.

1. Mucoepidermoid carcinoma

2. Definition
Mucoepidermoid carcinoma is a distinctive salivary gland malignancy composed
of mucinous, intermediate (clear cell), and squamoid tumour cells forming cystic
and solid patterns.
WHO Classification of Head and Neck Tumours, 4ed, (2017)
Or
a malignant glandular epithelial neoplasm characterized by mucous, intermediate
and epidermoid cells, with columnar, clear cell and oncocytoid features
(Simpson, Skálová, Di Palma, & Leivo, 2014)

3. Epidemiology
WHO Classification of Head and Neck Tumours, 4ed, (2017)
It is a rare tumour that most commonly manifests as intraoral salivary
gland carcinoma (in 37-53% of cases), with a slight female predilection.
A wide patient age has been reported, with the mean age in the sixth
decade of life
occurs over a wide age distribution, and is the most common salivary
gland with a peak incidence in he second decade

4. mucoepidermoid carcinoma is the most common malignant salivary gland
tumour, representing approximately 10% of all salivary gland tumours and
25% of malignant lesions.
Although most common in the parotid gland, mucoepidermoid carcinoma is
frequently encountered in the oral cavity in the palate, cheeks, lips, tongue
and retromolar region.
Importantly, mucoepidermoid carcinoma is the most common salivary
malignancy in children.
Epidemiology

5. Aetiology
MEC may develop secondary to radiation or chemotherapy during
childhood, with a median latency period of 8 years

6. Localization
The parotid is the most common site followed by the palate,
submandibular gland, and other intraoral minor salivary gland sites The
palate is the most common intraoral site, accounting for > 50% of
intraoral Cases.
carcinoma is frequently encountered in the oral cavity in the palate,
cheeks, lips, tongue and retromolar region.

8. Clinical features
The tumours are often asymptomatic, but may cause symptoms,
depending on the site and histological grade.
The clinical presentation varies depending on tumour size, and grade.
Cystic intraoral can mimic a mucocoele. mucinou MEC may fluctuate in
size due cyst rupture and may present as a mucin draining cutaneous
fistula.

9. Cytology
1- Aspirtes of low-grade, mostly cystic lesions Shows:
predominately mucus + macrophage + Occasional bland epithelial cells
may be seen.
2- Aspirates of higher-grade lesions:
more cellular, showing an admixture of epithelial cell types typical of
the lesions + Cytological pleomorphism + mitotic activity + necrosis
may be seen

10. Histopathology
is characterized by variable components of squamoid, mucin-
producing, and intermedia type cells. with a cystic and solid growth
pattern.
Keratinzation is rare but usually have Oncocytic, clear-cell and
sclerosing variants.
Mucicarmine stainng and periodic acid-Schiff (PAS) stain with diastase
demonstrate intracytoplasmic staining in mucinous cells.

11. A low grade, extensively cystic mucoepidermoid
carcinoma
of the tongue, showing intermediate (arrow), mucous
and clear cells in
the cyst lining.

12. Histological diagnosis of mucoepidermoid carcinoma is based on the
identification of an admixture of epidermoid cells and mucous cells.
The most frequent pattern is a multicystic tumour with cystic spaces
lined by pale staining, duct-like or epidermoid cells, and mucous cells.
In almost all cases more solid areas containing cytologically bland, so-
called “intermediate cells” are also seen. Clear cell change may be
extensive.

15. Mucoepidermoid carcinoma of the parotid.
(a) Lowgrade lesion
Comprising scattered cysts with cellular mural
thickenings present only focally
(b) Intermediate grade
tumour where solid islands predominate over the
cystic component

16. Note that !
Clear cells are frequently seen in mucoepidermoid carcinomas,
But
careful examination for the presence of: mucous, epidermoid and/or
intermediate cells should establish the correct diagnosis.

17. variants
1-oncocytic variant
Polygona / columnar oncocytic cells + scattered mucocytes
2-Sclerosing variant
Dense hyalinizing fibrosis
3-Solid MEC
Sequamoid and intermediate cells

19. Brandwein et al.(2001)
Low-grade : The cystic pattern is typical of low grade lesions and is seen in over 70% of cases
intermediate-grade: show more solid areas and an increased proportion of epidermoid cells.
High-grade: cytological atypia, perineural infiltration, necrosis and a more invasive growth pattern.
Focal keratinisation and squamous carcinoma-like areas are additional findings in some cases
Using this scheme it was shown that all patients with low grade lesions were disease free at 10
years, compared to 70% with intermediate grade and 40% with high grade lesions.

