A 73-year-old man presented to his local physician with a 1-month history of fever and a sore throat. Initially, he was diagnosed with a common cold and was prescribed antibiotics but later developed a recurrent fever of 38 C. After 1 week, he revisited his doctor and was treated with antipyretic analgesics; however, his high fever persisted. He subsequently developed pain in the peripheral joints and malaise, and was referred to our emergency department for a diagnostic investigation. A general fever work-up (general blood test, urine test, blood culture, chest radiography, and computed tomography scan of the chest and abdomen) in the emergency department did not reveal any obvious causes. The patient was referred to the general medical department for further evaluation. His medical and medications history was unremarkable.
The patient's vital signs were as follows: body temperature, 38.2 C; blood pressure, 143/68 mmHg; pulse, 90 beats/min; respiratory rate, 24 breaths/min. Physical examination revealed no abnormalities in the heart or respiratory sounds, and no skin abnormalities, such as erythema or purpura. Abdominal examination revealed hepatosplenomegaly, and no abnormalities were detected on neurological examination. A full blood count revealed leucocytosis (17,280/mul, normal: 3,300-8,600/mul) with neutrophil predominance (81.0%, normal: 45.5-69.8%); blood biochemistry revealed elevated levels of aspartate transaminase (AST) (185 IU/l, normal: 13-30 IU/l), alanine transaminase (ALT) (162 IU/l, normal: 10-42 IU/l), lactate dehydrogenase (LDH) (520 U/l, normal: 124-222 U/l), ferritin (1211.48 ng/ml, normal: 50-200 ng/ml) and soluble interleukin-2 receptor (sIL-2R) (3267 U/ml, normal: 122-496 U/ml). Contrast-enhanced computed tomography of the chest and abdomen revealed mild hepatosplenomegaly, but no pathological enlargement of the cervical, inguinal or axillary lymph nodes, and no abnormalities in the lung fields. A bone marrow biopsy and RSB were performed on the third day of hospitalization. Three skin biopsies were collected from normal-appearing skin of the left upper arm, abdomen and thigh, all of which showed tumour cells in the blood vessels of the subcutaneous adipose tissue (CD20-positive, CD3-negative, large atypical B lymphocytes) (Figs. 1 and 2). Based on the clinical presentation, blood test results, and the RSB histopathology, the patient was diagnosed with stage 4 IVLBCL. Brain magnetic resonance imaging was performed to search for central nervous system invasion, but no central nervous system lesions were detected.
Sore throat, hepatosplenomegaly, and elevated levels of AST, ALT, LDH, ferritin and sIL-2R, led us to consider viral infections such as Epstein-Barr virus, sepsis, miliary tuberculosis, haematological diseases such as intravascular lymphoma, and collagen diseases such as adult Still's disease, systemic lupus erythematosus and polyarteritis nodosa as differential diagnoses.
R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisolone 40 mg/m2) therapy combined with high-dose methotrexate plus intrathecal chemotherapy was initiated on the sixth day of hospitalization. The patient received six courses of R-CHOP chemotherapy.
By the end of the third course, the patient's fever, malaise and laboratory abnormalities, such as LDH and sIL-2R elevation, had improved. We performed bone marrow biopsy and RSB to evaluate the presence or absence of residual tumour cells. No invasion of tumour cells into the bone marrow was observed. RSB, from three areas near the initial biopsy sites, did not reveal tumour cells in any of the sites, and the patient was considered to be in remission. A complete response was achieved, and the patient has remained relapse-free a year after treatment.