Lesion presenting as an expanding mass of the palate

Vol. 113 No. 4 April 2012

CLINICOPATHOLOGIC CONFERENCE

Lesion presenting as an expanding mass of the palate Johnson C. Miin, DDS, MSE,a Harry V. Precheur, DMD,b and Sigurd O. Krolls, DDS, MS, MSEd,c Jackson, Mississippi UNIVERSITY OF MISSISSIPPI MEDICAL CENTER

(Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:442-447)

The patient was a 57-year-old African American woman who was referred from her general dentist for evaluation of a large soft tissue mass of the hard palate and a chief complaint of pain and “bleeding gums.” The patient reported a lesion that had slowly increased in size for the preceding 6 months. The patient reported a past medical history of congestive heart failure, hypertension, seizure disorder, and multiple surgeries for a brain tumor. Her medications were potassium chloride 20 mEq twice a day, furosemide 80 mg twice a day, lisinopril 15 mg every day, famotidine 20 mg every day, digoxin 0.125 mg every day, prednisone 10 mg every day, atorvastatin 10 mg every day, conjugated estrogen 0.625 mg every day, carbamazepine 40 mg twice a day, ferrous sulfate 325 mg twice a day, levothyroxine 150 ␮g every day, fluoxetine 20 mg every day, cyproheptadine 4 mg every day, vitamin D, and calcium. Her family history included hypertension, diabetes, and heart disease. She denied any history of tobacco, alcohol, or drug use. Review of systems revealed loss of vision in the left eye and occasional gingival bleeding. She denied having any fevers or chills. Physical examination revealed a 66.6-kg woman with stable vital signs, afebrile, alert, and oriented to person, place, and time. Her general appearance was unremarkable with the exception of noticeable difficulty in articulating words because of the intraoral mass. Examination of her head, face, and neck revealed left-sided ophthalmoplegia, anisocoria, and a left pupil a

Oral and Maxillofacial Surgery Resident, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Mississippi Medical Center. b Associate Professor and Chairman, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Mississippi Medical Center. c Professor Emeritus, Department of Oral and Maxillofacial Surgery and Pathology, School of Dentistry, University of Mississippi Medical Center. Received for publication Oct 9, 2010; returned for revision Aug 11, 2011; accepted for publication Aug 30, 2011. Published by Elsevier Inc. 2212-4403/$ - see front matter doi:10.1016/j.oooo.2011.08.013

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nonreactive to light. All other cranial nerves were intact. Intraoral examination revealed a large (35 ⫻ 45mm), broad-based, exophytic, firm, nonpulsatile, tender but not painful mass covered by keratinized palatal mucosa with normal pigmentation and texture (Figure 1). There were no obvious carious lesions detected, with the exception of the maxillary left first molar (#14). An orthopantomogram revealed fixation plates in the area of the left zygoma but was not of sufficient diagnostic quality to identify any pathosis (Figure 2).

DIFFERENTIAL DIAGNOSIS The clinical features of a large, exophytic, firm lesion of the hard palate, absent any radiographic pathosis, were highly suggestive of a soft tissue lesion. Our first impression was an inflammatory process resulting from a large carious lesion on #14. The patient denied most of the classical symptoms associated with an inflammatory process: calor (heat), dolor (pain), rubor (redness), and tumor (swelling). The patient reported no fevers or chills, mild tenderness of the lesion but no pain, asymptomatic tooth #14, and no erythema. Aspiration of the lesion yielded no purulence or aspirate. Tooth #14 was most likely not the etiology of this lesion. Other palatal lesions associated with inflammatory processes are brown tumors arising from excess osteoclastic activity in patients with primary or secondary hyperparathyroidism. Considerations for developmental lesions with similar clinical features aforementioned are usually fissural cysts that include the nasopalatine duct cyst and the median palatal cyst. These cysts are true cystic lesions that contain fluid or semisolid material and are present on the midline of the palate. It is believed the origin of a median palatal cyst is the same as nasopalatine duct cysts. They develop from embryonic remnants of nasopalatine duct epithelium within the nasopalatine canal; however, these would present as bony pathosis, which is not evident in this case. Neoplastic lesions of the palate can be divided into 2 main categories: benign and malignant. Benign lesions of the palate are most commonly associated with minor salivary glands. Pleomorphic adenomas are the most

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Fig. 1. A soft tissue lesion occupying the entire palatal vault. In the lateral dimension, it extends from the left molar to right molar. In the anterior-posterior dimension, it extends from the lingual aspect of the maxillary incisors to the soft/hard palate boundary. Image is available in color at www.ooooe.net.

common benign lesions of the palate. They account for nearly half of all minor salivary gland neoplasms, and more than half occur on the palate. Other considerations for benign neoplastic lesions of the palate are histiocytoma, schwannoma, neurofibroma, and leiomyoma. Malignant lesions of this size on the palate usually originate from epithelial or mesenchymal cells. Malignant epithelial lesions that may appear as a large swelling of the palate with minimal symptoms are squamous cell carcinoma of the maxillary sinus or mucoepidermoid carcinoma. Other malignant lesions for consideration are adenoid cystic carcinoma, adenocarcinoma, acinic cell carcinoma, and extranodal non-Hodgkin’s lymphoma. Mesenchymal malignant lesions, such as fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and osteosarcoma are extremely rare lesions of the palate. In summary, an asymptomatic palatal lesion of this magnitude could be an inflammatory, developmental, or neoplastic lesion. Further imaging studies were needed to narrow the list of possible lesions. The clinical and current radiographic findings were most compatible with pleomorphic adenoma, our working diagnosis. In the palate, other aforementioned lesions with similar clinical and radiographic characteristics have a lower occurrence than pleomorphic adenoma.

