Medical School · Year 3 · Pediatrics · includes a quiz and discussion video

Seminar 09: Pediatric Hematology and Oncology

Year 3: Pediatrics Clerkship

Learning Objectives

By the end of this seminar, students will be able to:

1. Evaluate anemia in pediatric patients
2. Recognize common bleeding disorders
3. Identify sickle cell disease and its complications
4. Describe common pediatric malignancies
5. Recognize oncologic emergencies
6. Understand supportive care for oncology patients

Lecture Outline

I. Approach to Anemia

Anemia in pediatrics is defined as hemoglobin below the normal range for age and sex, with normal values varying significantly throughout childhood due to physiologic changes in erythropoiesis. Newborns have the highest hemoglobin at 14-24 g/dL due to fetal erythrocytes, which then decline to a nadir of approximately 9-11 g/dL at 8-12 weeks (physiologic anemia of infancy) as fetal red cells are cleared and production transitions to adult-type hemoglobin. Infants and children gradually increase hemoglobin to 11.5-13.5 g/dL, with adolescent males developing higher values than females after puberty. These age-specific variations make interpretation of hemoglobin values and classification of anemia severity necessarily age-dependent.

The initial classification of anemia by mean corpuscular volume provides a structured approach to differential diagnosis. Microcytic anemia with MCV below normal for age suggests iron deficiency (most common), thalassemia trait, chronic disease, or lead poisoning, with red cell distribution width helping distinguish iron deficiency (elevated RDW reflecting anisocytosis) from thalassemia trait (normal RDW). Normocytic anemia suggests acute blood loss, hemolysis, chronic disease, bone marrow failure, or transient erythroblastopenia of childhood, requiring reticulocyte count to distinguish hypoproliferative from destructive causes. Macrocytic anemia is less common in children but suggests vitamin B12 or folate deficiency, bone marrow failure syndromes (Diamond-Blackfan anemia, Fanconi anemia), or drug effects.

Clinical evaluation combines history, physical examination, and targeted laboratory testing. History should assess diet and feeding practices (cow's milk intake limiting iron absorption, prolonged exclusive breastfeeding without supplementation), blood loss (menstrual history, gastrointestinal symptoms), family history of anemia or jaundice (suggesting hereditary causes), medications, and ethnicity (hemoglobinopathy risk). Physical examination evaluates pallor (conjunctivae, palmar creases, nail beds), jaundice or scleral icterus (hemolysis), splenomegaly (hemolysis, malignancy), heart murmur (high-output state), and signs of nutritional deficiency. Initial laboratory evaluation includes complete blood count with indices and smear review, reticulocyte count, and often iron studies, with additional testing guided by initial findings.

Treatment depends on underlying cause and severity, with transfusion reserved for severe symptomatic anemia while definitive treatment addresses the underlying condition. Iron deficiency anemia is treated with oral iron supplementation at 3-6 mg/kg/day of elemental iron in divided doses, continued for 2-3 months after hemoglobin normalizes to replete stores, with response assessed by reticulocyte count increase at 7-10 days. Thalassemia trait requires no treatment but genetic counseling about reproductive risks. Hemolytic anemias require specific management based on etiology, potentially including corticosteroids, splenectomy, or immunosuppression. Transfusion is indicated for hemodynamic instability, severe symptomatic anemia, or ongoing blood loss, with attention to transfusion-related complications including alloimmunization.

<image>Panel A: Age-specific hemoglobin normal ranges displayed as graph from birth through adolescence showing physiologic nadir in infancy and divergence between males and females at puberty. Panel B: MCV-based classification algorithm for anemia showing microcytic, normocytic, and macrocytic categories with differential diagnoses and distinguishing laboratory features for each. Panel C: Peripheral blood smear findings in different anemias including microcytic hypochromic cells of iron deficiency, target cells and hypochromia of thalassemia, spherocytes of hemolytic anemia, and macrocytes. Panel D: Iron deficiency anemia treatment protocol showing dosing, expected response timeline, duration of therapy, and dietary counseling components.</image>

II. Iron Deficiency Anemia

Iron deficiency represents the most common cause of anemia worldwide and the most common nutritional deficiency in developed countries, with highest prevalence in toddlers and adolescent females. The toddler age group (9-24 months) is particularly vulnerable due to rapid growth, depletion of birth iron stores by 4-6 months, transition to complementary foods, and excessive cow's milk consumption which provides minimal iron while displacing iron-rich foods and causing occult gastrointestinal blood loss. Adolescent females face increased risk due to menstrual blood loss, growth spurts, and dietary restrictions including vegetarianism or dieting.

