Childhood Cancers: Leukemia, Brain Tumors & Retinoblastoma
Blasts, posterior fossa masses, and a white pupil — spot them and act fast
Acute lymphoblastic leukemia: recognition and diagnosis
Epidemiology. Leukemias make up about 30% of childhood cancers, and ALL alone about 25%, making it the most common. Brain tumors are the most common solid tumors (about 25%) and now the leading cause of pediatric cancer death. ALL peaks at ages 2–5 and is roughly 10–20 times more common in Down syndrome; with modern risk-adapted therapy about 90% of children are cured.
Presentation. Replacement of the marrow produces anemia (pallor, fatigue), thrombocytopenia (petechiae, bruising), and neutropenia (fever, infections). Infiltration causes bone pain or a limp, often waking the child at night, plus hepatosplenomegaly and lymphadenopathy. Bone pain, organomegaly, or a second cytopenia separates leukemia from ITP, and steroids given before a marrow exam can mask ALL.
T-cell ALL. About 15% of cases, typically adolescent boys with a high white count and an anterior mediastinal (thymic) mass. The mass can compress the airway or cause SVC syndrome with orthopnea, stridor, and facial swelling. A chest radiograph is required before any sedation or anesthesia, because loss of muscle tone can cause fatal airway collapse.
Diagnosis. The CBC shows anemia and thrombocytopenia with a low, normal, or high WBC; blasts may or may not circulate. Bone marrow aspirate and biopsy (≥20–25% lymphoblasts) with flow cytometry confirm the diagnosis: precursor B-ALL (about 85%) expresses CD19, CD10, and TdT, while T-ALL expresses CD3, CD7, and TdT. Cytogenetics, a lumbar puncture for CNS disease, and a chest radiograph complete staging.
| Feature | Favorable | Unfavorable |
|---|---|---|
| Age | 1–10 years | Infant <1 year (often KMT2A-rearranged) or >10 years |
| WBC at diagnosis | <50,000/µL | ≥50,000/µL |
| Genetics | Hyperdiploidy; t(12;21) ETV6-RUNX1 | t(9;22) BCR-ABL1; hypodiploidy |
| Response | No minimal residual disease after induction | Persistent MRD; CNS disease |
ALL treatment and oncologic emergencies
Phases. Therapy lasts about 2–3 years: induction (a steroid, vincristine, asparaginase, with or without an anthracycline), consolidation and intensification, then maintenance with daily 6-mercaptopurine and weekly oral methotrexate. Children with TPMT or NUDT15 variants inactivate 6-mercaptopurine slowly and need dose reduction to avoid severe myelosuppression.
CNS-directed therapy. The CNS is a sanctuary site that systemic drugs penetrate poorly, so every child receives intrathecal chemotherapy; cranial radiation is reserved for select cases. Relapsed B-ALL may be treated with blinatumomab (a CD19-directed T-cell engager), CD19 CAR T cells, or stem cell transplant.
Tumor lysis syndrome. High WBC or bulky disease (T-ALL, Burkitt lymphoma) releases potassium, phosphate, and nucleic acids that become uric acid. Phosphate precipitates with calcium, causing hypocalcemia, and calcium phosphate and urate crystals injure the kidney, leading to AKI, arrhythmias, and seizures. Prevention is vigorous potassium-free IV hydration plus allopurinol, or rasburicase for high risk, with electrolytes checked every 4–6 hours. Rasburicase degrades existing uric acid but causes hemolysis and methemoglobinemia in G6PD deficiency, so screen first.
Fever with neutropenia during chemotherapy is an emergency: blood cultures and an empiric antipseudomonal β-lactam such as cefepime within an hour.
AML and leukemia in Down syndrome
AML. AML accounts for about 15–20% of childhood leukemia, with peaks in infancy and adolescence. It shares the marrow-failure picture of ALL but adds gingival hyperplasia and skin infiltration (monocytic subtypes), chloromas (myeloid sarcomas, for example in the orbit), and Auer rods in myeloperoxidase-positive blasts. Treatment is intensive chemotherapy, with stem cell transplant for high-risk disease. Acute promyelocytic leukemia, t(15;17), presents with DIC and needs all-trans retinoic acid (with arsenic trioxide) started immediately.
