Introduction
What is adenoid cystic carcinoma or ACC?
Adenoid cystic carcinoma (ACC) is a rare type of cancer derived mainly from the salivary glands (the glands in the mouth that produce saliva), so often develops in the head and neck region, but can often occur in other parts of the body, including the breast, eyes, lungs, prostate and skin.1 It can be a rare form of breast cancer occurring in predominantly females.2
Characteristics of ACC
Certain characteristics follow when ACC develops. This starts with the growth of the tumour. The growth rate of the tumour starts slow but tends to spread to different areas (highly distant metastases). The tumours form small, glandular-like cells and have three types of solid growth components; cribriform, tubular, and solid.
The cribriform growth pattern describes the cells with multiple small spaces, tubular patterns as elongated cells that look like small tubes, and the solid pattern as solid sheets of cells.
This large difference in growth patterns makes the diagnosis of ACC very challenging. ACC can also spread to and invade the nervous system, resulting in symptoms such as:
- Numbness
- Pain
- Weakness
This adds to the difficulty of diagnosing and treating ACC. When ACC doesn’t spread to the nervous system, it often presents itself as a painless lump in the affected body region.3
Prevalence and risk factors
ACC is rarely seen in children and adolescents and is often seen developing in people aged 50–60 years, although the exact cause is currently unknown. However, there are potential risk factors that contribute to the onset of ACC including:1,2
- Genetic mutation
- Exposure to harmful radiation (patients previously exposed to radiotherapy treatments).
- Viral infections (i.e. HPV)
- Low vitamin C intake
- Other cancers (i.e. breast cancer)
- Hormonal and salivary gland diseases
There is a combination of diagnostic tests that help confirm ACC to other inflammatory diseases.
- First, a physical examination is used to assess the patient and the affected area for the presence of lumps or swelling, skin scars on the scalp and face, and pain
- Imaging techniques are done to see the size and location of the tumour
- Ultrasound examination with colour imaging is a safe way to detect a tumour
- CT(Computed Tomography) or MRI(Magnetic Resonance Imaging) scans can create more detailed images of the affected area and are often mandatory when clinical symptoms are present
Finally, a biopsy is done to confirm the diagnosis of ACC; there are two methods of biopsy
- The fine-needle aspiration biopsy (FNAC)
- The ultrasound-guided core biopsy (USCB)
FNAC is when a thin needle is inserted into the affected region and cells or fluid from the tumour is extracted and examined. With USCB, a larger needle is used to take a larger sample of tissue from the tumour for evaluation. The samples taken from these biopsies are then examined under a microscope where the features of ACC are confirmed.2
Treatment options
The treatment options for ACC involve surgery to remove the tumour, followed by radiation therapy. However, the effectiveness of the treatment is also dependent on the size, location, stage, and invasion of the tumour, as well as the distant metastasis and solid growth type.
Surgery is the most common method to treat ACC, where complete removal of the tumour takes place. When the tumour is at a later stage and has invaded surrounding tissues, the patient also receives radiation therapy to kill the cancerous cells.3
Along with surgery, hormonal therapies are also a considered treatment route. Hormones like oestrogen and progesterone contribute to normal mammary gland development and influence cancer progression.4
Understanding hormonal therapies for ACC
Explanation of hormonal therapy
Rationale for use
Even after treatment using surgery and radiation therapy, it is very common for ACC to return, therefore more treatment approaches are needed that will target the root cause of ACC.4
Targeted hormones
The targeted hormones are:
- Oestrogen
- Progesterone
Effectiveness and benefits of hormonal therapies
Clinical evidence
Studies have shown the oral mucosa and salivary glands to be sensitive to oestrogen function. A study analysed oral mucosal and salivary gland samples for both subtypes of oestrogen receptors by immunohistochemistry and found oestrogen receptor type β to be the predominant subtype in human salivary glands.5
Studies have also shown that oestrogen and progesterone receptor expression is linked to a more favourable prognosis when it comes to a better chance of survival in breast cancer.6 This means hormonal therapies are effective as their target receptors are oestrogen receptors found on cancer cells.
Potential benefits
The benefits of hormonal therapy often depend on your age and menopause symptoms along with any other risk factors you may have and generally, it outweighs any risks associated. So, the hormonal therapeutic avenue is often considered.
Potential benefits include:
- Relieving menopause symptoms
- Preventing osteoporosis
- Maintaining muscle strength
Types of hormonal therapies
Anti-androgen therapies
Androgens is an important sex hormone that plays a crucial role in the development, growth and survival of certain cells, therefore they also have a role in cancer progression, hence it is becoming a target for treating hormone-related diseases.5
Some early research by the American Cancer Society found salivary gland tumours to have too many receptors for androgens, which are male hormones. Drugs such as bicalutamide and leuprolide that inhibit these receptors or even lower levels of these hormones are helping to treat these hormones.
Oestrogen receptor blockers
Oestrogen is a sex hormone that plays an important role in the development of certain glands and, hence may play a role in the development of tumours in these glands.4
Progesterone receptor blockers
These are also known as antigestagens or antiprogestins which are progesterone receptor blockers. They work by preventing P4 from regulating its functions by suppressing its formation or blocking its function.7
Other targeted hormone therapies
Targeted therapy is a treatment option which focuses on the cancer’s specific gene, proteins or surrounding tissue which is causing cancer growth and survival. For adenoid cystic carcinoma, ongoing clinical trials are using therapy drugs known as tyrosine kinase inhibitors including Lenvatinib or axitinib which you may know as Lenvima and Inlyta accordingly.8
Combination therapies
Surgery and radiation therapy
Currently, a combination of surgery and radiation therapy is being used as in most cases wide metastasis (spread of cancer) may require removal of the infected tissue.
