Atypical chronic lymphocytic leukaemia witht(ll;14)(ql3;q32): karyotype evolution and prolymphocytic transformation

Abstract

In order to define better the cytological and clinical features of atypical B-cell chronic lymphocytic leukaemia (B-CLL) with t(11:14)(q13;q32), sequential morphologic immunological and cytogenetic studies were performed in seven patients belonging to a series of 72 consecutive cases presenting with a diagnosis of CLL or atypical CLL according to the FAB criteria. Cytologic diagnosis in these seven patients with t(11;14) was typical CLL in two cases presenting with < 10% large lymphocytes (LL) and prolymphocytes (PL) and atypical CLL in five cases in which LL and PL comprised between 10% and 55%. The diagnosis was supported by histologic findings on bone marrow biopsy (five cases) or splenectomy specimens (two cases). A progressive increase of peripheral LL and PL was observed, resulting in a switch of FAB diagnosis over a 6-60-month period from typical CLL into atypical CLL in two cases and from atypical CLL into prolymphocytic leukaemia in five cases. Immunophenotyping showed a mature B-cell phenotype with CD19, CD22, CD24 positivity and CD10 negativity in all patients. A bright-staining pattern for surface immunoglobulins (SIg) was detected in 6/7 cases, CD5 positivity in 6/7 cases, and CD23 positivity in 1/7 cases. The FMC-7 monoclonal antibody was positive in > 40% cells in 5/6 cases. Chromosome changes in addition to t(11;14) were seen in five cases; in two cases unbalanced translocations involving the 3q21 chromosome region, resulting in partial trisomy for the long arm of chromosome 3, were detected early in the course of the disease. Karyotype evolution that was associated with disease progression occurred in 3/6 assessable patients. Comparison of these findings with similar data from 65 B-CLL patients without t(11:14) showed that atypical morphology, switch of FAB diagnosis during the course of the disease, and karyotype evolution were more frequently seen in cases with t(11;14) (5/7 v 15/65 cases, P = 0.015, 7/7 v 7/65 cases, P < 0.0001, and 3/6 v 5/45 assessable cases, P = 0.04, respectively). The frequency of positivity for CD23 and bright SIg staining differed significantly in the two groups. It is concluded that t(11;14) identifies a cytologically atypical subset of B-CLL, characterized by frequent cytologic and cytogenetic evolution and by a distinct immunological profile, sharing some biological features with mantle cell lymphoma.

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

“…Two previous reports describe primarily leukemic disorders with some similarities to the current patient series presented here. Cuneo et al (29) identified seven patients with t(11;14)-positive "atypical CLL" among a consecutive group of 72 CLL cases. These neoplasms were found to differ from typical CLL cases by virtue of variant morphology, karyotypic Table 3).…”

Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia

“…35 Both cases matched the clinicobiologic picture previously reported for CLL with t(11;14)/cyclin D1 overexpression, namely hyperleukocytosis, massively enlarged spleen, atypical morphology with a CD5+/CD23−/FMC7+ immunophenotype, and unfavorable outcome. 30,31 Both patients evolved to a RS 48 and 70 months after the initial CLL diagnosis, respectively (Table 1).…”

“…On the other hand, cyclin D1 overexpression has also been detected in a subset of atypical and clinically aggressive CLL. 30,31 Whether or not these cases are more prone to evolve into RS than typical CLL is not clear.…”

Quantitative RNA slot-blot analysis of CCND1/cyclin D1 expression in suspected mantle cell lymphoma

“…1 It has also Materials and methods been described in multiple myeloma (MM), splenic lymphoma with villous lymphocytes (SLVL), B prolymphocytic leukemia Patient and control material (B-PLL) and in rare cases of apparently typical chronic lymphocytic leukemia. 2,3 The majority of molecular analyses have CCND1 expression was assessed on cryopreserved diagnostic been performed in t(11;14) positive MCL. The breakpoints on material obtained, with informed consent, from patients inveschromosome 14 cluster within the immunoglobulin heavy tigated for, or to exclude, lymphoproliferative disorders.…”