Eosinophil granulocytes and histiocytes are present in varying densities. Distinct epidermotropy with formation of Pauterian microabscesses (characteristic of this phase). The epidermis is often acanthotic with parakeratotic keratinization. Frequently adnexotropy (follicles and sweat glands) with destruction of the adnexa.
  • Tumor stage: dense, diffuse or nodular, dermal or subcutaneous infiltrate of atypical, medium-sized lymphocytic cells. Eosinophilic granulocytes and histiocytes of varying density. High mitosis activity (MIB 1). Occasionally also immunoblasts or large anaplastic CD30+ cells. Mostly still distinct epidermotropy. Pauterian microabscesses may occur, but are never obligatory. Epidermotropism can be completely absent at this stage of development! The epidermis is acanthotic but also atrophic. Parakeratotic keratinization. The follicles are often destroyed. In the infiltrate, epithelial regeneration of the follicles is often detectable.
  • In about 25% of cases, transformation into a diffuse large cell lymphoma occurs in the tumor stage, which can be either CD30- or CD30+. The prognosis is then significantly worsened. The histological picture is then identical with primary cutaneous T-cell lymphomas, which occur without precursor stages.
  • Recent studies show that CD4-CD8-negative lymphocytes can immunohistochemically indicate an early form of mycosis fungoides.

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The diagnosis is made clinically; exact tumor staging is necessary for the definition of the disease, see Table 2. In addition to the routinely performed laboratory and organ analysis, the diagnosis is confirmed and the tumor is staged by histological, immunohistological, molecular biological and imaging radiological and sonographic examinations.
  • Immunophenotyping: This allows differentiation between T and B cell series; also detection of T cell subpopulations using CD4, CD8 and CD30 antibodies Antibodies against CD45RO+ memory T-lymphocytes are often detected in the early form of mycosis fungoides.
  • T-cell receptor gene rearrangement: Diagnostically important (although not conclusive); detection of monoclonality of T-cell infiltrates possible by this method.
  • FACS analysis: Diagnostically important: For leukaemic forms (always in Sézary syndrome).
  • Lymph node diagnostics: Sonographic examination of skin-near lymph nodes; if necessary lymph node biopsy and fine tissue diagnostics.
  • Bone marrow biopsy: As an infestation of the bone marrow is rare in the early forms of CTCL (T1-3, N0-1, M0), this diagnostic procedure is generally unnecessary.

