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Chronic Epstein-Barr virus infection causing both benign and malignant lymphoproliferative disorders.

Kwun Y, Hong SJ, Lee JS, Son da H, Seo JJ - Korean J Pediatr (2014)

Bottom Line: The results of in situ hybridization were positive for EBV, which led to a diagnosis of LIP.The diagnosis was confirmed by the results of a thoracoscopic lung biopsy.The EBV titer of the bronchoalveolar lavage specimens obtained after acyclovir treatment was found to be fluctuating.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Asan Medical Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT
The Epstein-Barr virus (EBV) is oncogenic and can transform B cells from a benign to a malignant phenotype. EBV infection is also associated with lymphoid interstitial pneumonia (LIP). Here, we report the case of a 14-year-old boy who was diagnosed with a latent EBV infection and underlying LIP, without any associated immunodeficiency. He had been EBV-seropositive for 8 years. The first clinical presentations were chronic respiratory symptoms and recurrent pneumonia. The symptoms worsened in the following 2 years. The results of in situ hybridization were positive for EBV, which led to a diagnosis of LIP. The diagnosis was confirmed by the results of a thoracoscopic lung biopsy. The EBV titer of the bronchoalveolar lavage specimens obtained after acyclovir treatment was found to be fluctuating. The patient had latent EBV infection for 8 years, until presented at the hospital with intermittent abdominal pain and distension. Physical examination and pelvic computed tomography revealed a large mesenteric mass. A biopsy of the excised mass led to a diagnosis of Burkitt's lymphoma (BL). The patient received combination chemotherapy for 4 months, consisting of vincristine, methotrexate, cyclophosphamide, doxorubicin, and prednisolone. He is now tumor-free, with the LIP under control, and is being followed-up at the outpatient clinic. This is the first report of a Korean case of chronic latent EBV infection that developed into LIP and BL in a nonimmunocompromised child.

No MeSH data available.


Related in: MedlinePlus

Lymphoid interstitial pneumonia (LIP) with latent Epstein-Barr virus (EBV) infection: highresolution computed tomography images and findings of the thoracoscopic biopsy. Thin-section computed tomography of the lungs taken 2 years after the first presentation of chronic recurrent respiratory symptoms. (A) Thickening of the interlobular septa (arrows) and bronchial wall. (B) Bronchial dilation with partial atelectasis in the medial segment of the right middle lobe. The thickened walls of the dilated bronchi can be observed. (C) Ectatic bronchi are seen in the left lower lobe. (D) Thoracoscopic biopsy of a lung specimen shows evidence of LIP, which is characterized by diffuse infiltration of the alveolar septa by lymphoplasmacytic cells and formation of the lymphoid follicle (H&E, ×200). (E) In situ hybridization analysis of lymph cells reveals EBV-infected cells (×200).
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Figure 1: Lymphoid interstitial pneumonia (LIP) with latent Epstein-Barr virus (EBV) infection: highresolution computed tomography images and findings of the thoracoscopic biopsy. Thin-section computed tomography of the lungs taken 2 years after the first presentation of chronic recurrent respiratory symptoms. (A) Thickening of the interlobular septa (arrows) and bronchial wall. (B) Bronchial dilation with partial atelectasis in the medial segment of the right middle lobe. The thickened walls of the dilated bronchi can be observed. (C) Ectatic bronchi are seen in the left lower lobe. (D) Thoracoscopic biopsy of a lung specimen shows evidence of LIP, which is characterized by diffuse infiltration of the alveolar septa by lymphoplasmacytic cells and formation of the lymphoid follicle (H&E, ×200). (E) In situ hybridization analysis of lymph cells reveals EBV-infected cells (×200).

