Hodgkin Lymphoma-Like Adult T-Cell Leukemia/Lymphoma Shows An Indolent Clinical Course: Analysis Of 7 Cases

Adult T-cell leukemia/lymphoma (ATLL) is a human T-lymphotropic virus type-1 (HTLV-1)-associated T-cell malignancy. The clonality of T-cells with HTLV-I proviral DNA integration changes from undetectable to polyclonal, and then further to monoclonal upon malignant transformation. Analysis of proviral DNA integrated in cellular DNA has shown that leukemic cells are always infected with HTLV-I. These cells are also consistently monoclonal with respect to proviral integration, which indicates that they originated from a single cell infected with HTLV-I. On the basis of findings related to changes in peripheral blood, the clinical stage gradually progresses from carrier to smoldering, chronic and acute-type leukemia. In a previous series of studies, we and other groups characterized the histopathological changes in HTLV-I-associated lymph node lesions. In addition to the typical ATLL pleomorphic and anaplastic large cell types, we identified lymph nodes with an unusual Hodgkin disease-like histology (Hodgkin-like ATLL) in HTLV-I-positive patients. Hodgkin-like ATLL showed prodromal clinical features, but the effect of conventional therapy was poor in patients with this type of lymph node lesion and most patients later developed typical ATLL. Recently, new drugs and therapies (stem cell transplantation) for ATLL have been developed, and the prognosis of ATLL has improved. It is now believed that Hodgkin-like ATLL has a relatively better prognosis than typical ATLL. In this study, we investigated the rare Hodgkin-like morphologic variant of ATLL and reexamined its prognosis.

Seven cases were retrieved from the archives of the Department of Pathology, Department of Pathology, Kurume University (from 2006 to 2010). Portions of the tissue samples were formalin-fixed, paraffin-embedded, and stained with hematoxylin-eosin (H&E). Two hematopathologists (D.N. and K.O.) reviewed all cases and classified them morphologically on the basis of WHO classification. Paraffin sections from each sample were immunostained with monoclonal antibodies against CD3, CD4, CD8, CD15, CD20, CD30, TIA1, PAX5 and CCR4. Heat-mediated antigen retrieval was performed. All analyses were performed in a single laboratory. EB virus-encoded small RNA (EBER) was detected by in situ hybridization. Other portions of the tissue samples were frozen and used for DNA isolation and gene analysis. The monoclonal or oligoclonal integration of HTLV-1 DNA was examined by digestion with EcoRI, as described previously.

In all cases, serum test results were positive for HTLV-1 and proviral HTLV-1 DNA bands were found, although the bands were weaker than those usually seen in typical ATLL. The median age of patients was 60 (range 40-69), with two males and five females. Laboratory data showed an elevation of lactic dehydrogenase (LDH) in six cases. Ann Arbor staging (I/II/III/IV) was 1/0/1/5 patients. Six patients received chemotherapy, one received chemotherapy with stem cell transplantation. Two patients died within 13 and 21 months, whereas five are still alive. The median survival was 31 months (range 13 to 58 months). The five-year overall survival is 71.4%.

Histologically, the lymph nodes exhibited a relatively preserved nodal architecture with diffuse infiltration of small-sized lymphocytes. Small aggregated foci or clusters of a few giant cells with irregularly lobulated nuclei were scattered throughout the expanded paracortex. In the immunohistological analysis, the giant cells were positive for CD30, CD15, and PAX5 but negative for CD20, CD3, TIA-1 and CCR4. The proliferating small lymphocytes were mainly positive for CD3, CD4 and CCR4 but negative for CD8 in all cases. All patients were positive for EBER in the nuclei of the giant cells.

The clinical outcome for patients with typical ATLL is generally poor with a median survival time of less than three years. However, patients with Hodgkin-like ATLL showed an indolent clinical course and relatively good survival with 71.4% five-year overall survival. Our findings indicate that pathologists and hematologists in HTLV-1 endemic areas should be more aware of ATLL and understand this morphologic variant.