Derivative (14)t(11;14)(q13;q32)t(11;14)(p11.2;p11.2): a novel unbalanced variant of the t(11;14)(q13;q32) translocation in mantle cell lymphoma

We report the case of a 62-year-old man who presented with splenomegaly, leukocytosis, anemia, and thrombocytopenia. Examination of the peripheral blood, bone marrow, and spleen revealed involvement by mantle cell lymphoma, with some blastoid features and an atypical phenotype. Spleen and bone marrow classical chromosome analysis followed by fluorescence in situ hybridization revealed a novel and unusual unbalanced variant of the t(11;14)(q13;q32) translocation, resulting in a complex derivative chromosome harboring the IGH/CCND1 fusion gene. This chromosome was designated as der(14)t(11;14)(q13;q32)t(11;14)(p11.1;p11.2).     

Detection of t(14;18)(q32;q21) in B-cell chronic lymphocytic leukemia

Cytomorphologic testing and multiparameter flow cytometry are the mainstays in diagnosing B-cell chronic lymphocytic leukemia, whereas fluorescence in situ hybridization that targets the translocation t(14;18)(q32;q21) often is used to identify follicular lymphoma. Therapy is highly diverse between both diseases. We describe a case with cytomorphologically and immunologically proven B-cell chronic lymphocytic leukemia in which t(14;18)(q32;q21) was found.     

Acute megakaryoblastic leukemia in infants with t(1;22)(p13;q13) abnormality.

Six infants with acute megakaryoblastic leukemia and a translocation (1;22)(p13;q13) were studied. There were five female infants and one male infant, and the age at initial examination varied from 0.8 to 6.5 months (median, 2.3 months). All the patients had hepatosplenomegaly and anemia (6 to 8.3 g/dL), and four patients had thrombocytopenia (9,000 to 63,000/mm3). The bone marrow showed prominent fibrosis in five cases and reticulin fibrosis in one patient at presentation. Crush artifact often made the histologic sections difficult to interpret, but typical megakaryoblasts could be identified in the smears. Biopsy specimens of the liver and lymph node were suggestive of a nonhematopoietic malignant condition because of the cohesiveness of the tumor cells, stromal fibrosis, and the prominent sinusoidal and vascular pattern of infiltration. Immunophenotyping of peripheral blood mononuclear cells was helpful in identifying the blasts as belonging to the megakaryoblastic lineage. Using a panel of mononclonal antibodies, it was also possible to confirm the nature of the infiltration in paraffin sections and to differentiate it from other childhood small round cell tumors, especially neuroblastoma in paraffin sections (typical staining pattern: CD45-, CD43+, vW Factor, Ulex europeus I+, CD20-, CD45RO-, synaptophysin-, chromogranin-, cytokeratin-, desmin-). This special type of infantile acute leukemia can be recognized with confidence if one is aware of its clinical features, peculiar pathologic characteristics, the morphologic features and immunophenotype of the megakaryoblasts, and the unique cytogenetic abnormality.     

t(14;19)(q32;q13): a recurrent translocation in B-cell precursor acute lymphoblastic leukemia

The recurrent t(14;19)(q32;q13) translocation associated with chronic B-cell lymphoproliferative disorders, such as atypical chronic lymphocytic leukemia, results in the juxtaposition of the IGH@ and BCL3 genes and subsequent overexpression of BCL3. We report six patients with B-cell precursor acute lymphoblastic leukemia who have a cytogenetically identical translocation with different breakpoints at the molecular level. Fluorescence in situ hybridization with locus-specific probes confirmed the involvement of the IGH@ gene but showed that the breakpoint on 19q13 lay outside the region documented in t(14;19)(q32;q13)-positive chronic lymphocytic leukemia. This newly described translocation constitutes a distinct cytogenetic subgroup that is confined to older children and younger adults with B-cell precursor acute lymphoblastic leukemia.     

Translocation t(11;14)(q13;q32) in chronic lymphoid disorders.

The translocation t(11;14)(q13;q32) has been described in a spectrum of B-lymphoproliferative diseases and involves a putative oncogene, BCL1, which maps to chromosome band 11q13. Recent evidence indicates that this abnormality may delineate particular subtypes of lymphoma, such as intermediate lymphocytic and centrocytic lymphomas. Thus the possible significance of the t(11;14) within B-cell disorders should be reexamined in the light of a more objective approach to classifying these diseases by morphology, histology, and immunophenotype. We describe 16 patients with t(11;14)(q13;q32) from a series of 90 patients with chronic lymphoid disorders in whom clonal chromosome abnormalities were detected. All the cases were leukemic: prolymphocytic (B-PLL; 4/15 cases), chronic lymphocytic leukemia (CLL) with increase in prolymphocytes (2/9 cases), or non-Hodgkin lymphoma in leukemic phase, intermediate (3/4 cases), lymphoplasmacytic (2/2 cases), splenic lymphoma with villous lymphocytes (4/18 cases), and follicular (1 case). None of the CLL (25) or hairy cell leukemia cases (15) had t(11;14). Our findings showed that t(11;14) occurred in leukemias of mature B cells with lymphoplasmacytic features as judged by morphology and immunophenotype.     