Risk factors for iron deficiency can be categorized into inadequate intake, increased requirements, and increased losses. Inadequate intake results from prolonged exclusive breastfeeding without supplementation, early introduction of cow's milk, limited dietary diversity, and poverty limiting access to iron-rich foods. Increased requirements occur during periods of rapid growth including infancy, the toddler period, and adolescence, as well as during pregnancy. Increased losses occur from gastrointestinal bleeding (cow's milk protein-induced colitis, parasites, inflammatory bowel disease), menstruation, or other bleeding sources.

Diagnosis of iron deficiency follows a predictable progression from depletion of stores through iron-deficient erythropoiesis to frank iron deficiency anemia. Early iron depletion shows decreased ferritin (the first laboratory abnormality) with normal hemoglobin and MCV. Iron-deficient erythropoiesis shows low serum iron, low transferrin saturation, and elevated total iron-binding capacity (TIBC), with early microcytosis and elevated RDW. Established iron deficiency anemia shows microcytic hypochromic anemia with all iron studies abnormal. The blood smear shows microcytic, hypochromic red cells with anisocytosis and occasional target cells. In complex cases or when initial response to iron is poor, soluble transferrin receptor (elevated in iron deficiency but not anemia of chronic disease) and reticulocyte hemoglobin content provide additional diagnostic information.

Prevention strategies target high-risk populations and include dietary counseling and iron supplementation. Iron-fortified formula or iron supplementation (1 mg/kg/day) is recommended for breastfed infants starting at 4-6 months when complementary foods are introduced. Cow's milk should be limited to 16-24 ounces daily in toddlers to prevent milk-induced iron deficiency. Dietary counseling emphasizes iron-rich foods including meats, fortified cereals, and legumes, along with vitamin C-containing foods to enhance absorption and avoidance of iron absorption inhibitors (tea, excessive dairy) with meals. Universal screening at 9-12 months of age or at 15-18 months targets early detection in high-risk populations, with additional screening for at-risk adolescents.

<image>Panel A: Risk factors for iron deficiency across age groups showing infants (prematurity, formula type, complementary feeding), toddlers (cow's milk excess, picky eating), and adolescents (menstruation, growth, dietary restriction). Panel B: Laboratory progression of iron deficiency from depletion through iron-deficient erythropoiesis to anemia showing sequential changes in ferritin, serum iron, TIBC, transferrin saturation, and MCV. Panel C: Peripheral blood smear in iron deficiency anemia showing microcytic hypochromic cells, anisocytosis with elevated RDW, pencil cells, and target cells. Panel D: Prevention strategies including infant iron supplementation timeline, appropriate cow's milk introduction, dietary iron sources by age, and screening recommendations.</image>

III. Hemolytic Anemias

Hemolytic anemias result from shortened red cell survival with accelerated destruction, classified by the mechanism of destruction and whether the defect is intrinsic to the red cell or extrinsic. Intrinsic defects include membrane disorders (hereditary spherocytosis), enzyme deficiencies (G6PD deficiency, pyruvate kinase deficiency), and hemoglobin disorders (sickle cell disease, thalassemia major). Extrinsic causes include immune-mediated destruction (autoimmune hemolytic anemia, alloimmune hemolysis), mechanical destruction (microangiopathic hemolytic anemia, heart valve hemolysis), and infections (malaria, Clostridium). Laboratory findings common to hemolytic anemias include anemia with elevated reticulocyte count reflecting marrow compensation, elevated indirect bilirubin and lactate dehydrogenase from red cell breakdown, and decreased haptoglobin from binding of free hemoglobin.

Hereditary spherocytosis is the most common inherited red cell membrane disorder in individuals of Northern European descent, transmitted as autosomal dominant in most cases. The underlying defect involves spectrin, ankyrin, or other membrane proteins causing loss of membrane surface area relative to cell volume, producing spherical cells with decreased deformability that are trapped and destroyed in the spleen. Clinical features range from well-compensated hemolysis with mild anemia to severe transfusion-dependent anemia, with most patients having moderate hemolysis with jaundice, splenomegaly, and gallstones. Diagnosis relies on family history, blood smear showing spherocytes, elevated mean corpuscular hemoglobin concentration (MCHC), and osmotic fragility testing or eosin-5-maleimide (EMA) binding test. Splenectomy eliminates the site of destruction and corrects the anemia, though the cellular defect persists.

G6PD deficiency is the most common enzyme deficiency worldwide, inherited as X-linked recessive and thus affecting males primarily, with carrier females occasionally affected due to lyonization. G6PD is essential for maintaining reduced glutathione that protects red cells from oxidant stress. Affected individuals have episodic hemolysis triggered by oxidant stress from infections, certain medications (sulfonamides, nitrofurantoin, dapsone, primaquine), or fava beans (favism). Clinical presentation includes acute hemolysis with dark urine, jaundice, and pallor occurring 1-3 days after exposure. Blood smear during acute hemolysis shows "bite cells" and Heinz bodies (denatured hemoglobin inclusions visualized with supravital stain). Management involves avoiding triggers, supportive care during hemolytic episodes, and transfusion for severe anemia.

