Lymphoma and plasma cell neoplasms
T / NK cell disorders
Mycosis fungoides

Author: Dragos Luca, M.D. (see Authors page)

Revised: 3 April 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Mycosis fungoides [title] "T cell lymphoma"

Cite this page: Mycosis fungoides. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonBmycosis.html. Accessed October 17th, 2017.
Definition / general
Terminology
  • Initially called pian fungoides (Jean-Louis Alibert, 1814), because it resembles yaws (caused by Treponema), which is also called pian
  • Later renamed as mycosis fungoides, due to its resemblence to mushrooms
  • Also called cutaneous T cell lymphoma (not a good term since nonspecific as to histological type)
Epidemiology
  • Most common type of cutaneous T cell lymphoma, almost 50% of all primary cutaneous lymphomas
  • Adults / elderly but also children and adolescents
  • M:F ratio 2:1, black:white ratio 1.7
  • Etiology unknown
Sites
  • Widespread cutaneous distribution but limited to the skin, as a rule
  • Extracutaneous involvement may occur in advanced stages (lymph nodes, liver, spleen, lungs, blood, rarely bone marrow)
Clinical features
  • Multiple skin lesions, progressing stepwise from a scaly rash to patches to plaques to tumors
  • Often misdiagnosed as psoriasis
  • Erythrodermic stage is uncommon; lacks criteria for Sézary syndrome
Case reports
Prognosis and treatment
  • Indolent (median survival 8 years) course with slow progression (years, decades) but may progress to Sézary syndrome
  • Single most important prognostic factor is clinical stage
  • Limited disease: excellent prognosis, survival similar to general population
  • Adverse prognostic parameters: skin tumors, extracutaneous dissemination, > 60 years of age, increased LDH, histologic transformation ( > 25% blast cells)
  • Spreads to lymph nodes and bone marrow; 25% have peripheral blood involvement resembling Sézary syndrome
  • Transformation to large T cell lymphoma occurs occasionally as a terminal event; may be associated with hyperdiploidy
  • Treatment: phototherapy or chemotherapy, topical therapy, radiotherapy
Postulated Normal Counterpart
  • Mature skin homing CD4+ T cell
Gross description
  • Patches, plaques, tumors, ulceration, erythroderma
Gross images

Images hosted on other servers:

Patches

Microscopic (histologic) description
  • See below for precursor lesions and variants
  • T cells (small and large) in epidermis and upper dermis with cerebriform nuclei (marked infolding of nuclear membrane), Pautrier microabscesses in epidermis; minimal papillary dermal fibrosis, may have granulomas
  • Patch stage: superficial band-like or lichenoid infiltrate, mainly lymphocytes and histiocytes but also a few atypical cells (small / medium sized, cerebriform nuclei, halo) usually confined to the epidermis (basal layer)
  • Plaque stage: more pronounced epidermotropism with occasional characteristic intraepidermal collections of atypical cells (Pautrier microabscesses)
  • Tumor stage: more diffuse dermal infiltrate, may lose epidermotropism, more size and shape variability of tumor cells, histologic transformation may occur ( > 25% large lymphoid cells in the dermal infiltrate)
  • Uninvolved but enlarged lymph nodes frequently show dermatopathic lymphadenopathy
  • Histologic staging for clinically abnormal lymph nodes ( > 1.5 cm): no involvement, early involvement, overt involvement (see staging of primary cutaneous lymphoma)
  • Can screen for Mycosis fungoides or Sézary syndrome in peripheral blood using flow cytometry for CD26 negative or dim expression
  • Tumor cells also have increased CD4 / CD8 ratio and lower CD4 surface expression (Am J Clin Pathol 2001;115:885)
  • CD8:CD3 ratio < 25% in epidermal component of lymphocytic infiltrate is supportive of diagnosis (Mod Pathol 2003;16:857)
Microscopic (histologic) images

Images hosted on other servers:

Various Images

Pautrier microabscesses

Halo lymphocytes

Mycosis fungoides and Hodgkin lymphoma

Positive stains
Negative stains
Molecular / cytogenetics description
  • Clonal rearrangement of T cell receptor genes but no specific chromosomal abnormalities
  • Complex karyotypes especially in advanced stages
  • Constitutive activation of STAT3 and inactivation of CDKN2A / p16 and PTEN may be associated with disease progression
  • TNF anti-apoptotic pathway activation in tumorigenesis
Differential diagnosis
Precursor Lesion - Parapsoriasis
  • Chronic recalcitrant erythematous scaling lesions
  • Benign form: parapsoriasis en plaques (Brocq disease), no malignant transformation
  • Large plaque forms with or without poikiloderma (LPP) may evolve into mycosis fungoides or cutaneous T cell lymphoma (10 - 50%)
  • Histology: subepidermal free zone, sparing of the papillary dermis, no significant epidermotropism
  • TCRγ gene rearrangements may be clonal (50%) but have no prognostic significance
Variants of Mycosis Fungoides

Folliculotropic Mycosis Fungoides:

Definition / General:
  • Follicular infiltrates of cerebriform CD4+ T lymphocytes
  • Frequent sparing of the epidermis and interfollicular areas
  • Mucinous degeneration of hair follicles (follicular mucinosis)
  • Preferential head and neck involvement with grouped follicular papules and associated alopecia
  • Less amenable to skin targeted therapy due to deep localization (5 year survival 70 - 80%, worse than plaque stage)

Micro Images:

Images hosted on other servers:

Various images



Pagetoid Reticulosis:

Definition / General:
  • Patches / plaques with intraepidermal neoplastic T cell proliferation and sponge-like disaggregation of the epidermis, typically on a distal limb
  • Term used only for the localized type (Woringer-Kolopp), NOT for the disseminated one (Ketron-Goodman) currently classified as either aggressive epidermotropic CD8+ CTCL or cutaneous γδ TCL
  • May be either CD4+ / CD8- or CD4- / CD8+
  • Often CD30+
  • No reported extracutaneous dissemination or disease related death

Gross Images:

Images hosted on other servers:

Various images


Micro Images:

Images hosted on other servers:

Various images



Granulomatous Slack Skin:

Definition / General:
  • Extremely rare, indolent clinical course
  • Slowly developing folds of lax skin (axillae, groin)
  • Granulomatous infiltrate of clonal CD4+ T cells, abundant macrophages and multinucleated giant cells
  • Associated with classical Hodgkin lymphoma (one third of cases) and classical MF

Gross Images:

Images hosted on other servers:

Axillary nodules

Various images


Micro Images:

Images hosted on other servers:

Dense dermal mononuclear infiltrate

Epithelioid and giant cell granuloma

CD4+

Various images



Hypopigmented Variant:

Definition / General:
  • Hypopigmentation occurs in the absence of classic lesions of mycosis fungoides
  • Usually affects young people with dark complexions with childhood onset; otherwise similar history, prognosis and histology of classic form, although most were CD8+ (classic forms are CD8-, Am J Surg Pathol 2002;26:450)


Syringotropic Variant:

Definition / General:
  • Rare; solitary, well circumscribed reddish brown plaque with hair loss
  • Predominant involvement of irregularly proliferating eccrine sweat glands by cerebriform lymphocytes


Other Variants:

  • Bullous,
  • Dyshidrotic,
  • Granulomatous,
  • Hyperkeratotic / Verrucous,
  • Hyperpigmented,
  • Ichthyosiform,
  • Palmoplantar,
  • Pigmented purpura-like,
  • Poikilodermic,
  • Pustular,
  • Unilesional,
  • Vegetating/papillomatous
Additional references