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
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(Stedman, 25th ed; Holland et al.,)
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rationale, review of the literature and experience in Orleans [Article
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National Cancer Data Base Report on Cancer of the Head and Neck: Acinic
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A. Pinkston MD, Herman R. Menck MBA.
Head and Neck - July 1999.
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1999
Section Editors: Frederic B. Askin, MD; William H. Westra, MD
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Oncology Group. Medical Research Council.
Laramore GE, Krall JM, Griffin TW, Duncan W, Richter MP, Saroja KR, Maor
MH, Davis LW
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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
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Lewis JE, Olsen KD, Weiland LH.
Cancer. 1991;67:172-179.
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postoperative radiotherapy.
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Pajak TF.
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Maor MH.
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Fast neutron radiotherapy for inoperable salivary gland tumors: is it
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Textbook of Uncommon Cancer, 2nd Ed., pp 408.
Section on Acinic Cell Carcinoma