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Neoplasia 
Not​ ​all​ ​masses​ ​are​ ​true​ ​neoplasms. 
Examples​ ​of​ ​tumors​ ​that​ ​are​​ ​not​​ ​true​ ​neoplasms:​ ​Hamartoma​ ​and​ ​Choristoma​. 
Hamartoma​ ​and​ ​choristoma​ ​are​ ​developmental​ ​or​ ​congenital​ ​malformations. 
Hamartoma​​ ​is​ ​a​ ​mass​ ​that​ ​consists​ ​of​ ​tissues​ ​that​ ​are​ ​normally​ ​present​ ​in​ ​the 
site​ ​of​ ​the​ ​mass​ ​but​ ​the​ ​organization,​ ​or​ ​the​ ​amount​ ​of​ ​cells​ ​and​ ​tissues​ ​at​ ​that 
site​ ​is​ ​different​ ​from​ ​the​ ​normal​ ​situation.   
Example​ ​of​ ​hamartoma:​ ​Lung​ ​Hamartoma​ ​(Pulmonary​ ​Hamartoma) 
Lung​ ​Hamartoma​ ​is​ ​a​ ​mass​ ​that​ ​consists​ ​mainly​ ​of​ ​mature​ ​cartilage​ ​with​ ​other 
components​ ​such​ ​as​ ​respiratory​ ​epithelium,​ ​stroma​ ​and​ ​connective​ ​tissue.  
Cartilage​ ​is​ ​found​ ​normally​ ​in​ ​the​ ​lung​ ​in​ ​the​ ​bronchial​ ​tree​ ​and​ ​the​ ​trachea 
contains​ ​cartilage​ ​rings,​ ​the​ ​cartilage​ ​preserves​ ​the​ ​potency​ ​of​ ​the​ ​bronchial​ ​tree 
and​ ​prevents​ ​it​ ​from​ ​closing.​ ​The​ ​terminal​ ​bronchioles​ ​(lung​ ​tissue)​ ​contain​ ​a 
small​ ​amount​ ​of​ ​cartilage,​ ​so​ ​a​ ​mass​ ​of​ ​cartilage​ ​with​ ​a​ ​few​ ​centimeters​ ​size​ ​is 
the​ ​tumor. 
Choristoma​​ ​is​ ​a​ ​congenital​ ​anomaly,​ ​tissues​ ​of​ ​choristoma​ ​are​ ​not​ ​normally 
present​ ​in​ ​the​ ​site​ ​where​ ​choristoma​ ​happens​ ​(where​ ​the​ ​mass​ ​is​ ​formed).  
Pancreatic​ ​tissue​ ​is​ ​found​ ​in​ ​the​ ​pancreas,​ ​but​ ​if​ ​a​ ​mass​ ​of​ ​pancreatic​ ​tissue​ ​is 
found​ ​in​ ​the​ ​wall​ ​of​ ​the​ ​stomach​ ​it​ ​forms​ ​a​ ​mass​ ​that​ ​is​ ​called​ ​choristoma​ ​and​ ​it 
is​ ​also​ ​called​ ​pancreatic​ ​heterotopia​ ​(Heterotopic​ ​pancreatic​ ​tissue​ ​is​ ​in​ ​a 
foreign​ ​place). 
 
Another​ ​example​ ​of​ ​choristoma:​ ​Meckel’s​ ​diverticulum.​ ​At​ ​the​ ​end​ ​of​ ​the​ ​small 
intestine​ ​ ​in​ ​the​ ​terminal​ ​ileum)​ ​some​ ​patients​ ​might​ ​have​ ​developmental 
anomalies​ ​which​ ​contain​ ​gastric​ ​mucosa​ ​(here​ ​the​ ​presence​ ​of​ ​gastric​ ​mucosa 
is​ ​abnormal​ ​as​ ​it​ ​forms​ ​a​ ​mass​ ​and​ ​this​ ​mass​ ​is​ ​called​ ​choristoma)​ ​so​ ​there​ ​is​ ​an 
ectopic​ ​gastric​ ​mucosa​ ​in​ ​that​ ​area.  
Hamartoma​ ​and​ ​Choristoma​ ​are​ ​not​ ​true​ ​neoplasms,​ ​they​ ​do​ ​not​ ​become 
malignant,​ ​i.e​ ​do​ ​not​ ​transform​ ​into​ ​malignancy.  
 
 

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How​ ​to​ ​differentiate​ ​between​ ​benign​ ​and​ ​malignant 
tumors:  
1. Differentiation​ ​and​ ​anaplasia. 
2. Rate​ ​of​ ​growth​ ​of​ ​the​ ​tumor. 
3. Presence​ ​of​ ​capsules​ ​around​ ​the​ ​tumor. 
4. Local​ ​invasion. 
5. Distant​ ​metastasis.  
 

General​ ​Characteristics​ ​of​ ​the​ ​Uterus: 

-Components​ ​of​ ​the​ ​Uterus:​ ​body​ ​of​ ​uterus,​ ​vagina,​ ​cervix,​ ​fallopian​ ​tubes,​ ​and 
ovaries. 
-The​ ​uterus​ ​has​ ​an​ ​endometrial​ ​lining​,​ ​a​ ​myometrium​ ​layer​​ ​(thick​ ​smooth 
muscle​ ​layer)​ ​and​ ​a​ ​serosal​ ​surface​. 

