Dysplasia
Dysplasia is change of phenotype (size, shape and organization of
tissue). This generally consists of an expansion of immature cells, with a
corresponding decrease in the number and location of mature cells.
Dysplasia is the earliest form of pre-cancerous lesion which
pathologists can recognize in a pap smear or in a biopsy. it can be low
grade or high grade.
The term dysplasia is typically used when the cellular abnormality
is restricted to the originating tissue and does not invade past the
basement membrane, as in the case of an early, in-situ neoplasm.
Carcinoma in situ represents the transformation of a neoplastic lesion to
one in which cells undergo essentially no maturation. In this state,
epithelial cells have lost their tissue identity and have reverted back to a
primitive cell form that grows rapidly and with abnormal regulation.
Of course, Invasive carcinoma is the final step in this sequence.
Dysplasia is characterized by four major pathological microscopic
changes:
• Anisocytosis (cells of unequal size)
• Poikilocytosis (abnormally shaped cells)
• Hyperchromatism (excessive pigmentation)
• Presence of mitotic figures (an unusual number of cells which are
currently dividing).
Metaplasia
Metaplasia (Greek: "change in form") is the reversible
replacement of one differentiated cell type with another mature
differentiated cell type that is more able to withstand the stresses it is
faced with.
When cells are faced with physiological or pathological stresses
(chronic physical or chemical irritation) they adapt by several ways, one
of them is metaplasia. If the stimulus that caused metaplasia is removed,
tissues return to their normal pattern of differentiation.
Thus metaplasia is not synonymous with dysplasia and is not
directly considered carcinogenic.
Pap smear Technique and Interpretation
A. FREQUENCY OF SCREENING:
 In USA the most recent recommendation is that first screen
should be 3 years after the onset of sexual activity Or before
age 21 (whichever comes first).
 ACOG(American College of Obstetricians and Gynecologists)
recommends annual Pap smear screening
American cancer society recommends every other year
screening when using liquid – based cytology
 After age 30, the interval between screening can be increased to
2-3 years .
 More frequent i.e. annual Pap smears are recommended for
women :
1) using DSE
2) Immunocompromised
3) Previous history of stage 2 or 3 cervical intraepithelial
neoplsia (CIN)
B. INTERPRETEATION OF RESULTS:
 The Bethesda guidelines recommend that 8000—12,000
squamous cells be obtained for conventional Pap smear but
only 5000 cells for a liquid- based sample.
 Cells can obscured by blood , mucous and inflammatory cells.
If more than 75% of the cells are obscured, the sample is
inadequate and a new sample must be tested.
 The presence of endocervical cells (at least 10) is required from
women older than 40 but it is not mandatory in those younger
than 40 years of age.
The pap smear can reveal one of the following:
1. Negative result: meaning the cells are normal
NILM: negative for intraepithelial lesion or malignancy
2. Atypical Squamous cells (ASC):
The Bethesda guidelines emphasize the ability to distinguish
between HSIL and LSIL. Overall it is thought that 10 – 30% of
women with a finding of ASC on a Pap smear have underlying
CIN grade 2 or 3, and 0.1% may have invasive cancer.
ASC falls into two different categories:
a. Atypical Squamous cells of Undetermined Significance
(ASC-US): It is estimated that 90 - 95% of all finding of ASC
fall into this category of ASC-US
 Women with a Pap smear result of ASC-US have a 5 -7%
chance of currently having CIN 2 and 3. On the other hand,
39% of women with CIN 2 or 3 have a previous finding of
ASC-US on Pap smear.
 ASC-US is associated with HPV in about 33 - 67% of
cases.
b. ASC-H: The category of ASC-H describes atypical cells that
are morphologically suspicious of HSIL but too few in number
to be considered an HSIL .
ASC-H is more highly associated with HSIL than ASC-US
and is the most common precursor lesion for CIN. Follow up of
women with a finding of ASC-H leads to diagnosis of CIN 2 &
3 in 68%.
