Exudative pericarditis in the evolution of a diffuse large B-cell lymphoma.

Cardiac involvement in non-Hodgkin's lymphoma is a rare occurrence with a dismal prognosis, which may evolve with different clinical presentations, the most frequent being heart failure. Diagnosis of cardiac involvement is generally made by cardiac ultrasound. We report a case of lymphomatous pericarditis in the evolution of a non-Hodgkin's lymphoma, diagnosed by PET-CT scan, and occurring concomitantly with complete isotopic remission of enlarged mediastinal lymph nodes following chemotherapy.

Breast implant-associated anaplastic large-cell lymphoma can be a diagnostic challenge for pathologists.

BACKGROUND: Primary anaplastic large-cell lymphoma (ALCL) occurring in women with breast implants is very rare. It is usually described as tumor cells infiltrating the periprosthetic capsule. These are most often revealed by a periprosthetic recurrent isolated effusion (seroma cavity), occurring late after implantation of the prosthesis. ALCL is more rarely a tumor or periprosthetic capsular contracture. CASE: We report a 66-year-old woman, initially diagnosed by cytological examination of breast effusion, in whom ALCL appeared two and a half months after the removal of a ruptured implant. Repeated biopsies of the periprosthetic capsule performed in parallel showed fibrous tissue, without tumor proliferation. Only meticulous histological examination of the total capsulectomy identified tumor cells as a thin and discontinuous layer along the inner surface of the capsule without capsular invasion. CONCLUSION: Awareness of the histological pattern of this new clinical entity is important. A total capsulectomy with a good sampling for microscopic examination should be conducted for any suspicion of breast implant-associated ALCL. Cytology-histology correlation is essential.

Screening by fluorescence in situ hybridization for MLL status at diagnosis in 239 unselected patients with acute myeloblastic leukemia.

A large number of abnormalities involving the MLL gene have been associated with hematological malignancies, including acute myeloblastic leukemias (AML). Given the overall unfavorable prognosis of AML with an MLL abnormality, its reliable and accurate detection is needed for informed treatment decision. We therefore investigated the occurrence of MLL abnormalities in 239 unselected consecutive AML patients, using conventional cytogenetic and fluorescent in situ hybridization (FISH) analyses. FISH analysis for MLL was performed using a commercial dual-color probe. Of the 239 patients, 30 (12.6%) showed MLL abnormalities under FISH analysis, 10 (4.2%) showed a split signal indicating the disruption of the MLL gene by translocation or insertion, and 20 (8.4%) showed overrepresentation of the MLL gene without evidence of rearrangement. MLL abnormalities were more frequently found in AML-M5 and M4, mainly as rearrangements, and in AML-M2, mainly as overrepresentation. Our results are in agreement with those reported in other studies. All M2, M4, and M5 AML patients without known recurrent translocations, such as t(8;21) and inv(16), should be investigated by FISH with an MLL probe because it allows the detection of MLL rearrangement that would go undetected by conventional cytogenetics and because it has the ability of detecting multiple copies of the MLL gene in, for example, marker chromosomes and double minutes.

Rearrangement of the MLL gene in acute myeloblastic leukemia: report of two rare translocations.

Band 11q23 is known to be involved in translocations and insertions with a variety of partner chromosomes. They lead to MLL rearrangement, resulting in a fusion with numerous genes. We report here 2 male adults in whom a diagnosis of acute myelomonoblastic leukemia (FAB M4) and acute monoblastic leukemia (FAB M5) was made. Conventional cytogenetic techniques showed a 45,XY,t(1;11)(p32;q23),-7 karyotype in the first case and a 46,XY, t(11;17)(q23;q21) in the second case. Fluorescent in situ hybridization (FISH) with a specific MLL probe showed the gene to be disrupted, the 3' region being translocated on the derivative chromosomes 1 and 17, respectively. Fourteen and 24 patients, including ours, with acute myeloblastic leukemia associated with a t(1;11)(p32;q23) and a t(11;17)(q23;q21), respectively have been reported in the literature. Several patients with the latter translocation have also been identified to have acute lymphoblastic leukemia (ALL). Although both translocations are preferentially associated with monocytic differentiation, the t(11;17)(q23;q21) is more common in adults and has been reported in many patients with ALL, compared to the t(1;11)(p32;q23).

Cytogenetic studies in T-cell acute lymphoblastic leukemia (1981-2002).

Chromosomal analysis was successfully performed in 34 of the 37 patients with T-cell acute lymphoblastic leukemia (ALL) seen at the University Hospital in Brest (France) between 1981 and 2002. A normal karyotype was observed in 29.4% of the patients. Numerical changes were rare, 79.2% of the abnormal karyotypes being pseudodiploid. All 24 abnormal karyotypes had at least a structural rearrangement. Translocations involving band 14q11, that contains the T-cell receptor (TCR) alpha and delta-genes, were observed in 8 patients; in 3 of them, a new partner chromosomal band was found. The short arms of chromosomes 11 and 12 were involved in 3 and 2 translocations respectively. Three patients had a del(6q). Our results are in agreement with those of the literature. Most of the recurrent abnormalities are different from those of B-lineage ALL. Some are known to involve TCR genes whereas others can lead to the discovery of new genes that are important to T-lineage leukemogenesis.

Insertion of chromosome 11 in chromosome 4 resulting in a 5'MLL-3'AF4 fusion gene in a case of adult acute lymphoblastic leukemia.