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-The​ ​uterus​ ​is​ ​a​ ​common​ ​site​ ​for​ ​tumors.​ ​Tumors​ ​that​ ​are​ ​found​ ​in​ ​the​ ​uterus​ ​are 
called​ ​fibroid​: 
If​ ​the​ ​tumor​ ​is​ ​benign,​ ​surgeons​ ​can​ ​remove​ ​the​ ​tumor​ ​alone. 
But​ ​if​ ​the​ ​tumor​ ​is​ ​malignant,​ ​the​ ​whole​ ​uterus​​ ​is​ ​removed.​ ​Also,​ ​if​ ​there​ ​are 
numerous​ ​tumors​ ​that​ ​cause​ ​distortion,​ ​the​ ​whole​ ​uterus​ ​is​ ​removed​ ​even​ ​if​ ​it’s 
not​ ​malignant. 
Different​ ​types​ ​of​ ​tumors​ ​in​ ​the​ ​uterus​ ​according​ ​to​ ​the​ ​above​ ​Picture: 
The​ ​tumor​ ​on​ ​the​ ​left​ ​side​ ​is: 
1-​ ​smaller​ ​in​ ​size   
2-​​ ​has​ ​a​ ​slow​ ​growth​ ​rate  
3-​ ​has​ ​clear,​ ​regular,​ ​and​ ​well​ ​defined​ ​borders  
4-​ ​Has​ ​a​ ​homogenous​ ​appearance   
5-​ ​well​ ​demarcated 
6-​ ​doesn’t​ ​cause​ ​invasion​ ​to​ ​the​ ​surrounding​ ​tissue 
7-doesn’t​ ​cause​ ​any​ ​damage​ ​to​ ​the​ ​blood​ ​vessels  
8-​ ​doesn’t​ ​cause​ ​necrosis​ ​or​ ​hemorrhage​ ​and​ ​has​ ​a​ ​uniform​ ​cut​ ​surface​. 
 
The​ ​tumor​ ​on​ ​the​ ​right​ ​side​ ​is:   
1-​ ​larger  
2-​ ​has​ ​a​ ​rapid​ ​growth​ ​rate  
3-​ ​it​ ​invades​ ​the​ ​surrounding​ ​myometrium​ ​and​ ​endometrium  
5-​ ​it​ ​is​ ​variable​ ​in​ ​appearance​ ​and​ ​contains​ ​variations​ ​in​ ​the​ ​shape​ ​and 
color:​​ ​(includes​ ​brown​ ​and​ ​red​ ​colors,​ ​the​ ​brown​ ​color​​ ​indicates​ ​necrosis​,​ ​and 
the​ ​red​ ​color​​ ​indicates​ ​hemorrhage​,​ ​it​ ​poorly​ ​demarcated,​ ​causes​ ​local​ ​invasion 
and​ ​has​ ​the​ ​ability​ ​to​ ​metastasize.  
The​ ​histologic​ ​appearance​ ​of​ ​the​ ​tumor​ ​on​ ​the​ ​left​ ​is​ ​very​ ​similar​​ ​to​ ​the 
microscopic​ ​appearance​ ​of​ ​the​​ ​normal​ ​smooth​ ​muscle​​ ​(the​ ​tumor​ ​is​ ​very​ ​close 
to​ ​the​ ​normal​ ​appearance​ ​and​ ​the​ ​differentiation​ ​level​ ​is​ ​high). 

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On​ ​the​ ​other​ ​hand,​ ​histologic​ ​appearance​ ​of​ ​the​ ​tumor​ ​on​ ​the​ ​right​ ​contains 
hemorrhage​​ ​and​ ​necrosis​,​ ​some​ ​of​ ​the​ ​cells​ ​are​ ​similar​ ​to​ ​the​ ​normal​ ​smooth 
muscle​ ​and​ ​other​ ​cells​ ​are​ ​rounded​ ​with​ ​larger​ ​nuclei​ ​and​ ​prominent​ ​nucleoli 
(these​ ​cells​ ​look​ ​different​ ​from​ ​the​ ​normal​ ​smooth​ ​muscle​ ​cells)​ ​and​ ​there​ ​is​ ​a 
variation​ ​in​ ​the​ ​level​ ​of​ ​differentiation,​ ​where​ ​some​ ​of​ ​the​ ​cells​ ​are​ ​well 
differentiated​ ​while​ ​other​ ​cells​ ​(the​ ​majority)​ ​are​ ​not​ ​well​ ​(poorly)​ ​differentiated.  
The​ ​tumor​ ​on​ ​the​ ​right​ ​(malignant)​ ​is​ ​less​ ​differentiated​ ​than​ ​the​ ​tumor​ ​on​ ​the​ ​left 
(benign). 
Fibroid​ ​is​ ​not​ ​a​ ​scientific​ ​medical​ ​pathological​ ​term​ ​so:  
The​ ​tumor​ ​on​ ​the​ ​left​ ​side​ ​is​ ​called​ ​leiomyoma. 
The​ ​tumor​ ​on​ ​the​ ​right​ ​side​ ​is​ ​called​ ​leiomyosarcoma. 
- Hemorrhage​ ​and​ ​necrosis​ ​are​ ​not​ ​major​ ​distinguishing​ ​points​ ​but​ ​they 
help​ ​to​ ​differentiate​ ​between​ ​the​ ​two​ ​types​ ​of​ ​tumors  
- The​ ​major​ ​two​ ​points​ ​to​ ​differentiate​ ​between​ ​benign​ ​and​ ​ ​malignant 
tumors​ ​is​ ​the​ ​ability​ ​to​ ​invade​ ​and​ ​the​ ​ability​ ​to​ ​metastasize.  
Differentiation:  
Differentiation​ ​indicates​ ​how​ ​much​ ​the​ ​cells​ ​are​ ​similar​ ​to​ ​the​ ​normal​ ​cells​ ​in 
terms​ ​of​ ​morphology​ ​and​ ​functionality.  
Examples​ ​of​ ​Differentiation:  
1-Functional​ ​Differentiation:   
A​ ​tumor​ ​produces​ ​a​ ​hormone​ ​that​ ​is​ ​exactly​ ​similar​ ​to​ ​the​ ​hormone​ ​produced​ ​by 
the​ ​normal​ ​cells​ ​of​ ​the​ ​organ(Example:​ ​Insulin)  
2-Morphological​ ​Differentiation: 
​ ​Lipoma​ ​cells​ ​look​ ​very​ ​similar​ ​to​ ​the​ ​normal​ ​fat​ ​cells,​ ​this​ ​is​ ​a​ ​morphological 
differentiation.  

