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Year : 2021  |  Volume : 17  |  Issue : 4  |  Page : 1115-1118

Acinic cell carcinoma of the parotid gland with neuroendocrine differentiation

1 Department of Pathology, Maulana Azad Medical College, New Delhi, India
2 Department of Otorhinolaryngology And Head And Neck Surgery, Maulana Azad Medical College, New Delhi, India

Date of Submission25-Aug-2019
Date of Acceptance30-Dec-2019
Date of Web Publication26-Nov-2020

Correspondence Address:
Reena Tomar
Department of Pathology, Maulana Azad Medical College, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_645_19

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 > Abstract 

Acinic cell carcinoma (ACC) is a malignant salivary gland tumor characterized by tumor cells displaying acinar features. Usually presenting as a slow-growing tumor, ACC, however, may show dedifferentiation to a higher grade including neuroendocrine carcinoma. In addition, ACC may rarely show focal neuroendocrine differentiation without any frank evidence of neuroendocrine carcinoma. We describe such a case of ACC of the parotid gland in a 65-year-old female, which showed neuroendocrine differentiation. The diagnostic clues, immunohistochemistry panel, and prognostic and treatment aspects are also presented.

Keywords: Acinic cell carcinoma, neuroendocrine, parotid gland, salivary glands

How to cite this article:
Rath A, Tomar R, Agarwal R, Singh M, Jain S, Khurana N, Rathore PK. Acinic cell carcinoma of the parotid gland with neuroendocrine differentiation. J Can Res Ther 2021;17:1115-8

How to cite this URL:
Rath A, Tomar R, Agarwal R, Singh M, Jain S, Khurana N, Rathore PK. Acinic cell carcinoma of the parotid gland with neuroendocrine differentiation. J Can Res Ther [serial online] 2021 [cited 2021 Dec 9];17:1115-8. Available from: https://www.cancerjournal.net/text.asp?2021/17/4/1115/301002

 > Introduction Top

Acinic cell carcinoma (ACC) is a malignant salivary gland tumor with acinar cell differentiation and usually involves the parotid gland. In general, considered a low-grade tumor, a proportion may show higher grade with metastatic potential. Zymogen granules are characteristic of ACC and give the acinic cells a basophilic granular appearance.[1] However, rarely, these acinic cells may show associated neuroendocrine differentiation. Only a few case reports and series are available in the English literature discussing this association. We present a case of ACC of the parotid gland with neuroendocrine differentiation.

 > Case Report Top

A 65-year-old female presented with the left preauricular painless swelling for 5 months, which progressed to three times the original size. On local examination, a 4 cm × 3 cm, firm, nontender, slightly mobile swelling was noted in the left parotid region. There were no associated features of facial palsy. Contrast-enhanced computed tomography of the head and neck showed a well-defined, heterogeneously enhancing lesion measuring 4.2 cm × 3.2 cm in the superficial part of the left parotid gland [Figure 1]a and [Figure 1]b. The deeper lobe was normal. Fine-needle aspiration of the swelling showed a highly cellular smear exhibiting large clusters of atypical cells, which at many places were forming an acinar pattern [Figure 2]a. These tumor cells showed a moderate amount of granular cytoplasm, round-to-oval pleomorphic nuclei with indistinct nucleoli. Focal areas showed stromal fragments. No areas of necrosis or significant mitosis were noted. A diagnostic possibility of ACC or carcinoma ex pleomorphic adenoma was rendered. Superficial parotidectomy was performed, and the specimen was sent for histopathological examination. Grossly, the cut surface of the tissue showed an infiltrating grayish-white growth measuring 4 cm × 3.5 cm × 2.5 cm [Figure 2]b. Microscopy showed an infiltrating tumor exhibiting large lobules, acini with the glandular pattern, and solid nests of tumor cells [Figure 2]c. Many of the lobules showed central necrosis [Figure 2]d. The tumor cells displayed moderate amount of granular, eosinophilic cytoplasm and round to oval, vesicular nuclei with indistinct nucleoli [Figure 2]e. However, many of the nuclei also showed stippled chromatin [Figure 2]f. Mitotic figures, including atypical ones, were noted. The tumor showed a moderate lymphomononuclear inflammatory response. No areas suggestive of pleomorphic adenoma were noted. The cytoplasmic granules stained positive for Periodic acid–Schiff (PAS) stain, were diastase resistant and negative for mucicarmine. However, the presence of these zymogen granules did not impart the characteristic basophilic appearance to the cytoplasm; rather, the cytoplasm was granular and eosinophilic. Considering the associated stippled nuclear chromatin, a panel of immunohistochemistry (IHC), including the neuroendocrine markers, was performed. On IHC, the tumor cells were positive for cytokeratin (CK), low molecular-weight CK, and DOG.1 [Figure 3]a, [Figure 3]b, [Figure 3]c and were negative for CK7, carcinoembryonic antigen (CEA), p63, smooth muscle actin, and MOC31. In addition, many of the foci of tumor cells were immunopositive for neuron-specific enolase (NSE), synaptophysin, and chromogranin [Figure 3]d, [Figure 3]e, [Figure 3]f, indicating the associated neuroendocrine differentiation. A final diagnosis of ACC with neuroendocrine differentiation was rendered. The patient is currently on follow-up and is contemplated for radiotherapy in view of positive resection margins.
Figure 1: (a and b) Contrast-enhanced computed tomography head and neck showing a well defined, heterogeneously enhancing lesion measuring 4.2 cm × 3.2 cm in the superficial part of the left parotid gland

