Acinic cell carcinoma is a neoplasm of low grade malignancy and composed of cells that have got differentiated towards serous acinar cells. It was originally described by Nasse in 1892 as a low grade, benign lesion with later studies confirming its malignant behavior which was in between that of adenoma and carcinoma [1]. Hence, it was initially termed acinic cell tumor in the earlier WHO classification in 1972 which was later revised to acinic cell carcinoma in 1991. Acinic cell carcinoma is considered to be the third most common major salivary gland tumor/malignancy [2].

De-differentiation or, high-grade malignant transformation (HGT) has been described in a variety of salivary gland tumors although the phenomenon is reported to be a relatively rare event. Authors preferably use the term HGT rather than de-differentiation for such cases [3]. De-differentiation is the progression of cells towards a less differentiated state in which the original line of differentiation is no longer evident. The first acinic cell carcinoma with high grade malignant transformation of salivary gland was reported by Stanley et al. in 1988. Thirty-five cases have been described in literature so far and most of them showed poor clinical outcome. Also, all cases reported to date were of parotid gland origin with involvement of both the superficial and/or, deep lobes. These tumors have a slight male predisposition, high recurrence rates, and a high propensity for cervical lymph node metastasis, suggesting a role for neck dissection in the management of affected patients [4] . Furthermore, vascular and peri-neural invasions are typically observed in acinic cell carcinomas.

The diagnosis is usually confirmed with a fine needle aspiration cytology (FNAC) procedure, while radical surgical excision of the tumor is the mainstay of treatment of this malignant neoplasm. Other treatment modalities include radiotherapy which might be indicated in some cases. Acinic cell carcinomas have a significant tendency to recur, to lead to metastases in cervical lymph nodes, and lungs rarely, and may have an aggressive evolution, therefore, making long-term follow-up, mandatory, post-treatment.

A 35-year-old female reported with a chief compliant of a swelling since one month and pain since 15 days in the lower left back tooth region. The swelling actually had an insidious origin and progression and started as a small imperceptible growth which was painless initially and gradually increased in size and became painful with the pain being continuous, dull, throbbing in nature which used to get aggravated on brushing and other mechanical trauma/provocation and on taking hard foods. Pain used to get temporarily relieved with medication. There was shedding of a tooth in the left lower back tooth region 15 days prior to the reporting of the patient. Since then, patient gave a history of increase in the size of the swelling. Patient had multiple, palpable submental and submandibular lymph nodes, present which were firm, mobile and tender. On clinical examination, there was a single, unilateral, ovoid-shaped, swelling present irt left lower third of face measuring approximately 4x5 cm in greatest dimensions (Figure 1). The skin overlying the swelling was normal in appearance without signs of any erythema and/or, discharge or, ulceration. The swelling had well-defined edges and the borders extended from 2 cm away from corner of the mouth anteriorly to 2 cm ahead of the angle of mandible posteriorly, and from below the imaginary line drawn from the corner of the mouth and lobule of ear superiorly to approximately 1 cm below the inferior border of the mandible inferiorly (Figure 2). On palpation, the swelling was well-defined, firm to hard in consistency, slightly tender and fixed to the underlying bone. On intra-oral examination, there was an ulcero-proliferative, exophytic growth seen irt teeth #35, #36, #37 region on the lingual side. The mucosa was perforated due to expansion of the buccal and lingual cortical plates with exposure of the white, necrosed bone (Figure 3). On palpation, tenderness and vestibular obliteration were present. Orthopantomograph (OPG) revealed a solitary, irregular radiolucency extending from the distal surface of tooth #34 till the mesial surface of tooth #37. (Figure 4). Incisional biopsy was performed and sent for histopathological examination which showed neoplastic cells arranged in solid, lobular pattern, separated by thin, fibrous connective tissue septae (Figure 5). Epithelial cells were pleomorphic in nature with increased mitotic activity and with keratin pearl formation suggestive of a de-differentiated acinic cell carcinoma (Figure 6). Based on the said clinical, radiological and histopathological features, a final diagnosis of a primary intraosseous salivary gland carcinoma was arrived-at. The patient was, then, referred for hemimandibulectomy and re-construction followed by radiotherapy and chemotherapy under guidance.

