Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: Histogenetic implications for salivary gland tumors

doi:10.1016/0030-4220(87)90173-3

Oral Surgery, Oral Medicine, Oral Pathology

Volume 64, Issue 6, December 1987, Pages 703-715

Oral Surgery, Oral M...

https://doi.org/10.1016/0030-4220(87)90173-3 Get rights and content

Abstract

The organization of salivary gland ducts, especially the presence or absence of myoepithelial cells, is central to histogenetic approaches to the classification of salivary gland tumors. Striated and excretory ducts are reported to be devoid of myoepithelial cells but do contain basal cells. To investigate the nature of such basal cells, tissue sections of normal human salivary glands were examined by means of immunohistochemical, ultrastructural, and fluorescent microscopic techniques. With the use of a mouse monoclonal anticytokeratin antibody (312C8-1) that, in salivary glands, is specific for myoepithelial cells, these cells associated with acini and intercalated ducts were strongly stained, as were the basal cells of striated and excretory ducts in each case. Ultrastructurally, some basal cells of both striated and excretory ducts had narrow, elongated cellular processes or the main portion of the cell containing parallel arrays of microfilaments with linear densities and micropinocytotic vesicles, whereas in other basal cells tonofilament bundles predominated. A similar range of cytoplasmic features existed in myoepithelial cells associated with acinar and intercalated duct cells. In addition, some duct basal cells have a complement of actin filaments similar to classic myoepithelium of acini and intercalated ducts. Striated and excretory ducts of human salivary glands, therefore, contain fully differentiated and modified myoepithelial cells, both of which express a specific cytokeratin polypeptide that is absent from duct luminal and acinar cells. Differentiation patterns in the intralobular and interlobular ducts suggest that these regions of salivary gland parenchyma cannot be excluded as histogenetic sites for the induction of salivary gland tumors in which neoplastic myoepithelial cells have been shown to have a major role.

References (51)

TamarinA.
Myoepithelium of the rat submaxillary gland
J Ultrastruct Res
(1966)
BarkaT.
Induced cell proliferation: the effect of isoproterenol
Exp Cell Res
(1965)
DardickI. et al.
Histogenesis of salivary gland pleomorphic adenoma (mixed tumor) with an evaluation of the role of the myoepithelial cell
Hum Pathol
(1982)
BatsakisJ.G.
Salivary gland neoplasia: an outcome of modified morphogenesis and cytodifferentiation
Oral Surg Oral Med Oral Pathol
(1980)
MollR. et al.
The catalogue of human cytokeratin polypeptides: patterns of expression of cytokeratins in normal epithelia, tumors and cultured cells
Cell
(1982)
MollR. et al.
Identification of Merkel cells in human skin by specific cytokeratin antibodies: Changes of cell density and distribution in fetal and adult plantar epidermis
Differentiation
(1984)
DairkeeS.H. et al.
Concurrent expression of basal and luminal epithelial markers in cultures of normal human breast analyzed using monoclonal antibodies
Differentiation
(1986)
KreplerR. et al.
Keratin-like proteins in normal and neoplastic cells of human and rat mammary gland as revealed by immunofluorescence microscopy
Differentiation
(1981)
DardickI. et al.
Pleomorphic adenoma: I. Ultrastructural organization of “epithelial” regions
Hum Pathol
(1983)
DardickI. et al.
Pleomorphic adenoma: II. Ultrastructural organization of “stromal” regions
Hum Pathol
(1983)

YoungJ.A. et al.

The morphology of salivary glands

CutlerL.S. et al.

Ultrastructure of the parotid duct. Cytochemical studies of the striated duct and papillary cystadenoma lymphomatosum of the human parotid gland

Arch Pathol Lab Med

(1977)

Testa-RivaF. et al.

The epithelium of the excretory duct of the human submandibular gland: a transmission and scanning electron microscope study

Am J Anat

(1981)

GarrettJ.R. et al.

Alkaline phosphatase and myoepithelial cells in the parotid gland of the rat

Histochem J

(1973)

TandlerB. et al.

Ultrastructure of human labial salivary glands. III. Myoepithelium and ducts

J Morphol

(1970)

TandlerB.

Unusual myoepithelium in the retrolingual salivary gland of the European hedgehog

J Submicrosc Cytol

(1986)

van LennepE.W. et al.

The ultrastructure of the sheep parotid gland

Cell Tissue Res

(1977)

DairkeeS.H. et al.

Monoclonal antibody that identifies human myoepithelium

PalmerR.W. et al.

Immunocytochemical identification of cell types in pleomorphic adenoma, with particular reference to myoepithelial cells

J Pathol

(1985)

PalmerR.M. et al.

“Epimyoepithelial” islands in lymphoepithelial lesions: an immunohistochemical study

Virchows Arch (Pathol Anat)

(1986)

PalmerR.M.

The identification of myoepithelial cells in human salivary glands. A review and comparison of light microscopical methods

J Oral Pathol

(1986)

TakaiY. et al.

Immunohistochemical detection of keratin proteins in salivary gland ducts of mammals

Acta Histochem Cytochem

(1985)

SchneyerC.A.

β-Adrenergic effects of autonomic agents on mitosis and hypertrophy in rat parotid gland

EversoleL.R.

Histogenic classification of salivary gland tumors

Arch Pathol

(1971)

EversoleL.R.

Histogenisis of salivary gland neoplasms

Otolaryngol Clin North Am

(1977)

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Citation Excerpt :
BCA, first described by Kleinasser and Klein in 1967,11 is a rare benign salivary gland tumor, predominantly composed of basaloid cells, sharply demarcated by the stroma. Formerly considered a proliferation of a single epithelial type having some relationship with the basal cells of the salivary ducts, ultrastructural and immunohistochemical investigations have shown that this tumor is composed of a variable admixture of basal, ductal, and myoepithelial cells.1-3,12-15 Recently, it has been proposed that this tumor could form part of a continuum of benign salivary gland tumors, also including pleomorphic adenoma and myoepithelioma.3
Basal cell adenoma (BCA) of the salivary gland with presence of abundant S-100–positive stromal cells has been rarely reported. A case occurring in a 75-year-old man is presented here, as well as a review of the literature on the subject. The patient presented with a nodule in the right parotid gland. In addition to the typical features of BCA, histologically the resected tumor showed a substantial amount of stroma rich in S-100–positive spindle cells, a rarely reported finding in BCA. These cells were unreactive with a panel of myoepithelial markers, including calponin, p63, muscle-specific actin (MSA), smooth muscle actin (SMA), cytokeratin 14 (CK14), and glial fibrillary acidic protein (GFAP). Our results, in accordance with other reports, do not support a myoepithelial nature of these S-100–positive cells, and their precise nature remains elusive.
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Citation Excerpt :
In two cases, the luminal cells of entrapped ducts within the tumor overexpressed cox-2. Although further studies are required, our results differ from previous reports which claim that PSCC shares a common histogenesis with MEC; the excretory duct reserve cell.4,6,26 Our results support the hypothesis that the malignant change of reserve cells which maintain the capacity to generate intercalated duct elements may then secondarily produce epidermoid cells.5
The classification system for malignant salivary gland tumors (MST) is largely dependent on its histogenesis. The histogenesis is uncertain but the “bicellular theory of origin” has been accepted by most and states that malignant transformation of reserve cells from either the intercalated or excretory duct are responsible for the development of MST. Cyclooxygenase-2 (cox-2), a potential molecular marker for MST, was analyzed on a series (n = 56) of MST with the aim of determining the morphological MST subtypes capable of cox-2 overexpression and correlating its expression with histogenesis.
Fifty six primary major and minor gland MST were stained with anti-cox-2 antibody and rated with a combined score that added a scale of intensity to the percentage of tumor cells that overexpressed the cox-2 protein. A score of <3: negligible or negative staining; score of 4–5; moderate staining; score of 6–7; strong staining. Tumor types were segregated by morphology, histological features and proposed histogenesis.
Strong cox-2 overexpression was noted in all MST of proposed excretory duct origin: salivary duct carcinoma (100%), mucoepidermoid carcinoma (MEC) (92%), and adenocarcinoma nos (AdC nos) (83%). Primary squamous cell carcinoma (PSCC) was the exception. Negative expression was noted in all tumors of proposed intercalated duct origin (adenoid cystic carcinoma, basal cell adenocarcinoma and acinic cell carcinoma) with the exception of one case of polymorphous low grade adenocarcinoma. Strong cox-2 overexpression was noted in the epidermoid cells of MEC, abluminal duct cells surrounding the duct-like structures and ductal cells of AdC nos and salivary duct carcinoma. Myoepithelial and acinar cells were unreactive.
Although preliminary, the results of our study support the concept that MST of proposed excretory duct origin share a common histogenesis. Negligible cox-2 expression in PSCC may provide a useful tool for diagnosing the often histologically indistinguishable cases of high grade MEC. Follow-up studies on a larger series of MST are warranted.
Immunocytochemistry of myoepithelial cells in the salivary glands
2003, Progress in Histochemistry and Cytochemistry
MECs are distributed on the basal aspect of the intercalated duct and acinus of human and rat salivary glands. However, they do not occur in the acinus of rat parotid glands, and sometimes occur in the striated duct of human salivary glands. MECs, as the name implies, have structural features of both epithelial and smooth muscle cells. They contract by autonomic nervous stimulation, and are thought to assist the secretion by compressing and/or reinforcing the underlying parenchyma. MECs can be best observed by immunocytochemistry. There are three types of immunocytochemical markers of MECs in salivary glands. The first type includes smooth muscle protein markers such as α-SMA, SMMHC, h-caldesmon and basic calponin, and these are expressed by MECs and the mesenchymal vasculature. The second type is expressed by MECs and the duct cells and includes keratins 14, 5 and 17, α1β1 integrin, and metallothionein. Vimentin is the third type and, in addition to MECs, is expressed by the mesenchymal cells and some duct cells. The same three types of markers are used for studying the developing gland.
Development of MECs starts after the establishment of an extensively branched system of cellular cords each of which terminates as a spherical cell mass, a terminal bud. The pluripotent stem cell generates the acinar progenitor in the terminal bud and the ductal progenitor in the cellular cord. The acinar progenitor differentiates into MECs, acinar cells and intercalated duct cells, whereas the ductal progenitor differentiates into the striated and excretory duct cells. Both in the terminal bud and in the cellular cord, the immediate precursors of all types of the epithelial cells appear to express vimentin. The first identifiable MECs are seen at the periphery of the terminal bud or the immature acinus (the direct progeny of the terminal bud) as somewhat flattened cells with a single cilium projecting toward them. They express vimentin and later α-SMA and basic calponin. At the next developmental stage, MECs acquire cytoplasmic microfilaments and plasmalemmal caveolae but not as much as in the mature cell. They express SMMHC and, inconsistently, K14. This protein is consistently expressed in the mature cell. K14 is expressed by duct cells, and vimentin is expressed by both mesenchymal and epithelial cells.
After development, the acinar progenitor and the ductal progenitor appear to reside in the acinus/intercalated duct and the larger ducts, respectively, and to contribute to the tissue homeostasis. Under unusual conditions such as massive parenchymal destruction, the acinar progenitor contributes to the maintenance of the larger ducts that result in the occurrence of striated ducts with MECs. The acinar progenitor is the origin of salivary gland tumors containing MECs. MECs in salivary gland tumors are best identified by immunocytochemistry for α-SMA. There are significant numbers of cells related to luminal tumor cells in the non-luminal tumor cells that have been believed to be neoplastic MECs.
Innervation and myoepithelial arrangements in the submandibular salivary gland of ferret investigated by enzyme, catecholamine and filament histochemistry
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Although the submandibular gland of ferret is useful for studying salivary secretory processes which are regulated by nerves and involve myoepithelial activity, little attention has been paid to its parenchymal innervation and myoepithelial arrangements. Therefore, glands obtained postmortem from mature ferrets of both sexes were here examined with the use of light-microscopic histochemical techniques for cholinesterases, phosphatases and phosphorylase, histofluorescence for catecholamines, and milling dyes. Acetylcholinesterase staining was associated with nerve trunks in the interlobular stroma and an extensive intralobular network of nerve fibres, presumably of a cholinergic type, embracing acini and ducts. There were fewer fibres containing fluorescing catecholamines, presumably adrenergic. They were largely associated with acini. Numerous stellate cells with fine branching processes embracing acini, presumably myoepithelial cells, and a few spindle-shaped basal cells, investing striated ducts, were demonstrated on frozen tissue by alkaline phosphatase, but not by adenosine triphosphatase, inosine diphosphatase and phosphorylase. Cells of similar shape and distribution were also demonstrated by staining with milling dyes on fixed tissues, indicating possibly a filamentous constituent conferring mechanical stability and/or contractile ability. Together, these results suggest, firstly, that a cholinergic-type parenchymal innervation is prominent in the submandibular gland of ferret, although many adrenergic nerves are also present, and, secondly that the gland has a very extensive myoepithelial network which is possibly involved in membrane transport, and the support and/or contraction of the secretory parenchyma.
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: This study was funded by a grant from the Moe Levin Family Foundation, Montreal, Quebec, Canada. We appreciate the manuscript preparation by Marilyn McDougall and the technical assistance in fluorescent microscopy by Judy Little.

