A 35-year-old woman from Mumbai presents with a 2-year history of progressive pain in the proximal humerus. Plain radiographs show a well-circumscribed, purely lytic lesion in the epiphysis with a thin sclerotic margin and no periosteal reaction. The lesion is eccentric and extends into the metaphysis. MRI shows low signal on T1 and high signal on T2 with a fluid-fluid level. Serum calcium is elevated. What is the most likely diagnosis?

Explanation

## Diagnosis: Giant Cell Tumor of Bone **Key Point:** Giant cell tumor (GCT) of bone is a benign but locally aggressive lesion that characteristically occurs in the epiphysis of long bones in skeletally mature patients (20–40 years), with a predilection for the distal femur and proximal tibia, though it can occur in the proximal humerus. ### Clinical and Radiological Features | Feature | GCT | Osteosarcoma | ABC | Chondroblastoma | |---------|-----|--------------|-----|----------------| | **Age** | 20–40 years | 10–25 years | 10–30 years | 10–20 years | | **Location** | Epiphysis (post-fusion) | Metaphysis | Metaphysis/diaphysis | Epiphysis | | **Pattern** | Lytic, well-demarcated | Mixed lytic-sclerotic | Lytic with fluid-fluid level | Lytic with stippled calcification | | **Periosteum** | Intact or minimal | Sunburst/Codman | Minimal | Intact | | **Margins** | Thin sclerotic rim | Aggressive, indistinct | Thin rim | Well-defined | | **Extension** | Eccentric, extends to metaphysis | Metaphyseal | Metaphyseal | Confined to epiphysis | **High-Yield:** The combination of **epiphyseal location in a 20–40 year-old with a well-demarcated lytic lesion and thin sclerotic margin** is pathognomonic for GCT. ### Imaging Characteristics **Plain Radiographs:** - Purely lytic lesion with thin sclerotic border - Eccentric location - Extends from epiphysis into metaphysis ("kissing" the articular surface) - No periosteal reaction (benign) - Well-circumscribed margins **MRI Findings:** - **Low signal on T1** (hemosiderin, fibrosis) - **High signal on T2** (cystic/hemorrhagic areas) - **Fluid-fluid levels** (hemorrhage and hemosiderin layering) — highly characteristic - No soft tissue mass (unlike malignant tumors) **Clinical Pearl:** The presence of a **fluid-fluid level on MRI** is a key finding that supports GCT, though it is not pathognomonic (also seen in aneurysmal bone cyst and osteosarcoma with hemorrhage). ### Pathology GCT is composed of: - Numerous multinucleated giant cells - Stromal fibroblasts - Hemosiderin-laden macrophages - Areas of hemorrhage and necrosis **Mnemonic: GIANT** — **G**iant cells, **I**ntermediate age (20–40), **A**ggressive locally, **N**ear articular surface (epiphysis), **T**hin sclerotic margin. ### Clinical Presentation - Pain and swelling (often chronic) - Hypercalcemia (from osteolytic activity and PTHrP production) - Pathological fracture possible - Recurrence rate ~10–15% after curettage [cite:Robbins 10e Ch 26; Helms CA Musculoskeletal Radiology 3e]