Salivary Gland Cancer: Symptoms, Types, Causes and Treatment

Salivary gland cancer is a rare and complex disease, accounting for a small fraction of head and neck tumors. Despite its rarity, this cancer presents a diverse clinical picture, ranging from slow-growing tumors to aggressive malignancies. Understanding its symptoms, types, causes, and treatment options is crucial for early detection and optimal care. This article provides a detailed, evidence-based overview to help patients, caregivers, and healthcare professionals navigate the intricate landscape of salivary gland cancer.

Symptoms of Salivary Gland Cancer

Recognizing the symptoms of salivary gland cancer can be challenging, as they often overlap with benign conditions or other head and neck disorders. Early detection, however, can significantly impact outcomes, making awareness of these signs essential.

Symptom	Description	Typical Gland Location	Source(s)
Lump/Swelling	Painless, persistent mass	Parotid, submandibular, minor glands	6 9
Pain	Discomfort or tenderness, sometimes radiating	Any salivary gland	6 9
Facial Nerve Weakness	Numbness or muscle weakness in the face	Parotid (facial nerve proximity)	9
Difficulty Swallowing	Trouble or pain when swallowing	Minor glands, submandibular	6 9
Other Symptoms	Dry mouth, changes in saliva, ulceration	Any	9

Table 1: Key Symptoms

Common Presentations

Most patients notice a painless lump or swelling in the area of a major salivary gland—usually the parotid, located near the jaw and ear. While most parotid lumps are benign, persistent masses warrant prompt evaluation. Tumors in the submandibular and minor salivary glands (located throughout the mouth and throat) may also present as lumps, though they are less common 6 9.

Pain and Nerve Involvement

Pain is less frequent but may indicate a more aggressive tumor or involvement of nearby nerves. Notably, facial nerve weakness or paralysis (such as drooping of one side of the face) is a red flag for malignancy, especially in parotid tumors, as the facial nerve passes through this gland 9.

Other Signs

Some patients experience difficulty swallowing, especially when tumors arise in minor salivary glands of the mouth, throat, or palate. Additional symptoms may include dry mouth, changes in taste, or ulceration if the tumor invades mucosal surfaces 9.

When to Seek Help

Early symptoms are often subtle, which can lead to delays in diagnosis. Any persistent, painless swelling near the jaw, under the tongue, or in the mouth—especially if accompanied by facial weakness or swallowing difficulties—should prompt a visit to a healthcare provider.

Types of Salivary Gland Cancer

Salivary gland cancers are among the most histologically diverse tumors in the human body. More than 20 malignant subtypes have been recognized, each with distinct biological behavior, genetic alterations, and clinical implications 1 2 5.

Type	Frequency/Prevalence	Notable Features	Source(s)
Mucoepidermoid Carcinoma	25–35%	Most common; variable grade	6 9
Adenoid Cystic Carcinoma	~30%	Slow-growing, perineural spread	6 9 3
Acinic Cell Carcinoma	Less common	Better prognosis, often in parotid	9
Salivary Duct Carcinoma	Rare, aggressive	HER2, androgen receptor positive	2 3 4
Polymorphous Adenocarcinoma	Rare	Minor glands; indolent	1 2 6
Secretory Carcinoma	Newly recognized	ETV6-NTRK3 fusion; sensitive to Trk inhibitors	2 3

Table 2: Major Types of Salivary Gland Cancer

Major and Minor Salivary Glands

Salivary gland cancers primarily arise in the three pairs of major salivary glands: parotid (most common), submandibular, and sublingual glands. Minor salivary glands, found throughout the mouth and throat, can also develop malignancies, often with different tumor types 6 9.

Most Common Types

• Mucoepidermoid Carcinoma (MEC): The most prevalent type, occurring mainly in the parotid. Can be low, intermediate, or high grade, affecting prognosis and treatment 6 9.
• Adenoid Cystic Carcinoma (ACC): Known for its tendency to invade nerves and recur years after treatment. Often arises in minor glands but can be found in any 6 9 3.
• Acinic Cell Carcinoma: Typically has a better prognosis and is most frequently located in the parotid gland 9.
• Salivary Duct Carcinoma: Rare but aggressive, often showing molecular similarities to breast ductal carcinoma (including HER2 positivity and androgen receptor expression) 2 3 4.
• Polymorphous Adenocarcinoma: Mostly affects minor salivary glands and has an indolent course 1 2 6.
• Secretory Carcinoma: Newly classified, it carries the ETV6-NTRK3 gene fusion, making it responsive to targeted therapies (Trk inhibitors) 2 3.

Rarity and Classification

The World Health Organization (WHO) has refined the classification to include new entities and recognize important genetic distinctions. Advances in molecular testing have improved diagnostic accuracy and may influence future treatment strategies 1 2 5.

Causes of Salivary Gland Cancer

While the precise causes of salivary gland cancer remain unclear, research has identified several risk factors and mechanisms that contribute to its development. The interplay of environmental exposures, genetic mutations, and rare viral associations shapes the risk profile for these tumors.

