2. Basic concepts
• The nucleus tells us information about the state of activity of the cell
and the cytoplasm about the functional differentiation.
• However, this is not a precise division.
• Frequently, interpretation of the state of activity and the functional
differentiation is based on the information obtained from both
compartments of the cell and their relation to each other
3. Functional activity of cells
• Normal (baseline) activity; the state of cells or tissue that
is normal or typical for that particular type– Euplasia
• Decreased activity; degeneration of a tissue or cell into a
more primitive type; cell death- Retroplasia
• Increased activity; state of cell or tissue in which activity is
increased above that of euplasia, characterized by
stimulation, repair, or regeneration- Proplasia
• Marked proliferation and growth producing masses-
Neoplasia
• Benign neoplasia
• Malignant neoplasia
4. Causes for all these changes
• Changes in the pH
• Physical and chemical agents and trauma
• Infections
• Inflammatory conditions (need not be due infections
alone)
• Atrophy or thinning
• Pregnancy
• Radiation
• Chemotherapy
• neoplasms
5. Reactive cellular Changes due to
inflammation
• Inflammatory changes affect
both squamous and
endocervical cells, but the
changes are often more
dramatic in endocervical
cells.
• Inflammation alone causes
minor cytologic abnormalities
such as dual staining reaction,
lysis or vacuolization of the
cytoplasm, slightly
disproportionate nuclear
enlargement, and an increase
N/C ratio. Nuclear chromatin
is more often hypochromatic
than hyperchromatic
7. Reactive cellular Changes due to
inflammation
• In post-menopausal women also, inflammatory processes may cause
a false maturation of the epithelium, resulting in many eosinophilic
cells.
• Therefore, in association with inflammation, intermediate and
superficial cells may be observed along with parabasal cells
• Increased eosinophilia associated with inflammation may be referred
to as “non-hormonal maturation”
8. Reactive cellular Changes due to
inflammation
• In inflammatory states the cytoplasm of the squamous and columnar
cell may be completely or partially disintegrated. However, the major
changes are observed within the nucleus.
• Karyopyknosis- shrinkage of the nucleus with the condensation of
the chromatin
• Karyorrhexis-fragmentation of the nucleus
• karyolysis- dissolution of the nucleus
• chromatolysis - disintegration of the chromatin
9.
10.
11. Nuclear features associated with inflammation
• Minimal Nuclear enlargement:
one and a half to two times the
area of normal intermediate
squamous cell nucleus
• Occasional bi-or multinucleation
• Mild hyperchromasia may be
present but the chromatin
remains finely granular and
evenly distributed
12. Nuclear features associated with
inflammation
• Nuclear degeneration,
karyopyknosis, karyorrhexis,
karyolysis, hydrophic degeneration
with swelling and / or vacuolization,
chromatolysis, smudgy chromatin,
dehydration resulting in shrinkage
and wrinkling of nuclei (raisinoid)
• Nuclear outlines are smooth,
rounded and uniform showing
minimal irregularities
• Prominent single or multiple
nucleoli may be present
• Differential diagnosis: ASC-US (in
squamous); AGUS (in glandular)
13. Repair in female genital tract –Definition & causes
• It occurs in response to healing of an erosion or ulceration
• Erosion – partial loss of epithelium
• Ulceration – partial loss of epithelium and portions of underlying connective
tissue
• Regeneration of epithelium occurs when basal/reserve cells in viable
epithelium adjacent to an area of damaged epithelium proliferates,
stretching out to cover the defect.
• Eventually this reparative epithelium will differentiate and mature.
