Enchondroma of the skull base secondary to generalized enchondromatosis: a case report and review of the literature.
Generalized enchondromatosis, of which Ollier disease is the most common type, is a rare bone dysplasia characterized by multiple intraosseous tumors near growth-plate cartilage. These cartilaginous tumors have a propensity to transform into chondrosarcomas. Enchondromas of the skull base are exceedingly rare. We present the case of a patient with generalized enchondromatosis who developed a large enchondroma of the clivus, and we discuss the clinical presentation and potential treatments for this entity.
Generalized enchondromatosis is a rare bone dysplasia that is characterized by multiple intraosseous tumors near growth-plate cartilage. These tumors can cause skeletal deformities, including limb-length discrepancy, and they may undergo malignant transformation into chondrosarcoma. (1,2) We describe the case of a patient with an extremely rare form of generalized enchondromatosis who presented with an enchondroma of the clivus.
A 15-year-old girl with a history of generalized enchondromatosis presented to her pediatrician with a mass in her left parotid gland. As part of the workup, a plain film of the temporomandibular joint showed amorphous, flocculent densities in the central skull base (figure 1). Magnetic resonance imaging (MRI) of the skull base in the long, transverse, and anteroposterior views detected a 5.4 x 4.8 x 5-cm heterogeneously enhancing mass arising from the sphenoid bone (figure 2). The lesion extended distally to the spheno-occipital synchondrosis, anteriorly into the nasopharynx, and superiorly into the suprasellar cistern. An associated mass effect was seen on the surrounding vessels; this effect included displacement of the carotid arteries and anterior circulation. Also noted were a partial obliteration and superior displacement of the third ventricle and some impingement onto the prepontine cistern. Positron-emission tomography/ computed tomography revealed no focal metabolically active skeletal lesion.
The patient denied headaches, vision changes, diplopia, facial numbness or weakness, dysphagia, and weight loss. Her surgical history was significant for excision of a right nasal cavity enchondroma for nasal obstruction, spine fusion, debulking of an extensive left shoulder enchondroma, and multiple foot surgeries.
Pertinent findings on physical examination included an unrelated 3-cm firm mass of the left parotid gland and normal cranial nerve function. Also noted was a rhizomelic and mesomelic shortening of all extremities with palpable osseous deformities secondary to enchondromas, especially of the shoulders, hands, and lower extremities. The hands and fingers were diffusely enlarged secondary to enchondromas (figure 3). No cutaneous hemangiomas were present.
Intraoperative rigid nasal endoscopy found no obvious mass, and biopsies of the nasopharynx revealed only adenoid tissue. Image-guided transnasal biopsy of the mass was performed and sent to the Armed Forces Institute of Pathology, where the lesion was identified as an enchondroma with atypical features that were suspicious for early malignant transformation, possibly a low-grade chondrosarcoma. A left parotidectomy was also performed, and the final pathology was consistent with acinic cell carcinoma with positive margins. Radiotherapy was administered to the positive margins.
An enchondroma is an intraosseous, usually benign tumor that develops in proximity to growth-plate cartilage. When multiple enchondromas are present in a single patient, the condition is called generalized enchondromatosis. If a patient demonstrates soft-tissue hemangiomas in addition to multiple enchondromas, the condition is called Maffucci syndrome.
The most common type of enchondromatosis is Ollier disease, a disorder characterized by multiple enchondromas arising in tubular and flat bones and sparing the skull and spine. A classification of the enchondromatoses has been delineated. (1) We believe that our patient had cheirospondyloenchondromatosis, which is an exceptionally severe and rare type of generalized enchondromatosis with spine involvement.
The exact cause of generalized enchondromatosis remains unknown. The PTHR1 gene-signaling pathway plays a critical role in the regulation of endochondral ossification. Recent research has identified a functionally deleterious mutation in the PTHR1 gene in the enchondromas of several patients with Oilier disease and Maffucci syndrome. (3) However, it is not yet clear whether enchondromatosis results from a single gene defect or from combinations of germ-line and somatic mutations.
[FIGURE 1 OMITTED]
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A recent genomic analysis of 28 patients with Oilier disease found no common genomic alterations, suggesting that small deletions, point mutations, or epigenetic mechanisms contribute to the development of the disease. (4) The disease is usually sporadic.
Skull base and intracranial cartilaginous tumors are rare. When they do occur, they usually arise from cartilaginous rests in the base of the skull, especially around the basal synchondroses. Imagawa et al reported an enchondroma in the left middle cranial fossa of a patient with generalized enchondromatosis. (5)
The natural history of chondroid skull base lesions remains unknown. Schmidinger et al published a case report in which they followed a patient with a skull base chondroid lesion with MRI for more than 12 years, and the only associated symptom they noted was a mild, nonprogressive abducens palsy. (6)
Obviously, the lesion in our patient had grown extensively to compress the surrounding brain and carotid arteries. This finding, and the fact that the mass could have represented a chondrosarcoma, necessitated intraoperative tissue biopsy.
