Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

Female Genital & Breasts

Q.1) A lady of 22 years presents with discrete, solitary, freely movable nodule,
4cm in diameter. Histopathology of the nodule reveals fibroadenoma.
(a) Give its gross and microscopic morphology.
(b) Enumerate variables which influence prognosis of breast carcinoma.
ANS:
Morphology of fibroadenoma:
Gross
 Typical fibroadenoma is a small, solitary, well- encapsulated, mobile, spherical or
discoid mass.
 The cut surface is firm, grey-white, slightly myxoid and may show slit- like spaces
formed by compressed ducts.
 Occurs mostly in the upper quadrants of the breast.
Microscopic
 Fibrous tissue comprises most of a fibroadenoma.
 The arrangements between the fibrous part of the tumour and the glandular part
may produce two types of patterns which may coexist in the same tumour. These are
intracanalicular and pericanalicular patterns.
(i) Intracanalicular pattern is one in which the stroma compresses the ducts so
that they are reduced to slit-like clefts lined by ductal epithelium.
(ii) Pericanalicular pattern is characterised by encircling masses of fibrous stroma
around the patent or dilated ducts.
 The fibrous stroma may be quite cellular, or full of collagen. Sometimes, the stroma is
loose and myxomatous.
 Occasionally, the fibrous tissue in the tumour is scanty, and the tumour is instead
predominantly composed of ducts or acini and is termed tubular adenoma.
 If an adenoma is composed of acini with secretory activity, it is called lactating
adenoma.
 Juvenile fibroadenoma is an uncommon variant of fibroadenoma which is larger and
rapidly growing mass but fortunately does not recur after excision.

Variables which influence prognosis of breast carcinoma:

 Invasiveness

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 Distant metastases
 Lymph nodes metastases
 Tumour size
 Inflammatory carcinoma
 Lympho-vascular invasion
 Molecular subtype
 Histological subtype
 Histological grade
 Proliferative rate
 Estrogen and progesterone receptors
 HER2 expression

Q.2) Classify ovarian tumors. Enumerate the surface epithelial tumors of ovary
and give brief account on serous cyst adenoma.
ANS:
Classification of ovarian tumors:
1. Surface epithelial-stromal tumors
 Serous tumors
 Mucinous tumors
 Endometrioid tumors
 Clear cell tumors
 Transitional cell tumors
 Epithelial-stromal tumors
2. Sex cord-stromal tumors
 Granulosa tumors
 Fibromas
 Fibrothecomas
 Thecomas
 Sertoli-leydig cell tumors
 Steroid cell tumors
3. Germ cell tumors
 Teratoma
 Dysgerminoma
 Yolk sac tumour
 Mixed germ cell tumors
4. Metastatic cancers

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 Colonic (*Krukenberg’s tumour)

 Gastric
 Breast

Surface epithelial tumors of ovary:

 Enumerated.

Serous cyst adenoma:

It’s a benign surface epithelial-stromal tumour of ovary.
Pathogenesis
 Nulliparity, gonadal dysgenesis, family history, heritable mutations  serous cyst
adenoma
Morphology
Gross
 Large cystic masses filled with serous fluid
 Smooth and glistening inner lining
Microscopic
 Lined by a single layer of tall columnar ciliated epithelium, occasionally forming
micro-papillae.
Clinical features
 Lower abdominal pain
 Abdominal enlargement
 Urinary frequency, dysuria, pelvic pressure
 Treatment  surgical resection

Q.3) What are the risk factors of cervical carcinoma? Give the pathogenesis of
cervical carcinoma caused by HPV. Give the morphology of cervical carcinoma.
ANS:
Risk factors for cervical carcinoma:

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 First coitus at an early age

 Multiple sexual partners
 Male partner with multiple previous sexual partners
 High risk HPV infection (serotypes 16 and 18)
 Low socio-economic status
 Smoking
 Multiparity
 Oral contraceptives usage
 Immunosuppression

Pathogenesis of cervical carcinoma caused by HPV:

Above mentioned risk factors + persistent HPV infection (high risk HPV serotypes 16 and 18)
 infection of immature basal cells of the squamous epithelium at the cervical squamo-
columnar junction (transformation zone)  integration of the virus into the host genome
 expression of E6 and E7 proteins  inactivation of the tumour suppressor genes TP-53
and RB  CIN-1  CIN-2 and CIN-3  invasive cervical cancer  metastasis

Morphology of cervical carcinoma:

Gross
 Can be exophytic or infiltrative (diffuse)
Microscopic
1. Squamous cell carcinoma
 Consists of malignant squamous epithelium which can be keratinizing or non-
keratinizing.

