Mycosis Fungoides, Sezary Syndrome or T-Cell Prolymphocytic Leukemia?.

Sézary syndrome (SS) is a cutaneous T cell lymphoma in which the demonstration of a T-cell clone in the skin and in the peripheral blood (PB) together with cytomorpho-immunophenotypical criteria are needed for a correct diagnosis besides the typical erytrhoderma and lymphadenopathies. In March 2004 a 63-year-old white man developed a rapidly growing and slightly itching squamous macular eruption on the interscapular region: skin biopsy revealed superficial dermal band-like infiltrates, consisting of small CD3+ CD4+ CD8- lymphocytes with epidermotropism and a few Pautrier’s microabscesses, suggesting a diagnosis of mycosis fungoides (MF). A simultaneous blood involvement was detected with lymphocytosis (14000/μl), increased CD4, CD3, CD2, CD5, CD7 positive T cells and T cell receptor (TCR) Vβ5.1 chain monoclonality. As for initial staging, bone marrow (BM) trephine biopsy demonstrated an interstitial infiltrate of small CD3+ and CD5+ lymphocytes and CT scan did not show any visceral involvement or lymphoadenopathies. TCRγ and TCRδ gene rearrangement patterns in PB and BM analyzed by PCR showed, respectively, a monoclonal Jpγ and a oligoclonal Vδ3Jδ1 rearrangement. Circulating Lutzner cells were seen by electronic microscopy. Cytogenetic analysis in PB using fluorescence in situ hybridization (FISH) techniques revealed multiple abnormalities (add7q, i8q, 10p+, 12p-). In September 2004 the patient started chemotherapy with fludarabine 25 mg/m² (days 1 to 5 every 4 weeks) for 5 courses. In April 2005 he was still in good condition, not showing skin lesions; CT scan was negative, but lymphocytosis had increased (45000/μl). A BM trephine biopsy and the cytogenetic analysis of PB confirmed the above mentioned alterations. Cytofluorimetric analysis of the CD4+ CD5+ CD7+ population showed two different pattern as regarding CD3 positivity; half of the T cells was expressing CD3 antigens on the membrane surface, the other half in the citosol; however both isoforms of the molecule expressed the same Vβ5.1 chain; another cytofluorimetric characteristic was the strong expression of CD5 and CD7 in terms of elevated fluorescence intensity, a characteristic feature of T-cell prolymphocytic leukemia (T-PLL). The study of TCRγ and TCRδ gene rearrangement in PB showed, respectively, a monoclonal Jpγ and a monoclonal Vδ3Jδ1 rearrangement. In May 2005 the patient started a second line therapy with 30 mg alemtuzumab administered subcutaneously 3 times a week. At the end of the 5^th week a complete haematological, immunophenotypical and cytogenetic response was obtained, even if the molecular analysis showed a persistent clonal expansion of T cells. This case demonstrates that the currently proposed haematological, flowcytometric and molecular criteria for SS are not forceful enough to differentiate between SS, MF with blood involvement and some T-PLL cases. A more detailed characterization of Sezary cells is therefore needed. Some investigators suggest that a loss of T-cell lineage markers together with the amount of CD4+ CD26- cells in PB in an appropriate clinical and histological contest, could be a more sensitive criterion of SS.