Update of Common Salivary Tumors
Moderators: Dr. John Eveson and Dr. Silloo Kapadia
Section 6 -
Acinic Cell Carcinoma
Acinic cell carcinoma (AciCC) constitutes about 17% of all malignant salivary gland tumors, and is
among the tumors most often seen in consultation practice. The majority of AciCCs (80-90%) arise in the
parotid gland, followed by minor salivary glands, especially of the oral cavity. AciCC occurs over a
wide age range with peak incidence in the 4th-5th decades. In addition, however,
AciCC is the second most common malignant salivary gland tumor in childhood next to mucoepidermoid
carcinoma . 
The typical clinical presentation is that of slowly growing painless mass and it often mimics a benign
tumor. AciCC may show bilateral parotid gland involvement, or may be associated with independent benign
or malignant tumors in ipsilateral or contralateral gland (synchronous tumors).
also be associated with other tumor type within the hybrid neoplasms.  Hybrid carcinomas are
rare salivary gland tumor entities, consisting of two or more histologically distinct types of carcinoma
within the same topographic area. Familial occurrence of AciCC of the parotid gland has been
While serous acinar cell differentiation is diagnostic for AciCCs, the spectrum of histologic growth
patterns and cellular features is extremely variable. The classic solid variant with abundant serous
cells is usually a straightforward diagnosis, but histological variants may pose a diagnostic challenge.
A wide spectrum of morphologic patterns is exhibited and a variety of cell types are encountered in
AciCCs, and therefore the differential diagnostic difficulties may be serious. The most common growth
patterns found in AciCC are solid, microcystic, follicular and papillary-cystic. The predominant
structural pattern and cell composition show correlation, with solid variant composed mostly of serous
acinar cells, microcystic pattern of serous and vacuolated cells, intercalated-duct related and
non-specific glandular cell being the most common cell type in papillary-cystic and follicular
With two exceptions, neither the degree of acinar cell differentiation nor various growth patterns in
acinic cell carcinoma seem to influence prognosis.
These exceptions include development of
poorly differentiated foci in otherwise typical AciCC, referred to as dedifferentiation of
Dedifferentiated acinic cell carcinoma is composed of a typical AciCC and a poorly
differentiated highly malignant component in a variable proportion. The high grade component is usually
non-mucin producing carcinoma not otherwise specified (NOS)
but the case recurring with
poorly differentiated areas with high mitotic rate and myoepithelial immunoprofile has been
described.  Although "dedifferentiation" is always associated with tumor progression, little
is known about the molecular genetic events that regulate it. Also, the prognostic value of
"dedifferentiation" is unknown because small number of published cases preclude statistically significant
conclusions. However, it is generally accepted that dedifferentiated AciCC are associated with poor
clinical outcome, as they tend to recur and invade facial nerve. 
On the other hand, excellent prognosis is associated with well differentiated AciCC with abundant
lymphoid stroma.  This tumor variant is characterized by solid and microcystic growth
patterns, low proliferative activity with MIB-1 index lower than 5%, and abundant mature lymphocytes in
the stroma with formation of well developped germinal centers.  A few additional variants
have been reported, such as clear cell AciCC ,
oncocytic variant  and hybrid
tumors associated with benign and malignant tumors. 
The clinical course of AciCC is characterized by moderate risk of local recurrences (30 to 50%) and
low risk of distant metastases (15%). Distant metastatic dissemination and tumor-related deaths are
often preceded by local recurrence, the risk of which is higher after simple enucleation than after
parotidectomy. Clinical stage at the time of diagnosis is the most powerful predictor of
prognosis.  Other prognostic factors predicting risk of more aggressive behavior include
presence of necroses, gross invasion, size larger than 6 cm, deep lobe involvement, extraglandular
extension, increased pleomorphism, high mitotic rate, and prominent infiltration of nerves and blood
vessels.  Some authors have attempted to develop histology-based grading system placing
tumors in high and low grade categories depending on such features as growth pattern, vascular extension
and local invasion.  However, strict criteria for histopathologic grading of AciCC have
never been generally accepted. In contrast, the Ki-67 proliferative index assessed using the MIB1
antibody was demonstrated as an useful prognostic indicator.
Appropriate treatment for AciCC is complete surgical removal. In the parotid gland, superficial or
total parotidectomy without sacrifice of facial nerve is recommended. Elective neck dissection and
radiotherapy are not warranted.
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