A Rare Case of Malignant T-Cell Non-Hodgkin Lymphoma in a HTLV 1 Carrier With History of Diffuse Large B-Cell Non-Hodgkin Lymphoma

Abstract

Abstract Introduction Human T-cell leukemia virus type 1 (HTLV-1), a human retrovirus, is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1–associated myelopathy. Infection by HTLV-1 is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma (ATLL). HTLV-1 is endemic in many geographic regions, principally Japan, the Caribbean, and central Africa. It is also found in Iran, Iraq, southern India, China, the Seychelles, Papua New Guinea, the Solomon Islands, and Australia. This report is a rare known case of diffuse large B-cell non-Hodgkin lymphoma (NHL) who was HTLV-1 carrier from Mashhad of Iran. Case Report A 49-year-old man was admitted to the hospital due to nausea, vomiting, and drowsiness. He had a history of diffuse large B-cell NHL since 14 months ago with involvement of the vallecula, tonsil, base of the tongue, and tip of epiglottis that pathology reviewed two times and immunohistochemistry staining (IHC) showed to be CD20 positive, CD3-negative, and Ki67 50%. He was treated with R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and radiotherapy. He was asymptomatic until about 3 months ago, when diffuse desquamative erythematous maculopapular rashes developed over the skin of his chest, and for 3 weeks he experienced persistently nausea and vomiting and drowsiness that in physical examination was conscious but drowsy. The tongue was very dry, and skin lesions as explained were present. No lymphadenopathy and organomegaly was detected in examinations, and abdominopelvic computed tomography (CT) scans also showed no lymphadenopathy and organomegaly, but thickness of stomach wall was present. Upper gastrointestinal endoscopy showed multiple gastric masses; the largest one was 33 mm that biopsy revealed malignant NHL T-cell type, and immunohistochemistry (IHC) revealed CD3 positive diffusely and scattered CD8 positive. Skin biopsy showed malignant lymphoma diffuse T-cell type, and IHC showed CD3 positive. Both pathologies were reviewed two times by expert pathologists. Peripheral blood smear and bone marrow aspiration and biopsy were normal. Laboratory tests results were serum calcium, 13.5 mg/dL; serum creatinine, 3.87 mg/dL; white blood cell, 12 × 10 9 /L with normal differentiation; hemoglobin, 14.5 mg/dL; and platelet count, 215 × 10 9 /L. He had a history of positive HTLV-1 serology involving himself and 4 members of his family that, repeating in our patient, was again positive. His sister had a history of adult T-cell lymphoma/leukemia 8 years ago with generalized lymphadenopathy and leukocytosis that by IHC has been CD45, CD3, CD5, and CD7 positive, who has been treated as ATLL, and who is now alive. Our patient came from Mashhad of Iran; HTLV-1 infection is endemic for this region. Discussion In this case we could find both B-cell type malignant NHL and typical T-cell-type malignant NHL, both of which being clonal diseases, and adult T-cell lymphoma/leukemia has been etiologically associated with the HTLV-1 virus. Human T-cell lymphotropic (HTLV) viruses are retroviruses that predominantly infect CD4 and CD8 cells, respectively. HTLV-1 is transmitted by the following routes: sexual, parenteral, by way of blood product transfusion, contaminated needles and syringes and vertically, through maternal milk. Other diseases may be associated with HTLV-1, including arthropathies, pneumopathies, uveitis, and dermatologic diseases. However, most patients infected with HTLV-1 remain an asymptomatic carrier throughout their lifetime. ATLL is more common in areas where HTLV-1 is endemic. Patients with ATLL are usually infected before the age of 20 years, and their relatives have a high prevalence of HTLV-1 infection. The disease does not usually appear in more than 1 member of the family. Epidemiologic studies focusing on ATLL demonstrate that some 2% to 4% of infected patients develop neoplasia after a latent period of 20-30 years. Although there is a long latency, carriers have a 1%-5% chance of developing ATLL, thus making ATLL more common in areas where HTLV-1 is endemic, a condition frequently complicated by marked and refractory hypercalcemia, and with a poor prognosis. The cutaneous manifestations of ATLL are common and have different types of lesions. Results Association between HTLV-1 and T-cell lymphoma-leukemia has been reported many times, but appearance of B-cell and T-cell type NHL in one patient is a very rare condition that has been reported rarely; also 5 members of his family were infected by this virus. More investigations need to assess the relationship between these types of diseases.