A 16-year-old boy presents with a 3-month history of pain and swelling in the mid-shaft of the femur. Radiographs show a lytic lesion with a 'onion-skin' periosteal reaction and a wide zone of transition. MRI reveals a large soft tissue mass. Regarding the clinical and pathological features of Ewing sarcoma, all of the following are TRUE EXCEPT:

Explanation

## Ewing Sarcoma: Clinical and Pathological Profile ### Age of Presentation **Key Point:** Ewing sarcoma is a tumor of the young — peak incidence is in the **second and third decades of life** (10–30 years), with 90% of cases occurring before age 40. A patient over 40 would be an outlier and should prompt consideration of alternative diagnoses (e.g., osteosarcoma, chondrosarcoma, or metastatic disease). ### Anatomical Location **High-Yield:** Ewing sarcoma characteristically arises in the **diaphysis (shaft) or diaphyseal-metaphyseal junction** of long bones. This is a key distinguishing feature: - **Osteosarcoma** → metaphysis - **Ewing sarcoma** → diaphysis - **Giant cell tumor** → epiphysis ### Histopathology **Clinical Pearl:** The hallmark microscopic finding is **uniform small round cells** with: - Scant cytoplasm (appears clear or pale) - Round to oval nuclei - Prominent nucleoli - High nuclear-to-cytoplasmic ratio - Minimal mitotic activity (deceptively "quiet" appearance) - Positive for CD99 and FLI1 immunohistochemistry (EWS-FLI1 translocation t(11;22)) ### Metastatic Pattern **Key Point:** At presentation, **10–20% of patients have clinically detectable metastases**, with the **lungs being the most common site** (90% of metastases). Skeletal metastases occur in ~25% of cases. ### Comparison Table: Primary Bone Tumors by Location | Feature | Osteosarcoma | Ewing Sarcoma | Giant Cell Tumor | |---------|--------------|---------------|------------------| | **Age** | 10–25 years | 10–30 years | 20–40 years | | **Site** | Metaphysis | Diaphysis | Epiphysis | | **Bone** | Distal femur, proximal tibia | Femur (mid-shaft) | Distal femur, proximal tibia | | **Radiograph** | Sunburst, codman triangle | Onion-skin, permeative | Eccentric, soap-bubble | | **Cells** | Malignant osteoblasts | Small round cells | Giant cells, hemosiderin | ### Why Option 4 is Wrong Ewing sarcoma is a **tumor of adolescents and young adults**. Age >40 is atypical and should trigger suspicion for a different diagnosis. This is a high-yield discriminator on exams. [cite:Robbins 10e Ch 26]