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Figure 2: (a) Fine-needle aspiration of the swelling displaying clusters of atypical cells forming an acinar pattern (MGG, ×400), (b) Gross image showing an infiltrative grayish-white growth (HE, x100). (c) An acinar pattern of the infiltrating tumor with the lymphoplasmacytic inflammatory response (HE, x100). (d) Tumor lobules showing central necrosis. (e) Tumor cells showing eosinophilic granular cytoplasm and round to oval, moderately pleomorphic clear to vesicular nuclei with indistinct nucleoli (HE, x400). (f) Nuclei of many of the tumor cells also show stippled chromatin (HE, x1000)

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Figure 3: Immunohistochemistry displaying tumor cells to be positive for cytokeratin (a); low molecular weight cytokeratin (b); DOG.1 (c); neuron-specific enolase (d); synaptophysin (e); and chromogranin (f)

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 > Discussion Top

ACC is a low-grade salivary gland tumor with acinar cell differentiation characterized by the zymogen granules. It commonly presents in the 4th–5th decades with a female preponderance; however, it is the second-most common salivary gland malignancy in children. The parotid gland is the most common organ involved (90%–95%), followed by the submandibular gland and other minor salivary glands.[1] However, recent studies have found many of the nonparotid ACCs to be mammary analog secretory carcinoma (MASC) characterized by ETV6-NRTK3 translocation.[2]

Painless swelling is the most common clinical feature, while facial palsy is seen in 5%–10% of cases.[1] Similarly, the present case was an elderly female with a painless parotid swelling. Grossly, the tumor is usually well delineated with an incomplete capsule. The cut surface is solid with or without cystic spaces. Microscopically, the tumor usually infiltrates in broad fronts with various patterns, including lobules, microcystic spaces, cords, solid tubules, acinar, papillary-cystic, and follicular patterns. The tumor may show dense lymphoid aggregates. The tumor cells are immunopositive for CK and CEA and do not show myoepithelial component. DOG.1 is a recently described acinic cell marker and is said to be positive in all cases of ACCs.[3]

Neuroendocrine differentiation in primary salivary gland tumors is reported to constitute 1% of all parotid gland tumors.[4] The WHO classifies poorly differentiated carcinoma into neuroendocrine and nonneuroendocrine carcinomas.[1] However, it is pertinent to differentiate such neuroendocrine carcinomas (NEC) from the primary salivary gland tumors with extensive neuroendocrine differentiation, since the former has a poorer prognosis and has to be managed aggressively. Among the primary tumors, adenoid cystic carcinoma, adenocarcinoma, and ACC are the reported cases to be associated with neuroendocrine differentiation.[5] ACC is known to show zymogen granules in the cytoplasm, which imparts a basophilia to it. However, cytologically the cells often show fragile, finely vacuolated cytoplasm and occasionally exhibit oncocytic changes.[6] In contrast, the present case, although showed PAS-positive, diastase-resistant cytoplasmic granules indicating acinar cell differentiation; however, the cytoplasm did not show the characteristic basophilia. In addition, the nuclei at many places showed stippled chromatin indicating the possible associated neuroendocrine differentiation, which was later confirmed by IHC. The extent of differentiation may vary as there are case reports which show extensive neuroendocrine differentiation in ACC which has to be differentiated from primary NEC of the salivary gland.[7] The present case showed neuroendocrine differentiation in the foci of many tumor lobules. Studies with similar findings have confirmed it by ultrastructural examination which has shown the presence of neurosecretory granules in the cytoplasm.[5],[8] Only a few case reports and series are available in the English literature on this association. Hayashi et al. studied neuropeptide expression (NSE and LEU-7) in various salivary gland neoplasms and found Leu-7 expression in 7 of 12 cases of ACC.[5] Roy et al. reported a similar case of ACC of the parotid gland in a 48-year-old female with extensive neuroendocrine differentiation.[7] Ito et al. also reported such an association in a 55-year-old female.[8] Thus, all the case reports, including the present case, have been seen in female adults.

