Malignant salivary gland neoplasms account for 0.5 to 1.2% of all cancers and 5% of head and neck cancers. They are more likely to affect women with a male-female ratio of 1 to 1.5. Malignant lesions are found in approximately 21.7% of all salivary gland neoplasms. Most malignancies of head and neck cancers occur in the major salivary glands (MSG): parotid glands, followed by the submandibular, sublingual and minor salivary glands (MiSG) [1].
What is Salivary Gland Cancer?
Salivary cancer or salivary gland tumors – are a rare group of complex, heterogeneous histological formations located in the parotid, submandibular, sublingual, and minor salivary glands of the upper parts of the aerodigestive tract. Rare head and neck cancers include malignant salivary gland tumors, adenoid cystic carcinoma, mucoepidermoid carcinoma, and other rare histological types that require an individualized and multidisciplinary approach to treatment.
The wide variety of salivary gland tumor etiology, microscopic histology, growth patterns, and tumor characteristics can complicate diagnosis and treatment for clinicians. The World Health Organization in 2005 recognized 24 different malignant salivary gland cancers; the most common histologies include mucoepidermoid carcinoma (MucoCa), acinic cell carcinoma, adenoid-cystic carcinoma (ACC), expleomorphic adenoma carcinoma and adenocarcinoma [2]. Squamous cell carcinoma of the salivary glands is less common than mucoepidermoid carcinoma, a rare disease, but usually has a more aggressive clinical course.
Mucoepidermoid carcinoma (MEC)
This is the most common type of salivary gland cancer. The tumor is formed from cells that produce mucus and skin-like cells. Because of this, it can look like a bone or a «bubble with a liquid» and sometimes do not cause serious symptoms for a long time. There are slow (low risk) and more aggressive forms of this cancer. The more dense cells in the tumor, the more aggressive it usually behaves. If such cancer occurs in the submandibular salivary gland, it often requires more active treatment.
Adenoid-cystic carcinoma (ACC)
This is a slow-growing but insidious type of most salivary gland tumors. It may hardly increase for years, but has a special ability to spread along the nerves. That is why patients sometimes feel pain, tingling or numbness. Some variants of this cancer are calmer, others - are much more aggressive and can metastasize through the blood. Even with slow growth, this type requires very careful long-term observation.
Acinic cell carcinoma
This cancer comes from cells that normally produce saliva. In most cases, it grows slowly and has a relatively favorable prognosis.
However, in rare situations, the tumor can change its behavior and become more aggressive. Therefore, even after successful treatment, regular follow-up examinations are important.
Carcinoma on the background of pleomorphic adenoma
This type of cancer develops from a previously benign salivary gland tumor that has existed for many years. At a certain point, part of the «cells degenerate» and begin to behave malignantly. The risk depends on how far the cancer has gone beyond the primary tumor. If the spread is significant, the likelihood of recurrence and metastasis is higher and treatment requires a comprehensive approach.
By the way, about benign tumors, the most common of them is pleomorphic adenoma. It grows slowly, usually does not hurt and often looks like a normal seal near the ear, under the jaw or on the palate for many years. It is most often found in women aged 30–50 years. Although the tumor is benign, it is important to remove it completely, as if it is not completely removed, it can reappear or, in very rare cases, behave more aggressively many years later.
Vartin's tumor is the second most frequent benign salivary gland tumor. Also, benign groups include myoepithelioma, lymphadenoma, sebaceous adenoma, oncocytoma, cystadenoma and other types.
Symptoms and Early Warning Signs of Salivary Gland Cancer
At the beginning of the disease, symptoms may be minimal. The salivary gland tumor can be mobile or, on the contrary, tightly fixed to the surrounding tissues – and this does not always allow you to immediately distinguish a malignant salivary gland tumor from a benign one. That is why any new or incomprehensible formation in the area of the salivary glands needs to be examined.
