Acinic / Acinar / Acinous Cell Carcinoma is a rare salivary gland cancer, comprising approx. 6%-10% of all salivary gland cancers. Salivary Gland cancers themselves only comprise between 0.3% and 0.9% of all cancers in the United States. Acinic cell carcinomas account for approx. 5% to 11% of those U.S. salivary cancers, although some studies have made that number much lower (2.5%). The National Cancer Database identified 1353 cases of acinic cell carcinoma of the head and neck in the U.S. from 1985 to 1995. That averages out to about 135 cases per year. Acinic cell carcinomas account for approx. 3-13% of all malignancies of the parotid gland, and are rarely seen in other salivary tissues. They make up approx. 4% of all minor, and 2-4% of all major salivary gland tumors.

Acinic cell carcinomas arise most frequently in the parotid gland (86.3% in largest study). Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands. There have been rare cases of primary tumors involving the parapharyngeal space and the sublingual gland. ACC has been reported to be the most likely of salivary gland carcinomas to occur bilaterally. One will occasionally find an even rarer acinic/acinar cell carcinoma of the pancreas, or of the lung (most lung versions are actually metastases). There is new (limited) data to indicate that a certain kind of breast cancer (secretory or juvenile carcinoma) is identical to acinic cell carcinoma.

Acinic cell carcinoma appears in all age groups, but presents at a younger median age (approx. 52 years) than most other salivary gland cancers. Occurrences in children are quite common. The cancer affects women more commonly than men (58.8% is one figure). Tumor growth, may go unreported and undiagnosed for a number of years, due to the slow growth of most neoplasms. The usual reported clinical presentation is a painless mass of several years duration. Tumors infrequently invade the facial nerve. Lymph node metastases occur in approx. 16% of patients, although this figure has varied in different studies, and may be higher. The most common sites of metastases are lungs and bone. Also noted are central nervous system, mediastinum (space in the chest between the pleural sacs of the lungs) liver and brain. (Definition notes: Metastases are secondary tumors in locations distant or distinct from the original tumor site, but with the same type of cells as the primary tumor. Neoplasms are any tumors, or abnormal/uncontrolled cell growth.)

In the past, the malignant nature of this cancer had been disputed or unrecognized. In older literature, it was classified as an "Acinic Cell Tumor" or benign "adenoma". Later literature detailing the high potential for recurrence, metastases and even death resulted in WHO re-classification as a "malignant carcinoma", though with more common low-grade behavior. Acinic Cell Carcinomas are typically slow-growing, low-grade (highly differentiated) neoplasms.

Although indolent in nature (slow-growing), ACCs are quite persistent in their potential for local recurrences and distant metastases, often MANY years later. Local and multiple recurrences may occur in up to half of patients. Recurrences and metastases after 3-10 years are common, especially after inadequate primary tumor removal. Recurrences more than 20 or 30 years after initial treatment are also noted throughout the literature. Figures for recurrences and metastases vary widely between studies. Local recurrence numbers in the literature range from 8% to 60%, but most authors report values in the range of 30%-50%. Metastases figures vary from 7% to 29%, with a median of approx. 20%. Death from disease has been reported in 1% to 26% of patients, depending on study location and period. Patients with lung metastases have a poorer prognosis. Overall however, acinic cell carcinoma has been identified as the least aggressive of the salivary gland cancers. And there is a recurrent observation that prolonged survival despite persistence of disease is possible.

Most authors consider ACC patients to have the most favorable outlook of all salivary gland patients, with survivals of approx. 70-85% at 10 years. The 1999 U.S. Natl. Cancer Data Base Report found five year survival to be 83.3% (observed) and 91.4% (disease specific). Other reviews note the 5-, 10-, and 20-year-survival rates at approx. 90%, 83%, and 67%, respectively. Worse survival has been associated with high grade, metastatic disease and age over 30 years.

