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Salivary glands

Normal histology


Reviewer: Fatima Aly, M.D. (see Reviewers page)
Revised: 21 January 2013, last major update July 2010
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
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● Compound exocrine glands with ductal and acinar portions
● Acinar portion is serous, mucinous or mixed
● Acini are lined by luminal cells, which are enclosed by myoepithelial cells

Serous acini:
● Dense, basophilic, PAS+ intracytoplasmic secretory granules containing amylase
● Have central lumen that is rarely visible by H&E

Mucous acini:
● Larger than serous acini
● Irregular pattern
● Cells have abundant cytoplasm with clear mucin, well-rounded, basal nuclei, and are arranged around empty lumina
● Produce acid (positive for Alcian blue and mucicarmine) and neutral (PAS+) sialomucins

Myoepithelial cells:
● Surround acini and intercalated ducts and mediate contraction
● Have both epithelial and mesenchymal structures and functions, and are important in the morphology of most salivary gland tumors
● Myoepithelial cells surrounding intercalated ducts are more spindled and have fewer processes than those surrounding acini

Ducts:
● Either intercalated, striated or interlobular, all with outer basal cells and inner luminal cells
● Intercalated ducts have reserve cells that regenerate acinar tissue and terminal duct system
● All epithelium is PSA+ (Pathol Int 1999;49:500)
● Sebaceous glands are attached to parotid and submandibular ducts, and are considered part of normal holocrine differentiation [holocrine secretions are produced within the cell, then are released into the lumen after rupture of the plasma membrane], based on the occurrence of salivary tumors with sebaceous differentiation (Am J Surg Pathol 1989;13:879)

Parotid gland:
● Serous acini only; contains numerous basophilic zymogen granules; nuclei are uniform, round and in basal half of cell
● Intercalated ducts are long but small in comparison to acini and striated ducts
● Striated ducts are larger than intercalated ducts, 3-6x size of acinus; striations are due to folds in basal plasma membranes
● Contains small lymph nodes near or within the gland, which arise from interstitial lymphocytes
● Resembles pancreatic tissue, but parotid gland has adipocytes and pancreatic tissue has islets and centroacinar cells

Submandibular/submaxillary gland:
● Predominantly serous but also mucinous acini

Sublingual gland:
● Predominantly mucinous but also serous acini

Minor salivary glands:
von Ebnerís glands of tongue (posterior dorsal and lateral): serous acini only
Palate, base and lateral border of tongue: predominantly mucous acini
Lip, cheek, apex of tongue: mixed serous and mucous acini

Physiology
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● The basement membrane protein perlecan/HSPG2 (heparan sulfate proteoglycan 2) triggers differentiation of salivary gland cells into self-assembling acini-like structures that express essential biomarkers and secrete alpha-amylase (Tissue Eng Part A 2009;15:3309)
● Serous glands produce thin watery fluid containing alpha amylase, which digests starches
● Mucinous glands produce viscous mucinous fluid higher in glycoproteins, which provides a lubricating film on oral mucosa

Diagrams
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Cytomorphologic features of various portions of the salivary system from the secretory end piece to the oral cavity are illustrated. From left to right are the acinus, intercalated duct, striated duct, excretory duct and oral cavity.

Micro images
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Parotid gland



Replacement of serous glands by sebaceous glands


Left: Clusters of large, pale-staining mucous cells (arrows) occasionally are present in the parotid gland, but the acini are overwhelmingly of serous type. Each serous acinus is composed of several pyramidal-shaped cells with basal nuclei and basophilic cytoplasmic granules.
Right: The serous cell granules are PAS+ and resistant to diastase digestion (PAS stain).



The cells of the intercalated duct (arrow) are small in comparison to the acinar cells and are cuboidal with pale-stained cytoplasm and central nuclei. A small lumen is evident.


The striated duct is larger than an acinus and much larger than the intercalated duct. The ductal cells are eosinophilic columnar cells with central nuclei and vertical cytoplasmic striations due to folds in the basal plasma membranes.


This small, interlobular excretory duct is lined by pseudostratified columnar epithelium and embedded in dense fibrous connective tissue.


Intraglandular adipose tissue in parotid gland
A: The parotid gland from a neonate contains no discernible adipose tissue.
B: There is a moderate amount of intralobular adipose tissue in parotid tissue from a middle-aged adult.
C: The intraparotid adipose tissue is quite prominent in the gland from an elderly person.



These intraparotid (left) and periparotid (right) lymph nodes are encapsulated and have subcapsular sinuses and germinal centers. Even the periparotid lymph node (right) is within the capsule and in contact with parenchymal tissue of the parotid gland.


