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Salivary glands

Primary salivary gland neoplasms

Benign

Oncocytoma

Authors: Jenny Tung Hiong Lee, M.D., Ruta Gupta, M.D.

Editorial Board Member: Marc Pusztaszeri, M.D.

Deputy Editor-in-Chief: Kelly Magliocca, D.D.S., M.P.H.

Last author update: 21 May 2025

Last staff update: 21 May 2025

Copyright: 2003-2025, PathologyOutlines.com, Inc.

PubMed Search: Oncocytoma

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Table of Contents

Cite this page: Lee JTH, Gupta R. Oncocytoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsoncocytoma.html. Accessed August 25th, 2025.

Definition / general

Benign tumor of salivary gland origin
Exclusively or predominantly composed of oncocytes
Accounts for 1 - 2% of salivary gland neoplasms

Essential features

Rare, benign salivary gland neoplasm
Usually unilateral and mostly occurs in parotid
Tumor is composed exclusively or predominantly of oncocytes
Cytoplasm is eosinophilic and granular due to the presence of abundant mitochondria within the cytoplasm
Can be positron emission tomography (PET) avid
Treated with local excision

Terminology

Oncocytic adenoma, oxyphilic adenoma

ICD coding

ICD-O: 8290/0 - oncocytoma
ICD-10: D11.9 - benign neoplasm of major salivary gland, unspecified

Epidemiology

Rare; constitutes < 2% of all salivary gland neoplasms (Head Neck Pathol 2024;18:126)
Age group: 60 - 80 years old
No sex predilection

Sites

Most (> 80%) occur in the parotid; ~10% occur in the submandibular gland
The rest occur in the sublingual gland, minor salivary glands and respiratory tract

Pathophysiology

Pathogenesis remains unclear; could be neoplastic / hyperplastic or metaplastic growth
Oncocytoma may arise in the background of multinodular oncocytic hyperplasia
Eosinophilic granular cytoplasm of oncocytes is due to the presence of increased intracytoplasmic mitochondrial content
Reference: Ann Maxillofac Surg 2018;8:330

Etiology

Associated with radiation exposure or radiotherapy
Smoking
Older age
Reference: Head Neck Pathol 2024;18:126

Clinical features

Usually presents as a unilateral, slow growing, painless and solitary mass
Rarely bilateral (Cancer Diagn Progn 2024;4:814)
Rarely presents with obstructive symptoms if occurring in the nasal or respiratory tract
Rarely occurs in Birt-Hogg-Dubé syndrome (BHD) (Case Rep Radiol 2018;2018:6265175, Head Neck Pathol 2024;18:52)

Diagnosis

Typically requires histopathologic examination for definitive diagnosis
Fine needle aspiration cytology along with clinical and radiologic correlation can often suggest the diagnosis

Radiology description

Ultrasound: sonographic features are nonspecific and include (J Ultrasound 2021;24:241)
- Ovoid mass, usually homogeneously hypoechoic but can be heterogeneous
- Typically well defined, occasionally lobulated
- Vascular
Computed tomography (CT): often seen as a well defined mass showing homogeneous enhancement (AJNR Am J Neuroradiol 2010;31:1413)
Magnetic resonance imaging (MRI): appearance can be variable (J Ultrasound 2021;24:241)
- T1: hypointense
- T2: isointense to hypointense
- T1C+: isointense
PET FDG: high fluorodeoxyglucose (FDG) uptake (due to mitochondrial accumulation) (J Ultrasound 2021;24:241)

Radiology images

Images hosted on other servers:

Ultrasound

MRI

Increased FDG uptake

Prognostic factors

Favorable prognosis of a benign tumor following removal
Low risk for local recurrence
Malignant transformation is extremely rare
Reference: Head Neck Pathol 2024;18:126

Case reports

73 year old man with right parotid swelling for 35 years (J Oral Maxillofac Pathol 2023;27:S41)
Case series of submandibular gland swelling (J Maxillofac Oral Surg 2023;22:127)

Treatment

Complete surgical removal is the treatment of choice (Head Neck Pathol 2024;18:126)

Clinical images

Images hosted on other servers:

Extraoral facial asymmetry

Gross description

Usually tumor presents as well circumscribed, lobulated, reddish brown nodules
Mean tumor size is 19.8 mm (AJNR Am J Neuroradiol 2010;31:1413)
Major salivary glands: tumor is usually encapsulated and solid
Minor salivary glands: tumor is unencapsulated and less well delineated; cystic change may be present

Gross images

Contributed by Jenny Tung Hiong Lee, M.D. and Ruta Gupta, M.D.

Multiple nodules

Well circumscribed nodule

Microscopic (histologic) description

Generally a well circumscribed nodule; may lack circumscription in the minor salivary glands
Solid sheets, nested, trabecular or ductular architecture; microcysts and macrocysts are rare
Exclusively or predominantly composed of oncocytes and separated by thin fibrovascular septae
Oncocytes are large, polyhedral shaped with distinct cell membranes and abundant granular eosinophilic cytoplasm (Head Neck Pathol 2024;18:126)
- Nuclei are centrally located, round, vesicular with prominent nucleoli
- Absence of significant nuclear pleomorphism, increased mitoses and necrosis
Absence of infiltrative growth
Psammoma bodies and tyrosine-like crystals may be present
Other cell types that may present in limited quantity within the tumor, especially following a fine needle aspiration: mucous cells, squamous cells or sebaceous cells
Basal cells can be seen at the periphery of the tumor
Clear cell oncocytoma is a histologic variant that consists entirely or predominantly of clear cells
Reasons for clear cytoplasm
- Fixation and tissue processing artifact
- Accumulated glycogen content that displaces the mitochondria to the periphery of cells

Microscopic (histologic) images

Contributed by Jenny Tung Hiong Lee, M.D. and Ruta Gupta, M.D.

Well circumscribed oncocytic tumor

Tumor cells arranged in nests

Oncocytes

PASD resistant mucous cells

CK7

p63

Cytology description

Smears are usually cellular
Oncocytes (cells with granular eosinophilic cytoplasm) are arranged in sheets, papillary fragments and individual cells
Cytologic atypia is absent to minimal
Absence or very sparse lymphoid component
Distinction of oncocytoma from oncocytosis or another salivary gland lesion with prominent oncocytic metaplasia may not be possible on cytology alone
Reference: Head Neck Pathol 2024;18:126

Cytology images

Contributed by Jenny Tung Hiong Lee, M.D. and Ruta Gupta, M.D.

Loosely cohesive tumor cells

Low N:C ratio

Papillary architecture

Dense, finely granular cytoplasm

Positive stains

Oncocytes: cytokeratin AE1 / AE3, CK7, CAM 5.2, EMA
Basal / myoepithelial cells: p63, p40, CK5/6 (scattered staining pattern)

Negative stains

S100, SOX10, SMA, GFAP, TTF1, thyroglobulin, PAX8, CAIX, CD10, NOR1 / NR4A3, diffuse p40 or p63

Electron microscopy description

Cytoplasm of the oncocytes is packed with abundant mitochondria, which are oval or elongated in shape with stacked cristae
Other organelles, such as endoplasmic reticulum and Golgi complex, are sparse
Continuous basement membrane around cell clusters
Reference: Cancer 1976;37:1606

Electron microscopy images

Images hosted on other servers:

Cytoplasm packed
with mitochondria
with stacked cristae

Sample pathology report

Left parotidectomy:
- Oncocytoma with background multinodular oncocytic hyperplasia (see comment)
- Comment: There is a dominant encapsulated oncocytic nodule. The salivary gland parenchyma shows occasional scattered microscopic oncocytic nodules. There is no evidence of malignancy.

Differential diagnosis

Oncocytic metaplasia:
- Metaplastic change
- No mass forming lesion
- Ductal and acinar epithelium transformed into oncocytes due to metaplastic process in aging
Oncocytosis:
- Proliferation of oncocytic cells within the salivary glands
- Often presents as multiple microscopic oncocytic nodules (nodular oncocytic hyperplasia)
- Difficulty in differentiating oncocytoma from diffuse oncocytosis with detectable mass
- Nonencapsulation, multiple nodules and presence of entrapped normal salivary gland parenchyma assist in distinction from oncocytoma
Pleomorphic adenoma with extensive oncocytic cells:
- Greater myoepithelial component as it is a biphasic tumor
- Stroma: chondromyxoid to hyalinized
- p63, p40, CK5/6, SMA, S100, SOX10, GFAP highlight the myoepithelial cells within the tumor
- FISH analysis shows PLAG1 gene rearrangement
Primary salivary gland carcinomas predominantly composed of oncocytic cells:
- Oncocytic mucoepidermoid carcinoma:
  - May be well demarcated
  - Goblet cells may be sparse
  - Diffuse staining for p63, p40 and CK5/6
  - Positive for MAML2 gene rearrangement
- Acinic cell carcinoma (zymogen poor variant):
  - Tumor cells are PAS positive, PASD resistant
  - They are also positive for DOG1, SOX10 and NOR1 / NR4A3
- Salivary duct carcinoma (oncocytic variant):
  - Aggressive and infiltrative tumor frequently involving adjacent structures
  - Tumor cells have apocrine phenotype: cytoplasm is granular and eosinophilic and nuclei are large, pleomorphic with prominent nucleoli
  - Perineural and lymphovascular invasion is present
  - Tumor cells are positive for AR; HER2 is positive in about 30% of cases
- Clear cell carcinoma:
  - Usually occurs in minor salivary glands, such as soft palate, buccal and floor of mouth
  - Tumor is infiltrative, usually composed of tumor cells with clear cytoplasm within densely hyalinized stroma; perineural invasion may be present
  - Diffuse staining for p63, p40 and CK5/6
  - Positive for EWSR1 gene rearrangement
Metastatic renal cell carcinoma:
- Positive for PAX8, CAIX, CD10; absence of p63 positive basal cells
Thyroid oncocytic carcinoma:
- Positive for thyroglobulin and TTF1

Additional references

WHO Classification of Tumours Editorial Board: Head and Neck Tumours, 5th Edition, 2024, Wenig: Atlas of Head and Neck Pathology, 4th Edition, 2024

Practice question #1

Which of the following statements regarding oncocytoma of the salivary gland is true?

The tumor is common in young patients
The tumor is malignant
The tumor is positive for PAX8
The tumor is rare and occurs mostly in the parotid gland

Practice answer #1

D. The tumor is rare and occurs mostly in the parotid gland. Oncocytoma constitutes about 1 - 2% of salivary gland neoplasms and mostly occurs in the parotid gland, followed by the submandibular gland and minor salivary gland. Answer A is incorrect because this tumor occurs mostly in middle aged to older people. Answer B is incorrect because oncocytoma is benign. Answer C is incorrect because oncocytoma is PAX8 negative, which is useful in differentiating this tumor from metastatic renal cell carcinoma.

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Reference: Oncocytoma

Practice question #2

Which of the following statements about oncocytic cells in oncocytoma of the salivary gland is true?

Cytology can differentiate oncocytosis from oncocytoma
FISH analysis is positive for MAML2 rearrangement
Oncocytic cells are diffusely positive for p63, p40 and CK5/6
The main organelle in the cytoplasm of oncocytic cells is the mitochondria

Practice answer #2

D. The main organelle in the cytoplasm of oncocytic cells is the mitochondria. The presence of increased intracytoplasmic mitochondrial content contributes to the eosinophilic granular cytoplasm of oncocytes. Answer C is incorrect because oncocytic cells are predominantly positive for cytokeratins such as CK7 and EMA but very focally positive for p63, p40 and CK5/6, which is useful in differentiating this tumor from mucoepidermoid carcinoma. Answer A is incorrect because cytology cannot differentiate oncocytosis from oncocytoma. Answer B is incorrect because MAML2 rearrangement is seen in mucoepidermoid carcinoma.

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Reference: Oncocytoma

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