Transformation of Benign Giant Cell Tumor of Bone Into Epithelioid Angiosarcoma
In this article, we report a case of transformation of a benign giant cell tumor (GCT) of the calcaneus into an epithelioid angiosarcoma. The patient presented to our service in 2003 and was followed until 2014. Transformation occurred 11 years after curettage, cryotherapy, cementation, and a well-documented disease-free interval. Longitudinal radiographs, magnetic resonance imaging, and histopathology were evaluated by the same medical team.
There are only a few case reports and case series of malignancy associated with GCT of bone. To our knowledge, this case report is the first to describe an assessment of the transformation of a benign GCT of bone into an epithelioid angiosarcoma. Orthopedic surgeons, radiologists, oncologists, and pathologists should be aware of the potential for transformation of benign GCTs to high-grade sarcomas after a long disease-free interval.
A postoperative splint was placed, and weight-bearing progressed over 6 weeks. The patient was followed at 2- to 3-month intervals over the first 5 postoperative years. She was able to work and perform activities of daily living, but her postoperative course was complicated by significant chronic pain in multiple extremities and long-term treatment by the chronic pain service. At no time did postoperative imaging—magnetic resonance imaging (MRI) at 6 years, whole-body bone scan at 7 years, plain radiographs at 10 years—show evidence of recurrence.
Radiographs showed stable postoperative changes with a small radiolucent area (with sclerotic rim) surrounding the cement-bone interface. Given its proximity to the Achilles tendon and more motion than usual at the wound site, the radiolucency likely was caused by small movements of the interface. The radiolucent area remained stable over a 15-month period.
Whole-body bone scan showed a small area of osteoblastic activity in the left calcaneus, consistent with inflammation surrounding the bone- cement interface, but the uptake was minor relative to other areas of signal, and there were no significant inflammatory reactive changes on MRI (Figures 3A, 3B).
Over 11 years, regular 6- to 12-month follow-up examinations revealed no significant changes in the left foot or in plain radiographs of the chest. In addition, physical examinations revealed no evidence of a palpable mass of the left foot.
In July 2014 (11 years after curettage and cementation), the patient presented to her pain clinic appointment with severe left foot pain. She said that, over a few weeks, she experienced a significant increase in pain and developed posterolateral foot swelling, which limited her ability to ambulate. Plain radiographs showed a significant soft-tissue prominence around the posterior calcaneus, increased lucency around the bone-cement interface in the calcaneus with elevation, and a cortical break of the superior margin of the posterior calcaneus (Figures 3C, 3D). MRI showed a large lobular mass in the calcaneus and surrounding soft tissue with T1 and T2 signal heterogeneity and enhancement after administration of gadolinium (Figures 4A-4D). There was a large extraosseous extension of the calcaneus-based mass laterally and superiorly with edema in the surrounding hindfoot region (Figure 4).
Physical examination revealed exquisite tenderness along the lateral and posterior aspects of the left hindfoot. The patient was unable to bear weight and had soft-tissue swelling throughout the foot and mid calf as well as a palpable mass in the posterior heel. She was otherwise neurovascularly intact through all distributions of the left lower extremity. It was unclear if the GCT of the calcaneus had recurred or if there was a new, secondary tumor. Given her severe pain and morbidity, the patient decided to proceed with open biopsy and a pathology-pending plan for possible amputation in the near future.
In August 2014, an open biopsy with intraoperative frozen evaluation yielded a diagnosis of malignant neoplasm not otherwise specified. Permanent sections showed a proliferation of malignant epithelioid cells with extensive necrosis, hemorrhage, and hemosiderin deposition but no multinucleated giant cells.
Transformation of the GCT into a high-grade epithelioid angiosarcoma prompted presentation of the patient’s case to a multidisciplinary board of physicians with a focused clinical practice in sarcoma management. The board included board-certified specialists in orthopedic oncology, pathology, musculoskeletal radiology, medical oncology, and radiation oncology. Although discussion included pre-resection use of neoadjuvant chemotherapy to evaluate for disease response, the patient’s severe pain led her to forgo this treatment and proceed directly to below-knee amputation.
Amputation revealed a 7.7-cm hemorrhagic necrotic mass composed of a highly cellular spindle and epithelioid malignancy with abundant hemosiderin deposition (Figure 5). In addition, several atypical mitotic figures and malignant multinucleated tumor giant cells were randomly scattered throughout the neoplasm.
At first follow-up, the patient reported significant pain relief and asked to begin titrating off her chronic pain medicine. Clinical staging, which involved performing whole-body positron emission tomography/computed tomography, revealed nothing concerning for metastases. When this report was being written, the patient was being monitored for recurrent disease in accordance with National Comprehensive Cancer Network guidelines. In the absence of residual sarcoma, our medical oncology team discussed adjuvant chemotherapy options with her. Subsequently, however, she proceeded only with observation and periodic imaging.