Down syndrome. About 10% of affected newborns have transient abnormal myelopoiesis, with circulating megakaryoblasts and hepatomegaly driven by a GATA1 mutation. It usually resolves within about 3 months, but roughly 1 in 5 of these infants later develop acute megakaryoblastic leukemia, typically before age 4. Blasts express platelet glycoproteins (CD41, CD61), and the disease is highly curable with reduced-intensity chemotherapy. The risk of ALL is also increased.
Pediatric brain tumors
Presentation. Between ages 1 and 10 most brain tumors are infratentorial. Raised intracranial pressure causes morning headache relieved by vomiting, papilledema, head tilt, and CN VI palsy; posterior fossa masses add ataxia. Infants show macrocephaly, a bulging fontanelle, "setting-sun" eyes, irritability, and developmental regression. The study of choice is MRI of the brain with and without contrast; a lumbar puncture before imaging risks herniation.
| Tumor | Location and clues | Pathology | Treatment and outlook |
|---|---|---|---|
| Pilocytic astrocytoma | Cerebellar cyst with enhancing mural nodule; most common pediatric brain tumor | Rosenthal fibers, GFAP+; BRAF alterations | Resection often curative; best prognosis |
| Medulloblastoma | Cerebellar vermis; truncal ataxia, hydrocephalus; drop metastases | Small round blue cells, Homer Wright rosettes | Resection, craniospinal radiation (age ≥3), chemotherapy |
| Ependymoma | Floor of 4th ventricle; hydrocephalus, lower cranial nerve palsies | Perivascular pseudorosettes | Extent of resection plus focal radiation |
| Diffuse midline glioma | Pons, ages 5–10; cranial neuropathies plus long-tract signs | H3 K27-altered | Unresectable; palliative radiation; median survival <1 year |
| Craniopharyngioma | Calcified cystic suprasellar mass; bitemporal hemianopia, growth failure, DI | Adamantinomatous; Rathke pouch origin | Surgery ± radiation; lifelong hormone replacement |
Key details. Medulloblastoma, the most common malignant pediatric brain tumor, spreads through the CSF, so staging requires MRI of the entire spine and CSF cytology. Ependymomas can extrude through the fourth-ventricle foramina. Craniopharyngioma compresses the chiasm and the hypothalamic-pituitary axis, causing GH deficiency, delayed puberty, central diabetes insipidus, and hypothyroidism; hypothalamic obesity is common afterward. Optic pathway gliomas in NF1 are also pilocytic, and pineal germ cell tumors cause Parinaud syndrome.
Retinoblastoma
Presentation. Retinoblastoma appears in the first 2–3 years with leukocoria (a white or absent red reflex, often first seen in flash photographs) or new strabismus. Any abnormal red reflex needs urgent ophthalmology referral for a dilated exam under anesthesia, with ultrasound or MRI showing a calcified retinal mass. Biopsy is avoided because it can seed tumor, and CT radiation is minimized. Other causes of leukocoria include congenital cataract, Coats disease, persistent fetal vasculature, retinopathy of prematurity, and Toxocara.
Genetics. RB1 on 13q14 is a tumor suppressor requiring two hits. About 40% of cases are heritable, with a germline first hit: bilateral or multifocal tumors, younger age at diagnosis, and autosomal dominant transmission. Sporadic cases (about 60%) are usually unilateral and unifocal. Germline survivors face second cancers, especially osteosarcoma (more so after radiation) and soft-tissue sarcomas, so genetic testing and screening of siblings and offspring are offered.
Rhabdomyosarcoma and Langerhans cell histiocytosis
Rhabdomyosarcoma. The most common soft-tissue sarcoma of childhood arises in the head and neck (orbital tumors cause rapidly progressive proptosis), the GU tract (bladder, prostate, vagina), and the extremities. The embryonal botryoid variant, "sarcoma botryoides", forms a grape-like mass protruding from the vagina of young girls. Tumor cells express desmin and myogenin. Alveolar tumors of adolescent extremities carry t(2;13) PAX3-FOXO1 and a worse prognosis. Treatment combines surgery, multiagent chemotherapy, and radiation.
Langerhans cell histiocytosis. A clonal proliferation of CD1a+ and CD207 (langerin)+ cells containing tennis-racket-shaped Birbeck granules, with BRAF V600E in about half, peaking at ages 1–3. It causes punched-out lytic skull lesions with painful swelling, a seborrheic-like scalp or diaper rash, central diabetes insipidus from pituitary stalk involvement, proptosis, and vertebra plana. Single bone lesions are treated with curettage; multisystem disease with vinblastine plus prednisone.