Diagnostic Applications of Nuclear Medicine: Pediatric Cancers

Abstract

Pediatric cancers are defined as cancers occurring before the age of 15 years and account for only 2% of all cancers. Intracranial tumors are the most common solid neoplasms in children. Although [¹⁸F]FDG uptake is associated with more malignant and aggressive tumor types, [¹⁸F]FDG-PET is not routinely used for the clinical management of pediatric brain tumors. PET/MRI coregistration/image fusion improves localization of the lesion. [¹⁸F]FDG-PET is also helpful to differentiate indolent and active components of the lesion and to improve the diagnostic yield of stereotactic biopsies and the accuracy of the radiosurgical dosimetry planning.

Lymphomas account for 10–15% of all childhood malignancies and are the third most common cause of cancer. Non-Hodgkin’s lymphoma is more frequent. Staging of Hodgkin’s lymphoma (HL) is performed according to the Cotswold revision of the Ann Arbor classification. Non-Hodgkin’s lymphoma in childhood is significantly different from adults. The predominant subtypes are Burkitt’s lymphoma, large B-cell lymphoma, and primary mediastinal B-cell lymphomas, followed by lymphoblastic lymphoma and anaplastic large-cell lymphoma. Most cases are extensive at diagnosis, corresponding to stages 3 and 4 of the St. Jude Children’s Research Hospital classification (Murphy staging). Contrast-enhanced diagnostic CT (ce-CT) or MRI together with thoracic CT remains mandatory at least at diagnosis (performed either simultaneously with [¹⁸F]FDG-PET by using hybrid PET/CT or PET/MRI scanners or separately). Diagnostic CT reliably detects enlarged lymph nodes, and contrast media are required to accurately distinguish lymphadenopathy. Diagnostic CT also allows detailed evaluation of the pulmonary parenchyma, pleura, and pericardium. Ultrasonography has a definite role in both initial evaluation and follow-up of superficial lymph nodes and is an effective method to detect testicular infiltration and to explore the liver and spleen. Chest radiography remains useful in HL to classify disease as “bulky” or “nonbulky.” MRI is superior to ce-CT for evaluation of the bone marrow, liver, soft tissue, and central nervous system.

⁶⁷Ga-citrate scintigraphy and bone scintigraphy have been replaced by [¹⁸F]FDG-PET/CT or PET/MRI, which depicts nodal and extranodal disease as well as focal bone marrow disease. The role of [¹⁸F]FDG-PET is well established to stage HL before treatment. Early response assessment can be evaluated by interim PET in HL. When interim PET is negative, no other examination needs to be performed at the end of therapy in the absence of clinical signs. Systematic [¹⁸F]FDG-PET is not indicated during follow-up.

In non-Hodgkin’s lymphoma, [¹⁸F]FDG avidity is high for Burkitt’s lymphoma, large B-cell lymphoma, lymphoblastic lymphoma, and anaplastic large-cell lymphoma. The main indications for [¹⁸F]FDG-PET in children with non-Hodgkin’s lymphoma are inconclusive. However, [¹⁸F]FDG-PET appears to be a useful tool for characterization of residual masses, as no reliable CT or MRI criteria are available for distinguishing residual disease from fibrosis or necrosis.

Wilms’ tumor is the most common renal malignancy in childhood. The diagnostic workup includes a CT or MRI scan of the abdomen and pelvis, lymph nodes, and intra-abdominal or pelvic tumor deposits. A Doppler ultrasound is recommended to evaluate if there is a tumoral thrombus in the renal vein and inferior vena cava. For the detection of bilateral disease and the assessment of nephroblastomatosis representing premalignant lesions, MRI is the imaging modality of choice. ¹²³I-MIBG scintigraphy can be very helpful for the differentiation of neuroblastoma from Wilms’ tumor. There is no major role for [¹⁸F]FDG-PET in these patients.

Neuroblastoma accounts for about 8% of pediatric malignancies and is responsible for 15% of cancer deaths in children. It arises from the neural crest cells, and the tumor is usually situated in the adrenal gland or anywhere else along the sympathetic nervous system chain. Staging is crucial in order to choose the appropriate treatment. Imaging of neuroblastoma consists of ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and ¹²³I-MIBG scintigraphy. ¹²³I-MIBG is sensitive and specific for the detection of neuroblastoma involvement. [¹⁸F]FDG-PET is less sensitive than ¹²³I-MIBG scintigraphy in neuroblastoma patients. However, in any case of a discrepancy between ¹²³I-MIBG scintigraphy and morphological imaging (CT and/or MRI), [¹⁸F]FDG-PET should be considered for further tumor evaluation.

Sarcomas are a heterogeneous group of neoplasms with different tumor biology, malignancy, and therapeutic options. The two major groups of primary bone tumors in children and adolescents are osteosarcomas and the Ewing family of tumors. As regards soft-tissue sarcomas, the most common histologic entities in children and adolescents are rhabdomyosarcoma, extraosseous Ewing sarcoma and peripheral neuroectodermal tumor, synovial sarcoma, neurofibrosarcoma, fibrosarcoma, and leiomyosarcoma. Langerhans cell histiocytosis (LCH) is a proliferation of Langerhans-type histiocytes. Despite its clonal origin, there is no definitive proof of malignancy. Primary bone tumors are best classified using a conventional planar x-ray. Local CT and MRI supply further information on tumor localization and extension. Bone scintigraphy is very sensitive in the detection of osseous metastases of osteosarcoma, and even soft-tissue metastases are often visible on the bone scan. [¹⁸F]FDG-PET has a high accuracy in detecting primary sarcomas and its metastases, with the exception of pulmonary metastases. Therefore, a thoracic CT is additionally necessary for staging sarcomas.