Mucoepidermoid carcinoma pathophysiology

Mucoepidermoid carcinoma Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Mucoepidermoid Carcinoma from other Diseases
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
Staging
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Mucoepidermoid carcinoma pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Mucoepidermoid carcinoma pathophysiology All Images X-rays Echo and Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Mucoepidermoid carcinoma pathophysiology
CDC on Mucoepidermoid carcinoma pathophysiology
Mucoepidermoid carcinoma pathophysiology in the news
Blogs on Mucoepidermoid carcinoma pathophysiology
Directions to Hospitals Treating Mucoepidermoid carcinoma
Risk calculators and risk factors for Mucoepidermoid carcinoma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2] , Maria Fernanda Villarreal, M.D. [3]

Overview

Mucoepidermoid carcinomas arise from mucous cells, which are normally involved in the secretion of mucous and the protection of the surrounding tissue. The pathogenesis of mucoepidermoid carcinoma consists of abnormal production of mucin from mucous cells, associated with the aberrant overgrowth of squamous and epidermoid cells. Genes involved in the pathogenesis of mucoepidermoid carcinoma include the MECT1 and MAML2 fusion genes. On gross pathology, mucoepidermoid carcinomas have a cystic, solid or mixed appearance, are normally located on the parotid or submandibular gland, and range in size from 1 to 8 cm.

Pathogenesis

• The origin of MEC is thought to be pluripotent cells of the excretory ducts of glandular structures.
• The tumour consists of mucous, intermediate and epidermoid cells.
• Mucoepidermoid carcinomas arise from mucous cells, which are normally involved in the secretion of mucous and protection of the surrounding tissue.
• The pathogenesis of mucoepidermoid carcinoma consists of abnormal production of mucin from mucous cells, associated with the aberrant overgrowth of squamous and epidermoid cells.

Genetics

• Development of mucoepidermoid carcinoma may be the result of multiple genetic mutations.

MEC is specifically associated with a unique t(11;19) translocation.

CRTC1-MAML2 fusion is a major oncogenic driver for MEC initiation and maintenance

• Genes involved in the pathogenesis of include:

In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has be identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• MECT1 fusion gene
• MAML2 fusion gene

• The CRTC1-MAML2 oncoprotein induced the upregulation of the epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) by co-activating the transcription factor CREB, and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival.
• aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival.

Associated Conditions

• Mucoepidermoid carcinomas have no associated conditions.

Gross Pathology

• On gross pathology, mucoepidermoid carcinoma has a cystic, solid, or mixed appearance. Mucoepidermoid carcinoma usually occurs in the parotid or submandibular gland.
• Macroscopically low grade MEC are small and partially encapsulated
• MECs appeared as fluctuant light blue or purplish submucosal lumps, thus resembling the reactive salivary gland mucocele (mucous retention phenomenon). The reason they possess similar clinical appearances is that low-grade MECs and mucoceles possess mucous cyst formation and mucous pseudocyst formation, respectively.
• Other findings on gross pathology include:

• Tumor size ranging from 1 to 8 cm
• Gray or white in color, with mucin filled cysts

Microscopic Pathology

The characteristic findings of mucoepidermoid carcinoma on microscopic histopathological analysis are listed below.

• Mucus secreting cells (visible with musicarmine staining)
• Composed of three cell types: epidermoid, intermediate, and mucin producing, (MEC) is a malignant epithelial neoplasm composed of varying proportions of mucous, epidermoid, intermediate, columnar, and clear cells and often demonstrates prominent cystic growth.
• Mucin vacuoles may be rare; in a superficial glance (mimics squamous cell carcinoma)

• Hallmark of these tumors are prominent cystic structures lined by mature mucous, intermediate, or epidermoid cells and solid areas are not evident and prominent fibrous stroma often is present. It grows in a well-circumscribed manner, without any small infiltrative islands at the tumor border

• Mucoepidermoid tumors are graded histologically into: low grade, intermediate grade, and high grade.
• Low grade is characterized by well-differentiated cells with little cellular atypia, high proportion of mucous cells, and prominent cyst formation.
• Intermediate grade is characterized by intermediate features
• High grade is characterized by poorly differentiated with cellular pleomorphism, high proportion of squamous cells, and solid with few if any cysts

Gallery

• 

  Histopathologic image of mucoepidermoid carcinoma of the major salivary gland. H & E stain.

• 

  Histopathologic image of mucoepidermoid carcinoma of the major salivary gland.

• 

  Histopathologic image of mucoepidermoid carcinoma. Postoperative recurrence of the submandibular tumor. Alcian blue-PAS stain.

• 

  Gross pathology mucoepidermoid carcinoma.

References

Template:WikiDoc Sources