Diagnosis of giant cell-rich bone tumors on core needle biopsy: A practical approach

Background: The differential diagnosis of giant cell-rich bone tumors comprises a broad spectrum of lesions with prominent reactive osteoclast-like and/or neoplastic giant cells, with substantial differences in biologic behavior and clinical management. Evaluation of giant cell-rich bone tumors on small biopsies can be challenging especially in specimens with limited representative material. An accurate diagnosis requires a high level of skill on the part of both radiologist and pathologist as correlation with clinical and radiologic characteristics is critical. The objective of the study was to assess the utility of touch preparations (TP), immunohistochemistry (IHC) for mutation-specific markers H3G34W and H3K36M, and fluorescence in situ hybridization (FISH) for USP6 rearrangements and MDM2 amplification in the diagnostic workup of core needle biopsy specimens. Methods: A total of 27 core needle biopsies with TPs from patients with primary giant cell-rich bone tumors (16 giant cell tumors of bone (GCTBs) (including 3 with lung metastasis), 3 chondroblastomas (CBs), 4 primary aneurysmal bone cysts (ABCs), 2 non-ossifying fibromas (NOFs), 1 low grade osteosarcoma (OS), and 1 conventional OS with tumor giant cells were analyzed with IHC for H3G34W and H3K36M and in select cases FISH for USP6 rearrangements and MDM2 amplification. Results: In all cases the core biopsies were sufficient for histologic examination and diagnostic workup. 16 of 16 GCTBs were positive for H3G34W and negative for H3K36M, and 3 of 3 CBs were positive for H3K36M and negative for H3G34W. All other cases were negative for H3G34W and H3K36M. 4 of 4 primary ABCs showed rearrangement of USP6 by FISH and the low grade OS showed amplification of MDM2 by FISH. Conclusions: On-site adequacy assessment of TPs proved to be an accurate, simple, and fast method for obtaining sufficient material for complete diagnostic workup. The application of IHC for H3G34W and H3K36M and FISH for detection of rearrangements of USP6 and amplification of MDM2 can improve the diagnostic accuracy in core needle biopsy specimens.