SQUAMOUS CELL CARCINOMA

APOF
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Squamous cell carcinoma (70-80%)
Adenocarcinoma (10-20%)
Other carcinomas ( ~ 10%)
Not epithelial malignancies (rare)
Squamous cell carcinoma is a malignant invasive
tumor showing differentiation toward
squamous cells.
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Symptoms of abnormal vaginal bleeding
Post coital bleeding
 Vaginal discharge
 Post menopausal bleeding
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Advanced disease
Weight loss
 Weakness
 Pelvic or abdominal pain
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Examination of cervix may show growth
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Cervical squamous cell carcinoma spreads
principally by local extension to the vagina,
parametrium, the ureters, bladder, rectum and
also to lymph nodes.
Involvement of lymphatic's or blood vessels =
poor prognosis
Compression/ infiltration of the ureters is
present in 2/3 of fatal cases.
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Involves:
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Cytology
Colpolscopy
Histology
Clinical and imaging assessment
Cytology smears from invasive cervical carcinoma are
usually dominated by blood cells and purulent exudate
Cells of invasive cancer may be more difficult to interpret
then those of SIL
Signs and symptoms of invasive carcinoma therefore are
indicator for referral to Colpolscopy
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Invasive carcinoma is recognised on histology
by the presence of abnormal squamous cells
which are no longer confined to the surface of
the cervix or endocervical crypts by intact
basement membrane.
They have extended into the underlying
stroma.
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Histology showing
abnormal cells
infiltrating beyond the
basal membrane into
the stroma
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Keratinizing squamous cell carcinoma
Large cell non keratinizing cell carcinoma
Small cell non keratinizing cell carcinoma
Verrucous carcinoma
The Bethesda system does not subdivide squamous cell
carcinoma. Only for descriptive purpose TBS id
dicussing nonkezatinizing and keratinizing SCC
separately.
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They may coexist on the same slide.
Historically, ‘’small cell carcinoma’’ comprised of
heterogenous group of neoplasms, including poorly
differentiated SCC and tumours demonstrating
neuroendocrine features.
Current classification limit the use of small cell
carcinoma to non-squamous tumours with evidence od
neuroendocrine differentiation.
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Very early invasion
Can be treated by conservative treatment such
as Cone biopsy as opposed to harsher
treatments such as a radical hysterectomy
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Relatively few cells may be present: often as isolated
single cells and less common in aggregates
Marked variation in cellular size and shape is typical,
with caudate and spindle cells, frequently with dense
orangeophilic cytoplasm
Nuclei vary in markedly in size, nuclear membranes
are irregular , numerous dense opaque nuclei
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Coarsely granular and irregulary distributed
chromatin with parachromatin clearing (windowing)
Macronucleoli may be seen but are less common than
in nonkeratinizing SCC
Associated keratotic changes ( hyperkeratosis or
pleomorphic parakeratosis ) may be present but are
not sufficient
Tumor diathesis may be present , but less then in
nonkeratinizing SCC
Tumour diathesis
Smear background including fibrin, leukocytes
and blood (old and fresh blood)
Invading neoplastic cells frequently show
greater maturation with more cytoplasmic
development than the cells of the CIN 3.
Bizarre shaped cells, fiber and tadpole shaped abnormal cells
Squamous cell carcinoma,keratinizing
Dysplastic squamous cells
with anisocytosis and
anisonucleosis including
keratinization and
tadpole cells are
diagnostic of invasive
squamous cell
carcinoma.
Squamous cell carcinoma,keratinizing
Squamous Cell Carcinoma, keratinizing
Tumor diathesis, variation in cell size and shape, evidence of keratinization, and
nuclear abnormalities.
Squamous cell carcinoma
Keratinized cells with pleomorphism of size and shape. The nuclei also show marked variation in size
and dense, opaque nuclear forms are seen in which chromatin may be difficult to discern.
However in other cells, the chromatin is irregularly distributed with parachromatin clearing
Chromatin may be difficult to discern in keratinized cells and macronucleoli are seen less commonly
seen as compared to non-keratinizing squamous carcinoma
Squamous cell carcinoma
Tumor diathesis and lysed blood provide the background for numerous small,
hyperchromatic malignant cells. Two large nuclei with coarsely granular chromatin and
prominent nucleoli are consistent with SCC.
Pleomorphism of shape and size is a feature of invasive squamous cell carcinoma, and is usually more
obvious in the keratinizing type.
Invasive squamous cell carcinoma (cell in cell, cannibalism)
Squamous cell carcinoma
"Litigation Cell"; shown as an example of single cell that can be missed or misclassified
as "atypical parakeratosis".
When cells such as this are encountered a detailed assessment for other abnormal cells and
the background features (diathesis) should be performed.
Invasive squamous cell carcinoma. Pleomorphic malignant cell, isolated or in cluster.
Squamous cell carcinoma
Slides from deeply invasive tumors show abundant tumor diathesis, a granular precipitate of lysed
blood and cell fragments. In such cases, the malignant cells can be hard to identify. In other
cases,the tumor diathesis is focal, and, if missed, the case is misclassified as HSIL
Squamous cell carcinoma, keratinizing.
