West Visayas State University – College of Medicine – Batch 2020

PATHOLOGY
Lecture 1
Block 14 Diseases of the Vulva, Vagina and Cervix
Module 3
04/10/18 Dr. R. Dotollo

TOPIC OUTLINE
I. Objectives
II. Vulva
A. Vulval Acute Dermatitis (Eczema)
B. Lichen Simplex Chronicus
C. Lichen Sclerosus of Vulva
D. Fibroepithelial Polyp
E. Squamous Papilloma/Tosis
F. Bartholin Cyst
G. Paget’s Disease of the Vulva
H. Condyloma Acuminata
I. Verrucous Carcinoma of the Vulva
J. Basal Cell Carcinoma
K. Malignant Melanoma
III. Vagina Figure 1. Vulva
A. Congenital Anomalies
B. Embryonal Rhabdomyosarcoma
C. Vaginitis Secondary to Trichomonas vaginalis
IV. Cervix
A. Anatomy of the Cervix
B. Squamous Metaplasia in the Transformation Zone
C. Cervicitis
D. Endocervical Polyp
E. Florid Condyloma of the Cervix
F. Carcinoma of the Cervix
Review Questions
References

LECTURER BOOK REFERENCE OLD TRANS

I. OBJECTIVES
• Describe the pathogenesis, gross and microscopic and Figure 2. Anatomy of the reproductive system in relation to the bladder
clinical features of diseases of the vulva, vagina, & and the rectum
cervix.
II. VULVA
• Identify and explain the risk factors in the pathogenesis A. VULVAL ACUTE DERMATITIS (ECZEMA)
of cervical cancer (CA).
• Describe the precursor lesions (dysplasia/CIN) in
cervical cancer.
• Correlate the overexpression of certain oncogenic
proteins in the pathogenesis of cervical cancer.
• Describe the gross, microscopic, clinical features, and
spread of cervical cancer.
• Describe the staging system in cervical cancer.
• Identify the methods in the diagnosis of cervical cancer.
• Enumerate the factors in the prognosis of cervical
cancer.

The vulva has a similar histology with that of the skin,

thus you can see dermatitis
 Pathogenesis:
Endogenous type – atopic dermatitis atopic
dermatitis and seborrheic dermatitis, seen as scaly
macular eruption

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 Exogenous type – irritant dermatitis (urine in vulva) Not malignant, but sometimes present in the
and contact allergic dermatitis (type 4 delayed margins of vulvar cancers
hypersensitivity), seen as acute or chronic Lymphocytic infiltration of dermis
dermatitis
 Gross features:
Erythematous vesiculated skin in the vulva
Edema and weeping vesicles
Linear excoriations due to scratching
Vesicles rupture onto surface and a crust forms
from the exudate
 Microscopic features:
Epidermis shows inflammation and spongiosis
(edema), and spongiotic vesicles rupture to produce
exudative lesions.
Dermis shows perivascular lymphocytic infiltrate
and edema, and separation of of collagen fibers.
Telangiectatic lymphatics and dilated capillaries

B. LICHEN SIMPLEX CHRONICUS

There is hyperkeratosis – w/ loss of nuclei

Parakeratosis – w/ nuclei still

C. LICHEN SCLEROSUS OF THE VULVA

You can see that in lichen simplex chronicus, it turned

white because of persistent scratching and scarring. It
is so itchy.
On microscopic examination, you will note that the
upper portion is keratinized. What happens when you
have consistent proliferation? Hyperkeratosis occurs.
You will see thickening of the epidermis. How do you
know that this is a reaction? Because of the presence
of inflammatory infiltrates.

