Blastic Mantle Cell Leukemia: An Unusual Presentation of Blastic Mantle Cell Lymphoma

Abstract

Six patients had blood and bone marrow manifestations characterized by the presence of morphologically immature or blastic B-lineage lymphoid cells expressing CD5 antigen. The median patient age was 70 years, and the male-to-female ratio was 5:1. The presence or degree of lymphadenopathy and splenomegaly was variable among this group at staging evaluation, although two patients did not have these features. One patient had an antecedent diagnosis of classical nodal mantle cell lymphoma, without prior morphologic blood or bone marrow involvement. Other patients lacked a history of underlying lymphoproliferative disorders. The median white blood cell count was 120 ؋ 10 9 /L. Most patients had thrombocytopenia, whereas only one patient had neutropenia at presentation. Leukemic peripheral blood cells in these six cases were small to medium in size with fine or granular nuclear chromatin and small or inconspicuous nucleoli. The pattern of marrow involvement was interstitial or diffuse, with cells showing immature nuclear features resembling acute leukemia or blastic lymphoma. All tumors demonstrated a consistent immunophenotype of B-cell lineage, surface immunoglobulin positivity, and CD5 antigen expression. The progenitor cell-associated markers CD34 and TdT were not expressed, and CD23 antigen was either negative (three of four cases) or only weakly present (one of four cases). The presence of a karyotypic t(11;14)(q13;q32) was documented in one tumor, whereas two other cases had BCL-1 gene rearrangements by either polymerase chain reaction or Southern blot analysis. Cyclin D1 mRNA overexpression was noted in three of four cases tested. This patient group was characterized by very poor overall survival (median, 3 months; range, 0.5 to 6 months). The aggregate clinical, pathologic, and genetic data in these unusual cases are consistent with de novo or predominant leukemic presentations of blastic mantle cell lymphoma. Accurate diagnosis in such cases is greatly facilitated by cytogenetic studies or the demonstration of BCL-1/ cyclin D1 abnormalities. The expression of surface immunoglobulin (SIg) generally signifies a mature B-cell phenotype and is usually accompanied by nuclear changes of chromatin condensation. However, exceptional lymphoid neoplasms characterized by blastic cytology and mature phenotype have been described. One example is a previous report of nine cases of "mature" B-cell acute lymphoblastic leukemia (ALL), characterized by non-L3 leukemic blast morphology and the presence of SIg positivity (1). These cases were phenotypically somewhat heterogeneous, although TdT was consistently negative in each case and CD10 expression was observed in all of five tumors tested for this antigen. Among these unusual blastic, SIg-positive leukemic cases, karyotypic analysis also revealed heterogeneity. Two tumors exhibited 8(q24) region translocations, implying C-MYC gene deregulation. Of interest, one of these lesions had a t(14;18) anomaly, in addition to 8(q24) rearrangement, suggesting blastic transformation of...

Acquired TERT promoter mutations stimulate TERT transcription in mantle cell lymphoma

“…Second, TERTp mutations correlated with more lymphoma proliferation and tumor burden, as suggested by the significantly higher number of lymphoma cells circulating in peripheral blood. Peripheral blood involvement is common in MCL patients [23] and associates with a poorer outcome [24][25][26][27]. Third, TERTp-mutant samples had TU or MBM IGHV status and all of them overexpressed SOX11.…”

Blastic mantle cell lymphoma developing concurrently in a patient with chronic myelogenous leukemia and a review of the literature

“…CT scan of the abdomen showed abdominal adenopathy, and extensive lymphomatous infiltration of the liver, gall bladder, stomach, pancreas, kidneys, and bladder. The peripheral blood smear and bone marrow aspirate and biopsy demonstrated an infiltrate of large cells featuring scant pale blue cytoplasm, fine chromatin, and prominent nucleoli consistent with a blastic subtype [7]. Flow cytometric studies of the bone marrow detected a monoclonal B-cell population similar to the peripheral blood results.…”

“…Morphologically, MCL consists of a monotonous proliferation of small-to medium-sized lymphocytes with scant cytoplasm, variably irregular nuclei with condensed chromatin, and inconspicuous nucleoli [21]. There is a blastic variant that has a very poor prognosis with a median survival of 14.5 months [7,[22][23][24]. Immunophenotypically, the neoplastic lymphocytes express pan B-cell markers CD19, CD20, and CD22, the T-cell marker CD5, strong sIg expression, kappa/lambda restriction, and absence of CD10 and CD23 [21,25].…”

Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings

“…[8][9][10][11] Peripheral blood involvement of mantle cell lymphoma at diagnosis has been reported in 20-60% of patients and has been associated with a worse outcome when compared with nonleukemic mantle cell lymphoma. [12][13][14][15] Lymphocytosis may be the first sign of this involvement, but it may not occur in some patients. 12 As complete remission is achieved in less than 35% of mantle cell lymphoma cases, 3,[16][17][18] most patients will eventually develop relapse.…”