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A possible familial lymphoproliferative disorder in two male siblings of children with recurrent wheezing and lung infections since infancy

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Abstract

Malignancies that result in wheezing in infants are very uncommon. Given its rarity in children, the diagnosis is challenging, and in the absence of a high index of suspicion, delayed diagnosis is not uncommon. Here we report two male siblings of children who presented with recurrent wheezing and recurrent lung infections since infancy. Both children showed no laboratory evidence of immunodeficiency. Lymphocytic interstitial pneumonia or hypersensitivity pneumonitis was histologically suspected in lung biopsy specimens from the older brother. He subsequently developed Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis and died. Based on the family history, we screened mutations among PRF1, Munc13-4, STX11, SH2D1A, and XIAP genes for the younger brother, but did not identify any mutations. He also underwent lung biopsy, which showed interstitial infiltration of lymphoid cells. In situ hybridization for EBV-encoded RNA showed a positive nuclear signal in the lymphoid cells. The presence of clonal B-cell proliferations was detected by clonally rearranged immunoglobulin studies. Lymphomatoid granulomatosis grade 3 was finally diagnosed. The progression of disease was rapid, and the patient died, despite rituximab therapy. The similar clinical manifestations in two male siblings suggest the possibility that a previously undescribed genetic defect contributed to these familial lymphoproliferative malignancies.

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Acknowledgments

This work was supported in part by the grants CMRPG4A0041-43 from Chang Gung Memorial Hospital, Taiwan, the grants NCS-100-2314-B-182A-063 from the National Science Council, Taiwan, and grants DOH102-TD-C-111-006 from the National Health Research Institute, Taiwan.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan 333, Taoyuan, Taiwan

    Shih-Hsiang Chen

  2. Division of Critical Care and Emergency Medicine, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Shao-Hsuan Hsia & Jainn-Jim Lin

  3. Division of Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Kin-Sun Wong

  4. Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Chih-Wei Wang

  5. Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Lee-Yung Shih

  6. Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

    Wen-I Lee

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  1. Shih-Hsiang Chen
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  2. Shao-Hsuan Hsia
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  3. Jainn-Jim Lin
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Correspondence to Shih-Hsiang Chen.

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Chen, SH., Hsia, SH., Lin, JJ. et al. A possible familial lymphoproliferative disorder in two male siblings of children with recurrent wheezing and lung infections since infancy. Int J Hematol 100, 407–412 (2014). https://doi.org/10.1007/s12185-014-1621-z

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  • DOI: https://doi.org/10.1007/s12185-014-1621-z

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