Cervix Flashcards
Follicular Cervicitis
- Caused by Chlamydia Trachomatis
- Treat with doxycycline
Risk factors:
* Sexually active
* OCP use
* Pregnancy
Micro:
* Lymphoid germinal centres in sub mucosa
* Plasma cells
* Reactive epithelial atypia
Endocervical Polyp
- Usually multigravidas in 4th to 6th decades
- Usually incidental findings
- Can present with vaginal bleeding
Macro:
* Rounded/elongated
* Smooth/lobulated surface
* Most commonly single
* Can measure from millimeters to a few centimeters
Micro:
* Varying amounts of squamous oit endocervical epithelium
* Depends on proximity to cervical os.
* Stroma consists of fibroconnective tissue
* Thin and thick walled vessels
Microglandular hyperplasia
- Benign non-neoplastic endocervical glandular proliferation
Clinical:
* Incidental finding
* Women of reproductive age
* Associated with OCP, pregnancy and postpartum condition
Macro:
* polypoid lesions
* single or multiple
Micro:
* Crowded glands
* Variable amount of mucin
* Focal squamous metaplasia
* Signet ring cells may be present
* Neurophils are commonly present in the glandular lumina
* Stoma separating glands shows acute and chronic inflammatory cells
IHC:
* CEA generally negative
* Mucin +ve
Tunnel Clusters
- Incidental finding
- Lobular aggregates of benign endocervical glands in cervical wall
Two Types:
Type A
* Small noncystic glands
* May show gastric metaplasia in up to 15% of cases
Type B
* Cystically dilated glands
- No risk of recurrence or malignant transformation
IHC:
* PAX2+
* Alcian blue/PAS +ve in Type A if gastric metaplasia present
* CEA focal or -ve
Mesonephric remnants/hyperplasia
- Embryonic remnants of mesonephric ducts
- Usually incidental
- Typically in lateral cervical wall
Micro:
* Small tubules lined by low columnar to cuboidal cells without cillia
* Surrounded by prominent smooth muscle
* Oesinophilic material in lumens in characteristic
IHC:
* CD10+ (Luminal, patchy)
* Calretinin+
* GATA3+
- CEA -ve
- ER/PR -ve
- P16 -ve
Lobular Endocervical Glandular Hyperplasia (LEGH)
- Benign condition
- Metaplastic process
- NOT related to high risk HPV
- Typically –> upper endocervix and inner half of cervical wall.
Molecular:
* Can be associated with Peutz-Jeghers Syndrome
* Germline STK11/LKB1 mutations
Micro:
* Well demarcated lesion
* Lobular/Acinar architecture
* Composed of central crypt, sometimes with cystic dilation
* Surrounded by smaller, round shaped glands and cysts arranged in a floret-like pattern
* Lined by columnar cells with basal nuclei
* Mild nuclear atypia
IHC:
* CEA -ve
* ER and PR -ve
Diffuse Laminar Endocervical Hyperplasia
- AKA nonspecific hyperplasia
- Usually incidental finding
Micro:
* Diffuse proliferation of medium sized, closely packed glands
* Well differentiated, mucious glands
* Inner third of cervical wall
* Sharply demarcated
* Basal nuclei
* Chronic inflammation
* Stromal oedema
* No significant cytological atypia
IHC:
* CEA -ve
Low Grade Squamous Intraepithelial Lesion (LSIL)/CIN1
Includes:
* Flat, low grade squamous intraepithelial lesion/CIN 1
* Exophytic/Papillary LSIL (condyloma)
Cause:
* Low grade –> HPV 6, 11 (low risk), HPV 16, 18 (high risk)
* Koilocytes in upper layers are characteristic
* Majority of LSIL regress spontaneously
High Grade Squamous Intraepithelial Lesion (LSIL)/CIN 2 and 3
- High risk HPV driven pre-cancerous lesion
- HPV 16 is most common
- Also HPV 18
Micro:
CIN 2:
* Superficial cytoplasmic maturation in the upper third of mucosa
* High rate of regression
CIN 3:
* Marked, full-thickness atypia
* Increased mitotic activity and atypical mitoses
* Highest risk of progression to SCC
Treatment:
Surgical excision –> unless pregnant or CIN 2 in <25yo
Staining:
p16 IHC
* Good surrogate test fot HPV in anogenital carcinomas/pre-malignant lesions.