As the disease progresses, pain, discomfort when chewing or swallowing, a feeling of fullness in the palate or deep throat, limited opening of the mouth, changes in the skin over the tumor, ulcers, or even formation of fistulas may appear. If the tumor is located in the minor salivary glands of the oral cavity, it may appear as a submucosal swelling, sometimes with ulceration. When localized in the nasal cavity or nasopharynx, nasal congestion and bleeding are possible.
Symptoms of salivary gland cancer
Tumors of minor salivary glands in the pharynx or larynx may present with difficulty swallowing, pain when swallowing, hoarseness of voice, shortness of breath, or a feeling of lack of air. Such symptoms are especially important not to ignore if they gradually worsen.
Disturbing signs that may indicate the malignant nature of the tumor include a rapid increase in the size of the mass, pain, impaired facial movements (weakness or asymmetry), as well as enlarged lymph nodes on the neck.
With tumors of the parotid salivary gland (parotid cancers), a large, dense formation in front of the ear can be combined with damage to the lymph nodes of the neck. Some patients experience paralysis of the facial nerve, which is manifested by a skew of the face, a lowering of the corner of the mouth or the inability to close the eye.
Submandibular salivary gland tumors often appear as a painless neck seal that becomes dense, bumpy over time, and can be "adherent" to skin or deeper tissues. In some cases, numbness of the tongue, impaired speech, or swallowing due to nerve involvement appear.
Tumors of the hyoid salivary gland usually appear as a painless mass at the bottom of the mouth, but about half of patients may experience pain or numbness [3].
Diagnosis of Salivary Gland Tumors
Before choosing treatment tactics, it is important to understand exactly which formation we are dealing with. Tumors of the salivary glands may look the same at the beginning, but have a completely different nature and course. That is why the diagnosis of salivary gland cancer is always step-by-step and comprehensive: it combines clinical examination, modern imaging methods and morphological confirmation of the diagnosis. This approach allows not only to distinguish a benign tumor from a malignant one, but also to determine its type, prevalence and the most effective way of treatment. Unlike pediatric forms, adult salivary gland cancer is more often associated with aggressive histological types and requires a multidisciplinary approach.
Ultrasound is the first non-invasive method of assessing tumors of major salivary glands, especially superficial lesions of the parotid glands. It can help localize tumors, distinguish solid masses from cystic clusters, and help conduct fine-needle aspiration biopsies. Heterogeneous echogenicity, local invasion, poorly defined margins and lymphadenopathy are sonographic signs of malignancy [4].
Routine CT can assess tumor prevalence, bone infiltration, and lymphadenopathy. However, it is limited by dental artifacts and has poor soft tissue resolution, especially for MEC, AdCC and ACC, leading to underestimation of the lesion.
MRI (nuclear magnetic resonance imaging) is recommended to assess tumor prevalence, soft tissue invasion, and nerve damage in lesions of the deep parotid lobe, sublingual glands, and minor salivary glands.
The role of PET is to detect locoregional and distant metastases. Compared to conventional CT, PET is more accurate in demonstrating tumor spread, lymphoid node involvement, local recurrence, and distant metastases due to higher standardized tissue uptake values.
However, PET cannot differentiate between benign and malignant tumors because benign tumors (such as pleomorphic adenoma and Vartin's tumor) show high glucose uptake values due to the presence of cells with high mitochondrial content [5].
Imaging cannot fully distinguish between benign and malignant lesions. Therefore, obtaining histological samples is key to determining the next steps of treatment. An incisional biopsy may be used for minor salivary glands in the mouth, but is not recommended for parotid lesions due to the risk of facial nerve damage and the possibility of tumor insemination. Therefore, ultrasound-guided fine-needle aspiration biopsy (FNA) is preferred.
Staging of Salivary Gland Cancer
Staging is a way to determine how far the cancer has spread at the time of diagnosis. This is very important because the stage of the disease affects the choice of treatment and prognosis.