There has been ongoing dispute in the literature as to whether histopathological features (visual appearance of cells/tissue seen through a microscope) are reliable predictors of biologic behavior, disease progression and patient survival. It is safe to say that this method is fallible. It should also be noted that low tumor grade is not a reliable predictor of prognosis, due to the occasional aggressive behavior of low-grade tumors. On the other hand, the high grade variants of the disease (which are uncommon) are definitely aggressive, and usually associated with much poorer survival. High-grade variants of acinic cell carcinomas have been described as papillocystic carcinoma (Spiro R, Cancer 41:924, 1978) or carcinomas with undifferentiated cells in a medullary pattern (Batsakis JG, et al. Annals of Otology, Rhinology & Laryngology 99:929, 1990), but there may be other strains as well.

Acinic/Acinar/Acinous Cell Carcinoma belongs to the family of Adenocarcinomas. Cancers with some similarities include Adenoid Cystic, Muco-Epidermoid, Low-grade Adenocarcinomas, and possibly some Breast Cancers. (As mentioned earlier, Secretory Carcinoma of the Breast may be an identical entity.)

The Pancreatic form of acinic cell carcinoma is a rare subtype of exocrine pancreatic cancer. Exocrine pancreatic cancers are the most common form of pancreatic cancer when compared to endocrine pancreatic cancer. (Cancers of the pancreas are classified by tissue type into exocrine and endocrine tumors.) Those arising from the exocrine pancreas include ductal and acinar cell tumors. ACC constitutes only 1 to 2 percent (or less) of exocrine tumors, or about 250 cases per year in the United States. ACC of the pancreas has been seen in children, although most cases arise in adults. More men than women get this form of the cancer. It has been reported to represent 1-13% of all pancreatic tumors, but most articles report 1-2%.


TREATMENT:

Due to the rare nature of Acinic Cell Carcinoma (in all tumor sites), treatment results are often anecdotal. Historically, head and neck treatment involves various levels of surgery, often with post-operative radiation. Although it is widely considered that surgical excision is the preferred primary treatment, debate continues regarding the extent of resection needed, as well as the role for neck dissection and adjuvant radiotherapy. The question of superficial versus total parotidectomy, and local versus radical excision is debated in the literature. The weight of more recent publications appears to support a less aggressive surgical approach to the uninvolved (N0) neck. And more recent conclusions are that patient outcome is more dependent on extent of tumor than the type of operation performed. What has clearly been established is that the primary goal of any surgery, if attempted, should be complete and total removal of the primary tumor, without residual disease.

Incomplete excision is associated with a lower chance of survival. So if complete and total tumor removal is not achievable, radiation options should always be considered. Over the past three decades, radiation treatment alone, specifically with fast neutron beam radiation, has shown promising and effective results, especially for inoperable tumors. That means that it is a viable option to surgery, not just a postoperative adjunct.

Postoperatively: North et al concluded that radiotherapy is recommended for all cases of salivary gland cancer except for those tumors staged as T1N0 or T2N0 with low grade histology, which were excised with negative margins. We think that these are reasonable criteria. The question again becomes one of WHAT to radiate with. Specifically, it is our opinion at ACCIC at this time, that fast neutron beam radiation should be strongly considered either instead of surgery, or post-operatively, in all the above described cases.

Traditionally, conventional radiation (photons and electrons) has been commonly used to treat this cancer, especially in cases characterized by high grade, residual disease after surgery and nodal metastases. The relative rarity of acinic cell carcinoma has prevented the execution of a disease-specific study capable of statistically demonstrating improved survival for ACC patients treated with postoperative conventional radiotherapy. And in fact, despite its frequent use, studies and reviews throughout the literature have found conventional radiation to be ineffective in the long term against this and similar salivary gland cancers. Most studies that support the use of conventional radiation do not have follow-up periods long enough to ascertain the long term effectiveness for THIS particular cancer. The literature that doubts the effectiveness of conventional radiation routinely describes acinic cell carcinoma as "radio-resistant".

