Unusual Histopathological Challenges in Diagnosis of Giant Cell Tumor Cases Treated with Neoadjuvant Denosumab Chemotherapy: A Rare Case Report.

Introduction: Giant cell tumor of bone (GCTB) is a rare yet locally aggressive neoplasm primarily affecting young adults. Its hallmark features include multinucleated osteoclast-type giant cells and mononuclear tumor cells. Treatment with denosumab, an anti-RANK ligand antibody, has shown efficacy, but it alters histomorphology, posing diagnostic challenges. Co-occurrence with achondroplasia, though rare, warrants consideration in bone lesion evaluations. Case Report: A 30-year-old male with achondroplasia presented with a proximal femur GCT, a rare association. Neoadjuvant denosumab was administered due to thin tumor cortex and cortical breech. Surgical excision with bone cement filling and Philo's plate supplementation was performed. Histopathological examination post-treatment revealed the absence of osteoclast-type giant cells, extensive necrosis, hyalinization, and mononuclear infiltrates. Discussion: Denosumab induces a reduction in osteoclast numbers, causing tumor shrinkage and sclerosis, while altering typical GCT histology. Similar findings were noted in the literature, including stromal changes like spindle-shaped cells, inflammation, vascular proliferation, and hemosiderin-laden foamy macrophages. Recognition of these alterations is crucial for accurate diagnosis. Conclusion: GCT, though rare, presents distinct histopathological features aiding diagnosis. Denosumab treatment modifies tumor morphology, necessitating thorough clinical evaluation for accurate diagnosis post-treatment. Understanding, these challenges is essential for optimal management of GCT cases.