Embryology, Anatomy, and Histology of The Salivary Glands

• • Salivary gland system composed of exocrine glanular
tissue that include major salivary glands and minor

salivary glands:
◦ ○ Major salivary glands include:
▪ – Parotid gland
▪ – Submandibular (submaxillary) gland
▪ – Sublingual gland
◦ ○ Minor salivary (seromucous) glands include:
▪ – Small aggregations within the submucosa of
the upper aerodigestive tract
• • All salivary glands share basic structure but vary per
site in their function, secretions, gross and
microscopic features:
◦ ○ Major and intraoral minor salivary glands
produce fluids that constitute oral saliva.
◦ ○ Minor salivary (seromucous) glands outside the
oral cavity including sinonasal tract, pharynx,
larynx, trachea, bronchi are morphologically
and functionally similar to oral minor salivary
glands but in contrast do not contribute to saliva
Embryology of the Salivary Glands

• • All salivary glands develop as solid proliferations or
buds from the epithelium of the stomodeum during
the fifth and sixth weeks of gestation:
◦ ○ Stomodeal epithelium is part ectoderm and part
endoderm.
• • Parotid gland:
◦ ○ First to form in humans
◦ ○ Arise from the ectodermal lining of the
stomodeum from which the ducts, lumina, and
acini evolve
◦ ○ Capsule and connective tissue develop from the
surrounding mesenchyme
• • Submandibular gland:
◦ ○ Develops from buds of the endoderm in the floor
of the stomodeum from which the ducts,
lumina, and acini evolve
• • Sublingual gland:
◦ ○ Appears later than the other glands
◦ ○ Develop from buds of the endoderm in the
paralingual sulcus from which the ducts,
lumina, and acini evolve
• • Minor salivary glands (seromucous glands):
◦ ○ Develop later in gestational life (third month)
◦ ○ Endodermally derived
NOTE: Parotid gland is last of the salivary glands to be
encapsulated resulting in either incorporation/entrapment
of lymphoid tissue within the parotid or
incorporation/entrapment of parotid ducts and acini
within the periparotid lymph nodes epithelium. (See next
chapter for discussion and illustrations.)
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Anatomic Borders of the Salivary Gland
• • See Fig. 18-1 .
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Open full size imageFig. 18-1 Salivary glands and related
anatomy. A, Left lateral drawing of the face with the body of
the mandible resected to show the floor of mouth structures.
The relationships of the parotid gland, submandibular gland,
and sublingual gland are shown. B, Left oblique view
drawing from above shows the relationships of the left
parotid gland to the mandibular ramus, pterygoid muscles,
carotid sheath, and pharyngeal wall. Note the course of the
facial nerve artificially dividing the parotid gland into a
superficial lobe (largest portion) and deep lobe (smallest
portion). C, Left lateral view of the floor of mouth as seen
with a midline cut. The submandibular gland can be seen to
extend around the back edge of the mylohyoid muscle. The
multiple ducts of the sublingual gland can be seen draining
into the lateral floor of the mouth. ( A, Modified from
www.netterimages.com . B, From Som PM, Curtin HD: Head
and neck imaging, ed 5, Philadelphia, 2011, Elsevier, p
2450, Fig. 40-1. C, Modified from Sobota Atlas of Human
Anatomy © Elsevier GmbH, Urban & Fischer, Munich.)
• • Parotid gland
◦ ○ Largest gland (average weight of 25 g)
◦ ○ Encapsulated and pyramidal-shaped palpable
between the ramus of the mandible and the
mastoid process
◦ ○ Artificially divided into two lobes by the coursing
of the facial nerve through the gland:
▪ – Superficial lobe (largest portion)
▪ – Deep lobe situated adjacent to the lateral
pharyngeal space
◦ ○ Anterior border:
▪ – Overlies the superficial surface of the
masseter muscle
◦ ○ Posterior border:
▪ – Overlaps the sternocleidomastoid muscle
and wraps around the lower ear
◦ ○ Lateral or superficial border:
▪ – Skin and dermis of the face
◦ ○ Medial or deep border:
▪ – Buttressed by the styloid process and its
associated muscles (styloglossus,
stylohyoid, stylopharyngeal) and by the
carotid sheath and its contents (internal
carotid artery, internal jugular vein, cranial
nerves IX, X, XII)
◦ ○ Superior border:
▪ – Zygomatic arch
◦ ○ Inferior border:
▪ – Sternocleidomastoid muscle (oblique
anterior border)
• • Parotid (Stensen) duct:
◦ ○ Approximately 4 to 7 mm long
◦ ○ Originates from the anterior portion of the
parotid coursing forward over the masseter
muscle, enters the buccal fat pad piercing the
buccinator muscle, and opens in the oral cavity
opposite the second maxillary molar (parotid
papilla)
◦ ○ In approximately 20% of the population,
accessory parotid tissue is found along the
anterior portion of the gland and Stensen duct.
• • Submandibular (submaxillary) gland
◦ ○ Each gland weighs from 10 to 15 g.
◦ ○ Encapsulated and walnut-shaped, located in the
submandibular triangle, situated below the
angle of the mandible
◦ ○ Divided into superficial and deep lobes; the latter
can only be palpated in the floor of the mouth
▪ – Anterior belly of the digastric muscle
▪ – Stylomandibular ligament, which separates
it from the lower part of the parotid
◦ ○ Lateral border:
▪ – In relation to the submandibular fossa on
the inner surface of the body of the
mandible
◦ ○ Medial border:
▪ – Bounded by several muscles (mylohyoid,
styloglossus, hyoglossus, stylohyoid, and
posterior belly of the digastric) and nerves
(hypoglossal, glossopharyngeal, and
lingual)
▪ – Inferior border of the body of the mandible
▪ – Skin, platysma, and deep fascia
◦ ○ Submandibular (Wharton) duct:
▪ – Runs forward along the inner surface of the
mandible, in parallel with the lingual nerve
passes medial to the lower border of the
sublingual gland, at which point the duct
may receive the major sublingual duct
(Bartholin) prior to opening in the oral
cavity at the sublingual caruncle or papilla
lateral to the frenulum
• • Sublingual gland
◦ ○ Smallest of the major salivary glands, weighing
between 2 and 4 g
◦ ○ Almond-shaped, located submucosally in the floor
of the mouth
▪ – Opposite sublingual gland
▪ – Deep part of the submandibular gland
◦ ○ Lateral border:
▪ – Internal aspect of the body of the mandible
◦ ○ Medial border:
▪ – Genioglossus muscle
▪ – Mucosa of the floor of the mouth, which it
raises to form the sublingual fold
▪ – Mylohyoid muscle
◦ ○ Has several ducts connecting to the oral cavity:
▪ – Several ducts unite to form the common
sublingual (Bartholin) duct, the largest
duct, which merges with the
submandibular duct prior to opening in the
oral cavity lateral to the frenulum
▪ – Smaller ducts known as Rivinus ducts open
into the oral cavity proper.
• • Minor salivary (seromucous) glands
◦ ○ Located beneath the mucosal epithelium
throughout the submucosa of entire upper
aerodigestive tract:
▪ – Are unencapsulated arranged in lobules
▪ – In tongue and lips lie in close contact with
structures around them, including:
▪ ▪ Skeletal muscle
▪ ▪ Nerves
▪ – Anterior hard palate and gingiva generally
devoid of seromucous glands

