Bone Tumors, Germ Cell Tumors, Retinoblastoma, Liver Tumors, LCH

Osteosarcoma · Ewing sarcoma · Germ cell tumors (teratoma, germinoma, yolk sac, choriocarcinoma, gonadoblastoma, sacrococcygeal, mediastinal, intracranial, gonadal) · Retinoblastoma · Liver tumors (hepatoblastoma, HCC) · Langerhans cell histiocytosis
🧬 Key concepts: Osteosarcoma (sunburst, metaphyseal), Ewing (t(11;22), small blue cell). Germ cell tumor markers (AFP, β-hCG). Retinoblastoma (RB1 gene, leukocoria). LCH (CD1a+, langerin, BRAF V600E). Multimodal therapy.

📖 Bone sarcomas, GCT, retinoblastoma, liver tumors, LCH

🦴 Osteosarcoma
Malignant bone tumor (peak 10-20y), metaphysis of long bones (distal femur, proximal tibia). X-ray: sunburst, Codman triangle. Neoadjuvant chemotherapy + surgery.
🔬 Ewing sarcoma
Small round cell tumor, diaphysis, t(11;22)(q24;q12) EWSR1-FLI1. Metastatic to lungs, bone. Chemosensitive, radiotherapy for local control.
🧬 Germ cell tumors
Sacrococcygeal (newborn), mediastinal, ovarian, testicular, intracranial. Markers: AFP (yolk sac), β-hCG (choriocarcinoma). Teratoma (mature benign, immature).
👁️ Retinoblastoma
Leukocoria, strabismus. RB1 germline (hereditary bilateral) vs sporadic unilateral. Chemoreduction + focal therapy (laser, cryo). Enucleation for advanced.
🩺 Langerhans cell histiocytosis (LCH)
CD1a+, langerin+, BRAF V600E. Single system (bone, skin) vs multisystem (risk organs: liver, spleen, bone marrow). Chemotherapy (vinblastine, prednisolone).
⚠️ Red flags: Bone pain (night pain, mass), leukocoria, proptosis, chronic skull lesions with diabetes insipidus, skin rash (seborrheic), otorrhea unresponsive.

🩺 Diagnostic approach: bone tumors, GCT, retinoblastoma, LCH

1
Bone tumor suspicion – Pain, swelling, night pain, functional impairment. Imaging: X-ray (sunburst, Codman triangle → osteosarcoma; lamellated onion-skin → Ewing). MRI for local extent, CT chest for metastases.
2
Germ cell tumor evaluation – Tumor markers (AFP, β-hCG). Imaging: ultrasound, CT, MRI. Sacrococcygeal: prenatal diagnosis common. Biopsy for histology.
3
Retinoblastoma diagnosis – Red reflex test (leukocoria). Ophthalmic exam under anesthesia. Orbital ultrasound, MRI brain/orbits. Genetic testing (RB1).
4
LCH workup – Skeletal survey, chest CT (cystic lesions), liver ultrasound, bone marrow biopsy. BRAF mutation analysis. CD1a/langerin immunohistochemistry.
📌 Clinical pearl: A child with a lytic skull lesion and diabetes insipidus → Langerhans cell histiocytosis (pituitary stalk infiltration).

📋 Stepwise management: osteosarcoma, GCT, retinoblastoma, LCH

1
Osteosarcoma – Neoadjuvant chemotherapy (MAP: methotrexate, doxorubicin, cisplatin). Limb-sparing surgery (or amputation). Adjuvant chemotherapy. Metastatic disease: poor prognosis.
2
Ewing sarcoma – Chemotherapy (VDC/IE: vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide). Local control: surgery or radiotherapy. Treat metastases with same regimen.
3
Germ cell tumors – Surgery (complete resection if possible). Chemotherapy (cisplatin, etoposide, bleomycin) for malignant GCT. Surveillance for mature teratoma.
4
Retinoblastoma – Chemoreduction (carboplatin, etoposide, vincristine) + focal therapy (laser, cryotherapy, brachytherapy). Enucleation for advanced unilateral. Genetic counseling.
5
Langerhans cell histiocytosis – Multisystem/risk organ involvement: vinblastine + prednisolone. Single-system bone: curettage, observation. BRAF inhibitors for refractory.
🚨 Emergency in LCH: Diabetes insipidus (desmopressin). Liver failure, pancytopenia (risk organ involvement). Prompt treatment.

🧠 Reflex prompts: bone tumors, GCT, retinoblastoma, LCH

🦴 Adolescent with knee pain, worse at night, swelling. X-ray shows 'sunburst' appearance. Diagnosis?
Osteosarcoma. MRI, CT chest, biopsy. Neoadjuvant chemotherapy + surgery.
🔬 10-year-old with thigh pain, fever, mass. X-ray shows lamellated 'onion-skin' periosteal reaction. Diagnosis?
Ewing sarcoma. t(11;22) EWSR1-FLI1. Chemotherapy + local control.
🧬 Newborn with large sacrococcygeal mass, no malignancy. AFP normal. Most likely?
Mature teratoma. Surgical excision. Excellent prognosis.
👁️ Infant with leukocoria on photo. Next step?
Urgent ophthalmology examination (retinoblastoma). MRI brain/orbits, genetic testing.
🩺 Child with skull lytic lesion, diabetes insipidus, eczematoid rash. Diagnosis?
Langerhans cell histiocytosis (LCH). Biopsy CD1a+, BRAF mutation. Chemotherapy for multisystem.
🧫 Which tumor marker is elevated in yolk sac tumor?
Alpha-fetoprotein (AFP).
🦴 Most common site of osteosarcoma?
Distal femur (metaphyseal), proximal tibia, proximal humerus.
🧬 Which gene is mutated in hereditary retinoblastoma?
RB1 (13q14).
🩺 First-line treatment for multisystem LCH with risk organ involvement?
Vinblastine + prednisolone (LCH-III protocol).
🧪 What is the classic translocation in Ewing sarcoma?
t(11;22)(q24;q12) EWSR1-FLI1.