Mentions: A 1-year-old boy made frequent visits to the local outpatient clinic due to a chronic cough and recurrent wheezing. He was tentatively diagnosed with maxillary sinusitis and bronchial asthma accompanying recurrent acute otitis media. There was no family history of chronic lung disease or asthma. At 5 years old, the boy was transferred to Asan Medical Center Children's Hospital in Seoul, Korea. He was suffering from chronic respiratory symptoms, including a chronic cough, excess sputum, and respiratory difficulties, which showed a poor response to asthma medication. Because the recurrent pneumonia was persistent, we performed high resolution computed tomography, which revealed mild bronchiectasis with peribronchial nodules (Fig. 1A-C). At 7 years old, when his respiratory symptoms were aggravated, a thoracoscopic lung biopsy was performed, which revealed LIP characterized by a dense polymorphous lymphoid infiltrate along the alveolar septa, with frequent lymphoid follicles (Fig. 1D). In situ hybridization for EBV-encoding RNA (EBER) showed frequent positive nuclear signals in small lymphocytes (Fig. 1E). The EBV genome was also detected by polymerase chain reaction (PCR). The initial EBV titer ranged from 24 copies/500 ng DNA in the blood to 204 copies/500 ng DNA and bronchoalveolar lavage (BAL) fluid. The EBV titer in the BAL waxed and waned after two cycles of acyclovir therapy and the virus remained latent. Laboratory tests performed when the boy was 5-year-old revealed the following: immunoglobulin (Ig) G, 3,660 mg/dL (normal range for the same age group, 345-1,236 mg/dL); IgM, 112 mg/dL (normal range, 43-207 mg/dL); IgA, 88.7 mg/dL (normal range, 14-159 mg/dL); C3, 122 mg/dL (normal range, 77-195 mg/dL); C4, 14.4 mg/dL (normal range, 7-40 mg/dL); and CH50, 58.2 U/mL (normal range, 60-144 U/mL). Mild hypergammaglobulinemia was also noted. Analysis of lymphocyte subsets showed the following: T cells, 50.7% (normal range, 56%-7%); CD4+ lymphocytes, 28.6% (normal range, at 2-6 years of age, 35%-51%); CD8+ lymphocytes, 20.7% (normal range, 22%-38%); natural killer cells, 30.9% (normal range, 5%-35%), and CD19+ B cells, 14.6% (normal range, 5%-23%). These results suggested normal T and B cell levels. IgG subclass analysis showed the following: IgG1, 13.7 g/L (normal range at 4-7 years of age, 2.09-9.02 g/L); IgG2, 3.78 g/L (normal range, 0.44-3.16 g/L); IgG3, 1.03 g/L (normal range, 0.11-0.95 g/L); and IgG4, 0.19 g/L (normal range, 0.008-0.82 g/L). The serum antinuclear antibody (ANA) titer was initially <1:40, but later showed a positive speckled titer of 1:80, suggesting a possible nonspecific autoimmune disorder. The patient was seronegative for human immunodeficiency virus antigen and antibodies, confirming a nonimmunocompromised state. After discharge, he was referred back to his local hospital for follow-up, and was doing relatively well, with only mild respiratory symptoms.


Chronic Epstein-Barr virus infection causing both benign and malignant lymphoproliferative disorders.

Kwun Y, Hong SJ, Lee JS, Son da H, Seo JJ - Korean J Pediatr (2014)

Lymphoid interstitial pneumonia (LIP) with latent Epstein-Barr virus (EBV) infection: highresolution computed tomography images and findings of the thoracoscopic biopsy. Thin-section computed tomography of the lungs taken 2 years after the first presentation of chronic recurrent respiratory symptoms. (A) Thickening of the interlobular septa (arrows) and bronchial wall. (B) Bronchial dilation with partial atelectasis in the medial segment of the right middle lobe. The thickened walls of the dilated bronchi can be observed. (C) Ectatic bronchi are seen in the left lower lobe. (D) Thoracoscopic biopsy of a lung specimen shows evidence of LIP, which is characterized by diffuse infiltration of the alveolar septa by lymphoplasmacytic cells and formation of the lymphoid follicle (H&E, ×200). (E) In situ hybridization analysis of lymph cells reveals EBV-infected cells (×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4198958&req=5