• Aka hyperplastic dystrophy, vulvar chronic dermatitis, You can see the whitened areas. In this particular
and squamous cell hyperplasia lesion, if we look into the microscope, you have a
thinned out epidermis.
 Pathogenesis: In lichen sclerosis, the epidermis is flattened. No
epithelium is present. Instead, it is replaced by an
Nonspecific condition due to rubbing or scratching area of edema and hyalinization.
of the skin to relieve pruritus • Nonneoplastic cause of leukoplakia – opaque, white,
End stage of many vulvar inflammatory diseases: pruritic, scaly plaques
lichen planus, psoriasis, lichen sclerosus • Inflammatory disease associated with autoimmune
 Gross features: diseases like vitiligo, pernicious anemia, and thyroiditis
Appears as area of leukoplakia  Pathogenesis:
Scaling and excoriations present Autoimmune character is suggested by activated T
Thickening (acanthosis) and exaggerated skin cells in the dermis
markings (lichenification)  Gross features:
 Microscopic features: Smooth, white plaques or macules that may enlarge
Marked hyperkeratosis of epidermis buts lacks and coalesce, producing a surface that resembles
cellular atypia porcelain or parchment

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 Labia may atrophy and agglutinate, constricting the obstruction by the inflammatory cells, you will note
vaginal orifice that it will be cystic.
 Microscopic features:
 Pathogenesis:
Hyperkeratosis
Loss of rete ridges
Epithelial thickening with flattening of rete pegs Bartholin Gland Adenitis Abscess
Cytoplasmic vacuolation of the basal layer
Homogenous, acellular zone in the upper dermis Obstruction of
duct by Bartholin
Band of chronic inflammatory cells, lymphocytes inflammatory
Duct cyst
Gland Cyst
with few plasma cells in dermis process
 Clinical features: • Infection of the Bartholin glands produce adenitis and
Most common in postmenopausal women abscess
Insidious and progressive • Bartholin cyst result from obstruction of the duct by
Itching and dyspareunia inflammatory processes
• Formerly associated with gonorrhea, but staphylococci,
D. FIBROEPITHELIAL POLYP chlamydia, and anaerobes are now the common causes
 Gross features:
Cystic structures up to 3-5 cm in diameter
Pain and local discomfort
 Microscopic features:
Cysts lined by transitional or squamous epithelium