A, In keratinizing carcinomas, the cells have markedly aberrant shapes, as
seen here. “Fiber cells” are numerous.
B, Tadpole cell and some tumour diatheses are seen in this tumour.
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Cells occur singly or in syncytial aggregates with poorly defined
cells borders
Cells are somewhat smaller than those of HSIL, but display most of
the feratures of HSIL
Nuclei demonstrate markedly irregular distribution of
coarsely clumped chromatin
A tumour diathesis consisting of necrotic debris and old blood is
often present
Large cells variation tumours may show prominent macronucleoli
and basophilic cytoplasm
Squamous cell carcinoma
Cells on the left with scant cytoplasm display nuclei with irregularly distributed, coarsely
granular chromatin and prominent nucleoli.
On the right, lysed blood and a stripped nucleus, tumor diathesis, is evident.
Invasive carcinoma with prominent nucleoli may suggest adenocarcinoma; however, in this
case centrally located nuclei and flat arrangement of cells is consistent with SCC
Non-keratinizing squamous cell carcinoma, "large cell variant," shows a fair amount of
cyanophilic cytoplasm, granular chromatin, and prominent nucleoli.
Squamous cell carcinoma - non keratinizing
Numerous isolated cells display nuclei with irregular membranes, uneven chromatin
distribution, hyperchromasia, and irregular membranes. While the cells display all the
features of HSIL, they also contain nucleoli, and markedly irregular distribution of
chromatin. An associated tumor diathesis is often present, but is not pictured.
Squamous cell carcinoma
At low magnification, nuclear abnormalities such as irregularly distributed coarse
chromatin, hyperchromasia, and high nuclear to cytoplasmic ratio can be appreciated.
Ragged borders favor carcinoma, not SIL.
Squamous cell carcinoma nonkeratinizing.
The malignant cells have irregularly distributed chromatin and a prominent nucleolus,
characteristic features of invasive SCC.
Squamous cell carcinoma nonkeratinizing.
The sheetlike arrangement of poorly differentiated squamous carcinoma cells with
nucleoli and mitoses mimics the appearance of reparative epithelium, but the crowding
and haphazard arrangement of the cells are not typical of repair.
Squamous cell carcinoma
Highly atypical cluster of cells with loss of polarity, variable N/C ratios, nuclear membrane irregularities
(better appreciated by focusing up and down), and prominent nucleoli. Intracytoplasmic nuclear debri
s and mitosis are also present.
Explanatory Notes:
Both repair and invasive carcinoma have prominent nucleoli; however the atypia seen in carcinoma, as
well as isolated malignant cells and diathesis were useful in making the correct interpretation.
The malignant cell clusters show more rounding on liquid preparations and in an individual cell group
distinction between a squamous and glandular lesion may be difficult. Attention should be given to
looking for isolated dysplastic cells in the background.
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Invasive smear being mistaken for an
inadequate / poor smear
Not assessing the detail of the abnormal cells
present may lead to the under grading of the
abnormal keratinizing cells
Repair cells
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Additional testing
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Colposcopy
 Cervix is viewed through a colposcope and the surface
of the cervix can be seen close and clear.
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Cervical Biopsies
 Colposcopic biopsy – removal of small section of the
abnormal area of the surface.
 Endocervical curettage – removing some tissue lining
from the endocervical canal.
 Cone biopsy – cone-shaped piece of tissue is removed
from the cervix
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FIGO System (International Federation Of Gynecology and
Obstetrics)
Five stages – 0 to 4
Stage 0 Carcinoma in situ
 Stage 1 Invaded cervix, but has not spread.
 Stage 2 Has spread to nearby areas, not leaving pelvic area.
 Stage 3 Cancer has spread to the lower part of the vagina.
 Stage 4 Cancer has spread to nearby organs; metastasis.
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Surgery
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Preinvasive cervical cancer
 Cryosurgery
 Laser surgery
 Conization
Invasive cervical cancer
 Simple hysterectomy
 Removal of the body of the uterus and cervix.
 Radical hysterectomy and pelvic lymph node dissection
 Removal of entire uterus, surrounding tissue, upper part of
the vagina, and lymph nodes from the cervix.
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Radiation
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Chemotherapy
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The very success of the Pap test in cervical cancer screening has
fostered an unrealistic expectation that the test is perfect.
It is not. Pap test sensitivity for high-grade cervical intraepithelial
neoplasia (CIN) is in the range of 70 to 80 percent.
Factors that limit test sensitivity include: small size of a lesion,
inaccessible location of the lesion, the lesion not being sampled,
the presence of only a few abnormal cells on the slide, small size
of the abnormal cells, or the presence of inflammation and/or
blood obscuring cell visualization.
False-negative results occur even in optimized screening programs
and can not be entirely eliminated.
Approximately half of the cervical cancers diagnosed in the United
States are in women who have never been screened, and an
additional 10 percent of cancers occur in women who have not
been screened within the past five years.
“ The detection and classification of
cytologic abnormalities in cervicovaginal
material, whether in the form of direct
smears or material prepared from liquid
samples, belongs to the most difficult
human tasks.” ( Koss 2005.)