Differential diagnosis
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  • The clinical differential diagnosis of Mycosis fungoides depends on the clinical stage of the disease and also on its clinical variants (see classification below). Therefore, this chapter will not include a generally valid differential diagnosis.
  • Initial stage: Depending on the stage of development and spread of the spots, very different clinical pictures appear. An important indicative sign is the longitudinal alignment of the patches in the cleavage lines (tension lines) of the skin. This macro pattern is only common to a few diseases ( see there).
    • Parapsoriasis en plaques: A few (on average up to 6) mostly only discreetly inflammatory, larger (usually more than 10 cm in diameter), roundish or oval, sharply defined, little scaling spots or plaques. Longitudinal axes usually aligned according to the splitting lines. Often precursors of Mycosis fungoides. Histological clarification.
    • Microbial eczema: Initially usually small, reddish-brownish, itchy, red scaly or crusty papules or papulo vesicles. Gradual growth in size to sharp or blurred, 1.0-6.0 cm large, red coin-like ("nummular eczema") plaques with yellowish crusts or scaly crusts. No knot formation. The distinct "eczema character" speaks against the diagnosis "Mycosis fungoides". Further histological clarification!
    • Psoriasis vulgaris: The classical distribution pattern on the extensor side speaks against mycosis fungoides. The typical psoriasis phenomena such as Auspitz- and Köbner phenomenon are always missing.
    • Eczema, atopic: Important here is the medical history with the typical type I allergies; in the eczematous form there are scaly, partly eroded, scratched and encrusted plaques of different red colour. Itching is always clearly present. Histology: typical eczemmorphs.
    • Pityriasis rosea: exanthema of stem, relapsing, lasting for 1-2 weeks; oriented according to the cleavage lines (Christmas tree pattern). Flock: 0.2-1.0 cm large, oval or elongated, slightly raised, scaly plaque. Acute manifestations speak against Mycosis fungoides. :
  • Plaque stage: In the classic form of the disease, a plaque stage will always be combined with pre-mycoside (eczema-like) changes. In this respect, this picture is characterized by a variety of manifestations. To clinically confirm the diagnosis, histological and immunohistological confirmation will always be necessary.
    • Pseudo-lymphomas of the skin: rather monomorphic appearance. No history for years. Histology not with the typical changes of the mycoside infiltrate.
    • Leukaemias of the skin: Very different clinical pictures, mostly exanthematic spread. No stage-like course as in mycosis fungoides. No poikiloderma.
    • Lupus erythematodes tumidus: Mostly disseminated, chronically stationary, 0.5-5.0 cm large, red, mostly non-hypersensitive, sharply defined papules and plaques with smooth, shiny, non-scalying surface. Pronounced photosensitivity. No stage-like course as in mycosis fungoides.
    • Urticaria pigmentosa: Flat, oval or round, greyish-brownish or brown spots of various sizes with urticarial reaction (this phenomenon is completely absent in Mycosis fungoides). Frequently eliminated dermographism.
    • Tinea corporis: This differential diagnosis can only be used in the case of untreated extensive forms. Marginal emphasis of the flock, itching, scaling; native and cultural pizza detection.
  • Tumor stage:
    • Other cutaneous T-cell lymphomas: Here the phased course is missing. Mostly primary knot formation. Histology is conclusive.
    • Cutaneous B-cell lymphomas: Here the phased process is missing. Mostly primary nodulation. Histology is conclusive.

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Therapy depends on the individual stages of mycosis fungoides. Aggressive therapy modalities in the early stages of the disease have not proven successful! There is a risk of tumour growth. Thus, in stage IA, the expectional concept of "watchful waiting" is rightly followed by most dermatological centres. A distinction must be made between local and systemic measures, which can be combined with each other. Basically, the following therapeutic modalities can be considered (see also table):

  • glucocorticoids, external or systemic
  • Climatic therapy
  • Heliotherapy (UVB; SUP)
  • PUVA therapy, systemic or as bath PUVA
  • Interferon alfa as monotherapy or in combinations
  • Retinoids in combination with PUVA therapy
  • Chemotherapeutic agents externally or systemically
  • Photopheresis (extracorporeal)
  • Brentuximab vedotin (Adcetris®): Approved since 2017 for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy [Wiley, Supplement to JDDG No. 8/2018].
  • Experimental: Interleukin-12: Experimental study approaches with initial positive results include therapy modalities with recombinant interleukin-12 in clinical stage 1A, 1B, IIA (2 times/week 300 ng/kg bw s.c., maintenance dose: 100 ng/kg bw s.c.).
Therapy recommendations for MF according to stages (according to S2k guideline)
Stage Recommended therapy (first line) Recommended therapy (second line)
IA watch and see

Bexarotene gel

Topical immunotherapies (e.g. Imiquimod)

UVB/UVB narrowband radiation
PUVA therapy
Topical glucocorticoids (class III-IV)
Unlesional MF Pagetoid reticulosis Radiotherapy (soft X-ray therapy or linear accelerator) 30-36 Gy

Local glucocorticoids class III-IV

PUVA local

IIB PUVA + INF-alfa and X-ray therapy or linear accelerator for tumours Low dose MTX
Oral bexarotene
Liposomal doxorubicin
Denileukin Diftitox

PUVA cream

UVB (311nm);

Low dose MTX
Oral bexarotene
Cladribine (approved for hairy cell leukemia)
Extracorporeal photopheresis possibly combined with MTX or INF-alpha Fast electrons
Whole body irradiation
Chlorambucil + glucocorticoid
IVA PUVA+INF-alpha Low dose MTX
Oral bexarotene
Linear accelerator total body irradiation
Chlorambucil + glucocorticoid
IVB Oral bexarotene
PUVA + INF-alpha Cladribine
Chlorambucil + glucocorticoid CHOP Polychemotherapy
Liposomal doxorubicin Denileukin Diftitox
Alemtuzumab (anti CD52 AK)
Targeted localized or generalized "whole body electron irradiation" (generalized plaques or nodules) using linear accelerator. Vorinostat

