CELLULAR CHANGES ASSOCIATED WITH HUMAN PAPILLOMAVIRUS
Cytomorphological
Criteria:
•Cellular
changes is caused by oncogenic type of HPV that is commonly from group 16 and
11.
•The
changes can be divided into 2 groups. Which are:
–a)
Classical Changes (CC) – Cellular
changes that occur as a confirmatory criteria of HPV infection
–b)
Non-classical Changes (NCC) - Cellular changes that occur at the early stage of
the HPV infection. May be vary or have little differences from other cellular
changes that caused by other viral infection.
Classical changes:
vKoilocytes – 60 – 70% cases
vKoilocytes is the term used to
classified the cell that has perinuclear halos.
vIn
HPV infection, the infected squamous cells will be seen having cytoplasmic
condensation at the periphery giving hallow central portion.
Non-Classical Changes:
vKoilocytes are hardly be seen.
30 – 20% cases
vSquamous
epithelial cell will appear to have heterogenous cytoplasm , unevenly stained. Mimicking dried smear.
vNuclei
is small and pyknotic- slightly
eccentrically placed
vNuclei
varies from single to bitinucleated due to cytopathic effect.
vHyperchromatic nucleus with
enlargement and eccentrically placed with slight, almost insignificant halos.
In
the figure above, both are from the CP Pap-smear that shows characteristics of
the infection due to HPV. In diagram “a”, the cytoplasm has shown irregularity
of the outline. Besides, the heterogenousity of the nucleus is seen in variety in shapes and colours. Meanwhile in
diagram “b”, the hyperchromatic nucleus is
significantly clear with coarse chromatin. There is also binucleation occur one of the
infected cells marked with “#”.
CELLULAR CHANGES CONSISTENT WITH HERPES SIMPLEX VIRUS
Cytomorphological
criteria (Cellular changes) :
§ Nuclei have a “ ground glass” appearance due to intranuclear viral particles.§ Enhancement of
nuclear envelope caused by peripheral margination of chromatin. (Crowdy type A inclusion
which contains virion push host chromatin
to the periphery).§Dense eosinophilic intranuclear inclusions
surrounded by a halo are variably present.§Large multinucleated
epithelial cells with molded nuclei are characteristic but not always be
present; mononucleate cells with nuclear
features described above may be the only finding.§ ‘3M’ for nuclear
infected with Herpes : Margination of nuclei, molding and multinucleation.§Sometimes necrotic
epithelial cells are seen in Pap smear with HSV infection.
The
figure shows multinucleate
giant cells with
ground glass
appearance of the nuclei and margination of the chromatin. Molding of the nuclei is a characteristic feature of herpes
infected multinucleate cells.
BACTERIA MORPHOLOGICALLY CONSISTENT WITH ACTINOMYCES
Actinomyces-like organism are identified cytologically as ball-like clusters of bacteria which have radiating filaments. These filaments can sometimes have a central core. Care should be taken when reporting actinomyces as other bacterial types appear very similar
Organism :
§Tangled clump of
filamentous organisms, often with acute angle branching, are recognizable as
‘cotton-ball’ clusters.§Filaments sometimes
have a radial distribution or have an irregular ‘wooly body’ appearance.§ Also known as “Gupta
bodies”.§ Associated with
Intrauterine device (IUD).
Cellular changes and slides background
:
§ Inflammatory perinuclear halo may be seen.
§Masses of leukocytes
adherent to microcolonies of the organisms,
with swollen filaments or ‘clubs’ at the periphery.
§ Neutrophils often present.
CELLULAR CHANGES ASSOCIATED WITH BACTERIAL VAGINOSIS
Figure 5 :
The figures show a) Cellular changes of squamous cell with small perinuclear halo is apparent associated with bacterial vaginosis and filmy background
of slide are seen. Inflammatory response
is apparent. . b) Squamous cells are covered
with coccobacilli, they accumulate on
the surface of large squamous cell to produce the
so called “clue cells. However, the background is clean.
CELLULAR CHANGES ASSOCIATED WITH CANDIDA SPP
Candida can be seen in a cervical sample as segmented hyphae and spores. The hyphae often protrude from groups of squamous cells or they can be seen as kebabs. This is where the hyphae skewer groups of vertically aligned squamous cells.
Figure 4 :
shows the skewered of the squamous cell,”shish-kebab” appearance. The pseudohyphae appears to be
pinkish-purple. There is one cell that
shows the nucleoli in the nucleus clearly.
There are also the cells that has been recognized to be having pseudokeratinization.
Figure 5 : The figure above shows fungal organism morphologically
consistent with Candida glabrata. Candida glabrata consists of small, uniform, round
budding yeast forms surrounded by clear halo on Papanicolaou stain. Unlike other Candida species,
it does not form pseudohyphae in vivo or in culture.
CELLULAR CHANGES ASSOCIATED WITH TRICHOMONAS VAGINALIS
Trichomonas Vaginalis (TV) is a pear shaped organism. It can contain a faintly visible intracellular structure known as polar bodies. Cervical samples containing TV can show inflammatory epithelial changes such as altered cytoplasmic staining, perinuclear halos and mild nuclear enlargement. TV can congregate in clusters around intermediate squamous cells.
Organism :
§ Size ranging from 15 – 30 µm
§ Cyanophilic small, round to oval
“pear shaped” organism with an indistinct eccentric pale basophilic nucleus and eosinophilic cytoplasmic granules.
§Flagella are not
usually seen (CP).
§Leptothrix is associated with T.vaginalis in about 80% cases.
§On LBP, eosinophilic granules better
visualized and flagella are preserved.
Cellular changes :
§ Dirty, fuzzy
background with round aggregates of neutrophils (“cannonballs” or “pus ball”)
§Reactive nuclear
changes, inflammatory perinuclear halos, and pseudoeosinophilia of the cytoplasm and
nucleus of squamous epithelial cells.
Figure 1: The figure shows T. vaginalis are stained bluish,
are often attached to the glycogen-rich and orange-colored superficial squamous cells. Cannon ball
appearance (clustering of neutrophils) is also noted. (CP)
Figure 2 :
The Figure shows a dirty fuzzy background of slide with increased cellular
maturation or eosinophilia and aggreagtes of inflammatory
cells. Smears containing trichomonads often contain
highly eosinophilic mature squamous cells and the nuclei
of the squamous are sometimes
surrounded by a small perinuclear halo.
Figure
3 : The figure shows
long filamentous organism ( Leptothrix) are seen overlying on the cells and smear background.
These organism are long and look like a child scribbles on conventional smear.
INTRODUCTION OF CELLULAR CHANGES ASSOCIATED WITH INFECTIONS IN PAP SMEAR
Cellular changes may due to a lot of causes but one of the cause are due to infections :
- The colonization and
abundant of infectious organisms able to alter the cytomorphological of the cells
in vaginal and cervical.
- The infectious
organism can be determined by cervical screening, pap smear analysis.
- There are various
types organisms infected the vaginal and cervical comprised of bacteria,
viruses, parasites and fungus infection.
- The organisms that
commonly determined by the cervical screening are :
a)
Bacteria
- Gardrenella Vaginalis, Lepthrothrix
spp. , Actinomyces
spp.
b)
Parasites
- Trichomonas vaginalis
c) Viruses
- Herpes Simplex Virus
(HSV) and Human Papillomavirus (HPV)
d) Fungus
- Candida
spp.
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