Systemic Epstein-Barr Virus–Positive T-cell Lymphoma of Childhood
We report a case of a 7-year-old Chinese boy who presented with acute fever, multiple oral ulcers, and skin nodules. A diagnosis of systemic Epstein-Barr virus (EBV)–positive T-cell lymphoma of childhood was established using systemic laboratory examination, imaging studies, bone marrow and skin biopsy with immunohistochemistry, and in situ hybridization for EBV-encoded RNA (EBER) and gene rearrangements. Notable features of this case include the absence of pancytopenia and hemophagocytic syndrome as well as spontaneous resolution without chemotherapy for several months; however, the condition relapsed, and the patient died.
Practice Points
- Systemic Epstein-Barr virus (EBV)–positive T-cell lymphoma of childhood is a fulminant illness with a predilection for Asians and indigenous populations from Mexico and Central and South America. In most patients, the disease has an aggressive clinical course with high mortality.
- The disease often is complicated by hemophagocytic syndrome, coagulopathy, sepsis, and multiorgan failure. When these severe complications are absent, the prognosis might be better.
- In situ hybridization for EBV-encoded RNA and for T-cell receptor gene rearrangements is an important tool to establish the diagnosis as well as for treatment options and predicting the prognosis.
Laboratory Results
Laboratory testing revealed a normal total white blood cell count (4.26×109/L [reference range, 4.0–12.0×109/L]), with normal neutrophils (1.36×109/L [reference range, 1.32–7.90×109/L]), lymphocytes (2.77×109/L [reference range, 1.20–6.00×109/L]), and monocytes (0.13×109/L [reference range, 0.08–0.80×109/L]); a mildly decreased hemoglobin level (115 g/L [reference range, 120–160 g/L]); a normal platelet count (102×109/L [reference range, 100–380×109/L]); an elevated lactate dehydrogenase level (614 U/L [reference range, 110–330 U/L]); an elevated α-hydroxybutyrate dehydrogenase level (483 U/L [reference range, 120–270 U/L]); elevated prothrombin time (15.3 s [reference range, 9–14 s]); elevated activated partial thromboplastin time (59.8 s [reference range, 20.6–39.6 s]); and an elevated D-dimer level (1.51 mg/L [reference range, <0.73 mg/L]). In addition, autoantibody testing revealed a positive antinuclear antibody titer of 1:320 and a strong positive anti–Ro-52 level.
The peripheral blood lymphocyte classification demonstrated a prominent elevated percentage of T lymphocytes, with predominantly CD8+ cells (CD3, 94.87%; CD8, 71.57%; CD4, 24.98%; CD4:CD8 ratio, 0.35) and a diminished percentage of B lymphocytes and natural killer (NK) cells. Epstein-Barr virus (EBV) antibody testing was positive for anti–viral capsid antigen (VCA) IgG and negative for anti-VCA IgM.
,Smears of the ulcer on the tongue demonstrated gram-positive cocci, gram-negative bacilli, and diplococci. Culture of sputum showed methicillin-resistant Staphylococcus aureus. Inspection for acid-fast bacilli in sputum yielded negative results 3 times. A purified protein derivative skin test for Mycobacterium tuberculosis infection was negative.
Imaging and Other Studies
Computed tomography of the chest and abdomen demonstrated 2 nodular opacities on the lower right lung; spotted opacities on the upper right lung; floccular opacities on the rest area of the lung; mild pleural effusion; enlargement of lymph nodes on the mediastinum, the bilateral hilum of the lung, and mesentery; and hepatosplenomegaly. Electrocardiography showed sinus tachycardia. Nasal cavity endoscopy showed sinusitis. Fundus examination showed vasculopathy of the left retina. A colonoscopy showed normal mucosa.
Histopathology
Biopsy of the nodule on the left arm showed dense, superficial to deep perivascular, periadnexal, perineural, and panniculitislike lymphoid infiltrates, as well as a sparse interstitial infiltrate with irregular and pleomorphic medium to large nuclei. Lymphoid cells showed mild epidermotropism, with tagging to the basal layer. Some vessel walls were infiltrated by similar cells (Figure 2). Infiltrative atypical lymphoid cells expressed CD3 and CD7 and were mostly CD8+, with a few CD4+ cells and most cells negative for CD5, CD20, CD30, CD56, and anaplastic lymphoma kinase. Cytotoxic markers granzyme B and T-cell intracellular antigen protein 1 were scattered positive. Immunostaining for Ki-67 protein highlighted an increased proliferative rate of 80% in malignant cells. In situ hybridization for EBV-encoded RNA (EBER) demonstrated EBV-positive atypical lymphoid cells (Figure 3). Analysis for T-cell receptor (TCR) γ gene rearrangement revealed a monoclonal pattern. Bone marrow aspirate showed proliferation of the 3 cell lines. The percentage of T lymphocytes was increased (20% of all nucleated cells). No hemophagocytic activity was found.
Diagnosis
A diagnosis of systemic EBV-positive T-cell lymphoma was made. Before the final diagnosis was made, the patient was treated by rheumatologists with antibiotics, antiviral drugs, nonsteroidal anti-inflammatory drugs, and other symptomatic treatments. Following antibiotic therapy, a sputum culture reverted to normal flora, the coagulation index (ie, prothrombin time, activated partial thromboplastin time) returned to normal, and the D-dimer level decreased to 1.19 mg/L.
The patient’s parents refused to accept chemotherapy for him. Instead, they chose herbal therapy only; 5 months later, they reported that all of his symptoms had resolved; however, the disease suddenly relapsed after another 7 months, with multiple skin nodules and fever. The patient died, even with chemotherapy in another hospital.
