The Holy Organs Flashcards
(36 cards)
Tumours Associated With Endometriosis
Polypoid endometriosis
Endometrioma
Seromucinous borderline tumour
Endometrioid carcinoma of ovary
Clear cell carcinoma
Rarely: mesonephric-like carcinoma, adenosarcoma, ESS, somatically derived YST.
NB:
Once seromucinous borderline tumour invades it is classed as an endometrioid carcinoma.
Need to do MMR on all endometrioid carcinomas, both ovary and endometrial.
Classification of Ovarian Tumours
Surface Epithelial:
Brenner, seromucinous borderline tumour / endometrioid, clear cell, SBT / LGSC, HGSC
Germ Cell:
Teratoma, yolk sac tumour, dysgerminoma, choriocaricinoma, embryonal carcinoma
Sex-Cord Stromal:
Fibroma, fibrothecoma, AGCT, JGCT, SCTAT, sclerosing stromal tumour, microcystic stromal tumour, signet ring stroma ltumour, Sertoli-Leydig cell tumours, steroid cell tumour
Metastases
Misc: Small cell carcinoma of hypercalcaemic type, FATWO, gonadoblastoma
Gynae Biomarkers
ER, PR, HER2
p53, p16
MMR proteins
Tumour Syndromes Associated with Gynae Neoplasms
Hereditary breast and ovarian cancer (BRCA1/BRCA2)
Lynch syndrome (endometrial & ovary)
PJS (SCTAT, HPV independent cervical adeno)
DICER1 (SCCOHT)
FIGO Staging Tube / Ovary / Peritoneum
Features to Include from Macro:
Intact / Ruptured (and timing of rupture)
Omental biopsy
Perintoneal washings
FIGO STAGING
I - Limited to one or both ovaries / fallopian tubes
- substaged based on surgical spill and positive washings
II - Extension / implants on uterus / pelvic tissues below brim
III - LN involvement / peritoneal disease outside pelvis
IV - Distant metastases incl: positive pleural cytology, extension to liver / spleen / intestine, extraabdominal organs
Molecular Classification of Endometrial Cancer
Based on TCGA data the PROMISE risk classifier divided endometrial carcinom into four molecular groups:

1. POLE mutated (ultramutated ) (PCR / NGS)
2. MMR deficient (hypermutated) (IPX)
3. p53 mutant (CN high / “serous like” (IPX)
4. p53 WT / CN low / NSMP
FIGO Staging Endometrial Carcinoma
I : Confined to uterine corpus
IA < 50% myometrial invasion
IB > 50% myometrial invasion
II : Invasion of cervical stroma
III: Local / Regional spread
IIIA uterine serosa and / or adnexal structures
IIIB: vaginal and / or parametrial involvement
IIIC: Pelvic and / or paraaortic nodes
IV: Invasion of bladder / bowel / distant metastases
FIGO Grading Endometrial Carcinoma
High grade by definition:
Serous
Clear cell
Carcinosarcoma
Dedifferentiated and undifferentiated carcinoma
Endometrioid carcinomas
Grade 1
< 5% solid, non glandular, non squamous growth
Grade 2
5 - 50% solid, non glandular, non squamous growth
Grade 3
> 50% solid, non glandular, non squamous growth
NB:
Can increase grade by one if there is significant cytologic atypia. Also, some authorities suggest using a binary grading system (low - grade 1 / 2 and high = grade 3).
Sentinel Lymph Nodes in Endometrial Carcinoma
(sn) prefix if sentinel node
(it) suffix if ITC’s only
(mi) suffix if micrometastasis
Size criteria same as breast i.e.
ITC’s = < 0.2mm or < 200 cells
Micrometastasis = 0.2 - 2mm
Macrometastasis = > 2mm
Nodal Staging: pTNM / AJCC
N1 = regional nodal micrometastasis
N2 = regional LN macrometastasis or paraaortic nodes
pM = metastases to inguinal lymph nodes
Syntopic Reporting Elements in Endometrial Cancer
Specimen type
Site and size of tumour
Histologic subtype
FIGO grade
FIGO staging - depth of myometrial invasion, involvement of cervical stroma, involvement of uterine serosa, adnexal structures, parametria and vagina
MELF pattern of invasion
LVI
Peritoneal washings
Omental biopsy
Immunomolecular classification and biomarkers:
MMR (+/- methylation profile) and p53
ER / PR
FIGO Staging Cervix
I - Strictly confined to cervix (extension to corpus allowed)
IA substage based on depth of stromal invasion (3, 5 mm)
IB substage based on greatest tumour size (2, 4 cm)
II: Into upper vagina or parametria
III: Into lower vagina, pelvic side wall, hydronephrosis, pelvic and paraaortic lymph nodes
IV: Beyond true pelvis, bladder or bowel mucosa, distant organs
Discordance Cervical Histology and Cytology?
Do levels and review cytology
Discuss at MDM
Consider lesion elsewhere in lower anogenital tract and need for re-examination or re-biopsy
All else fails need to consider and exclude a specimen mix up
Benign Mimics of HSIL on Cytology
Atrophy (basal / parabasal cells only)
High sampling (LUS post LLETZ)
Squamous metaplasia
Reactive atypia
Radiation atypia
Endometrial cells
Mimics of LSIL on Cytology
Reactive atypia (associated with infections e.g. Candida, BV, trichomonas)
HSV viral cytopathic effect
IUD cells - degenerative vacuolar changes
Tubal and tuboendometrioid metaplasia
Endometrial cells
Why is P16 positive in HSIL
HR HPV (subtypes 16 / 18) integrate into host genome
Production of viral oncoprotein E7 which binds to RB causing it to degrade
Without RB acting as a brake on the cell cycle, the CDKN2A gene can continue to produce p16 protein
When overexpressed p16 causes downstream effects on cellular proliferation and increased cell survival
NB: E6 viral oncoprotien binds to p53 with similar downstream effects

