Post transplant lymphoproliferative disorder

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: PTLD;

Overview

Post-transplant lymphoproliferative disorder (also known as PTLD) is defined as a B-cell proliferation due to therapeutic immunosuppression after organ transplantation. Patients with post-transplant lymphoproliferative disorder may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. In some cases, B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma. The malignant cell clone can become the dominant proliferating cell type, leading to a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant.

Historical Perspective

• Post transplant lymphoproliferative disorder was first discovered by Denis Parsons Burkitt, an Irish physician, in 1965.

Classification

• Post transplant lymphoproliferative disorder may be classified according to World Health Organization (WHO) classification system, into 4 subtypes:

• Early hyperplastic lesions
• Polymorphic lesions
• Monomorphic lesions
• Classic Hodgkin-type lymphomas

Pathophysiology

• Post transplant lymphoproliferative disorder arises from germinal center or post-germinal center B cells (B-PTLD), which are normally involved the production of antibodies and durable memory B cells.
• The pathogenesis of post transplant lymphoproliferative disorder is characterized by the production of interleukin-10.
• The overexpression of bcl-2 has been associated with the development of post transplant lymphoproliferative disorder.
• On gross pathology, characteristic findings of post transplant lymphoproliferative disorder, include:

• No remarkable findings

• On microscopic histopathological analysis, characteristic findings of post transplant lymphoproliferative disorder, include:

• Resemblance to large cell lymphomas
• Large lymphoid cells with a diameter (2x a resting lymphocyte)

Causes

• The most common causes of post transplant lymphoproliferative disorder is Epstein-Barr virus.

Differentiating Post Transplant Lymphoproliferative Disorder from Other Diseases

• Post transplant lymphoproliferative disorder must be differentiated from other diseases that cause fatigue, weight-loss, and fever, such as:

• Infectious mononucleosis
• Diffuse large B-cell lymphoma
• Lymphoblastic lymphoma
• Blastic mantle cell lymphoma (MCL)

Epidemiology and Demographics

• Post transplant lymphoproliferative disorder is very rare.
• The prevalence of post transplant lymphoproliferative disorder remains unknown.

Age

• Post transplant lymphoproliferative disorder is more commonly observed among young patients.

Gender

• Females are slightly more affected with post transplant lymphoproliferative disorder than men.

Race

• There is no racial predilection for post transplant lymphoproliferative disorder.

Risk Factors

• The most common risk factors in the development of post transplant lymphoproliferative disorder is B cell neoplasm associated with Epstein-Barr infection.

Natural History, Complications and Prognosis

• The majority of patients with post transplant lymphoproliferative disorder are symptomatic at the time of diagnosis.
• Early clinical features include fatigue, fever, and weight-loss.
• If left untreated, patients with post transplant lymphoproliferative disorder may progress to develop organ failure.
• The most common complication of post transplant lymphoproliferative disorder is fatal infection.
• Prognosis is generally poor, and the 5-year survival rate of patients with post transplant lymphoproliferative disorder is approximately 37- 61%

Diagnosis

Symptoms

• Post transplant lymphoproliferative disorder is usually asymptomatic.
• Symptoms of post transplant lymphoproliferative disorder may include the following:

• Swelling in the lymph nodes in the neck or underarms

Physical Examination

• Patients with post transplant lymphoproliferative disorder usually appear pale and malnourished.
• Physical examination may be remarkable for:

• Fever
• Night sweats
• Persistent fatigue
• Loss of appetite
• Nausea
• Vomiting
• Unexplained weight loss

Laboratory Findings

• There are no specific laboratory findings associated with post transplant lymphoproliferative disorder.

Imaging Findings

• There are no imaging findings associated with post transplant lymphoproliferative disorder.

Treatment

Medical Therapy

• The medical treatment for post transplant lymphoproliferative disorder, includes:

• Immunosuppression
• Antiviral therapy
• Interferon alpha therapy
• CD20 antibody therapy
• Chemotherapy

• Post-transplant lymphoproliferative disorder may regress spontaneously on reduction or cessation of immunosuppressant medication anti-viral therapy.

Surgery

• Surgery is not recommended for patients with post transplant lymphoproliferative disorder.

Prevention

• There are no primary preventive measures available for post transplant lymphoproliferative disorder.