Denosumab Therapy Related Changes in Giant cell Tumor (Osteoclastoma) of Bone : A New Osteosarcoma Mimicker

Vol 4 | Issue 2 | July-Dec 2018 | Page 4-6 | Pradnya Manglekar, Sujit Joshi, Yogesh Panchwagh.


Authors: Pradnya Manglekar [1], Sujit Joshi [1], Yogesh Panchwagh [1].

[1] Dept. of Pathology Deenanath Mangeshkar Hospital and Research Centre, Pune
[2] Orthopaedic Oncology Clinic, Pune, India.

Address of Correspondence
Dr. Sujit Joshi,
Dept. of Pathology Deenanath Mangeshkar Hospital and Research Centre, Pune
Email: sujitjoshi30@gmail.com


Abstract

Objectives: Giant cell tumor (Osteoclastoma)of bone is locally aggressive osteolytic tumor. Denosumab–A monoclonal antibody against RANKL is recently being used to treat this tumor. We discuss histopathological changes occurring in giant cell tumor of bone after Denosumab treatment.
Method: A retrospective study of 12 cases from January 2014 to March 2018. All patients included were diagnosed as giant cell tumor (osteoclastoma) of bone on needle or open biopsy. Subsequently these patients received Denosumab therapy followed by surgical resection (extended curettage or wide excision). Histomorphological features after Denosumab therapy were evaluated in these specimens and compared with morphological features of prior biopsy samples.
Results: Needle or open biopsy samples studied prior to receiving Denosumab therapy showed typical morphological features of osteoclastoma i.e. presence of uniformly distributed osteoclastic cells and sheets of mononuclear stromal cells. No atypical mitoses or matrix production noted. Post Denosumab therapy resection specimens showed marked reduction in number of osteoclastic giant cells. There was predominance of mononuclear stromal cells along with abundant, irregular new bone (osteoid) formation with osteoid matrix deposition. Occasional mitotic activity was seen. Few foci of necrosis were noted.
Conclusion: Denosumab treatment causes significant giant cell depletion accompanied by abundant new bone formation separated by cellular stromal proliferation. These features bear very little resemblance to their pre-treatment counterparts and can mimic morphological features of osteosarcoma and other bone forming tumors. Hence, one should be aware of these changes so that a misdiagnosis of osteosarcoma can be avoided.
Keywords: Giant cell tumor (osteoclastoma), Denosumab, RANKL.


References

1. Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease.9th edition. Saunders Elsevier: Philadelphia; 2015. Chapter 26, Bones, Joints and Soft tissue tumors; p1179 – 1226.
2. Rosai J. Rosai and Ackerman’s Surgical Pathology. 10thedition. Elsevier Mosby: St.Louis, Missouri; 2011. Chapter 24, Bone and joints; p2013-2104.
3. Branstetter DG, Nelson SD, Manivel JC, Blay JY et al. Denosumab induces Tumor Reduction and Bone formation in Patients with Giant-Cell Tumor of Bone. Clin Cancer Res; 18(16); 4415-24.2012 AACR.
4. Singh AS, Chawla NS, Chawla SP. Giant-cell tumor of bone: treatment options and role of denosumab. Biologics: Targets and Therapy 2015;9, 69-74.
5. Huang L, Teng XY, Cheng YY, Lee KM, Kumta SM. Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts instromal tumour cells of giant cell tumour of bone. Bone 2004 Mar;34 (3):p393–401.
6. James IE, Dodds RA, Olivera DL, Nuttall ME, Gowen M. Human osteoclastoma-derived stromal cells: correlation of the ability to form mineralized nodules in vitro with formation of bone in vivo. J Bone Miner Res 1996 Oct;11 (10):1453–60.
7. Wojcik J, Rosenberg AE, Bredella MA, et al. Denosumab-treated giant cell tumor of bone exhibits morphologic overlap with malignant giant cell tumor of bone. Am J SurgPathol 2016 Jan; 40(1): 72-80.
8. Rekhi B, Verma V, Gulia A, et al. Clinicopathological features of a series of 27 cases of post-denosumab treated giant cell tumors ofbones: a single institutional experience at a tertiary cancer referralcentre, India. PatholOncol Res 2017 Jan; 23 (1): 157-64.
9. Chang-Che Wu, Pin-Pen Hsieh. Denosumab-Treated Giant Cell Tumor of the Bone Mimicking Low-Grade Central Osteosarcoma.Journal of Pathology and Translational Medicine 2018; 52: 133-135.


How to Cite this article: Manglekar P, Joshi S, Panchwagh Y. Denosumab Therapy Related Changes in Giant cell Tumor (Osteoclastoma) of Bone : A New Osteosarcoma Mimicker. Journal of Bone and Soft Tissue TumorsJuly-Dec 2018;4(2):4-6.


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