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The​ ​yellow​ ​mass​ ​in​ ​the​ ​above​ ​picture​ ​is​ ​removed​ ​from​ ​a​ ​superficial​ ​part​ ​of​ ​the 
body​ ​and​ ​it​ ​is​ ​covered​ ​by​ ​a​ ​capsule​ ​(looks​ ​shiny​ ​in​ ​the​ ​picture)​ ​and​ ​it​ ​has​ ​regular 
borders.(Regular​ ​borders​ ​means​ ​it’s​ ​benign) 
The​ ​picture​ ​in​ ​the​ ​bottom​ ​left​ ​is​ ​the​ ​section​ ​that​ ​is​ ​taken​ ​from​ ​the​ ​mass: 
-Well​ ​differentiated​ ​mass,​ ​the​ ​cells​ ​are​ ​very​ ​similar​ ​to​ ​fat​ ​cells.  
When​ ​studying​ ​this​ ​mass​ ​under​ ​low​ ​magnification,​ ​it​ ​is​ ​noticed​ ​that​ ​it​ ​consists​ ​of 
lobules​ ​of​ ​mature​ ​adipocytes,​ ​these​ ​lobules​ ​indicate​ ​that​ ​this​ ​is​ ​a​ ​neoplasm​ ​(it​ ​is 
benign​ ​and​ ​more​ ​specifically​ ​lipoma). 
  
Differences​ ​between​ ​lipoma​ ​and​ ​liposarcoma:  
1-Nuclei: 

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-The​ ​nuclei​ ​in​ ​the​ ​liposarcoma​​ ​cells​ ​are​ ​more​ ​obvious​​ ​than​ ​in​ ​the​ ​lipoma. 
Because​ ​the​ ​liposarcoma​ ​fat​ ​cells​ ​contain​ ​multiple​ ​small​ ​vacuoles​ ​that​ ​maintain 
the​ ​nucleus​ ​in​ ​the​ ​center​ ​and​ ​it​ ​appears​ ​more​ ​obvious​ ​and​ ​hyperchromatic. 
(Hyperchromatic:​ ​stains​ ​more​ ​darkly​ ​than​ ​normal​ ​nuclei) 
-​Lipoma​​ ​Benign​ ​or​ ​normal​ ​fat​ ​cells​ ​contain​ ​a​ ​single​ ​large​ ​vacuole​ ​in​ ​each​ ​cell 
that​ ​causes​ ​expansion​ ​and​ ​pushes​ ​the​ ​nucleus​ ​to​ ​the​ ​periphery.​ ​(the​ ​nucleus 
becomes​ ​invisible​). 
 
2-​ ​Cell​ ​Size​ ​Variety​: 
Liposarcoma​ ​fat​ ​cells​ ​are​ ​diverse​ ​in​ ​size.​ ​(Some​ ​cells​ ​are​ ​large​ ​and​ ​some​ ​are 
small). 
3-​ ​Presence​ ​of​ ​Lipoblasts​ ​in​ ​Liposarcoma: 
Another​ ​indication​ ​of​ ​liposarcoma​ ​is​ ​the​ ​presence​ ​of​ ​lipoblasts​ ​which​ ​are 
mature​ ​fat​ ​cells​ ​that​ ​contain​ ​multiple​ ​vacuoles​ ​and​ ​a​ ​large​ ​hyperchromatic 
nucleus​ ​that​ ​can​ ​be​ ​in​ ​the​ ​center​ ​or​ ​toward​ ​the​ ​periphery. 
4-​ ​Level​ ​of​ ​Differentiation: 
-Lipoma​ ​cells​ ​are​ ​very​ ​well​ ​differentiated.​ ​They​ ​are​ ​almost​ ​identical​ ​to​ ​the​ ​normal 
cells. 
-Liposarcoma​ ​cells​ ​varies​ ​in​ ​differentiation.​ ​May​ ​be​ ​well,​ ​moderately​ ​or​ ​poorly 
differentiated​ ​or​ ​undifferentiated.​ ​We​ ​may​ ​know​ ​that​ ​these​ ​are​ ​from​ ​a​ ​fat​ ​tissue. 
 
 

Features​ ​of​ ​differentiation​ ​include:  

1. Epithelial​ ​cells​:  
-Glandular​ ​or​ ​Columnar​ ​Differentiation:​ ​If​ ​the​ ​epithelial​ ​cells​ ​form​ ​glands​ ​or 
produce​ ​mucin​ ​(to​ ​the​ ​outside​ ​of​ ​the​ ​cell​ ​or​ ​inside​ ​the​ ​cytoplasm)​ ​this​ ​indicates 
glandular​ ​or​ ​columnar​ ​differentiation​ ​(even​ ​if​ ​the​ ​cells​ ​don’t​ ​look​ ​columnar).​ ​If​ ​the 
tumor​ ​is​ ​benign​ ​then​ ​it​ ​is​ ​called​ ​adenoma​​ ​and​ ​if​ ​it​ ​is​ ​malignant​ ​then​ ​it​ ​is​ ​called 
adenocarcinoma​.  
 
-Squamous​ ​Differentiation:​ ​If​ ​the​ ​cells​ ​produce​ ​keratin​ ​then​ ​it​ ​is​ ​a​ ​squamous 
differentiation​ ​(the​ ​cells​ ​are​ ​not​ ​necessarily​ ​squamous​ ​in​ ​shape).​ ​If​ ​the​ ​tumor​ ​is 

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benign​ ​then​ ​it​ ​is​ ​called​ ​papilloma​​ ​ ​and​ ​if​ ​it​ ​is​ ​malignant​ ​then​ ​it​ ​is​ ​called 
squamous​ ​cell​ ​carcinoma​. 
  