Radiation therapy may be used before, during or after any other treatment to improve the chance of the treatment working.
Radiation therapy uses a high level of radiation to either shrink or completely kill cancer-infected cells by damaging the DNA material inside these cells.
Sequential or concurrent use
Like everything, there is a limit to how much radiation your body can be safely exposed to over your lifetime. This may impact how you can receive radiation therapy in the future unless the area affected in your body is distant enough from the previous location where radiation was received.9
Side effects and considerations
Common side effects
There are side effects to radiation therapy as there is a chance for healthy cells to be killed alongside cancerous cells. The side effects that you experience will depend on the part of the body being treated. For specific side effects, you can find out more here.
General side effects include:9
- Fatigue
- Hair loss
- Memory issues
- Skin changes
- Nausea
Ongoing trials and studies
Due to adenoid cystic carcinoma being a rare diagnosis at present, and with chemotherapy making a limited difference, it is recommended to anyone with adenoid cystic carcinoma to refer to and ask about ongoing clinical trials to treat the disease.
Clinical trial access
If you are interested in finding treatment options through clinical trials, you can click here to view more information about what clinical trials involve and where to sign up.
Support organisations
Some organisations that can provide you with more information and support groups are listed.
- Adenoid Cystic Carcinoma Research Foundation
- Salivary Gland cancer UK
- Adenoid Cystic Carcinoma organisation international
- Macmillan cancer support
You are never alone, speak to someone if you have any questions and always refer to your specialist health advisor for personal care.
Summary
Adenoid cystic carcinoma (ACC) presents a complex challenge in diagnosis and treatment due to its rare nature and diverse growth patterns. While surgery and radiation therapy remain primary treatment modalities, hormonal therapies have emerged as a promising avenue, targeting receptors such as estrogen and progesterone.
These therapies offer potential benefits including symptom relief and improved prognosis, supported by clinical evidence demonstrating receptor expression in ACC cells. Various hormonal therapies, including anti-androgen, estrogen receptor blockers, and progesterone receptor blockers, are being explored, alongside targeted therapies like tyrosine kinase inhibitors.
Combining surgery and radiation therapy remains a cornerstone in managing ACC, albeit with associated side effects. Ongoing clinical trials offer hope for advancing treatment options, emphasising the importance of considering participation in research. Support organisations provide invaluable resources and community for individuals navigating the complexities of ACC, reinforcing the message that no one faces this journey alone, and seeking guidance from healthcare professionals is paramount.
Any information in this article is not meant to be or replace professional advice, only guidance. Ensure you seek a GP or a medical professional if you are unsure about anything.
References
- Fang Y, Peng Z, Wang Y, Gao K, Liu Y, Fan R, et al. Current opinions on diagnosis and treatment of adenoid cystic carcinoma. Oral Oncology [Internet]. 2022 Jul [cited 2024 Apr 9];130:105945. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1368837522002342
- Cantù G. Adenoid cystic carcinoma. An indolent but aggressive tumour. Part A: from aetiopathogenesis to diagnosis. Acta Otorhinolaryngol Ital [Internet]. 2021 Jun [cited 2023 Oct 19];41(3):206–14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283400/
- Cantù G. Adenoid cystic carcinoma. An indolent but aggressive tumour. Part B: treatment and prognosis. Acta Otorhinolaryngol Ital [Internet]. 2021 Aug [cited 2023 Oct 19];41(4):296–307. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448184/
- Sumida T, Ishikawa A, Kamata Y, Nakano H, Yamada T, Mori Y. Estrogen enhances malignant phenotypes in human salivary adenoid cystic carcinoma cells. Anticancer Research [Internet]. 2016 Jun 1 [cited 2024 Apr 9];36(6):2793–8. Available from: https://ar.iiarjournals.org/content/36/6/2793
- Student S, Hejmo T, Poterała-Hejmo A, Leśniak A, Bułdak R. Anti-androgen hormonal therapy for cancer and other diseases. European Journal of Pharmacology [Internet]. 2020 Jan 5 [cited 2024 Apr 9];866:172783. Available from: https://www.sciencedirect.com/science/article/pii/S0014299919307356
- Zhang M, Liu Y, Yang H, Jin F, Zheng A. Breast adenoid cystic carcinoma: a report of seven cases and literature review. BMC Surgery [Internet]. 2022 Mar 24 [cited 2023 Oct 19];22(1):113. Available from: https://doi.org/10.1186/s12893-022-01560-9
- Valimaa H, Savolainen S, Soukka T, Silvoniemi P, Makela S, Kujari H, et al. Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. Journal of Endocrinology [Internet]. 2004 Jan 1 [cited 2024 Apr 9];180(1):55–62. Available from: https://joe.bioscientifica.com/view/journals/joe/180/1/55.xml
- Kowalewski MP, Pereira MT, Papa P, Gram A. Progesterone receptor blockers: historical perspective, mode of function and insights into clinical and scientific applications. Tierarztl Prax Ausg K Kleintiere Heimtiere [Internet]. 2020 Dec [cited 2024 Apr 9];48(06):433–40. Available from: http://www.thieme-connect.de/DOI/DOI?10.1055/a-1274-9290
- Barrera JE, Shroyer KR, Said S, Hoernig G, Melrose R, Freedman PD, et al. Estrogen and progesterone receptor and p53 gene expression in adenoid cystic cancer. Head Neck Pathol [Internet]. 2008 Mar [cited 2023 Oct 20];2(1):13–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807605/