Disorders of Cell Growth & Differentiation- An Introduction Dysplasia Metaplasia Anaplasia Neoplasia

1. Disorders of
Cell Growth & Differentiation
Presented By:
Dr J
Mwaura

2. Objectives
• Introduction
• Definitions
• Normal cell growth & Regulation – Recap
• Types of cell growth disorders
• Discussion
www.linkedin.com/in/josephmwaura 2

3. Introduction
• Differentiation- Extent to which neoplastic cells resemble
cell of origin morphologically & functionally
• Growth and differentiation a tightly controlled process
• Critical in survival of the organism
• Error prone system… evolved sophisticated repair
mechanism.
• Failure of control of growth & differentiation – Leads to
disordered growth
www.linkedin.com/in/josephmwaura 3

4. Cell Cycle
www.linkedin.com/in/josephmwaura 4

5. Cellular Differentiation
www.linkedin.com/in/josephmwaura 5

6. Question
How many cell types are
there in the Human
Body?
www.linkedin.com/in/josephmwaura 6

7. Cellular differentiation
• process where a cell changes from one cell type to another
• Usually to more specialized cells
• Embryogenesis -zygote to highly complex tissues /organ/organism
• Mature – Normal turn over, tissue repair
• Causes changes a cell's size, shape, membrane
potential, metabolic activity, and responsiveness to signals
• Highly controlled modifications in gene expression
• Almost never involves a change in the DNA sequence itself.
www.linkedin.com/in/josephmwaura 7

8. Types of Disorders of Growth
Agenesis
Aplasia
Metaplasia
Dysplasia
Anaplasia
Neoplasiawww.linkedin.com/in/josephmwaura 8

9. Hypoplasia
• Underdevelopment or incomplete development of a
tissue or organ, due to inadequate or below-normal
number of cells
• A less severe form of aplasia…a continuum
• The organ does not achieve its size for age and stage of
development
• Hypoplasia is usually congenital in origin, mostly due to
genetic disorders
• Can affect almost any organ in the bodywww.linkedin.com/in/josephmwaura 9

10. HYPOPLASIA : Examples
• Testes in Klinefelter's syndrome
• Ovaries in Fanconi anemia, gonadal dysgenesis, trisomy X
• Thymus in DiGeorge syndrome
• Labia majora in popliteal pterygium syndrome
• Corpus callosum
• Cerebellum caused by mutation in the Reelin gene
• Teeth Turner's hypoplasia
• Chambers of the heart in hypoplastic heart syndrome
www.linkedin.com/in/josephmwaura 10

11. HYPOPLASIA : Examples
•Optic nerve in optic nerve hypoplasia
•Sacrum in sacral agenesis
•Facial muscle in asymmetric crying facies
•Thumb from birth
•Lungs, often as a result of oligohydramnios during gestation
or the existence of congenital diaphragmatic hernia
•Small bowel in coeliac disease
•Fingers and ears in Harlequin type ichthyosis
•Mandible in congenital hypothyroidism
www.linkedin.com/in/josephmwaura 11

12. Aplasia
• Complete absence of some cells or whole tissue.
• Congenital or acquired, genetic factors/ mutations play a major
role
 Acquired pure red cell aplasia
 Aplasia cutis congenita
 Aplastic anemia
 Germ cell aplasia, also known as Sertoli cell-only syndrome
 Radial aplasia
 Thymic aplasia, which is found in DiGeorge syndrome and
www.linkedin.com/in/josephmwaura 12

13. Agenesis
• Complete failure development of an organ during
embryogenesis
• Can affect almost any organ
• Generally Rare
• Clinical symptoms show great variability for each
abnormality
www.linkedin.com/in/josephmwaura 13

14. Agenesis: Examples
• Renal Agenesis
• Agenesis of Corpus collusum
• Mullerian agenesis
• Gall bladder agenesis
• Amelia
• Eye agenesis
• Dental & Oral agenesis
• Ear agenesis, Microtiawww.linkedin.com/in/josephmwaura 14

15. Causes: Agenesis, Hypoplasia, agenesis
• Hereditary /Genetic factors
• Somatic mutations
• Stress or Injury
 Infections
 Irradiation
 Chemical
 Mechanical injury
 Nutritional
 Ischemia www.linkedin.com/in/josephmwaura 15

