1/7. Unusual case of leukemic mantle cell lymphoma with amplified CCND1/IGH fusion gene.We describe a case of leukemic mantle cell lymphoma (MCL) with complex karyotype and amplification of the CCND1/IGH fusion gene. Testing for the presence of t(11;14), the hallmark of MCL, revealed multiple copies of the fusion signals. We therefore conducted extensive molecular cytogenetic studies to delineate the nature and consequences of such an abnormality. We localized the amplification to the der(14)t(11;14) and to a der(2) chromosome in a form of interspersed chromosome 11 and 14 material. This resulted in high expression of cyclin d1 mRNA and the protein expressed independently of the cell cycle phase. CGH analysis revealed that the overrepresentation on chromosome 11 included chromosomal band 11q23 in addition to the CCND1 locus at 11q13. The band 11q23 harbors the ataxia telangiectasia mutated (ATM) gene recently proposed to be involved in the pathogenesis of MCL with high incidence of deletions in this locus. Using YAC 801e11, containing the ATM gene, we demonstrated several hybridization signals, suggesting that this region also formed part of the amplicon. This case also showed TP53 gene abnormalities: protein expression, monoallelic deletion, and a mutation in exon 5. The clinical course was aggressive, and the patient died within 6 months of presentation. This is to our knowledge the first description of amplification of the CCND1/IGH fusion gene in a human neoplasm, which may have played a role in the fulminating course of the disease in this patient.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/7. Clinical applications of color Doppler imaging in the management of orbital lesions.PURPOSE: To present the clinical applications of color Doppler imaging (CDI) as an adjunctive study in the diagnosis and treatment of orbital lesions. methods: Retrospective noncomparative case series. medical records of 17 patients with orbital lesions who underwent orbital CDI were reviewed, and their orbital CDI results, diagnosis, and treatment were studied. The main outcome measures were detection of abnormal orbital vascular flow and presence or absence of blood flow within orbital lesions by CDI. RESULTS: Absence of intralesional flow was associated with an orbital lesion considered benign. Tumors in which flow was present were more frequently malignant or had malignant potential. Reversal of flow in the superior ophthalmic vein was observed in patients with carotid-cavernous fistula and orbital varix. CONCLUSIONS: CDI is a useful adjunctive imaging study for evaluating the vascularity of orbital tumors. The absence or presence of intratumoral blood flow as demonstrated by CDI can help determine the nature of the orbital mass and can assist with surgical planning.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
3/7. Blastoid mantle cell lymphoma: evidence for nonrandom cytogenetic abnormalities additional to t(11;14) and generation of a mouse model.Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32), which is associated with cyclin d1 hyperexpression and a poor prognosis. MCL cases have been shown to progress to a more aggressive disease but the molecular events responsible of this phenomenon have not been determined. We have established two cell lines from the pleural effusions of two patients with MCL that we have used for further cytogenetic characterization to better define the incidence and nature of secondary chromosome abnormalities using multicolor fluorescence in situ hybridization, whole chromosome paint, and specific probes. Both cell lines grew independently without growth factors. Using CCND1/IGH-specific probes, patient UPN1 was found to have a masked t(11;14). Numerous and complex chromosomal abnormalities were found in both cell lines affecting chromosomes 2, 8, 13, 18, 22, X, and Y. These abnormalities included 8p losses, suggesting the presence of an anti-oncogene in this region, rearrangements of 8q24, MYC gene, and translocations involving 8, X, and Y chromosomes, which might be significant in the pathogenesis of MCL progression. The use of the cell lines (UPN1) allowed us to generate a mouse model of human MCL, mimicking a disseminated lymphoma and leading to the death of the animals in 4 weeks. This blastoid MCL model could be of major interest to determine molecular events involved in MCL progression, allowing isolation of involved genes and their functional characterization, and to study the effects of new chemotherapy regimens in mouse models.