G. PAGET’S DISEASE

• Aka acrochordon, squamous papilloma, skin tags

• Gross features:
Soft, flesh-colored, bag-like tumors that are often
attached to skin by a slender stalk
• Microscopic features:
Consists of fibrovascular cores covered by benign
squamous epithelium
• Clinical features: We have Paget’s disease of the vulva shown in the
Usually inconsequential, but occationally associated picture. We also have Paget’s disease of the nipple.
with diabetes, obesity, and intestinal polyposis The cells are very distinct and easy to identify. Both
Polyps may undergo necrosis due to torsion, of them have large tumor cells.
causing pain • Aka extramammary Paget’s Disease
• Named after similar-appearing tumor in the nipple and
E. SQUAMOUS PAPILLOMA & PAPILLOMATOSIS extramammary sites, such as axilla and perianal regions
• Benign exophytic proliferations covered by  Pathogenesis:
nonkeratinized squamous epithelium Intraepithelial proliferation of malignant cells (Paget
• Develops on vulvar surfaces cells)
• May be single or numerous Presumably arise from multipotent cells found within
• Etilogy unknown the mammary-like gland ducts of the vulvar skin
“Many polyps”  Gross features:
Pruritic, red, crusted, maplike area usually on labia
F. BARTHOLIN CYST majora
 Microscopic features:
Paget cells larger than surrounding keratinocytes,
and are seen singly or in small clusters in the
epidermis
With perinuclear halo
Pale cytoplasm with mucopolysaccharide that stains
with PAS, Alcian blue, or mucicarmine stains
Express cytokeratin 7
Note the location of the Bartholin’s glands. When you Display apocrine, eccrine, and keratinocyte
have Bartholin’s gland involvement, when there is differentiation
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 H. CONDYLOMA ACUMINATA In HPV positive, you have vulvar intraepithelial
proliferation. It is differentiated. Remember that you
have well differentiated, moderately differentiated and
poorly differentiated. If it is well differentiated, you can
still see cells that are going into maturity.
Remember what differentiation means in neoplasia.
When you say well differentiated carcinoma, it is
almost like the normal appearance. When you say
poorly differentiated, that particular lesion does not
contain any normal cell. It has no maturity. You can’t
even know if it is squamous or sarcoma.
A. Classic Vulvar B. Differentiated VIN
 Histopathology of condyloma acuminatum showing Intraepithelial Neoplasia (HPV Negative)
acanthosis, hyperkeratosis, and koilocytic atypia with (HPV positive)
enlarged, atypical nuclei and cytoplasmic vacuolation. With diffuse cellular Showing maturation of the
You can see white patches. You will note that this is atypia, immaturity, nuclear superficial layers,
the overlying skin and it gives you an idea on what crowding, and increased hyperkeratosis, and basal
type of organ system is involved. You can see the mitotic activity.
cell atypia (arrow).
changes. • Atypia almost involve the full thickness of the epidermis
 Pathogenesis:
or epithelium.
Benign genital warts caused by low oncogenic risk
HPVs, mainly types 6 and 11
On microscopic
Sexually transmitted examination, this is a well
Are not precancerous differentiated carcinoma.
 Gross features: Why? Because there are
Benign, exophytic, papillomatous signs of keratinization
May grow as papules, plaques, nodules and (keratin pearls).
eventually as spiked or cauliflower-like Nests of
neoplastic squamous
excrescences
cells, some with keratin
Verrucous lesions that involve the vulvar, perineal, pearls, are evident in this
perianal, vaginal, and cervical areas well-differentiated tumor.
 Microscopic features:
Papillary, exophytic, dendritic cores of stroma • Squamous cell carcinoma – most common type of
covered by hyperkeratotic squamous epithelium vulvar cancer
Koilocytic atypia – viral cytopathic changes in • Vulvar Intraepithelial Neoplasia (VIN) is a precursor
squamous epithelium characterized by perinuclear lesion of invasive squamous cell carcinoma of the vulva
halo, nuclear enlargement, hyperchromasia, and • Two type of VIN: classic and simplex
wrinkled nucleus that contains HPV particles Classic VIN
Viral DNA remains episomal, and extensive virus ─ 30% of cases
replication causes extensive cytoplasmic injury, ─ Aka undifferentiated VIN
creating the koilocyte (from Greek koilos, “hollow”) ─ Low-risk progression to invasive carcinoma
except in older and immunosuppressed women
I. VULVAR INTRAEPITHELIAL NEOPLASIA (VIN) AND ─ Includes carcinoma in situ/Bowen’s disease
VULVAR SQUAMOUS CELL CARCINOMA ─ Pathogenesis:
HPV 16
─ Gross features:
Develops to warty and basaloid
carcinoma
Discrete, white, hyperkeratotic or slightly
raised, pigmented lesion
─ Microscopic features:
Classic VIN: Epidermal thickening, nuclear
atypia, increased mitosis, and lack of cellular
maturation
(A) Classic (HPV +) vulvar intraepithelial neoplasia, Basaloid CA: nests and cord of small, tightly
(B) Differentiated (HPV -) VIN packed cells tha lack maturation and
resemble basal layer of normal epithelium
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 Warty CA: exophytic, papillary architecture J. VERRUCOUS CARCINOMA OF THE VULVA
and prominent koilocytic atypia
VIN Simplex
You can see that the
whole vulva is almost
already removed because
of the presence on
lesions seen on the
picture.
The tumor is situated
in an extensive area of
lichen sclerosus (white).
─ 70% of cases
─ Aka differentiated VIN You can see an outgrowth. The morphology is well
differentiated. It is almost normal but there are some
─ Pathogenesis:
lesions present.
Not HPV-associated  Pathogenesis:
Develops from long-standing lichen sclerosus HPV 6 or 11
or squamous cell hyperplasia  Gross features:
T53 involvement Large fungating mass resembling a giant
─ Gross features: condyloma acuminatum
Develops to keratinizing squamous cell  Microscopic features:
carcinoma Well-differentiated with large nests of squamous
─ Microscopic features: cells with abundant cytoplasm and small bland
VIN simplex: Marked atypia of the basal layer nuclei
of the squamous epitheliym and normal- Keratin pearls common
appearing differentiation of the more Mitoses rare
superficial layers Invades with broad tongues, and stromal interface
Keratinizing CA: nests and tongues of frequently exhibits a heavy infiltrate of lymphocytes
malignant squamous epithelium with and plasma cells
prominent central keratin pearls Rarely metastasizes

