The Autoimmune Lymphoproliferative Syndrome (ALPS) is an inherited disorder associated with defective lymphocyte apoptosis, which is clinically characterized by prominent non-malignant lymphadenopathy, hepatosplenomegaly and overt autoimmune diseases such as hemolytic anemia, autoimmune thrombocytopenia and neutropenia. Additionally, ALPS patients have a significantly increased risk of developing non-Hodgkin's and Hodgkin's lymphoma.

The diagnosis of lymphoma is particularly troublesome in ALPS because many ALPS manifestations overlap with clinical features suggestive of lymphoma. Therefore, individuals with ALPS may undergo repeated biopsies during the course of the disease. Finding a non-invasive test that can predictably discriminate benign from malignant lymphadenopathy in ALPS, and that can help discern whether a more invasive lymph node biopsy is necessary, would be very desirable.

Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is an increasingly used non-invasive imaging technique for staging and monitoring therapeutic responses in patients with lymphoma. This technique might be able to assist us in distinguishing whether enlargement of lymph nodes is due to ALPS versus ALPS associated lymphoma. However, FDG-PET has not been studied in patients with ALPS. This study will first explore whether ALPS patients with lymphadenopathy show FDG uptake. If uptake is shown, the study will obtain initial quantitative data to compare FDG uptake in ALPS patients with lymphadenopathy, and ALPS patients with associated lymphoma. The ultimate goal is to assess FDG-PET as a reliable non-invasive method to differentiate lymphadenopathy due to ALPS versus that of ALPS associated lymphoma.

• INCLUSION CRITERIA:

ALPS Patients without Lymphoma:

Participants must:

1. Fulfill current criteria for the diagnosis of ALPS as follows:

   1. Documented chronic nonmalignant lymphadenopathy and/or splenomegaly, and
   2. Greater than 1% or greater than 17 absolute TCR alpha/beta+ CD4- CD8- T cells in the peripheral blood.
2. Be enrolled in ALPS Natural History Protocol 93-I-0063.
3. Have clinical evidence of lymphadenopathy as defined by multiple palpable lymph nodes of at least 1cm or radiographic evidence of lymphadenopathy as defined by multiple lymph nodes of at least 1 cm on CT scan, during an evaluation at the NIH Clinical Center.
4. Be 8 years of age or older. The study will be targeted to children 8 years of age or older and adults because younger children may not be able to stay still for the duration of the FDG-PET scan procedure. Sedation will not be used in children in this study, except for clinically indicated procedures such as FDG-PET scans in children with lymphoma.
5. Be due for their routine [every 2 years] CT scan under protocol 93-I-0063, or be in need of a CT scan for medical reasons [e.g. marked change in adenopathy]. CT scan within 3 months prior to FDG-PET scan is necessary to locate the nodes for appropriate FDG-PET analysis.

ALPS Patients with Lymphoma:

Patients must:

1. Fulfill current criteria for the diagnosis of ALPS as follows:

   1. Documented chronic nonmalignant lymphadenopathy and/or splenomegaly.
   2. Greater than or equal to 1% or greater than 17 absolute TCR alpha/beta + CD4- CD8 -T cells in the peripheral blood.
2. Be enrolled in ALPS Natural History Protocol 93-I-0063.
3. Have a histologically proven diagnosis of lymphoma, confirmed by the Laboratory of Pathology, NCI (Anatomic Pathology Dept, CC) whether yet treated or not. Lymphomas will be classified according to the HWO classification, using appropriate immunophenotypic and histological features .

EXCLUSION CRITERIA:

1. Patient will be excluded if any of the following are present:
2. Concurrent infection or inflammatory disease (e.g., sarcoidosis), which itself often shows increased FDG uptake by PET and which could interfere with the interpretation of study results.
3. Active neoplasia other than lymphoma.
4. History of chemotherapy or radiation treated malignancy within 5 years prior to study procedure, except for lymphoma.
5. Hyperglycermia (regardless of etiology) determined by fasting glucose of greater than 130 mg/dl. Individual with an underlying defect of glucose metabolism may exhibit abnormal metabolism of FDG.
6. Weights in excess of 136 kg, which will exceed the weight limit for the scanner table.
7. Pregnancy and breast-feeding. For women of childbearing potential, a negative urine or serum pregnancy test is required within 24 hours prior to an FDG-PET scan.