3. Atypical Glandular Cells (AGC): These cells are further
subdivided according to whether they are: Endocervical,
Endometrial, Or not otherwise specified.
Finding AGC is relatively rare, occurring in 0.17- 1.8% of
all Pap smears. However, the presence of these cells has serious
medical implications because women with a finding of AGC have
9.7 times higher risk of progressing to CIN 2.
a) AGC favoring neoplasia: This finding may correspond
with high-grade lesions on tissue examination (27-96% of
the time)
b) Adenocarcinoma in situ (AIS): It corresponds with high
rates of advanced lesions on tissue examination.
4. Low-grade and High grade squamous intraepithelial
lesion (LSIL and HSIL): Studies have shown that the finding
of LSIL is more variable and less reproducible than HSIL and
repeatable in only 80% of smears. Bethesda guidelines further
specify (with features suspicious of invasion) when histological
evidence supporting cancer is present.
C. COUNSELING WOMEN WITH ABNORMAL PAP
SMEAR
Women with abnormal Pap smear findings should be
counseled that HPV infection has been linked with the
development of cervical cancer, and that HPV is the most common
viral STD, affecting up to 70% of the sexually active population.
Uterine fibroid (Uterine leiomyoma)
is a benign tumor composed of uterine muscles plus fibrous
connective tissue. It is common and present in 20% of all females. It is
more in Negros than in white women
It is of unknown cause and may be found outside the uterine organs
(Vagina, broad ligament, vulva)
Female sex hormones have been incriminated as a cause because it
rarely appears before puberty and after menopause. In addition, there is a
rapid growth during pregnancy, and is frequently seen in conditions
associated with hyperestrogenism that are not antagonized by
progesterone like anovulation, endometrial Polyps, and endometrial
hyperplasia.
Grossly: It is a firm round tumor of hypertrophied uterine wall. It has a
pseudo capsule which differentiates it from adenomyosis. Since its blood
supply is peripheral, the center is susceptible to degenerative changes.
Cross section of the tumor reveals a solid, smooth, pinkish or white
surface with whorl- like appearance.
Microscopically: It is composed of groups & bundles of smooth
muscles in a twisted whorl fashion, with some connective tissue .
Types:
1) Intramural (the commonest)
2) Sub
serous
myomas:
projecting
towards
the
peritoneal cavity ± pedicle
may reach a large size without
producing symptoms
3) Interligamentory tumor
4) Sub mucosal
5) Cervical
Fibroids may be single or multiple
The clinical presentation depends on the size, number and location of the
fibroid and could be one of the following:
1) Symptomless: discovered accidentally.
2) Abnormal uterine bleeding: heavy and prolonged.
It may be due to enlargement of uterine cavity by submucous
fibroids, increased vascularity of the tumor, or due to necrosis of
endometrium overlying the submucous myoma. Frequently,
myomas may be associated with polyps and endometrial
hyperplasia.
3) Inter menstrual bleeding in case of submucus fibroid
4) pain
a) reappearance of dysmenorrhea (congestive type) due to
increase vascularity
b) Backache incase of posterior fibroids of moderate size with
retroversion
c) Colicky pain in case of sub mucous uterus
d) can be caused by torsion
5) Degenerative changes
6) Abdominal distention
7) Pressure symptoms which include:
 edema due to pressure on vena cava
 urinary frequency due to pressure on bladder
 dyspnea
Degenerative changes of uterine fibroids:
Occur due to arterial, venous, secondary infections or malignant
transformation. There are several types:
1) Hyaline degeneration:
Here the tumor becomes soft and jellylike, the cells fuse
together and form a structureless esonophilic mass.
2) Cystic degeneration: Liquefaction may occur after menopause
leading to cystic cavity formation.
3) Red degeneration (Necrobiosis): could be diffuse or local.
Usually occurs in pregnancy or near menopause that leads to a
fibromyomatous pattern.
Pathology: There is thrombosis of peripheral vessels with absence
of cell nuclei. The blood vessels are distended with thin wall and
are engorged with R.B.C.s. Thus the tumor is stained red and
resembles raw meat.
