A 6-month-old girl presented to our clinic with bilateral hip joint pain, which began 1 year prior to her admission. The pain drastically affected her physical activity and was more evident in the morning. No other symptoms were presented. She then received Plain MRI and enhanced scanning of the hip joints, which revealed a small amount of effusion within the bilateral joints. Both colored ultrasound examination of retroperitoneum and Plain CT scanning of the chest and abdomen showed no evident abnormalities; thus, no special treatment was given to the child at that time.
The child still complained of recurrent hip pain, and her parents treated her with physical therapy, with no significant improvement. In September 2019, the girl was admitted to our clinic for the first time, and the Plain MRI and enhanced scanning showed a small amount of bilateral hip joint effusion. Cytological examinations of the bone marrow were normal. However, her parents treated the child with irregular traditional Chinese medicine and still did not see any significant improvement.
In December 2019, the girl was admitted to another hospital and diagnosed with JIA. At that time, EBV-DNA quantification was normal. From then on, she received oral administration of methotrexate (MTX, 14 mg/m2, once per week), methylprednisolone pills (0.75 mg/kg/d), and subcutaneous injections of Recombinant Human Tumor Necrosis Factor-alpha Receptor II; lgG Fc Fusion Protein (0.8 mg/kg, once per week). The pain was relieved after 4 weeks of continuous treatment. Two months later, the child did not follow-up and stopped all treatment. On May 12, 2020, the pain in the bilateral hip joints became more severe and was accompanied by occasional headaches. The patient was then admitted to our hospital on May 14 for further examinations. No other symptoms were present (Figure 1).
The girl was diagnosed with immune thrombocytopenia (PLT: 87 x 109/L) in 2017. At that time, cytological examination of the bone marrow showed active bone marrow hyperplasia, maturation disorders of megakaryocytes, and diffused distribution of platelets. The platelet count returned to a normal level after venous infusion of immunoglobulin. No history of organ transplantation or repeated infection was reported. In addition, no remarkable family history was reported.
Upon physical examination, her vital signs were in a normal range with a body weight of 16 kg. The examination of her chest and abdomen showed no obvious abnormalities. No swelling or pressing pain was found in the joints of limbs. However, the 4-shaped sign showed positive results.
During routine laboratory and blood examinations: C-reactive protein (CRP), IL-6, serum ferritin, ASO, and rheumatoid factors (RF) were all within a normal range. Autoimmune antibody (ANCA, ANA, ANA spectrum, PR3-IgG, MPO-IgG, GBM-IgG, and anti-CCP) and pathogenic examination (tuberculosis antibody, tuberculosis infection-specific T cells, mycoplasma antibody, HIV, and fungi) were all negative. EB-VCA-IgG and EB-NA-IgG levels were elevated; EB-VCA-IgM and EB-EA-IgG levels were normal. EBV-DNA quantification showed normal results. Examination of HBsAg, HBeAg, and HBcAb showed positive, and serum quantification of HBV-DNA was 3.38 x 107 IU/ml. The levels of immunoglobulins (A, E, G, and M) and complements C3 and C4 were all within a normal range (Table 1). Lymphocyte subsets were normal.
Colored ultrasound examination of the retroperitoneum showed no masses or abnormalities. Plain CT scanning of the lungs showed multiple nodules and stripe-shaped shadows bilaterally in the lungs. The largest was 0.63 x 0.74 cm. Plain and enhanced MRI scanning of the knee and hip joints revealed that the synovium of the bilateral knee and hip joints were slightly thickened and enhanced, with a small amount of effusion in the joints. Plain and enhanced CT scanning of the lumbar vertebrae showed the adnexa area left to the L2 vertebral body had osteolytic bone destruction and was accompanied by soft tissue masses. Plain and enhanced MRI scanning of the skull, pituitary, and spine showed nodular lesions at the parasellar and meninges of the right parietal lobe and bone mass destruction of the L2 vertebral body and left vertebral pedicle (Figure 2). Electromyography (EMG) of bilateral lower limbs showed no abnormalities in nerve conduction or muscle contraction.
Bone marrow biopsy examination showed active bone marrow hyperplasia, substantially reduced erythroid hyperplasia, and elevated lymphocytes. Biopsy of the inguinal lymphocytes revealed that the microscopy and immunohistochemistry findings agreed with the changes of reactive hyperplasia of the lymph node.
So far, the diagnosis of the child is still not clear. Two biopsies were performed within the L2 vertebral lesion tissues. The first biopsy was not diagnosed because EBER in-situ hybridization was not performed. The diagnosis was not made until after the second biopsy of a positive EBER in-situ hybridization was performed (Figure 3).
The girl's pathological examination showed EBER (+); thus, she was diagnosed with EBV-SMT. However, she was not previously infected with HIV or had any organ transplantation. In addition, the girl had no history of immunodeficiency-related diseases. In order to clarify the possibility of undiagnosed immunodeficiency or other causes, blood was obtained for whole-exome sequencing. The results showed no related pathogenic genes.
The patient was admitted to the hospital for arthritis. The imaging examinations after admission showed multiple lesions in the skull, lungs, and vertebral body. Other hematological tumors or Langerhans cell histiocytosis were considered during the diagnosis, which was not in agreement with the pathological and other examination results. Biopsy of the L2 vertebral body was then performed to clarify the diagnosis. Finally, the in-situ hybridization of the tumor of the lumbar vertebrae suggested non-HIV/transplantation-related EBV-SMT. The patient then received surgery (lumbar lesions resection + fusion bone grafting and internal fixation) without chemo or radiotherapy. The hip pain improved except for occasional headache. The patient is still under regular follow-up now.
Imaging examination. (B) Plain CT scanning of lungs showed multiple nodules and stripe-shaped shadows in bilateral lungs, and the size of the largest shadow was 0.63 x 0.74 cm.