Autoimmune hemolytic anemia results from antibodies directed against red cell antigens, classified as warm (IgG antibodies active at 37 degrees C) or cold (IgM antibodies active at lower temperatures). Warm AIHA is more common in children and may be primary (idiopathic) or secondary to infections (EBV, CMV, mycoplasma), autoimmune diseases, immunodeficiencies, or lymphoproliferative disorders. Presentation includes rapid onset of pallor, jaundice, and dark urine, with splenomegaly from extravascular hemolysis. The direct antiglobulin test (Coombs test) is positive, detecting IgG and/or complement on the red cell surface. Treatment includes supportive care, corticosteroids as first-line therapy inducing remission in most patients, and second-line options including rituximab, immunosuppression, and splenectomy for refractory cases.

<image>Panel A: Classification of hemolytic anemias showing intrinsic defects (membrane, enzyme, hemoglobin) versus extrinsic causes (immune, mechanical, infectious) with common examples of each category. Panel B: Hereditary spherocytosis showing membrane protein defects, spherocyte formation, splenic trapping, clinical features, and diagnostic tests including osmotic fragility and EMA binding. Panel C: G6PD deficiency pathway showing role in oxidant defense, X-linked inheritance pattern, common triggers, acute hemolysis presentation, and characteristic blood smear findings. Panel D: Autoimmune hemolytic anemia showing warm versus cold types, direct antiglobulin test mechanism, treatment algorithm with corticosteroids first-line and second-line options.</image>

IV. Sickle Cell Disease

Sickle cell disease results from homozygosity for the sickle hemoglobin mutation (HbSS) or compound heterozygosity with another beta-globin variant (HbSC, HbS-beta thalassemia), causing hemoglobin polymerization under deoxygenated conditions leading to red cell sickling, vaso-occlusion, and hemolysis. The mutation involves substitution of valine for glutamic acid at position 6 of the beta-globin chain, producing hemoglobin S that polymerizes when deoxygenated, distorting red cells into rigid sickle shapes that obstruct microvascular flow. Disease severity varies with genotype, with HbSS and HbS-beta-zero thalassemia causing severe disease, HbSC causing moderate disease, and HbS-beta-plus thalassemia causing milder disease. Newborn screening identifies affected infants before symptom onset, enabling early intervention.

Acute vaso-occlusive crisis is the hallmark of sickle cell disease, characterized by acute pain from tissue ischemia caused by microvascular occlusion. Pain commonly affects the long bones, spine, chest, and abdomen, with dactylitis (hand-foot syndrome) often the first manifestation in infants aged 6 months to 2 years. Precipitants include dehydration, cold exposure, infection, and hypoxia, though episodes often occur without identifiable trigger. Management centers on aggressive hydration, analgesia (often requiring opioids), and treatment of any identified precipitant. Assessment for complications including acute chest syndrome, stroke, and aplastic crisis occurs during each admission.

Acute chest syndrome represents the leading cause of death in sickle cell disease and requires urgent recognition and management. Definition includes new pulmonary infiltrate on chest radiograph with at least one of fever, respiratory symptoms (cough, chest pain, dyspnea), or hypoxia. Etiology involves vaso-occlusion, infection, fat embolism from marrow infarction, or combination of factors. Clinical presentation may begin as vaso-occlusive crisis with subsequent respiratory deterioration. Management includes incentive spirometry (reduces incidence when used prophylactically during admissions), antibiotics covering atypical organisms, simple or exchange transfusion targeting hemoglobin S less than 30%, bronchodilators, and respiratory support as needed.

Disease-modifying therapies aim to reduce sickling, vaso-occlusion, and disease complications. Hydroxyurea increases fetal hemoglobin (HbF) production, which interferes with HbS polymerization, and is indicated for patients with frequent vaso-occlusive crises, acute chest syndrome, severe anemia, or other complications, now recommended starting at age 9 months. Chronic transfusion therapy maintains HbS below 30% and is indicated for primary stroke prevention in patients with abnormal transcranial Doppler, secondary stroke prevention, severe recurrent acute chest syndrome, and pregnancy complications. L-glutamine reduces oxidative stress and is approved for reducing vaso-occlusive crises. Voxelotor increases hemoglobin oxygen affinity, reducing sickling. Crizanlizumab blocks selectin-mediated adhesion and reduces vaso-occlusive episodes. Hematopoietic stem cell transplantation offers potential cure for selected patients with severe disease and suitable donor.

