Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma (MEC) is the commonest malignant salivary gland tumour in adults and children, accounting for about 30 to 35 percent of salivary malignancies. It arises mostly in the parotid (45 percent) and the palate and other minor salivary glands, and also the submandibular gland. Peak incidence is the fourth to sixth decade, and it is the most frequent salivary cancer in children. It can also arise in the bronchial tree, as a late complication of radiation, and within the jaw (central MEC).

Tumours contain mucous, epidermoid and intermediate cells, graded as low, intermediate or high grade by cystic component, neural invasion, necrosis, mitoses and anaplasia.

About 50 to 80 percent carry the CRTC1-MAML2 fusion (CRTC3-MAML2 in a minority), which correlates with low and intermediate grade and better prognosis.

Five year survival is above 90 percent for low grade, 70 to 80 percent for intermediate grade, and 30 to 50 percent for high grade. Spread is by regional lymph nodes (high grade, 40 to 50 percent) and haematogenous routes to the lung, bone and liver.

• Painless, slow growing, firm or cystic mass in the parotid, submandibular region, palate, buccal mucosa, tongue, or retromolar area; palatal lesions may be bluish, mucocele like.
• High grade tumours: rapid growth, pain, fixation to skin or muscle, facial nerve palsy, trismus, ulceration, and cervical lymphadenopathy.
• Minor gland tumours: submucosal nodule, ulceration, bleeding, loose teeth.
• Bronchial MEC: cough, wheeze, haemoptysis, recurrent pneumonia.
• Red flags: facial nerve weakness, pain, rapid growth, nodes, trismus, dysphagia, and distant metastasis symptoms.

• Clinical examination of the head and neck, facial nerve grading, and staging of nodes.
• Ultrasound guided FNAC or core biopsy: mucous, intermediate and epidermoid cells in a cystic background; core biopsy gives better grading.
• MRI of the head and neck with contrast: ill defined infiltrative mass with T2 intermediate signal (high grade), well defined T2 hyperintense cystic mass (low grade); perineural spread; CT for bony and nodal assessment.
• Histological grading on the resected specimen; fluorescence in situ hybridisation or RT-PCR for MAML2 rearrangement in challenging cases.
• Staging with CT chest (and PET-CT for high grade disease or nodal involvement) for distant metastasis.
• Exclude pleomorphic adenoma, Warthin tumour, adenoid cystic carcinoma, necrotizing sialometaplasia, mucocele, squamous cell carcinoma, and metastasis.

• Surgery is the primary treatment: wide local excision with negative margins (at least 1 cm for high grade); superficial parotidectomy for low grade superficial lobe tumours; total parotidectomy with facial nerve sacrifice only if nerve invaded; submandibular gland excision; palatal tumours need excision with underlying bone (partial maxillectomy) when involved.
• Neck: elective neck dissection (levels I to IV or II to V) for intermediate and high grade tumours, T3 to T4 disease, or clinically positive nodes (therapeutic neck dissection, levels I to V).
• Adjuvant radiotherapy 60 to 66 Gy in 30 to 33 fractions over 6 to 6.5 weeks for high grade disease, close or positive margins, perineural or vascular invasion, nodal metastasis, T3 to T4 stage, or recurrence; low grade tumours with clear margins need no adjuvant therapy.
• Concurrent chemotherapy for high risk features (positive margins, extracapsular nodal spread): cisplatin 100 mg/m2 intravenously on days 1, 22 and 43 (or weekly 40 mg/m2 for 6 weeks), with pre-hydration, antiemetics (ondansetron 8 mg and dexamethasone 8 mg intravenously), and monitoring of renal function, audiometry, and magnesium.
• Advanced or metastatic disease: systemic therapy with carboplatin and paclitaxel (carboplatin AUC 5 intravenously on day 1 with paclitaxel 175 mg/m2 on day 1, every 21 days for 6 cycles) or cisplatin with doxorubicin; targeted agents (EGFR inhibitors) have limited activity; palliative radiotherapy.
• Perioperative: cefazolin 1 g intravenously at induction (single dose), analgesia with paracetamol 1 g every 6 hours.
• Complications: facial nerve weakness, Frey syndrome, trismus, osteoradionecrosis, xerostomia (radiotherapy), hypocalcaemia and other late effects.
• Follow up: clinical examination every 3 months for 2 years, every 6 months to 5 years, then yearly; MRI at 3 to 6 months post radiotherapy; CT chest yearly for 5 years in intermediate or high grade.
• Counselling: grade determines prognosis; late recurrence is possible.