21. Genetic profile
Mucoepidermoid carcinomas do not have a characteristic immunohistochemical
profile, but most lesions do show a characteristic (11;19)(q21;p13) translocation
and CRTC1-MAML2 (55%-70%)
(Gupta, Balasubramanian, & Clark, 2015)
gene fusion can be detected by FISH and is a useful marker in difficult cases and in
small indeterminate biopsies.
Tumours with the translocation were thought to be low to intermediate grade and
have a better prognosis in terms of recurrence rates, metastases and tumour-related
deaths.
(Khurram, Barrett, & Speight, 2017)

22. Mucoepidermoid carcinoma:
FISH analysis using break apart
rearrangement probe—Vysis
ZytoLight SPEC :
MAML2 Dual Colour Break Apart Probe (11q21)
• nuclei with one fusion (yellow),
• one orange and one green (split) signal pattern
indicative of:
A rearrangement of one copy of the
MAML2 gene region

23. Most cases of MEC harbour one of two recurrent translocations,
either t(11;19)(q21;p13) resulting in a fusion of the genes, CRTC1 to MAML2.
or in a small number of mutually exclusive cases t(11;15)(q21;q26) leading to
a CRTC3-MAML2 fusion
(Simpson, Skálová, Di Palma, & Leivo, 2014)

24. Tests
(Simpson, Skálová, Di Palma, & Leivo, 2014) ;
Most cases of MEC can be readily identified on haematoxylin and eosin
(H & E), but mucin stains and high molecular weight cytokeratins are useful
when respectively mucous or epidermoid cells are few
(Hunt, 2011) ;
The MECT1-MAML2 translocation can be identified using fluorescent in situ
hybridization or with assays based on reverse transcription–polymerase
chain reaction (RT-PCR).

25. differential diagnosis
1-adenosquamous carcinoma of the oral mucosal surface
2-metastatic squamous and primary salivary duct carcinoma
3-Sialometaplasia
(Gupta, Balasubramanian, & Clark, 2015);
Presence of MAML2 rearrangement may aid in distinction of high-grade
mucoepidermoid carcinomas from metastatic squamous cell carcinoma
or salivary duct carcinoma.

26. Prognosis and predictive factors
This tumour has a favourable outcome. Most patients present with low-grade tumour and low-
stage tumour
The median survival of fusion-positive patients appears
to be better than those without it ‘low grade better’
Amongst MECs
of high histological grade, there is recent evidence that fusion negative
tumours behave much more aggressively than fusion-positive ones
(Simpson, Skálová, Di Palma, & Leivo, 2014)

27. Prognosis and predictive factors
Low- and intermediate-grade MECs :
1-less aggressive and are generally cured by complete surgical excision.
2-The 10 -year overall survival rates for MECs are approximately
Low grade = 90%
Intermediate grade = 70%
High grade = 25%
(Vargas, Cheng, Barrett, Craig, & Speight, 2008)

29. References:
1. Gupta, R., Balasubramanian, D., & Clark, J. R. (2015). Salivary gland lesions: Recent advances
and evolving concepts. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 119(6),
661–674.
2. Hunt, J. L. (2011). An update on molecular diagnostics of squamous and salivary gland tumors
of the head and neck. Archives of Pathology & Laboratory Medicine, 135(5), 602–609.
3. Khurram, S. A., Barrett, A. W., & Speight, P. M. (2017). Diagnostic difficulties in lesions of the
minor salivary glands. Diagnostic Histopathology, 23(6), 250–259.
4. Simpson, R. H. W., Skálová, A., Di Palma, S., & Leivo, I. (2014). Recent advances in the
diagnostic pathology of salivary carcinomas. Virchows Archiv, 465(4), 371–384.
5. Speight, P. M., & Barrett, A. W. (2009). Leading article Prognostic factors in malignant tumours
of the salivary glands, 47, 587–593.
6. Vargas, P. A., Cheng, Y., Barrett, A. W., Craig, G. T., & Speight, P. M. (2008). Expression of Mcm-2
, Ki-67 and geminin in benign and malignant salivary gland tumours, 44, 309–318
7. Zhu, S., Schuerch, C., & Hunt, J. (2005). Review and Updates of Immunohistochemistry in
Selected Salivary Gland and Head and Neck Tumors.
8. Regezi, J., 2012. Oral Pathology clinical pathological correlation. 6th ed. Missoury: Elsevier,
p.204.
9. WHO Classification of Head and Neck Tumours, 4ed, (2017)