<image>Panel A: Sickle cell pathophysiology showing HbS polymerization under deoxygenation, red cell sickling, vaso-occlusion mechanism, and hemolysis with clinical consequences. Panel B: Vaso-occlusive crisis management algorithm showing hydration, analgesia escalation, precipitant identification, and complication assessment checklist. Panel C: Acute chest syndrome definition, etiology components, clinical progression from VOC to respiratory deterioration, and management protocol including transfusion threshold. Panel D: Disease-modifying therapies showing hydroxyurea mechanism and indications, chronic transfusion indications, newer agents (L-glutamine, voxelotor, crizanlizumab), and stem cell transplant candidacy criteria.</image>

V. Bleeding Disorders

Evaluation of bleeding in children requires systematic assessment to distinguish normal variants from pathologic bleeding and to classify disorders by the component of hemostasis affected. Screening questions assess for prolonged bleeding from minor cuts, easy bruising, epistaxis duration and frequency, heavy menstrual bleeding, bleeding with procedures (circumcision, dental extractions, tonsillectomy), and family history of bleeding. Physical examination evaluates for petechiae (platelet or vascular disorders), ecchymoses, joint swelling or deformity (hemophilia), mucosal bleeding, and signs of underlying disease. Initial laboratory evaluation includes complete blood count with platelet count, prothrombin time (PT) assessing the extrinsic and common pathways, and activated partial thromboplastin time (aPTT) assessing the intrinsic and common pathways.

Von Willebrand disease is the most common inherited bleeding disorder, affecting approximately 1% of the population, resulting from quantitative or qualitative deficiency of von Willebrand factor (vWF). VWF mediates platelet adhesion to injured vessel walls and serves as carrier protein for factor VIII. Type 1 (most common, approximately 75%) involves partial quantitative deficiency with mild to moderate bleeding. Type 2 involves qualitative defects with variable severity. Type 3 is rare but severe with complete vWF deficiency. Clinical features include mucocutaneous bleeding (epistaxis, heavy menses, prolonged bleeding from cuts), with symptoms often mild and unrecognized until surgical challenge. Laboratory findings show prolonged aPTT (when factor VIII is sufficiently reduced), low vWF antigen, low vWF activity (ristocetin cofactor), and low or normal factor VIII. Treatment for bleeding episodes or surgical prophylaxis includes desmopressin (DDAVP) for type 1, releasing stored vWF, and vWF/factor VIII concentrates for severe bleeding or types 2 and 3.

Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are X-linked recessive disorders causing deficiency of coagulation factors essential for the intrinsic pathway. Hemophilia A is more common, comprising 80-85% of hemophilia cases, with severity classified by factor level: severe (less than 1% activity) causes spontaneous bleeding, moderate (1-5%) causes bleeding with minor trauma, and mild (5-40%) causes bleeding primarily with surgery or significant trauma. Clinical features differ from platelet disorders, with deep tissue bleeding including hemarthrosis (joint bleeding, the hallmark of severe hemophilia), muscle hematomas, and excessive bleeding after procedures. Laboratory findings show prolonged aPTT with normal PT and platelet count, and low factor VIII or IX level confirms diagnosis. Treatment involves factor replacement, with prophylactic factor infusions recommended for severe disease to prevent joint damage, and newer non-factor therapies including emicizumab (bispecific antibody mimicking factor VIII function) transforming hemophilia A management.

Immune thrombocytopenic purpura is the most common cause of isolated thrombocytopenia in otherwise healthy children, resulting from autoantibodies against platelet surface glycoproteins causing accelerated platelet destruction and suppressed production. Most pediatric cases are acute, self-limited, and follow viral illness by 1-4 weeks. Presentation includes sudden onset of petechiae and bruising in an otherwise well-appearing child, with platelet count often below 20,000/microL. Diagnosis is clinical, requiring exclusion of other causes; bone marrow examination is not routinely needed unless atypical features exist. Management is observation for most children with minor bleeding, as 80-90% resolve spontaneously within 6-12 months. Treatment options for significant bleeding or very low platelets include corticosteroids, intravenous immunoglobulin, and anti-D immunoglobulin, which raise platelet count temporarily while awaiting spontaneous resolution.

<image>Panel A: Approach to bleeding child showing screening history questions, physical examination findings for platelet versus coagulation disorders, and initial laboratory evaluation with interpretation. Panel B: Von Willebrand disease types comparison showing quantitative versus qualitative defects, laboratory findings, severity spectrum, and treatment with DDAVP versus concentrates. Panel C: Hemophilia presentation and management showing hemarthrosis development, factor severity classification, treatment with factor replacement, and prophylaxis protocols. Panel D: ITP presentation, diagnosis by exclusion, natural history showing spontaneous resolution rates, and treatment options based on bleeding severity.</image>

VI. Leukemia

Acute lymphoblastic leukemia is the most common pediatric malignancy, accounting for approximately 25% of all childhood cancers and 75% of childhood leukemias, with peak incidence at ages 2-5 years. The malignancy arises from clonal proliferation of lymphoid precursors in the bone marrow, which accumulate and suppress normal hematopoiesis while spreading to blood, lymph nodes, liver, spleen, central nervous system, and testes. Risk factors include genetic syndromes (Down syndrome with 15-20 fold increased risk, neurofibromatosis), prior chemotherapy or radiation, and possibly environmental exposures, though most cases have no identifiable risk factor. The disease is classified by immunophenotype as B-cell (approximately 85%, best prognosis) or T-cell (approximately 15%), with further risk stratification by genetics and response to therapy.