Dedifferentiation of ACCs to high-grade adenocarcinoma, poorly differentiated carcinoma, or undifferentiated carcinoma has been described.[3] On this basis, there might be a possibility of dedifferentiation to the neuroendocrine type of poorly differentiated carcinoma. However, in dedifferentiated ACC, the two components are usually juxtaposed to each other rather than showing a transition.[3] The present case did not show any components of classic ACC juxtaposed with undifferentiated carcinoma, and there were no areas exhibiting greater nuclear pleomorphism or increased mitotic figures. Furthermore, dedifferentiated ACC usually presents with rapid tumor growth, significant pain, and frequent facial nerve palsy none of which were present in our case, ruling out a possibility of such an entity.[3] Other differential diagnoses that may be considered are primary NEC and metastatic NEC. These can be small-cell or large-cell NEC which show features typical of these entities as described in other organs and do not display any foci of classic ACC.[7] The absence of basophilia, eosinophilic granular cytoplasm, and stippled chromatin are also characteristically seen in MASC. However, MASC is described in minor salivary glands; is immunoreactive for S100, mammaglobin, and GCDFP-15; and is negative for p63 and DOG.1.[3] The present case shows immunoreactivity to DOG.1.

ACC, as has already been mentioned, is usually a low-grade tumor. However, recurrences as high as 35% and metastasis to cervical lymph nodes and lungs have been mentioned.[1] Clinical stage and resection margin status are the most important prognostic indicators.[3] The present case, though did not show cervical lymph node metastasis, exhibited positive resected margins. Histological features, though not reliable, mentioned in literature imparting poor prognosis are focal necrosis, neural invasion, frequent mitosis, MIB1 index >5%, atypia, and lymphocytic depletion in the stroma.[3],[6] The present case exhibited necrosis, and the lymphocytic infiltrate was not dense, indicating the higher grade of the tumor.

The primary management of ACC includes complete excision of the tumor by superficial or total parotidectomy. Subsequent radiotherapy may be administered in cases with recurrences, dedifferentiated ACC, positive margin status, or metastasis. As recurrences are not uncommon, especially in incompletely excised tumors, long-term follow-up of the patients is necessary.[6] The present case is also on regular follow-up and is being considered for radiotherapy in view of the higher grade of the tumor and positive resection margins.

 > Conclusion Top

ACC with neuroendocrine differentiation is rarely reported and is important to identify to differentiate it from possibilities of dedifferentiated ACC, primary NEC, and metastatic NEC which have a relatively poorer prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO Classlfication of Head and Neck Tumours. 4th ed. Lyon: IARC; 2017. p. 166-7.  Back to cited text no. 1
Bishop JA, Yonescu R, Batista D, Eisele DW, Westra WH. Most nonparotid “acinic cell carcinomas” represent mammary analog secretory carcinomas. Am J Surg Pathol 2013;37:1053-7.  Back to cited text no. 2
Chan JK, Cheuk W. Tumors of the salivary glands. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 4th ed. Philadelphia: Elsevier; 2013. p. 324-31.  Back to cited text no. 3
Pontius AT, Ducic Y. Metastatic neuroendocrine tumors of the parotid gland. Am J Otolaryngol 2004;25:129-33.  Back to cited text no. 4
Hayashi Y, Deguchi H, Nakahata A, Kurashima C, Hirokawa K. Immunopathological study of neuropeptide expression in human salivary gland neoplasms. Pathobiology 1990;58:212-20.  Back to cited text no. 5
Al-Zaher N, Obeid A, Al-Salam S, Al-Kayyali BS. Acinic cell carcinoma of the salivary glands: A literature review. Hematol Oncol Stem Cell Ther 2009;2:259-64.  Back to cited text no. 6
Roy S, Dhingra KK, Gupta P, Khurana N, Gupta B, Meher R. Acinic cell carcinoma with extensive neuroendocrine differentiation: A diagnostic challenge. Head Neck Pathol 2009;3:163-8.  Back to cited text no. 7
Ito K, Kakudo K, Mori I, Horiuchi M, Osamura Y. Neuroendocrine differentiation in a case of acinic cell carcinoma of the parotid gland. Acta Pathol Jpn 1990;40:279-87.  Back to cited text no. 8


  [Figure 1], [Figure 2, [Figure 3]


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