Figure 1: Lymphoid interstitial pneumonia (LIP) with latent Epstein-Barr virus (EBV) infection: highresolution computed tomography images and findings of the thoracoscopic biopsy. Thin-section computed tomography of the lungs taken 2 years after the first presentation of chronic recurrent respiratory symptoms. (A) Thickening of the interlobular septa (arrows) and bronchial wall. (B) Bronchial dilation with partial atelectasis in the medial segment of the right middle lobe. The thickened walls of the dilated bronchi can be observed. (C) Ectatic bronchi are seen in the left lower lobe. (D) Thoracoscopic biopsy of a lung specimen shows evidence of LIP, which is characterized by diffuse infiltration of the alveolar septa by lymphoplasmacytic cells and formation of the lymphoid follicle (H&E, ×200). (E) In situ hybridization analysis of lymph cells reveals EBV-infected cells (×200).
Mentions: A 1-year-old boy made frequent visits to the local outpatient clinic due to a chronic cough and recurrent wheezing. He was tentatively diagnosed with maxillary sinusitis and bronchial asthma accompanying recurrent acute otitis media. There was no family history of chronic lung disease or asthma. At 5 years old, the boy was transferred to Asan Medical Center Children's Hospital in Seoul, Korea. He was suffering from chronic respiratory symptoms, including a chronic cough, excess sputum, and respiratory difficulties, which showed a poor response to asthma medication. Because the recurrent pneumonia was persistent, we performed high resolution computed tomography, which revealed mild bronchiectasis with peribronchial nodules (Fig. 1A-C). At 7 years old, when his respiratory symptoms were aggravated, a thoracoscopic lung biopsy was performed, which revealed LIP characterized by a dense polymorphous lymphoid infiltrate along the alveolar septa, with frequent lymphoid follicles (Fig. 1D). In situ hybridization for EBV-encoding RNA (EBER) showed frequent positive nuclear signals in small lymphocytes (Fig. 1E). The EBV genome was also detected by polymerase chain reaction (PCR). The initial EBV titer ranged from 24 copies/500 ng DNA in the blood to 204 copies/500 ng DNA and bronchoalveolar lavage (BAL) fluid. The EBV titer in the BAL waxed and waned after two cycles of acyclovir therapy and the virus remained latent. Laboratory tests performed when the boy was 5-year-old revealed the following: immunoglobulin (Ig) G, 3,660 mg/dL (normal range for the same age group, 345-1,236 mg/dL); IgM, 112 mg/dL (normal range, 43-207 mg/dL); IgA, 88.7 mg/dL (normal range, 14-159 mg/dL); C3, 122 mg/dL (normal range, 77-195 mg/dL); C4, 14.4 mg/dL (normal range, 7-40 mg/dL); and CH50, 58.2 U/mL (normal range, 60-144 U/mL). Mild hypergammaglobulinemia was also noted. Analysis of lymphocyte subsets showed the following: T cells, 50.7% (normal range, 56%-7%); CD4+ lymphocytes, 28.6% (normal range, at 2-6 years of age, 35%-51%); CD8+ lymphocytes, 20.7% (normal range, 22%-38%); natural killer cells, 30.9% (normal range, 5%-35%), and CD19+ B cells, 14.6% (normal range, 5%-23%). These results suggested normal T and B cell levels. IgG subclass analysis showed the following: IgG1, 13.7 g/L (normal range at 4-7 years of age, 2.09-9.02 g/L); IgG2, 3.78 g/L (normal range, 0.44-3.16 g/L); IgG3, 1.03 g/L (normal range, 0.11-0.95 g/L); and IgG4, 0.19 g/L (normal range, 0.008-0.82 g/L). The serum antinuclear antibody (ANA) titer was initially <1:40, but later showed a positive speckled titer of 1:80, suggesting a possible nonspecific autoimmune disorder. The patient was seronegative for human immunodeficiency virus antigen and antibodies, confirming a nonimmunocompromised state. After discharge, he was referred back to his local hospital for follow-up, and was doing relatively well, with only mild respiratory symptoms.

Bottom Line: The results of in situ hybridization were positive for EBV, which led to a diagnosis of LIP.The diagnosis was confirmed by the results of a thoracoscopic lung biopsy.The EBV titer of the bronchoalveolar lavage specimens obtained after acyclovir treatment was found to be fluctuating.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Asan Medical Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT
The Epstein-Barr virus (EBV) is oncogenic and can transform B cells from a benign to a malignant phenotype. EBV infection is also associated with lymphoid interstitial pneumonia (LIP). Here, we report the case of a 14-year-old boy who was diagnosed with a latent EBV infection and underlying LIP, without any associated immunodeficiency. He had been EBV-seropositive for 8 years. The first clinical presentations were chronic respiratory symptoms and recurrent pneumonia. The symptoms worsened in the following 2 years. The results of in situ hybridization were positive for EBV, which led to a diagnosis of LIP. The diagnosis was confirmed by the results of a thoracoscopic lung biopsy. The EBV titer of the bronchoalveolar lavage specimens obtained after acyclovir treatment was found to be fluctuating. The patient had latent EBV infection for 8 years, until presented at the hospital with intermittent abdominal pain and distension. Physical examination and pelvic computed tomography revealed a large mesenteric mass. A biopsy of the excised mass led to a diagnosis of Burkitt's lymphoma (BL). The patient received combination chemotherapy for 4 months, consisting of vincristine, methotrexate, cyclophosphamide, doxorubicin, and prednisolone. He is now tumor-free, with the LIP under control, and is being followed-up at the outpatient clinic. This is the first report of a Korean case of chronic latent EBV infection that developed into LIP and BL in a nonimmunocompromised child.

No MeSH data available.


Related in: MedlinePlus