History and Physical Examination

Whether posttransplant lymphoproliferative disease (PTLD) presents as localized or disseminated disease, the tumors are often aggressive, rapidly progressive, and potentially life-threatening. Clinical presentation is variable and includes the following:

Fever (57%)
Lymphadenopathy (38%)
Gastrointestinal symptoms (including obstruction [27%])
Infectious mononucleosis–like syndrome, which can be fulminant (19%)
Pulmonary signs and symptoms (15%)
Central nervous system (CNS) symptoms (13%)
Weight loss (9%)

Involvement of the allografted tissue can cause a decline in its function. This organ failure may be the presenting symptom.

Having a high index of suspicion and clinical vigilance is critical, because patients may present with nonspecific symptoms or systemic signs (eg, hepatosplenomegaly, fever, fatigue) that may otherwise not initially suggest a diagnosis of PTLD. A rising blood level of EBV viral load by quantitative polymerase chain reaction (PCR) measurement in this clinical setting should raise concern for PTLD.^{[40, 4, 24, 41, 42]}

The most common sites of involvement are are as follows^{[43, 36]}:

Lymph nodes
Liver
Lung
Kidney
Bone marrow
Small intestine
Spleen
CNS
Large bowel
Tonsils
Salivary glands

Less common sites of involvement include the oral cavity, skin, and subcutaneous lesions. T-cell lymphoproliferative disorders not associated with EBV infection tend to occur at extranodal sites.

Differential Diagnoses

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Media Gallery

Biopsy of gingival tissue (400 X) with hematoxylin and eosin stain demonstrates polymorphous infiltrate of atypical lymphoid cells, which is consistent with posttransplant lymphoproliferative disease (PTLD).
Biopsy of gingival tissue (400 X). Epstein-Barr virus encoded RNA (EBER) study shows numerous positive cells, which is consistent with posttransplant lymphoproliferative disease (PTLD).

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Author

Phillip M Garfin, MD, PhD Senior Medical Director, Department of Oncology, Zymeworks Biopharmaceuticals, Inc

Phillip M Garfin, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society for Cell Biology, American Society for Transplantation and Cellular Therapy, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Immunotherapy of Cancer

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Zymeworks inc, Seagen inc.

Coauthor(s)

Clare J Twist, MD Associate Professor of Pediatrics, Division of Hematology/Oncology, Medical Center Line, Stanford University School of Medicine; Medical Staff, Lucile Packard Children’s Hospital and Stanford University Medical Center

Clare J Twist, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Ron Shapiro, MD Professor of Surgery, Surgical Director, Kidney/Pancreas Transplant Program, The Recanati/Miller Transplantation Institute at Mount Sinai Hospital

Ron Shapiro, MD is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, American Society of Transplantation, American Surgical Association, Association for Academic Surgery, Central Surgical Association, International Pancreas and Islet Transplant Association, International Pediatric Transplant Association, Society of University Surgeons, Transplantation Society

Disclosure: Nothing to disclose.

Acknowledgements

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Mary Prendergast, MD Department of Internal Medicine, University of Nebraska Medical Center

Mary Prendergast, MD is a member of the following medical societies: Royal College of Physicians

Disclosure: Nothing to disclose.

Vinay Ranga, MD Assistant Professor, Department of Internal Medicine, Division of Nephrology, Hartford Hospital

Disclosure: Nothing to disclose.

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