K. BASAL CELL CARCINOMA

They arise from the basal cells. You can see picket-
fencing because they are vertical in appearance. This
one is in the skin.
Palisade arrangement
• Identical to those in the skin
• Not associated with HPV
• Rarely metastasize
• Cured by surgical excision

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 L. MALIGNANT MELANOMA • Primary lesions of the vagina are rare; the most serious
of which is primary vaginal carcinoma.
• The end result of a multistep process that begins with
VIN (Vulvar Intraepithelial Neoplasia).
• The most common cancer of the vulva (86%).
• 2/3 of larger tumors are exophytic; the others are
ulcerative and endophytic.
• Pruritus of long duration is commonly the first symptom;
Others: ulceration, bleeding, and secondary infection.
Grow slowly, and then extend to the contiguous skin,
vagina, and rectum.

• Second most common cancer of the vulva (5%)

B. EMBRYONAL RHABDOMYOSARCOMA (SARCOMA
• Occurs at 6th and 7th decade of life BOTRYOIDES)
• Highly aggressive and poor prognosis
• Prognosis is linked to depth of invasion, with 60%
moratlity for lesions invading deeper than 1 mm
• Highly metastatic
• 5-year survical less than 32%

 Pathogenesis:
Sun exposure
Usually seen in children. The origin in sarcoma is
Mutations in cell cycle regulators (p16/INK4a,
mesenchymal. It has a grapelike appearance. On
CDK4), pro-growth signaling factors (KIT, RAS, microscopic examination, those are supposed to be
BRAF), and telomerase rhabdomyocytes. Beneath the epithelium, the tumor
 Gross features: cells are crowded.
Initially, may resemble Paget disease both grossly • Botryoides, “grapes”
and histologically • Rare, vaginal tumor
ABCDE: Asymmetry, irregular Borders, variegated • Most frequently found in children and infants
Color, increasing Diameter, Evolution overtime  Gross features:
Radial growth – macular area Polypoid, rounded, bulky masses that have the
Vertical growth – raised area consistency of grapes
 Microscopic features:  Microscopic features:
Same as in skin melanoma Consists of primitive spindle rhabdomyoblasts with
Differentiated by its uniform reactiity withantibodies cross-striations
to S100 protein, absence of reactivity with ─ Rhabdomyoblast – immature type of skeletal
antibodies to cytokeratin,a nd lack of muscle
mucopolysaccharides, both of which are present in A dense zone of round rhabdomy-oblasts (the
Paget disease cambium layer) is present beneath the vaginal
Presence of invasive melanocytes with excessive epithelium
melanin production Deep to this layer the stroma is myxomatous and
shows fewer neoplastic rhabdomyoblasts
III. VAGINA
A. DEVELOPMENTAL ANOMALIES
• Septate, or double, vagina is an uncommon anomaly C. VAGINITIS SECONDARY TO TRICHOMONAS
VAGINALIS
that arises from failure of total fusion of the müllerian
ducts and accompanies a double uterus (uterus
didelphys).

