Annals of RSCB
Vol. XVIII, Issue 2/2013
MYOEPITHELIAL CELLS: REVISITED
- Review Harini Nirmalkumar, Nithya Jagannathan
DEPARTMENT OF ORAL PATHOLOGY, SAVEETHA DENTAL COLLEGE,
SAVEETHA UNIVERSITY, CHENNAI, INDIA
Summary
Myoepithelial cells are important components of salivary gland which are stellate
shaped with cytoplasmic extensions and present between the basement membrane and the
plasma membrane of the acinar structures and ductal cells. They have structural features of
both epithelium and smooth muscle cells and so they are called the myoepithelial cells.
They enable the contraction of the structural apparatus and this expulses the secretions
from the acinar cells. They can be demonstrated by special stains and enzyme
histochemistry. The article reviews on the developmental process of the myoepithelial
cells, structure, function, the differentiation patterns and its role in salivary gland tumours
Keywords: differentiation, immunohistochemistry, salivary gland, secretion.
[email protected]
Introduction
Prenatal and Postnatal development of
myoepithelial cells:
Early development stage (10-18 weeks):
The primitive myoepithelial cells
appear in the salivary gland epithelium at
about 15-16 weeks of gestation even before
the cytodifferentiation of acinar and ductal
luminal cells takes place. At this phase they
demonstrate
irregular
fibrillar
demonstration. These cells are immature
initially and gradually over a period of time
increase in number and they get closely
apposed to the tubule alveolar structure of
the salivary gland (Caselitz et al., 1981)
Early
intermediate
developmental
stage(19-24 weeks):
The myoepithelial cells in the fetal
salivary gland express actin filaments
before the maturation of the acinar and
ductal luminal cells takes place. This
suggests that myoepithelial cells antedate
the
secretary
epithelium
during
embryogenesis. With maturation of the
acinar cells, the myoepithelial cells undergo
cytoplasmic extension and took place in the
basal portins of the acini and intercalalted
duct and they were extruded in the
excretory and striated ducts (Caselitz et al.,
1981; Lee et al., 1991).
Late intermediate developmental stage
(25-32 weeks):
The human salivary gland system is
composed of three major salivary gland and
numerous minor salivary glands. The
Myoepithelial
cells
are
important
component salivary gland and are located
beneath the basement membrane and the
basal plasma membrane of the acinar cells.
They are usually found in the glandular
epithelium as a thin layer beneath the
luminal cells. They are seen in sweat
glands, lacrimal glands, mammary glands
and salivary glands.
Myoepithelial cells are spindle
shaped and the cell body contains four to
eight
cytoplasmic
processes
which
normally run parallel to the direction of the
duct. Myoepithelial cells are also called as
basket cells as they have a stellate shaped
appearance with embracing cytoplasmic
process the secretary unit. They are present
in both minor and major salivary glands
(Raubenheimer et al.,1987; Gnepp., 2001).
This structural unit was first described by
Zimmerman in 1898. The myoepithelial
cells of the salivary gland are ectodermal in
origin and envelope the acinar, glandular
and ductal elements of the salivary gland.
They are predominant in the acinar areas
followed by the intercalated duct and it is
almost absent in the excretory ducts
(Dardick et al., 1984)
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The myoepithelial cells undergo
morphological changes during this phase
and the cells get further flattened and
dendritic at the basal portions of the acinar
and intercalated duct structures. The
development of myoepithelial cells and
secretary cells begins at the same time,
However
the
myoepithelial
cells
differentiate asynchronously with the
secretary cells. The dendritic myoepithelial
cells mature at 25-26th week and become
more conspicuous. They increase in number
during this stage and mature earlier to push
the secretary material out of the acini
towards the excretory ducts against the
amniotic fluid pressure (Lee et al., 1991;
Chi et al.,1996 ).
Late developmental stage (33-40 weeks):
The myoepithelial cells increase in
number and develops contractile properties.
The cells which first developed in the
acinar and intercalated ductal areas move
towards the excretory ducts through the
basal portions of the duct (Lee et al., 1991;
Chi et al.,1996 ).
