Pediatric Solid Tumors of Infancy: An Overview

Wendy Allen-Rhoades, MD, FAAP Sarah B. Whittle, MD, MS, FAAP Nino Rainusso, MD, FAAP Distribution of Pediatric Cancers in Children 0-14 years Pediatric solid tumors represent approximately 40% of all pediatric cancers in patients <14 years of age

21% Central Nervous 7% System Tumors 4% Neuroblastoma Retinoblastoma 10% 2% 4% Wilms tumor Lymphoma 39% Hepatic tumors 5% Solid Tumors MaligantMalignant bone bone tumors tumor Soft tissue sarcoma 8% 30% 3% Germ cell/Gonadal tumors Leukemia Other 6% Tumor Location and Differential Diagnosis of Common Malignant Solid Tumors in Pediatric Patients

The age of the patient can be helpful in the differential diagnoses for any mass identified on physical examination

Tumors Newborn (<1 y) Infant (1-3 y) Child (3-11 y) Adolescent/young adult (12-21 y) Abdominal Neuroblastoma Neuroblastoma Neuroblastoma Germ cell tumor Mesoblastic nephroma Wilms tumor Wilms tumor Soft tissue sarcoma Hepatoblastoma Hepatoblastoma Rhabdomyosarcoma Hepatocellular carcinoma Wilms tumor Rhabdomyosarcoma

Extremity Fibrosarcoma Fibrosarcoma Rhabdomyosarcoma Osteosarcoma Rhabdomyosarcoma Ewing sarcoma Ewing sarcoma Ewing sarcoma Soft tissue sarcoma Genitourinary Teratoma Rhabdomyosarcoma Rhabdomyosarcoma Germ cell tumor Yolk sac tumor Teratoma Clear cell sarcoma of the kidney Head and neck Retinoblastoma Retinoblastoma Rhabdomyosarcoma Soft tissue sarcoma Neuroblastoma Neuroblastoma Nasopharyngeal carcinoma Rhabdomyosarcoma Rhabdomyosarcoma Thoracic Neuroblastoma Neuroblastoma Neuroblastoma Ewing sarcoma Teratoma Rhabdomyosarcoma Teratoma Common Presenting Signs and Symptoms in Malignant Pediatric Solid Tumors

• Abdominal mass • Thoracic mass, which may be associated with respiratory symptoms, back pain, or neurologic deficits • Fever • Bone pain Common Pediatric Solid Tumors in Young Children

• Retinoblastoma • Neuroblastoma • Hepatoblastoma • Wilms tumor Retinoblastoma

• There are approximately 280 new cases of retinoblastoma diagnosed each year in the United States. • 75% of patients with retinoblastoma are diagnosed <2 years of age. • Retinoblastoma can occur as a heritable or nonheritable disease. • Germline mutation in the RB1 gene characterizes patients with heritable retinoblastoma. • The role of primary care providers is essential in the prompt recognition of leukocoria or strabismus. Retinoblastoma

Photograph of leukocoria on the right eye of a patient with retinoblastoma (Photo courtesy of Dan S. Gombos, MD, FACS) Retinoblastoma

• The treatment of retinoblastoma requires a multidisciplinary team approach in specialized centers. • The 3 main goals of retinoblastoma treatment are to save the patient’s life, to preserve vision, and to avoid late-treatment sequelae. • Retinoblastoma is a highly curable disease when detected in the early stages. • Primary care providers should ensure that families and patients diagnosed as having retinoblastoma seek genetic counseling and molecular testing. Neuroblastoma

• There are approximately 700 new cases of neuroblastoma diagnosed each year in the United States. • The median age at diagnosis in patients with neuroblastoma is 19 months. • The role of primary care providers is to recognize the myriad of symptoms with which patients with neuroblastoma may present and initiate their evaluation and prompt referral. Neuroblastoma • Neuroblastoma has a varied clinical presentation: -- Abdominal masses account for 75% of primary tumors -- Thoracic tumors may cause respiratory symptoms, Horner syndrome, or superior vena cava syndrome -- Paraspinal tumors can cause spinal cord compression (weakness, bowel and bladder dysfunction, and paralysis) -- Half of patients present with metastatic disease at diagnosis (may have systemic symptoms, including fever, weight loss, cachexia, and bone pain) -- Neuroblastoma frequently spreads to the skull and orbital bones, causing periorbital ecchymosis, referred to as “raccoon eyes” -- Two paraneoplastic syndromes are associated with neuroblastoma: opsoclonus myoclonus syndrome and vasoactive intestinal peptide syndrome Neuroblastoma

