Propensity for Hemorrhagic Presentation of Skull Base Chondrosarcoma in Patients with Ollier Disease and Maffucci Syndrome

Background: While genetic tumor predisposition syndromes may produce histologically identical tumors to their sporadic counterparts, syndromic forms often manifest more diverse and aggressive clinical behavior. Patients with Ollier disease and Maffucci syndrome harbor point mutations in IDH1 or IDH2 genes and develop benign cartilaginous growths called enchondromas. These patients are also predisposed to develop chondrosarcomas, which are thought to arise as a result of malignant transformation of a precursor enchondroma. Given the rarity of Ollier disease and Maffucci syndrome, comparison between syndromic and sporadic forms of skull base chondrosarcoma has not yet been reported.

Methods: We performed a retrospective analysis of patients treated for skull base chondrosarcoma at the University of Pittsburgh from 2004 to 2018, which included 72 operations in 43 patients. Out of these 43 patients, one had Ollier disease and two had Maffucci syndrome.

Results: Two of the three patients with syndromic forms of chondrosarcoma presented with tumor hemorrhage causing symptomatic brainstem compression and cranial neuropathy. In contrast, none of the 40 patients with sporadic chondrosarcomas had evidence of hemorrhage on MRI or CT scans. There was a statistically significant relationship between Ollier disease/Maffucci syndrome and hemorrhagic tumor presentation (p <  0.0033, Fisher’s exact test).

The first patient presented with hemiplegia and multiple cranial neuropathies and was treated with an endoscopic endonasal transpetroclival approach for near total resection of the tumor and hematoma, followed by proton beam radiotherapy. She was last seen 6 years after her surgery and had good recovery of her right-sided strength with no evidence of tumor recurrence.

The second patient presented with obtundation and a large posterior fossa hematoma. She was taken for an emergent far lateral suboccipital craniectomy for tumor and hematoma resection. After a recovery phase, she underwent a second-stage endoscopic endonasal transpetroclival approach to resect the ventral component followed by Gamma knife radiosurgery. She was seen at eight years followup with only mild facial numbness.

Interestingly, histopathology from all three patients with Ollier disease and Maffucci syndrome revealed grade I conventional chondrosarcoma, with no evidence of aggressive features or increased vascularity. None received radiation prior to their hemorrhage, and none had evidence of metastasis. We hypothesize that the mutation in the IDH1/2 gene that underlies Ollier disease and Maffucci syndrome predisposes these patients to a more aggressive form of skull base chondrosarcoma with a higher risk of hemorrhagic presentation.

Fig. 1 Patient 1 (Ollier disease) presented with hemiplegia, cranial neuropathy and large left petroclival chondrosarcoma (A, B) with hemorrhage compressing the pons (C). She underwent an endoscopic endonasal transpetroclival approach for a near-total resection (D, E, F).

Fig. 2 Patient 2 (Maffucci syndrome) presented with obtundation and large posterior fossa hematoma (A) and tumor outlined on CT-angiography (B) with middle and posterior fossa components centered at the left petroclival junction. She underwent a far lateral approach for resection of the posterior fossa component and hemorrhage (C), followed by a second stage endoscopic endonasal transpetroclival approach for near total resection (D).