Natural Course of Submandibular Salivary Gland Cancer
Submandibular gland cancer follows an aggressive natural course with high rates of locoregional progression, distant metastasis, and mortality, with approximately 80% of patients dying from their disease if left untreated or inadequately treated. 1
Disease Progression Pattern
The natural history is characterized by progressive local invasion with eventual locoregional and distant spread:
- Tumor size and clinical stage are the most critical determinants of disease progression and survival. 2
- Local extension manifests as facial paralysis, trismus, and cutaneous infiltration as the tumor invades adjacent structures. 2
- Regional lymph node metastases occur in approximately 16-20% of patients at presentation, with an occult metastasis rate of 4%. 3, 4
- Distant metastases are present in 7% of patients at diagnosis, with distant-only recurrence occurring in 28% of cases. 3, 4
Histologic Patterns and Their Impact
The submandibular gland has a higher proportion of malignant tumors compared to the parotid gland, making these tumors inherently more dangerous:
- Adenoid cystic carcinoma is the most common histology (41-56% of cases), followed by adenocarcinoma (15%), mucoepidermoid carcinoma (15%), and malignant mixed tumors (11%). 3, 4, 5
- High-grade histology and adenoid cystic carcinoma independently predict worse disease-free survival. 6
- Perineural invasion, present in a significant proportion of cases, is an independent predictor of shorter disease-free survival. 6
Survival and Recurrence Without Treatment
The untreated natural course results in poor outcomes:
- Five-year cause-specific survival is 60% and 10-year survival is 48% even with treatment, suggesting dismal outcomes without intervention. 3
- Disease recurrence occurs in 44% of treated patients, with locoregional control at 5 years being only 30% with surgery alone. 3, 4
- Five-year disease-free survival is 63-68% with treatment, indicating that untreated disease would have substantially worse outcomes. 4, 5
- The 15-year survival for submandibular gland malignancies is only 21-47%, reflecting the aggressive biology of these tumors. 1
Clinical Presentation During Natural Progression
As the disease progresses untreated, patients develop:
- Progressive enlargement of the submandibular mass with locoregional extension. 2
- Signs of malignancy including facial nerve paralysis, trismus, and skin infiltration. 2
- Cervical lymphadenopathy as regional metastases develop. 2
- Systemic symptoms from distant metastases, particularly to lungs and bones. 3
Important Clinical Caveat
Only 12% of patients (3 out of 25) show clinical signs of probable malignancy at presentation, making early detection challenging and emphasizing the insidious nature of disease progression. 4 This underscores why submandibular masses require prompt surgical evaluation rather than observation, as the natural course involves silent progression until advanced stages.