• Elevated urine or serum catecholamine levels may help to establish the diagnosis of neuroblastoma. • Neuroblastoma is diagnosed on tumor histopathology from a biopsy. • Staging evaluation includes cross-sectional imaging of chest, abdomen, and pelvis using computed tomography. • Distant metastatic disease is evaluated using 123I-meta-iodo- benzylguanidine (123I-MIBG) scintigraphy. • Bone marrow aspirate and biopsy from at least two sites are performed to evaluate for bone marrow metastasis. Neuroblastoma

• The treatment of neuroblastoma requires a multidisciplinary team approach in specialized centers. • Patients with neuroblastoma are divided into 3 risk groups – low, intermediate, and high – for treatment and prognostic purposes. • Neuroblastoma in infants (<1 year of age) tends to spontaneously regress without treatment. • Patients with low- and intermediate-risk neuroblastoma require surgery and a moderate dose of chemotherapy and have excellent outcomes. • Patients with high-risk neuroblastoma require very intensive treatment (multiagent chemotherapy, surgery, radiotherapy, autologous stem cell transplant, differentiation agents, and immunotherapy) and have a poor outcome. Hepatoblastoma

• There are approximately 150 new cases of hepatoblastoma diagnosed each year in the United States. • The median age of diagnosis in patients with hepatoblastoma is 19 months. • Most cases of hepatoblastoma are sporadic. • Hepatoblastoma is associated with Beckwith-Wiedemann syndrome, familial adenomatous polyposis, trisomy 18, and numerous gestational factors. Hepatoblastoma

• Hepatoblastoma presents with abdominal distention or palpable abdominal mass. • The gold standard imaging for liver tumor evaluation is either triphasic contrast-enhanced abdominal computed tomography or magnetic resonance with hepatocyte-specific contrast agents. • Alpha-fetoprotein (AFP) is a very useful biomarker in the diagnosis and monitoring of hepatoblastoma treatment. • The diagnosis of hepatoblastoma is established after obtaining a biopsy of the mass. Hepatoblastoma

• The treatment of hepatoblastoma requires a multidisciplinary team approach in specialized centers. • Complete surgical resection is required to achieve a definitive cure for hepatoblastoma. • Neoadjuvant chemotherapy is administered in patients with unresectable disease at diagnosis. • Patients with hepatoblastoma may be listed for orthotopic liver transplant if surgical resection will never become possible. • Patients with resectable hepatoblastoma at diagnosis have an excellent overall survival. Wilms Tumor • There are approximately 650 new cases of Wilms tumor diagnosed each year in the United States. • The median age at diagnosis in patients with unilateral Wilms tumor is 41 to 46 months. • Wilms tumor is associated with Beckwith-Wiedemann syndrome, isolated hemihypertrophy, WAGR syndrome, and Denys-Drash syndrome. • Children with increased predisposition to develop Wilms tumor should have periodic abdominal ultrasonography until they reach age 8 years. • Genetic counseling should be considered for children with the aforementioned syndromes. Wilms Tumor • Asymptomatic abdominal mass found by a parent or pediatrician is the most common presenting sign. • Patients with Wilms tumor may also present with abdominal pain, hypertension, and gross or microscopic hematuria. • Physical examination should be performed gently, as Wilms tumor can be fragile and rupture. • Abdominal ultrasonography can be performed to confirm that the mass arises from the kidney, to evaluate the contralateral kidney, and to identify intravascular tumor thrombus using color Doppler. • Advanced imaging studies with enhanced contrast computed tomography of the abdomen are indicated for evaluation of all renal tumors. Wilms Tumor

Computed tomography of the abdomen in a patient with Wilms tumor (left side). The patient presented with intermittent gross hematuria and left flank “fullness.” Wilms Tumor

• The histopathologic diagnosis is established after radical nephrectomy either upfront or after administration of chemotherapy. • Biopsy (preoperative or intraoperative) generally is not recommended. • The treatment of Wilms tumor requires a multidisciplinary team approach in specialized centers. • The treatment of Wilms tumor includes surgery, chemotherapy, and sometimes radiotherapy. • The outcome for favorable histology of Wilms tumor is considered excellent.