Salivary glands
Primary salivary gland neoplasms
Malignant
Acinic cell carcinoma

Resident / Fellow Advisory Board: David B. Chapel, M.D.
Arash H. Lahouti, M.D.
Rema A. Rao, M.D.

Minor changes: 29 March 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Acinic cell carcinoma[TI] salivary[TI]

Arash H. Lahouti, M.D.
Rema A. Rao, M.D.
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Cite this page: Lahouti AH, Rao RA. Acinic cell carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsaciniccell.html. Accessed April 19th, 2021.
Definition / general
Essential features
  • Approximately 6 - 8% of all salivary gland neoplasms and 10 - 17% of primary salivary gland malignancies
  • Parotid gland is the most common site
  • Solid, microcystic, papillary cystic or follicular growth of acinar cells, with granular to vacuolated cytoplasm and eccentric round nuclei with conspicuous nucleoli
  • Neoplastic cells positive for pankeratins, DOG1, SOX10 and PAS-D
  • Favorable prognosis, with low rates of local recurrence, distant metastasis and high grade transformation
ICD coding
  • ICD-O: 8550/3 - acinic cell carcinoma
  • ICD-10: C08.9 - malignant neoplasm of salivary gland, unspecified
Epidemiology
Sites
  • Most common site: parotid gland (80%)
  • Submandibular, sublingual and minor salivary glands rarely involved (13 - 17%)
    • Most common sites in the oral cavity are the buccal mucosa and upper lip (Cancer 1983;52:542)
Etiology
Clinical features
  • Typical clinical presentation is a slow growing mass
  • Pain, fixation to surrounding tissues and cranial nerve VII dysfunction are uncommon
  • Cervical lymph node metastasis uncommon (up to 10%)
  • Reference: Cancer 1991;67:172
Diagnosis
  • Radiology (ultrasound, CT or MRI) demonstrates presence and extent of mass lesion
    • MRI superior to CT in assessing invasion of adjacent structures
  • Fine needle aspiration cytology and core biopsy
    • Low sensitivity in parotid:
      • High false negatives due to morphologic overlap with normal acini (Arch Pathol Lab Med 2005;129:26)
      • Diagnosis more challenging if tumor cells lack secretory granules
      • Diagnostic accuracy higher in cases with high grade transformation
  • Definitive diagnosis most often established on a surgical excision specimen (e.g., parotidectomy)
  • Positron emission tomography (PET) may be done postoperatively in cases of high grade transformation (Eur Arch Otorhinolaryngol 2016;273:3511)
Radiology description
  • Ultrasound: well demarcated, lobular, hypoechoic, heterogeneous and poorly vascularized
  • Computed tomography (CT):
    • Findings are nonspecific and there is an overlap with benign tumors
    • Solid to cystic mass
    • Focal low attenuating portions on CT may be present corresponding to cystic degeneration or hemorrhage (J Comput Assist Tomogr 2005;29:121)
Radiology images

Images hosted on other servers:

MRI: cystic lesion of the upper lip

CT and US: right parotid nodule

Prognostic factors
  • 5 year survival: 97%
  • May recur years or decades after initial diagnosis
  • Metastatic rate ~ 16%
  • Local recurrence rate is up to 33%; 12% in another large series (Cancer 1978;41:924, Cancer 1983;52:542)
  • Adverse prognostic factors include
    • Male gender
    • Age > 45 (JAMA Otolaryngol Head Neck Surg 2013;139:1195)
    • Tumor > 3 cm at presentation (Oral Oncol 2018;82:53)
    • Metastatic disease
    • Tumor necrosis
    • Nuclear pleomorphism
    • Mitosis (> 2/10 high power fields)
    • Ki67 index > 5%
    • High grade transformation
    • Vascular and perineural invasion
    • Extracapsular extension (Cancer 2009;115:2128)
    • Positive resection margins
    • Invasion of the skull base
    • Depletion of lymphocytes within the stroma
Case reports
Treatment
  • Complete surgical excision (J Oral Maxillofac Surg 2005;63:917)
  • Radiotherapy may be indicated for tumors that cannot be completely excised or metastatic disease
  • Systemic therapy may be indicated for high grade tumors, positive margins, advanced stage disease, or metastatic tumors
Clinical images

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1.2 cm upper lip nodule

Gross description
  • Tumor dimensions range from less than 1 cm to 13 cm (85% of the lesions less than 3 cm) (Cancer 1983;52:542)
  • Well circumscribed, soft rubbery, tan-yellow to pink mass with homogeneous cut surface
  • Cystic change and hemorrhage may occur
Gross images

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Well circumscribed multilobulated mass

Microscopic (histologic) description
  • Multiple cell types are noted
    • Cell types include serous acinar, intercalated ductal, vacuolated, nonspecific glandular and clear cells
  • Acinar cells are large and polyhedral, with basophilic granular cytoplasm and eccentric nuclei
    • Cytoplasmic diastase resistant positive periodic acid-Schiff (PAS) reaction may be focal
  • Variety of morphologic patterns, including solid, microcystic, papillary cystic and follicular (Cancer 1983;52:542)
  • Prominent lymphoid infiltrate may be present (tumor associated lymphoid proliferation varies from randomly scattered, patchy collections of lymphocytes to diffuse, dense infiltrates with well formed follicles throughout the tumor) (Oral Surg Oral Med Oral Pathol 1994;77:19)
  • Mitosis, necrosis and significant pleomorphism usually absent
  • No specific histologic grading system
Microscopic (histologic) images