Innervation of the Salivary Glands
• • Parotid gland
◦ ○ Auriculotemporal branch of the IX cranial nerve
traverses the parotid gland and provides its
sensory and secretomotor functions:
▪ – Frey syndrome, or auriculomotor nerve
syndrome: occurs after parotidectomy
when misdirected regeneration of the
secretomotor fibers with innervation of the
cutaneous sweat glands results in facial
sweating during eating
◦ ○ VII (facial) nerve passes through the deep and
posterior aspects of the parotid gland prior to
dividing into its branches to the face:
▪ – Any surgical procedure to remove portions
of the parotid gland, unless it involves only
the superficial part, carries the danger of
damage to the nerve; maintaining the
integrity and function of the facial nerve in
the face of a total parotidectomy is a
difficult and delicate procedure.
• • Submandibular and sublingual glands:
◦ ○ Facial nerve (VII) provides the sensory and
secretomotor function of these glands via the
chorda tympani accompanying the lingual nerve
(a branch of the mandibular division of V nerve)
passing through the submandibular ganglion.
• • Blood supply and lymphatic drainage
◦ ○ Parotid gland:
▪ – Arterial supply is via branches of the
external carotid artery and includes the
posterior auricular, maxillary, superficial
temporal, and transverse facial arteries.
▪ – Venous structures parallel those of the
arteries and empty into the external jugular
vein
▪ – Lymphatic drainage is to the superficial and
deep cervical lymph nodes via the
superficial parotid lymph nodes.
◦ ○ Submandibular and sublingual glands:
▪ – Arterial supply to the submandibular gland
is via branches of the external carotid
artery the facial and lingual arteries;
arterial supply to the sublingual gland is by
the sublingual and submental arteries
branches of the lingual and facial arteries,
respectively.
▪ – Venous structures parallel those of the
arteries and empty into the external and
internal jugular veins.
▪ – Lymphatic drains to the superficial and deep
cervical lymph nodes via submandibular
and sublingual lymph nodes.