The table is distorted in the display, the right column is quite narrow. Maybe this is just in my version, but you can't quite read it that way, unfortunately.
Thank you

Radiation therapy
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  • Radiological therapy methods (targeted irradiation with fast electrons) are successful in uniläsional or few foci and are rightly used.
  • In the generalized patch or plaque stage (T2-3), whole-body electron irradiations are an important therapeutic option (ED 1.5-2.0Gy; GD <30Gy). In several studies, complete remissions of 75% were achieved in stage T2 and 47% in stage T3.

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  • "Indolent course." The duration of the pre-mycosid stage can range from 5 years to more than 20 years. Recurrences and regressions are possible.
  • 5-year survival rate: 66,1%
  • 10-year survival rate: 43.2%
  • Mean survival rate (all stages): 11.4 years
  • Mean survival rate (depending on stage):
    • T2 patients: 12.1 years
    • T3/T4 patients: 3-4 years
    • N0 patients: 17.5 years
    • N1 patients: 6.5 years
    • N2 patients: 1.7 years
    • B0 patients: 12.3 years
    • B1 patients: 3.0 years.

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Staging of Mycosis fungoides

Premycoside stage (patch stage)

Low pruritus or uncharacteristic red, more rarely urticarial, eczematous spots. Duration of the patch stage: 5 years to > 20 years. Reductions and recurrences are possible. 5-year survival rate: 66.1%, 10-year survival rate: 43.2%.

Infiltrative stage (plaque stage)

Plate-shaped infiltrated, sharply defined, bizarrely configured, slightly scaly or encrusted, highly itchy, red, reddish-purple or brownish-red lesions that slowly increase in size. Sharply defined islands with normal skin in the middle of these areas (nappes claires). In the capillitium area: circumscribed alopecia. Swelling of lymph nodes.

Mycoside (tumorous) stage (tumor stage)

Tumour development in the area of the infiltrated foci after usually years or decades of disease. Hemispherical, possibly lobed, mostly soft, mushroom-shaped, blue to brown-red, on the surface eroded, weeping and ulcerous tumours. Usually rapid progression with exitus lethalis.

T (skin)

T1 limited skin infestation with plaques (< 10% KO)

T2 generalized plaques(>10% KO)

T3 cutaneous tumours (> 1cm in diameter)

T4 Generalised infestation (> 80% KO) or erythroderma

N (lymph node)

N0 no lymph node enlargement, histologically without infestation

N1 Enlarged lymph nodes, histologically without infestation

  • clone negative

  • clone positive

N2 no lymph node enlargement, but histologically affected

  • clone negative

  • clone positive

N3 Lymph node enlargement with histological involvement (Dutch Grade 3-4)

  • clone negative

  • clone positive

M (Visceral organs)

M0 no organ infestation

M1 Organ infestation

B0 no atypical lymphocytes in peripheral blood (< 5%)

B1 atypical lymphocytes in peripheral blood (> 5%)

B2 High tumor load in peripheral blood (>1000 /ml Sézary cells with positive clone)

M0 No involvement of visceral organs

M1 Histologically confirmed involvement of visceral organs

Stage I

limited (IA) or generalised plaques (IB) (T1 N0 M0 or T2 N0 M0)

stage II

limited or generalized plaques with lymph node enlargement (IIA) or cutaneous tumors with/without lymph node enlargement (IIB), histologically without lymph node or organ involvement (T1-2 N1 M0 or T3 N0-1 M0)

Stage III

generalized erythroderma with/without lymphadenopathy, no histological involvement of lymph nodes or organs (T4 N0-1 M0)

Stage IV

histological involvement of lymph nodes (IVA) or organs (IVB) (T1-4 N2-3 M0 = IVA or T1-4 N0-3 M1 = IVB)























































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  • Tumour stage Ia and Ib: clinical examination and palpation of the lymph nodes every 6-12 months.
  • In more advanced stages, a closer control with imaging (LK sonography, CT thorax/abdomen) and laboratory chemical (differential blood count, FACS analysis) diagnostics.