Occurrence of trisomy 12, t(14;18)(q32;q21), and t(8;14)(q24.1;q11.2) in a patient with B-cell chronic lymphocytic leukemia

Trisomy 12, t(14;18)(q32;q21), and t(8;14)(q24.1;q11.2) were found in a 59-year-old man with B-cell chronic lymphocytic leukemia (CLL). While trisomy 12 is one of the most common cytogenetic abnormalities in chronic lymphocytic leukemia, the t(14;18) rearrangement has a strong association with follicular lymphoma and the t(8;14) is associated with T-cell neoplasia. Occurrence of these three abnormalities in CLL are rare, and the significance of this finding is unclear. Further studies of similar cases may shed additional insight into this finding.     

A novel t(2;3)(q31;p13) in acute myelocytic leukemia

We report a case of acute myelocytic leukemia without maturation exhibiting a novel t(2;3)(q31;p13). Conventional cytogenetics showed the concomitant occurrence of a single metaphase with 47,XX,+8. Nevertheless, interphase cytogenetics by fluorescence in situ hybridization using a chromosome 8 alpha-satellite DNA probe showed that the percentage of cells with three hybridization signals was within the control range.     

Detection of t(12;14)(p13;q32) in a patient with IGH-CCND1 negative mantle cell lymphoma resembling ultra-high risk chronic lymphocytic leukemia

t(12;14)(p13;q32) is a rare recurrent chromosomal translocation, which has only been identified in a small subgroup of mantle cell lymphoma (MCL) without typical t(11;14)(q13;q32). This rearrangement causes aberrant over-expression of cyclin D2 (CCND2), which disrupts the normal cell cycle. Here we report a subtle case of MCL with t(12;14)(p13;q32) that was initially misdiagnosed as ultra-high risk chronic lymphocytic leukemia (CLL). A 60-year-old male patient presented with obvious leukocytosis and progressive weakness. Morphology of peripheral blood and immunophenotyping by flow cytometry pointed to a diagnosis of chronic lymphocytic leukemia. Fluorescence in situ hybridization (FISH) using IGH-CCND1 probe was negative for CCND1 abnormality, but demonstrated IGH breakapart signals. The initial diagnosis of CLL was established and the patient was treated with six courses of immunochemotherpy with fludarabine, cyclophosphamide and rituximab (FCR). Complete remission (CR) was achieved at the end of treatment, but disease relapsed quickly. The patient was transferred to our hospital, flow cytometry using additional markers showed that the clonal cells were CD200+(dim), CD148+(strong), and chromosome analysis revealed a complex karyotype, 47, XY, t(12;14)(p13;q32), +12, del(9p21), which indicated over-expression of CCND2, and immunostaining showed strong positivity of SOX11 further confirming the characteristics of CCND1-negtive MCL. The final diagnosis was revised to rare subtype of MCL with CCND2 translocation and intensive regimens were employed. This confusable MCL case illustrates the importance of cytogenetic analysis and clinicopathologic diagnosis of this rare category of MCL.     

Acute lymphoblastic leukemia characterized by t(8;14)(q11.2;q32)

The t(8;14)(q11.2;q32) is emerging as an uncommon, though recurrent cytogenetic finding. As of yet, too few cases of acute lymphoblastic leukemia (ALL) characterized by this translocation have been studied to determine its prognostic significance with confidence. We therefore report three new patients (two male children and one adult female) and present their hematologic, immunophenotypic, and clinical data. The clinical and laboratory characteristics of 26 other patients with t(8;14)(q11.2;q32) are summarized. The total number of patients now reported in the literature is 29 with a mean age of 14 years. Early relapse, that is, relapse within 6 months, does not appear to be a common feature of this group. The gender distribution is 19 males: 9 females (gender not reported in one case). Twenty-three t(8;14) patients show a pre-B immunophenotype and 24 of 24, on whom information is available, achieved complete remission after induction chemotherapy for B-ALL. Approximately one third of patients with t(8;14) have Down syndrome, 19 of 27 have additional acquired cytogenetic abnormalities, 5 of these have the t(9;22), and 4 show duplication of the abnormal chromosome 14, which is derived from the t(8;14). Hemoglobin and platelet counts are low at presentation in 10 of 10 and 8 of 9 patients, respectively, and the average white blood count is 38.9 x 10(9)/L. Of the 7 patients for whom IgH status has been determined, all show rearrangement of the IgH locus. Two of the present three patients are included in this group; their IgH rearrangement was demonstrated by fluorescence in situ hybridization with IgH break-apart probes.     

