University of Virginia Health System

Leukemic Phase of Mycosis Fungoides and Sézary Syndrome

(a) Clonal T cell in a case of mycosis fungoides- Peripheral blood smear, Wright-Giemsa stain, 1000x

(b) Clonal T cell in a case of Sezary syndrome- Peripheral blood smear, Wright-Giemsa stain, 1000x

(c) Positive PAS staining vacuoles in a case of Sezary syndrome- Peripheral blood smear, PAS stain, 1000x 

Description:

Cutaneous T cell lymphoma (CTCL) is by far the most common presentation for all peripheral T cell lymphomas, representing approximately 85% of all cases. Mycosis fungoides (MF) comprises >50% of CTCLs and Sezary syndrome (SS) <5%. Small numbers of MF-SS cells are not infrequently seen on a peripheral blood smear during the course of the disease in patients with MF. The extent of peripheral blood involvement is used in the TNMB staging system. The designation BO indicates <5% and B1 >5% as determined by a differential count from a Wright-Giemsa stained peripheral blood smear. The prognostic significance of finding small numbers of circulating cells is minimal. When the number of MF-SS cells is >20%, and if associated with generalized erythrodermia, a diagnosis of SS is made, and the course is much more aggressive, whether SS occurred de novo and emerged during the course of MF. Other evidence of systemic spread is usually present, (e.g. generalized lymphadenopathy) in SS.

Description:

The circulating MF-SS cells have a characteristic though not pathognomonic appearance by light microscopy. Those seen in MF cannot be distinguished from those seen in SS (a,b). They range in size from that of a normal small peripheral blood lymphocyte up to 2 times larger. The nuclear:cytoplasmic ratio is high with only scant cytoplasm that is grey to light blue in color. Vacuoles are frequently seen surrounding the nucleus, and contain glycogen (positive on PAS staining) (c). The characteristic convoluted (cerebroform) nuclear chromatin is the most distinguishing though not diagnostic feature. Nuclear clefting is also seen.

Cytochemistry:

PAS positive cytoplasmic vacuoles.

Immunophenotype:

• Clonal MF cells- CD3+, CD4+, CD8-, and CD7-
• Clonal SS cells- CD3+, CD4+, CD8-, and CD7±.
• The presence or absence of CD7 cannot be used to differentiate between MF and SS cells. Other pan T markers, CD2 and CD5, may also be negative. Rare cases are CD8+.

Cytogenetics:

No signature cytogenetic abnormality has been identified. Complex abnormalities are frequently noted.

Clinical and Laboratory Manifestations and Prognosis:

Patients with MF usually pursue an indolent course over years or decades with the disease confined to the skin in the form of plaques or erythematous patches. Symptoms can be controlled by topical therapy such as phototherapy with PUVA (psoralen and ultraviolet light A), corticosteroids, and retinoid gels for long periods of time. Patients who have progressed to the tumor stage also respond to topical therapy and localized orthovoltage radiation. Patients with more disseminated cutaneous disease not responding well to topical measures respond well to total skin electron beam therapy. In patients who progress with systemic spread, the prognosis is poor due to a relative resistance to presently available chemotherapeutic agents and other regimens. The prognosis in SS is also quite poor for the same reasons.

General References:

• Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Pathology and genetics of tumours of hematopoietic and lymphoid tissues. Vol. 3 of World Health Organization classification of tumors, Lyon, France: IARC Press, 2001
• Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 105:3768, 2005
• Koh HK, Charif M, Weinstock MA. Epidemiology and clinical manifestations of cutaneous T cell lymphoma. Hematol Oncol Clin North Am. 9:943, 1995
• Keehn CA, Belongie IP, Shistik G, et al. The diagnosis, staging, and treatment options for mycosis fungoides. Cancer Control 14(2):102, 2007
• Kim EJ, Lin J, Junkins-Hopkins JM, et al. Mycosis fungoides and Sezary syndrome: an update. Curr Oncol Rep 8:376, 2006

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