Histology of the Salivary Glands
• • See Figs. 18-2 through 18-5 ; Tables 18-1 and 18-2 .
Open full size imageFig. 18-2 Schematic drawing of salivary

duct system. A, The drawing shows the major salivary gland
ductal system. B, The ductal system is shown with cross-
sections at the various ductal levels. ( A, Modified from
Batsakis JG: Tumors of the head and neck: clinical and
pathological considerations, ed 2, Baltimore, 1979, Williams
& Wilkins. B, From Som PM, Curtin HD: Head and neck
imaging, ed 5, Philadelphia, 2011, Elsevier, 2454, Fig. 40-
7B.) Open full size
image Open full size



imageFig. 18-3 Histologic features of acinar cell types in
various salivary glands. A, The parotid gland is composed of
serous acini characterized by triangular to pyramidal cells
with a narrow apex toward the luminal aspect, round nuclei
near the basal one third of the cell, and abundant cytoplasm
containing numerous basophilic zymogen granules situated
at the apical portion. B, Although considered to be wholly
composed of serous acini, mucous cells (arrows) can be
seen in parotid gland parenchyma. C, The submandibular
(and sublingual) gland is composed of an admixture of
mucous and serous acini; serous cells typically arranged as
crescent-shaped caps (referred to as demilunes) along the
periphery of the mucous acinar cells. D and E, Palatal minor
salivary glands are situated in the submucosa with a lobular
arrangement and are wholly composed of mucous acini-
appearing pyramidal cells with basally located, flattened
nuclei and clear to faintly basophilic, finely granular-
appearing cytoplasm. F and G, Minor salivary glands
(seromucous glands) are situated in the submucosa with a
lobular arrangement and composed of an admixture of
mucous and serous cells. H, Lingual and labial minor salivary
glands can be seen in close contact with structures, around
them including skeletal muscle and nerves, the latter
including ganglion cells.

Fig. 18-4 Histology of salivary gland ducts. A, Intercalated
ducts are lined by low cuboidal cells with centrally located
oval nuclei and scant amphophilic to eosinophilic cytoplasm.
B, Striated ducts are larger than intercalated ducts and are
lined by columnar cells with centrally located round nuclei
displaying deep basal vertical striations. C, Transition from
intercalated duct to striated duct. D, Small interlobular
excretory duct lined by pseudostratified columnar cells and
located within dense fibrous connective tissue.