2. Connective​ ​tissue​ ​cells: 
-​ ​If​ ​a​ ​mass​ ​of​ ​connective​ ​tissue​ ​cells​ ​produces​ ​a​ ​cartilage​ ​matrix​ ​then​ ​this​ ​is​ ​an 
indication​ ​of​ ​cartilaginous​ ​differentiation. 
-The​ ​production​ ​of​ ​osteoid​ ​matrix​ ​indicates​ ​bone​ ​differentiation.  
-The​ ​presence​ ​of​ ​lipoblasts​ ​indicates​ ​fatty​ ​differentiation. 
-The​ ​presence​ ​of​ ​cells​ ​that​ ​contain​ ​striations​ ​of​ ​the​ ​cytoplasm​ ​indicates​ ​skeletal 
muscle​ ​differentiation. 
 

 
The​ ​top​ ​picture​ ​on​ ​the​ ​left​ ​is​ ​a​ ​section​ ​taken​ ​from​ ​a​ ​normal​ ​organ​ ​where​ ​the 
epithelial​ ​cells​ ​form​ ​glands​ ​(glandular​ ​or​ ​columnar​ ​differentiation). 
Pictures​ ​1,​ ​2​ ​and​ ​3​ ​are​ ​epithelial​ ​tissues​ ​(neoplasms)​ ​that​ ​form​ ​glands. 

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In​ ​picture​ ​1​:​ ​All​ ​the​ ​structures​ ​are​ ​forming​ ​glands​ ​that​ ​contain​ ​secretions​ ​and 
the​ ​differentiation​ ​level​ ​is​ ​high​ ​(well​ ​differentiated)​. 
In​ ​picture​ ​2​:​ ​there​ ​is​ ​formation​ ​of​ ​glands​ ​(columnar​ ​cells​ ​forming​ ​glands)​ ​but 
part​ ​of​ ​the​ ​tissue​ ​appears​ ​solid​ ​and​ ​some​ ​glands​ ​have​ ​stratified​ ​cells​ ​and​ ​they 
are​ ​uglier​ ​than​ ​other​ ​cells.​ ​Some​ ​of​ ​the​ ​cells​ ​are​ ​similar​ ​to​ ​the​ ​normal​ ​columnar 
cells​ ​and​ ​other​ ​cells​ ​have​ ​a​ ​morphological​ ​appearance​ ​deviated​ ​from​ ​the​ ​normal 
cells​ ​but​ ​in​ ​general​ ​these​ ​cells​ ​form​ ​glands​ ​in​ ​a​ ​high​ ​percentage.​ ​This​ ​is​ ​a 
moderately​ ​differentiated​​ ​neoplasm.  
In​ ​picture​ ​3:​​ ​There​ ​is​ ​no​ ​formation​ ​of​ ​glands.​ ​All​ ​the​ ​cells​ ​that​ ​form​ ​the​ ​tumor​ ​in 
the​ ​picture​ ​are​ ​abnormal​ ​(they​ ​have​ ​an​ ​abnormal​ ​and​ ​prominent​ ​nucleus)​ ​but 
some​ ​of​ ​these​ ​cells​ ​(pointed​ ​with​ ​the​ ​arrows)​ ​contain​ ​a​ ​good​ ​amount​ ​of 
cytoplasm​ ​and​ ​contain​ ​mucin,​ ​the​ ​presence​ ​of​ ​mucin​ ​indicates​ ​that​ ​there​ ​is​ ​a 
columnar(glandular)​ ​differentiation​ ​in​ ​this​ ​tissue.​ ​This​ ​tumor​ ​is​ ​invasive​ ​and​ ​it​ ​is 
called​ ​adenocarcinoma.​ ​This​ ​tumor​ ​is​ ​poorly​ ​differentiated​​ ​NOT 
undifferentiated.​ ​(characteristics​ ​of​ ​undifferentiated:no​ ​gland​ ​formation,​ ​no 
squamous​ ​arrangement,​ ​no​ ​keratin​ ​formation). 
The​ ​cells​ ​that​ ​produce​ ​mucin​ ​are​ ​called​ ​signet-ring​ ​cells​​ ​because​ ​look​ ​like​ ​a 
ring.  
 

Dysplasia  
When​ ​a​ ​tumor​ ​cell​ ​loses​ ​differentiation,​ ​it​ ​gradually​ ​gains​ ​features​ ​of​ ​dysplasia.  
(Dysplasia​ ​is​ ​related​ ​to​ ​differentiation). 
Dysplasia​ ​is​ ​mainly​ ​used​ ​with​ ​the​ ​epithelium​ ​more​ ​than​ ​other​ ​organs​ ​and​ ​the 
main​ ​example​ ​is​ ​the​ ​squamous​ ​epithelium.​ ​Dysplasia​ ​is​ ​related​ ​to​ ​changes​ ​in​ ​the 
epithelium,​ ​these​ ​changes​ ​are​ ​limited​ ​to​ ​the​ ​epithelial​ ​surface​ ​and​ ​not​ ​developed 
to​ ​cancer​ ​or​ ​carcinoma.  
Dysplasia​ ​is​ ​a​ ​disorderly,​ ​non-neoplastic​ ​proliferation​ ​of​ ​cells​ ​with​ ​loss​ ​of 
architectural​ ​orientation.  
Disorderly:​ ​no​ ​arrangement. 
Non-neoplastic:in​ ​an​ ​earlier​ ​stage​ ​and​ ​not​ ​developed​ ​in​ ​a​ ​tumor​ ​or​ ​cancer. 
Dysplasia​ ​involves​ ​the​ ​squamous​ ​epithelium​ ​found​ ​in: 
1. The​ ​metaplastic​ ​squamous​ ​epithelium​ ​in​ ​the​ ​lungs​ ​as​ ​a​ ​result​ ​of​ ​smoking. 

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 2. ​ ​The​ ​squamous​ ​epithelium​ ​of​ ​the​ ​skin. 
3. The​ ​squamous​ ​epithelium​ ​of​ ​the​ ​exocervix​ ​(the​ ​outer​ ​part​ ​of​ ​the​ ​uterus 
cervix). 
If​ ​there​ ​is​ ​proliferation​ ​of​ ​the​ ​cells​ ​in​ ​the​ ​epithelium​ ​with​ ​changes​ ​in​ ​the 
arrangement​ ​and​ ​the​ ​shape​ ​of​ ​the​ ​cells​ ​and​ ​the​ ​cells​ ​gain​ ​specific​ ​features​ ​this 
will​ ​cause​ ​dysplasia. 
- Metaplasia​ ​is​ ​reversible​ ​and​ ​if​ ​the​ ​smoking​ ​is​ ​stopped​ ​the​ ​lung​ ​goes​ ​back 
to​ ​its​ ​normal​ ​state​ ​of​ ​columnar​ ​epithelium,​ ​but​ ​if​ ​the​ ​dysplasia​ ​stage​ ​is 
reached,​ ​it​ ​can​ ​not​ ​go​ ​back​ ​to​ ​normal​ ​or​ ​progress​ ​to​ ​an​ ​even​ ​more 
abnormal​ ​state​ ​even​ ​if​ ​the​ ​smoking​ ​is​ ​stopped​ ​(so​ ​if​ ​you​ ​stop​ ​smoking​ ​in 
the​ ​dysplasia​ ​stage​ ​you​ ​can​ ​get​ ​benefits​ ​and​ ​sometimes​ ​you​ ​can’t 
because​ ​of​ ​mutations).   
 
Dysplasia​ ​cells​ ​are​ ​either: 
​ ​1.​ ​Differentiated​ ​cells​​ ​that​ ​went​ ​through​ ​maturation​ ​then​ ​the​ ​maturation 
process​ ​is​ ​reversed​ ​so​ ​they​ ​lose​ ​the​ ​features​ ​of​ ​differentiation​ ​(there​ ​is​ ​a 
process​ ​of​ ​gradual​ ​loss​ ​of​ ​differentiation​ ​of​ ​mature​ ​cells)​ ​or 
​ ​2.​ ​they​ ​are​ ​stems​ ​cells​​ ​of​ ​the​ ​epithelium​ ​that​ ​gained​ ​features​ ​other​ ​than​ ​the 
normal​ ​features​ ​(tumor​ ​stem​ ​cells). 
 
Dysplasia​ ​may​ ​precede​ ​malignancy​.  
Total​ ​loss​ ​of​ ​differentiation​ ​is​ ​called​ ​severe​ ​dysplasia  
Severe​ ​Dysplasia​ ​=​ ​Anaplasia  
 
Example​ ​of​ ​Severe​ ​Dysplasia/Anaplasia:  
 

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The​ ​cells​ ​in​ ​this​ ​picture​ ​are​ ​different​ ​from​ ​each​ ​other. 
The​ ​nuclear​ ​sizes​​ ​and​ ​shapes​​ ​are​ ​variable​ ​(pleomorphism)​. 
The​ ​colors​​ ​of​ ​the​ ​nuclei​ ​are​ ​different​​ ​(light, 
slightly​ ​dark,​ ​much​ ​darker). 
The​ ​darker​ ​the​ ​nucleus​ ​is,​ ​the​ ​higher​ ​the​ ​level​ ​of  
hyperchromatism​.  
The​ ​presence​ ​of​ ​abnormal​ ​mitosis​ ​(tripolar​ ​mitosis).  
Mitosis​ ​(normal​ ​proliferation)​ ​can​ ​be​ ​found​ ​in​ ​the​ ​basal​ ​layer​ ​of​ ​any​ ​squamous 
epithelium​ ​and​ ​in​ ​the​ ​glands​ ​of​ ​the​ ​intestine​ ​(specifically​ ​colon​ ​glands).​ ​These 
tissues​ ​have​ ​continuous​ ​capacity​ ​of​ ​regeneration​ ​in​ ​cases​ ​of​ ​inflammation, 
damage​ ​or​ ​injuries.  
Abnormal​ ​mitosis​ ​is​ ​an​ ​indication​ ​of​ ​dysplasia​ ​or​ ​a​ ​tumor.  
In​ ​the​ ​picture​ ​above,​ ​in​ ​the​ ​tumor​ ​there​ ​is​ ​no​ ​keratin,​ ​mucin​ ​or​ ​gland​ ​formation 
and​ ​there​ ​isn’t​ ​any​ ​osteoid​ ​matrix​ ​or​ ​cartilage​ ​matrix​ ​and​ ​it​ ​is​ ​not​ ​possible​ ​to 
determine​ ​the​ ​origin​ ​(site)​ ​of​ ​the​ ​tumor​ ​so​ ​it​ ​is​ ​severe​ ​dysplasia.  

Cytological​ ​features​ ​of​ ​Dysplasia:  

1.Increased​ ​nuclear​ ​size,​ ​increased​ ​nucleus/cytoplasm​ ​(N/C)​ ​ratio: 
The​ ​nucleus​ ​size​ ​increases​ ​relatively​ ​to​ ​the​ ​cytoplasm​ ​size. 
2.​ ​Variation​ ​in​ ​nuclear​ ​and​ ​cell​ ​size​ ​and​ ​shape:​ ​Pleomorphism. 
3.​ ​Loss​ ​of​ ​differentiating​ ​features. 
4.​ ​Increased​ ​nuclear​ ​DNA​ ​content:​ ​Hyperchromatism. 
5.​ ​Nucleoli:​ ​prominent,​ ​may​ ​be​ ​multiple. 
6.​ ​Mitotic​ ​figures:​ ​Increased. 
7.​ ​Abnormal​ ​mitosis:​ ​may​ ​be​ ​present. 
8.​ ​Loss​ ​of​ ​polarity:​ ​failure​ ​of​ ​orientation​ ​and​ ​polar​ ​arrangement​ ​of​ ​an​ ​epithelial 
surface.​ ​(due​ ​to​ ​change​ ​in​ ​the​ ​arrangement​ ​of​ ​cells) 
 

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This​ ​picture​ ​is​ ​a​ ​section​ ​of​ ​squamous​ ​epithelium​ ​of​ ​the​ ​cervix​ ​with​ ​the 
underlying​ ​subepithelial​ ​tissue. 
In​ ​the​ ​right​ ​side,​ ​there​ ​is​ ​hyperchromatism,​ ​the​ ​cells​ ​are​ ​more​ ​crowded,​ ​the 
nucleus​ ​size​ ​in​ ​increased​ ​(so​ ​the​ ​nuclei​ ​are​ ​larger​ ​and​ ​closer​ ​to​ ​each​ ​other)​ ​also 
mitosis​ ​can​ ​be​ ​noticed​ ​above​ ​the​ ​basal​ ​layer​ ​(mitosis​ ​must​ ​be​ ​in​ ​the​ ​basal​ ​layer) 
and​ ​some​ ​cells​ ​have​ ​prominent​ ​nucleoli. 
● In​ ​the​ ​top​ ​part​ ​of​ ​normal​ ​squamous​ ​epithelium,​ ​squamous​ ​cells​ ​with 
large​ ​nuclei​ ​and​ ​heavily​ ​staining​ ​cytoplasm​ ​should​ ​not​ ​be​ ​found. 
Also​ ​in​ ​the​ ​right​ ​side​ ​the​ ​cells​ ​have​ ​lost​ ​their​ ​polarity. 

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In​ ​the​ ​normal​ ​squamous​ ​epithelium,​ ​the​ ​basal​ ​layer​ ​is​ ​more​ ​primitive​ ​and​ ​it​ ​can 
produce​ ​mitosis​ ​and​ ​regenerate.​ ​Moving​ ​towards​ ​the​ ​surface,​ ​the​ ​nucleus 
becomes​ ​smaller,​ ​the​ ​cytoplasm​ ​increases​ ​and​ ​the​ ​squamous​ ​epithelial​ ​cells 
become​ ​arranged​ ​above​ ​each​ ​other.  
So​ ​the​ ​right​ ​side​ ​of​ ​the​ ​picture​ ​is​ ​Dysplasia​ ​while​ ​the​ ​left​ ​side​ ​is​ ​almost​ ​normal. 

 
 
Intraepithelial​ ​Neoplasia:  
Intraepithelial​ ​Neoplasia:​ ​Dysplasia​ ​involving​ ​an​ ​epithelial​ ​surface. 
(In​ ​general​ ​Dysplasia​ ​happens​ ​mainly​ ​in​ ​the​ ​epithelial​ ​surfaces​ ​but​ ​it​ ​can​ ​happen 
in​ ​connective​ ​tissues). 
Dysplasia​ ​of​ ​the​ ​epithelial​ ​surface​ ​is​ ​divided​ ​into​ ​low​ ​grade​ ​and​ ​high​ ​grade. 
High​ ​grade​ ​dysplasia​ ​is​ ​severe​ ​dysplasia​ ​(anaplasia)​ ​that​ ​is​ ​still​ ​limited​ ​by​ ​the 
epithelial​ ​basement​ ​membrane​ ​and​ ​it​ ​is​ ​also​ ​called​ ​Carcinoma​ ​In​ ​Situ​.  
Carcinoma​ ​In​ ​Situ:​ ​Severe​​ ​dysplasia​ ​involves​ ​the​ ​entire​ ​thickness​ ​of​ ​the 
epithelium,​ ​but​ ​it​ ​is​ ​not​ ​invasive,​ ​so​ ​it​ ​doesn’t​ ​cross​ ​or​ ​attack​ ​the​ ​basement 
membrane​ ​and​ ​the​ ​abnormal​ ​cells​ ​are​ ​kept​ ​in​ ​the​ ​epithelium.  
 
 
 
 
 

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This​ ​picture​ ​represents​ ​full​ ​thickness​ ​dysplasia​ ​from​ ​the​ ​basal​ ​layer​ ​to​ ​the​ ​top 
part.​ ​(High​ ​grade​ ​Intraepithelial​ ​Neoplasia)  
Dysplasia​ ​is​ ​divided​ ​into​ ​high​ ​grade​ ​and​ ​low​ ​grade​ ​and​ ​it​ ​can​ ​also​ ​be​ ​divided 
into​ ​mild,​ ​moderate​ ​and​ ​severe.  
- If​ ​the​ ​dysplasia​ ​is​ ​in​ ​the​ ​cells​ ​in​ ​the​ ​lower​ ​third​ ​of​ ​the​ ​squamous 
epithelium,​ ​this​ ​is​ ​mild​ ​dysplasia. 
- If​ ​the​ ​dysplasia​ ​involves​ ​two​ ​thirds,​ ​this​ ​is​ ​moderate​ ​dysplasia  
- If​ ​the​ ​dysplasia​ ​involves​ ​three​ ​thirds​ ​(full​ ​thickness),​ ​this​ ​is​ ​severe 
dysplasia​ ​(Carcinoma​ ​In​ ​Situ)​.  
 