16. Metaplasia
• Replacement of one differentiated cell type with another
• Exposure to stressful stimuli – new cell type thought to
withstand the toxic environment better
• Usually seen in epithelial cells
• Can lead to loss of function
• Usually reverts to original cell type if stimulus is removed
• But ..If continued…risk to progress to more severe and
permanent changes that can lead to cancer
www.linkedin.com/in/josephmwaura 16

17. Metaplasia- Examples
Tissue Stimulus Original Epithelial
Cell
Replacement
Epithelium
Clinical correlates
Respiratory
Epithelium
Cigarette
Smoke
mucus-secreting
ciliated
pseudostratified
columnar
Stratified squamous
epithelium
Cancer, respiratory
infections
Esophagus Gastric Acid Simple Columnar Pseudostratified
columnar (Intestinal),
goblet cells= Barrett's
Risk of progression to
gastric cancer
Ureters Ureteric
Stones
Transitional
Epithelium
Nephrogenic
metaplasia
Transformation to
cancer potential
uncertain
www.linkedin.com/in/josephmwaura 17

18. Metaplasia Ctd
Tissue Stimulus Original
Epithelial Cell
Replacement
Epithelium
Clinical correlates
Cervical OS/ SC
Junction
Inflammation/
HPV
Columnar
epithelium
Squamous
epithelium
Irreversible
Progression to cancer
Biliary duct Biliary stones Secretory
Columnar
epithelium
Stratified
squamous
Biliary carcinoma
Renal cortex Vit A Deficiency Transitional
Epithelium
Keratinising
Epithelium
Renal/ureteric / Bladder
stones
Respiratory Vit A Deficiency Mucocilliary
epithelium
Keratininising
squamous
epithelium
Predisposition to
infections
www.linkedin.com/in/josephmwaura 18

19. Esophageal Metaplasia – Barrette Esophagus
www.linkedin.com/in/josephmwaura 19

20. Cervical Metaplasia
www.linkedin.com/in/josephmwaura 20

21. Metaplasia of Bronchial Epithelium
www.linkedin.com/in/josephmwaura 21

22. Cell of Origin in Metaplasia
• The cell of origin for many types of metaplasias are controversial or
unknown.
• Thought to be stem cells in tissue of origin
• Eg Barrett's esophagus.
 direct transdifferentiation of squamous cells to columnar cells,
 the stem cell changing from oesophageal type to intestinal type,
 migration of gastric cardiac cells,
 population of resident embryonic cells which are present
through adulthood. www.linkedin.com/in/josephmwaura 22

23. Dysplasia
 Disordered proliferation/ growth of the epithelium
that remains confined within the basement
membrane of the tissue from which it arises
 Syn: intraepithelial neoplasia…
 Considered preneoplastic
 Always pathologic
 May present as clinically identifiable lesions, allowing
for early detection and surveillance.
www.linkedin.com/in/josephmwaura 23

24. Characteristics - Microscopy
4 major pathological microscopic changes:
1. Anisocytosis (cells of unequal size)
2. Poikilocytosis (abnormally shaped cells)
3. Hyperchromatism (nuclear excessive
pigmentation)
4. Presence of mitotic figures (an unusual
number of cells which are currently dividing).
www.linkedin.com/in/josephmwaura 24

25. Nuclear Abnormalities
• Nuclear Pleomorphism
• Irregular contour, with hyperchromatic
coarse chromatin or vesicular chromatin.
• Size – Increased N/C ratio to 1: 1
• Increased normal and abnormal mitosis
• Shape – Odd shaped nucleus with unclear margins
• Prominent / multiple nucleoli
www.linkedin.com/in/josephmwaura 25

26. Other Microscopic Changes
 Drop-shaped rete processes
 Basal cell hyperplasia
 Irregular epithelial stratification
 Enlarged nucleoli
 Individual cell keratinization
 Loss or reduction of cellular cohesion
 Loss of basal cell polarity
 Koilocytosis www.linkedin.com/in/josephmwaura 26

27. Dysplasia- Macroscopy
Leukoplakia (white patch)
Erythroplakia (red patch) and
speckled lesions.
• Erythroplakia and speckled lesions demonstrate a
stronger association with microscopic dysplasia,
compared to leukoplakia.
www.linkedin.com/in/josephmwaura 27

