3. Differentiation refers to the extent to which
neoplastic cells resemble comparable normal
cells, both morphologically and functionally.
Anaplasia is lack of differentiation
3
4. Morphologic Features of Anaplasia,
Lack of Differentiation
• Pleomorphism: (pleo = more) (Variation in size & shape
of the cells and nuclei) Some cells/nuclei may be
many times larger compared to their neighbors
and some other may be small and primitive.
• Abnormal nuclear morphology: The nuclei contain an
abundance of DNA, are hyperchromatic and
larger and show higher nucleo-cytoplasmic ratio.
Nuclei vary in shape and chromatin is clumped along
the nuclear membrane. Nucleoli are enlarged and
prominent.
• Mitoses: Atypical and bizarre mitotic figures with
multipolar spindles are features of anaplasia.
(Increased number of normal mitotic figures are
seen in bone marrow and hyperplastic tissue.) 4
5. • Loss of polarity: Orientation of anaplastic cells is
markedly disturbed. Sheets and large masses of
tumor cells grow in anarchic, disorganized fashion.
• Tumor giant cells: Cancer giant cells are common in
some malignant growth. These have large
hyperchromatic pleomorphic nuclei varying in
size and shape. Cancer giant cells may have single
or multiple nuclei. (Macrophage derived multinucleated
Langhans and foreign body giant cells have normal nuclei).
• Areas of ischemic necrosis may be seen in the
malignant growth as blood supply falls short of the
need for rapid growth.
Morphologic Features of Anaplasia, continued
5
6. • Poorly differentiated anaplastic tumors also demonstrate
a total disarray of tissue architecture as in
anaplastic cervical malignancy, the normal orientation
of squamous epithelial cells relative to each other is lost.
• Well differentiated tumors, whether benign or malignant,
tend to retain the functional characteristics of their
normal counterparts. Thus there may be hormone
production by endocrine tumors or keratinproduction
by squamous epithelial tumors.
6
7. Dysplasia
• Dysplasia literally means “disordered growth”
• Dysplasia is disorderly but non-neoplastic growth.
• It is usually encountered in epithelia (usually in ut. cervix)
• Pleomorphism, hyperchromasia, loss of normal
orientation and mitotic activity may occur short of
malignancy. The lesion is reversible if the cause is
removed. Dysplasia may be mild, moderate or severe.
• When dysplastic changes are marked and involves
the entire thickness of the epithelium, the lesion is
considered a preinvasive intraepithelial neoplasm
(Carcinoma in situ).
• Cervical Intraepithelial Neoplasia (CIN) may be
described as CIN I, CIN II, CIN III (Carcinoma in situ)
7
8. BA
A. Carcinoma in situ: The entire
thickness of the epithelium is
replaced by atypical dysplastic
cells. There is no orderly
differentiation of squamous cells.
The basement membrane is intact
and there is no tumor in the
subepithelial stroma.
B. A high-power view of an other
region shows failure of normal
differentiation, marked nuclear and
cellular pleomorphism, and
numerous mitotic figures
extending towards the surface. The
basement membrane is not seen.
Carcinoma in situ
8
9. Anaplastic tumor showing cellular and nuclear
variation in size and shape. The prominent cell
near the center field has
an abnormal tripolar spindle.
07 - 09 9
10. Squamous cell carcinoma
Well-differentiated squamous cell carcinoma of the
skin. The tumor cells are strikingly similar to normal
squamous epithelial cells, with intercellular bridges
and nests of keratin pearls (arrow). 10
12. Spectrum of Cervical Intraepithelial Neoplasia (CIN)
Normal squamous epithelium for comparison
Normal CIN I with koilocytic atypia
(Gr koilos = hollow)
12
13. Spectrum of Cervical Intraepithelial Neoplasia (CIN)
CIN II, with progressive atypia in
all layers of the epithelium.
CIN III, (carcinoma in situ)
with diffuse atypia and loss of
maturation. 13
14. The cytology of
Cervical Intraepithelial Neoplasia
(CIN), Papanicolaou* smear.
Normal exfoliated
superficial squamous
epithelial cells
CIN I,
exfoliated squamous
epithelial cells
(* Greek physician & anatomist, in USA, 1881 – 1962)
14
15. The cytology of
Cervical Intraepithelial Neoplasia
(CIN), Papanicolaou smear.
CIN III,
exfoliated squamous
epithelial cells
CIN II,
exfoliated squamous
epithelial cells
15
16. Spread of Tumors
16
Dissemination of cancer may occur through one of
three pathways:
1. Lymphatic spread
2. Hematogenous spread
3. Seeding of body cavities and surface
• Seeding of body cavities & surfaces: This occurs
when carcinoma penetrate to reach the surface
of a viscus, most often peritoneal cavity but also
pleural, pericardial, subarachnoid and joint space.
Such seeding is usually seen in carcinoma of the
ovaries coating the surface of the peritoneum.
Appendiceal mucinous carcinoma may spread to
peritoneum forming pseudomyxoma peritonei.
17. 17
• Lymphatic Spread: is the most common pathway
for initial spread of carcinomas. Sarcomas may
also use this route. The pattern of lymph node
involvement follows the natural routes of
lymphatic drainage.
Sentinal node: The first node in a regional lymphatic basin
that receives lymph flow from a primary tumor.
In many cases the regional nodes serve as
effective barrier for some time.
Drainage of tumor cell debris and/or tumor
antigens also induces reactive changes in the nodes
with their enlargement.
Thus regional node enlargement does not
always mean dissemination of the primary lesion.
18. • Hematogenous Spread: is typical of sarcomas but
is also seen with carcinomas.
◘ The liver and the lungs are most frequently
involved secondarily in hematogenous
dissemination.
All portal area drainage flows to the
liver and
All caval blood flows to the lungs.
◘ Cancers arising close to the vertebral column
often embolize through paravertebral vascular
plexus (Vertebral metastasis from prostate and thyroid).
◘ Certain cancers may invade veins. Renal cell
carcinoma and hepatocellular carcinoma may
involve branches of renal vein and portal /
hepatic veins respectively.
18
20. The metastatic
cascade - 2.
Schematic
illustration of
the sequential
steps involved
in the
hematogenous
spread of a
tumor
Platelets
Tumor cell
embolus
Adhesion to
basement
membrane
Extravasation
Metastatic
deposit
Angiogenesis
Growth
20
