R D Gascoyne

Regimens using cyclosporin (CSP) and either methylprednisolone (MP) or methotrexate (MTX) have been useful in the prophylaxis of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). However, CSP produces a number of side effects, including neurologic toxicity. A retrospective review of recipients of 239 BMTs given CSP-based prophylactic regimens revealed that 10 patients (4.2%, 95% confidence interval 0% to 10.4%) experienced a syndrome characterized by hypertension, severe visual disturbances, seizures and occipital lobe density changes on brain computed tomography (nine patients) or nuclear magnetic resonance imaging (one patient). Neurologic findings were reversible in all cases, usually after temporary discontinuation of CSP. Univariate analysis identified the following risk factors for neurotoxicity: use of unrelated or HLA-mismatched related donors, administration of etoposide (VP-16) or total body irradiation as part of conditioning, use of corticosteroids for prophylaxis or treatment of acute GVHD, or development of either acute GVHD or clinically significant microangiopathic hemolytic anemia (MAHA) post-BMT. In multivariate analysis, the most important predictors were the use of VP-16 (p = 0.008), the use of a continuous infusion CSP plus MP prophylactic regimen for GVHD (p = 0.003) and the development of MAHA after BMT (p less than 0.001). The strong association with MAHA suggests that endothelial damage is related to the development of this complication.

Epstein-Barr-associated lymphoproliferative disorders have been described as complications of immunodeficiency states including allogeneic BMT. There is, however, only one report in the English language literature of such a disorder after autografting. We report a 56-year-old man undergoing autologous BMT for CML in whom a rapidly progressive lymphoproliferative disorder showing the histology of typical post-transplant lymphoproliferative disorder with latent EBV presence developed at approximately 30 days after BMT. Therapy with corticosteroids, acyclovir and alpha-interferon was instituted and led to prompt resolution of symptoms and signs. There was no evidence of lymphoproliferative disease at 7 months after BMT. It is concluded that EBV-associated lymphoproliferative disorders may be a complication, albeit a rare one, of intensive therapy with autologous stem cell support.

Successful therapy for most of the non-Hodgkin's lymphomas requires an accurate pathologic diagnosis. Routine morphologic examination of excisional biopsies from nodal or extranodal sites provides the cornerstone for establishing a definitive diagnosis. The list of ancillary studies, however, used to complement these routine approaches is increasing both in number and complexity. Proper use of these diagnostic tools can be of great help in arriving at the correct diagnosis in difficult cases. Fine-needle aspiration and needle-core biopsies have a role in lymphoma staging and in the assessment of recurrent disease, but are limited as primary diagnostic tests. This review will focus on the standard approaches used to establish a diagnosis of malignant lymphoma, and the clinical utility of immunophenotypic, molecular genetic, and cytogenetic studies in providing useful data for diagnosis. The standard practice of synthesizing all of the data from multiparameter analysis to arrive at a diagnosis in difficult cases will be emphasized.

This study reports on fourteen biopsies from patients presenting to our orbital and oncology service with ocular adnexal lymphoid proliferations between November 1988 to September 1991. The biopsies were studied using histologic, immunophenotypic and genotypic analyses. By histologic criteria, there were two reactive, five indeterminate and seven lymphomatous lesions. On immunophenotypic analysis, there were two monoclonal and 10 polyclonal lesions in the 12 specimens analysed. Genotypic analysis confirmed the histopathologic diagnoses for the reactive lesions by showing them to be germline. It also confirmed that both the histopathologic lymphomas and immunophenotypically monoclonal lesions were clonally rearranged. Genotypic analysis was able to separate the histologically indeterminate group into two subsets: clonally rearranged, of which there was one, and germline, of which there were four. In addition, it demonstrated that immunophenotypic polyclonality cannot always be equated with genotypic polyclonality as was the situation in four out of 10 lesions in our series. The significance of clonal arrangements in the histologically indeterminate and immunophenotypically polyclonal groups can only be determined by prospective study.