DIAGNOSIS AND MANAGEMENT Because the orthopantomogram was not of sufficient diagnostic quality to identify any pathosis, a cone-beam computed tomogram (CT) was taken. While the computer was reconstructing the image, an incisional biopsy performed under local anesthesia revealed a yellowish soft tissue mass. This specimen was sent to pathology.

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Histopathologic evaluation revealed an abundance of large clear tumor cells with a loosely textured myxomatous background, epithelioid cells, and dominated by the presence of cartilaginous-type vacuolated cells consistent with physaliferous cells (Figure 3). There were some separations of physaliferous cells from the mucosal epithelium by a band of fibrous tissue. Immunoperoxidase stain demonstrated a strong presence of cytokeratin and vimentin, and was negative for S-100 proteins. Both cytokeratin and vimentin stains displayed diffuse positivity of physaliferous cells. The pathologist diagnosed the specimen as chordoma with chondroid features. The patient could not provide a detailed history, and it became necessary to obtain her medical records. These records revealed the following history. In November of 1995 (15 years previously), the patient developed diplopia, which persisted for several months, prompting her to see her physician. A magnetic resonance image revealed a large intracranial mass invading and destroying the clivus, extending into the left cavernous sinus, sphenoid sinus, apex of the left orbit, and compressing cranial nerves III and IV. An incisional biopsy at that time revealed a chordoma with chondroid features. In 1995, the planned treatment was a staged approach involving surgical debulking followed by stereotatic radiosurgery and further surgical excision if necessary. Despite removal of an estimated 90% of the tumor followed by the radiosurgery in 1996, the tumor demonstrated radiographic progression in 1997. In 1998, the patient had additional radiosurgery and 2 attempts at resection, the last through a transoral sublabial approach. The patient was then lost to follow-up but returned in 2006 with recurrence of the tumor and underwent another procedure via an orbital-zygomatic craniotomy. In Figure 2, owing to ghost images of maxillary alveolar processes and remaining hard palate, it was impossible to quantitatively or qualitatively assess the extent of destruction of the hard plate, if any. This necessitated further radiographic imaging. Following the review of the patient’s medical records, the patient had a cone-beam CT taken (Figure 4). The invasive soft tissue mass extended from the clivus, through the sphenoid sinus, into the right maxillary sinus, obliterating the bony hard palate. The incisional biopsy was performed after a negative aspiration, and this resulted in a histologic diagnosis of recurrent chordoma. The head and neck conference reviewed the patient’s case and recommended proton beam therapy. Radiation oncology treated the patient with a total dose of 70 gray at the rate of 200 centigray per fraction using intensity modulated radiation therapy to the extracranial part of the

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Fig. 2. Orthopantomogram is unremarkable with the exception of metal plates of the left lateral orbital region, and large carious lesion on tooth #14. Maxillary soft tissue mass is not appreciated here.

tumor. Speech language therapy and radiation oncology currently follow the patient. The patient declined any further surgical intervention.

DISCUSSION Chordomas are generally considered slow growing, rare (less than 1 in 1 million), malignant neoplasms that account for about 2% to 4% of cranial bone tumors.1 They have a low predilection for metastasis and are derived from cellular remnants of the notochord.1 They are almost exclusively found in the Caucasian population between the ages of 30 and 60, but can occur at any age, with a 2:1 male predilection.1 They are usually located anywhere from the base of the skull to the sacrum with 32% in the cranium, 29.2% in the sacrum, 32.8% along the spine, and 6% found in other sites.1 Chordomas are deemed malignant tumors because of their destruction of bone and neural compression. We present a rare and unusual case of a 57-year-old African American female patient with near total destruction of the maxilla by a malignant, locally aggressive chordoma that extended from the cranial base into the maxilla. Initially, clival chordomas insidiously produce symptoms of pain, diplopia, and/or unresolving headaches or muscle weakness in the extremities, sensory abnormalities, and dysfunction of the bowel, bladder, and sex organs.2-4 Usually, these symptoms persist for several months to years before a definitive diagnosis is made. Symptoms are dependent on the location of the tumor. Chordoma located in the sacral region usually presents with pain in the lower back, constipation, and neurological deficit. In the mobile spine, complaints include compromised airway, dysphagia, and/or dysphonia. In the clival region, patients sometimes complain of proptosis, nasal obstruction, epistaxis, and otalgia, but they