• Causes might include:
• Pathogenic organisms such as Trichomonas, Candida, Herpes and bacteria
• Surgical removal of tissue, laser surgery, cryotherapy (freezing)
• Trauma during childbirth
• Uterine prolapse, polyp, foreign body (IUD, pessary)
• Radiation therapy
14. Cytologic features of repair
• Cells occur in cohesive flat,
monolayer sheets (no single cells)
with good polarity (slimy, stretched
out or pulled look)
• Nuclei are round to oval, centrally
placed in abundant cytoplasm and
no crowding
• Nuclei may be enlarged – 1-2x
normal size, may vary
• Nuclear chromasia- frequently
hypochromatic (washed out, blend
into the cytoplasm)
• Chromatin pattern tends to be
uniform for all the nuclei in the
sheet
15. Cytologic features of repair
• Nucleoli – usually prominent,
macro, present in every nucleus,
may be irregular
• Mitotic figures may be present
• Cytoplasmic staining – often
cyanophilic, may be gray or even
eosinophilic
• Cytoplasmic texture – thinned
and stretched, may be even
vacuolated occasionally
• Smear background – clean or
inflammatory
16. Benign proliferative reactions
• Squamous Metaplasia
• Associated with the endocervix
• Reserve cells differentiate into
metaplastic cells under the
influence of estrogen in the
endocervix
• Eventually differentiate to
resemble native squamous
epithelium
• Rounded cell outlines, dense
cytoplasm
17. Benign proliferative reactions
• Parakeratosis (PK) is another
protective reaction
characterized by the presence of
various numbers of layers of
miniature squamous cells with
pyknotic nuclei.
19. Benign proliferative reactions
Hyperkeratosis (HK)
• Histologically characterized by multiple layers of keratinized, anucleate
squamous cells on the surface of the epithelium
• Cytologic features include:
• Anucleate squamous cells appear singly or in sheets, clusters, plaques
• Cells are often shrunken or wrinkled
• Cytoplasm may stain yellow, orange or pink
• Nuclei are absent
• A pale zone, “nuclear ghost” may mark the place of the missing nucleus
• Nucleated cells, containing dark blue cytoplasmic keratohyalin granules, may
be associated from the pre-keratin of the superficial cell
21. Benign proliferative reactions
• Important note: HK and PK may occur in response to inflammation or
irritation (such as uterine prolapse or pessary use) but also may occur
on the surface of intraepithelial squamous lesions or even on the
surface of invasive carcinoma, masking the underlying process
22. Chronic follicular cervicitis-cytology (CFC)
• Small (mature) and large (immature) lymphocytes and
Plasma cells
• Macrophages, may have ingested material (tingible body
macrophages)
• Cells appear singly, no molding, no epithelial cell
groupings
• There may be only a few patches of lymphoid cells in the
smear without any reactive cellular changes in the
squamous epithelial cells
24. Degenerate Changes
• Degenerative changes may occur as a result of an inflammatory
process
• Enzymes released from rupturing neutrophils are often responsible
for this cellular destruction
• Other types of insult or injury such as radiation, chemotherapy,
invasive cancer, surgery or other invasive diagnostic and therapeutic
procedures will cause cellular degeneration-*Patient history is VITAL!
• Degenerative changes affect normal, atypical, premalignant and
malignant cells
27. Degenerative changes – altered staining reaction due to partial
air-drying
With inflammation, the cells can take up too much water (hydropic
degeneration).
This fluid absorption leads to nuclear and cytoplasmic enlargement and
decreased nuclear staining intensity
28. Degenerative changes – increased vacuolization
• Vacuole surrounding the nucleus – perinuclear halo which
can also be due to nuclear shrinkage
29. Degenerative changes – increased vacuolization
• These vacuoles are not secretory vacuoles seen in glandular cells but
are due to degeneration- post radiation treatment
• Numerous vacuoles (clear, round) in both nuclei and in cytoplasm
32. Cornflaking
• A brown artifact results from
bubbles of air trapped on
superficial cells resulting in the
obscuring of the nuclei
• It can be reversed by returning
the slide through xylene and
alcohol to water, then re-stain
and re-coverslip
33. Reference
• Benson J (CT)(ASCP)CM, Albany College of Pharmacy and health
Science, Reactive, repair hyperkeratosis and parakeratosis, 2014
• Benson J (CT)(ASCP)CM, Albany College of Pharmacy and health
Science, Cytologic features of cellular degenerate changes, 2014