Fig. 18-5 Immunohistochemical staining of salivary gland
parenchyma. Immunohistochemical reactivity in normal
salivary gland structures include (A) high and low molecular
weight cytokeratin (CAM 5.2) expression in acinar cells,
intercalated cells and striated duct cells (arrowheads) , and
interlobular duct cells (arrow) ; myoepithelial and basal cells
are also reactive; (B) high molecular weight cytokeratin
(CK5/6) expression of myoepithelial cells of both acini and
striated ducts (arrowheads) and basal cells of interlobular
duct (arrow) ; (C) p63 expression seen in myoepithelial cells
of acini (left) and basal cells of striated duc t (arrowhead) and
interlobular duct (arrow) ; (D) S100 protein expression in
myoepithelial cells of acini and striated ducts (arrowheads)
but negative in basal cells of interlobular duct (arrow) ; note
adipocytes are also S100 protein positive; (E) calponin
expression is similar to that of S100 protein, including
expression in myoepithelial cells of acini and striated ducts
(arrows) but negative in basal cells of interlobular duct
(arrowhead) ; (F) discovered on GIST-1 (DOG1) expression
is primarily restricted to acinar cells with moderate apical
membranous staining. TABLE 18-1 Salivary Gland Acinar
Cell Types
A, Acinar cells; B, basal cells; CAL, calponin; CEA,
carcinoembryonic antigen; DOG1, discovered on GIST 1; ED,
excretory duct; EMA, epithelial membrane antigen; GFAP, glial
fibrillary acidic protein; HMWK, high molecular weight cytokeratin
(e.g., CK5/6); ID, intercalated duct; LMWK, low molecular weight
cytokeratins (e.g., CK7, CK8, CK19); M, myoepithelial cells; PanK,
pancytokeratin (AE1/AE3; CAM5.2); SD, striated duct; SMA,
smooth muscle actin; V+, variably positive; VIM, vimentin.
* Weak to moderate apical staining. † Moderate apical
membranous staining.
• Common to all salivary glands is their arborizing
epithelial ductal system with production of saliva
from the specialized secretory cells in the distal
segments and delivery of these secretions via the
complex branching structures to the oral cavity:
◦ ○ Main secretory duct of the gland divides into
progressively smaller striated ducts that, in
turn, branch into smaller intercalated ducts,
which terminate in the terminal secretory end
structures.
• • From distal to proximal the system includes:
◦ ○ Acini represent the terminal secretory cells and
include serous and/or mucous cells, which
produce the saliva:
▪ – Serous cells:
▪ ▪ Triangular to pyramidal cells with a
narrow apex toward the luminal
aspect, round nuclei near the basal
one third of the cell, and abundant
cytoplasm containing numerous
basophilic zymogen granules situated
at the apical portion
▪ ▪ Zymogen granules are diastase-
resistant, periodic acid Schiff positive,
and mucicarmine negative.
▪ – Mucous cells:
▪ ▪ Pyramidal cells with basally located,
flattened nuclei and clear to faintly
basophilic, finely granular-appearing
cytoplasm
▪ ▪ Mucicarmine, alcian blue, and diastase-
resistant, periodic acid Schiff positive
▪ – Immunohistochemical staining of acinar
cells includes:
▪ ▪ Pancytokeratins and low molecular
weight cytokeratins (AE1/AE3,
CAM5.2, CK7, CK8, CK19), EMA and
CEA positive
▪ ▪ Amylase positive
▪ ▪ Discovered on GIST-1 (DOG-1) positive:
▪ □ Diffuse moderate (2+) apical
membranous staining pattern in
normal serous acini, 1+ apical
membranous pattern in mucous
acini
▪ □ Myoepithelial cells, striated and
excretory ducts negative
▪ ▪ p63, calponin, smooth muscle actin,
S100 protein, and vimentin negative
▪ ▪ High molecular weight keratins (e.g.,
CK5/6) typically negative
◦ ○ Intercalated ducts
▪ – Lined by low cuboidal cells with centrally
located oval nuclei and scant amphophilic
to eosinophilic cytoplasm
▪ – More conspicuous in the parotid gland than
in other salivary glands
▪ – Immunohistochemical staining of
intercalated duct cells includes:
CAM5.2, CK7, CK8, CK19), EMA,
CEA, and estrogen receptor positive
▪ ▪ DOG-1 positive in distal intercalated
cells:
▪ □ Weak to moderate (1-2+) apical
staining
▪ ▪ Amylase negative
◦ ○ Myoepithelial cells:
▪ – Ectodermally derived, flat, elongated cells
lying at the periphery of the acinar cells
and the intercalated cells in the space
between the basement membrane and the
basal plasma membrane
▪ – Generally, myoepithelial cells are difficult to
identify by light microscopy; appear as
flattened, stellate, and spindle-shaped cells
with cellular processes that extend around
acini and intercalated ducts
▪ – Their contractile function is similar to
smooth muscle, assisting in the movement
of saliva through the duct system.
▪ – Immunohistochemical staining of
myoepithelial cells includes:
▪ ▪ Pancytokeratins, low and high