Stage I – localized cancer
In the first stage, the tumor is small and located only within the salivary gland from which it arose. It does not grow into neighboring tissues, does not affect lymph nodes and does not spread to other organs. Often at this stage, the tumor appears as a slow-growing induration without pain or other pronounced symptoms. It is at this stage that treatment is usually most effective, and the prognosis – is the most favorable.
Stage II – localized cancer of a larger size
The second stage is also considered localized, but the tumor is already larger in size. It is still limited to the salivary gland and does not extend to lymph nodes or other organs. Some patients may develop a feeling of pressure, discomfort or facial asymmetry, but in general the tumor remains operable and treatable well.
Stage III – locally advanced cancer
In the third stage, the tumor either becomes even larger or begins to spread to the nearest lymph nodes of the neck. It can go beyond the gland itself and involve adjacent tissues. At this stage, the symptoms are usually more significant: pain, difficulty swallowing, limited opening of the mouth, changes in facial expressions. Cancer at this stage is called locally advanced, and treatment often requires a combination of surgery with radiation therapy and sometimes other methods.
Stage IV – advanced or metastatic cancer
The fourth stage covers several variants of the course of the disease. In some cases, the tumor grows deep into the surrounding structures – skin, bones, nerves, or other important anatomical areas. In other – the cancer spreads to several or large lymph nodes. If tumor cells appear in distant organs such as the lungs, bones, or liver, it is called metastatic cancer.
Metastatic cancer means that the disease has gone beyond the head and neck. Treatment at this stage is usually comprehensive and aimed not only at tumor control, but also at preserving the quality of life.
Standard Treatment Options for Salivary Gland Cancer
Standard treatment for salivary gland cancer is always selected individually. It does not depend on one factor, but on a combination of several important characteristics of the tumor. Medical oncologists take into account the stage of the disease, the type of tumor, its aggressiveness (degree of differentiation), exact localization, as well as whether it was possible to treat and completely remove the tumor during surgery. The general condition of the patient, the function of the nerves and the possible consequences of the treatment for appearance and quality of life also play an important role.
In the first stage, the cancer is usually localized and has not spread beyond the salivary gland, so in many cases it can be cured. If the tumor has low aggressiveness, the main treatment method is surgical removal. In most such situations, this is enough for a full recovery. Radiation therapy may be recommended additionally if the tumor has not been completely removed during surgery or if repeated surgery may result in significant impairment of function or appearance [6]. External beam radiation therapy, particularly photon beam radiation therapy, is widely used in salivary gland cancer as an adjuvant or radical treatment method to improve local tumor control and reduce the risk of recurrence with maximum preservation of surrounding healthy tissues.
If the tumor has a more aggressive structure, even at the first stage, the treatment may be wider. The basis is still surgery, but after it, doctors often recommend postoperative radiation therapy, especially if the tumor was close to the nerves or if there is doubt about complete removal. This approach helps reduce the risk of disease return and improve disease control.
In stage III, cancer is considered locally advanced, so treatment is usually combined [7].
Regardless of the aggressiveness of the tumor, the main method of treatment remains surgery with the removal of the primary tumor, and if necessary – and affected lymph nodes of the neck. In most cases, postoperative radiation therapy is recommended after surgery, especially if the tumor has spread to the lymph nodes, sprouted into the nerves, or has not been completely removed. In squamous cell carcinoma of the salivary glands, perineural invasion and regional lymph node involvement are often noted, which influences the choice of treatment tactics.
If the tumor is inoperable, relapsing, or does not respond to standard treatment, radiation therapy may be used as a primary treatment or palliative treatment. In specialized centers, extended radiation regimes are used, which can be more effective in complex clinical situations.
Chemotherapy is the basis of salivary gland lymphoma treatment. The benefit of chemotherapy is limited for other malignancies of the salivary glands. In patients who are not candidates for surgical or radiation treatment, palliative chemotherapy in certain studies has shown a partial response in 20-25% of cases [8].