It gives a fishy odor on cutting due to presence of fatty acids.
Cystic degeneration may occur in the center and the cyst becomes
full with greasy brown debris.
4) Fatty degeneration
5) Calcifications: Fat may be
deposited in fibroid which
undergoes saponification. Co3
and Po4 in blood react with the
soppy
mass
leading
to
deposition of CaCo3 and
calcium phosphate
Grossly: It has a gritty
appearance on cross section
A thin peripheral shell can be seen by X -ray
In addition to degenerative changes, complications of fibroids
include:
 Sarcomatous (malignant) changes Sarcomatous changes that
occur in 0.5% of fibroids, 2/3 of sarcoma of the uterus arise from
uterine fibroids.
 Necrosis
 Infection
 Atrophy
 Torsion
Differential diagnosis (of an abdominal mass)
o
o
o
o
Pregnancy
Ovarian tumor
Endometrial or cervical polyp
Adenomyosis
Treatment
A. Conservative for small and asymptomatic fibroid.
o Frequent U/S every 6 months.
o LH RH agonist
B. Surgical
o Myomectomy either by laparotomy or laparoscopy
o Hysterectomy
o Uterine artery embolisation
Endometrial hyperplasia:
Endometrial hyperplasia is when the endometrium becomes too
thick. It is not cancer but it can lead to cancer formation in some cases.
Etiology:
Endometrial hyperplasia most often is caused by excess estrogen
without progesterone. If ovulation does not occur, progesterone is not
made, and the lining is not shed. The endometrium may continue to grow
in response to estrogen. The cells that make up the lining may crowd
together and may become abnormal (This is called Hyperplasia).
Factors predisposing to endometrial hyperplasia:
 Postmenopausal women, when ovulation stops and progesterone
is no longer made. It can also occur during perimenopause, when
ovulation may not occur regularly.
 Long-term use of high doses of estrogen after menopause (in
women who have not had a hysterectomy) or estrogen like drugs.
 Irregular menstrual periods, especially associated with
polycystic ovary syndrome or infertility
Other risk factors include:




Age older than 35 years
White race
Never having been pregnant
Early onset of menarche
 Personal history of certain conditions, such as diabetes mellitus,
polycystic ovary syndrome, gallbladder disease, or thyroid disease
 Cigarette smoking
 Family history of ovarian, colon, or uterine cancer
 Obesity
Types of endometrial hyperplasia
Endometrial hyperplasia is classified as simple or complex. It is
also classified by whether certain cellular changes are absent or present as
typical or atypical respectively. These terms are combined to describe
the exact kind of hyperplasia:
 Simple hyperplasia
 Complex hyperplasia
 Simple atypical hyperplasia
 Complex atypical hyperplasia
Clinical presentation:
The most common sign of hyperplasia is abnormal uterine
bleeding.
o Bleeding during the menstrual period that is heavier or lasts
longer than usual
o Menstrual cycles that are shorter than 21 days (counting from the
first day of the menstrual period to the first day of the next
menstrual period)
o Any bleeding after menopause
Diagnosis:
o Transvaginal ultrasound may be done to measure the thickness of
the endometrium.
o Endometrial biopsy, dilation and curettage, or hysteroscopy is done
in cases suspicious of malignancy.
Treatment:
 many cases are treated with Progestin (orally, in an intrauterine
device, or as a vaginal cream). Duration of treatment depends on
the age of the patient and the type of hyperplasia.
Treatment with progestin may cause vaginal bleeding resembling
menstruation.
 If there is atypical hyperplasia, especially complex atypical
hyperplasia, there is an increased of cancer so Hysterectomy is
done. It is the best option for those who do not want to conceive.
Prevention of endometrial hyperplasia:
 Estrogen treatment after menopause should be combined with
progestin or progesterone.
 If there is irregular menstrual period combined oral contraceptive
pills may be recommended.
 Decrease weight if obese.