Pseudosarcomatous changes in Denosumab treated giant cell tumor of the bone;
a diagnostic pitfall
Suhair Al Salihi, MD1; Josh Showalter, MD1; Marylee Kott, MD1; Jaiyeola Thomas, MD1; and Michael Covinsky, MD1
1- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, McGovern Medical School.
Texas
Background
Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels
of receptor activator of nuclear factor k-B ligand (RANKL). We report here a case of pseudosarcomatous evolution in a GCT treated with Denosumab, a RANKL inhibitor, to illustrate the diagnostic issues that raise
concern for malignancy, and the difficulties in histological assessment of a treated giant cell tumor of bone, that may mimic osteosarcoma.
Discussion
Materials and Methods
• A 38 year old female presented with a 3-month history of left
wrist swelling.
• Initial magnetic resonance imaging showed heterogeneous
enhancement of the mass (8.5 x 7.1 x 6.1 cm) that displaced
the ulnar nerve, median nerve and tendons without
encasement.
• Initial biopsy showed classical features of GCT.
• Denosumab therapy was initiated to induce tumor size
reduction, and to facilitate second-step surgical excision.
• A 3-month therapy regimen was instituted and a significant
response on radiographs with formation of new bone was
identified. Surgical en bloc resection with reconstruction was
performed thereafter.
Fig 1
Fig: 1 & 2: The gross images show the mass at the distal radius. The mass is abutting
the cortical surfaces
Results
• Gross examination showed a tumor that expanded and filled the
distal radius epiphysis and a portion of the metaphysis. The
lesion appeared to abut the majority of the cortical surfaces of
the bone however did not appear to penetrate through the
cortical bone.
• On histological evaluation, no area reminiscent of classical GCT
was observed. In particular, there were no giant cells. Additional
osteoid deposition mimicked high-grade osteosarcoma;
however, no atypical mitotic figures were seen, the total mitotic
rate was low, osteoid did not show the classical lace-like
pericellular deposition characteristic of high-grade
osteosarcoma, and the tumor remained intra-osseous and was
rimmed by periosteum and reactive new bone.
• Taking in consideration the radiographic findings of stable tumor
size combined with a review of the literature a diagnosis of GCT
with treatment effect was rendered.
• Denosumab, a RANKL inhibitor, which is clinically used to treat
GCT, leads to a marked alteration in the histologic appearance
of the tumor with giant cell depletion and new bone deposition,
leading to substantial histologic overlap with other primary
tumors of bone.
• In the literature rare cases have been described as sarcoma
arising in giant cell tumor of bone treated with Denosumab;
however, the radiographic and histologic findings do not support
the sarcomatous transformation in our case.
• This case illustrates the difficulties in histological assessment of
a treated GCT, resected early in the course of therapy. An initial
phase of highly cellular proliferation and immature bone
overgrowth may mimic malignant transformation.
• Histological findings after short duration Denosumab treatment
should be interpreted with caution, with specific emphasis on
absolute criteria of malignancy.
References
Fig 3
Fig 4
Fig: 3 & 4: Low and high power views show spindle cells proliferation with no giant cells
seen. H&E 4X, 10X
Fig: 5 & 6: Medium & high power views show spindle cells with mild atypia and osteoid
deposition with occasional mitotic figures. H&E 10X, 20X
1. Xu S.F, Adams B, Yu X.C, Xu M. Denosumab and giant cell tumour of bone-a
review and future management considerations. Current Oncology. 2013 Oct.
20(5):442-7.
2. Polgreen L E, Ogilvie C, Manivel J C, Skubitz K M, Lipsitz E. Denosumab
Treatment of Metastatic Giant-Cell Tumor of Bone in a 10-Year-Old Girl. Journal
of Clinical Oncology. 2013 April 31(12): 200-2.
3. Singh A S, Chawla N S, Chawla S P. Giant-cell tumor of bone: treatment options
and role of denosumab. Biologics: Targets and Therapy. 2015:9 69–74.
4. Yamagishi et al. Bone formation in metastasis of giant-cell tumor following
Denosumab treatment. Oncology Letters. 2016 11: 243-246.
5. Wojcik et al. Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic
Overlap With Malignant Giant Cell Tumor of Bone. Am J Surg Pathol 2016 Jan.
40:72–80.
6. Broehm C J et al. Two cases of sarcoma arising in giant cell tumor of
bonetreated with Denosumab. Case Reports in Medicine. 2015, Article ID
767198, 1-6. http://dx.doi.org/10.1155/2015/767198