Chapter
18
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:
m Major salivary glands include:
Parotid gland
Submandibular (submaxillary) gland
Sublingual gland
m 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 micro-
scopic features:
m Major and intraoral minor salivary glands
produce fluids that constitute oral saliva.
m Minor salivary (seromucous) glands outside the
oral cavity including sinonasal tract, pharynx,
larynx, trachea, bronchi are morphologically between the ramus of the mandible and the
and functionally similar to oral minor salivary
glands but in contrast do not contribute to m Artificially divided into two lobes by the coursing
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:
m Stomodeal epithelium is part ectoderm and part
endoderm.
Parotid gland:
m First to form in humans
m Arise from the ectodermal lining of the stomo-
deum from which the ducts, lumina, and acini
evolve
m Capsule and connective tissue develop from the
surrounding mesenchyme
Submandibular gland:
m Develops from buds of the endoderm in the floor
of the stomodeum from which the ducts, lumina,
and acini evolve
Sublingual gland:
m Appears later than the other glands
m Develop from buds of the endoderm in the para-
lingual sulcus from which the ducts, lumina, and
acini evolve
Minor salivary glands (seromucous glands):
m Develop later in gestational life (third month)
m 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.)
ANATOMIC BORDERS OF THE
SALIVARY GLAND
See Fig. 18-1.
Parotid gland
m Largest gland (average weight of 25g)
m Encapsulated and pyramidal-shaped palpable
mastoid process
of the facial nerve through the gland:
Superficial lobe (largest portion)
Deep lobe situated adjacent to the lateral pha-
ryngeal space
m Anterior border:
Overlies the superficial surface of the masseter
muscle
m Posterior border:
Overlaps the sternocleidomastoid muscle and
wraps around the lower ear
m Lateral or superficial border:
Skin and dermis of the face
m Medial or deep border:
Buttressed by the styloid process and its associ-
ated muscles (styloglossus, stylohyoid, stylo-
pharyngeal) and by the carotid sheath and its
contents (internal carotid artery, internal
jugular vein, cranial nerves IX, X, XII)
m Superior border:
Zygomatic arch
m Inferior border:
Sternocleidomastoid muscle (oblique anterior
border)
Parotid (Stensen) duct:
m Approximately 4 to 7mm long
m Originates from the anterior portion of the
parotid coursing forward over the masseter
805
806 SECTION 6 Major and Minor Salivary Glands

Stensens duct piercing the

buccinator muscle

Frenulum of tongue

Sublingual fold and opening of

sublingual ducts
Parotid
Opening of submandibular gland
(Whartons) duct

Sublingual gland
Cut surface of the mylohyoid muscle
Anterior belly of the digastric muscle Lingual nerve bending around
A Superficial portion of the submandibular gland Whartons duct

Internal carotid artery

Pharyngeal constrictor muscle Retromandibular (deep)

portion of parotid gland

Styloid muscles
Facial nerve
Palatine tonsil Posterior belly of
digastric muscle
Pterygomandibular raphe
Sternocleido-
Masseter muscle
mastoid
muscle
Stensens duct
running over the
buccal fat pad External
carotid artery

Buccinator Retromandibular
muscle (posterior facial)
vein

Superficial portion
B of parotid gland

Fig. 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).
 CHAPTER 18 Embryology, Anatomy, and Histology of the Salivary Glands 807

Cut surface of
medial pterygoid
muscle

Openings of sublingual
gland in the floor of mouth
(along the sublingual line)

Sublingual
gland

Mylohyoid
muscle

Submandibular
gland
Cut anterior belly
of digastric muscle
Whartons Hyoid bone
C duct

Fig. 18-1, contd

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.)

muscle, enters the buccal fat pad piercing the m Lateral border:
buccinator muscle, and opens in the oral cavity In relation to the submandibular fossa on the
opposite the second maxillary molar (parotid inner surface of the body of the mandible
papilla) m Medial border:

m In approximately 20% of the population, Bounded by several muscles (mylohyoid, stylo-

accessory parotid tissue is found along the glossus, hyoglossus, stylohyoid, and posterior
anterior portion of the gland and Stensen belly of the digastric) and nerves (hypoglossal,
duct. glossopharyngeal, and lingual)
Submandibular (submaxillary) gland m Superior border:

m Each gland weighs from 10 to 15g. Inferior border of the body of the mandible
m Encapsulated and walnut-shaped, located in the m Inferior border:

submandibular triangle, situated below the angle Skin, platysma, and deep fascia
of the mandible m Submandibular (Wharton) duct:

m Divided into superficial and deep lobes; the Runs forward along the inner surface of the
latter can only be palpated in the floor of mandible, in parallel with the lingual nerve
the mouth passes medial to the lower border of the sub-
m Anterior border: lingual gland, at which point the duct may
Anterior belly of the digastric muscle receive the major sublingual duct (Bartholin)
m Posterior border: prior to opening in the oral cavity at the
Stylomandibular ligament, which separates it sublingual caruncle or papilla lateral to the
from the lower part of the parotid frenulum
808 SECTION 6 Major and Minor Salivary Glands
Sublingual gland
m Smallest of the major salivary glands, weighing
between 2 and 4g
m Almond-shaped, located submucosally in the
floor of the mouth
m Anterior border:
Opposite sublingual gland
m Posterior border:
Deep part of the submandibular gland
m Lateral border:
Internal aspect of the body of the mandible
m Medial border:
Genioglossus muscle
m Superior border:
Mucosa of the floor of the mouth, which it
raises to form the sublingual fold
m Inferior border:
Mylohyoid muscle
m Has several ducts connecting to the oral cavity:
Several ducts unite to form the common deep cervical lymph nodes via the superficial
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
m Located beneath the mucosal epithelium through-
out 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
m Auriculotemporal branch of the IX cranial nerve
traverses the parotid gland and provides its
sensory and secretomotor functions:
Frey syndrome, or auriculomotor nerve syn-
drome: occurs after parotidectomy when mis-
directed regeneration of the secretomotor fibers
with innervation of the cutaneous sweat glands
results in facial sweating during eating
m 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:
m Facial nerve (VII) provides the sensory and secre-
tomotor 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
m Parotid gland:
Arterial supply is via branches of the external
carotid artery and includes the posterior auric-
ular, maxillary, superficial temporal, and trans-
verse facial arteries.
Venous structures parallel those of the arteries
and empty into the external jugular vein
Lymphatic drainage is to the superficial and
parotid lymph nodes.
m 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 sub-
mental 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.
Common to all salivary glands is their arborizing
epithelial ductal system with production of saliva
from the specialized secretory cells in the distal seg-
ments and delivery of these secretions via the complex
branching structures to the oral cavity:
m Main secretory duct of the gland divides into
progressively smaller striated ducts that, in turn,
branch into smaller intercalated ducts, which ter-
minate in the terminal secretory end structures.
From distal to proximal the system includes:
m 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
 CHAPTER 18 Embryology, Anatomy, and Histology of the Salivary Glands 809

Excretory duct
Excretory duct

Striated duct
Striated duct

Intercalated
duct
Intercalated duct

Mucous acini

A Secretory alveoli Serous acini

Serous cells

Serous secretory unit

Myoepithelial cell

Striated (intralobular) Intercalated ducts

duct Mucous secretory unit

To interlobular
excretory ducts

Fig. 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.)

abundant cytoplasm containing numerous Mucous cells:

basophilic zymogen granules situated at the Pyramidal cells with basally located, flat-

apical portion tened nuclei and clear to faintly basophilic,

Zymogen granules are diastase-resistant, finely granular-appearing cytoplasm
periodic acid Schiff positive, and mucicar- Mucicarmine, alcian blue, and diastase-
mine negative. resistant, periodic acid Schiff positive
810 SECTION 6 Major and Minor Salivary Glands

A B

C D

E F

Fig. 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.
 CHAPTER 18 Embryology, Anatomy, and Histology of the Salivary Glands 811

G H

Fig. 18-3, contd

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.

A B

C D

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.
812 SECTION 6 Major and Minor Salivary Glands

A B

C D

E F

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 duct (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.
 CHAPTER 18 Embryology, Anatomy, and Histology of the Salivary Glands 813

Immunohistochemical staining of acinar cells m Intercalated ducts

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+
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:
Pancytokeratins and low molecular weight

apical membranous pattern in mucous cytokeratins (AE1/AE3, CAM5.2, CK7,

acini CK8, CK19), EMA, CEA, and estrogen
Myoepithelial cells, striated and excretory receptor positive
ducts negative p63, calponin, smooth muscle actin, S100

p63, calponin, smooth muscle actin, S100 protein, and vimentin negative
protein, and vimentin negative DOG-1 positive in distal intercalated cells:

High molecular weight keratins (e.g., CK5/6) Weak to moderate (1-2+) apical staining

typically negative Amylase negative

High molecular weight keratins (e.g., CK5/6)