The enchondromas in patients with generalized enchondromatosis exhibit a tendency to undergo malignant transformation into chondrosarcomas. The choice of treatment for these enchondromas and/or low-grade chondrosarcomas depends on their location. Curettage and adjuvant cryosurgery with liquid nitrogen has recently yielded excellent oncologic and functional results in lesions of the peripheral skeleton. (7) However, this method of surgery seems to be unrealistic for a lesion in the clivus. Our patient's lesion had already compressed the third ventricle and carotid arteries.
Photon and proton therapies are currently being evaluated for the treatment of primary bony malignancies of the skull base and cervical canal in children. The rapid decrease in dose at the end of the proton beam makes proton therapy a good option for skull base chondromas and chondrosarcomas. (8) A recent study revealed excellent local control with minimal long-term toxicity in children with low-grade chondrosarcomas or aggressive chondromas that were treated with high-dose combined fractionated photon-proton therapy. (9)
The parotid acinic cell carcinoma in our patient seemed to be unrelated to her generalized enchondromatosis. Our review of the literature found no association of parotid tumors with enchondromatosis. In a case report, Jaehne et al described the case of a 79-year-old man with generalized enchondromatosis and a parotid gland chondrosarcoma that metastasized from his left femoral bone; he was successfully treated with a superficial parotidectomy. (2) Our patient underwent radiation therapy for her positive margins.
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In conclusion, generalized enchondromatosis is a rare disorder characterized by multiple enchondromas throughout the body. These enchondromas can originate from the skull base, and they have a propensity for malignant transformation into chondrosarcomas. Enchondromas and chondrosarcomas of the skull base present a unique challenge to surgeons and oncologists.
(1.) Bhargava R, Leonard NJ, Chan AK, Spranger J. Autosomal dominant inheritance of spondyloenchondrodysplasia. Am J Med Genet A 2005;135(3):282-8.
(2.) Jaehne M, Jakel KT, Ussmuller J. First report of parotid gland metastasis in multiple enchondromatosis with secondary CHOSA (G-III). Eur Arch Otorhinolaryngol 2002;259(3):142-5.
(3.) Couvineau A, Wouters V, Bertrand G, et al. PTHR1 mutations associated with Oilier disease result in receptor loss of function. Hum Mol Genet 2008;I 7(18):2766-75.
(4.) Pansuriya TC, Oosting J, Krenacs T, et al. Genome-wide analysis of Ollier disease: Is it all in the genes? Orphanet J Rare Dis 2011;6:2.
(5.) Imagawa K, Toda I, Hayashi M, et al. A case of enchondroma of the skull base--a manifestation of generalized chondromatosis [in Japanese]. No Shinkei Geka 1977;5(5):457-63.
(6.) Schmidinger A, Rosahl SK, Vorkapic P, Samii M. Natural history of chondroid skull base lesions--case report and review. Neuroradiology 2002;44(3):268-71.
(7.) van der Geest IC, de Valk MH, de Rooy JW, et al. Oncological and functional results of cryosurgical therapy of enchondromas and chondrosarcomas grade 1. J Surg Oncol 2008;98(6):421-6.
(8.) DeLaney TF. Proton beam therapy in the management of bone and soft tissue sarcomas. Curr Opin Orthop 2002;13(6):434-9.
(9.) Habrand JL, Schneider R, Alapetite C, et al. Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies. Int J Radiat Oncol Biol Phys 2008;71(3):672-5.
Derek J. Rogers, MD; Mark E. Boseley, MD; Mark J. Stephan, MD; Samuel Browd, MD, PhD; David C. Semerad, MD
From the Division of Otolaryngology, Dwight David Eisenhower Army Medical Center, Augusta, Ga. (Dr. Rogers); the Division of Pediatric Otolaryngology (Dr. Boseley), the Division of Pediatrics and Dysmorphology (Dr. Stephan), and the Department of Radiology (Dr. Semerad), Madigan Army Medical Center, Tacoma, Wash.; and the Division of Pediatric Neurosurgery, Seattle Children's Hospital (Dr. Browd). The case described in this article occurred at the Madigan Army Medical Center.
Corresponding author: Derek I. Rogers, MD, Division of Otolaryngology, Dwight David Eisenhower Army Medical Center, 300 Hospital Rd., Augusta, GA 30905. Email: Derek.John.Rogers@us.army.mil
Disclaimer: The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of Defense or the Department of the Army.
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|Title Annotation:||ORIGINAL ARTICLE|
|Author:||Rogers, Derek J.; Boseley, Mark E.; Stephan, Mark J.; Browd, Samuel; Semerad, David C.|
|Publication:||Ear, Nose and Throat Journal|
|Article Type:||Case study|
|Date:||Nov 1, 2011|
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