2. Adenocarcinoma
 Glandular but no mucin production

3. Adeno-squamous carcinoma
 Malignant squamous cells mixed with glandular structures

4. Neuro-endocrine carcinoma
 Similar to small cell carcinoma lungs

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

Q.4) Classify tumors of ovary. Give the morphology of serous tumors of the
ovary. Enumerate the investigations for the diagnosis of serous tumour.
ANS:
Classification of ovarian tumors:
 Classified previously.

Morphology of serous ovarian tumors:

Gross
 Large cystic masses filled with serous fluid
 Benign cystadenomas have a smooth and glistening inner lining
 Cystadenocarcinomas may have small mural nodularities or papillary projections
Microscopic
 Benign tumors (cystadenomas)  lined by a single layer of tall, columnar, ciliated
epithelium occasionally forming micro-papillae
 Borderline tumors  mild atypia with complex micro-papillary epithelium. No
invasion.
 Malignant tumors (cystadenocarcinomas)  lined by multi-layered epithelium with
many papillary areas. Stromal invasion is present.

Investigations for serous ovarian tumors:

 Ultrasound of the abdomen and pelvis
 X-rays abdomen and pelvis
 Serum CA-125 levels
 Laparoscopy
 Exfoliative cytology

Q.5) A 60 years old nulliparous woman presented with the history of irregular
bleeding per vagina for more than two years. Past history of irregular
menstrual cycles is positive. Recently she has noticed weight loss.
(a) Diagnosis?
(b) Name other conditions that can produce irregular bleeding in this age

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

group.
(c) Tabulate the characteristics of different types of endometrial carcinoma.
ANS:
Dx: Endometrial Carcinoma
Other conditions that can produce abnormal bleeding at the age of 60:
 Endometrial atrophy
 Endometrial hyperplasia
 Endometrial polyps

Characteristics of different types of endometrial carcinoma:

Characteristics Type I (endometrial) Type II (serous)

Age 55-65 years 65-75 years
Clinical setting Unopposed Estrogen Atrophy
Obesity Thin physique
Hypertension
Diabetes
Morphology Endometrioid Serous
Clear cell
Mixed mullerian tumour
Precursor Hyperplasia Serous endometrial
intraepithelial carcinoma
Mutated genes PTEN, KRAS, PIK3CA TP-53, PIK3CA, CHD4

Behaviour Indolent Aggressive

Spreads via lymphatics Intra-peritoneal and lymphatic
spread

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

Q.6) A 30 years old female presented with pelvic pain for more than 8 months.
Sonography reveals left ovarian mass of 9 cm diameter. Cystectomy specimen
reveals unilocular mass filled by straw coloured fluid. Histological evaluation
shows that the cyst is lined by columnar to cuboidal epithelium showing
stratification at places. There is no nuclear atypia or stromal invasion.
(a) Diagnosis?
(b) How would you histologically differentiate b/w other types of the tumor
diagnosed.
(c) Name other cystic ovarian tumors.
ANS:
Dx: Ovarian serous cystadenoma (benign)
Histological differentiation:
 Benign tumors (cystadenomas)  lined by a single layer of tall, columnar, ciliated
epithelium occasionally forming micro-papillae
 Borderline tumors  mild atypia with complex micro-papillary epithelium. No
invasion.
 Malignant tumors (cystadenocarcinomas)  lined by multi-layered epithelium with
many papillary areas. Stromal invasion is present.

Cystic ovarian tumors:

 Mucinous cystadenoma
 Mucinous cystadenocarcinoma
 Endometrioid cystadenoma
 Endometrioid cystadenocarcinoma
 Immature teratoma
 Cystic mature teratoma (dermoid cyst)
 Brenner tumour

Q.7) A 25 years old woman presented with left breast mass which was non-
tender, firm and well circumscribed.
(a) Enumerate the likely causes for lump in this case.
(b) Discuss the relevant investigations to reach the diagnosis.
(c) Write the microscopic appearance of fibroadenoma.

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

ANS:
Likely causes of lump in this case:
 Fibroadenoma
 Cysts
 Hamartoma

Investigations for this case:

 Mammography
 Fine needle aspiration cytology (FNAC)
 Ultrasound
The 3 above mentioned procedures are used for all cases of breast lumps.

