Case Presentation Conference Children’s Hospital of New Orleans James M. Roth M.D. Evelyn Kluka M.D.

History 13 year-old Hispanic male R.G. Chief Complaint: Headache, Left Ear Pain with radiation of the pain to the cheek

History of Present Illness 1 month history of progressive left sided facial pain and tingling Recent stuffy nose with clear discharge Odynophagia

Past Medical History Esophageal Varices Hematochezia Jaundice Cirrhotic liver disease

Past Surgical History Liver Transplant 6 months prior to admission Left myringotomy by an ENT in Dallas secondary to disequilibrium, tinnitus, and serous fluid collection

Medications Bactrim- prophylaxis Ganciclovir- prophylaxis Procardia XL Magnesium Prednisone Neoral- Cyclosporine anti-rejection drug Cellcept-

Allergies/ Immunizations No known drug allergies No immunizations since liver transplant Immunizations up to date till then

Social History Born in Mexico Lives with mother currently in Dallas

Physical Exam Vital Signs normal General: Awake alert Ears: Right TM clear; Left TM slightly reddened with some fluid present Nose: Reddened inferior turbinates no drainage

Physical Exam Oropharynx: Tonsils 1-2+ symmetric, uvula midline normal tongue mobility tongue soft to palpation Neck: Small < 1 cm nodes scattered throughout neck Face: Slight swelling to the left midface

Physical Exam Neurological: V 2 and V 3 with decreased sensation on the left side. Remaining cranial nerves grossly intact.

Admission Originally evaluated Dallas and CT scan showed a nasal mass Admitted by GI/Transplant team and ENT service was consulted for biopsy

MRI Mass filling the nasopharynx compressing or encompassing the left Eustachian tube with area of central necrosis

Intraoperative Findings Fungating gray mass filling most of the nasopharynx slight more on the left than the right Very solid in nature and avascular

Lab Work EBV titers IgM elevated CBC wnl Chem 7 wnl PT/PTT wnl

Surgical Pathology Large lesion 3.5x1.5x.5 cm Lymphoid lesion Polyclonal cells: small mature lymphocytes, large active immunoblast, T cells, B cells, Strongly EBV positive

Diagnosis Post Transplant Lymphoproliferative Disease (PTLD): Polyclonal Variant

PTLD The presence of an abnormal proliferation of lymphoid cells Highly related to EBV infection Related to the type of solid organ transplanted More common in children Originally described in 1969 in 5 renal transplant patients

Pathology Several variants from benign polyclonal B cell hyperplasia to malignant monoclonal lymphoma The progression to a monoclonal population leads to a more aggressive and malignant tumor

Why transplant patient’s? Immunosuppression is targeted against T cells especially cytotoxic T cells These cells help to self regulate the immune system With certain viral infection you get B cell proliferation These cells can progress in an unregulated manner

EBV Infection Causes an active B cell proliferation Linked to Burkitt’s lymphoma and nasopharyngeal cancer R.G. was originally seronegative prior to transplantation His runny nose and sore throat may have represented a recent EBV infection

Common Presentation Mononucleosis type infection Febrile illness with leukopenia Focal organ system failure –GI tract: endoscopy, CT scans –CNS: lumbar puncture –Lymph node involvement

Solid Organ Transplant Renal- 1% Liver- 2-3% Heart- 4-10%

Risk Factors Young age: Increased risk of primary EBV infections in the early post transplant period Agents: Not any single agent more responsible but the cumulative intensity of immunosuppression seems to be most important.

Treatment Decrease immunosuppression Antivirals: acyclovir ganciclovir Immunoglobulins: IVIG which helps to target CMV Chemotherapuetics: Rituximab (CD20 ligand) Radiotherapy

Conclusions PTLD is a rare complication of transplantation- 2% of all solid organ transplant recipients More common in children secondary to primary exposure to EBV May present in the head and neck especially do to the rich lymphatic system Treatable as long as there is not monoclonal proliferation

R.G. Underwent treatment at a variety of levels Immunosuppression was decreased Given IVIG, Acyclovir, Ganciclovir Started on Rituximab Received radiation therapy treatments Repeat MRI did eventually show regression of disease