T. vaginalis. You can see them on routine urinalysis.

• A large flagellated ovoid protozoan

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• Identified on wet mount preparations and pap smears produces macroscopically visible cystic dilations of
• Sexually transmitted and develops within 4 days to these glands.
weeks
• 25% of infected women are asymptomatic carriers
 Clinical features:
Heavy, yellow, thick, foamy discharge
Severe itching
Vulvovaginal discomfort
Dysuria
Dyspareunia
Vaginal and cervical mucosa has a fiery red
appearance, with marked dilatation of cervical
mucosal vessels resulting in a characteristic
colposcopic finding of “strawberry cervix”

IV. CERVIX
A. ANATOMY OF THE CERVIX
• Cervix – the inferior portion of the uterus that connects
the corpus to the vagina.
Exocervix – the exposed portion that protrudes into
the upper vagina and is covered by glycogen-rich
squamous epithelium
Endocervix - the canal that leads to the endometrial
cavity, lined by longitudinal mucosal ridges made of
fibrovascular cores lined by a single layer of
mucinous columnar cells.
External os – the macroscopically visible junction
between the exocervix and endocervix
B. SQUAMOUS METAPLASIA IN THE
TRANSFORMATION ZONE
• The exocervix remodels continuously throughout life.
During embryonic development, squamous cells meets
the columnar epithelium of the endocervix to form the
initial squamocolumnar junction.
• In some young women, the SCJ is located at the internal
os.
• In most, the columnar epithelium extends onto the
exocervix, so the SCJ is also located on the exocervix.
The areas of the exocervix lined by columnar epithelium
are referred to as endocervical ectropion and appear as
reddish discolorations.
• With age, the columnar epithelium of the ectropion
undergoes squamous metaplasia, and the new
squamocolumnar junction is located at the internal os.

C. CERVICITIS
A microscopic view of the squamocolumnar junction. The endocervix is
lined by a single layer of columnar mucus-producing cells that abruptly
meets the exocervix lined by mature squamous cells. In specimens in
which the squamocolumnar junction is on the ectocervix or in the
endocervical canal, the region between it and the external os is called
the transformation zone.

It is important for you to know that there are to lining

epithelium. The squamocolumnar junction is very
important because of its reference with the
transformation zone.

• Squamocolumnar junction – the microscopic anatomical
junction of the squamous and mucinous columnar
epithelia
• Nabothian cysts – when the outlet of the endocervical
glands become blocked, mucin is retained and
There is inflammation of the cervix. In this particular
picture, you can see the lining epithelium and a
lymphoid follicle. It is predominantly lymphocytic.
 Pathogenesis:
Endogenous vaginal aerobes and anaerobes

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 Streptococcus, Staphylococcus, Enterococcus
Chlamydia trachomatis
Neisseria gonorrhea
HSV 2
Sexually transmitted
Introduced by foreign bodies, such as tampons,
pessaries, and toys
 Gross and Microscopic features:
Acute cervicitis – cervix grossly red, swollen,
edematous with copious dripping from the external
os
Extensive infiltrate of PMNs and stromal edema
Chronic cervicitis – hyperemic mucosa and This is related with HPV 16. You have inactivation of
the suppressor genes.
epithelial erosion
Stroma infiltrated by lymphocytes and plasma cells
F. CARCINOMA OF THE CERVIX
Metaplastic squamous epithelium of the INCIDENCE:
transformation zone may extend into cervical • 50 years ago – leading cause of cancer death in women
glands, forming clusters of squamous epithelium, PAPs – increase frequency of detection of early
which must be differentiated from carcinoma cancers and precancerous conditions
Followed by colposcopy
D. ENDOCERVICAL POLYP
• Endocervical polyps are the most common cervical Then biopsy for definitive diagnosis
growths
• They appear as single smooth or lobulated masses, PAP colposcopy biopsy
usually under 3 cm in greatest dimension.
• They typically manifest as vaginal bleeding or discharge.
because of this, in the presence of atypical cells,
• The lining epithelium is mucinous, with variable the doctor will now make a biopsy so there is early
squamous metaplasia, but may feature erosions and detection and management. The lesion is not
granulation tissue if women are symptomatic. advanced yet (maybe still in dysplasia)
George Papanicolaou - the greek pioneer in
cytopathology and early cancer detection and
inventor of the “pap smear”; also include
precancerous cellular detection.