On the other hand, Fast Neutron beam radiation has shown considerably more effectiveness against ACC and other slow-growing salivary gland cancers. Studies have shown that High LET radiations such as fast neutron beam are more effective in dealing with the biology of slow-growing cancers. Clinical trials have been completed in the United States and England indicating that fast neutron radiation improves disease-free and overall survival in salivary gland cancer patients with unresectable tumors, or for those with recurrent neoplasms.

There has been ongoing debate for years regarding the question of conventional versus fast neutron radiation, largely having to do with the question of potential increased risks of fast neutrons to healthy tissue. It is now largely considered that most of the “anti-neutron” opinion is based on outdated results from older and primitive treatment facilities. (This does not discount the fact that there are inherent risks of side effects with any radiation treatment.) Weighing all the pros and cons, it is our opinion that for this cancer, at this time, Fast Neutrons are the first "treatment of choice" to consider in most ACC cases. We feel that this treatment provides the best chance for long term local control of disease. This is especially the case for inoperable or unresectable tumors, incomplete tumor removal, residual disease, and recurrences. Unfortunately there are a very limited number of high energy fast neutron treatment centers worldwide. This sometimes provides a logistical challenge.

If fast neutron treatment is not an option for the patient, accelerated hyperfractionated dosing of conventional beams should be considered. This method has also resulted in high rates of long-term loco-regional controls in salivary gland cancers. This method gives more frequent but lower doses than conventional dosing schedules. It is unclear at this time whether this particular method is more or less effective on acinic cell carcinoma than fast neutrons, as no comparative study has been executed. But due to the biologic characteristics of the cancer, it is likely that neutrons are still more effective.

Chemotherapy for ACC has largely been considered ineffective, except for pain-relief, or partial responses. The use of chemotherapy for malignant salivary gland tumors in general remains under evaluation. ACC has been considered chemo-resistant in the literature. This is likely due to the (usually) slow metabolism of this cancer (once again). It is important to keep in mind however, that most of the data on this cancer and chemotherapy is anecdotal, and the literature often refers to "salivary gland cancers" in general. (Little research is done on this cancer specifically.) Some anecdotal evidence indicates that chemotherapy may prove useful for shrinking ACC tumors, especially in conjunction with other modalities (such as radiation, or biologic agents). In addition, chemotherapy is more likely indicated for treating systemic (throughout the body) or metastatic disease in some locations, or for high grade (fast growing) variants. A new role for chemotherapy as an angiogenesis inhibitor (blocking blood vessel growth to tumors) also holds some promise, utilizing more frequent (yet lower) dosing schedules.

The pancreatic version of ACC has been treated in a number of cases using intra-arterial infusion chemotherapy (delivering the chemo directly to the liver via an artery), which has been noted to produce reasonable results. However, it is noted that chemotherapy for this version of the cancer is (also) not well studied.

Overall, surgery and radiation results with acinic cell carcinoma have proven most successful with smaller early-stage tumors. A key factor with treating ACC (and cancer in general) is diagnosing and treating any tumors early, when they are small and have not had a chance to spread. Another key is dealing with each site as effectively as possible. Radiation results with larger tumors are often not curative. Chemotherapy results that we know of are usually only partial responses. And all these treatments deal only with the symptoms, and not the causes. Because of all these factors, exploration of clinical trials and new protocols is strongly suggested. New areas of cancer research such as targeting of growth hormones and overexpressed substances in cancer cells, angiogenesis inhibitors, genetic-based treatments, immunotherapy, and other new modalities may hold the key for acinic cell carcinoma treatment in the future, and hopefully even in the near future. Patients and physicians are encouraged to investigate promising protocols. We also encourage complementary methods such as diet/nutrition, vitamins and other supplements that may inhibit cancer growth.

More details on all areas of treatment can be found on the "ACC Treatment" pages of this website. Information on numerous other aspects of this cancer and dealing with it can be found on the many other pages of this site.