Cause/Risk Factor	Description	Strength of Evidence	Source(s)
Radiation Exposure	Therapeutic or accidental	Well established	7 8
Genetic Alterations	Fusion genes, oncogene mutations	Strong (subtype-specific)	2 3 5
Viral Infections	EBV (lymphoepithelial carcinoma)	Specific subtypes only	7
Smoking	Linked to Warthin’s tumor, not cancers	Tumor-specific	7
Occupational Exposures	Hairdressers, beauty salon workers	Weak, unconfirmed	7

Table 3: Main Causes and Risk Factors

Radiation Exposure

The most consistently documented environmental risk is exposure to ionizing radiation. Patients who’ve received radiation therapy to the head and neck (for conditions like lymphoma) or survived atomic bomb exposure exhibit a higher risk of developing both benign and malignant salivary gland tumors. The latency period can be significant, often over a decade 7.

Genetic and Molecular Factors

Recent advances have uncovered a range of genetic alterations that drive salivary gland cancers. These include:

• Fusion genes (e.g., CRTC1-MAML2 in MEC, MYB-NFIB in ACC, ETV6-NTRK3 in secretory carcinoma)
• Oncogene mutations and chromosomal translocations that are often unique to specific tumor types 2 3 5

These genetic findings not only clarify the pathogenesis but also open doors for personalized therapy.

Viral and Occupational Risks

Epstein-Barr Virus (EBV) is implicated in lymphoepithelial carcinomas, especially in certain geographic populations (e.g., Eskimo, Chinese). There is no clear evidence linking other viruses (herpes, HIV, papillomavirus) to salivary gland cancer 7.

Smoking is strongly associated with Warthin’s tumor—a benign salivary gland tumor—but not with malignant forms. Some studies have suggested a higher risk in women employed as hairdressers or beauty salon workers, though this finding remains unconfirmed 7.

Malignant Transformation of Benign Tumors

Occasionally, benign tumors (like pleomorphic adenomas) undergo malignant transformation, especially if left untreated for many years. This process involves accumulation of genetic mutations and changes in cell cycle regulation 8.

Treatment of Salivary Gland Cancer

Treatment for salivary gland cancer is tailored to the tumor’s type, stage, location, and molecular profile. As these cancers are rare and diverse, management often requires a multidisciplinary team approach. Advances in surgery, radiotherapy, and targeted therapies are improving outcomes for many patients.

Treatment Modality	Indication/Use	Key Considerations	Source(s)
Surgery	Mainstay for localized tumors	Extent, nerve preservation	10 11 12
Radiotherapy	Adjuvant or primary for high-risk/recurrent	Dose, side effects	10 11 12
Chemotherapy	Advanced/metastatic, rarely curative	Modest response	3 10 12 13
Targeted Therapy	HER2+, NTRK+, AR+ tumors	Molecular testing essential	2 3 4 10
Experimental/Other	Clinical trials, PSMA therapy	For refractory disease	3 12 14

Table 4: Main Treatment Approaches

Surgical Management

Surgery is the primary and often curative treatment for most localized salivary gland cancers. The goal is complete tumor removal with clear margins while preserving function (especially facial nerve function in parotid tumors). In some cases, lymph node dissection is performed 10 11.

• Early-stage, low-risk tumors can often be treated with surgery alone.
• High-risk features (e.g., positive margins, high grade, perineural invasion) may require additional therapy 11.

Radiotherapy

Radiation therapy is commonly used after surgery for patients with high-risk factors or inoperable tumors. It helps control local disease and improve outcomes but carries risks of side effects such as dry mouth and tissue fibrosis 10 11 12.

• Adjuvant radiotherapy improves local control, particularly in advanced or high-grade tumors.
• Definitive radiotherapy is considered when surgery is not possible.

Systemic Therapy and Targeted Treatments

Traditional chemotherapy has limited effectiveness but may be used for advanced, metastatic, or recurrent disease 3 10 12 13.

Recent breakthroughs in molecular profiling have enabled:

• Trk inhibitors for secretory carcinomas with ETV6-NTRK3 fusion
• HER2-targeted drugs (like trastuzumab) for HER2-positive salivary duct carcinoma
• Anti-androgen therapy for androgen receptor-positive tumors (e.g., salivary duct carcinoma) 2 3 4

Experimental and Palliative Treatments

Clinical trials are crucial, given the rarity and diversity of these tumors. Experimental approaches, such as radionuclide therapy targeting PSMA in select cases, have shown promise in advanced, refractory disease 14.

Follow-up and Supportive Care

Long-term follow-up is important due to the risk of late recurrence, especially in adenoid cystic carcinoma. Supportive care addresses symptoms like dry mouth, swallowing difficulties, and psychological impact 10 12.

Conclusion

Salivary gland cancer is a rare but complex group of tumors requiring nuanced diagnosis and personalized care. Key points include:

• Symptoms are often subtle, with painless lumps being the most common sign. Facial nerve weakness or difficulty swallowing are red flags.
• Types of salivary gland cancer are highly diverse, with distinct behaviors and genetic profiles.
• Causes involve radiation exposure, genetic mutations, and, in some cases, viral infection or malignant transformation of benign tumors.
• Treatment is centered on surgery and radiotherapy, with promising advances in targeted therapies for select molecular subtypes.
• Multidisciplinary care and clinical trials are essential to improving outcomes in this challenging disease.

Awareness, early detection, and advances in molecular medicine are opening new avenues for personalized treatment, bringing hope to patients with this rare cancer.