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/7. Burkitt transformation of mantle cell lymphoma.The associated poor prognosis and potentially aggressive behavior of mantle cell lymphoma and its blastoid variants make differentiation from other non-Hodgkin B-cell lymphomas especially important. We present a case of mantle cell lymphoma with a marked leukemic component, which demonstrated both a typical nodular mantle cell pattern and burkitt lymphoma within a single lymph node removed at the time of splenectomy. The presence of CD5, CD10, and Bcl-1 co-expression by immunohistochemistry and detectable t(11;14) and cMYC gene rearrangement by FISH analyses in the Burkitt region support a transformation of mantle cell lymphoma over a concomitant malignancy. A limited number of mantle cell lymphomas demonstrating dual t(11;14) and chromosome 8q24 cMYC gene rearrangements have been previously reported in the literature. They demonstrate an extremely aggressive course with a very poor prognosis. Although the accelerated terminal phase of this patient's clinical course mirrors these previous published cases; none have described the combined morphologic and immunophenotypic features of burkitt lymphoma reported here. This case provides further support for the aggressive nature of these lymphomas and demonstrates the utility of flow cytometry, immunohistochemistry, and cytogenetic techniques in avoiding potential errors in their diagnosis, prognosis, and treatment.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/7. Lymphomatous proptosis as a novel feature of mantle cell lymphoma.We describe eight cases of acute proptosis due to mantle cell lymphoma (MCL), among 26 consecutive MCL cases. The median time of onset was 29 months (range 0-102) from diagnosis. Two cases presented initially with orbital masses while five as sudden disease progression after multiple courses of chemotherapy. In each case, there was dramatic loss of vision and severe proptosis, which uniformly responded to radiotherapy and/or further chemotherapy. Unilateral blindness only occurred in two cases, with recurrent orbital relapse and repeated retinal irradiation and retro-orbital optic nerve involvement, respectively. The high incidence, as well as bilateral and recurrent nature, of orbital involvement suggested a homing mechanism of MCL to this site. Despite the absence of central nervous system involvement, most cases died of refractory disease. Apart from lymphomatous polyposis of the gut, MCL cells also show predilection to ocular presentation, and must be considered as a differential diagnosis to maltoma in the two anatomical sites.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
6/7. trisomy 12-associated, t(11;14)-negative mature B-cell leukemia with gene expression profile resembling mantle cell lymphoma.trisomy 12 can be seen in many different lymphoid neoplasms. However, many or most mature B-cell leukemias associated with isolated trisomy 12 are reported in the literature as chronic lymphocytic leukemia (CLL) or 'atypical CLL'. This study reports a case of a mature B-cell leukemia, morphologically and immunophenotypically similar to cases previously published as atypical CLL, in which cytogenetic evaluation revealed an isolated clonal trisomy 12 but no evidence of the mantle cell lymphoma-associated t(11;14)(q13;q32). Further analysis confirmed absence of cyclin-D1 expression. Subsequent lymph node biopsy revealed evidence of large cell transformation of the underlying chronic lymphoproliferative disorder. gene expression profiling of the initial peripheral blood sample using a cDNA micro-array of approximately 10,000 expressed genes revealed a close resemblance between the reported case and 2 cases of known mantle cell lymphoma. When further compared to 7 known 'typical' CLL cases, the reported case was classified as mantle cell lymphoma by hierarchical cluster analysis. The case reported here raises interesting questions regarding the nature of cases reported previously as trisomy 12-associated CLL and reinforces the fact that other leukemic lymphoproliferative disorders should be included in the differential diagnosis of such cases. Further study is indicated to elucidate the nature and diversity of disorders previously reported as trisomy 12-associated chronic lymphocytic leukemia.- - - - - - - - - - ranking = 2keywords = nature (Clic here for more details about this article) |
7/7. Molecular characterization of composite mantle cell and follicular lymphoma.Composite lymphomas are rare associations of two distinct lymphoma types at the same anatomical site. Reporting of such cases is important because they pose major biologic, diagnostic, and therapeutic dilemmas. In this study, we describe the third reported case of mantle cell and follicular lymphoma. We performed accurate immunohistochemical and molecular studies to define the mono- vs biclonal nature of this neoplasm. We used both manual and LASER-capture microdissection combined to multiple molecular approaches for clonality determination, including detection of heavy and light chain recombination, as well as presence of kappa/Kde recombination and sequence analysis. By immunohistochemistry and FISH, we confirmed the presence of two distinct lymphoma types characterized by specific translocations [namely, t(11;14) and t(14;18)], while we demonstrated two distinct and not clonally related cell populations by molecular techniques. The light chain approach, and particularly the kappa and kappa/Kde recombination detection, proved very useful for solving the clonality issue.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |