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as a thin layer above the basement membrane but generally beneath the luminal cells. They can contract and expel the secretions of exocrine glands. Presence of myoepithelial cells in a hyperplastic tissue proves the benignity of the gland and, when absent, indicates cancer. Only rare cancers like adenoid cystic carcinomas contains myoepithelial cells as one of the malignant components.
The plamsa memb of myoep cells is characterized by the presence of pinocytic vesicles which are now classified as caveolae. The cytoplasm of myoepithelial cells contain numerous actin filaments as well as myosin. They also contain intermediate filament that belong to the cytokeratin family, which confirms their epithelial origin.
Myoepithelial cells contribute significantly to basement membrane production by expression and deposition of fibronectin, collagen IV, nidogen and the bioactive laminins. They also possess basement memb receptors, including integrins, which mediate cell to basement memb attachment and occasionaly cell-cell interactions . Inpartcular β 4 and 𝛼 1 integrins are expressed in mec. A number of tumor suppressor protein including p63, p73,14-3-3 sigma, maspin, and Wilms Tumor have been preferentially detected on in mec, consistent with the apparent endogenous tumor suppressor function of myoepithelial cells.
Cross-section of a bilayered duct. Secretory luminal epithelial cells (LEPs) are apically located to contractile myoepithelial cells (MEPs) and the basement membrane (BM). Milk proteins and cleaved Muc1 are secreted into the luminal space during lactation. Desmosomes containing desmoglein (Dsg)2 and desmocollin (Dsc)2 form between adjacent luminal cells and between adjacent LEPs and MEPs. Desmosomes between MEPs contain Dsg3 and Dsc3. MEPs as contractile cells contain smooth muscle actin and adhere to the BM via hemidesmosomes.
Schametic drawing of TDLU showing Luminal epithelial cells (Red) and surrounded by myoepithelial cells (yellow) and (basement membrane) black line.
The basic functional unit in the breast is the lobule, also called the terminal ductal lobular unit (TDLU). The TDLU consists of 10-100 acini, that drain into the terminal duct. The terminal duct drains into larger ducts and finally into the main duct of the lobe (or segment), that drains into the nipple. The breast contains 15-18 lobes, that each contain 20-40 lobules. The terminal ductal lobular unit is an important structure because most invasive cancers arise from the TDLU. It is also the site of origin of ductal carcinoma in situ (DCIS), lobular carcinoma in situ, fibroadenoma and fibrocystic disease, like cysts, apocine metaplasia, adenosis and epitheliosis. Most calcifications in the breast form either within the terminal ducts (intraductal calcifications) or within the acini (lobular calcifications).
Microanatomy of normal adult female breast tissue showing extra lobular ducts(ELD), terminal ducts and lobules (L) the latter composed of groups of small glandular structures, the acini
The mammary duct lobular system is lined by a dual cell population an inner epithelial cell layer and an outer layer of myoepithelial cells. A High power view of lobule. The myoepithelial cells surrounding the acinar epithelial cells are variably conspicuous. High power view of an extralobular duct showing distinct epithelial and myoepithelial cell layers.
Myoepithelial cells are true epithelial cells positive for keratins, not to be confused with myofibroblasts which are true mesenchymal cells positive for vimentin
Smooth muscle myosin heavy chain
Extra lobular duct (A) and lobule (B) immunostained for p63.The myoepithelial cells show strong nuclear reactivity , where as the epithelial cell nuclei are negative.
Immunostain for the basal cytokeratin C5/6 highlighting the myoepithelial cells around ductules and acini
The term adenosis refers to a group of benign breast lesions that have in common a pathologic increase in the number of mammary glandular units . Simple form of adenosis are characterized by an increase in the number of lobular acini without distortion of the lobular architecture simple adenosis. The most common form of adenosis is sclerosing adenosis, a lesion of the TDLU characterized by a lobulocentric proliferation of gland and tubules accompanied by a stromal proliferation that produces variable glandular compression and distortion. If indoubt IHC demonstratiand on of myoepithelial cells can additionally exclude an invasive process
Low power view illustrating numerical increase and elongation of glandular elements accompanied by stromal proliferation High power view of one area of the lesion showing several open glands lined by attenuated epithelium. The myoepithelial layer is difficult to appreciate
Intra ductal proliferative lesions are a diverse group of epithelial proliferation confined to the mammary ductal-lobular system. They are divided into 3 major categories based on their architectural and cytologic features: they usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ.
The cells and the nuclei very in size shape and orientation
Benign tumor composed of myoepithelial cells are termed myoepitheliomas. When epi and myo cells participate in the proliferation the term adenomyoepithelioma is appropriate.
Adenomyoepithelioma . At lower power, a relatively circumscribed nodule composed of epithelial cell forming glands and nests. The spaces between the epithelial cells are occcoupied by myoepithelial cells.
Adenomyothelioma: Small glands composed of epithelial cells with eosinophilic cytoplasm are surrounded by myoepithelial cell with clear cytoplasm.
characteristic collections of acellular, eosinophilic basement membrane material
Myoepithelial cells 28th jan
ROLE OF MYOEPITHELIAL CELLS IN HEALTH & DISEASE Maj Ganesh Parajuli Guide: Col N. Moorchung
PLAN FOR DISCUSSION MEC Health Health Disease DiseaseStructure & BenignStructure & Benign Benign Benign neoplastic Malignant MalignantFunctionsFunctions Non-neoplastic Non-neoplastic neoplastic Biphasic lesion 1. Mixed tumor Biphasic lesion 1. Mixed tumor 2. Most Ad My Ep 1.Ad My Ep 1.Ad My Ep 2. Most Ad My Ep 2.Myo Ep Ca 2.Myo Ep Ca 3.Mec Rich IDC 3.Mec Rich IDC
Myoepithelial Cells In Health… Where it is found ? What does it do? Latin –myoepitheliocytus (myoepithelium) Usually found in the glandular epithelium above basement membrane and beneath luminal cellsFound in the sweat glands, mammary glands, lacrimal glands, and salivary glands
The myoepithelial cell at a glance Myoepi cells are attached to the basement memb by hemidesmosomes Adjacent luminal epithelial cells by desmosomes. The myoepi cells lining the ducts are spindle-shaped cells ,oriented parallel to the long axis of ducts as a continuous layer. The myoepi cells in TDLUs discontinuous, stellate -shaped and form a basket like network around acini allowing some luminal epithelial cell to directly contact to basement membrane.
..at a glance Contribute significantly to basement membrane production by expression and deposition of fibronectin, collagen IV, nidogen and the bioactive laminins. Inparticular β4 and �1 integrins are expressed in mec. � Possess basement memb receptors, including integrins, Endogenous tumor suppressor function
Schematic Diagram of a bilayered duct Adriance et al. Breast Cancer Research 2005 7:190
Acinar Unit Two ep cell layer line entire duct and lobular unit of breast Inner secretory and luminal layer Outer incomplete myoepithelial layer Because myoepithelial is incomplete, luminal cells can reach the BM Myo-ep cells in contrast donot reach luminal surface
E M of Myoepithelium Myoepithelial cells attached to BM by hemidesmosomes and ep by desmosomes Cells have pinocytic visicles containing microfilaments and dense bodies resembling smooth muscle Myofilaments better develop in interlobular ducts and terminal ducts than in acinus proper.
Myoepithelial cells ignored ? Myoepithelial cells of breast – like Cinderella largely ignored in breast pathology Cells role in lactational physiology well recognized but this is a minor component ltd to milk ejection during suckling in response to oxytocin
Myo-epithelial cells Form an integral part of the secretory and ductal portion of the gland Share a common origin with luminal ep cells Influence proliferation and differentiation of developing terminal glandular buds by producing a scaffold of basement membrane Have contractile capacity controlled by hormonal and neural mechanisms Imp role in propulsion of secretions Maintains glandular structural integrity and transport metabolites to secretory cells
Myoepithelial cells functions ? Role in lactation- milk propulsion Contributes significantly to the manufacture of basement membrane material (Laminin 1) Probably exerts a paracrine effect on glandular epithelium Helps to signal correct polarity of epithelial structures Known to selectively express mapsin and certain proteinase inhibitors in situ Perhaps have anti angiogenic activities
The myoepithelial defense: host defence against a cancer Probably regulates the progression of DCIS to IDC MECs secrete low levels of matrix degrading proteinases but high level of mapsin and various other anti-invasive proteinase inhibitors Myoeo tumors exhibit the property of accumulating (not degrading ) extracellular matrix material
What are the MEC markers? Immunorective to: Specific muscle actin HHF-35 S-100 protein Cytokeratin Vimentin NSE Calponin P63
Benign lesions (Combinations of ep+myoep cells) Sclerosis adenosis (multifocal myoepitheliosis) Ductal hyperplasia (Epitheliosis ) Papilloma FCC spectrum including Radial Scar Mixed tumors (Exception to the rules is Micro glandular adenosis
Sclerosing Adenosis The most common & imp pathological form of adenosis Def: numerical increase & elongation of glandular elements accompanied by stromal proliferation Imp because it can mimic carcinoma both on mammo & in FS, and in small Bx Florid form called ‘Adenosis tumor’ or nodular adenosis’ and presents as a palpable pink mass
Ductal hyperplasia Usual ductal hyperplasia refers to a proliferation of cells within the ducts.( Ep+myop proliferation) Features of usual ductal hyperplasia include the following:The cells are cytologically benign very in size, shape and orientation arranged in a haphazard pattern and have a poorly defined borders
UDH showing solid proliferation of cells filling the space
Ductal hyperplasia (Epitheliosis) “Benign” hyperplasia is characterized by: the presence of MYOEPITHELIAL cells, and absence of necrosis and cellular atypia
Papillomas A papilloma benign lesion with papillary architecture characterized by: finger like projections or fronds of variable length and thickness ,composed of central fibrovascular core and a surrounding duct lined by myoepithelial cells. Intraductal papilloma :ClinicalAge 30-50 years at presentationMaybe central or peripheral
Central lesions most often present as nipple discharge or subareolar mass. Histologically Variably fibrotic fibrovascular cores covered by epithelial and myoepithelial cellsEpithelium consists of one to several layers of cuboidal to columnar cells that may exhibit usual ductal hyperplasia.
Intra ductal papilloma. The papillary fronds consists of fibrovascular cores covered by an inner myoe cell layer and an outer epi cell layer
Intra ductal papilloma. Calponin Immunostain highlights the myoep layer
Intraductal papilloma. P63 immunostain demonstrates myoepithelial cells within the papillae and around the periphery of the involved duct
Adenomyoepithelioma of breast (Ad-myo-ep) Typically multinodular, lobulated lesion composed of a combination of epithelial and myoepithelial elements Myoepithelial cells comprise a prominent component of the lesion, with clear and polygonal or spindle shaped.
Tavassoli describe 03 variants of adenomyoepithelomaSpindle cell type: the predominant pattern of the myoepithelial cells is spindled with few epithelial lined spacesThe tubular pattern: proliferation of rounded tubules with unusually prominent and hyperplastic myoepithelial cellsThe lobulated pattern: solid nests of myoepithelial cells proliferating around compressed epithelial lined spaces
Ad-myo-ep: Small glands composed of epethelial cells surrounded by myoepithelial cells
Epimyoepithelial carcinoma Uncommon tumor more in women in 7th and 8th decades of life Most are painless swellings Multinodular with and incomplete capsule Cells form ducts or larger spaces
Large cells myoep cells surround small dark cell which line ducts Clear cell may predominate Mitosis rare Perineural and intravascular spread may occur About 1/3rd recur and few gets metastasis
Malignant Myo-epithelial lesions Terms used: Myoepithelial carcinoma Malignant myoepitheliomaRare malignant tumor of the breast composed of cytologically malignant myoepithelial cells
Some of these which may be undifferentiated and sarcomatoid appear to arise on the basis of adenomyoepitheliomaHistologicallyComposed purely of myoepithelial cellsCells are pleomorphic and mitotically active
Epithelial islands surrounded by spindle-shaped myoepithelial cells
ADENOID CYSTIC CARCINOMA Morphologically distinct form of invasive breast ca associated with excellent prognosis Rare lesion accounts only 0.1%of all best cancers.Clinical presentation Median age of patients varies among studies: Usually in sixth or early seven decade
The tumor present as palpable mass majority of lesion in the sub areolar or central region of breast.Mammography: Well defined lobulated mass or speculated lesion Microcalcification.
Histologically these tumor are similar to adenoid cystic ca that arise in the salivary gland Composed of epithelial cells with variable degree of glandular, squamous or sebaceous differentiation. Characteristic collection of acellular, eosinophilic basement membrane material
Immunostain for cytokeratin 7 highlight glandular epithelial cells forming ductal structures within the solid cell nests & Immunostain for p63highlights the basoloid cells. The glandular luminal cells are p63 negative
IHCThese tumor are usually ER and PR negative & typicallylack HER2 protein overexpression and gene amplificationExpression of CD 117 (c-kit) is a characteristic featureof adenoid cystic carcinoma.
IHC profile Epithelial marker: CK, EMA Myoepithelial marker : SMA S100, Calponin, CD10 Mesenchymal markers: Vimentin, Desmin, Myoglobin Basement membrane: antibodies to laminin and collagen IV
SUMMARY MEC Health Health Disease DiseaseStructure & BenignStructure & Benign Benign Benign neoplastic Malignant MalignantFunctionsFunctions Non-neoplastic Non-neoplastic neoplastic Biphasic lesion 1. Mixed tumor Biphasic lesion 1. Mixed tumor 2. Most Ad My Ep 1.Ad My Ep 1.Ad My Ep 2. Most Ad My Ep 2.Myo Ep Ca 2.Myo Ep Ca 3.Mec Rich IDC 3.Mec Rich IDC
REFERENCES Biopsy Interpretation of the Breast.Stuart J. Schnitt Laura C. Collins Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia Thorarinn Gudjonsson1,2,6, Melissa C. Adriance3, Gudjonsson1,2,6, Adriance3, Breast pathology Diagnosis by Needle Core Biopsy Paul Peter Rosen, Syed A.Hoda The mammary myoepithelial cell - Cinderella or ugly sister? Sunil R Lakhani1 and Michael J OHare2 Robbins and Cotran pathologic basis of disease. – 8th ed Sternberg’s Diagnostic Surgical pathology 5 th ed Wheater’s Functional Histology 5 th ed Essentials of Diagnostic Breast Pathology Farid Moinfar