Reversible Epstein-barr Virus-negative Lymphadenopathy And Bone Marrow Involved By Hodgkin's Lymphoma In A Rheumatoid Arthritis Patient Undergoing Long-term Treatment With Low-dose Methotrexate: A Case Report And Review Of The Literature
Svensson, A. M., Jacobson, E. R., Ospina, D., & Tindle, B. H. (2006). Reversible Epstein-Barr virus-negative lymphadenopathy and bone marrow involved by Hodgkin's lymphoma in a rheumatoid ARThritis patient undergoing long-term treatment with low-dose methotrexate: a case report and review of the literature. International journal of hematology, 83(1), 47–50. https://doi.org/10.1532/IJH97.NA0503
View Original Source →Abstract
We report a case of spontaneous regression of Epstein-Barr virus (EBV)-negative methotrexate-associated lymphadenopathy occurring with Hodgkin's lymphoma in the bone marrow of a 48-year-old woman with rheumatoid arthritis. Following 10 years of treatment with low-dose methotrexate, the patient developed pancytopenia, hypercalcemia, and elevated levels of liver enzymes over the course of 2 months. A computed tomography scan of the abdomen revealed splenomegaly and enlarged abdominal lymph nodes. A bone marrow biopsy demonstrated cellular marrow with 2 paratrabecular granuloma-like lesions composed of histiocytes, fibroblasts, small lymphocytes, a few plasma cells, and scattered CD30(+)CD15(+) Hodgkin's cells, including a classic Reed-Sternberg cell. The results of EBV studies of the bone marrow were negative. Within a month from withdrawal of methotrexate treatment, the patient's symptoms and the abnormalities in the laboratory results had regressed completely. A positron emission tomography scan failed to detect lymphadenopathy. Twelve months later, the patient remains free of symptoms.
Case Details
Disease Location
Abdominal lymph nodes upper aspect of pelvis bone marrow
Personal Characteristics
48 -year-old female rheumatoid arthitis with low-dose pulsed mtreatment treatment for the past 10 years she was also taking prednisone, piroxicam, folic acid, calcium and multivitamin
Clinical Characteristics
She was found to have a mild normocytic anemia and mild leukopenia (hemoglobin 11.1g/dl, mean corpuscular volume 91.9 fl, wbc count 3100 cells/microl with 44% neutrophils and 8% band forms. Platelet count was normal she was hypercalcemic (ca 13.2mg/dl) and liver enzyme levels were elevated (aspartate aminotransferase 68 u/l, alanine aminotransferase 84 u/l, alkaline phosphatase 222 u/l. She complained of mild abdominal discomfort and nausea. The results of an ultrasound of the pelvis were unremarkable over 2 months, her loss of appetite, vomiting, fatigue, and dyspnea on exertion, and severe weakness progressed. Over this period she gained 40 pounds, there was no symptoms of feer or sweats 2 months follow-up after intital evaluation found more pronounced anemia, leukopenia, platelet count decreased to 77k/microl peripheral blood smear revealed rare spherocytes and no schistocytes and didnt suggest hemolysis she was found with acute renal insufficiency, blood urea nitrogen 41mg/dl, and hypercalcemia physical exam revealed signs of anemia i.e. Heart rate was 110 bpm and a systolic murmur grade 2/4 along the left sternal border; the liver edge was felt below the ribs. The spleen tip was felt at approx 3 fingerbreadths below the rib margin. There were no palpable cervical, supraclavicular or axillary lymph nodes. Methotrexate was discontinued and patient was hospitalized CT of the abdomen without IV contrast revealed enlargement of the spleen with a questionable small hypodense lesion within the parenchyma retroperitoneal lymphadenopathy was seen within the abdomen and in the upper aspect of the pelvis. Lymphadenopathy was also noted in the perigastric and porta hepatis areas. The liver and gallbladder appeared unremarkable possible clinical diagnosis included possible aleukemic leukemia, plasma cell dyscrasia, lymphoma, aplastic anemia and hypersplenism. To evaluate further, bone marrow biopsy was performed 1 month after methotrexate withdrawal, follow-up took place, she reported complete regression of all symptoms morphology of the bone marrow showed a cellular marrow with fat-cell ratio of 60:40, myeloid-erythroid ratio was 3:1 to 4:1. The number of megakaryocytes average 4 per high-power field with a few 2-cell clusters and spectrum of forms. Moderate plasmacytosis was seen. Granulopoiesis evaluation showed mild cytologic changes with large meutrophils. The erythropoiesis features included mild cytologic changes with rare, large late-stage forms. Less than 1% blasts were seen the most prominent feature of the biopsy was the present of 2 paratrabecular noncaseating granuloma-like lesions these lesions were fairly discrete but their margins seemed to intermingle with the surrounding hematopoietic tissue. They were composed of histiocytes, fibroblasts, small lymphocytes, a few plasma cells, and a few scattered large pleomorphic cells some what resembling transformed lymphocytes. The large cells included mononuclear forms, some appeared to be polyploid and a few appeared to have segmented nuclei. Some of the cells had single or multiple large nucleoli rare classic bilobed r-s cells were identified in sections routinely stained with hematoxylin and eosin as well as the in the immunohistochemical preps staining with b- and t-cell antibodies demonstrated scattered small b-lymphocytes and small t-lymphocytes. Most of the lymphocytes in the granuloma-like lesions were small t-cells with a few small b-lymphocytes scattered throughout the lesions staining with CD15/leu-m1 and CD30/ki-1 antibodies found the large pleomorphic cells in the granuloma-like lesions to be positive for both antibodies. Diagnostic r-s cell was identified in the CD30 study. The results of the study with an antibody to cd1a to evaluate changes for langerhans cells was negative results for ziehl-neelsen staining and gomori methenamine stinging were negative. Results of prussian blue staining were normal flow cytometry evaluation of bone marrow revealed a mixed population of hematopoietic cells and didn't demonstrate a monoclonal lymphoid population the majority of gated cells were t-lymphocytes (CD2, 3, 5, 7 positive). Of the t-cells, the CD4+ and 8+ subsets occurred in approx. Equal proportions. The remaining lymphocytes were mainly natural killer cells (CD2+, CD3-, CD16+, CD56+) only a small number of b-lymphocytes were present presence of ebv RNA in bone marrow was negative. A test for vca immunoglobulin g in the serum was positive, whereas anti-vca IGG in serum was negative
Remission Characteristics
After 1 month without mtreatment, she reported complete regression of all symptoms. Hemoglobin was 11.5g/dl, wbc was 9800/microl, and platelet count was 273k/microl PET was essentially normal when trying to detect nodes suitable for biopsy PET scan showed complete regression of lymphadenopathy no follow-up bone biopsy was performed, the patient is still free from any recurrence 12 months after the discontinuation of mtreatment
Treatment & Mechanisms
Proposed Remission Mechanisms
Discontinuation of mtreatment
Clinical Treatment
Mtreatment treatment for the past 10 years she was also taking prednisone, piroxicam, folic acid, calcium and multivitamin
Non-Clinical Treatment
None reported