—  SYMPOSIUM #51  —

Update of Common Salivary Tumors
Moderators: Dr. John Eveson and Dr. Silloo Kapadia

Section 6 - Acinic Cell Carcinoma

Alena Skálová
Czech Republik


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 . [1]

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). [1, 2] AciCC can also be associated with other tumor type within the hybrid neoplasms. [3] 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 described. [4]

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 variants. [5]

With two exceptions, neither the degree of acinar cell differentiation nor various growth patterns in acinic cell carcinoma seem to influence prognosis. [1, 5] These exceptions include development of poorly differentiated foci in otherwise typical AciCC, referred to as dedifferentiation of AciCC. [6, 7, 8, 9] 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) [6, 8, 9], but the case recurring with poorly differentiated areas with high mitotic rate and myoepithelial immunoprofile has been described. [7] 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. [7]

On the other hand, excellent prognosis is associated with well differentiated AciCC with abundant lymphoid stroma. [10] 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. [10] A few additional variants have been reported, such as clear cell AciCC [11], oncocytic variant [12] and hybrid tumors associated with benign and malignant tumors. [3]

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. [5] 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. [13] 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. [13] 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. [14, 15]

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.

References
  1. Dardick I, Kini S, Bradley G, et al. Atlas of Salivary Gland Tumor Cytopathology, Oral and Surgical Pathology. Pathology Images Inc, 2006.

  2. Mayorga M, Fernandez N, Val-Bernal JF. Synchronous ipsilateral sebaceous lymphadenoma and acinic cell adenocarcinoma of the parotid gland. Oral Surg Oral Med Oral Pathol Radiol Endod 1999;88:593-596.

  3. Nagao T, Sugano I, Ishida Y, et al. Hybrid carcinomas of the salivary glands: report of nine cases with clinicopathologic, immunohistochemical, and p53 gene alteration analysis. Mod Pathol 2002;15:724-733.

  4. Depowski PL , Setzen G, Chui A, et al. Familial occurrence of acinic cell carcinoma of the parotid gland. Arch Pathol Lab Med 1999; 123:1118-20.

  5. Barnes L, Eveson JW, Reichert P, Sidransky D (Eds). World Health organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. IARC Press: Lyon 2005, pp. 216-218.

  6. Stanley RJ, Weiland LH, Olsen KD, et al. Dedifferentiated acinic cell (acinous) carcinoma of the parotid gland. Otolaryngol Head Neck Surg 1988;98:155-161.

  7. Piana S, Cavazza A, Pedroni C, et al. Dedifferentiated acinic cell carcinoma of the parotid gland with myoepithelial features. Arch Pathol Lab Med 2002;126:1104-1105.

  8. di Palma S, Corletto V, Lavarino C, et al. Unilateral aneuploid dedifferentiated acinic cell carcinoma associated with bilateral low grade diploid acinic cell carcinoma of the parotid gland. Virchows Arch 1999;434:361-365.

  9. Henley JD, Geary WA, Jackson C, et al. Dedifferentiated acinic cell carcinoma of the parotid gland: a distinctive rarely described entity. Hum Pathol 1997;28:869-873.

  10. Michal M, Skálová A, Simpson RHW, et al: Well differentiated acinic cell carcinoma of salivary glands associated with lymphoid stroma. Hum Pathol 1997; 28(5):595-600.

  11. Echevarria RA. Ultrastructure of acinic cell carcinoma and clear cell carcinoma of parotid gland. Cancer 1967;20:563-571.

  12. Gnepp DR , Brandwein MS, Henley JD. Salivary and Lacrimal Glands: Acinic cell carcinoma, In: Diagnostic Surgical Pathology of the Head and Neck, Gnepp DR (ed). W.B. Sanders Company, Philadelphia . 2001; 376-379.

  13. Batsakis JG, Luna MA, El-Naggar AK. Histopathologic grading of salivary gland neoplasms: II. Acinic cell carcinomas. Ann Otol Rhinol Laryngol 1990;99:929-933.

  14. Skálová A, Leivo I, Boguslawsky K, et al: Cell proliferation correlates with prognosis in acinic cell carcinomas of salivary gland origin. Immunohistochemical study of 30 cases using the MIB 1 antibody in formalin-fixed paraffin sections. J Pathol 1994;173:13-21.

  15. Hellquist HB, Sundelin K, Di Bacco A, et al. Tumor growth fraction and apoptosis in salivary gland acinic cell carcinomas: Prognostic implications of Ki-67 and bcl-2 expression and of in situ end labelling (TUNEL). J Pathol 1997;181:323-329.