In cases of recurrent salivary gland cancer, the choice of tactics depends on the location of recurrence, the histological type of the tumor, and the possibility of repeated local or regional treatment.
Advanced and Innovative Treatments for Salivary Gland Cancer in Germany
Regional chemotherapy
Advanced treatment for salivary gland cancer includes innovative combination approaches, such as targeted therapy, immunotherapy, regional chemotherapy, and modern radiation treatment methods, which allow to improve disease control and preserve the quality of life of patients. The standard method of administration of chemotherapeutic drugs is intravenous infusion. The infusion time ranges from 30 minutes to several hours. The drug is distributed throughout the volume of circulating blood, and its concentration in the tumor is similar to that in other body tissues.
There is such an innovative method as regional chemotherapy. An alternative method of administration is intraarterial infusion. Unlike conventional intravenous administration, the drug is administered directly into the artery that feeds the tumor. This makes it possible to achieve a high concentration of drugs in the tumor with a much lower load on the entire body. Such a method can reduce overall side effects and at the same time preserve the effectiveness of treatment.
Clinical experience shows that in some patients, intraarterial chemotherapy allows you to avoid a tracheostomy and a feeding tube, quickly reduce the tumor and maintain the quality of life. At the same time, this method requires specialized equipment and experience and is not the standard of care for all patients. The main criterion for short-term intraarterial infusion is an infusion time of 5-12 minutes.
Studies were performed in which patients with head and neck cancer received short-term intra-arterial infusion chemotherapy. The one-year survival rates were 59%, 82% and 93%, respectively, for stages IVB/C, IVA and I–III. The two-year survival rates for these same stages were 22%, 53% and 86%. Three-year survival rate – 17%, 42% and 65%, respectively [9].
Dendritic cell therapy
Dendritic cell therapy – is one of the methods of immunotherapy, that is, treatment that does not directly attack the tumor, but activates the person's own immune system so that it itself recognizes and kills cancer cells.
Dendritic cells – are "conductors" of immune responses. They are responsible for showing the immune system which cells are dangerous. It was for the discovery of the role of dendritic cells that the Nobel Prize was awarded to the American immunologist Ralph Steinman in 2011 [10], which emphasizes the fundamental importance of this discovery for modern medicine and oncology.
The essence of the therapy is that the patient's own immune cells are taken from them, dendritic cells are created from them in laboratory conditions, «teach them to recognize tumor antigens, and then returned to the body. After that, dendritic cells activate T-lymphocytes, which begin to purposefully attack cancer cells.
Dendritic cell therapy is considered as an additional or innovative method of treatment, especially in recurrent or metastatic salivary gland cancer, when standard methods are exhausted or do not give the expected effect, as well as in the composition of individualized immunotherapy programs.
In salivary gland neoplasms dendritic cells, along with macrophages and lymphocytes, play a significant role in regulating the immune response within the cancer cells and tumor microenvironment. The interaction between epithelial and mesenchymal components is critical for tumor growth, and dendritic cells are involved in this process [11].
Scientists demonstrated research in which it has been proven that the participation of dendritic cells at various stages of their maturation in most salivary gland tumors can serve as an important prognostic tool and a potential target for antitumor therapy.
Electrochemotherapy
A modern local method of treatment that already has clinical confirmation of effectiveness. Its main advantages are high accuracy, local effect on the tumor and significantly fewer systemic side effects. Electrochemotherapy combines the administration of an anticancer drug, which itself poorly penetrates cells and short electrical impulses fed directly into the tumor site.
Under the influence of these pulses, the membranes of cancer cells temporarily "open", and the drug can penetrate into the cancer cell much more effectively. As a result, malignant tumor cells are destroyed, and the surrounding healthy tissues are minimally damaged.
In order for electrochemotherapy to be as effective as possible, the correct choice of the drug and its dose, accurate treatment planning, optimal mode of electrical impulses, and correct choice of electrodes are very important. A separate role is played by the preliminary assessment of the distribution of the electric field in the tumor and surrounding tissues. The success of treatment largely depends on this [12].
