Nursing lecture

1. Pathology of Female Reproductive System

2. Vulvo-Vaginal Leukoplakia (white plaques)
Lichen sclerosus
Autoimmune disease results in atrophic
epidermis dermal fibrosis and mild
perivascular, mononuclear inflammatory
infiltrate. In symptomatic cases 1% to 5%
develop squamous cell carcinoma
Squamous hyperplasia
Chronic irritation and pruritus leads to
hyperplastic epidermis; no epithelial
atypia and dermal inflammatory infiltrate
with no increased predisposition to cancer
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3. Condylomas – Vulvar Warts
Condylomata lata:
Flat, slightly elevated lesions, in secondary syphilis
Condylomata acuminate:
More common, papillary and elevated lesions on
anogenital surface, strongly associated with HPV
subtypes 6 and 11.Single or multiple, many cm in
diameter, red-pink to pink-brown in color
Epidermal cells shows koilocytosis (large cells with
perinuclear cytoplasmic vacuolization and wrinkled
nuclei) a hallmark of HPV infection, do not commonly
progress to cancer
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4. Malignant Lesions of Vulva
Paget Disease of the Vulva
Clinically; red, scaly plaque
Histology; proliferation of large malignant
epithelial cells within the epidermis having
abundant clear PAS positive cytoplasm, usually
with no underlying carcinoma
Squamous cell carcinoma
Precursor; Vulvar intraepithelial neoplasia (VIN)
HPV-related vulvar squamous cell carcinomas
Non-HPV-related vulvar squamous cell
carcinomas, often associated with lichen
sclerosis
Melanoma of Vulva
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5. Vaginal Lesions
Vaginitis: Common causes; Candidiasis & Trichomoniasis
Squamous Cell Carcinoma: Rare, occurs above 60 years of
age, nearly always associated with HPV infection
Clear Cell Adenocarcinoma: Very rare, seen in few young
women whose mothers took diethylstilbestrol during
pregnancy for threatened abortion
Embryonal Rhabdomyosarcoma (Sarcoma botryoides):
Rare primary vaginal cancer, manifests as soft polypoid
masses, usually in infants and children younger than 5 years
of age

6. Normal Histology of Cervix
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7. Non-neoplastic Lesions of Cervix conti….
Cervicitis: Acute and
Chronic Non-specific and
Chronic Granulomatous
Cervicitis (TB)
Cervical erosions
Endocervical
microglandular hyperplasia
Nabothian cysts
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8. Non-neoplastic Lesions of Cervix
Endocervical polyp: Up to few
centimeters, surface smooth, soft and
shiny, stroma contain cystically dilated
spaces lined by endocervical columnar
epithelium
Ulcerations and superimposed chronic
inflammation may lead to squamous
metaplasia of the surface epithelium, no
malignant potential

9. Cervical Intraepithelial Neoplasia (CIN)
A precancerous lesion, usually precedes, an invasive cancer by many years,
sometimes decades
Peaks incidence, 30 years of age, whereas carcinoma about 45 years
Pathogenesis: HPV-related carcinogenesis
Histological Types/Grades of CIN
CIN I; epithelial dysplasia, lower third & koilocytosis in superficial layers
CIN II; epithelial dysplasia extends to middle third with supra basal cells
layer mitoses and koilocytic change
CIN III; epithelial dysplasia full thickness, normal/abnormal mitoses,
koilocytotic change usually absent
Clinically CIN is divided into LSIL (CIN I) and HSIL(CIN II and CIN III)

10. Spectrum of CIN
Koilocyte ISH Ki-67 p16INK4

11. Cervical Neoplasia
Risk factors for cervical carcinoma includes;
1. Early age at first intercourse
2. Multiple sexual partners
3. High parity
4. Cigarette smoking
5. Use of oral contraceptives
6. Certain HLA subtypes
7. Immunodeficiency
8. Infection by "high-risk" Human Papilloma Viruses HPV(16,18, 45,
31, and others)
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12. Invasive Carcinoma of the Cervix
Histologic types:
Squamous cell carcinoma (75%)
Adenocarcinoma, adenosquamous carcinoma (20%)
Small cell neuroendocrine carcinoma (less than 5%)
Etiology: Majority carcinomas are caused by HPV
Squamous cell carcinoma;
Peak incidence at the age of about 45 years, some 10 to 15 years after
detection of precursor CIN
Progression of CIN to invasive carcinoma is variable and unpredictable and
requires HPV infection as well as mutations in genes LKB

13. Invasive Carcinoma of the Cervix
Risk factors for cervical carcinoma are related to;
1. Exposure to high-risk HPV types 16, 18, 31, & 33
2. Early age at first intercourse
3. Multiple sexual partners
4. Cigarette smoking
5. Human immunodeficiency virus infection