INCIDENCE OF CARCINOMA AMONG WOMEN:

1. Lung
2. Breast
3. Colon
4. Pancreas
5. Ovary
6. Lymph nodes
There is a projection from the mucosa. You will have 7. Blood
to know where it came from. In the picture above, you 8. Cervix
still have the mucosa but there is a marked fibrous
stroma. RISK FACTORS:
• Simple excision or curettage is curative.
• Early age at first intercourse
• Cancer rarely arises in an endocervical polyp (0.2% of
• Multiple sexual partners
cases).
• Increased parity
• Male partner with multiple previous partners
E. FLORID CONDYLOMA OF THE CERVIX • Presence of carcinoma-associated HPV
• Condyloma acuminatum on the cervix, visible with the
• Persistent detection of high risk HPV in high
naked eye as cauliflower-like excrescences.
concentration (Viral Overload): most important
High risk (specific types)= 16, 18, 31, 33, 35, 39,
45, 51, 52, 56, 58, 59, 68

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 Low risk (Condylomata) = 6, 11, 42, 44, 53, 54, 62,
66
(HPV is associated with cancer in general; and
cancer of the cervix in particular.)
• Certain HLA and viral subtypes
• Exposure to oral contraceptives and nicotine
• Genital infections (chlamydia)
• Factors other than HPV: co-carcinogens
• factors that act in concert), immune status and nutrition
(These will influence whether HPV will remain
subclinical, becomes pre-cancerous or progresses to
CA)
Remember there are general etiologies of cancer.
Radiation, viral infection, bacterial infection.
If the immune status is weak then the person is
susceptible.
e.g. putting the etiologies together will determine if
HPV will remain subclinical, precancerous, or
progress to carcinoma.
If the immune status and nutrition is good but the
patient had HPV infection, will they become
precancerous? They are no other co-carcinogens or
exposure to chemicals and radiation so it will just be
subclinical (no presentation).
PRECURSOR LESIONS
Cervical CA arises from precursor lesions
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Intraepithelial neoplasia meaning it remains in the
epithelium. No invasion of the basement
membrane.
1) They represent a continuum of morphologic
changes with indistinct boundaries
2) They do not invariably progress to cancer and may
spontaneously regress
Mild to moderate dysplasia will not invariably
develop CA. It can even spontaneously
progress.
3) Associated with papilloma viruses
─ Eg. Overexpression of certain oncogenic
proteins (E6, E7) in HPV (16, 18)
p53 and BAX are tumor suppressor genes. In
their presence, there is supposed to be
apoptosis. P53 can also influence p21. You have
cyclin dependent kinases and retinoblastoma
protein(regulator of cell cycle). Normally, there
will be growth arrest. Suppose you have HPV E6
affecting p53. Because of that, the process will be
disrupted. The tumor will develop and keep on
growing because there will be no apoptosis and
growth arrest.
When there are genetically damaged cells, they
are not supposed to grow. The tumor suppressor
genes will act on them.
If there is damage to the DNA or there is hypoxia,
p53 is activated. Therefore there will be repair to
bring them back to normal.
4) Begins at the squamo-columnar junction
5) Cell Alterations in dysplasia and cancer are
qualitatively similar and remain constant
─ Dysplasia (can be graded to mild moderate
severe),
Mild dysplasia = CIN I
Moderate = CIN II
Severe = CIN III
─ CIN (I, II, III/CIS)
Cervical intraepithelial neoplasia
which is now vaginal CIS 1,2, or 3 or
carcinoma in situ
─ Microinvasive cancer
─ Invasive Cancer
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 ─ Stimulates apoptosis and also p21.

6) Eradication of dysplasia or cancer in situ will

prevent the development of invasive cancer
Go back to the Pap’s smear. If the cytology
smear shows mild dysplasia, and when
checked actually showed moderate to severe
dysplasia what will we do? It will lead the doctor
to do biopsy.