Novel clonal der(8)t(8;14)(p11;q11),del(9)(q13q22) and t(14;22) (q13;q13) in a patient with fulminant adult T-cell leukemia/lymphoma

We describe a 70-year-old man with fulminant adult T-cell leukemia/lymphoma. He died of progressive disease 1 week after the onset of symptoms. The integrated viral DNA of human T-lymphotropic virus type I was detected in the bone marrow aspirate by polymerase chain reaction. Cytogenetic analysis of bone marrow cells showed novel clonal aberrations consisting of 46,XY,der(8)t(8;14)(p11;q11),del(9) (q13q22),t(14;22)(q13;q13).     

A der(14)t(1;14)(q12;p11) in chronic myelomonocytic leukemia

Duplication of the long arm of chromosome 1 (1q) is widely reported in human neoplasia, including the myelodysplastic syndromes (MDS). So far, it has not been described as a single aberration in the chronic myelomonocytic leukemia (CMML), a subtype of MDS. Rather, trisomy 1q was always a part of complex chromosome changes affecting the subtypes of MDS other than CMML. We report on a patient with CMML with an unbalanced translocation of the entire 1q onto the short arm of chromosome 14 as a sole cytogenetic abnormality. Fluorescence in situ hybridization (FISH) analysis with an alpha-satellite probe for the paracentric region of the long arm of chromosome 1 confirmed the presence of trisomy 1q in a derivative chromosome, der(14)t(1;14)(q12;p11). The discrepant results between the metaphase cytogenetics (100% abnormal) and interphase cytogenetic (71% nuclei with 3 signals) suggest that trisomy 1q, even in the absence of additional cytogenetic changes, has a sufficient leukemogenic potential to confer a proliferative advantage on hematopoietic cells committed to monocyte stemline both in vitro and in vivo. The literature data on partial and complete trisomy 1q in CMML is reviewed.     

B-cell acute lymphoblastic leukemia with tandem t(14;14)(q11;q32).

Translocation (14;14)(q11;q32) was associated with acute lymphoblastic leukemia in a child. The B-cell lineage of the leukemic cells led us to perform FISH studies, which showed that the chromosomal breakpoints were telomeric to TCRA/D and IGH loci. These findings show that FISH analyses are necessary when unusual features are associated with a recurrent translocation.     

Chronic lymphocytic leukemia with t(14;19)(q32;q13) is characterized by atypical morphologic and immunophenotypic features and distinctive genetic features

The t(14;19)(q32;q13) involving the IGH@ and BCL3 loci is an infrequent cytogenetic abnormality detected in B-cell malignancies. We describe the clinicopathologic, cytogenetic, and molecular genetic characteristics of 14 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with t(14;19)(q32;q13). All patients (10 men and 4 women) had lymphocytosis; 10 had lymphadenopathy. Blood and bone marrow lymphocytes were predominantly small, but cytologically and immunophenotypically atypical. In all cases, t(14;19) was found in the neoplastic stem line; it was the sole abnormality in 4. Ten cases showed additional cytogenetic abnormalities, including trisomy 12 in 9 and complex karyotypes in 7. Fluorescence in situ hybridization demonstrated IGH@/BCL3 fusion gene in all cases. In all cases, the IGHV genes were unmutated, but only 7 expressed ZAP70. Seven cases preferentially used IGHV4-39. Our results indicate that t(14;19)(q32;q13) identifies a subset of CLL/SLL with distinctive clinicopathologic and genetic features. Furthermore, t(14;19) may represent an early, possibly primary, genetic event.     

Translocation t(13;17)(q12-14;p12-13) in two patients with lymphocytic lymphoma

Cytogenetic studies were performed at the time of diagnosis on two patients with diffuse small cell lymphocytic lymphoma. Both patients had a similar simple karyotype with a t(13;17)(q12-14;p12-13). These observations confirm the nonrandom involvement of band 13q13 in chronic lymphoproliferative diseases.     

Acute mixed lineage leukemia and a t(6;14)(q25;q32) in two adults

Acute mixed lineage leukemia (AMLL) is a rare form of leukemia in which both myeloid and lymphoid markers are present. Few chromosome abnormalities have been identified associated with this form of leukemia. A translocation involving the long arms of chromosomes 6 and 14 was previously described in four young individuals with acute leukemia and in three of these cases the diagnosis was mixed lineage. We identified a translocation involving the same chromosomes in two additional cases of adults with AMLL. The q32 breakpoint on chromosome 14 is shared by all six cases and five out of six cases also share the q25 breakpoint on chromosome 6. The rarity of the t(6;14) and the AMLL suggests a non-random association between these two events. The near cryptic appearance of the translocation might indicate that its occurrence is underestimated.