Microscopy of fibroadenoma:
 Described previously.

Q.8) Classify breast tumors. Give the risk factors for carcinoma breast. Give an
account of clinical staging of breast carcinoma.
ANS:
Classification of breast tumors:
Benign
1. Epithelial
 Ductal papilloma
 Pure adenoma

2. CT
 Neurofibroma
 Lipoma

3. Mixed
 Fibroadenoma
 Phyllodes tumor

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

Malignant
1. Non-invasive
 Ductal carcinoma in situ
 Lobular carcinoma in situ
 Intraductal papillary carcinoma
2. Invasive
 Invasive ductal carcinoma
 Invasive lobular carcinoma
 Medullary carcinoma
 Colloid carcinoma
 Paget’s disease

Risk factors for breast carcinoma:

Major factors
1. Geography  more in developed countries
2. Age  increased risk in women aged 30+
3. Family history  increased risk if a first degree relative has a breast cancer
4. Genetic factors  TP-53 mutations, BRCA1 and BRCA2 mutations, HER2/NEU
overexpression
5. Increased endogenous estrogen
 Early menarche
 Late menopause
 Late pregnancy
 Nulliparity
 Estrogen producing tumors
Minor Factors
1. Oral contraceptives usage
2. Lack of breastfeeding
3. Radiation exposure
4. Fibrocystic disease of breast
5. Obesity
6. High fat diet
7. Alcohol consumption
8. Cigarette smoking

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

AJC clinical staging of breast carcinoma:

 Stage 0  DCIS or LCIS (carcinoma in situ)

 Stage I  Tumour 2 cm or less in diameter. No nodal spread.

 Stage II  Tumour more than 2 cm in diameter. Regional lymph nodes involved.

 Stage III A  Tumour more than 5 cm in diameter. Regional lymph nodes involved on
same side.

 Stage III B  Tumour more than 5 cm in diameter. Supraclavicular and infraclavicular

lymph nodes involved

 Stage IV  Tumour of any size. With or without regional spread but with distant
metastasis.

Q.9) List the important germ cell tumors of the ovary. What are immature
teratomas? Briefly describe dermoid cyst or mature teratoma.
ANS:
Germ cell tumors of the ovary:
 Teratoma
 Dysgerminoma
 Yolk sac tumour
 Mixed germ cell tumors

Immature teratoma:
 Rare malignant ovarian germ cell tumor.
 It contains tissues (hair, muscles, bones, cartilage etc.) that resemble embryonal and
fetal tissues.
 Found mostly in young women (18 years old).

Dermoid cyst (mature teratoma):

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 Benign ovarian germ cell tumour which contain mature tissues from all three germ
cell layers (ectoderm, mesoderm and endoderm).
 Cystic and are lined by skin like structures, hence the name dermoid cyst.
 Found in young reproductive women.
Morphology
Gross
 Unilocular cysts containing hair and sebaceous material
 Lined by epidermis with protruding hair
 Tooth structures and calcifications are common in the wall
Microscopic
 Lined by stratified squamous epithelium.
 Sebaceous glands, hair and other skin structures are present.
 Cartilage, bone, bronchial epithelium, gastric epithelium, thyroid tissue and neural
tissue may also present.

Clinical features
 Can produce infertility
 Can undergo torsion
 Can cause limbic encephalitis
 Rarely transforms into malignant squamous cell carcinoma

Q.10) Enlist benign tumors of breast. Describe the gross and microscopic
features of fibroadenoma. Describe the etiology of carcinoma breast.
ANS:
Benign tumors of breast:
 Enumerated previously.
Morphology of fibroadenoma:
 Described previously.
Etiology of carcinoma breast:
Risk factors

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 Enumerated previously.
Pathogenesis
3 factors are involved in the development of breast cancer;
1. Genetic changes
 Mutations in proto-oncogenes and tumour suppressor genes.
(i) Overexpression of HER2/NEU proto-oncogene
(ii) RAS and MYC mutations
(iii) TP-53 and RB mutations
(iv) Inherited mutations  BRCA1 and BRCA2
(v) Li-fraumeni syndrome
(vi) Cowden syndrome