14. Cervical Neoplasia
Pathogenesis
HPV E6 & E7 proteins cause inactivation of
p53 & RB genes, resulting in increased
cell proliferation and suppression of
apoptosis
Loss of LKB1 gene is also involved
High-grade CIN (II & III) contain HPV
incorporated into the cell genome
Not all HPV infections progress to CIN III or
invasive carcinoma it may take 10 years or
more
HPV vaccine is effective in preventing
infection due to HPV16 &18
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16. Carcinoma Cervix
Gross Features
Tumors may be invisible or exophytic encircling the
cervix and penetrating into the underlying stroma
produce a "barrel cervix," which can be identified by
direct palpation
Application of acetic acid to the suspected area of
the cervix highlights abnormal areas as white,
confirm by biopsy

17. Carcinoma Cervix
Microscopic Features
Squamous cell carcinoma keratinizing or non
keratinizing type,
Graded as 1 to 3 on cellular differentiation
Microinvasive carcinoma; stromal invasion no greater
than 3 mm and no wider than 7mm
Spread to pelvic lymph nodes is determined by tumor
depth and the presence of capillary-lymphatic invasion
Distant metastases; including para-aortic lymph nodes
or remote organ involvement
Local spread; invasion of adjacent structures such as
bladder or rectum and extension into the parametrial soft
tissues can fix the uterus to the pelvic structures
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18. Staging of Carcinoma Cervix
Stage 0. Carcinoma in situ (CIN III)
Stage I. Carcinoma confined to the cervix
Stage II. Carcinoma extends beyond the cervix but not onto the pelvic wall/
involves upper two third of the vagina
Stage III. Carcinoma has extended onto pelvic wall/ involves the lower third
of the vagina
Stage IV. Carcinoma has extended beyond the true pelvis; metastatic
dissemination or has involved the mucosa of the bladder or rectum
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19. Self-Assessment
Q1.Identify the organs and give stage
of the cervical cancer as shown in
this image.
Q2. What is the histologic type
of this cervical carcinoma
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20. OVARIES

21. Ovarian Neoplasms
Fifth leading cause of cancer
mortality in women, originate from
three cell types of the ovary:
1. Multipotent surface epithelium
2. Totipotent germ cells
3. Sex cord– stromal cells
Surface epithelial 90% of ovarian
cancers
Germ cell and sex cord–stromal
cell tumors constitute 20% to 30%
of ovarian tumors

22. Frequency of Major Ovarian Tumors
Tumor Type % of Malignancy % of Bilaterally
Serous 40
•Benign (60%) 25
•Borderline (15%) 30
•Malignant (25%) 65
Mucinous 10
•Benign (80%) 5
•Borderline (10%) 10
•Malignant (10%) <5
Endometrioid carcinoma 20 40
Undifferentiated carcinoma 10 —
Clear cell carcinoma 6 40
Granulosa cell tumor 5 5
Teratoma 15
•Benign (96%)
•Malignant (4%) 1 Rare
Metastatic 5 >50
(Krukernberg tumor, mets from breast and lung cancers)
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23. Ovarian Surface Epithelial Tumors
Risk Factors:
• Null parity
• Family history
• Heritable mutations
• Unmarried
• Married with low parity
• Gonadal dysgenesis
• 5% to 10% of ovarian cancers familial, associated with mutations in
BRCA1, BRCA2 and p53 tumor suppressor genes
• Express HER2/neu
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24. Serous Ovarian Neoplasms: Morphology
Gross
Most , large, rounded cystic mass up to 30 to
40 cm in diameter
Benign tumors, serosal surface smooth and
glistening as compare to nodular irregularities
in the malignant
On cut section, unilocular to multilocular cystic
masses filled with a clear serous fluid
Cystic cavities shows papillary projections,
more prominent in malignant tumors

25. Serous Ovarian Neoplasms: Morphology
Microscopy
Benign; a single layer of tall columnar
epithelial cells lines the cyst cavity Psammoma
bodies in the tips of papillae
Malignant; multilayered lining
epihtelium,complex papillary pattern and nests
or sheets of malignant cells invade axial fibrous
tissue
Borderline; exhibit less cytologic atypia and no
stromal invasion Metastases; spread
into peritoneal cavity and periaortic lymph
nodes

26. Mucinous Neoplasms
Gross
Larger, multicystic masses, with mucinous
cystic contents
Capsular penetration and solid areas of
growth; suggestive of malignancy
Microscopy;
Cysts lined by mucin-producing columnar
epithelial cells
Malignant tumors; characterized by the
presence of architectural complexity,
including solid areas of growth, cellular
stratification, cytologic atypia and stromal
invasion

27. Endometrioid Tumors
Sometimes develop with endometriosis
15% to 30% of women have concomitant
endometrial carcinoma
Benign, borderline and malignant tumors
Gross
Solid or cystic masses
Microscopy
Tubular glands, similar to endometrium
Endometrioid carcinomas of ovary have
mutations in PTEN tumor suppressor gene
similar to endometrioid carcinoma of uterus

