A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories.

The current World Health Organization (WHO) classification of hematopoietic malignancies defines several types of mature T-cell leukemia including T-cell prolymphocytic leukemia (T-PLL), Sezary syndrome (SS), and T-cell large granular lymphocytic (T-LGL) leukemia. These neoplasms can show overlapping features with each other and with T-cell lymphomas involving peripheral blood (PB). We analyzed the spectrum of clinicopatho-logic features in 102 mature T-cell leukemias and compared them to 10 hepatosplenic T-cell lymphomas that involved PB. T-PLL, defined as a T-cell leukemia showing rapidly rising PB lymphocyte counts, was the only tumor type expressing the oncoprotein TCL1 (71% of cases) and could present with relatively low lymphocyte levels or small tumor cell morphology. SS, defined by accompanying erythrodermic skin disease, was frequently associated with peripheral eosinophilia but could also develop high numbers of prolymphocytes, especially late in the disease course. T-LGL leukemia, defined by accompanying cytopenias or autoimmune phenomena (or both), had the best clinical outcome and generally showed the lowest circulating lymphocyte levels with only a few cases developing marked lymphocytosis. Using the dominant clinical or phenotypic feature, we describe here the degree of overlap among currently recognized WHO categories and identify areas where further clarification is needed. Our results indicate that incorporation of additional criteria, such as TCL1 expression status and hematologic parameters, can assist in a more accurate classification.

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy.

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2-8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy.

Less apoptosis in patients with 5q-syndrome than in patients with refractory anemia.

The WHO classification of hematological malignancies includes 5q-syndrome as a separate category within myelodysplastic syndromes (MDS). Clinically, patients with 5q-syndrome have a milder disease than patients with other MDS. The basis for this difference is not known. Identifying 5q-syndrome can be difficult because some of its morphologic and cytogenetic features are similar to those of other MDS. We compared apoptosis between 5q-syndrome and other refractory anemias. We found lower levels of apoptosis in 5q-syndrome as detected by less disruption of mitochondrial potential (P=0.008) and decreased annexin V positivity (P=0.01). Our results suggest that lower apoptosis in 5q-syndrome may explain the milder clinical course of the disease and distinguish 5q-syndrome from other MDS.

Myeloid disorders with deletion of 5q as the sole karyotypic abnormality: the clinical and pathologic spectrum.

The 5q-syndrome has been recognized as a distinct subtype of myelodysplastic syndrome (MDS) with characteristic clinical and pathologic features. Nevertheless, the definition of this syndrome is imprecise. To better understand how the 5q-syndrome is related to other "5q- only" myeloid disorders, we searched our conventional cytogenetics file for cases with 5q- as the sole karyotypic abnormality. 31 cases of "5q- only" myeloid disorders were found, and they were refractory anemia (n = 16), refractory anemia with excess blasts (RAEB) (n = 5), RAEB in transformation (n = 1), chronic myelomonocytic leukemia (n = 1) and acute myeloid leukemia (n = 8). They included 15 men and 16 women, with a median age of 67 years (range, 40-84 years). The marrow blast count was < or = 11% in 22 cases and > or = 25% in the remaining nine cases. The following morphologic features were common in the marrow: megakaryocytic hypolobation (30/31, 97%), erythroid hypoplasia (26/31, 84%), basophilia (19/31, 62%) and eosinophilia (16/31, 52%). Of those with < or = 11% blasts, 7/22 cases met the criteria of the 5q-syndrome, as defined by high mean corpuscle volume (MCV), normal/high platelet counts, and megakaryocytic hypolobation. Except for the two defining parameters for the 5q-syndrome (MCV and platelet count), there was no significant difference in hematologic parameters between the 5q-syndrome and other cases with < or = 11% blasts. Furthermore, no significant difference in the chromosomal breakpoints or survival was found between these two groups. We conclude that "5q- only" MDS show consistent morphologic features, suggesting a common pathogenesis related to their similar cytogenetic abnormality. In "5q- only" MDS with < or = 11% marrow blasts, strict application of the conventional criteria of the 5q-syndrome may not be necessary in predicting the overall prognosis.