Mycosis fungoides / Sézary's syndrome

Definition

Mycosis fungoides: A T-cell lymphoma of skin characterised by epidermal and dermal infiltration by small to medium size cells with cerebriform nuclei.

Sézary syndrome; a variant of mycosis fungoides with a leukaemic component and much more aggressive behavior.

Synonyms

Epidemiology

Mycosis fungoides accounts for only 0.5% of all non-Hodgkin lymphomas, but is the most common cutaneous T-cell lymphoma. Rarely, Mycosis fungoides occurs in children, where the histology and immunohistochemistry are as for adult disease¹.

Sézary syndrome is a rare disease of adults.

Clinical features

 Mycosis fungoides: usually remains confined to the skin for years, with late dissemination to lymph nodes liver spleen, lungs and blood. The initial lesions are patches or plaques on the trunk, eventually progressing to tumours. Variants are discussed below.

Sézary syndrome: there is disseminated disease involving the skin, lymph nodes and blood. Patients present with erythroderma, pruritus, alopecia and lymphadenopathy.

Histopathology

Mycosis fungoides: there is an epidermotropic infiltrate of small to medium size cells with cerebriform nuclei. The formation of Pautrier abscesses is highly characteristic but is not always present. The dermal infiltrate may be patchy, band-like or diffuse. It is often accompanied by an infiltrate of small lymphocytes and eosinophils. Lymph node involvement may be staged:

category 0; a dermatopathic picture but no visible neoplastic cells. However, T-cell receptor gene rearrangement studies may show involvement, with an associated worse prognosis.

category I; scattered cerebriform lymphocytes in foci of 3 to 6.

category II; partial effacement by clusters of neoplastic cells, often in the paracortex.

• category III; complete effacement by a massive diffuse infiltrate.

Variants

• large plaque parapsoriasis (LPP, parapsoriasis en plaque, prereticulotic poikiloderma, parapsoriasis variegata). Regarded by some as a precursor lesion, this probably represents an early "latent" stage of mycosis fungoides. The plaques are defined as being larger than 5 cm. The clinical appearance varies form hyperpigmented to hypopigmented, with telangestasia and atrophy to prominently reticulate (parapsoriasis variegata). Early lesions show mildly hyperkeratotic psoriasiform hyperplasia with patchy parakeratosis overlying a superficial perivascular lymphocytic infiltrate, which may be indistinguishable from benign small plaque parapsoriasis. Fully developed lesions show epidermal atrophy, epidermotropism and a superficial dermal lymphocytic infiltrate with nuclear atypia. There is usually pigmentary incontinence and telangectatic vessels are common. 10-30% of cases of LPP progress to overt mycosis fungoides¹.

• pagetoid reticulosis: the infiltrate is strictly epidermal. The cells are often CD30+ and may be CD4-/CD8+, CD4+/CD8- or CD4-/CD8-. Because it is localised, and does disseminated and is CD8+, pagetoid reticulosis probably should be classified separately¹. Woringer-Kolopp disease is an acronym for the localised form while Ketron-Goodman disease (so-called generalised pagetoid reticulosis) shows multiple skin lesions; the latter is probably a particularly epidermotropic form of true mycosis fungoides¹.

• Syringotropic mycosis fungoides. There are plagues studded with red-brown papules. Hyperplastic sweat gland epithelium is surrounded and infiltrated by the neoplastic lymphocytes.

• Folliculotropic mycosis fungoides. There are folliculocentric papules, cysts and comodomes. The neoplastic lymphocytes home to the follicular epithelium. There is no associated mucinosis. Similar homing may rarely be seen in Sezary syndrome.

• Mycosis fungoides-associated follicular mucinosis: the infiltrate is follicular rather than epidermal and is associated with mucinous degeneration of hair follicles. There is preferential involvement of the head and neck. This condition needs to be distinguished from benign follicular mucinosis.

• granulomatous mycosis fungoides. This variant is clinically indistinguishable from the conventional type. However, histology shows abundant macrophages forming nodules. There may be lymphophagocytosis but there is no loss of elastic tissue. Granulomatous slack skin disease clinically distinct and is probably best regarded as a specific entity.

Sézary syndrome: skin lesions are similar to those of Mycosis fungoides. Lymph node show a diffuse or paracortical infiltrate. The circulating cells may be small (Lutzner cells) or large (classical Sézary cells). There may be an elevated CD4/CD8 ratio. The bone marrow infiltrate is often sparse.

Immunohistochemistry

	Mycosis fungoides	Sézary's syndrome
CD1a
CD2	positive
CD3	positive
CD4	positive	usually positive
CD5	positive
CD7	usually negative	variable
CD8	usually negative	rarely positive
CD11b
CD16
CD25	variable
CD30	often positive in pagetoid reticulosis
CD56
CD57
TCR	b-positive, rarely d-positive	b-positive
TdT
TIA-1
HECA	usually positive
ALK

†: fresh frozen tissue only

Differential diagnosis

• Cases presenting with skin tumours ab initio (d'emblee lesions) probably represent other types of T-cell lymphoma.

• benign cutaneous lymphoid lesions; may also be CD7-.

• lymphomatoid drug reaction

• lymphomatoid papulosis

• pigmented purpura; mycosis fungoides may occasionally present with a purpuric clinical appearance, but most cases of pigmented purpura are not early mycosis fungoides¹.

• Mycosis fungoides-associated follicular mucinosis: must be distinguished from benign follicular mucinosis / "alopecia mucinosa". Only the presence of overt lymphocytic atypia or of more typical mycosis fungoides elsewhere will establish a definite malignant diagnosis and prolonged follow-up may be indicated¹.

• granulomatous mycosis fungoides needs to be distinguished from non-neoplastic granulomatous dermatitides; granuloma annulare, necrobiosis lipoidica, sarcoid and a granulomatous response to infection.

• see cutaneous T-cell lymphoproliferative disorders

Prognosis

• Mycosis fungoides: depends greatly on the extent of disease. 20-50% of advanced cases undergo large cell transformation giving rise to CD30-positive anaplastic large cell lymphoma; t(2;5) is not seen¹.

• Sézary syndrome: an aggressive disease with a five year survival of 10-20%.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

¹Liu, V. and McKee, P.H. Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues. Adv Anat Pathol 2002;9:79-100.

This page last revised 23.12.2002.

©SMUHT/PW Bishop