# Immunohistochemical Characterization of Feline Giant Cell Tumor of Bone (GCTb): What We Know and What We Can Learn from the Human Counterpart

## TL;DR

This study compares feline and human giant cell tumors of bone, revealing similar immunohistochemical features and highlighting the need for better diagnostic criteria in veterinary medicine.

## Contribution

The study provides the first immunohistochemical characterization of feline GCTb, showing similarities to the human form and emphasizing the importance of further research in veterinary medicine.

## Key findings

- Multinucleated giant cells in feline GCTb are positive for Iba1, TRAP, and RANK, indicating an osteoclastic origin.
- Mononuclear cells in feline GCTb show positivity for osteoblast markers like RUNX2, SATB2, and KPNA-2.
- Diagnostic criteria for GCTb in cats are currently lacking, but this study enhances understanding for improved diagnosis.

## Abstract

Giant cell tumor of bone (GCTb) is a benign tumor in human medicine, still, in veterinary medicine, where it is more commonly described in cats, its recognition and diagnosis are still a challenge. With this study, we provide new insights into the histological and immunohistochemical phenotype of the tumor, confirming similarity with the human tumor, and encouraging further studies on this neoplastic entity also in our pets.

Giant cell tumor of bone (GCTb), formerly also known as osteoclastoma, is a pathological entity that in veterinary medicine is still undefined and, probably, underdiagnosed. In humans, GCTb is recognized as a primary benign bone tumor, locally aggressive, with high local recurrence rates, with controversial histogenesis that can rarely progress or present as a malignant form. In pets, this tumor is still considered rare, though the possibility of underdiagnosis is significant. Hence, the aim of the present study is to provide a histological and immunohistochemical characterization of a small case series of presumptive feline GCTb, comparing our results to the data reported for the human counterpart. Searching our archive, we found, from 2010 to 2023, only three diagnosed cases of GCTb from domestic cats (felis catus). After diagnosis revision, the samples were submitted to immunohistochemistry for Iba1, TRAP, SATB2, RUNX2, RANK, karyopherin α2 (KPNA-2), and osteocalcin. Ki-67 index was also evaluated. Results showed that the multinucleated giant cells were positive for Iba1, TRAP, and RANK, accounting for their osteoclastic origin. On the other side, mononuclear cells were mostly positive for osteoblast markers such as RUNX2, SATB2, and KPNA-2, whereas tumor-associated macrophages showed positivity for Iba1. Hence, results on the cell types characterizing the feline GCTb were comparable to those described in the human form of the tumor. Currently, diagnostic criteria for GCTBs in cats and, in domestic animals more broadly, are still lacking. This study provides valuable data into the immunohistochemical characteristics of the cell populations in feline GCTBs, enhancing veterinarians’ and pathologists’ knowledge for its diagnosis, ultimately improving patient care. Larger case series, complete with follow-up information, molecular analyses for specific mutations, and imaging of both tumors and patients, are needed to improve identification and achieve greater sensitivity in diagnosing this unique tumor.