Acinic cell carcinoma is a low grade malignant epithelial neoplasm of salivary gland tissue origin in which at least few of the neoplastic cells demonstrate serous acinar differentiation characterized by the presence of cytoplasmic zymogen secretory granules. These carcinomas account for about 4% of all salivary gland neoplasms with around 7–17.5% going for malignant transformation [5]. Numerous reports indicate primary salivary gland neoplasms to be completely intra-bony, yet, non-neoplastic salivary gland tissues have rarely been found in such locales, with few reports suggesting odontogenic origin of such tumors, although, the rate of occurrence of salivary gland choristomas, hamartomas, embryonic rests, and aberrant salivary gland tissues within the alveolar bone, is less than 2.6 of every 1000 marrow samples biopsied with this providing an additional and quite seemingly logical histogenetic explanation for the presence of intraosseous salivary gland neoplasms [6]. Neoplastic transformation of intra-bony salivary gland tissues, in particular, is an uncommon phenomenon with mandible being one of the most common sites for such neoplasia, accounting for around 75% of all the cases seen [7]. Entrapment of salivary gland tissue within the jaw bones during initial stages of development and metaplastic transformation of the epithelial lining of odontogenic cysts are the two significant hypotheses that have been proposed for such rare, intraosseous salivary gland neoplasms [8]. Acinic cell carcinomas may be found in all age groups, including children and early adolescence, with the peak incidence noted in the fifth and sixth decades of life. The most important clinical features include slow-growing lesions with an insidious onset and progression, most of the times, and which are attended by pain, later, in the course of development due to secondary changes and/or, as a result of mechanical trauma after they reach sufficient sizes [9]. Histopathologically, large lobules or, nests of tumor cells with little intervening stroma are characteristic. The arrangement of neoplastic cells is quite variable. Generally, cells are arranged in solid masses with blunted or, pushing margins. Other variants include microcystic, papillary, and follicular forms. Radical surgical excision of the tumors is the preferred treatment although recurrences are not uncommon [10].

To conclude, despite the rarity of intraosseous acinic cell carcinomas, one should be well aware of this diagnostic possibility, emphasizing the need for histopathological analysis, a clearly defined and guided treatment strategy, and an adequate follow-up to check for the possibility of any recurrences.

1. Ellis G, Simpson RHW. Acinic cell carcinoma. In: Barnes L, Eveson JW, Reichert P, Sidransky D eds. World Health Organization Classification of Tumors, Pathology and Genetics of Head and Neck Tumors. Lyon: IARC Press; 2005. p. 216–8.    
2. Thackray AC, Sobin LH. Histological typing of salivary gland tumors. International Histological Classification of Tumors. Geneva: WHO; 1972.    
3. Stanley RJ, Weiland LH, Olsen KD, Pearson BW. Dedifferentiated acinic cell (acinous) carcinoma of the parotid gland. Otolaryngol Head Neck Surg 1988 Feb;98(2):155–61.   [CrossRef]   [Pubmed]    
4. Skálová A, Sima R, Vanecek T, et al. Acinic cell carcinoma with high-grade transformation: A report of 9 cases with immunohistochemical study and analysis of TP53 and HER-2/neu genes. Am J Surg Pathol 2009 Aug;33(8):1137–45.   [CrossRef]   [Pubmed]    
5. Chiosea SI, Griffith C, Assaad A, Seethala RR. The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. Am J Surg Pathol 2012 Mar;36(3):343–50.   [CrossRef]   [Pubmed]    
6. Johnykutty S, Miller CH, Hoda RS, Giampoli EJ. Fine-needle aspiration of dedifferentiated acinic cell carcinoma: Report of a case with cyto-histological correlation. Diagn Cytopathol 2009 Oct;37(10):763–8.   [CrossRef]   [Pubmed]    
7. Hyun OJ, Yoo IeR, Jung CK, Hoon Kim S, Chung SK. F-18 FDG PET/CT findings of dedifferentiated acinic cell carcinoma. Clin Nucl Med 2010 Jun;35(6):473–4.   [CrossRef]   [Pubmed]    
8. Piana S, Cavazza A, Pedroni C, Scotti R, Serra L, Gardini G. Dedifferentiated acinic cell carcinoma of the parotid gland with myoepithelial features. Arch Pathol Lab Med 2002 Sep;126(9):1104–5.   [CrossRef]   [Pubmed]    
9. Prasad M, Kraus DH. Acinic cell carcinoma of the parotid gland presenting as an external auditory canal mass. Head Neck 2004 Jan;26(1):85–8.   [CrossRef]   [Pubmed]    
10. González-Peramato P, Jiménez-Heffernan JA, López-Ferrer P, Vicandi B, Viguer JM. Fine needle aspiration cytology of dedifferentiated acinic cell carcinoma of the parotid gland: A case report. Acta Cytol 2006 Jan-Feb;50(1):105–8.   [Pubmed]