typically negative
m Myoepithelial cells:
TABLE 18-1 Salivary Gland Acinar Cell Types
Ectodermally derived, flat, elongated cells lying
Salivary Gland Acinar Type* at the periphery of the acinar cells and the
Parotid Serous (scattered mucous intercalated cells in the space between the
cells can be found) basement membrane and the basal plasma
Submandibular (submaxillary) Serous and mucous membrane
Sublingual Mucous and serous Generally, myoepithelial cells are difficult to
identify by light microscopy; appear as flat-
Palate Mucous
tened, stellate, and spindle-shaped cells with
Tongue Mucous and serous cellular processes that extend around acini and
Buccal Mucous and serous intercalated ducts
Lip Mucous and serous Their contractile function is similar to smooth
muscle, assisting in the movement of saliva
All other upper aerodigestive Mucous and serous
tract sites through the duct system.
Immunohistochemical staining of myoepithe-
*Predominant type first. lial cells includes:
Adapted from Ellis GL, Auclair PL: The normal salivary glands. In Pancytokeratins, low and high molecular
Silverberg SG, editor: Tumors of the salivary glands. AFIP
Atlas of tumor pathology, series 4, fascicle 9, Washington, weight cytokeratins (AE1/AE3, CAM5.2,
2008, ARP Press. CK7, CK8, CK19) positive

TABLE 18-2 Immunohistochemistry: Normal Salivary Gland Structures

Cell PanK LMWK HMWK EMA CEA S100 p63 SMA CAL VIM GFAP DOG1
ED + + + +
SD + + + +
ID + + + + +*
A + + + + +
M + + + + + + + + V+
B + + + + +

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.

814 SECTION 6 Major and Minor Salivary Glands
p63, calponin, smooth muscle actin, S100
protein, and vimentin positive
Variable GFAP reactivity
EMA and CEA negative
DOG-1, amylase negative
m Striated ducts:
Larger than intercalated ducts
Lined by columnar cells with centrally DOG-1, amylase negative
located, round nuclei displaying deep basal ver-
tical striations representing basal folds in
plasma membranes for which these ducts Histologic differences between the salivary glands
are named
Due to large numbers of cytoplasmic mito-
chondria the cells of striated ducts:
Have prominent eosinophilic granular
cytoplasm
Are intensely reactive with phosphotungstic
acid-hematoxylin
Immunohistochemical staining of striated duct
cells includes:
Pancytokeratins and low molecular weight
cytokeratins (AE1/AE3, CAM5.2, CK7,
CK8, CK19), EMA and CEA positive
p63, calponin, smooth muscle actin, S100
protein, and vimentin negative
DOG-1, amylase negative
High molecular weight keratins (e.g., CK5/6)
typically negative
m Excretory (interlobular) ducts:
Lined by pseudostratified columnar cells adja-
cent 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:
Pancytokeratins and low molecular weight
cytokeratins (AE1/AE3, CAM5.2, CK7,
CK8, CK19), EMA and CEA positive
p63, calponin, smooth muscle actin, S100
protein, and vimentin negative
DOG-1, amylase negative
High molecular weight keratins (e.g., CK5/6)
typically negative
m Basal cells:
Located around striated and excretory (inter-
lobular) 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.
rests with the composition of their respective acinar
cells:
m 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 proportion-
ally increases with age.
m 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
m Sublingual gland:
Mixed mucous and serous (demilunes) with the
majority of acinar cells being mucous
m 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:
m Oncocytes:
Characterized by cells with abundant eosino-
philic 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 dis-
cussion and illustrations.
 CHAPTER 18 Embryology, Anatomy, and Histology of the Salivary Glands 815
m 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
m Fatty infiltration:
In particular relative to parotid gland repre-
sents a normal finding and proportionally
increases with age
Presence increased under other conditions
including but not limited to malnutrition (see
next chapter)
m Metaplasia may include presence of:
Squamous cells with keratinization and inter-
cellular bridges
Mucous cells
Metaplastic changes not infrequently seen after
a traumatic event such as prior fine-needle aspi-
ration or biopsy but may occur spontaneously
unrelated to a traumatic event
m Hyperplasia
m Atrophy
Age-related and metaplastic changes of salivary
gland discussed in Chapter 19
FURTHER READING
References may be accessed online at ExpertConsult
.com.
 CHAPTER 18 Embryology, Anatomy, and Histology of the Salivary Glands 815.e1
FURTHER READING
Embryology, Anatomy, and
Histology of the Salivary Glands
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pathology of the salivary glands, Philadelphia, 1991, W.B. Saun-
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Ellis GL, Auclair PL: The normal salivary glands. In Silverberg SG,
editor: Tumors of the salivary glands. AFIP Atlas of tumor pathol-
ogy, Series 4; Fascicle 9, Silver Spring, 2008, ARP Press,
pp 124.
Hiatt JL, Sauk JJ: Embryology and anatomy of the salivary glands. In
Ellis GL, Auclair PL, Gnepp DR, editors: Surgical pathology of
the salivary glands, Philadelphia, 1991, W.B. Saunders Company,
pp 29.
Hollinshead WH: The face. In Hollinshead WH, editor: Anatomy for
surgeons (vol 1), ed 3, Philadelphia, 1982, Harper and Row, pp
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Hollinshead WH: The jaws, palate and tongue. In Hollinshead WH,
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