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The term Mycosis fungoides should only be used for the classic "Alibert-Bazin" type. An early form of mycosis fungoides can be evaluated according to an algorithm developed by Pimpinelli et al. (> 4 points = MF probable):
  • Clinic:
    • Persistent or progressive patches or plaques (1 point)
    • Non-sun-exposed/large area, poikilodermic (1 point)
  • Histology:
    • Superficial lymphoid infiltrate, cell and nuclear atypia, epidermotropism (1 point)
  • molecular biology:
    • Clonal T-cell pattern (1 point)
  • Immunohistology:
    • < 50% of T cells express CD2, Cd3 and/or CD5
    • < 10% CD7 (1 point)
    • Increased number of lymphocytes (CD2, CD3, CD5, CD7) in the epidermis (disproportional epidermotropism) (1 point).

Case report(s)
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The efficacy of pegylated liposomal doxorubicin for the treatment of mycosis fungoides has been described in several studies. Controversy continues to surround the efficacy of the therapy. In 2000, Wollina et al. reported a clinical response of 83% in a case report with 6 patients. Subsequent studies have also published similarly good results. However, the significance of these studies is limited by the small number of subjects.

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  1. Alibert JLM (1806) Description des maladies de la peau observees a l'Hospital Saint-Louis et exposition des meilleures methodes suivies pour leur traitement. Paris, Barrois l' aine et fils: 157
  2. Auspitz H (1885) A case of granuloma fungoides (mycosis fungoides Alibert). Vierteljahresschrift für Dermatologie und Syphilis (Vienna) 12: 123-143.
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  4. Diederen PV et al (2003) Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study. J Am Acad Dermatol 48: 215-219
  5. Duvic M et al (2006) A phase II open-label study of recombinant human interleukin-12 patients with stage IA, IB, or IIA mycosis fungoides. J Am Acad 55: 807-813
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  7. Glusac EJ (2003) Criterion by criterion, mycosis fungoides. Am J Dermatopathol 25: 264-269
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  9. Hodak E et al (2006) CD4/CD8 double-negative epidermotropic cutaneous T-cell lymphoma: an immunohistochemical variant of mycosis fungoides. J Am Acad Dermatol 55: 276-284
  10. Kempf W et al (2003) Cutaneous T-cell lymphomas. In: Histopathology of the skin. Kerl H et al (eds) Springer Verlag Berlin, Heidelberg, New York pp 872-876.
  11. Kim YH et al. (2003) Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol 139: 857-866
  12. Krokowski M et al. (2003) Mycosis fungoides in childhood and adolescence with clonal T-cell receptor gamma gene rearrangement. Two cases. Dermatologist 54: 536-540
  13. Nasimi M et al (2020) Childhood mycosis fungoides: A clinicopathologic study of 30 cases from Iran. Australas J Dermatol 61: e259-e261.

  14. Navi D et al (2011) The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol.147:561-567

  15. Paech V et al (2002) Remission of a cutaneous mycosis fungoides after topical 5-ALA sensitisation and photodynamic therapy in a patient with advanced HIV-infection. Eur J Med Res 7: 477-479
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  18. Roenigk HH et al (1990) Photochemotherapy alone or combined with interferon alfa-2a in the treatment of cutaneous T-cell lymphoma. J Invest Dermatol 95: 1988 -2058
  19. Talpur R et al.(2008) Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome.Br J Dermatol 159:105-112
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  21. Wollina U et al (2000) Treatment of relapsing or recalcitrant cutaneous T-cell lymphoma with pegylated liposomal doxorubicin. J Am Acad Dermatol 42: 40-46
  22. Zackheim HS et al (1990) Topical carmustine (BCNU) or cutaneous T-cell lymphoma: a 15-year experience in 143 patients. J Am Acad Dermatol 22: 802-810
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Last updated on: 27.11.2021