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ROLE OF MYOEPITHELIAL  CELLS IN HEALTH &       DISEASE       Maj Ganesh Parajuli    Guide: Col N. Moorchung
PLAN FOR DISCUSSION                      MEC Health Health                                      Disease                   ...
HEALTH
Myoepithelial Cells In Health…   Where it is found ?   What does it do?   Latin –myoepitheliocytus (myoepithelium)    U...
The myoepithelial cell at a glance   Myoepi cells are attached to the basement memb by    hemidesmosomes   Adjacent lumi...
..at a glance   Contribute significantly to basement membrane    production by expression and deposition of    fibronecti...
Schematic Diagram of a    bilayered duct          Adriance et al. Breast Cancer Research 2005 7:190
Schametic diagram of TDLU
Anatomy      The basic functional unit       in breast : Lobule      Also called TDLU       consist of 10-100 acini    d...
Normal histologyNormal adult female breast tissue
High power view of lobules&           ELD
Acinar Unit   Two ep cell layer line entire duct and lobular unit of    breast   Inner secretory and luminal layer   Ou...
E M of Myoepithelium   Myoepithelial cells attached to BM by hemidesmosomes    and ep by desmosomes   Cells have pinocyt...
Myoepithelial cells ignored ?   Myoepithelial cells of breast – like Cinderella largely    ignored in breast pathology  ...
Myo-epithelial cells   Form an integral part of the secretory and ductal portion of    the gland   Share a common origin...
Myoepithelial cells functions ?   Role in lactation- milk propulsion   Contributes significantly to the manufacture of  ...
The myoepithelial defense: host       defence against a cancer   Probably regulates the progression of DCIS to IDC   MEC...
What are the MEC markers?   Immunorective to:   Specific muscle actin HHF-35   S-100 protein   Cytokeratin   Vimentin...
Myoepithelial markers            Location      Sensitivity   SpecificitySMA         Cytoplasmic   +++           +SM -MHC  ...
Immunostained for p63Extra lobular duct (A) and lobule  (B) immunostained for p63.
Immunostain for the basal cytokeratinCK5/6highlighting the myoepithelial cells
DISEASE
Benign lesions    (Combinations of ep+myoep cells)   Sclerosis adenosis (multifocal myoepitheliosis)   Ductal hyperplasi...
Sclerosing Adenosis   The most common & imp pathological form of    adenosis   Def: numerical increase & elongation of g...
Sclerosing adenosis
Ductal hyperplasia   Usual ductal hyperplasia refers to a proliferation of cells    within the ducts.( Ep+myop proliferat...
UDH showing solid proliferation of cells filling                the space
Ductal hyperplasia               (Epitheliosis)   “Benign” hyperplasia is characterized by: the    presence of MYOEPITHEL...
Papillomas   A papilloma benign lesion with papillary architecture    characterized by: finger like projections or fronds...
   Central lesions most often present as nipple discharge    or subareolar mass.   Histologically Variably fibrotic fibr...
Intra ductal papilloma. The papillary fronds consists of fibrovascular cores       covered by an inner myoe cell layer and...
Intra ductal papilloma. Calponin Immunostain highlights the                         myoep layer
Intraductal papilloma. P63 immunostain demonstrates myoepithelial  cells within the papillae and around the periphery of t...
Myoepithelial Tumors   Adenomyoepithelioma   Adenoid cystic carcinoma   MEC rich IDC
Adenomyoepithelioma of breast           (Ad-myo-ep)   Typically multinodular, lobulated lesion composed of a    combinati...
   Tavassoli describe 03 variants of adenomyoepithelomaSpindle cell type: the predominant pattern of the myoepithelial ce...
Adenomyoepithelioma   at lower power
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 swelling...
   Large cells myoep cells surround small dark cell which    line ducts   Clear cell may predominate   Mitosis rare   ...
Malignant Myo-epithelial lesions   Terms used:    Myoepithelial carcinoma    Malignant myoepitheliomaRare malignant tumor...
   Some of these which may be undifferentiated and    sarcomatoid appear to arise on the basis of    adenomyoepitheliomaH...
Epithelial islands surrounded by spindle-shaped myoepithelial cells
   IHC: CK, SMA, Calponin positive
ADENOID CYSTIC              CARCINOMA   Morphologically distinct form of invasive breast ca    associated with excellent ...
   The tumor present as palpable mass majority of lesion    in the sub areolar or central region of breast.Mammography:  ...
   Histologically these tumor are similar to adenoid cystic    ca that arise in the salivary gland   Composed of epithel...
Adenoid cystic carcinoma: Cribriform &          Trabecular pattern
Immunostain for cytokeratin 7 highlight glandular epithelial cells forming   ductal structures within the solid cell nests...
IHCThese tumor are usually ER and PR negative & typicallylack HER2 protein overexpression and gene amplificationExpressi...
IHC profile   Epithelial marker: CK, EMA   Myoepithelial marker : SMA S100, Calponin, CD10   Mesenchymal markers: Vimen...
SUMMARY                      MEC Health Health                                      Disease                               ...
REFERENCES   Biopsy Interpretation of the Breast.Stuart J. Schnitt    Laura C. Collins   Myoepithelial Cells: Their Orig...
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Myoepithelial cells 28th jan

Myoepithelial cells 28th jan

  1. 1. ROLE OF MYOEPITHELIAL CELLS IN HEALTH & DISEASE Maj Ganesh Parajuli Guide: Col N. Moorchung
  2. 2. 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
  3. 3. HEALTH
  4. 4. 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
  5. 5. 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.
  6. 6. ..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
  7. 7. Schematic Diagram of a bilayered duct Adriance et al. Breast Cancer Research 2005 7:190
  8. 8. Schametic diagram of TDLU
  9. 9. Anatomy  The basic functional unit in breast : Lobule  Also called TDLU consist of 10-100 acini drain into terminal duct Finally main duct of a lobe  Why TDLU is an important Structure?
  10. 10. Normal histologyNormal adult female breast tissue
  11. 11. High power view of lobules& ELD
  12. 12. 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
  13. 13. 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.
  14. 14. 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
  15. 15. 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
  16. 16. 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
  17. 17. 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
  18. 18. What are the MEC markers? Immunorective to: Specific muscle actin HHF-35 S-100 protein Cytokeratin Vimentin NSE Calponin P63
  19. 19. Myoepithelial markers Location Sensitivity SpecificitySMA Cytoplasmic +++ +SM -MHC Cytoplasmic +++ +Calponin Cytoplasmic ++ ++p63 Nuclear +++ +++
  20. 20. Immunostained for p63Extra lobular duct (A) and lobule (B) immunostained for p63.
  21. 21. Immunostain for the basal cytokeratinCK5/6highlighting the myoepithelial cells
  22. 22. DISEASE
  23. 23. 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
  24. 24. 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
  25. 25. Sclerosing adenosis
  26. 26. 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
  27. 27. UDH showing solid proliferation of cells filling the space
  28. 28. Ductal hyperplasia (Epitheliosis) “Benign” hyperplasia is characterized by: the presence of MYOEPITHELIAL cells, and absence of necrosis and cellular atypia
  29. 29. 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
  30. 30.  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.
  31. 31. Intra ductal papilloma. The papillary fronds consists of fibrovascular cores covered by an inner myoe cell layer and an outer epi cell layer
  32. 32. Intra ductal papilloma. Calponin Immunostain highlights the myoep layer
  33. 33. Intraductal papilloma. P63 immunostain demonstrates myoepithelial cells within the papillae and around the periphery of the involved duct
  34. 34. Myoepithelial Tumors Adenomyoepithelioma Adenoid cystic carcinoma MEC rich IDC
  35. 35. 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.
  36. 36.  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
  37. 37. Adenomyoepithelioma at lower power
  38. 38. Ad-myo-ep: Small glands composed of epethelial cells surrounded by myoepithelial cells
  39. 39. 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
  40. 40.  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
  41. 41. Malignant Myo-epithelial lesions Terms used: Myoepithelial carcinoma Malignant myoepitheliomaRare malignant tumor of the breast composed of cytologically malignant myoepithelial cells
  42. 42.  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
  43. 43. Epithelial islands surrounded by spindle-shaped myoepithelial cells
  44. 44.  IHC: CK, SMA, Calponin positive
  45. 45. 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
  46. 46.  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.
  47. 47.  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
  48. 48. Adenoid cystic carcinoma: Cribriform & Trabecular pattern
  49. 49. 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
  50. 50. IHCThese tumor are usually ER and PR negative & typicallylack HER2 protein overexpression and gene amplificationExpression of CD 117 (c-kit) is a characteristic featureof adenoid cystic carcinoma.
  51. 51. 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
  52. 52. 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
  53. 53. 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
  54. 54. THANK YOU
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