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Salivary glands

Primary salivary gland neoplasms

Malignant

Mucoepidermoid carcinoma

Authors: Saeed Asiry, M.D., Rema A. Rao, M.D.

Editorial Board Member: Lisa Rooper, M.D.

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

Last author update: 15 October 2021

Last staff update: 1 April 2024

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PubMed Search: Mucoepidermoid carcinoma salivary gland

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Table of Contents

Cite this page: Asiry S, Rao RA. Mucoepidermoid carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsMEC.html. Accessed July 15th, 2024.

Definition / general

Malignant glandular epithelial neoplasm characterized by mucous, intermediate and epidermoid cells, with columnar, clear cell or oncocytoid features

Essential features

Malignant epithelial neoplasm
Characterized by mucous, intermediate and epidermoid cells, with columnar, clear cell or oncocytoid features
Most common malignant salivary gland neoplasm in both adults and children
Prognosis influenced by tumor stage, tumor site, surgical margins (WHO 2017)
Associated with a specific translocation t(11;19)(q14-21;p12-13) with CRTC1(MECT1)-MAML2 fusion

Terminology

Mucoepidermoid carcinoma (MEC)
Not recommended: mucoepidermoid tumor

ICD coding

ICD-O: 8430/3 - mucoepidermoid carcinoma
ICD-10 (depends on site):
- C08.0 - malignant neoplasm of submandibular gland
- D48.7 - neoplasm of uncertain behavior of other specified sites
- C07 - malignant neoplasm of parotid gland
- C08.9 - malignant neoplasm of major salivary gland, unspecified

Epidemiology

Most common malignant salivary gland tumor (adults and children) (Br J Oral Maxillofac Surg 2013;51:399)
Represents 10 - 15% of all salivary gland tumors (Br J Oral Maxillofac Surg 2013;51:399)
Adults: wide age range (15 - 86 years, median 49 years) (Am J Surg Pathol 2001;25:835)
Children: 11 - 15 years (median 13 years) (Int J Pediatr Otorhinolaryngol 2019;120:93)
F > M (slight predominance) (Br J Oral Maxillofac Surg 2013;51:399)

Sites

Occurs in major and minor salivary glands (predominance of major > minor) (Eur J Surg Oncol 2021;47:1376)
Major: parotid > submandibular > sublingual (Eur J Surg Oncol 2021;47:1376)
Minor: palate, buccal mucosa, retromolar region (Indian J Pathol Microbiol 2018;61:397)
Rarely occurs in sinonasal tract, nasopharynx, lungs and intraosseous mandible (Int Forum Allergy Rhinol 2019;9:1046, Expert Rev Respir Med 2018;12:249, Case Rep Dent 2018;2018:9348540)

Etiology

Possible association with ionizing radiation (Indian J Pathol Microbiol 2018;61:397)

Clinical features

In one study, 33% of patients are asymptomatic; however, varies with tumor site and size (J Stomatol Oral Maxillofac Surg 2020;121:713)
Most common presentation is painless swelling with pressure and discomfort
Can be variably fixed, rubbery or soft mass (J Stomatol Oral Maxillofac Surg 2020;121:713)

Diagnosis

Preoperative assessment (radiology) may consist of:
- Ultrasonography (USG) for small tumors in major salivary glands
- Larger recurrent tumors: CT imaging for bone involvement, MRI for soft tissue delineation (Semin Radiat Oncol 2012;22:245)
- Evidence of (18)-fluorodeoxyglucose positron emission tomography CT in locoregionally advanced tumors (Nucl Med Commun 2013;34:211)
Preoperative assessment (fine needle aspiration)

Radiology description

Influenced by tumor size, location and possibly tumor grade
Ultrasonography:
- Typically a well circumscribed hypoechoic lesion, with a partial or completely cystic appearance against a relatively hyperechoic normal parotid gland
CT:
- Lower grade tumors are well circumscribed with cystic component (see Radiology images)
- Enhancing solid component and calcifications occasionally seen
- Higher grade tumors are solid and show poorly defined, infiltrative margins
MRI:
- Low grade tumors are similar in appearance to a pleomorphic adenoma
- Higher grade tumors are solid, with a lower signal on T2 and poorly defined margins
Reference: Radiopaedia: Mucoepidermoid Carcinoma of Salivary Glands [Accessed 8 January 2021]

Radiology images

Images hosted on other servers:

Parotid mucoepidermoid carcinoma, CT

Prognostic factors

Adults:
- Excellent prognosis, with approximately 98.8% 5 year survival rate in low grade and 97.4% in intermediate grade tumors
- About 67% 5 year survival rate for high grade tumors
Children:
- 5 year survival of 98%, as they predominantly present with low to intermediate grade tumors
Negative prognostic variables
- Tumor arising in the submandibular gland: lymph node metastases common
- Positive surgical margins
- Extraparenchymal extension
- Nodal / distant metastases
- Increased expression of MUC1
References: J Stomatol Oral Maxillofac Surg 2020;121:713, Wenig: Atlas of Head and Neck Pathology, 3rd Edition, 2016

Case reports

16 year old boy with a mandibular radiolucent lesion (Case Rep Dent 2018;2018:9348540)
36 year old man with a left parotid gland mass (Anticancer Res 2019;39:3213)
69 year old woman with a right submental mass (Eur Ann Otorhinolaryngol Head Neck Dis 2017;134:355)

Treatment

Complete surgical resection
- Conservative approach for stage I and stage II tumors
- Wide excision with wide margin for high grade tumors or tumors with positive margins
Neck lymph node dissection (depends on nodal status and histologic grade)
Adjuvant radiotherapy and chemotherapy might be considered for higher grade tumors
Reference: J Stomatol Oral Maxillofac Surg 2020;121:713

Gross description

Incompletely encapsulated or unencapsulated
Well circumscribed
Low grade: often cystic
High grade: often solid, necrotic, tan-pink
References: J Stomatol Oral Maxillofac Surg 2020;121:713, Wenig: Atlas of Head and Neck Pathology, 3rd Edition, 2016

Gross images

Contributed by Kelly Magliocca D.D.S., M.P.H.

Cut surface, high grade

Frozen section description

Higher grade tumors can be mistaken for squamous cell carcinoma, a pitfall (Cancer 2004;100:1876)

Frozen section images

Contributed by Rema A. Rao, M.D. and Saeed Asiry, M.D.

Positive margin for tumor

Microscopic (histologic) description

Solid, cystic or mixed growth patterns
Can show papillary or glandular growth pattern
Areas suggesting a capsule can be seen in low grade mucoepidermoid carcinoma
Varying proportions of epidermoid cells, intermediate cells and mucocytes
Solid nests, sheets or cords of epidermoid cells
Overt keratinization is rare
Mucous cells embedded in epidermoid cell nests or lining cystic spaces
Intermediate cells found within epidermoid cell nests or forming separate nests
Background stromal sclerosis
Luminal or extracellular pools of mucin may be present
Mitosis, necrosis and pleomorphism more commonly seen in high grade tumors
Limited number of mucocytes and cystic spaces in high grade tumors
Perineural and lymphovascular invasion possible (Wenig: Atlas of Head and Neck Pathology, 3rd Edition, 2016)
Focal clear cell changes can occur due to accumulation of glycogen
Histologic variants: clear cell, oncocytic, sclerosing, Warthin-like, ciliated, spindle cell and mucoacinar (Am J Surg Pathol 2015;39:1479, Am J Surg Pathol 2018;42:130, Int J Surg Pathol 2017;25:705, Am J Surg Pathol 2021;45:1028, Am J Surg Pathol 1999;23:523)
Reference: J Stomatol Oral Maxillofac Surg 2020;121:713

Histopathologic grading:

4 histologic grading systems (2 quantitative and 2 qualitative)
2 different morphologic quantitative point systems, although histologic grading using any grading system appears to be inconsistent (Am J Surg Pathol 2019;43:885)
Significant grading disparity between pathologists (Am J Surg Pathol 2019;43:885)
Armed Forces Institute of Pathology (AFIP) grading scheme (quantitative) (Am J Surg Pathol 2019;43:885)
- Criteria:
  - Intracystic component less than 20% (2)
  - Neural invasion (2)
  - Necrosis (3)
  - 4 or more mitoses (3)
  - Anaplasia (4)
- Grade:
  - Low grade (0 - 4)
  - Intermediate grade (5 - 6)
  - High grade (7 or more)
Brandwein et al. grading scheme (quantitative) (Am J Surg Pathol 2001;25:835)
- Criteria:
  - Intracystic component less than 25% (2)
  - Tumor front invades in small nests and islands (2)
  - Pronounced nuclear atypia (2)
  - Lymphovascular invasion (3)
  - Bony invasion (3)
  - 4 or more mitoses (3)
  - Perineural invasion (3)
  - Necrosis (3)
- Grade:
  - Low grade (0)
  - Intermediate grade (2 - 3)
  - High grade (4 or more)
Modified Healy grading system (qualitative)
- Low grade
  - Macro and microcysts
  - Rare intermediate cells
  - Rare mitotic figures
  - Absent or minimal nuclear pleomorphism
  - Well circumscribed tumor with broad edges
  - Extravasated mucin and fibrotic stroma present
- Intermediate grade
  - Microcysts and solid component
  - More intermediate cells
  - Few mitotic figures
  - Slight nuclear pleomorphism
  - Uncircumscribed tumor
  - Fibrotic stroma separating tumor nests
- High grade
  - Predominantly solid, with or without microcysts
  - Perineural invasion present
  - Lymphovascular invasion present
  - Surrounding soft tissue invasion present
  - Many mitotic figures
  - Nuclear pleomorphism, including presence of prominent nucleoli
  - Predominance of intermediate cells
  - Desmoplastic stoma
Memorial Sloan Kettering Cancer Center (MSKCC) grading system (qualitative)
- Low grade
  - Predominantly cystic growth pattern (> 80%)
  - 0 - 1 mitotic figures/10 high power fields (HPF)
  - Well circumscribed
  - No necrosis
- Intermediate grade
  - Predominantly solid growth pattern
  - 2 - 3 mitotic figures/10 high power fields (HPF)
  - Well circumscribed or infiltrative
  - No necrosis
- High grade
  - Any growth pattern but usually solid
  - ≥ 4 mitotic figures/10 high power fields (HPF)
  - Usually infiltrative
  - Necrosis is present

Microscopic (histologic) images

Contributed by Rema A. Rao, M.D. and Saeed Asiry, M.D.

Tumor architecture

Tumor cell types

Epidermoid cells

Mucus cells

Intermediate cells

Clear cell changes

Case #346

4 year old boy

Ki67

Mucicarmine

Virtual slides

Images hosted on other servers:

Low grade mucoepidermoid carcinoma

Cytology description

Most often graded as low grade or high grade on FNA
Low to intermediate grade:
- Can be acellular or hypocellular smears
- Extracellular mucin may be the prominent feature
- Cystic background
- Aggregates of epidermoid cells, intermediate cells and mucocytes
- Epidermoid cells appear as bland cohesive flat sheets with squamoid / dense cytoplasm and well defined cellular borders
- Predominantly mucus cells floating in extracellular mucin (low grade)
- No keratinization seen
- Lympocytes present in about 20% of cases and are abundant
High grade:
- Highly cellular aspirates
- High grade nuclear features with pleomorphic nuclei, prominent nucleoli
- Intermediate cells and mucous cells are rare
- Increased mitosis
- Necrotic background
References: J Clin Diagn Res 2017;11:ER04, Cibas: Cytology - Diagnostic Principles and Clinical Correlates, 5th Edition, 2020

Cytology images

Contributed by Rema A. Rao, M.D. and Saeed Asiry, M.D.

Background mucin

Neoplastic cells

Mucus cells

Neoplastic cells in sheets

Keratinizing cells

Single keratinizing cells

Crowded squamous cells

Images hosted on other servers:

Low grade and oncocytic tumors

Positive stains

Pancytokeratin, CK5/6, p63, p40, EMA, CK7, CK14
Membrane bound mucins: MUC1, MUC2, MUC4, MUC5AC and MUC5B
Mucocytes: mucin positive for mucicarmine and PASD (diastase resistant) stains
Reference: J Stomatol Oral Maxillofac Surg 2020;121:713

Negative stains

S100, GFAP, calponin, muscle specific actin, androgen receptor, HER2, DOG1, CK20 (Arch Pathol Lab Med 2015;139:55)
SOX10: rare cases may be positive (Hum Pathol 2016;56:134)
Mammaglobin: some cases may show positive cells (Hum Pathol 2016;56:134)
GATA3: occasional cells may be positive (Hum Pathol 2016;56:134)

Electron microscopy description

Epidermoid cells attached to each other with desmosomes and mucus cells showing mucous globules with stellate mucoid material (Oral Surg Oral Med Oral Pathol 1979;47:247)

Molecular / cytogenetics description

t(11;19)(q14-21;p12-13) with CRTC1(MECT1)-MAML2 fusion (Nat Genet 2003;33:208)
- Present in 80% of mucoepidermoid carcinoma (Am J Surg Pathol 2016;40:1151)
- Low to intermediate grade (78%), high grade (84%) (Am J Surg Pathol 2016;40:1151)
- Detected by fluorescence in situ hybridization (FISH) or RT-PCR (Am J Surg Pathol 2019;43:885)

Molecular / cytogenetics images

Images hosted on other servers:

FISH analysis of MAML2

Sample pathology report

Parotid gland, right, parotidectomy:
- Mucoepidermoid carcinoma, intermediate grade (2.3 cm)
- The tumor is confined to the parotid gland.
- No lymphovascular or perineural invasion is identified.
- Three lymph nodes, negative for carcinoma (0/3).
- Surgical margins negative for carcinoma.
- Carcinoma 0.3 cm of closest margin, medial.
- See synoptic report.

Differential diagnosis

For low to intermediate grade tumors:
- Necrotizing sialometaplasia (Acta Otorrinolaringol Esp 2020;71:328):
  - Lobular pattern, lacks cystic pattern, no intermediate cells
- Pleomorphic adenoma with squamous and mucinous cell metaplasia (J Oral Maxillofac Pathol 2018;22:S69):
  - Composed of epithelial and myoepithelial cells and extracellular matrix material
- Warthin tumor with squamous metaplasia (J Med Case Rep 2019;13:12):
  - Lacks the translocations seen in mucoepidermoid carcinoma
  - Shows bilayered oncocytic epithelium
- Acinic cell carcinoma (Eur Arch Otorhinolaryngol 2016;273:3511):
  - DOG1 and SOX10 positive
- Mammary analogue secretory carcinoma (MASC) (Bosn J Basic Med Sci 2016;16:237):
  - S100 positive
For high grade tumors:
- Squamous cell carcinoma (primary or secondary) (J Cancer Res Ther 2015;11:664):
  - Shows keratinization and intercellular bridges
  - Lacks intermediate cells and mucocytes
- Salivary duct carcinoma (Head Neck Pathol 2017;11:288):
  - GATA3, HER2 and androgen receptor positive
  - Shows a Roman bridge pattern, comedonecrosis

Additional references

Goldblum: Rosai and Ackerman's Surgical Pathology, 11th Edition, 2017, El-Naggar: WHO Classification of Head and Neck Tumours, 4th Edition, 2017

Board review style question #1

Which of the following is true about mucoepidermoid carcinoma?

Associated with t(12;15)(p12;q25) and ETV6-NTRK3 gene fusion
Highly associated with smoking
Most common malignant salivary tumor in children
Positive for HER2 and AR by immunohistochemistry
Prognosis is poor regardlesss of histologic grade

Board review style answer #1

C. Most common malignant salivary tumor in children

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Reference: Mucoepidermoid carcinoma

Board review style question #2

Which of the following histologic features is more commonly seen in low to intermediate grade mucoepidermoid carcinoma?

4 or more mitoses
Bone invasion
Intracystic component more than 30%
Necrosis
Perineural invasion

Board review style answer #2

C. Intracystic component more than 30%

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Reference: Mucoepidermoid carcinoma

Board review style question #3

The focal clear cell change seen in this mucoepidermoid carcinoma case is due to

Accumulation of glycogen
Accumulation of mucin
Degradation of neoplastic cells
Fixation artifact
High grade transformation

Board review style answer #3

A. Accumulation of glycogen

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