A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty‐four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan‐B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23. Sixteen cases, which were followed by consecutive biopsies, showed only slight morphological changes during the course of the disease and only four cases showed histological progression. Forty cases were documented by cytogenetics, of which 15 showed t(11; 14)(q13;q32). We examined 28 cases for DNA rearrangement of the BCL‐1 locus; it was detected in 50% of the cases, with most breakpoints occurring at the major translocation cluster. This study demonstrates that when selection criteria are strictly applied, mantle cell lymphoma represents a disease entity with a uniform presentation, distinctive morphology, immunophenotype and a strong association with t(11;14)(q13;q32).
Here we present the case of a patient with diagnosis of chronic lymphocytic leukaemia (CLL) on routine protocol biopsy 3 months following kidney transplantation. Genetic analysis confirmed the origin of the malignancy, being the recipient. Differential diagnosis with post-transplant lymphoproliferative disorder (PTLD) is extremely important in order to avoid unnecessary devastating treatment. This case is challenging, both in terms of making the correct diagnosis and in terms of optimal treatment. The case underscores that it is extremely important to distinguish between a pre-existing lymphoma diagnosis after transplantation and a true PTLD as the treatment options of both are very divergent.
Banks, P. M. M.D.; Chan, J. M.D.; Cleary, M. L. M.D.; Delsol, G. M.D.; De Wolf-Peeters, C. M.D.; Gatter, K. M.D.; Grogan, T. M. M.D.; Harris, N. L. M.D.; Isaacson, P. G. M.D.; Jaffe, E. S. M.D.; Mason, D. M.D.; Pileri, S. M.D.; Ralfkiaer, E. M.D.; Stein, H. M.D.; Warnke, R. A. M.D. Author Information
Abstract Two t(14;18)‐negative follicular B‐non‐Hodgkin's lymphomas with the same chromosomal abnormality, dup(12)(q13→qter), are presented. The absence of a BCL2 gene rearrangement was confirmed by molecular studies in both cases. Instead, duplication of a 12q segment was found. Further evidence for the presence of the dup(12)(q13→qter) was found using fluorescence in situ hybridization. dup(12q) may be equivalent to the trisomy 12 originally described in B‐chronic lymphocytic leukemia. This chromosome anomaly has also been reported in B‐non‐Hodgkin's lymphomas, usually in association with other chromosome anomalies and a more aggressive tumor phenotype. Occurrence of dup(12q) in two histologically similar cases of follicular small cleaved‐cell lymphoma without a typical t(14;18), suggests that this karyotypic change may play a critical role in some cases of follicle center‐cell lymphomas.
To investigate the hypothesis that Freund's complete adjuvant (CFA) plays an essential role in the induction of collagen-induced arthritis in mice, by testing whether CFA by itself is able to induce arthritis in interferon-gamma receptor-knockout (IFNgammaR-KO) mice.IFNgammaR-KO and wild-type mice were sensitized with a single intradermal injection of CFA containing heat-killed Mycobacterium butyricum. Flow cytometric analysis and in vitro osteoclastogenesis assays were performed on blood, spleen, and bone marrow cells. Tumor necrosis factor (TNF) levels were measured in the serum, and levels of RANKL, osteoprotegerin (OPG), and TNFalpha in the synovium were determined by quantitative reverse transcriptase-polymerase chain reaction. Effects of treatment with the TNFalpha antagonist etanercept were assessed.Symptoms of arthritis appeared in IFNgammaR-KO mice but not in wild-type mice, and reached an incidence of 55%. The onset coincided with an expansion of CD11b+ splenocytes that spontaneously produced TNFalpha and with increased osteoclastogenesis in spleen and blood cells. Expansion of CD11b+ splenocytes and osteoclast precursor cells was more pronounced in arthritic than in nonarthritic mice. There was a >100-fold increase in the RANKL:OPG ratio in the synovia of CFA-sensitized mice compared with those of naive animals. Treatment with etanercept prevented the development of arthritis and mitigated the increased expansion of myeloid cells as well as the increase in osteoclast precursor numbers in the spleen and blood.These results indicate that sensitization of mice with CFA creates a condition in which dysregulation of a single cytokine leads to arthritis by triggering TNFalpha-driven osteoclastogenesis.
