Introduction
Giant cell tumor of bone (GCTB) are generally localized at the epiphysis of long bones and are characterized by regional progressive and destructive lesions. GCTs of bone are commonly benign neoplasms but they have malignant potential and the capacity to metastasis (1,2). The first line treatment strategy for GCTBs is surgical resection and other alternatives are localized radiotherapy or chemotherapy. The mainstay molecular pathology of GCTB has been discovered recently in that GCTB overexpress receptors activator of nuclear factor-kappa B (RANK) and its ligand (RANKL) in stromal cells. This interaction causes bone resorption due to the activation of osteoclasts. Denosumab, a monoclonal humanized antibody to RANKL, block RANK-RANKL interaction, has been reported as curative in some patients over 12 years old (3). A newborn presented with GCT of the occipital bone and was treated with chemotherapy and we concluded that chemotherapy is a successful alternative strategy when surgical resection, radiotherapy, and other therapies are not applicable for GCTBs.
Case Report
A male baby weighing 3.6 kg at birth and delivered via C-section at the 39th week of pregnancy presented at our hospital on his 10th day of life suffering from persistent vomiting. Cranial magnetic resonance imaging (CMRI) was performed to evaluate his condition and a “suspected 4x3 cm bone-derived malignant-looking mass at the left posterior fossa” was noted (Figure I). Surgical resection was not possible because of the location of the mass, especially its proximity to major blood vessels. The biopsy showed spindle cells with pleomorphic cells and a variable proliferation index with some areas as high as 20% as demonstrated by Ki-67 staining. Given this information, the presence of giant cell areas and spindle cell areas containing necrosis indicated a grade 1-2 GCT according to the classification by Jaffe et al. (4). Metastasis was not observed in computed tomography of the thorax. Loss of hearing in the left ear was determined via brainstem auditory evoked potential (BAEP) and was probably due to the mass. The patient was not suitable for surgery or radiotherapy, but chemotherapy was the one strategy available in this particular case. The chemotherapy regimen consisted of cisplatin 1 mg/kg/day (1-3 days) and doxorubicin 1 mg/kg/day (1,2 days) and was applied four times monthly. Using MRI, we noted complete regression after four sessions. The patient was given regular follow-ups with no evidence of recurrence or co-morbidity over the next 60 months. The CMRI showed no residual mass at posterior fossa at the 60th month after chemotherapy (Figure II a,b,c,d). Bilateral BAEP has proven normal as has his general neurological and mental development during this time with his motor functions and speech as well as his emotional and cognitive abilities testing appropriate to his age. Informed consent was received from family.
Discussion
Pain is the leading symptom when GCTB is localized in the long bones but neurologic symptoms or failures are revealed when GCTB is present in the skull. Unfortunately, various benign or malignant tumors may be confused with GCTB (3). Histological examination of GCTB shows a heterogeneous tumor occurring in stromal cells and multinucleated giant cells with over-expressed RANK and RANKL (2,4). The preferred treatment of GCTB is resection with surgery or extended intralesional curettage, but this is not always suitable given the location and size of the tumor. Radiotherapy has been used as a treatment option in combination with surgery or chemotherapy for GCTBs, but this carries the risk of malignant transformation, local recurrence and some side effects (1,2).
Table I lists the pediatric cases of GCTB in the skull reported in the literature since 2000. They are mostly adolescents with base of the skull treated with surgical intervention, radiation or embolization (5-10). Our case was one of the youngest patients described in the literature. Treatment is determined by location and age. The location of the mass and patient’s age prohibited us from performing wide resection, radiotherapy or using denosumab in this case. Conventional chemotherapy was used following an informed consensus between the physician and the infant’s family. The patient has had no recurrence or co-morbidity, nor was any toxicity as a result of chemotherapy detected over five years of follow-up.
Although the pathology prognosis in our case was not completely compatible with malignant (grade 3) GCTB according to the classification by Jaffe et al. (4) the chemotherapy response has led us to believe that that the mass would have become malignant. We recommend chemotherapy as a successful option for treating GCTB if other strategies are not possible or suitable.
Ethics
Informed Consent: Informed consent was received from family.
Peer-review: Externally and internally peer-reviewed.
Authotship Contributions
Surgical and Medical Practices: E.T., B.D., Ş.Ç., T.T., B.D., Design: E.T., B.D., Data collection or Processing: E.T., B.D., Analyses or Interpretration: E.T., B.D., Literature Search: E.T., B.D., Writing: E.T., B.D.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.
