A. Criel

Trisomy 3 in marginal zone B-cell lymphoma: A study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B‐cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non‐recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.

Trisomy 12 is uncommon in typical chronic lymphocytic leukaemias

The incidence of trisomy 12 was studied by conventional chromosome analysis in 111 patients referred as B‐cell chronic lymphocytic leukaemia (B‐CLL). Fluorescent in situ hybridization (FISH) was also applied in 34 of those patients with either a normal karyotype or no analysable mitoses. By karyotyping, trisomy 12 was present in 11.7% (13/111), whereas additional FISH increased the incidence to 14.4% (16/111). When subdividing our cases in either typical CLL (n= 90), fulfilling the FAB classification criteria, or atypical CLL (n= 21), with one or more variations from those criteria, the incidence of +12 by metaphase analysis was 3% and 48%, respectively. Additional FISH increased the incidence to 4% and 57%. The most common aberration in atypical CLL was FMC7 positivity (n= 11), followed by CD5 negativity (n= 8), strong surface immunoglobulin staining (n= 7) and atypical morphology (n = 6). Trisomy 12 could only be demonstrated in a small proportion of neoplastic cells in all positive cases. By FISH and/or karyotyping, all available samples at diagnosis of the disease were positive.

High-incidence of Chromosome-abnormalities in Igg3 Myeloma

Chromosomes were studied in 33 untreated myeloma patients, and results were correlated with the class of Ig secreted by the myeloma cells. A high incidence of clonal karyotypic anomalies seemed to be present in IgG3 myeloma patients, in whom the disease was advanced at diagnosis and rapidly progressing. Among the chromosome anomalies, the t(11;14)(q14;q32) was particularly prominent, and this chromosome anomaly, in analogy with the Ph1 chromosome, may characterize a family of lymphoproliferative disorders.

Lymph node histology in typical and atypical chronic lymphocytic leukemia

According to the French-American-British (FAB) proposal on the classification of chronic lymphoid leukemia (CLL), the disorder can be subdivided into typical and atypical CLL. We recently demonstrated the prognostic significance of this subgrouping and based on these results we suggested that typical and atypical CLL represent two closely related, but different entities. These results prompted us to investigate 42 patients diagnosed with CLL based on the results of lymph node biopsy in order to identify the histologic counterpart of the CLL variants. A first group of 14 cases showed a monomorphic proliferation of small round lymphocytes associated with the occurrence of small pseudofollicles. All these cases were diagnosed as typical CLL on peripheral blood (13 cases) or bone marrow smear (1 case). The remaining 28 cases showed aberrant histologic features characterized by the presence of large numbers of paraimmunoblasts and prolymphocytes, forming very large pseudofollicles, and/or by nuclear irregularities of the neoplastic cells. Based on peripheral blood smears (22 cases) or bone marrow smears (six cases), two cases showed no peripheral blood involvement, 21 cases were diagnosed as atypical CLL, and five as typical CLL. From these data we can conclude that a histologic counterpart of the CLL variants recognized in the FAB proposal does exist; moreover, our data may explain reports on lymph node involvement by CLL composed of small cleaved cells and clarify the occurrence of pseudofollicles in cases described as mantle cell lymphomas.

Hypercalcemia and diffuse osteolytic lesions in the acute phase of chronic myelogenous leukemia a possible relation between lymphoid transformation and hypercalcemia

A patient with blastic crisis of chronic myelogenous leukemia (CML) is presented. The acute phase was localized in the lymph nodes and bones, causing severe osteolytic lesions and hypercalcemia. The blast cells were undifferentiated in light microscopy and by histochemical stains. As viewed under electron microscopy, a considerable proportion of the blast cells were of myeloid origin, while immunologic markers and cytogenetics indicated a lymphoid origin. It seems plausible that the patient had a mixed myeloid‐lymphoid blast crisis, but that the lymphoid blasts were responsible for the severe osteolytic lesions and the hypercalcemia.

Isodicentric (X)(q13) in haematological malignancies: presentation of five new cases, application of fluorescence in situ hybridization (FISH) and review of the literature

Summary. Idic(X)(q13) represents a rare but recurrent chromosomal abnormality in haematological malignancies. We present five new cases characterized by this particular aberration and review the literature on this subject.

Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in ‘unmutated’ B-CLL

Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgVH. Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.

Elliptocytosis and Schistocytosis in Myelodysplasia: Report of Two Cases

Marked elliptocytosis and schistocytosis are described as unusual manifestations of haematopoietic dysplasia in two patients. The first patient, whose history was negative for inherited haemolytic anaemias, presented these prominent features on his first admission; 22 months later he developed an acute myeloblastic leukaemia. In the second patient, followed since 4 years for an autoimmune thrombocytopenic purpura, elliptocytosis and schistocytosis appeared 17 months before a pancytopenia established. The patient is now on follow-up and is treated for a refractory anaemia. In both cases bone marrow examinations revealed the typical criteria for myelodysplasia and this diagnosis was confirmed by cytogenetic analysis.

Philadelphia-positive T-acute lymphoblastic leukemia

A case of typical T-acute lymphoblastic leukemia (T-ALL) is reported in which, at diagnosis, 100% of bone marrow metaphases showed a Philadelphia (Ph) translocation, t(9;22). These cells completely disappeared following chemotherapy. The significance of the Ph chromosome in T and B leukemic cells is discussed.

Trisomy 3q11-q29 is recurrently observed in B-cell non-Hodgkin's lymphomas associated with cold agglutinin syndrome

Abstract Three cases of low-grade B-cell non-Hodgkins lymphoma associated with cold agglutinin syndrome, cytogenetically characterized by partial trisomy 3, are presented in this report. Our data suggest that the long arm of chromosome 3 might be of particular importance in the pathogenesis of this subgroup of lymphomas.