The above information is based on correlation of data from numerous published sources, as of August, 2002. Some of those sources are listed below. This information is subject to change and updating, and may not reflect the most recent data. This overview was written by Edgar Stroke, the creator of this website, who has been an acinic cell carcinoma patient since the early 1980s. He is not a medical professional, but has been researching this cancer and treatments (as well as experimenting on himself) for quite a long time. Opinions expressed are based on published materials, as well as personal experience and consultation with numerous medical professionals.
The information provided on this website is for informational purposes only. It is not intended as a substitute for professional health care. Any medical treatment advocated here (even if offered by health care professionals) is offered as an opinion, and not as licensed medical advice. The reader is advised to make decisions based on multiple information sources.

 

Sources for ACC Overview (included at least these items)

The Doctors' Doctor Acinic Cell Carcinoma Overview -
http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm
current as of 7/14/02

National Cancer Institute: cancer.gov
Salivary Gland Cancer (PDQ®) (Adult Treatment)
Health Professional Version
Date Last Modified: 02/2002

UCLA School of Medicine, Dept. of Pathology website, 2002
http://wwwpathnet.medsch.ucla.edu/med-edu/pathrev/saliv/mt/acinic.htm
Acinar Cell Carcinoma (ACC) of the Pancreas
Last updated on 1/4/00.

Rare and Exotic Cancers website, 2002
http://home.pacbell.net/markmcc/RARE_CANCERS/rare.html

Acinic Cell Carcinoma of the Salivary Gland
Oncolink "Ask the Experts"
Kenneth Blank, MD, and Jason Lee, MD, OncoLink Editorial Assistants
Abramson Cancer Center of the University of Pennsylvania
http://www.oncolink.com/templates/experts/article.cfm?c=3&s=17&ss=40&id=1472
Last Reviewed: November 1, 2001

Cancer: Principles & Practice of Oncology, 6th Edition
Author(s): Vincent T. DeVita, Jr., MD, Samuel Hellman, MD, Steven A. Rosenberg, MD, PhD
Date: January 2001

Chapter 30.4: Tumors of the Salivary Glands and Paragangliomas
Major Salivary Gland Tumors
Section: Acinic Cell Carcinoma
Roy B. Sessions
Louis B. Harrison
Arlene A. Forastiere

Cancer Medicine, 3d ed, p1240; from DeVita Jr et al.,
Cancer: Principles & Practice of Oncology, 3d ed, p575)
(Stedman, 25th ed; Holland et al.,)

Use of fast neutrons in the treatment of tumors of the salivary glands: rationale, review of the literature and experience in Orleans [Article in French]
Breteau N, Wachter T, Kerdraon R, Guzzo M, Armaroli L, Chevalier D, Darras JA, Coche-Dequeant B, Chauvel P.
Service d'oncologie, radiotherapie et hematologie clinique, CHR, Orleans, Italie.
Cancer Radiother 2000 May-Jun;4(3):181-90

National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma
(multi-institution report).
Henry T. Hoffman MD, Lucy Hynds Karnell PhD, Robert A. Robinson, MD, John A. Pinkston MD, Herman R. Menck MBA.
Head and Neck - July 1999.

Pathologic Diagnosis: Acinic cell carcinoma of the deep lobe of the parotid gland involving the right parapharyngeal space
Archives of Otolaryngology - Head and Neck Surgery: Vol. 125 No. 6, June 1999
Section Editors: Frederic B. Askin, MD; William H. Westra, MD
And Archives of Otolaryngology online: Head and Neck Surgery Diagnosis Pathologic Quiz Case / http://archotol.ama-assn.org/issues/v125n6/ffull/orp0699-1b.html

Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors.
Douglas JG, Lee S, Laramore GE, Austin-Seymour M, Koh W, Griffin TW.
Department of Radiation Oncology, University of Washington Medical Center, Seattle 98195-6043, USA.
Head Neck 1999 May;21(3):255-63

Improved results with accelerated hyperfractionated radiotherapy of advanced head and neck cancer
Felix Leborgne MD, Eduardo Zubizarreta MD et al
1999 Int. J. Cancer (Radiat. Oncol. Invest.)

