Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: report of an autopsy case.

We report clinicopathological features of a 23-year-old woman with Down syndrome (DS) presenting with subacute myelopathy treated with chemotherapy, including intravenous and intrathecal administration of methotrexate (MTX), and with allogenic bone-marrow transplantation for B lymphoblastic leukemia. Autopsy revealed severe demyelinating vacuolar myelopathy in the posterior and lateral columns of the spinal cord, associated with macrophage infiltration, marked axonal loss and some swollen axons. Pathological changes of posterior and lateral columns were observed from the medulla oblongata to lumbar cord. Proximal anterior and posterior roots were preserved. Cerebral white matter was relatively well preserved. There were no vascular lesions or meningeal dissemination of leukemia. Longitudinal extension of cord lesions was extensive, unlike typical cases of subacute combined degeneration (SACD), but distribution of lesions and histological findings were similar to that of SACD. DS patients show heightened sensitivity to MTX because of their genetic background. Risk factors for toxic myelopathy of DS are discussed, including delayed clearance of MTX despite normal renal function, alterations in MTX polyglutamation and enhanced folic acid depletion due to gene dosage effects of chromosome 21. Alteration of folate metabolism and/or vitamin B12 levels through intravenous or intrathecal administration of MTX might exist, although vitamin B12 and other essential nutrients were managed using intravenous hyperalimentation. To the best of our knowledge, this is the first report of an autopsy case that shows myelopathy mimicking SACD in a DS patient accompanied by B lymphoblastic leukemia. The case suggests a pathophysiological mechanism of MTX-related myelopathy in DS patients with B lymphoblastic leukemia mimicking SACD.

Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan.

BACKGROUND: Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in pediatric patients are relatively rare. PROCEDURE: We performed a retrospective analysis in patients with PTCL over an 18-year period (1991-2008). RESULTS: We could analyze clinical data in 21 patients with non-anaplastic PTCL; 10 were female and 10 male. Median age of onset was 11 years (range: 1-21 years). There were nine patients with PTCL, not otherwise specified (PTCL-NOS); ten with extranodal NK/T-cell lymphoma, nasal type; one with angioimmunoblastic T-cell lymphoma; and one with subcutaneous panniculitis-like T-cell lymphoma. Initial lesions involved cervical lymph nodes in five patients, and the skin in five patients. In five patients, hemophagocytic syndrome (HPS) was the initial clinical feature. There were 12 patients with advanced stage disease (stages III and IV). Chemotherapy and radiation was administered in 18 and 2 patients, respectively. Among the two patients who did not receive chemotherapy and radiation, one patient died while being treated for HPS but another improved spontaneously. Although 5 patients relapsed, 18 of 21 patients remained alive without disease at last follow-up. Five-year overall survival rate was 85.2%. CONCLUSIONS: Generally, the outcome results of conventional chemotherapy for high-risk PTCL are poor in adult patients. However, the excellent results in our study suggest that PTCL of childhood is quite different from that of adulthood. Although this study is first report about PTCL of Asian children, the number of patients was small in this study. Larger studies are needed to confirm these findings.

[Tumor markers of childhood cancer].

Tumor markers are the substances which are produced from malignant cells and are detectable from peripheral blood or body fluid. These markers are used for the evaluation of treatment effectiveness or the detection of relapse. In most cases of pediatric cancer, specific molecular abnormalities of tumor cells have been able to be identified. Evaluation of these molecular markers is critical for the diagnosis and the choice of treatment. Recently, these molecular markers have also come to be used for the detection of minimal residual disease. Such a system can be regarded as a kind of tumor marker.

Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan.

This report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10.5 months after the initial diagnosis. Twenty-four patients achieved a second remission. After a median follow-up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse-free survival rates were 61 +/- 12% and 51 +/- 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.