28. Mild Cervical Dysplasia
www.linkedin.com/in/josephmwaura 28

29. Cervical Dysplasia -Moderate
www.linkedin.com/in/josephmwaura 29

30. HPV-infected cells
 enlarged (x2 or x3) nuclei
 Increased N/C ratio
 hyperchromasia.
Pap Smear Prep
Normal cervical cells www.linkedin.com/in/josephmwaura 30

31. Grading
Mild
Moderate
Severe
Carcinoma In Situ- Most severe form
Note:
 Based on histologic examination
 Specific pattern vary depending on tissue
 Useful in prognosis and Rx decision
 NB: Not always linear
www.linkedin.com/in/josephmwaura 31

32. What happens to Dysplasia (Cervical)
• 10% will progress to moderate, then severe and
eventually invasive carcinoma
– Mean duration – 10yrs
• 90% may remain the same or regress 1
• Implications for Management?
www.linkedin.com/in/josephmwaura
32

33. Anaplasia
• Loss of cellular differentiation & morphological features
of mature cells
• Loss of orientation to each other and other structures eg
basement membrane
• Loss of structural and functional differentiation of
normal cells
• May be no resemblance to tissue of origin
• Most extreme disturbance in cell growth encountered in
the spectrum of cellular proliferations
• Marker of malignancywww.linkedin.com/in/josephmwaura 33

34. Anaplasia: Characteristics
• Pleomorphism
 Cellular – Anisocytosis, Poikilocytosis, Tumor giant cells
 Nuclear – Anisonucleosis *
 Nucleus away from basal membrane
• Increased N/C ratio
 Large nucleus
• Hyperchromatism- darkly staining nucleus
 Due to increased amount & clumping of nucleoproteins
• Nucleolar Changes
 Prominent nucleolus/nucleoliwww.linkedin.com/in/josephmwaura 34

35. Anaplasia: Characteristics
• Abnormal Mitotic figures
 Tripolar, quadripolar, multipolar spindles
• Chromosomal Abnormalities
 Transmitted to progeny on division
• Spread beyond the tissue of origin
 local invasiveness, infiltration, destruction of local tissues/
 distant by metastasis
• Capacity for multiplication
www.linkedin.com/in/josephmwaura 35

36. Anaplasia: Characteristics
• Functional(Cytoplasmic Changes)
 Quantitative /qualitative changes in cytoplasmic
constituents
• Loss of cellular architecture and relationships
 Fail to develop recognizable patterns of orientation
to one another (Loss of polarity)
• High proliferation Index => Malignant transformation
• Breaching of basement membraneswww.linkedin.com/in/josephmwaura 36

37. Summary of Cellular Changes in anaplasia
www.linkedin.com/in/josephmwaura 37

38. Large Cell Carcinoma - Lung
www.linkedin.com/in/josephmwaura 38

39. Grading
 Four Tier
 3 tier
 2 tier
• NB: Most tumors
neoplasia have
specific grading
system
www.linkedin.com/in/josephmwaura 39

40. Neoplasia
• New Growth
• “An abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of normal
tissues and persists in the same excessive manner
after cessation of the stimuli that evoke the change”
Sir Rupert Willis
www.linkedin.com/in/josephmwaura 40

41. Main features
 Autonomous: The growth of neoplastic cells is
independent of growth factors and regulatory mechanisms
operating inside the normal tissues.
 Excessive: This excess may be evident in the size of the
outgrowths and the duration of the proliferation.
 Disorganized: The structures formed by tumor cells differ
from normal tissues and do not fit into the general
organization scheme of the normal body.
www.linkedin.com/in/josephmwaura 41

42. Classification- ICD 10
 Benign neoplasms
 In situ neoplasms
 Malignant neoplasms
 Neoplasms of uncertain or unknown
behaviour.
www.linkedin.com/in/josephmwaura 42

43. Benign Vs Malignant
www.linkedin.com/in/josephmwaura 43

44. Question
What is the difference between:
Dysplasia & Anaplasia?
Anaplasia & Neoplasia?
www.linkedin.com/in/josephmwaura 44

45. End
Discussion
www.linkedin.com/in/josephmwaura 45