Clinical presentation of ALL reflects bone marrow failure and extramedullary disease involvement. Bone marrow failure produces anemia (pallor, fatigue), neutropenia (infections, fever), and thrombocytopenia (petechiae, bruising, bleeding). Extramedullary involvement causes lymphadenopathy, hepatosplenomegaly, bone pain (from marrow expansion), and rarely mediastinal mass (T-cell ALL), CNS involvement (headache, cranial nerve palsies, increased intracranial pressure), or testicular involvement. Laboratory findings include abnormal complete blood count with varying degrees of cytopenia, with white blood cell count ranging from low (leukopenia) to markedly elevated (hyperleukocytosis above 100,000), and peripheral blood smear often showing blasts. Diagnosis requires bone marrow aspiration demonstrating greater than 25% blasts with lymphoid morphology and immunophenotype.

Treatment of ALL involves multi-agent chemotherapy over 2-3 years, stratified by risk classification. Risk factors determining treatment intensity include age (infants and older adolescents higher risk), initial white count, genetics (favorable: hyperdiploidy, ETV6-RUNX1; unfavorable: hypodiploidy, KMT2A rearrangement, BCR-ABL), CNS involvement, and response to initial therapy. Treatment phases include induction (approximately 1 month, achieving remission), consolidation (intensification), CNS-directed therapy (intrathecal chemotherapy, with cranial radiation reserved for high-risk CNS disease), and maintenance (2-3 years). Prognosis has improved dramatically, with overall survival now exceeding 90% for standard-risk ALL, though certain subgroups and relapsed disease have worse outcomes.

Acute myeloid leukemia accounts for approximately 20% of childhood leukemias, arising from myeloid precursors, with distinct biology and treatment compared to ALL. Risk factors include Down syndrome (particularly for acute megakaryoblastic leukemia), Fanconi anemia, Li-Fraumeni syndrome, and prior chemotherapy. Presentation is similar to ALL, with bone marrow failure symptoms and extramedullary involvement, though certain features are more common including chloromas (localized tumor deposits), gingival hyperplasia, and disseminated intravascular coagulation (particularly acute promyelocytic leukemia). Diagnosis requires bone marrow aspiration with greater than 20% myeloid blasts, with cytogenetic and molecular studies guiding risk stratification. Treatment involves intensive chemotherapy (shorter but more intensive than ALL regimens) and hematopoietic stem cell transplantation for high-risk patients or after relapse. Prognosis is generally worse than ALL, with overall survival approximately 60-70%.

<image>Panel A: ALL pathophysiology showing lymphoid precursor proliferation in marrow, normal hematopoiesis suppression, and spread to blood, CNS, testes, and lymphoid organs with corresponding clinical manifestations. Panel B: ALL diagnostic evaluation showing CBC findings, peripheral smear with blasts, bone marrow aspiration with immunophenotyping, and cytogenetic/molecular testing for risk stratification. Panel C: ALL treatment phases showing induction, consolidation, CNS prophylaxis, and maintenance with timeline and key agents, along with risk stratification factors affecting intensity. Panel D: AML distinguishing features showing myeloid blast morphology, Auer rods, specific presentations (chloromas, gingival hyperplasia), and treatment approach with intensive chemotherapy and transplant indications.</image>

VII. Solid Tumors

Brain tumors are the most common solid tumors in children and the leading cause of cancer-related death in pediatrics, with location and histology determining presentation and prognosis. Posterior fossa tumors account for approximately 60% of pediatric brain tumors and include medulloblastoma (most common malignant brain tumor), ependymoma, and pilocytic astrocytoma. Supratentorial tumors include low-grade and high-grade gliomas, craniopharyngioma, and germ cell tumors. Presentation depends on location and includes symptoms of increased intracranial pressure (headache worse in morning, vomiting without nausea, papilledema), cerebellar dysfunction (ataxia, nystagmus), cranial nerve palsies, seizures, and endocrine dysfunction. Diagnosis requires neuroimaging with MRI and often surgical resection or biopsy for histologic confirmation. Treatment involves surgery, radiation (often deferred in young children due to neurocognitive effects), and chemotherapy depending on tumor type.