In addition, after conducting ECT, the release of molecules associated with cancer cell damage occurs, which leads to an increase in the number of tumor antigens. This, in turn, increases the immune response against the tumor and increases the effectiveness of drugs. Cancer treatment abroad is chosen by patients with complex or rare forms of cancer when they need access to highly specialized centers. Medical treatment in Germany for cancer is valued for its high quality standards, access to modern technologies, innovative treatment methods, and clearly organized multidisciplinary medical care.
An important factor in choosing the treat of salivary gland cancer is the availability of the method and its cost. Traditional approaches are usually more widely available, but may require long-term treatment and significant associated costs. Innovative methods, on the contrary, are often limited to specialized centers and can have a higher initial price, but sometimes allow to reduce the duration of therapy and reduce additional costs. The following table compares the availability and estimated cost of traditional and current salivary gland cancer treatments to help patients better navigate possible treatment options.
| Treatment type | Cost Germany | Cost USA | Cost GB | Cost Australia |
|---|---|---|---|---|
| Surgery | €25,000 - €45,000 | €65,000 - €85,000 | €35,000 - €55,000 | €20,000 - €40,000 |
| Chemotherapy | €80,000 - €150,000 full course | €100,000 - €180,000 full course | €90,000 - €165,000 full course | not available |
| Radiation therapy | €28,000 - €42,000 | €40,000 - €80,000 | €35,000 - €65,000 | €25,000 - €50,000 |
| DC therapy | €20,000 - €38,000 | €100,000 - €150,000 | not available | not available |
| Regional chemotherapy | €45,000 per session | €37,000 - €150,000 | €30,000 - €118,000 | not available |
| Electrochemo-therapy | €7,500 - €12,000 per session | €40,000 - €100,000 | €25,000 - €45,000 | not available |
History of patient with salivary gland cancer
Mark has a complex and long oncological history. He was diagnosed with highly malignant carcinoma of the parotid salivary gland with signs of a locally widespread process and perineural invasion. In the primary phase, the patient underwent radical surgery followed by adjuvant radiotherapy. Despite the treatment, after a certain time, a locoregional recurrence was recorded, accompanied by pain syndrome, swelling in the face area and chewing disorders, which significantly worsened the quality of life.
Attempted systemic chemotherapy has been limited due to low tolerability of treatment, development of significant side effects, and lack of meaningful clinical response. Considering the tumor localization, previous exposure and high risk of functional complications in repeated surgery, the patient was offered an innovative regional approach – intraarterial chemotherapy.
The goal of the treatment was to achieve the maximum concentration of cytostatics directly in the tumor focus due to the selective intraarterial administration of the drug with minimal systemic load on the body. Treatment was carried out by a multidisciplinary team with the participation of an oncologist surgeon, interventional radiologist, clinical oncologist and anesthesiologist, with careful angiographic control of tumor nutrition.
The patient's family notes clear coordination of treatment, constant contact with the medical team and an understandable explanation of each stage of therapy, which significantly reduced anxiety and psychological burden. Already after the first courses of intraarterial chemotherapy, a pronounced decrease in tumor mass, disappearance of pain syndrome and improvement of chewing function were recorded.
According to the results of the control examination, a partial and later – complete local response was achieved, confirmed clinically and according to the data of imaging methods. Systemic adverse events were minimal and did not require prolonged hospitalizations or dose reduction. The patient has returned to daily life, maintains a satisfactory functional state and does not require constant pain relief.
The patient's family expresses high confidence in the chosen treatment strategy and team of specialists, emphasizing:
"We have come a long way and lost a lot of hope after standard methods. Intra-arterial chemotherapy has become a turning point for us. Here they treat not only the disease, but also the person. Today we see a result that we did not expect, and again we can make plans for the future".
