What are the common pediatric malignant tumors, their diagnostic work‑up, and standard treatment protocols?

Common Pediatric Malignant Tumors

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, representing 75-80% of acute leukemias in children, followed by CNS tumors (the leading cause of cancer-related death in children), neuroblastoma (most common extracranial solid tumor), and Wilms' tumor. 1, 2, 3

Most Common Pediatric Malignancies by Frequency

Leukemias (Most Common Overall)

• Acute lymphoblastic leukemia (ALL) accounts for 23.6% of all childhood cancers and 75% of childhood leukemias 1, 4
• Acute myelogenous leukemia has the poorest survival at 26.4% 5-year relative survival 4
• ALL presents with fatigue, constitutional symptoms (fevers, night sweats, weight loss), bone/joint pain, easy bruising/bleeding, lymphadenopathy, hepatosplenomegaly, or splenomegaly 1

CNS Tumors (Leading Cause of Cancer Death)

• CNS tumors are the second most common pediatric malignancy but the leading cause of cancer-related death in children 2
• Age 0-4 years: embryonal tumors (including medulloblastoma), pilocytic astrocytoma, malignant gliomas, and ependymomas are most common 1
• Age 5-9 years: brainstem high-grade gliomas peak at 0.56 per 100,000 population 1
• Throughout childhood: pilocytic astrocytoma remains common; astrocytoma accounts for 9.6% of childhood cancers 1, 4
• Pediatric diffuse high-grade gliomas have <20% 5-year survival despite multimodal therapy 1

Solid Tumors

• Neuroblastoma (6.6% of childhood cancers): most common extracranial and intra-abdominal solid tumor, arises from sympathetic nervous tissue, most often in the abdomen 2, 3, 4
• Wilms' tumor (6.4% of childhood cancers): presents with abdominal mass, hypertension, hematuria, or abdominal pain; 80% cure rate with modern therapy 2, 3, 4
• Lymphomas: Hodgkin's disease (56% nodular sclerosing subtype) and non-Hodgkin's lymphoma (one-third Burkitt's/Burkitt-like with 5.7:1 male predominance) present as painless masses with local compression symptoms, fever, and weight loss 3, 4
• Rhabdomyosarcoma: accounts for 51% of soft tissue sarcomas, more than half embryonal type 4

Diagnostic Work-Up Algorithm

Initial Evaluation for Suspected Malignancy

• Complete blood count with differential: look for abnormal bleeding, unexplained cytopenias, or circulating blasts suggesting leukemia 1, 3
• Bone marrow aspirate and biopsy: ≥20% lymphoblasts required for ALL diagnosis (≥25% used in treatment protocols) 1
• Physical examination specifics: lymphadenopathy, hepatosplenomegaly, splenomegaly, bone tenderness, cranial nerve abnormalities (chin numbness, facial palsy), mediastinal mass in T-ALL 1, 3

CNS Tumor Work-Up

• MRI with gadolinium contrast is essential for diagnosis 1
• Obtain detailed patient demographics (age is crucial for differential diagnosis) and clinical history including hereditary syndromes 1
• Neuropathology review by experienced neuropathologist is mandatory, requiring both histologic and molecular analyses per WHO CNS5 classification 1
• Multidisciplinary team involvement: pediatric oncologists/neuro-oncologists, pediatric radiation oncologists, neuropathologists with molecular expertise, pediatric neuroradiologists, and pediatric neurosurgeons 1, 2

Solid Tumor Work-Up

• Imaging: CT or MRI to define tumor extent and metastases 3
• Tissue biopsy: sufficient tissue required for accurate pathologic diagnosis with molecular testing 1
• For abdominal masses: distinguish neuroblastoma (sympathetic chain origin, catecholamine elevation) from Wilms' tumor (renal origin, hypertension, hematuria) 3
• For musculoskeletal tumors: evaluate for pain/dysfunction disproportionate to trauma history 3

Risk Stratification Considerations

• Hereditary cancer syndromes increase specific tumor risks: neurofibromatosis type 1 (pilocytic astrocytoma, especially optic pathway), Li-Fraumeni syndrome (astrocytomas, embryonal tumors, choroid plexus carcinoma), Gorlin/Turcot 2 syndromes (medulloblastoma), Von Hippel-Lindau (hemangioblastoma), tuberous sclerosis (SEGA), rhabdoid predisposition syndrome (AT/RT) 1
• Down syndrome increases cancer risk and requires heightened vigilance 3
• Prior ionizing radiation exposure increases risk with 7-9 year latency, particularly for meningiomas and gliomas 1

Standard Treatment Protocols

ALL Treatment Approach

• Treatment at specialized cancer center with pediatric ALL expertise is mandatory given complexity of regimens and supportive care requirements 1
• Risk-adapted therapy based on age, immunophenotype (B-ALL vs T-ALL), cytogenetics (Philadelphia chromosome status), and minimal residual disease 1
• Modern intensive chemotherapy achieves 89% 5-year overall survival in children, 61% in adolescents/young adults 1
• Infants <1 year have poorest outcomes at 58.2% 6-year survival with no improvement over 30 years 1
• T-ALL outcomes now equivalent to B-ALL with modern intensive T-ALL-focused chemotherapy 1

CNS Tumor Treatment Approach

• Maximal safe surgical resection when feasible, as extent of resection affects prognosis 1
• Combined modality therapy: surgery, radiation therapy, and systemic chemotherapy for high-grade gliomas 1
• Pediatric diffuse high-grade gliomas have poor prognosis despite aggressive treatment: <20% 5-year survival 1
• Treatment decisions depend on age, tumor location, sex, extent of resection, histologic subtype, and genomic profile 1

Solid Tumor Treatment Principles

• Wilms' tumor: 80% cure rate with modern diagnostic and therapeutic approaches 2
• Clinical trial enrollment should be offered and encouraged for all pediatric cancer patients 2, 5
• Adolescents aged 15-21 years have superior outcomes when treated at pediatric cancer centers (26% vs 4% clinical trial enrollment at adult centers) 5

Critical Treatment Pitfalls

• Age-appropriate protocols are essential: adolescents/young adults with ALL have better outcomes on pediatric protocols than adult protocols 1, 5
• Avoid treatment delays: cancer is the second leading cause of death in children >3 months old 2
• Long-term effects matter more in children than adults, requiring careful consideration of treatment toxicity 6
• Low participant numbers in pediatric trials pose challenges for evaluating novel strategies 6