Central Mucoepidermoid Carcinoma: A Rare Entity Analysis of Five Cases

According to Pires et al., (2003), the diagnosis and treatment of salivary gland tumors (SGT) constitute a challenge for the clinician. In the book by Dardick (1996) is mentioned that clinical and radiographic manifestations of these neoplasms are diverse and they are characterized by the most complicated histology of any tissue in the human body.

Ezsias et al., (1994) stated that MC is the most common malignant salivary gland tumor in children and the most common intra-osseous salivary gland carcinoma. Approximately 3% of all mucoepidermoid carcinomas are intra-osseous, and in that case, they are called Central Mucoepidermoid Carcinoma (CMC). Besides the occurrence of mucoepidermoid carcinoma in the oral cavity and bone, it has been reported   in other anatomic locations as nasal cavity, (Deepak et al., 1998) thyroid, (Jayaram et al., 1998) and Eustachian tube   (Kim et al., 2003). 

While the pathogenesis of CMC is not known, some theories of its origin do exist. It has been theorized that embryological pluripotential cells can give rise to dental or salivary gland tissues. The most likely source for an intra-osseous salivary gland neoplasm is odontogenic epithelium.  Mucous—producing cells are commonly seen in odontogenic cyst linings. Furthermore, glandular tumors   can develop in association with non-erupted teeth. An odontogenic condition called glandular odontogenic cyst, often mimics CMC, clinically, radiographically and histologically.
       
CMC appears most commonly in middle-aged adults but has been reported in all ages. No ethnicity predilection has been identified. The usual location is the posterior area of the mandible, followed by the posterior maxilla. But CMC may appear in any tooth bearing area of the jaws.  Frequent symptoms are cortical swelling, pain, often radiating to other body areas, paresthesia, numbness and trismus.

Radiographic imaging is often a multilocular, well circumscribed radiolucency. Displacement of the teeth, cortical perforation and root resorption are not uncommon. A few reported cases of a mixed radiolucent/radiopaque presentation of CMC are in the English literature.  The fifth case analyzed in this paper, (Velez et al., 2008) which was characterized by radiolucent/radiopaque manifestation, was previously reported by one of the authors.

Report of Four New Cases:

Case # 1

70 year old male patient, Slight expansion of posterior right mandible is noted upon extra-oral examination.  Intra-oral exam exhibits   swelling of the mandible and a 2 cm soft mass on the alveolar ridge covered by discolored, smooth mucosa.  Patient stated that an extraction was performed “several” years previously due to a “cyst with an unerupted tooth”.  The soft tissue nodule had been growing for months. Panoramic radiography exhibits a large radiolucent, well circumscribed, multilocular manifestation with cortical destruction this lesion clearly originated inside bone and the soft tissue lesion is an extension of the intraosseous mass. With a differential diagnosis of ameloblastoma and odontogenic keratocystic tumor, a biopsy was performed. A salivary gland tumor was diagnosed as intermediate grade central mucoepidermoid carcinoma. Hemi-mandibulectomy and reconstruction followed the diagnosis. No recurrence found after four years.

Case # 2

25 year old oriental female consulted for extreme pain on the right maxilla, radiating to teeth, palate, nose and face, present for some months. It was previously diagnosed as a traumatic condition and pain medications were prescribed. Clinical examination disclosed a red/bluish flat area on posterior right maxilla over the palatine foramen (Fig # 1) Imaging shows a well circumscribed lytic lesion with cortical compromise. (Fig # 2-3)The soft tissue discoloration is a manifestation of the intraosseous tumor.  Incisional biopsy showed  a tumor composed of squamoid cells with mitotic activity and  perineural invasion, goblet cells, and micro cysts, it was  diagnosed as central mucoepidermoid carcinoma intermediate to high grade.( Fig # Block resection with 2.0 cm margin was performed and an temporary obturator was placed. The patient is free of tumor one year later.

Misdiagnosis of CMC occurs frequently, due to several factors, such as the rareness of the location for a salivary gland tumor, the clinical manifestations and the radiographic appearance, which are suggestive of an odontogenic lesion. Furthermore, the histologic finding of mucous cells in odontogenic cysts and the existence of sialo-odontogenic/glandular odontogenic cyst may misguide the pathologist.  It may result in a more invasive treatment and worst sequelae for the patient. (Simon et al., 2003)

According to Zhow et al., (2012) the histologic grading of Mucoepidermoid carcinoma for prognostic purposes is based in the degree of cystic formation, the amount of intermediate and epidermoid cells and the grade of anaplasia. Low grade tumors infrequently develop large numbers of epidermoid cells. Most CMC are low grade tumors.  Current surgical treatment of choice is block resection, which means removal of the entire specimen as one piece, including at least 1.0 cm margins.  Brookstone et al., (2008) reported 40% recurrences after marginal resection and 4% recurrence after block resection.  CMC is not as rare as it was previously thought, and metastases are reported by Lebsack et al., (1990) in about 9 %.
 
The main symptom of CMC found in the cases reported in this paper is pain. All the cases were painful; however, the type of pain was different. In two of the patients, the pain was extreme. Two had radiating symptoms to the face and to the left arm and left mandible. In those cases is easy to misdiagnose the condition. Radiating left arm pain, as well as left mandible, is an important symptom of a heart attack, especially when it is associated, like in case # 3, with numbness or tingling sensations.  Radiating pain to teeth, palate, nose and face from the palatine foramen in case # 2 may mislead the clinician to focus on dental, neural or maxillary sinus problems. The case # 5 was characterized by extreme pain, especially upon percussion, suggesting dental origin.

Misdiagnosis is of common occurrence: Three cases were associated to unerupted teeth and one was periapical located. Case # 1 was misdiagnosed clinically and radiographically as dentigerous cyst, and treated as such. Case # 2 was clinically diagnosed for months as “traumatic lesion” therefore the treatment was delayed. The symptoms of case # 3 were suggestive of a heart attack. Case # 4 was misdiagnosed clinically, radiographically and histologically as dentigerous cyst with mucous cells, and therefore a wrong treatment was performed. The pain in case # 5 was suggestive of endodontic problem. Even worst, the radiographic image of this later patient combined with the associated pain was reminiscent of osteoblastoma.

Even further, case # 4 had a negative PET scan. (Table # 1) This is another factor that contributes to the wrong diagnosis and treatment. It is well known that malignant tumors with a large amount of mucin or pus are FDG PET negative because the FDG uptake correlates with the cellularity of the tumor and the amount of mucin. These tumors do not have enough nuclei to uptake the radioactive material.

Central mucoepidermoid carcinoma, due to the extensive variation of the clinical and imagenologic presentation, is often no treated in time or treated inappropriately, leaving undesired sequelae.