A Medical Journey: Every Step of the Way With Booking Health
Finding the best treatment strategy for your clinical situation is a challenging task. Being already exhausted from multiple treatment sessions, having consulted numerous specialists, and having tried various therapeutic interventions, you may be lost in all the information given by the doctors. In such a situation, it is easy to choose a first-hand option or to follow standardized therapeutic protocols with a long list of adverse effects instead of selecting highly specialized innovative treatment options.
To make an informed choice and get a personalized cancer management plan, which will be tailored to your specific clinical situation, consult medical experts at Booking Health. Being at the forefront of offering the latest medical innovations for already 12 years, Booking Health possesses solid expertise in creating complex cancer management programs in each case. As a reputable company, Booking Health offers personalized salivary gland cancer treatment plans with direct clinic booking and full support at every stage, from organizational processes to assistance during treatment. We provide:
- Assessment and analysis of medical reports
- Development of the medical care program
- Selection of a suitable treatment location
- Preparation of medical documents and forwarding to a suitable clinic
- Preparatory consultations with clinicians for the development of medical care programs
- Expert advice during the hospital stay
- Follow-up care after the patient returns to their native country after completing the medical care program
- Taking care of formalities as part of the preparation for the medical care program
- Coordination and organization of the patient's stay in a foreign country
- Assistance with visas and tickets.
- A personal coordinator and interpreter with 24/7 support
- Transparent budgeting with no hidden costs
Health is an invaluable aspect of our lives. Delegating management of something so fragile yet precious should be done only to experts with proven experience and a reputation. Booking Health is a trustworthy partner who assists you on the way of pursuing stronger health and a better quality of life. Contact our medical consultant to learn more about the possibilities of personalized treatment with innovative methods for salivary gland cancer with leading specialists in this field.
Advanced Cancer Treatment: Patient Success Stories with Booking Health
Frequently Asked Questions About Salivary Gland Cancer
Send request for treatmentThe main salivary gland cancer symptoms include painless or painful swelling in the face, neck or mouth, facial asymmetry, difficulty chewing or swallowing, numbness, pain, facial nerve weakness and enlarged lymph nodes. Often, a salivary gland tumor in the early stages may not cause pronounced symptoms.
The survival rate for salivary gland cancer depends on the stage, histological type and grade of malignancy. In the early stages, the prognosis is favorable, while in advanced salivary gland cancer survival rates are lower, but vary significantly depending on the treatment.
Yes, salivary gland cancer can be cured, especially with early detection and the right choice of the best treatment, which usually includes surgery with or without radiation therapy.
Stage 1 is a localized salivary gland tumor confined to the salivary gland, without lymph node involvement or distant metastases.
The rate of progression of salivary gland cancer varies. Some types grow slowly, while others are aggressive and spread early. The rate of growth depends on the histology and stage of the disease.
Yes, salivary gland cancer is treatable, even in the later stages. Modern treatment options allow you to control the disease and maintain quality of life.
The best treatment for parotid gland cancer usually involves surgical removal of the tumor. In cases of high risk of recurrence, radiation therapy is added, and in some cases, systemic or regional treatment..
Diagnosis is based on clinical examination, ultrasound, MRI or CT, fine-needle or core biopsy and histological confirmation of the salivary gland tumor.
The main treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and innovative regional methods depending on the stage and type of salivary gland cancer.
The prognosis for advanced salivary gland cancer is more modest, however, modern combined and innovative treatment methods allow to achieve long-term control of the disease.
Yes, medical treatment abroad is a common choice for patients with salivary gland cancer, especially in complex or recurrent cases, where innovative treatment methods are available.
The cost of treatment for salivary gland cancer in Germany depends on the stage, the chosen method and the duration of treatment. The total cost can range from a few thousand to tens of thousands of euros, especially with combined or high-tech approaches.
Choose treatment abroad and you will for sure get the best results!
Authors:
This article was edited by medical experts, board-certified doctors Dr. Nadezhda Ivanisova, and Dr. Daria Sukhoruchenko. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!
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Sources:
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