Structure of myoepithelial cells:
Myoepithelial cells appear to have
the same morphology, irrespective of the
organ or species in which they are studied.
The cells embracing the acini are the
secretory endpieces which contains four –
eight cytoplasmic process. The cytoplasmic
process gives two or more secondary
branches and this gives an appearance of an
octopus sitting on a rock appearance
(Young et al., 1978). The myoepithelium
contains an outer and inner surface. The
outer
surface
contains
caveolar
invaginations and they are numerous in
areas where nerve fibres are present. The
inner surface or the visceral surface is
smooth and they are attached to the
secretary cells by desmosomes. The
cytoplasmic process of the cell contains
extension of the cytoplasmic membrane
which are protruded deep inside (Tandler.,
1965).
Electron microscopy shows an
ellipsoidal cell containing few ribsomes and
mitochondrial scattered through the
cytoplasm of the body. Other organs
including the golgi apparatus, endoplasmic
reticulum are seen in the juxtranuclear
position (Young et al., 1978). They contain
cytoplasmic filaments which are uniform in
diameter. They have varying densities with
varying distance between the individual
elements. They have a compact distribution
resembling the dense bodies and terminate
in the attachment devices. Intermediate
sized filaments are demonstrated in the
cytoplasm are of cytokeratin type (Caselitz
et al., 1981).
Myeoepithelial cells demonstrate an
electron lucent cytoplasm devoid of any
organelles adjacent to the cells. These cells
are believed to be clear cells which had
undergone
a
transformation.
The
myoepithelium therefore has properties of a
secretary intercalated duct cell suggesting
an ancestral origin (Riva et al.,1976).
Functions of myoepithelial cells:
The role of myoepithelial cells
begins from the embryonic development
from the branching morphogenesis and
promotes epithelial cell differentiation. The
myoepithelial cells of the salivary gland
have a dual innervations by sympathetic
and parasympathetic synapses and the
impulses from both results in contraction of
a cell (Garrett et al., 1979). The diffusion of
transmitter substances synchronizes with
the contraction made by the gap junction
and the overlap between the myoepithelial
cell process (Tamarin., 1966; Brocco et al.,
1979). The myoepithelial contraction helps
in expulsion of the secretions by the rupture
of a ripe mucous cell, preventing distention
of secretary endpiece thus reducing the
luminal volume. The secretary cells lacking
the myoepithelial cells usually secrete a
watery or serous saliva (Tandler., 1965).
The contraction of the myoepithelial
cells decrease the surface area of the
secretary apparatus exposed to interstial
fluid and thereby modifies the salivary
secretion The myoepithelial cilia act as
chemoreceptors and has a sensory function.
Contraction of the myoepithelial cells
around the intercalalted ducts results in
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Vol. XVIII, Issue 2/2013
reduction of the luminal volume and
shortens and widens the structure
decreasing the peripheral resistance (Young
et al., 1977).
The myoepithelial cells also helps in
transportation of the metabolites to and
from the secretary cells. The basal surface
of the myoepithelium demonstrates
numerous infoldings which increase the
surface area exposed to the tissue fluid
(Nagai et al., 1985). There is presence of
pinocytic vesicles, which demonstrates
positivity for iron binding protein ferritin,
increased alkaline phosphatase and
magnesium
dependent
adenosint
triphosphatase activity (Toto et al., 1985;
Yoshikara et al., 1984)..
The myoepithelial cells helps in
formation and maintainence of the
basement membrane components namely
fibronectin, laminin and elastin (Toto et
al., 1985). These are not just essential for
the
epithelial
proliferation
and
differentiation, but also plays a role in
epithelial mesenchymal junctions through
which the metabolites of or role as a tumour
suppressor the saliva are communicated
(Han et al., 1976; Kleinman et al., 1981)
Myoepithelial cells beyond all these
functions, have a major role as a tumour
suppressor
by
exerting
paracrine
antiinvasive role by promoting epithelial
differentiation,
basement
membrane
secretion, by secreting proteinase inhibiting
angiogenesis ( Ellis., 1991; Batsakis et al.,
1983).