2. Hormonal changes
 Endogenous estrogen excess  stimulation of growth factors  tumour
development

3. Environmental factors
 Geography, diet, radiations etc.

Genetic changes + Hormonal imbalance + Environmental factors  Breast cancer

Q.11) What is dysfunctional uterine bleeding? Enumerate the causes of

dysfunctional uterine bleeding. Give morphology of endometrial hyperplasia.
ANS:
Dysfunctional Uterine Bleeding:
“Abnormal bleeding from the uterus in the absence of an organic uterine lesion.”
Causes:
1. Failure of ovulation (most common cause)
 Thyroid dysfunction, adrenal dysfunction, pituitary tumors
 Functioning ovarian tumors, polycystic ovarian disease
 Obesity, malnutrition, debilitation
 Physical or emotional stress

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

2. Inadequate luteal phase

3. Contraceptives

4. Endomyometrial disorders
 chronic endometritis
 endometrial polyps
 Leiomyomas

Morphology of endometrial hyperplasia:

Non-atypical hyperplasia
 Increased gland to stroma ratio
 Back to back glands with little intervening stroma
Typical hyperplasia
 Overall it is very similar to endometrial adenocarcinoma
 Complex proliferating glands with nuclear atypia
 Back to back glands with branching structures
 Disorientation of cells
 Open chromatin, prominent nucleoli

Q.12) Briefly discuss the pathogenesis of carcinoma cervix. Give an account of

staging of carcinoma cervix. Give morphology of carcinoma cervix.
ANS:
Pathogenesis of carcinoma cervix:
 Described previously.

Staging of carcinoma cervix:

Stage 0  Carcinoma in situ
Stage I  Carcinoma confined to the cervix
 Ia  pre-clinical carcinoma

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 Ia1  stromal invasion no deeper than 3 mm and no wider than 7 mm

 Ia2  stromal invasion no deeper than 5 mm and no wider than 7 mm
 Ib  greater invasion than stage Ia2
Stage II  carcinoma extends beyond the cervix but no to the pelvic wall. Involves the
vagina but not the lower third.
Stage III  extended to the pelvic wall and lower third of the vagina.
Stage IV  extended beyond pelvis to involve the bladder and rectum.

Morphology of carcinoma cervix:

 Described previously.

Q.13) Short note on endometriosis. (Read only)

ANS:
Endometriosis
“The presence of functioning ectopic endometrial glands and stroma outside the uterine
cavity.”
Occurs mostly in 3rd or 4th decades.
Can cause infertility, dysmenorrhea and pelvic pain. It may also invade the tissue in which
it’s present and cause severe complications e.g. invasion of intestinal wall.

Sites of occurrence:
Descending order of frequency;
 Ovaries
 Uterine ligaments
 Rectovaginal septum
 Cul de sac
 Pelvic peritoneum
 Intestines and appendix
 Cervical, vaginal and fallopian tube mucosa

Pathogenesis:

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

Not completely known. Proposed theories are;

1. The regurgitation theory
 Retrograde flow of menses  endometrial tissue implants at ectopic sites
 This theory can explain only endometriosis in the peritoneum.
2. The benign metastases theory
 Endometrial tissue spreads to distant sites via blood or lymphatics.
3. The metaplastic theory
 Endometrium arises from coelomic epithelium (mesothelium of pelvis or
abdomen).
 Mesonephric remnants may also give rise to ectopic endometrial tissue.
4. The extra-uterine stem cell theory
 Stem cells from the bone marrow differentiate into endometrium in various
ectopic sites.
 Latest theory.
Ectopic endometrial tissue express increased amount of inflammatory mediators and
estrogen which help it to survive in ectopic environment.

Morphology:
 Contains functioning endometrium which undergoes cyclic bleeding.
 Appears as red-brown nodules due to accumulation of blood.
 Lie on or just under the serosa.
 When ovaries are involved, the lesion may convert into a large blood filled brown
cyst (chocolate cyst).
 Seepage and subsequent organization of blood leads to fibrosis which further causes
adhesion of pelvic structures and sealing of fallopian tube etc.
 Histological diagnosis can be done if two of these three features are present; (i)
endometrial glands (ii) endometrial stroma (iii) hemosiderin pigment.

Clinical features:
Depend on the distribution of the lesions
 Discomfort in the lower abdomen
 Severe dysmenorrhea and pelvic pain
 Sterility
 Pain on defecation if rectum is involved
 Painful coitus if uterus is involved.

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 Female Genital & Breasts Pathology | Hasnat Hussain (Reus-11)

 Dysuria if bladder is involved.

Prepared By: Hasnat Hussain (Reus-11) 

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