* Positive p16 –> strong continuous nuclear and cytoplasmic staining
* Negative p16 –> cytoplasmic only staining
HPV ISH
* High specificity
* Relatively low sensitivity compared to p16 IHC
LAST Project
- Lower Anogenital Squamous Terminology
Recommendations for p16 IHC:
* To distinguish HSIL from mimickers –> atrophy, Immature metaplasia
* Morphological CIN 1 vs 2
* Professional disagreement on diagnosis when HSIL is in consideration
* Biopsies showing LSIL or lesser in patients at high risk for missed HSIL based on prior pap or HPV testing
Warning:
* HPV independant p16 overexpression seen in ovarian and uterine serous carcinomas
Adenocarcinoma in situ
- AKA High grade cervical glandular intraepithelial neoplasia (HG-CGIN)
- Precursor for invasive endocervical adenocarcinoma.
- Associated with high risk HPV
- Seen in 3rd or 4th decade
Micro:
* Normal glandular architecture is preserved
* High N:C ratio
* Mitotic activity and apoptotic bodies
IHC:
* p16+
* CEA+
* Mucin+
Types of cervix Ca
SCC
75-80%
HPV-associated
Adenocarcinoma
20-25%
-
HPV associated (90%)
-Usual type endocervical adenocarcinoma
-Intestinal type
-Signet ring cell type
-Villoglandular carcinoma -
Non-HPV associated (10%)
-Gastric type endocervical adenocarcinoma
-Clear cell carcinoma
-Mesonephric carcinoma
Squamous Cell Carcinoma of Cervix
Can be microinvasive or invasive
Risk Factors:
* HPV
* HIV
* Smoking
* Younger age at first sexual intercourse
* Greater number of sexual partners
* OCP >5yrs
* 4+ full term pregnancies
* STIs
Macro:
* Microinvasive: Red papule, White plaque or irregular ulcerated lesion
* Invasive: Exophytic papillary mass or endophytic ulcer. Usually solitary
Micro:
* Usually associated with high grade dysplasia or CIS
* Full-thickness involvement of epithelium or cervical glands
* Pleomorphic, high N:C ratio and mitotic activity
* Variable degree of squamous differentiation including keratin pearls
Microinvasive:
* Tumour depth <3mm
* Measured from basal layer of overlying surface epithelium to deepest invasion by tumour
* If invasion present only adjacent to an involved gland –> measure from top of gland to deepest invasion.
Invasive:
* Greater than 3mm in depth of invasion
* Generally greater than 7mm in diameter
Types:
* Keratinising
* Non-Keratinising
* Basaloid
* Verrucous
* Warty
* Papillary
* Lymphoepithelioma-like carcinoma
IHC:
* p16
* Cytokeratin and p63 positive
* CEA focally positive
* Mucin negative
Endocervical Carcinoma
HPV-Associated:
- 80% of cases
- Younger patients (4th decade)
- Smaller tumour, Lower stage, Negative margins
- Better prognosis
Mutations:
* PIK3CA
* KRAS
Micro:
* Floating mitotic figures/apoptotic bodies visible on scanning magnification.
* Silva pattern relevant for prediciting LN involvement
* Positive for p16 and HPV ISH
Non-HPV-Associated:
- 20% of cases
- Older patients (5th decade or higher)
- Larger tumour size, Higher stage, Propensity for positive margins
- Poor prognosis
Mutations:
* TP53
* KRAS
* ERBB2
* STK11
Micro:
* Lack of floating mitotic figures/apoptotic bodies visible on scanning magnification.
* Silva pattern NOT relevant
* Usually negative for p16 and HPV ISH
- Referral to hereditary cancer program for suspected Peutz-Jegher Syndrome
Gastric type adenocarcinoma
- Non-HPV
- Negative for p16
- Gastric type differentiation
- Clear to eosinophilic cytoplasm
- Nuclear atypia
- Atypical glands extend below the normal level expected for benign endocervical glands
- Grading is not recommended –> even well-differentiated tumours behave aggressively
- worse prognosis
Minimal Deviation Adenocarcinoma:
- A well-differentiated gastric type adenocarcinoma.
- Ususally sporadic
- Can be associated with Peutz-Jeghers –> Germline STK11 mutation
Micro:
- Diagnosis made on the basis of abnormal location of these glands –> deep in the wall of the cervix (>5mm)
- Increased number of glands at the surface
- Stomal desmoplasia may be present
- Tumour cells have tall apical mucin
- May have foamy cytoplasm
- Basally located nuclei
- Variable mitotic activity
- May have intestinal differentiation –> Goblet cells, paneth0like neuroendocrine cells
IHC:
* p16 negative
* p53 aberrant/mutant –> diffuse or completely absent
* CEA/mCEA –> Diffuse or focal
* CK7 +
* PAX8 +