Demonstration of Myoepithelial cells:
The
identification
and
demonstration of myoepithelial cells in
important, especially in salivary gland
neoplasms. The routine stains used in
histopathology does not clearly visualize
the cell and allows only the nucleus to be
seen However special stains and
immunohistochemistry for the myofibrils
makes them evident. A combination of
histochemistry and electron microscopy
have been used to highlight the intact layer
and helps in identifying in neoplasm. As
they contain both the epithelial and smooth
muscle phenotype, most of the markers
used are directed against the smooth
muscle antigens. Histochemical stains such
as Phosphotunstic acid hematoxylin and
iron hematoxylin, levanol fast cyanine (
Coomasie Blue), silver impregnation
methods enables us to visualize better
(Ellis., 1991)
Markers
for
demonstration
of
myoepithelial cells:
The various markers used for
demonstrating myoepithelial cells are alpha
smooth muscle actin, smooth muscle
myosin heavy chain (Ellis.,1991), calponin,
h-caldesmon (Prasad et al., 1999), S-100
(Foschini et al., 2008), cytokeratin 14
(Jones et al., 1992). The cells also
demonstrates positivity for maspin, p63,
CD10 which also differentiates the normal
from neoplastic myoepithelial cells (Reis et
al., 2001; Barbareschi et al.,2001).
Morphologic
patterns
of
the
myoepithelial cells in tumours:
Neoplastic myoepithelial cells takes
complex patterns resulting from interplay
of three factors namely the (i) Cytological
Differentition (ii) Extracellular matrix
production and (iii) Architectural patterns
Cytological Differentiation:
The
myoepithelial
cells
differentiates into cells of various
morphological types. The forms taken by
these cells are angulate/ basaloid cells(
demonstrate small hyperchromatic nuclei
with
faint
eosinophilic cytoplasm),
epitheloid cells ( cells are polygonal with
vesicular nuclei and ample cytoplasm),
clear cells ( contain clear cytoplasm due to
glycogen), spindle cells ( elongates and
fusiform with pale cytoplasm) and
plasmacytoid cells ( contains bright
esinophilic cytoplasm with eccentric nuclei)
(Fig 1). A tumour undergoing myoepithelial
cell differentiation has a morphological
heterogeneity and sometimes they also
undergo metaplastic changes such as
chondroid, squamous and oncocytic area (
Ellis., 1991; Batsakis et al., 1983).
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Vol. XVIII, Issue 2/2013
Figure 1: The differentiation pattern of
myoepithelial cell in tumours
Architectural Patterns:
Dardick et al. (1989) suggested the
diverse
architectural
patterns
of
myoepithelial cells which are enumerated
as follows. The various patterns that a
myoepithelial cell can produce are myxoid
pattern, solid pattern, reticular pattern,
microcytic pattern, cribriform patterm (Fig
1).
The myxoid pattern demonstrates
loosely arranged tumour cells which are
produced due to production of abundant
chondromyxoid matrix. The solid pattern
are non myxoid in which the cells are
arranged in the form of nests and sheets
seen in intervening hyalinizzed stroma.
Reticular pattern shows anatamosing
pattern
composed
of
epithelial
myoepithelial
cells
intervened
by
extracellular material. Microcystic pattern
are otherwise called as pseudocystic pattern
and shows cystic space formed by
accumulation of myxoid matric within nests
of tumour cells. Cribriform pattern are
called pseudoglandular pattern in which the
epithelial cells form cribriform structures
and pseudoumen due to myxoid matrix
production ( Ellis., 1991; Batsakis et al.,
1983).
Role of myoepithelial cells in benign and
malignant salivary gland tumours:
Pleomorphic
adenoma
and
myoepithelioma:
The tumours are benign tumours
with various morphological diversities.
The
predominant
myoepithelial
differentiation in these tumours are
responsible
for
the
mesenchymal
components and morphological diversity.