TYPES OF TRANSFORMING GENES

• Reserve cells in the transformation zone are continuous

with the basal cells of the ectocervix and may undergo
columnar and squamous differentiation (metaplasia)

EPITHELIAL CHANGES IN THE CERVICAL

TRANSFORMATION ZONE

• Suppressor Genes – negative regulators of cell growth

(anti-oncogenes)
Eg. RB protein – regulator of cell cycle
P53 – “guardian of the genome”
─ Acts as transcription factor
─ Prevents propagation of genetically damaged
cells
─ Blocks cell cycle progression
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The transformation zone goes down and the columnar cells become
exposed to acidic vagina. There will be reserve cell hyperplasia and
squamous cell metaplasia that goes back at the post-menopausal
period
CERVICAL CANCER CLASSIFIED IN DIFFERENT
WAYS:
• Dysplasia/carcinoma in situ system – the oldest; mild
dysplasia on one end and severe dysplasia/carcinoma
in situ on the other
• Cervical intraepithelial neoplasia (CIN) classification –
mild dysplasias termed CIN grade 1 and carcinoma in
situ lesions termed CIN III
CIN I – with koilocytotic atypia, contains abundant
papillomavirus nucleic acids
CIN II – with progressive atypia in all layers of the
epithelium
CIN III (carcinoma in situ) – with diffuse atypia and
loss of maturation
• Low-grade and high-grade intraepithelial lesions
Raised lesions (acuminatum) – contain low-risk
HPV
Flat CIN – usually contain high-risk HPV
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Dysplasia System
• Disordered growth; atypical epithelial hyperplasia
• Does not necessarily progress to cancer (mild to
moderate dysplasia maybe reversible)
• Severe dysplasia frequently antedates cancer
Bethesda System
We have dysplasia system, CIM system, and now we
have this system. It incorporates all these system.
• Low grade squamous intraepithelial lesion (LSIL) =
HPV/mild dysplasia/CIN 1
Associated with a productive HPV infection
High level of viral replication and only mild
alterations in the growth of host cells
Does not progress directly to invasive carcinoma
and in fact most cases regress spontaneously
• High grade squamous intraepithelial lesion (HSIL) =
Moderate & Severe dysplasia /CIN2 & CIN3/CIS
Progressive deregulation of the cell cycle by HPV
which results in increased cellular proliferation,
decreased or arrested epithelial maturation, and a
lower rate of viral replication
Derangement may become irreversible and lead to
a fully transformed malignant phnotype
DIAGNOSIS
• Cytology detects possible presence of cancer. It is
effective in preventing cervical cancer because majority
of cancers are preceded by a long-standing
precancerous lesion. This lesion may exist in the
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 noninvasive stage for years and shed abnormal cells • Colposcopy
that can be detected on cytologic examination. the doctor will be able to take a biopsy
• Schiller’s test or Schiller’s Iodine test is a medical test in
which Lugol’s iodine solution is applied to the cervix in
order to diagnose cervical cancer. Normal cervical
mucosa contains glycogen and stains brown, whereas
abnormal areas, do not take up the stain. The abnormal
areas can then be biopsied and examined histologically.
Schiller’s test is not specific for cervical cancer.

Swede Score for interpreting colposcopy findings

Score 0 1 2
Uptake 0 or Shady, milky Distinct,
of acetic transparent stearin-like
acid
A. Normal – either red or blue.
Margins 0 or diffuse Sharp, but Sharp and
B. Koilocytes.
C. CIN II and irregular, even
D. CIN III surface jagged, difference in
• As the stage increases, there is reduction in the “geographical” surface level
cytoplasm and the increase in the nucleus-to-cytoplasm satellites such as
ratio, which occurs as the grade of the lesion increases. “cutting”
This reflects the progressive loss of cellular Vessels Fine, Absent Coarse or
differentiation on the surface of the lesions from which regular atypical
these cells are exfoliated. Lesion <5mm 5-15 or >15mm or
size spanning 2 spanning 3-4
quadrants quadrants or
endocervically
undefined
Iodine Brown Faintly or Distinct yellow
staining patchy yellow

