The Leukemic Presentation of Mantle-cell Lymphoma: Disease Features and Prognostic Factors in 58 Patients

Abstract

Mantle-cell lymphoma (MCL) is a B-cell malignancy with distinct molecular genetics and pathological features. Peripheral blood involvement has been reported with variable frequency, but information on the natural history of cases presenting with leukemia is lacking. This study aimed to determine the clinical and prognostic features of such cases. We studied clinical features, tumor characteristics, prognostic factors and outcome in 58 patients with leukemic presentation of MCL. Diagnosis was based on morphology, immunophenotype, presence of t(11;14), histology and cyclin D1 expression. The median age was 62 years and male:female 2.4:1. Presenting features included splenomegaly (74%), lymphadenopathy (45%), hepatomegaly (17%) and, in a minority, gastro-intestinal involvement or involvement of Waldeyer's ring; 10% had lymphocytosis alone. Six patients developed central nervous system disease. Median lymphocyte count was 58 x 10(9)/l, 55% had anemia and 17% had thrombocytopenia. Morphology of peripheral blood showed small-cell MCL in 15% of cases, typical MCL in 46% and blastoid MCL in 39%. Immunological markers showed a typical phenotype (CD5+ CD23 -) in 68%, and atypical phenotypes, CD5- CD23- in 17% or CD5+ CD23+ in 15%. CLL scores were 0, 1 or 2 in 96%. Median overall survival was 36 months. Good response to first-line treatment (P = 0.0008) and splenomegaly (P = 0.03) were favorable prognostic factors, while other features including morphology and CD38 expression had no impact on survival or treatment response. This analysis demonstrates that except for splenomegaly, survival of MCL patients presenting with leukemia is not significantly influenced by clinical or tumor characteristics. Splenectomy is a useful treatment option in this group of patients.

IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL)

“…In MCL, ZAP-70 tends to be negative 18,28 and CD38 is expressed in more than half of the cases, although their prognostic value is not clear. 19,20,29,30 In SMZL, CD38 is expressed in about half of the cases 22,31 and in a recent report it appears to correlate with unmutated IgVH and aggressive clinical behavior. 31 Our series is too small to firmly demonstrate if these markers have a prognostic impact.…”

A novel scoring system combining expression of CD23, CD20, and CD38 with platelet count predicts for the presence of the t(11;14) translocation of mantle cell lymphoma

“…These data, however, were largely extrapolated from immunohistochemistry on paraffin embedded tissue sections. With flow cytometry CD23 positive MCL is a much more frequent finding: estimates of prevalence range from 15% to 55% (13)(14)(15)(16). The difference between CD23 expression on MCL in lymph nodes and that in circulation may also be because of a variation in LPD behavior.…”

How I diagnose and treat splenic lymphomas

“…[44][45][46] Moreover, BM assessment makes it possible to reach an accurate diagnosis in most cases of MCL, HSTL, LPL, and SMZL, even in the absence of lymph node or spleen assessment. 12,17,27,35 SLs of germinal center B-cell derivation may be difficult to classify in the BM because of the lack of germinal centerassociated phenotypic and cytogenetic/molecular markers, which has been reported in a considerable fraction of primary splenic FL cases. 22 In addition, diagnosis of micronodular T-cell/histiocyterich large B-cell lymphoma in the BM may prove challenging, given the puzzling effect of the rich and heterogeneous cloneassociated reactive environment.…”

“…Such circulating components may rarely configure an overt leukemic picture or, more frequently, consist of a subtle spillover of splenic and marrow infiltrates, such as in some cases of SMZL or hairy cell leukemia (HCL). 18,35,36 PB examination is therefore a mandatory step in the diagnostic workup of SLs. We pay particular attention to data that can be inferred by the morphologic evaluation of May-GrunwaldGiemsa-stained PB smears.…”