molecular weight cytokeratins
(AE1/AE3, CAM5.2, CK7, CK8, CK19)
positive
S100 protein, and vimentin positive
▪ ▪ Variable GFAP reactivity
▪ ▪ EMA and CEA negative
▪ ▪ DOG-1, amylase negative
◦ ○ Striated ducts:
▪ – Larger than intercalated ducts
▪ – Lined by columnar cells with centrally
located, round nuclei displaying deep basal
vertical striations representing basal folds
in plasma membranes for which these
ducts are named
▪ – Due to large numbers of cytoplasmic
mitochondria the cells of striated ducts:
▪ ▪ Have prominent eosinophilic granular
cytoplasm
▪ ▪ Are intensely reactive with
phosphotungstic acid-hematoxylin
▪ – Immunohistochemical staining of striated
duct cells includes:
CEA positive
◦ ○ Excretory (interlobular) ducts:
▪ – Lined by pseudostratified columnar cells
adjacent to the striated duct cells
▪ – Goblet cells may be present intermixed
among the pseudostratified columnar cells.
▪ – Lined by stratified squamous cells as these
ducts merge with the oral mucosal
epithelium
▪ – Immunohistochemical staining of excretory
(interlobular) duct cells includes:
CEA positive
◦ ○ Basal cells:
▪ – Located around striated and excretory
(interlobular) ducts
▪ – Differ from myoepithelial cells by absence of
myoid markers by immunohistochemistry
and myofilaments on ultrastructural
evaluation
▪ – Play role in regeneration and metaplastic
changes
▪ – Immunohistochemical staining of basal cells
includes:
▪ ▪ Pancytokeratins, low and high
molecular weight cytokeratins
(AE1/AE3, CAM5.2, CK7, CK8, CK19)
positive
▪ ▪ p63 positive
▪ ▪ Calponin, smooth muscle actin, S100
protein, and GFAP negative
▪ ▪ EMA and CEA negative
• • Salivary glandular component separated into lobules by
fibrous tissue septa.
• • Histologic differences between the salivary glands rests
with the composition of their respective acinar cells:
◦ ○ Parotid gland:
▪ – Entirely serous although mucinous acini
may be identified
▪ – Sebaceous glands and/or scattered
sebaceous cells may be identified:
▪ ▪ Stains for mucin are negative.
▪ – Mature adipose tissue is a normal finding in
parotid gland parenchyma, and it
proportionally increases with age.
◦ ○ Submandibular (submaxillary) gland:
▪ – Mixed serous and mucous with the majority
of acinar cells being serous
▪ – Serous cells typically arranged as crescent-
shaped caps (referred to as demilunes)
along the periphery of the mucous acinar
cells
◦ ○ Sublingual gland:
▪ – Mixed mucous and serous (demilunes) with
the majority of acinar cells being mucous
◦ ○ Minor salivary glands vary depending on site:
▪ – Most of upper aerodigestive tract including
oral cavity, sinonasal tract, pharynx, and
larynx is seromucous, with the majority of
acinar cells being mucous.
▪ – In anterior ventral portion of tongue
(referred to as Blandin or Nunn glands)
composed of pure mucous type
▪ – In the region of the circumvallate papillae on
the posterior and lateral portions of the
tongue (referred to as von Ebner glands)
composed of pure serous type
▪ – Palate is purely mucous.
• • Age-related and/or reactive cellular changes may
include:
◦ ○ Oncocytes:
▪ – Characterized by cells with abundant
eosinophilic granular cytoplasm owing to
presence of abundant mitochondria
▪ – Uncommon cell type in salivary gland in
patients under 50 years of age but presence
increases with age
▪ – See Chapters 19 and 20 for more detailed
discussion and illustrations.
◦ ○ Sebaceous cells:
▪ – Present in most parotid glands but generally
are few in number
▪ – Appear as small collections of sebaceous
cells
▪ – Do not stain with mucicarmine.
▪ – Immunoreactive for EMA
◦ ○ Fatty infiltration:
▪ – In particular relative to parotid gland
represents a normal finding and
proportionally increases with age
▪ – Presence increased under other conditions
including but not limited to malnutrition
(see next chapter)
◦ ○ Metaplasia may include presence of:
▪ – Squamous cells with keratinization and
intercellular bridges
▪ – Mucous cells
▪ – Metaplastic changes not infrequently seen
after a traumatic event such as prior fine-
needle aspiration or biopsy but may occur
spontaneously unrelated to a traumatic
event
◦ ○ Hyperplasia
◦ ○ Atrophy
• Age-related and metaplastic changes of salivary gland
discussed in Chapter 19

Embryology, Anatomy, and Histology of The Salivary Glands

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• • Salivary gland system composed of exocrine glanular

tissue that include major salivary glands and minor

Embryology of the Salivary Glands

• end ngRepeat: item in XocsCtrl.sections

• end ngRepeat: item in XocsCtrl.sections

• end ngRepeat: item in XocsCtrl.sections

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