Contributed by Rema A. Rao, M.D. and Arash H. Lahouti, M.D.
Well circumscribed tumor

Well circumscribed tumor

Finely vacuolated cytoplasm

Finely vacuolated cytoplasm

TALP

Tumor associated lymphoid proliferation

Cystic pattern and hemorrhage Cystic pattern and hemorrhage

Cystic pattern and hemorrhage


NR4A3 nuclear stain NR4A3 nuclear stain

NR4A3 nuclear stain

Virtual slides

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Acinic cell carcinoma, parotid

Acinic cell carcinoma, cystic change

Cytology description
  • Cellular aspirates
  • Cytologic diagnosis based on identifying acinar-like cells
  • Tend to form small groups and loosely cohesive clusters as well as single cells (Diagn Histopath 2018;24:417)
  • Cells are large but morphologically resemble normal acinar cells
    • Round nuclei with tiny nucleoli
    • Abundant finely vacuolated to granular cytoplasm
  • Stripped or bare nuclei may be present in the background, can mimic lymphocytes
  • Lymphocytic infiltrate may be prominent
  • Laminated psammoma body-like calcification may be present
  • Pitfall: acinic cells may resemble oncocytes and in the presence of lymphocytic infiltrate, the tumor may be misdiagnosed as Warthin tumor
Cytology images

Contributed by Rema A. Rao, M.D. and Arash H. Lahouti, M.D.
Loosely cohesive groups

Loosely cohesive groups

Cellular smears

Cellular smears

Finely vacuolated to granular cytoplasm

Finely vacuolated to granular cytoplasm

Round eccentric nuclei

Round eccentric nuclei

Loosely cohesive clusters

Loosely cohesive clusters

PASD

PASD

Positive stains
Negative stains
Molecular / cytogenetics description
  • Recurrent (t[4;9][q13;q31]) genomic rearrangement (resulting in translocation of active enhancer regions from the secretory Ca binding phosphoprotein [SCPP] gene cluster to the region upstream of nuclear receptor subfamily 4 group A member 3 [NR4A3], leading to NR4A3 IHC overexpression) (Cancer Cytopathol 2021;129:104)
Molecular / cytogenetics images

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FISH, NR4A3 break apart probe

Sample pathology report
  • Parotid gland, right, inferior, partial parotidectomy:
    • Acinic cell carcinoma, 1.7 cm (see synoptic report)
    • No lymphovascular invasion identified
    • No perineural invasion identified
    • Resection margins uninvolved by carcinoma
    • Two lymph nodes, negative for carcinoma (0/2)
    • Tumor associated lymphoid proliferation present
Differential diagnosis
Board review style question #1
Which of the following statements is true regarding acinic cell carcinoma of salivary glands?

  1. Acinic cell carcinoma is a high grade malignant neoplasm
  2. Most commonly occurs in minor salivary glands
  3. Younger age at presentation and presence of tumor associated lymphocytes are associated with a poor prognosis
  4. Neoplastic cells express DOG1 and SOX10
Board review style answer #1
D. Neoplastic cells express DOG1 and SOX10. DOG1 and SOX10 are expressed in benign acinar cells and intercalated duct cells and other salivary gland neoplasms. However, strong diffuse expression of these markers can help distinguish acinic cell carcinoma from other salivary gland neoplasms. Acinic cell carcinoma is considered low intermediate grade malignancy of salivary glands, although high grade transformation may occur (answer A). The majority of cases arise in the parotid gland (answer B). Older age at the onset (> 45) and depletion of lymphocytes within the stroma are linked to worse outcomes (answer C).

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Reference: Acinic cell carcinoma
Board review style question #2

A 51 year old woman presents with a left parotid mass. CT images show a well circumscribed cystic lesion measuring 3 cm. An excisional biopsy is performed (see image above). The neoplastic cells are positive for periodic acid-Schiff with diastase (PASD). Which of the following statements is true regarding this lesion?

  1. Pain and facial nerve dysfunction are uncommon presenting symptoms
  2. Mitosis, necrosis and significant pleomorphism are usually present
  3. MYB immunohistochemical staining in FNA specimens is useful in diagnosis of this tumor
  4. Cytology aspirates of this tumor can show predominance of extracellular mucin
Board review style answer #2
A. Pain and facial nerve dysfunction are uncommon presenting symptoms

The most common initial presentation in patients with acinic cell carcinoma is painless mass. Clinical examination shows a firm, mobile nodule in the parotid gland. Facial nerve paralysis or paresis is an uncommon initial finding. MYB immunohistochemical staining is useful in diagnosis of adenoid cystic carcinoma. The presence of extracellular mucin in aspirates is a feature of mucoepidermoid carcinoma.

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Reference: Acinic cell carcinoma
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