title: A possible familial lymphoproliferative disorder in two male siblings of children with recurrent wheezing and lung infections since infancy.
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.
authors.affiliation: 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, samechen@adm.cgmh.org.tw.
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Chen
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Hsia
authors.forename: Jainn-Jim
authors.initials: JJ
authors.lastname: Lin
authors.forename: Kin-Sun
authors.initials: KS
authors.lastname: Wong
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wang
authors.forename: Lee-Yung
authors.initials: LY
authors.lastname: Shih
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000473:pathology; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007223:Infant; D017563:Lung Diseases, Interstitial / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008230:Lymphomatoid Granulomatosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D011014:Pneumonia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012135:Respiratory Sounds; D000069283:Rituximab; D035781:Siblings
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab