Advanced therapeutic strategy for radiation-induced osteosarcoma in the skull base: a case report and review

Abstract

A review of patients with skull base osteosarcoma secondary to radiation (radiation-induced osteosarcoma: RIOS) of the pituitary tumor shows the mean survival of approximately 7 months (2 weeks-16 months). This warning prognosis seems to stem from two factors, 1) the anatomical complexity of the skull base for total resection of the tumor, and 2) standard adjuvant therapies for the tumor yet to be established. Contrary to the general belief, the authors report an unusually long survival of a 75-year-old woman with a history of osteosarcoma that developed in the same sequence 20 years after pituitary tumor radiation. On her recent admission, she complained of frontal headaches and MRI studies showed a tumor in the sphenoid sinus. Endoscopic trans-nasal tumor removal allowed for histological diagnosis of an osteosarcoma. However, further rapid tumor growth necessitated a radical tumor resection followed by a combined chemotherapy with ifosfamide, cisplatin, and etoposide (ICE). Despite temporary suppression of the tumor growth, the chemotherapy was discontinued due to severe pancytopenia that occurred after three courses of treatment. Shortly after the discontinuation of ICE therapy, the tumor size increased again rapidly, requiring a novel radiation therapy, Cyber-knife treatment. Following this radiation, the tumor growth was arrested, and the patient remains healthy without neurological symptoms over 24 months. The outcome of Cyber-knife in this case suggests that this specific therapy must be considered for the unresectable skull base RIOS.

Figure 1

Before and after the first tumor resection. A. MRI shows an enhanced mass in the sphenoid sinus. The tumor extends into both cavernous sinuses surrounding internal carotid arteries. The pituitary gland and stalk are clearly identified (white arrow), and there is no tumor invasion in the sellaturcica. B. The photo shows a trans-nasal endoscopic view of the tumor. The anterior wall of sphenoid sinus is absent, and a whitish tumor (black arrow) is seen through the nasal cavity. The tumor was elastic and bled easily. There is no tumor invasion in the dura mater in the sellaturcica (black arrowhead). C. The tumor in the sphenoid sinus was totally removed; however, residual tumor is noted in cavernous sinuses (white arrowheads).

Figure 2

Histological findings. A: a. Hematoxylin and eosin staining shows condensed tumor cells with pleomorphism, and depositions of osseous tissue are recognized. b. Vimentin was strongly positive. c. Anti-cytokeratin (CAM 5.2) staining is negative, indicative of no malignancy of squamous epithelium. d. Ki-67 scoring (MIB-1 index) is extremely high at 20%. B: The tumor tissue, resected from the patient 20 years ago, consists of typical pituitary adenoma cells, which are entirely different from the pathological features identified in A.

Figure 3

Recurrence of the tumor. A. Four months after the first surgery, MRI demonstrates rapid regrowth of the tumor filling sphenoid and ethmoid sinuses and nasal cavity. B. A residual tumor is seen in the cavernous sinuses after massive tumor resection.

Figure 4

After chemotherapy and cyber-knife treatment. A. Tumor regrowth is noted after discontinuation of ICE chemotherapy on MRI. B. The cavernous sinus portion of the tumor is noted after the third tumor resection. C. No obvious tumor recurrence is identified seven months after cyber-knife radiation.