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Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: Histogenetic implications for salivary gland tumors

Abstract

J Ultrastruct Res

Exp Cell Res

Hum Pathol

Oral Surg Oral Med Oral Pathol

Cell

Differentiation

Differentiation

Differentiation

Hum Pathol

Hum Pathol

The morphology of salivary glands

Ultrastructure of the parotid duct. Cytochemical studies of the striated duct and papillary cystadenoma lymphomatosum of the human parotid gland

Arch Pathol Lab Med

The epithelium of the excretory duct of the human submandibular gland: a transmission and scanning electron microscope study

Am J Anat

Alkaline phosphatase and myoepithelial cells in the parotid gland of the rat

Histochem J

Ultrastructure of human labial salivary glands. III. Myoepithelium and ducts

J Morphol

Unusual myoepithelium in the retrolingual salivary gland of the European hedgehog

J Submicrosc Cytol

The ultrastructure of the sheep parotid gland

Cell Tissue Res

Monoclonal antibody that identifies human myoepithelium

Immunocytochemical identification of cell types in pleomorphic adenoma, with particular reference to myoepithelial cells

J Pathol

“Epimyoepithelial” islands in lymphoepithelial lesions: an immunohistochemical study

Virchows Arch (Pathol Anat)

The identification of myoepithelial cells in human salivary glands. A review and comparison of light microscopical methods

J Oral Pathol

Immunohistochemical detection of keratin proteins in salivary gland ducts of mammals

Acta Histochem Cytochem

β-Adrenergic effects of autonomic agents on mitosis and hypertrophy in rat parotid gland

Histogenic classification of salivary gland tumors

Arch Pathol

Histogenisis of salivary gland neoplasms

Otolaryngol Clin North Am