Neuroblastoma is the most common extracranial solid tumor in children, arising from neural crest cells and most commonly presenting before age 5 years. The tumor typically originates in the adrenal medulla or sympathetic ganglia along the paraspinal region. Clinical presentation varies dramatically based on location and stage, ranging from incidental finding or localized mass to metastatic disease with bone marrow involvement, bone lesions, and the classic pattern of periorbital ecchymoses from orbital metastases. Unique features include spontaneous regression in infants (stage 4S disease), paraneoplastic syndromes (opsoclonus-myoclonus-ataxia syndrome), and production of catecholamines with elevated urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA). Prognosis varies from excellent (low-risk, observation only) to poor (high-risk, intensive multimodal therapy) based on age, stage, and tumor biology including MYCN amplification.

Wilms tumor (nephroblastoma) is the most common primary renal malignancy in children, typically presenting between ages 2-5 years as an asymptomatic abdominal mass. The tumor arises from embryonal kidney cells and may be associated with syndromes including WAGR (Wilms, aniridia, genitourinary anomalies, intellectual disability), Denys-Drash, and Beckwith-Wiedemann. Presentation most commonly involves a parent or physician noting an abdominal mass, sometimes with abdominal pain or hematuria, and rarely hypertension from renin production. Imaging shows a large intrarenal mass, often with characteristic imaging features. Treatment involves nephrectomy, chemotherapy, and radiation for higher stages or unfavorable histology. Prognosis is excellent, with overall survival exceeding 90% for favorable histology, though anaplastic histology carries worse prognosis.

Lymphoma includes Hodgkin lymphoma and non-Hodgkin lymphoma, together comprising approximately 10% of childhood cancers. Hodgkin lymphoma typically presents in adolescents with painless cervical or supraclavicular lymphadenopathy, sometimes with B symptoms (fever, night sweats, weight loss) and mediastinal involvement. Non-Hodgkin lymphoma in children is usually high-grade, with subtypes including Burkitt lymphoma (rapidly growing abdominal or jaw mass), lymphoblastic lymphoma (mediastinal mass in adolescent male, closely related to T-cell ALL), and diffuse large B-cell lymphoma. Evaluation includes imaging for staging (CT, PET), tissue biopsy for histologic diagnosis, and bone marrow and cerebrospinal fluid examination for NHL. Treatment involves chemotherapy with excellent cure rates, adding radiation for selected Hodgkin lymphoma cases. Prognosis is generally favorable, with survival exceeding 90% for Hodgkin lymphoma and 80-90% for most NHL subtypes.

<image>Panel A: Pediatric brain tumor types by location showing posterior fossa tumors (medulloblastoma, ependymoma, astrocytoma) and supratentorial tumors (gliomas, craniopharyngioma) with clinical presentations for each location. Panel B: Neuroblastoma features showing adrenal/paraspinal origin, age and stage-dependent prognosis, periorbital ecchymoses from orbital metastases, and urinary catecholamine testing. Panel C: Wilms tumor presentation as asymptomatic abdominal mass, associated syndromes, surgical and chemotherapy approach, and excellent prognosis for favorable histology. Panel D: Lymphoma comparison showing Hodgkin (adolescent, cervical nodes, B symptoms) versus NHL subtypes (Burkitt, lymphoblastic) with staging and treatment approach.</image>

VIII. Oncologic Emergencies

Tumor lysis syndrome results from rapid release of intracellular contents during cancer cell death, causing life-threatening metabolic derangements. The classic electrolyte abnormalities include hyperuricemia (from purine breakdown), hyperphosphatemia (from cell lysis), hypocalcemia (from phosphate binding calcium), and hyperkalemia (from intracellular release). Acute kidney injury results from uric acid and calcium phosphate precipitation in renal tubules. Risk factors include high tumor burden, rapidly proliferating tumors (ALL, Burkitt lymphoma, neuroblastoma), and large tumor mass at presentation. Prevention involves hydration, allopurinol (inhibits uric acid formation), or rasburicase (breaks down existing uric acid, more effective but expensive and contraindicated in G6PD deficiency). Treatment addresses specific electrolyte abnormalities and may require dialysis for refractory cases.

Febrile neutropenia represents a medical emergency in oncology patients, requiring immediate evaluation and broad-spectrum antibiotics due to high mortality risk from bacterial infection. Definition includes fever (single temperature 38.3 degrees C or sustained 38.0 degrees C) with absolute neutrophil count below 500/microL or expected to fall below 500/microL. The absence of neutrophils prevents normal inflammatory response, so typical infection signs (purulence, infiltrate, fluctuance) may be absent. Evaluation includes history and examination seeking infection source (oral mucosa, perianal area, catheter sites), blood cultures (central and peripheral if central line present), urinalysis and culture, and chest radiograph if respiratory symptoms. Treatment involves immediate empiric broad-spectrum antibiotics (often monotherapy with antipseudomonal beta-lactam such as ceftazidime or piperacillin-tazobactam), with modification based on clinical course and culture results.

