Non-Hodgkin's lymphoma in a woman with adult-onset Still's disease: a case report
© Otrock et al; licensee BioMed Central Ltd. 2008
Received: 14 June 2007
Accepted: 06 March 2008
Published: 06 March 2008
Adult onset Still's disease is a chronic multisystemic inflammatory disorder characterized by high spiking fever, polyarthralgia and rash. Lymphadenopathy is a prominent feature of adult onset Still's disease and is seen in about 65% of patients. Searching the medical literature using the MEDLINE database from January 1966 through November 2007 we could only find two reported cases of adult onset Still's disease that had progressed to lymphoma.
We describe a woman who was diagnosed with adult onset Still's disease and developed lymphoma 10 months after the onset of her symptoms. She initially presented with fever and arthritis of the knees, ankles and shoulders, along with a nonpruritic skin rash, myalgia and weight loss. On physical examination she was found to have several enlarged anterior cervical lymph nodes and left posterior auricular lymph nodes all of which were non-tender, immobile and rubbery. Excisional biopsy of the cervical lymph nodes was negative for malignancy. Bone marrow biopsy was also negative for malignancy. She was treated with prednisone. She remained in good health until she presented 10 months later with low back pain, dyspnea and weight loss. Work up revealed malignant lymphoma. She was treated with chemotherapy and was doing well until she presented with abdominal pain. Work up revealed a cirrhotic liver and ascites. She then passed away from hepatorenal syndrome 13 years after the diagnosis of lymphoma. To our knowledge, this is the third reported case of such an occurrence.
Although the association between adult onset Still's disease and lymphoma has been rarely reported, careful screening for this malignancy in patients suspected to have adult onset Still's disease is warranted.
Adult onset Still's disease (AOSD) is a chronic multisystemic inflammatory disorder of unknown origin characterized by a high spiking fever, polyarthralgia, a salmon pink evanescent rash, and hepatosplenomegaly . Notable laboratory features of the disease are increased serum levels of C-reactive protein (CRP), leukocytosis, liver dysfunction, negative results for both rheumatoid factor and antinuclear antibodies, and an increased incidence of hyperferritinemia [2, 3]. Lymphadenopathy is a prominent feature of AOSD seen in about 65% of patients  and necessitating in most instances a biopsy to rule out lymphoma.
We describe a woman who was diagnosed with AOSD and developed non-hodgkin's lymphoma (NHL) 10 months after the onset of her symptoms. To our knowledge, this is the third reported case of such an occurrence.
A 32-year-old woman presented in 1991 with a 2-month history of fever reaching 39.5°C and associated with arthritis in the knees, ankles and shoulders, a nonpruritic skin rash, myalgia and weight loss. Her laboratory studies, including liver function tests, were within the normal ranges except that she had an elevated erythrocyte sedimentation rate (ESR) of 110 mm/hr and lactate dehydrogenase (LDH) of 1975 IU/L (Normal Range: 200–480). The rheumatoid factor and antinuclear antibodies were negative. Blood cultures were also negative. On physical examination she was found to have several enlarged right anterior cervical lymph nodes (2 × 3 cm in size) and left posterior auricular lymph nodes (0.5 × 1 cm in size) all of which were non-tender, immobile and rubbery. In addition, she had swelling in both knee joints and ankle joints. Papular skin lesions on the neck and upper abdomen were evident. No hepatosplenomegaly was detected. A chest radiograph revealed pleural effusion in the left lower lung lobe. Computed tomography (CT) scan of the abdomen and pelvis was normal. Excisional biopsy of cervical lymph nodes done at another hospital and reviewed by our pathologist was negative for malignancy. Bone marrow biopsy was negative for malignancy. Celiac angiogram to rule out vasculitis was negative. A diagnosis of AOSD was made based on the Yamaguchi criteria . She had 2 major criteria: arthritis and fever, and 3 minor criteria: lymphadenopathy, elevated LDH and negative rheumatoid factor and antinuclear antibodies. The patient was started on steroid therapy.
We described a case of a woman with AOSD who was diagnosed with lymphoma 10 months after the onset of symptoms. The patient satisfied the criteria of Yamaguchi et al for AOSD . In this case, there is a possibility that the lymphoma had latently existed from the beginning of the clinical course. However, 10 months had elapsed after the onset of Still's disease before the development of symptoms of lymphoma and a previous lymph node biopsy had been negative for lymphoma.
AOSD is commonly considered in the differential diagnosis of fever of unknown origin, especially if associated with multiple organ involvement [4, 6]. In the absence of specific clinical, laboratory and histological features for AOSD, the exclusion of infections, malignancies and other rheumatologic diseases is crucial.
Lymphadenopathy commonly occurs in AOSD . Although most of the histopathologic studies performed have shown non-diagnostic reactive hyperplasia in AOSD, histological patterns simulating malignant lymphoma have been reported. Besides necrotizing lymphadenitis , some authors have described a distinctive, intense paracortical hyperplasia characterized by an expansion of immunoblastic cells and prominent arborizing vessels [8, 9]. It has been pointed out that the intensity of the process, along with the apparent nodal architecture effacement and the atypical proliferating cells, may suggest an erroneous diagnosis of malignancy. Sometimes it may be difficult to differentiate AOSD from malignant hematologic disorders . In addition to clinical features, histopathological features of lymph node biopsy may also mimic lymphoma [11, 12].
Summary of reported cases with AOSD who developed lymphoma.
Age at diagnosis of AOSD (years)
Time elapsed from symptoms to lymphoma diagnosis (months)
Trotta et al
Absent but with hepatosplenomegaly
Sono et al
Fever, arthritis, myalgia
3 month follow-up
Written informed consent was obtained from the patient's family for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Adult Onset Still's Disease
erythrocyte sedimentation rate
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