Salivary Gland Tumors; Clinical and Pathological Features
S Tabibzadeh
BioScience.org - FRONTIERS IN BIOSCIENCE; LECTURE SERIES
[Vol 3, z1-129, January 1, 1998]
Dept of Pathology, Moffitt Cancer Center and University of South Florida,
12902 Magnolia Drive, Tampa, FL 33612
http://www.bioscience.org/lecture/tabibza/list.htm

European results in neutron therapy of malignant salivary gland tumors.
Krull A, Schwarz R, Engenhart R, Huber P, Lessel A, Koppe H, Favre A, Breteau N, Auberger T
Bull Cancer Radiother; 83 Suppl:125-9s 1996

Acinic cell carcinoma of the parapharyngeal space: case report.
Yokoyama M, Nomura Y, Semba T.
Head Neck. 1993;15:67-69.

Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council.
Laramore GE, Krall JM, Griffin TW, Duncan W, Richter MP, Saroja KR, Maor MH, Davis LW
Int J Radiat Oncol Biol Phys; 27(2):235-40 1993

The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms.
Buchholz TA, Laramore GE, Griffin BR, Koh WJ, Griffin TW
Cancer; 69(11):2779-88 1992 June 1

Acinic cell carcinoma of the salivary glands. A long term follow-up study of 15 cases.
Oliveira P, Fonseca I, Soares J. - Servico de Patologia Morfologica, Instituto Portugues de Oncologia de Francisco Gentil-Centro de Lisboa.
Eur J Surg Oncol 1992 Feb;18(1):7-15

Recent advances in radiation therapy for head and neck cancer.
Awan AM, Vokes EE, Weichselbaum RR.
Department of Radiation and Cellular Oncology, University of Chicago,
Pritzker School of Medicine, Illinois.
Hematol Oncol Clin North Am 1991 Aug;5(4):635-55

Acinic cell carcinoma: clinicopathic review.
Lewis JE, Olsen KD, Weiland LH.
Cancer. 1991;67:172-179.

Carcinoma of the major salivary glands treated by surgery or surgery plus postoperative radiotherapy.
North CA, Lee D-J, Piantadosi S, Zahursk M, Johns ME.
Int J Radiation Oncology Biol Phys 1990; 18: 1319-1326

Fast neutron radiation for inoperable and recurrent salivary gland cancers.
Koh WJ, Laramore G, Griffin T, Russell K, Griffin B, Parker R, Davis L, Pajak TF.
University of Washington, Department of Radiation Oncology, Seattle.
Am J Clin Oncol 1989 Aug;12(4):316-9

Neutron vs photon irradiation of inoperable salivary gland tumors: results of an RTOG-MRC Cooperative Randomized Study.
Griffin TW, Pajak TF, Laramore GE, Duncan W, Richter MP, Hendrickson FR, Maor MH.
Department of Radiation Oncology, University of Washington Hospital/School of Medicine, Seattle 98195.
Int J Radiat Oncol Biol Phys 1988 Nov;15(5):1085-90

Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice?
Laramore GE:
International Journal of Radiation Oncology, Biology, Physics 13(9): 1421-1423, 1987 Sept.

Salivary neoplasms: overview of 25 years' experience with 2,807 patients.
Spiro R.
Head Neck Surg 1986;8:177

Acinic cell carcinoma of salivary origin. A clinicopathologic study of 67 cases.
Spiro RH, Huvos AG, Strong EW.
Cancer 1978 Mar;41(3):924-35

Acinic cell carcinomas arising in salivary glands: a clinicopathologic study.
Perzin KH, LiVolsi VA.
Cancer. 1979;44:1434-1457.

Textbook of Uncommon Cancer, 2nd Ed., pp 408.
Section on Acinic Cell Carcinoma


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