 

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The​ ​right​ ​and​ ​left​ ​sides​ ​of​ ​the​ ​picture​ ​above​ ​are​ ​Carcinoma​ ​In​ ​Situ​ ​(full 
thickness​ ​dysplasia)​ ​but​ ​in​ ​the​ ​middle​ ​the​ ​basement​ ​membrane​ ​has​ ​been 
broken​ ​by​ ​some​ ​of​ ​the​ ​tumor​ ​cells​ ​and​ ​the​ ​tumor​ ​has​ ​invaded​ ​the 
subepithelial​ ​cells.  
​ ​The​ ​picture​ ​above​ ​is​ ​an​ ​example​ ​of​ ​invasive​ ​cancer,​ ​there​ ​are​ ​islands​ ​of 
squamous​ ​epithelial​ ​cells​ ​that​ ​are​ ​invading​ ​the​ ​subepithelial​ ​tissue​ ​(dysplasia 
has​ ​broken​ ​the​ ​basement​ ​membrane​ ​and​ ​moved​ ​through​ ​to​ ​cause​ ​invasion 
to​ ​the​ ​underlying​ ​tissue). 
 
 
 
 
 
 
 

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Dysplasia​ ​features​ ​can​ ​occur​ ​in​ ​both​ ​Carcinomas​ ​and​ ​Sarcomas​ b ​ ut​ ​there 
is​ ​no​ ​In-Situ​ ​Sarcoma.​ ​(Dysplasia​ ​term​ ​can​ ​be​ ​used​ ​in​ ​the​ ​epithelium​ ​and 
connective​ ​tissue​ ​abnormal​ ​proliferation​ ​but​ ​Carcinoma​ ​In-Situ​ ​term​ ​is​ ​used 
in​ ​the​ ​epithelial​ ​dysplasia​ ​but​ ​there​ ​is​ ​no​ ​In-Situ​ ​Sarcoma​ ​because​ ​the 
connective​ ​tissue​ ​doesn’t​ ​have​ ​a​ ​basement​ ​membrane). 
Not​ ​all​ ​dysplasias​ ​progress​ ​to​ ​higher​ ​grade​ ​or​ ​Carcinoma​ ​In​ ​Situ.  
Not​ ​all​ ​Carcinoma​ ​In​ ​Situ​ ​progress​ ​to​ ​invasive​ ​Carcinoma,​ ​although​ ​they​ ​have​ ​a 
high​ ​chance​ ​of​ ​doing​ ​so.  
(For​ ​example:​ ​Dysplasia​ ​in​ ​the​ ​squamous​ ​epithelium​ ​of​ ​the​ ​lung,​ ​if​ ​the​ ​smoking 
is​ ​stopped​ ​the​ ​dysplasia​ ​might​ ​remain​ ​in​ ​the​ ​same​ ​stage​ ​or​ ​it​ ​might​ ​progress 
back​ ​or​ ​progress​ ​to​ ​cancer). 

The​ ​second​ ​important​ ​point​ ​to​ ​differentiate​ ​between​ ​benign​ ​and 

malignant​ ​tumor: 

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The​ ​tumor​ ​growth​ ​rate. 
The​ ​general​ ​rule:​ ​Usually​ ​slow​ ​in​ ​benign​ ​and​ ​rapid​ ​in​ ​malignant​ ​tumors. 
The​ ​rate​ ​of​ ​growth​ ​usually​ ​correlates​ ​with​ ​level​ ​of​ ​differentiation. 
Benign​ ​neoplasm​ ​is​ ​usually​ ​well​ ​differentiated. 
The​ ​growth​ ​rate​ ​is​ ​important​ ​in​ ​malignant​ ​neoplasms​ ​because​ ​they​ ​are​ ​divided 
into​ ​different​ ​levels​ ​of​ ​differentiation,​ ​and​ ​the​ ​rate​ ​of​ ​growth​ ​depends​ ​on​ ​the 
differentiation​ ​level,​ ​when​ ​the​ ​level​ ​of​ ​differentiation​ ​increases​ ​the​ ​tumor​ ​grows 
more​ ​rapidly.   
Exceptions:  
(Exceptions​ ​to​ ​the​ ​general​ ​rule)   
1. Hormonal​ ​influences:​ ​e.g​ ​Leiomyoma​ ​of​ ​uterus​ ​in​ ​pregnancy​ ​ ​ ​(hormones 
may​ ​cause​ ​the​ ​benign​ ​to​ ​grow​ ​more​ ​rapidly). 
2. Pressure​ ​constraints:​ ​(when​ ​a​ ​tumor​ ​grows​ ​in​ ​an​ ​organ​ ​or​ ​a​ ​site​ ​that​ ​is 
confined​ ​by​ ​an​ ​anatomic​ ​border,​ ​for​ ​example​ ​in​ ​the​ ​brain​ ​the​ ​pituitary 
gland​ ​is​ ​surrounded​ ​by​ ​a​ ​bone,​ ​this​ ​bone​ ​prevents​ ​the​ ​free​ ​growth​ ​of​ ​the 
tumor​ ​and​ ​can​ ​also​ ​cause​ ​pressure​ ​on​ ​the​ ​blood​ ​supply​ ​which​ ​can​ ​cause 
necrosis​ ​even​ ​if​ ​the​ ​tumor​ ​is​ ​benign). 
3. Some​ ​malignant​ ​tumors​ ​may​ ​outgrow​ ​their​ ​blood​ ​supply.  
(C.​ ​Ischemic​ ​n.) 
Some​ ​tumor​ ​growths​ ​are​ ​hormone​ ​–​ ​dependent:  
These​ ​tumors​ ​need​ ​hormones​ ​to​ ​grow. 
Examples:​ ​-​ ​Breast​ ​cancer  
​ ​ ​ ​ ​ ​ ​ ​ ​-​ ​Endometrial​ ​cancer  
​ ​ ​ ​ ​ ​ ​ ​ ​-​ ​Prostatic​ ​cancer  
*​ ​There​ ​are​ ​many​ ​types​ ​of​ ​breast​ ​cancers​ ​and​ ​the​ ​majority​ ​of​ ​these​ ​types 
depend​ ​on​ ​the​ ​hormone​ ​estrogen​ ​and​ ​also​ ​progesterone,​ ​so​ ​these​ ​tumors​ ​have 
receptors​ ​for​ ​estrogen. 
*​ ​Prostate​ ​cancer​ ​depends​ ​on​ ​the​ ​hormone​ ​testosterone. 
*​ ​Endometrial​ ​cancer​ ​depends​ ​on​ ​the​ ​hormone​ ​estrogen.  