Superior vena cava syndrome and superior mediastinal syndrome result from compression of the superior vena cava and/or trachea by mediastinal masses, most commonly T-cell ALL/lymphoma in pediatrics. Clinical features include facial and upper extremity edema, plethora, distended neck veins, orthopnea, and respiratory distress that worsens when supine. The primary concern is airway compromise, which may deteriorate acutely with sedation, anesthesia, or supine positioning. Evaluation must be performed carefully to avoid precipitating airway compromise; tissue diagnosis from less invasive sources (peripheral blood, pleural fluid, bone marrow) is preferred over mediastinal biopsy when possible. Management priorities include keeping the patient upright, avoiding sedation and intubation if possible, obtaining tissue diagnosis with minimal risk, and initiating treatment (often corticosteroids for lymphoma) promptly.

Spinal cord compression requires urgent recognition and treatment to preserve neurological function. Causes include direct tumor extension (neuroblastoma, sarcomas), epidural metastases, or vertebral collapse from tumor involvement. Presenting symptoms include back pain (often the earliest symptom), lower extremity weakness or sensory changes, and bowel or bladder dysfunction (late signs indicating severe compression). Any oncology patient with new back pain requires urgent evaluation with MRI of the entire spine. Management involves immediate high-dose corticosteroids (dexamethasone) to reduce edema, followed by definitive treatment with surgery (decompression and/or stabilization), radiation, or chemotherapy depending on tumor type and stability. Outcomes depend on neurological status at diagnosis, making early recognition critical.

<image>Panel A: Tumor lysis syndrome pathophysiology showing cell lysis releasing purines, phosphorus, and potassium, with downstream effects on uric acid, calcium binding, and renal tubular precipitation, plus prevention and treatment strategies. Panel B: Febrile neutropenia evaluation and management algorithm showing immediate antibiotic timing, infection site assessment, culture priorities, and antibiotic selection. Panel C: Superior mediastinal syndrome showing mediastinal mass compressing SVC and trachea, clinical features, positioning importance, and diagnostic approach avoiding sedation. Panel D: Spinal cord compression presentation with back pain as early sign, progression to weakness and bowel/bladder dysfunction, MRI findings, and urgent management with steroids and definitive treatment.</image>

IX. Late Effects of Cancer Treatment

Late effects of childhood cancer treatment affect virtually all survivors and require lifelong surveillance and management. Second malignancies represent a significant concern, with risk increased by radiation (breast cancer after chest radiation, thyroid cancer after neck radiation, sarcomas in radiation fields) and certain chemotherapy agents (alkylating agents, topoisomerase inhibitors causing leukemia). Surveillance includes education about warning signs, regular physical examination, and specific screening based on exposures (mammography beginning at age 25 or 8 years after chest radiation for breast cancer risk).

Cardiotoxicity results primarily from anthracycline chemotherapy (doxorubicin, daunorubicin) and chest radiation. Anthracyclines cause dose-dependent cardiomyopathy, which may manifest as asymptomatic decreased function, symptomatic heart failure, or sudden cardiac death, appearing years to decades after treatment. Risk factors include cumulative dose, younger age at treatment, female sex, and concurrent chest radiation. Surveillance involves periodic echocardiography for life in patients who received anthracyclines, with frequency based on exposure and findings. Radiation causes accelerated coronary artery disease, valvular disease, and pericardial disease with delayed onset. Management includes standard heart failure therapy when dysfunction develops and aggressive cardiovascular risk factor modification.

Endocrine complications affect growth, fertility, and thyroid function. Growth impairment results from cranial radiation affecting hypothalamic-pituitary function, spinal radiation affecting vertebral growth, or direct effects on growth hormone secretion. Growth hormone replacement is indicated for documented deficiency. Gonadal dysfunction varies by treatment exposure, with alkylating agents causing dose-dependent gonadal toxicity particularly affecting males, and radiation causing gonadal failure depending on dose and field. Fertility preservation (sperm banking, oocyte cryopreservation) should be discussed before treatment when feasible. Hypothyroidism commonly follows neck or craniospinal radiation and requires regular thyroid function screening and hormone replacement.

Neurocognitive effects result from cranial radiation, intrathecal chemotherapy, and systemic chemotherapy crossing the blood-brain barrier. Deficits include decreased IQ, executive function impairment, memory difficulties, attention problems, and slow processing speed. Risk is highest with younger age at treatment and higher radiation doses. Educational support, neuropsychological testing, and rehabilitation services address these deficits. Psychological effects including anxiety, depression, and post-traumatic stress symptoms are common in survivors and require screening and appropriate mental health support. Transition to adult survivorship care, with providers knowledgeable about late effects, ensures continued appropriate surveillance and management.