Sebaceous cells in parotid gland.
The cells in two foci of sebaceous differentiation (arrows) are large with central nuclei and clear reticulated cytoplasm that is unreactive with mucicarmine stain. Small foci of sebaceous cells occur frequently in the parotid gland (Mucicarmine stain).



Facial nerve branches in parotid gland
A relatively large nerve lies adjacent to a lobule of parotid glandular tissue (left) while a smaller nerve branch is within a lobule and in contact with serous acini (right).


Submandibular gland



Left: In the submandibular gland, mucous acini comprise about 10% of acinar tissue. Serous cells are frequently located at the periphery of mucous acini as crescent-shaped cells (arrow). The striated ducts (arrowheads) are more prominent and the intercalated ducts are shorter than those in the parotid gland.
Right: The mucous cells are highlighted among the serous acini as rose pink cells (Mucicarmine stain).


Sublingual gland

The sublingual gland acini are typically elongated tubules of mucous cells with serous cell demilunes (a demilune is a cap in the shape of a half-moon)

Minor salivary glands of palate

Left: The palate contains the largest foci of intraoral salivary gland tissue, which is composed of mucous acini but no striated ducts.
Right: At high magnification, the mucous acini are round with central lumens. The mucous cells are pyramidal with very pale granular cytoplasm and nuclei located next to the basal plasma membranes.


Minor salivary glands of tongue

The minor salivary glands are small aggregates of unencapsulated mucous or serous glands. In the tongue they are in intimate contact with the striated muscle tissue.


Keratin cocktail stains intercalated, striated and interlobular ducts, but acinar and myoepithelial cells are mostly negative.


Left: Normal parotid tissue is S100 negative.
Right: In this parotid tissue adjacent to a mixed tumor, some of the myoepithelial and intercalated duct cells are S100+.



Left: The normally indistinct, elongated and flattened myoepithelial cells at the periphery of the acini, intercalated ducts and striated ducts are conspicuous due to their immunostaining for alpha-smooth muscle actin.
Right: The serous acinar cells immunostain for alpha-amylase.


Positive stains
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Luminal cells:
● AE1-AE3

Acinar cells:
● CK8/18, VEGF, GCDFP-15
● Estrogen receptor is variable (Eur J Oral Sci 2009;117:498)
● Parotid zymogen granules are PAS+, diastase resistant

Myoepithelial cells:
● Actin, myosin, CK5/6, CK14, p63, maspin
● Negative for vimentin (but neoplastic myoepithelial cells stain differently, Hum Pathol 1987;18:1218)

Electron microscopy description
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Acinar cells:
● Numerous cytoplasmic secretory (zymogen) granules in apical portion of cell
● Extensive rough ER and golgi
● Numerous mitochondria
● Numerous folds are present in basal lamina of acinar cells that are not distended with secretory product
● Mucous acinar cells have larger, more irregular secretory droplets that are more electron lucent than in serous acinar cells

Intercalated duct cells:
● Few special ultrastructural features
● May have some secretory granules
● Scant cytoplasm has basal rough ER, apical Golgi and mitochondria
● Lateral membranes interdigitate with neighboring cells

Myoepithelial cells:
● Between basal plasma membrane of acinar and intercalated duct cells and basal lamina
● Flattened and elongated with cytoplasmic processes extending around acinar and intercalated duct cells
● Long / irregular nuclei
● Desmosomes attach the myoepithelial cells to acinar and ductal cells

Striated duct cells:
● Striations are due to basal vertical folds
● Numerous mitochondria present

Electron microscopy images
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Variable-sized secretory granules occupy most of the apical portion of the cytoplasmic compartment. Parallel arrays of rough endoplasmic reticula lie adjacent to the basally located, round nucleus. The intercellular space contains interdigitations of adjacent cells and represents a canaliculus that is connected to the acinar lumen and is actually the beginning of the duct system (X11,300).


The myoepithelial cell lies between the basal lamina and the basal plasma membranes of the acinar cells. The cell body is flattened and the nucleus is elongated. In the cytoplasm are numerous microfilaments with focal dense bodies (arrow) (X13,300).


The relatively small cytoplasmic compartment contains a round nucleus, mitochondria, lipid vacuoles and an endoplasmic reticulum. There are a few short microvilli on the luminal surface, and intercellular connections are apical junctional complexes with several desmosomes (X6,000).


The basal plasma membranes have prominent vertical folds, and there are numerous mitochondria. The lateral surfaces have processes that interdigitate with adjacent cells. Apical junctional complexes and desmosomes connect adjoining cells (X6,000).

Videos
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Parotid gland


Submandibular gland


Sublingual gland

End of Salivary glands > Normal histology


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