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Case Report ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pediatr. | doi: 10.3389/fped.2018.00402

Evaluation of Lymphoproliferative Disease and Increased Risk of Lymphoma in Activated Phosphoinositide 3 Kinase Delta Syndrome: a case report with discussion

  • 1Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, United States
  • 2Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, United States
  • 3Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, United States

Activated phosphoionositide-3 kinase delta syndrome (APDS) is a rare disorder caused by activating mutations in phosphoionositide 3-kinase delta (PI3Kδ). This syndrome usually presents in childhood with recurrent sinopulmonary infections and immune deficiency as is seen in the case discussed in this report. Patients with APDS also experience other complications including lymphoid hyperplasia, autoimmunity, increased susceptibility to herpes viruses, especially Epstein-Barr virus and cytomegalovirus, and an increased incidence of B-cell lymphoma. The clinical implications for lymphoid hyperplasia and lymphoma are profound and frequently, it is challenging to distinguish between the two.

This case report is of a young girl with a mutation in PIK3CD, the gene encoding the catalytic subunit of PI3Kδ, who presents with asymmetrical cervical lymphadenopathy and parotid swelling. After little improvement in lymphadenopathy on antibiotics, an excisional biopsy of a cervical lymph node was obtained which was initially concerning for lymphoma. This case recounts the clinical decisions made to evaluate this lymphadenopathy and concern for malignancy due to the increased incidence of B-cell lymphoma in this population. It was concluded after careful evaluation of her lymph node histology and cytometry, bone marrow biopsy, and CSF studies that her findings were consistent with lymphoid hyperplasia and not lymphoma and she was treated with rituximab.

This case highlights the many comorbidities present in patients with this disease and the current treatments for complications in patients with APDS, including new targeted therapies.

Keywords: Phosphoinositide 3-kinase, activated phosphoinositide 3-kinase δ syndrome, immunodeficiency, Activating mutation, Hypogammaglobinaemia, Lymphoproliferative disease, malignancy

Received: 15 Sep 2018; Accepted: 04 Dec 2018.

Edited by:

Ivan K. Chinn, Baylor College of Medicine, United States

Reviewed by:

Pamela L. Schwartzberg, National Institutes of Health (NIH), United States
Tanya I. Coulter, Belfast Health and Social Care Trust, United Kingdom  

Copyright: © 2018 Pham and Cunningham-Rundles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Charlotte Cunningham-Rundles, Icahn School of Medicine at Mount Sinai, Division of Clinical Immunology, Department of Medicine, New York, 10029, New York, United States,