28. UTERINE TUMORS
Dr. IMRANA TANVIR
Associate Professor of Pathology
Faculty of Medicine Rabigh KAU
2020
UTERINE
TUMORS

29. Endometrial Hyperplasia
Endometrial proliferation; glandular architectural abnormalities resulting in
glandular crowding, may give rise to either;
Simple Hyperplasia; gland to stroma ratio slightly increased greater than
1:1 with prominent variability in size of the gland, glandular budding and
cystic glandular dilatation
Complex Hyperplasia; crowded, architecturally complex glands with little
intervening stroma, the gland to stroma is elevated at least 3:1
Based on presence or absence of cytologic atypia it is further classified as;
- Simple hyperplasia with/without atypia
- Complex hyperplasia with/without atypia
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30. Simple Endometrial Hyperplasia
Tubular/Cystic without atypia With atypia
Thick soft folds of endometrium

31. Complex Endometrial Hyperplasia
With out atypia With atypia

32. Causes of Endometrial Hyperplasia
An excess of estrogen relative to progestin, if sufficiently prolonged or
marked, can induce exaggerated endometrial proliferation (hyperplasia), an
important precursor of endometrial carcinoma
Potential causes of estrogen excess:
Failure of ovulation (such as is seen in perimenopause)
Prolonged administration of estrogenic steroids without counterbalancing
progestin
Estrogen producing ovarian lesions (such as polycystic ovary disease and
granulosa-theca cell tumors)
Obesity, a common cause, as adipose tissue converts steroid precursors
into estrogens

33. Risk of Carcinoma in Endometrial Hyperplasia
Complex hyperplasia without cellular atypia; carries a low risk (less
than 5%)
Complex hyperplasia with cellular atypia; associated with higher risk
(20% to 50%)
In a significant number of cases, the hyperplasia is associated with
inactivating mutations in the PTEN tumor suppressor gene which is
believed to be one of several key steps in the transformation of
hyperplasia to endometrial carcinoma

34. Endometrial Polyp
Sessile, range from 0.5 to 3 cm in
diameter, may project into the uterine
cavity
Histologically, composed of normal to
cystically endometrial glands
resembling the basalis, frequently
with small muscular arteries
Clinically present with abnormal
uterine bleeding rarely risk of giving
rise to a cancer

35. Endometrial carcinomas
Peak age incidence 55 to 65 year, they classified into;
Type I (80%): Majority well differentiated (Endometrioid carcinoma); Grade1
Associated with estrogen excess, endometrial hyperplasia, inactivation of
DNA mismatch repair genes and PTEN tumor suppressor gene in 30-80%
Associated risk factors; Obesity, DM, HTN and Infertility
Type II (15%): Poorly Differentiated; Grade 3
Usually arise in the setting of endometrial atrophy, mutation in p53, and
PIK3CA, KRAS seen
Histological subtypes; Clear cell and Papillary serous carcinomas,
aggressive behavior
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36. Endometrioid carcinomas
Morphology
Gross; exophytic or infiltrative growth
Histology; Well defined glandular pattern,
graded I to III
Sub types, mucinous, tubal (ciliated),
squamous differentiation
May infiltrate myometrium and enter vascular
spaces
Metastasize to regional lymph nodes
Serous carcinomas, form small tufts and
papillae and exhibit much greater cytologic
atypia and behave aggressively

37. Leiomyomas
Most common benign tumor of uterine myometrium of smooth muscle origin
Affects 30% to 50% of women of reproductive age
Tumors monoclonal, associated with several different recurrent
chromosomal abnormalities, including rearrangements of chromosomes 6
and 12 that are also found in endometrial polyps and lipomas
Estrogens and possibly oral contraceptives stimulate their growth and these
tumors shrink in post menopausal

38. Leiomyomas
Gross
Circumscribed, firm gray-white single often multiple
masses with a characteristic whorled cut surface
Ranging in size from small nodules to large tumors
Intramural, submucosal or subserosal in location
Microscopy
Interlacing bundles of uniform smooth muscle cells
Foci of fibrosis, calcification, and degenerative
softening may be present

39. Leiomyosarcoma
Occur in postmenopausal women
Gross; Single, soft, hemorrhagic, necrotic masses
Microscopy; interlacing bundles of atypical
smooth muscle fibers
Diagnostic criteria of malignancy includes;
coagulative necrosis, cytologic atypia, and
increased mitotic activity
(increased mitotic activity alone and sometimes
cellular atypia can be seen in degenerated
leiomyoma)
Borderline category called; smooth muscle tumors
of uncertain malignant potential
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40. References
• Basic Pathology, 10th Edition 2017, Kumar, Abbas, Aster
• www.webpathology.com