POSTULATED STEPS IN CERVICAL NEOPLASIA

Figure. Interrelations of Naming Systems in Premalignant Cervical

disease MICROINVASIVE CARCINOMA
• Earliest stage (Ia) of invasive cervical cancer
• • Arises from overlying CIN

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• About 7% show focal microinvasive cancer • Appearance similar to small-cell carcinoma of the lung;
• Staging based on width and depth of invasion however, in contrast to the lung tumor, cervical small-
• Invasion less than 3mm (stage Ia1) or 5mm (stage Ia2) cell carcinomas are positive for high oncogenic risk
below basement membrane HPVs.
• 7-mm maximum lateral extension
STAGING
INVASIVE CARCINOMA Stage 0 Carcinoma in situ (CIN III)
 Pathogenesis:
Stage I Carcinoma confined to cervix:
Gross features: Fungating, ulerating, infiltrative
Ia. Preclinical carcinoma (diagnosed only
Microscopic features: Squamous cell carcinoma
by microscopy)
(75-90%)
Ia1. Stromal invasion is 3mm
• Clinical features: Leukorrhea, bleeding, pain on coitus,
(microinvasive carcinoma)
dysuria
Ib. Histologically Invasice Carcinoma
• Spread/ Metastases:
confined to cervix > Ia2
Direct (contiguous) = uterus, vagina, peritoneum,
urinary bladder, ureters, rectum
Stage II Carcinoma extends beyond the cervix but
Lymph nodes, hematogenous
not onto the pelvic wall.
Lungs, bones
Carcinoma involves the vagina but not the
OTHER MORPHOLOGIC TYPES: lower thrid.
Adenocarcinoma (5-15%) Stage III Carcinoma has extended onto pelvic wall.
Stage IV Carcinoma has extended beyond the true
pelvis. This stage obviously includes
metatastic dissemination.

• HPV (16, 18 and 45) infection found in most

• Endometrial adenocarcinoma is an important
consideration in differential diagnosis
If adenocarcinoma is in the cervix, you have to
identify if it is primary or just merely an extension.
• Cervical adenocarcinoma- second most common tumor
type (15% of cervical cancer)
• Proliferation of glandular epithelium
• Composed of malignant endocervical cells with large,
hyperchromatic nuclei
• Mucin-depleted cytoplasm, resulting in dark appearance
of the glands
Neuroendocrine

• Atypical carcinoid tumor appearing as a small cell

carcinoma
• Rare

CCetC
PATHOLOGY: Diseases of the Vulva, Vagina, and Cervix 13 of 14
MD 2
 4. Most important risk factor in developing cervical
cancer
A. Early age of first intercourse
B. Multiple sex partners
C. High-risk HPV detection
D. Cigarette smoking

5. Most commonly found in infants with a gross feature

of polypoid, rounded, bulky masses that have the
consistency of grapes.
A. Sarcoma botryoides
B. Invasive melanoma
C. Adenocarcinoma
D. Basal cell carcinoma

BCCCA

PROGNOSTIC FACTORS
• Clinical stage
• LN status (size of largest LN and number of positive
LNs)
• Size of primary tumor
• Depth of invasion
• Ebdometrial invasion
• Parametrial involvement
• Blood vessel invasion
• Microscopic grade/type

REVIEW QUESTIONS

1. A 29-year-old single woman with a history of having

several sexual partners during the past 10 years
receives a routine pelvic examination. A Pap smear
followed by a cervical biopsy revealed a high grade
intraepithelial neoplasm. What are her risk factors for
cancer?
A. Infection with HPV 6 or 11
B. High production of proteins E6 and E7 by HPV
C. High production of proteins E1 and E2 by HPV
D. Co-infection with HSV-2 or gonorrhea

2. HPV found in adenocarcinoma

A. HPV 12
B. HPV 54
C. HPV 45
D. HPV 21

3. CIN corresponding to carcinoma in situ

A. CIN I
B. CIN II
C. CIN III
D. CIN IV

CCetC
PATHOLOGY: Diseases of the Vulva, Vagina, and Cervix 14 of 14
MD 2