5.1 Osteosarcoma and Ewing Sarcoma

A 14-year-old soccer player reports six weeks of night pain just above the knee. Urgent care called the joint radiograph normal. A dedicated femur film shows a distal femoral metaphyseal lesion with a sunburst periosteal reaction and a Codman triangle. That presentation is osteosarcoma until an orthopedic oncologist biopsies it. CPHON items on bone sarcomas ask you to separate osteosarcoma from Ewing sarcoma by age, bone site, imaging, genetics, and local-control strategy—and to keep a child alive through high-dose methotrexate, anthracyclines, ifosfamide, and fever-neutropenia.

Osteosarcoma: metaphysis, adolescents, lungs

Osteosarcoma is the most common primary malignant bone tumor of childhood and adolescence. Incidence peaks with the adolescent growth spurt. Classic sites are the metaphysis of long bones: distal femur, proximal tibia, and proximal humerus. Around-the-knee locations dominate. The history is progressive pain, a firm mass, limp, night pain that does not match a sprain timeline, and sometimes a pathologic fracture after modest trauma. Do not close the workup because a sports-medicine film of the joint missed the metaphysis.

Plain films classically show a mixed lytic-sclerotic lesion, sunburst periosteal reaction, and Codman triangle. Magnetic resonance imaging of the entire involved bone maps skip metastases—discontinuous tumor in the same bone or across the adjacent joint—that change surgical margins. Chest computed tomography hunts the most common distant site: lung. Bone scan or positron-emission tomography looks for skip lesions and skeletal metastases. Alkaline phosphatase and lactate dehydrogenase may be elevated; they support suspicion but do not replace biopsy. Biopsy belongs to the treating orthopedic oncology team so the tract can sit inside the future resection.

MAP-like chemotherapy, limb salvage, and the implant

Contemporary pediatric osteosarcoma uses neoadjuvant multi-agent chemotherapy, surgical local control, then adjuvant chemotherapy informed by histologic necrosis. The MAP-like backbone is high-dose methotrexate with leucovorin rescue, doxorubicin, and cisplatin. Osteosarcoma is relatively radioresistant. Radiation is not first-line local control for an extremity lesion that can be resected with a functional reconstruction.

Limb-salvage with wide resection and reconstruction—endoprosthesis, allograft, or rotationplasty—is preferred when an oncologically adequate, usable limb can be preserved. Amputation remains correct when the neurovascular bundle cannot be spared, when infection or pathologic fracture destroys reconstruction, or when the team and family judge function better with an external prosthesis. Rotationplasty is not a consolation prize; for a growing athlete it can provide durable below-knee–style function.

Endoprosthesis teaching is lifelong. No contact sports that torque the implant. Fever plus a reconstructed joint is infection until proven otherwise. Growing children need planned revisions for limb-length discrepancy and loosening. Physical therapy is part of oncologic care, not an afterthought. A warm, swollen salvage knee at home is an emergency visit, not a wait-until-clinic-Monday plan.

Toxicities the CPHON nurse owns on MAP

High-dose methotrexate is a timed rescue, not a once-daily home tablet. Hydrate. Alkalinize urine, typically targeting pH of 7 or higher. Give leucovorin on the protocol clock. Third-space fluid—pleural effusion, ascites, obstructed bowel—delays clearance. Hold interacting drugs the protocol names, commonly including nonsteroidal anti-inflammatory drugs and trimethoprim-sulfamethoxazole around the methotrexate window. Serial serum methotrexate levels drive how long rescue continues. Glucarpidase is the concept used when delayed clearance plus toxic methotrexate levels threaten the kidneys and mucosa: a carboxypeptidase that cleaves methotrexate, given with expert pharmacy support, not as a casual extra leucovorin dose.

Doxorubicin drives cumulative cardiotoxicity. Track lifetime milligrams per square meter, obtain protocol echocardiograms, and teach families that activity tolerance and future heart-failure risk are part of survivorship. Cisplatin drives ototoxicity and nephrotoxicity. Serial audiograms belong on the roadmap; classroom hearing support is a nursing referral, not a surprise at parent-teacher night. Hydrate around cisplatin, replete magnesium, watch creatinine, and avoid stacking nephrotoxins. Antiemetic premedication is a safety intervention; MAP nausea is not optional discomfort.

Ewing sarcoma: diaphysis, flat bone, soft tissue, and the infection mimic

Ewing sarcoma is a small-round-blue-cell tumor of bone or extraosseous soft tissue. Peak age is often slightly younger than classic osteosarcoma and includes school-age children, though teenagers are common. Typical sites are the diaphysis of long bones, flat bones (pelvis, scapula, ribs, vertebrae), chest wall, and pure soft-tissue masses. Fever, weight loss, malaise, and a high erythrocyte sedimentation rate or C-reactive protein make Ewing look like osteomyelitis. Do not treat a lytic diaphyseal lesion as culture-negative chronic infection for weeks without a planned biopsy; delayed diagnosis delays systemic therapy.

Imaging classically shows onion-skin (lamellated) periosteal reaction and a large soft-tissue mass. Magnetic resonance imaging defines extraosseous extent. Staging includes chest imaging, skeletal or positron-emission tomography survey, and bilateral bone-marrow evaluation on many protocols, because marrow joins lung and bone as a classic metastatic site. The teaching genetic point is t(11;22) producing EWSR1-FLI1. Other EWSR1 partners exist. The CPHON distinction is that Ewing is a translocation-defined sarcoma, not osteosarcoma in a younger child.

VDC/IE-style cycles, mesna, methylene blue, fever

Treat Ewing as systemic disease from day one. Interval-compressed VDC/IE-style cycles use vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide, plus local control with surgery, radiation, or both. Unlike osteosarcoma, Ewing is radiosensitive. Unresectable pelvic or vertebral disease often needs radiation. Surgery is chosen when complete resection with acceptable function is realistic.

Mesna accompanies ifosfamide and higher-dose cyclophosphamide to bind acrolein and prevent hemorrhagic cystitis. Nursing means timed mesna, vigorous hydration, and heme-positive urine as an emergency signal—not a wait for the next voiding diary. Ifosfamide neurotoxicity—somnolence, confusion, hallucinations, seizures—is a supportive-care concept. Methylene blue is used in selected cases with the oncology team after hypoglycemia and other metabolic causes are considered. Ifosfamide also wastes renal tubular electrolytes; check phosphate, potassium, bicarbonate, and urine protein.

Vincristine constipation and neuropathy need a bowel regimen before the next dose, not after obstruction. Anthracycline echo rules still apply. Fever during neutropenia after these intensive cycles is an emergency: cultures, prompt broad-spectrum antibiotics, and no instruction to wait until morning clinic. Families hear that looking well at 18:00 does not cancel 38.3°C at 02:00.

A 9-year-old with fever, a painful tibial shaft, and onion-skin periosteum is not chronic osteomyelitis until Ewing is excluded. A 15-year-old with a distal femoral metaphyseal mass and pulmonary nodules is osteosarcoma until proven otherwise. Keep the maps separate so MAP hydration and VDC/IE mesna are not swapped at the chairside.