We report on a 69-year-old woman with B-lineage acute lymphoblastic leukemia. Cytogenetic studies at diagnosis with R banding showed an insertion, ins(4;11)(q21;q13q23). Fluorescence in situ hybridization (FISH) with whole chromosome painting probes confirmed the insertion of chromosome 11 material into chromosome 4. FISH using the MLL probe showed the translocation of the 5' end of MLL into chromosome 4. Since the 5'MLL-3'AF4 fusion transcript was detected by a reverse transcriptase polymerase chain reaction, we concluded that the insertion of part of chromosome 11 split the AF4 gene in two, resulting in the presence of the 5'MLL-3'AF4 fusion gene on the der(4) instead of the der(11), as commonly observed. Our findings stress the value of combining banding cytogenetics with FISH and molecular techniques to better assess rearrangements in leukemia.

A fluorescence in situ hybridization study of TEL-AML1 fusion gene in B-cell acute lymphoblastic leukemia (1984-2001).

Acute lymphoblastic leukemia (ALL) is associated with recurrent chromosomal abnormalities. The cryptic translocation t(12;21)(p13;q22), which leads to the TEL-AML1 fusion gene, is the most common abnormality in childhood B-cell ALL. The aim of this retrospective study was to determine the incidence of TEL-AML1 fusion in childhood and adult B-cell ALL using interphase fluorescence in situ hybridization (I-FISH) and its association with additional changes. FISH, using dual-color extra-signal (ES) DNA probe specific for the TEL and AML1 genes, was performed either on blast cells suspensions stored in liquid nitrogen immediately after Ficoll or on leukemic cells preserved in fixative solution at -20 degrees C after short-term culture. No TEL-AML1 fusion was observed in the 26 ALL adults. The fusion was found among 19.6% of the 57 ALL children, additional changes being identified by conventional cytogenetics in 80% of the cases. A deletion of the untranslocated TEL was observed in 36.3% of the ALL with the TEL-AML1 fusion. The coexpression of myelocytic and B-lymphoid antigens was found in 3 of the 11 of TEL-AML1 fusion positive-ALL. Our results (frequency of TEL-AML1 fusion in children and of the deletion of the untranslocated TEL allele, mean age of the patients and white blood cell count) are within the range observed by others. Structural chromosomal abnormalities other than the t(12;21) are frequent and may play a role in the prognosis of these patients.

t(4;11)(q21;p15), including one complex translocation t(1;4;11)(p32;q21;p15), in adult T-cell acute lymphoblastic leukemia.

We report two adults with T-cell acute lymphoblastic leukemia (ALL). Cytogenetic studies at diagnosis with R banding showed a 46,XX,t(4;11)(q21;p15)/46,XX karyotype in one patient and 46,XY,t(1;4;11)(p32;q21;p15)/46,XY in the other. Fluorescence in situ hybridization with whole chromosome paints (WCP1, WCP4, and WCP11) confirmed the complex rearrangement in the latter patient. Only 10 T-cell ALL patients with the t(4;11)(q21;p15) have been described, all, but one of them, being over 15 years old. Although recurrent in T-cell ALL, its frequency appears to be very low; indeed, it has been identified in only 4 of 193 adults and in 1 of 734 children with T-cell ALL thus far reported in the literature.

Translocation (12;21) followed by insertion of chromosome 3 material in the derivative chromosome 12 in a case of childhood acute lymphoblastic leukemia.

We report a 2-year-old boy with B-cell acute lymphoblastic leukemia. Cytogenetic studies at diagnosis with R-banding showed a 46,XY,ins(12;3)(p13;q?21q?22)/46,XY karyotype. Fluorescence in situ hybridization with TEL/AML1 probes and chromosome paints revealed complex rearrangements. The TEL/AML1 fusion gene was located on the derivative chromosome 21 but a segment of the long arm of a chromosome 3 was inserted between the proximal part of the short arm of the derivative chromosome 12 and the reciprocal part of the AML1 gene. This is consistent with an insertion of chromosome 3 into chromosome 12 after the t(12;21) took place, therefore indicating a probable secondary event due to clonal evolution.

Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib.

Amplification of the bcr-abl fusion gene has recently been associated with resistance to imatinib therapy in chronic myeloid leukemia (CML). A 55-yr-old man was diagnosed with Philadelphia (Ph) chromosome-positive CML. Resistance to interferon treatment and occurrence of blastic phase lead to the decision of imatinib therapy. After two autologous stem cell transplantation, the patient reverted to chronic phase with a decrease in the proportion of Ph chromosome-positive cells under imatinib. A second blastic phase occurred 4 months after transplantation, of which the patient died. Cytogenetic studies, including fluorescent in situ hybridization, showed a (9;22)(q34;q11) translocation and one bcr-abl fusion gene during the whole evolution, but for the last 2 months. Bcr-abl gene amplification (over 25 copies) was noted while banding cytogenetics showed a karyotype of 55-62 chromosomes with multiple double minutes (dmin). To the best of our knowledge, dmin containing amplified bcr-abl gene has never been reported in patients with CML. Therefore, although we cannot exclude that the gene amplification was strictly associated with disease progression, our data may suggest that the amplification resulted in resistance to imatinib.

AML1 amplification in a case of childhood acute lymphoblastic leukemia.

We report an 8-year-old girl with B-cell acute lymphoblastic leukemia (ALL). The blast cell karyotype at diagnosis included a marker chromosome revealed by fluorescence in situ hybridization to be a derivative of chromosome 21. A high level amplification of the AML1 gene was identified, but it disappeared upon complete remission. This rare but recurrent abnormality warrants research of B-cell ALL, especially when a marker chromosome is present in the blast cell karyotype.