Myoepithelially differentiated cells are
arranged in the form of Sheets and islands
with varying proportions of spindle cells,
clear cell, plasmacytoid, and epitheloid
cells. Most tumors are composed of a just a
single cell type but combinations of two or
more types may occur (Hirano et al.,
1990)
Basal cell adenoma and myoepithelial
cells:
The basal cell adenoma was first
described in 1967 by Kleisasser and they
Extracellular matrix production:
Neoplastic myoepithelial cells
alters the matrix synthesizing property and
produces excess of basement membrane
and non basement membrane components.
Chondroitin sulfate is a non Basement
membrane matrix which is produced in
excess resulting in bluish gray appearance
which is alcian blue positive. They also
produce eosinophilic hyalinized material (
type IV collagen and laminin) related to
basement membrane and the components
of interstitial matrix ( Fibronectin, type I, II
Collagen).(Fig 2) Accumulation of these
materials in varying proportions results in
alteration of the basement membrane
structure on salivary gland tumours
(Raubenheimer et al.,1987; Dardick et al.,
1984; Ellis., 1991; Dardick et al., 1989).
Figure
2:
Differentiation
of
myoepithelial cells in extracellular
matrix formation
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Vol. XVIII, Issue 2/2013
lack the myxochondroid component and
are generally monomorphic. Myoepithelial
cells participate in this tumour and produce
a hyalinized matrix. Variable amounts of
myxoid matrix also occur and the
neoplastic myoepithelial cells produce
basement membrane related and interstial
matrix. This results in formation of hyaline
droplets in this tumour (Zarbo et al., 2000)
Adenoid
cystic
carcinoma
and
myoepithelium:
ACC exhibits a dual differentiation
pattern of epithelial and myoepithelial
cells resulting in three patterns: the
cribriform , solid and tubular pattern. The
myoepithelial cells are arranged in the
form of small basaloid aggregate of
angulated cells in the periductal location
and cribriform areas. The solid variant
also demonstrates scatted or peripheral
basaloid myoepithelial cells arranged in the
form of small sheets/ nests. The
myoepithelial differentiation also gives rise
to a collagenous and hyalinized stroma
with a bluish myxoid material
in
cribriform pattern (Szanto et al., 1984)
Epihtelial Myoepithelial carcinoma:
This tumour similar to the adenoid
cystic carcinoma shows a dual epithelial
myoepithelial differentiation and this is
reflected as a nodular growth pattern with
the
epithelial
tubules
cuffed
by
myoepithelial cells. Bimorphic type is
similar to ACC but the stainin pattern
differs. The outer cells are clear with
expression of myoepithelial markers.
However when all the cells are
predominantly
having
myoepithelial
differentiation, it is difficult to distinguish
from primary clear cell carcinoma, clear
cell
myoepithelial
carcinoma
and
hyalinizing clear cell carcinoma (Simpson
et al., 1991; Hagiwara et al., 1995)
Polymorphous low grade
adenocarcinoma:
The myoepithelial differentiation is
rarely present in this tumour and only a
focal stain with smooth muscle markers
has been demonstrated. The participation
of myoepithelial cells in this tumour is
however suggested by the presence of a
myxoid hyalinized matrix as seen in other
tumours (Batsakis et al., 1983; Dardick et
al., 1989).
Mucopeidermoid
carcinoma
and
myoepithelial cells:
The histopathology of MEC as
reported by Dardick et al. (1989), suggests
the presence of luminal epithelial cells
surrounded by modified intermediate cells.
They are believed to be the modified
myoepithelial cells. However, whether the
tumour originates from the reserve duct
cells or the myoepithelial cells is still
controversial. The two theories of
histogenesis reported by Dardick states that
the MEC differentiates from the luminal
epithelial cells or from the modified
myoepithelial
cells.
The
modified
myoepithelium
corresponds
to
the
intermediate cells and shows possibilities
for
undergoing
squamous
metaplasia(Dardick et al., 1989).
Conclusion:
The myoepithelial cells are
important because they play a fundamental
role in secretion of saliva by its contractile
function. They are also considered as the
key for various morphogenetic processes
as they give various histological
appearances to the gland. The role of
myoepithelial cells in salivary gland
tumours needs to be understood because
they differentiate into a variety of
morphological pattern. Knowledge on the
differentiation pattern thus paves a way for
the diagnosis of salivary gland tumours.
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