<image>Panel A: Second malignancy risks showing radiation-associated cancers by field (breast after chest, thyroid after neck, sarcomas in field) and chemotherapy-associated leukemia risk with screening recommendations. Panel B: Anthracycline cardiotoxicity showing dose-dependent mechanism, clinical spectrum from asymptomatic to heart failure, risk factors, echocardiographic surveillance schedule, and management approach. Panel C: Endocrine late effects showing growth impairment mechanisms, gonadal dysfunction by gender and agent, thyroid dysfunction after radiation, and fertility preservation options. Panel D: Neurocognitive effects showing affected domains, risk factors (age, radiation dose), educational interventions, and comprehensive survivorship care model with multidisciplinary support.</image>

X. Supportive Care

Central venous access provides reliable vascular access for chemotherapy, blood products, and supportive medications, with several device options. External tunneled catheters (Hickman, Broviac) have lumens exiting the skin and require regular flushing and dressing changes but allow immediate use and easy removal. Implanted ports (Port-a-Cath) are completely subcutaneous, accessed by needle through the skin, and require less maintenance but need surgical placement and removal. Peripherally inserted central catheters (PICCs) offer intermediate-term access without tunneling or surgical placement. Complications include catheter-related bloodstream infections (requiring blood cultures, antibiotics, and sometimes catheter removal), thrombosis (treated with anticoagulation), and mechanical complications (occlusion, malposition, breakage).

Transfusion support is essential during intensive chemotherapy causing cytopenias. Red blood cell transfusions are indicated for symptomatic anemia, typically when hemoglobin falls below 7-8 g/dL, administered as packed red blood cells at 10-15 mL/kg. Platelet transfusions maintain counts above threshold for bleeding prevention, typically above 10,000/microL for prophylaxis and higher for procedures or active bleeding. All blood products should be irradiated to prevent transfusion-associated graft-versus-host disease in immunocompromised patients and CMV-negative or leuko-reduced products used for CMV-seronegative recipients. Transfusion reactions range from mild (febrile, allergic) to severe (acute hemolytic, anaphylaxis, TRALI) and require recognition and appropriate management.

Infection prophylaxis and management reduce morbidity and mortality during immunosuppression. Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole is standard during and after treatment for most patients. Antifungal prophylaxis with fluconazole or other agents is used during periods of prolonged neutropenia. Antiviral prophylaxis (acyclovir) prevents herpes simplex reactivation. Immunizations require special consideration: live vaccines are contraindicated during immunosuppression and for 3-6 months after treatment completion, while inactivated vaccines may be given but may have diminished response. Household contacts should receive appropriate vaccines, avoiding recently administered live oral vaccines.

Nausea, pain, and nutritional support address quality of life and treatment tolerance. Antiemetic prophylaxis with 5-HT3 antagonists (ondansetron), corticosteroids, and NK1 antagonists (aprepitant) has dramatically improved chemotherapy tolerance. Pain management follows WHO ladder principles, using multimodal approaches including non-pharmacologic strategies, NSAIDs, and opioids as appropriate, with particular attention to procedure-related pain and mucositis. Nutritional support addresses increased needs and decreased intake, using oral supplementation, enteral nutrition (nasogastric or gastrostomy feeding), or parenteral nutrition as needed to maintain weight and support healing. Psychosocial support for patients and families addresses the profound impact of cancer diagnosis and treatment on the entire family unit.

<image>Panel A: Central venous access device comparison showing external tunneled catheters, implanted ports, and PICCs with indications, advantages, disadvantages, and maintenance requirements for each. Panel B: Blood product transfusion showing RBC and platelet indications, dosing, special processing requirements (irradiation, leukoreduction), and transfusion reaction recognition and management. Panel C: Infection prevention showing Pneumocystis prophylaxis regimen, antifungal prophylaxis indications, antiviral prophylaxis, and immunization considerations during and after treatment. Panel D: Supportive care domains showing antiemetic prophylaxis regimen, pain management ladder, nutritional intervention escalation, and psychosocial support resources.</image>

Summary

• Anemia classification by MCV guides differential: microcytic (iron deficiency, thalassemia), normocytic (hemolysis, marrow failure), macrocytic (B12/folate, bone marrow failure syndromes)
• Iron deficiency is most common in toddlers (cow's milk excess) and adolescent females (menstruation); treat with oral iron for 2-3 months after hemoglobin normalizes
• Hemolytic anemia features elevated reticulocyte count, indirect bilirubin, LDH, and decreased haptoglobin
• Sickle cell disease: vaso-occlusive crises treated with hydration and analgesia; acute chest syndrome requires antibiotics and transfusion
• Hydroxyurea reduces sickle cell complications by increasing fetal hemoglobin; indicated starting at age 9 months
• ALL is the most common childhood cancer; treatment stratified by risk with greater than 90% survival for standard risk
• Tumor lysis syndrome: hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia; prevent with hydration and allopurinol/rasburicase
• Febrile neutropenia requires immediate broad-spectrum antibiotics
• Late effects of cancer treatment require lifelong surveillance for cardiac, endocrine, and second malignancy risks

Key Terms

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