What are the malignant tumors of the major salivary glands (parotid, submandibular, sublingual) and can you provide a brief discussion of each?

Malignant Major Salivary Gland Tumors

The major malignant salivary gland tumors include mucoepidermoid carcinoma and adenoid cystic carcinoma as the most common types, followed by acinic cell carcinoma, salivary duct carcinoma, carcinoma ex pleomorphic adenoma, adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma. 1, 2

Distribution by Gland Location

The likelihood of malignancy varies significantly by anatomic site:

• Parotid gland: 15-30% of tumors are malignant 2
• Submandibular gland: 40-45% of tumors are malignant 2
• Sublingual gland: 70-90% of tumors are malignant 2

This inverse relationship between gland size and malignancy risk is a critical clinical principle—smaller glands harbor proportionally more malignant disease. 2

Common Histologic Types

Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma is the most common malignant salivary gland tumor overall. 1, 2 This tumor has a formalized grading system (low, intermediate, high grade) that directly impacts prognosis and treatment decisions. 2 Low-grade mucoepidermoid carcinomas have excellent prognosis with 5-year survival rates exceeding 90%, while high-grade variants behave more aggressively. 1 Recent molecular studies have identified specific genetic translocations (CRTC1-MAML2 fusion) that characterize this tumor. 2

Adenoid Cystic Carcinoma

Adenoid cystic carcinoma is the second most common malignancy and has distinctive behavior characterized by perineural invasion and late distant metastases. 1, 2 This tumor demonstrates a propensity for lung metastases that can occur years or even decades after initial treatment. 1 The 5-year survival may appear favorable (69.6% overall), but 15-year survival drops dramatically to 36.7%, reflecting the indolent but relentless nature of this disease. 1 Postoperative radiotherapy significantly improves outcomes for adenoid cystic carcinoma. 1

Acinic Cell Carcinoma

Acinic cell carcinoma has a relatively favorable prognosis compared to other malignant salivary tumors. 1, 2 This tumor occurs almost exclusively in the parotid gland and demonstrates low-grade behavior in most cases. 2 The 5-year survival approaches that of mucoepidermoid carcinoma. 1

Carcinoma Ex Pleomorphic Adenoma

Carcinoma ex pleomorphic adenoma represents malignant transformation of a pre-existing pleomorphic adenoma, typically occurring after 15-20 years of untreated benign disease. 3 This entity accounts for 5-25% of untreated pleomorphic adenomas. 3 Warning signs include rapid enlargement, pain, and facial nerve palsy after years of stable disease. 3 The malignant component is most commonly adenocarcinoma or undifferentiated carcinoma, and most cases are high-grade. 3 Five-year survival ranges from 30-76%, with surgical treatment (with or without postoperative radiation) providing the best locoregional control. 3

Salivary Duct Carcinoma

Salivary duct carcinoma is an aggressive high-grade malignancy that histologically resembles ductal carcinoma of the breast. 2 This tumor has poor prognosis and frequently presents with advanced stage disease. 2

Adenocarcinoma (Not Otherwise Specified)

Adenocarcinoma NOS represents a heterogeneous group with generally poor prognosis. 1 These tumors lack the specific architectural features that would classify them into more defined categories. 2

Polymorphous Low-Grade Adenocarcinoma

This tumor occurs almost exclusively in minor salivary glands, particularly the palate. 2 Despite its infiltrative growth pattern, it has excellent prognosis with rare metastases. 2

Myoepithelial Carcinoma

Myoepithelial carcinoma is a rare entity composed of malignant myoepithelial cells. 2 Behavior ranges from low-grade to high-grade depending on histologic features. 2

Squamous Cell Carcinoma and Undifferentiated Carcinoma

These represent the most aggressive histologic types with significantly worse prognosis than mucoepidermoid or acinic cell carcinomas. 1 Primary squamous cell carcinoma of salivary glands must be distinguished from metastatic disease or direct extension from adjacent mucosal sites. 1

Prognostic Factors

Tumor size and clinical stage are the most critical determinants of survival and local control. 4, 5 Histologic grade (low versus high) independently predicts outcome. 4 Quality of surgical excision with negative margins is essential. 4 Submandibular gland tumors have the worst prognosis among major salivary gland sites, while minor salivary gland tumors have the best survival rates. 1, 6

Clinical Presentation

Painless submandibular swelling is the most common presentation, with an average symptom duration of 3 months. 6 Signs suggesting malignancy include facial nerve paralysis, trismus, cutaneous infiltration, rapid growth, and pain. 4, 5, 3 Cervical lymphadenopathy occurs in 15.3% of cases at presentation. 1

Recurrence and Metastases

The overall recurrence rate is 40.2%, cervical lymph node metastases occur in 15.3%, and distant metastases develop in 11.1% of patients. 1 Metastatic disease accounts for 30% of deaths. 6