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​ ​ ​-​ ​Endometrial​ ​hyperplasia​ ​is​ ​a​ ​response​ ​to​ ​an​ ​endogenous​ ​source 
or​ ​exogenous​ ​source​ ​of​ ​extra​ ​estrogen,​ ​endometrial​ ​hyperplasia​ ​ ​can​ ​develop 
into​ ​endometrial​ ​carcinoma.  
The​ ​effect​ ​of​ ​hormones​ ​is​ ​very​ ​important​ ​in​ ​the​ ​management​ ​of​ ​tumors:​ ​certain 
drugs​ ​were​ ​developed​ ​for​ ​tumors​ ​that​ ​depend​ ​on​ ​hormones,​ ​these​ ​drugs​ ​attach 
to​ ​the​ ​hormone​ ​receptors​ ​to​ ​block​ ​them.  
Examples:​ ​In​ ​case​ ​of​ ​breast​ ​cancer,​ ​anti-estrogen​ ​drugs​ ​are​ ​used. 
In​ ​case​ ​of​ ​prostate​ ​cancer,​ ​one​ ​of​ ​the​ ​treatment​ ​ways​ ​is​ ​to​ ​remove​ ​the​ ​patient’s 
testicles​ ​to​ ​reduce​ ​the​ ​testosterone​ ​levels​ ​and​ ​this​ ​may​ ​cause​ ​a​ ​shrinkage​ ​in​ ​the 
size​ ​of​ ​the​ ​cancer. 
So​ ​the​ ​hormone​ ​therapy​ ​relies​ ​much​ ​on​ ​this​ ​phenomena.  
 

The​ ​third​ ​important​ ​point​ ​to​ ​differentiate​ ​between​ ​benign​ ​and 

malignant​ ​tumors:  
The​ ​presence​ ​of​ ​a​ ​capsule​ ​and​ ​the​ ​presence​ ​or​ ​absence​ ​of​ ​local​ ​invasion. 
(Local​ ​invasion​ ​and​ ​Encapsulation)  
Benign​ ​tumors​ ​frequently​ ​have​ ​a​ ​capsule​ ​and​ ​are​ ​well​ ​defined​ ​or​ ​are​ ​well 
defined​ ​but​ ​without​ ​a​ ​capsule.  
Examples:​ ​Lipoma​ ​is​ ​surrounded​ ​by​ ​a​ ​capsule. 
Leiomyoma​ ​is​ ​confined​ ​and​ ​the​ ​borders​ ​are​ ​well​ ​defined​ ​but​ ​not​ ​surrounded​ ​by 
a​ ​capsule. 
Malignant​ ​tumors​ ​have​ ​the​ ​ability​ ​to​ ​cause​ ​invasion​ ​to​ ​the​ ​surrounding​ ​tissues 
(Malignant​ ​tumors​ ​progressively​ ​invade​ ​and​ ​destroy​ ​the​ ​surrounding​ ​tissue)​ ​e.g, 
Leiomyosarcoma.   
e.g​ ​-​ ​ ​Breast​ ​cancer​ ​infiltrating​ ​skin. 
​ ​ ​ ​ ​ ​-​ ​ ​ ​Basal​ ​cell​ ​carcinoma​ ​face​ ​infiltrating​ ​nerves. 
Local​ ​invasion​ ​and​ ​Encapsulation​ ​are​ ​considered​ ​the​ ​second​ ​most 
important​ ​feature​ ​to​ ​differentiate​ ​between​ ​benign​ ​and​ ​malignant​ ​tumors.  
Metastasis​ ​is​ ​the​ ​most​ ​important​ ​feature​ ​to​ ​differentiate​ ​between​ ​benign 
and​ ​malignant​ ​tumors.  

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Metastasis:​ ​Spread​ ​of​ ​malignant​ ​tumors​ ​to​ ​distant​ ​sites​ ​away​ ​from​ ​the​ ​main 
tumor. 
The​ ​ability​ ​to​ ​have​ ​distant​ ​spread​ ​is​ ​a​ ​feature​ ​of​ ​malignant​ ​neoplasm​ ​not​ ​benign. 
(this​ ​is​ ​the​ ​general​ ​rule​ ​and​ ​there​ ​are​ ​some​ ​exceptions)  
For​ ​example:​ ​a​ ​bone​ ​tumor​ ​that​ ​moves​ ​to​ ​the​ ​lung​ ​is​ ​a​ ​malignant​ ​tumor. 
Metastasis​ ​is​ ​proportionate​ ​to​ ​the​ ​size​ ​and​ ​to​ ​the​ ​degree​ ​of​ ​differentiation​ ​of​ ​the 
primary​ ​tumor.  
When​ ​the​ ​differentiation​ ​decreases,​ ​this​ ​increases​ ​the​ ​risk​ ​of​ ​having​ ​a​ ​malignant 
tumor​ ​that​ ​is​ ​able​ ​to​ ​metastasize.  
All​ ​malignant​ ​tumors​ ​can​ ​potentially​ ​metastasize​ ​except​ B ​ asal​ ​cell​ ​carcinoma 
and​ ​Most​ ​primary​ ​brain​ ​tumors​ ​(both​ ​can​ ​have​ ​local​ ​invasion​ ​and​ ​rarely​ ​can 
metastasize). 
 

End​ ​of​ ​lecture  

Good​ ​luck  

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