most often complain of headaches and visual disturbances (diplopia and/or blurred vision) related to cranial nerve palsy (especially cranial nerves III, IV, and VI), which account for 20% and 60% to 70% of the symptoms, respectively.5,6 Chordomas are classified into 3 types based on histology: conventional, chondroid, and dedifferentiated. Conventional chordomas are the most common of chordomas. They are slow growing. They have myxoid stroma containing sulfated mucopolysaccharides resistant to hyaluronidase. Chondroid chordomas are often confused with chondrosarcomas owing to the presence of cartilaginous stroma in both chordomatous and chondromatous features.7 Dedifferentiated chordomas are similar to conventional chordomas but with sarcomalike components, such as fibrosarcoma, osteosarcoma, or chondrosarcoma, and can resemble malignant fibrous histiocytoma.7 They are rapidly growing chordomas with a poor prognosis. Chordoma cells contain an abundance of vacuolated cytoplasm along with hyaline cartilagelike matrices and physaliferous, bubble-bearing or grapelike cells containing glycogen and mucin. The physaliferous characteristics of chordomas histologically distinguish them from chondrosarcomas and adenocarcinoma.7 Cytologic assays testing for immunoreactivity to S-100 protein, cytokeratin, vimentin, and/or epithelial membrane antigen confirm the diagnosis of chordoma.7 Radiographically, chordomas are expansile, causing bone resorption with highly irregular scalloped borders that are sometimes sclerotic.8,9 Approximately 30% to 70% of the cases have matrix calcifications.8,9 They present with similar radiodensities as surrounding soft tissues and as large soft tissue masses extending from clivus or infiltrating intervertebral disk space spreading to adjacent vertebral bodies. Low-density areas reflect

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Fig. 3. Biopsied lesion from the palatal vault stained with hematoxylin and eosin. Microscopic examination at ⫻10 magnification (A) and ⫻40 (B) magnification reveals tumor mass separated from mucosal epithelium by a band of fibrous tissue. The tumor is chiefly composed of loosely textured myxomatous background with epithelioid cells and dominated with cartilaginous-type cells.

the presence of myxoid and gelatinous materials.8,9 Magnetic resonance T1-weighted images are hypointense to isointense compared with muscle tissue, and T2-weighted images are hyperintense, reflecting the high fluid content of vacuolated cytoplasm.8,9 A definitive diagnosis of chordoma cannot be based on radiographs alone. A biopsy is needed for confirmation. The difficulty of access to the tumor is attributed to the location of the tumor in proximity to vital structures, particularly cranial base chordomas. They usually involve vital structures, such as cranial nerves and carotid and basilar arteries. In most situations, a fineneedle biopsy is usually indicated; however, there is a

high incidence of recurrence along the biopsy track. Chordomas have a higher incidence of recurrence for open biopsy than fine-needle biopsy.10-12 Biopsy tracks should avoid oral, nasal, and rectal cavities. The path of the biopsy needle needs to be clearly marked and documented for potential subsequent recurrence and surgical resection.10 The tumor in our patient recurred along the sublabial, transnasal path of surgical access. Treatment of chordoma involves radical surgical resection of the tumor with wide margins and/or radiotherapy. Sacral chordomas involve wide resections with intentional resection of sacral roots, thereby impairing or causing erectile, bowel, and bladder dysfunction.13

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increase in survival rates; however, radiation has delayed the onset of symptoms, such as cranial III, IV, and VI palsies.16-20 The recurrence rate has been reported to be as high as 75% either in situ or along the path for surgical access.11,21-26 The 5-year survival rate ranges from 50% to 80% and a 10-year survival rate ranges from 30% to 65%.5,16-18,20,26 Chordomas usually present in the Caucasian population with a 2:1 male predilection.1 We present a case of a rare, atypical presentation of a chordoma as a large soft tissue mass in the oral cavity in a 57-year-old African American woman. This chordoma originated from the clivus and progressed along the path of previous surgical access and eroded through the hard palate. REFERENCES

Fig. 4. Sagittal (A) and coronal (B) views of a large chordoma destroying the clivus, maxilla, and hard palate. The white arrows outline the soft tissue mass in the maxillary sinus.

Sacral amputations involve S1 to S3.13 Chordomas of the mobile spine usually require spondylectomy, the complete removal of vertebral segments, which usually are vertebral segments C2 and C3.14 Cranial base chordomas are particularly difficult to treat because of their location and proximity to vital structures. Multidisciplinary teams involving otolaryngology, oral and maxillofacial surgery, plastic surgery, and neurosurgery are needed for access via osteotomies (i.e., Le Fort I), removal of tumor, and closure.15 The purpose of cranial base surgical removal of chordomas is decompression of arterial and neurovascular structures. Surgical removal of cranial base chordomas does not increase length of survival, but does minimize symptoms associated with recurrence, and maximizes the efficacy of radiotherapy.16 Chordomas are considered to be highly resistant to radiation therapy and studies do not demonstrate an

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Reprint requests: Johnson C. Miin, DDS, MSE University of Mississippi Medical Center 2500 North State St. Jackson, MS 39216-4505 [email protected]