How does p57 help in the diagnosis of molar pregnancy?
Poor interobserver variability between CHM, PHM and hydropic abortus on histology alone. Can use p57 IPX and FISH to distinguish these.
Partial mole:
p57 positive (nuclear expression in at least 10% of villous stromal cells and cytotrophoblasts)
NB: p57 also positive in normal fetus / hydropic abortus
FISH shows triploidy in partial mole
Complete mole:
p57 negative
FISH shows diploidy (diandric)
P57 negative in CHM because p57 is a paternally imprinted, maternally expressed gene and complete moles are diandric (dispermy, empty ova)
What are the TORCH infections?
The acronym ‘TORCH’ has been used as a reminder of infections that cause congenital defects.
Toxoplasmosis
Others (syphilis, listeria, parvovirus B19, VZV, HIV)
Rubella
Cytomegalovirus (CMV)
Herpes (simplex) virus (HSV).
Features and Significance of CMV in Placenta
DNA virus that causes 10% of chronic villitis cases
Often no clinical symptoms.
Hearing and visual loss, neurologic deficit, IUGR
Macro:
Placenta may be large and edematous or small and fibrotic
Micro:
Lymphocytic or plasmacytic villitis with hyalinized villi
Hofbauer cell (fetal macrophage) hyperplasia
Rare intranuclear and cytoplasmic inclusions

Features and Significance of Listeria in Placenta
Gram positive bacteria strongly associated with stillbirth, premature delivery and sepsis
Macro: Small white nodules (microabcesses) scattered throughout parenchyma
Micro: Acute intervillositis with intervillous microabcesses; organisms identified with gram stain

Features and Significance of Syphilis in Placenta
Often associated with stillbirth or early neonatal death
Macro: Umbilical cord often normal but 36% have necrotizing funisitis; large oedematous disc
Micro: Immature, edematous villi with increased fetal erythroblasts, endarteritis and perivasculitis of stem vessels and lymphoplasmacytic villitis
Necrotizing funisitis or acute villitis have also been reported
Ancillary: Most cases with positive PCR have negative histology so do PCR of placental tissue if suspect syphilis
Positive stains: visualize spirochetes in cord using silver (Warthin-Starry) stain and / or Spirochete IPX

Synoptic Report for Vulval Cancer
Location & Laterality of Tumour
Uni / Multifocal
Macroscopic Size
Histologic Subtype of tumour: SCC-HPV associated, SCC HPV-independent, adenocarcinoma, carcinosarcoma, NEC, MINEN.
LVI / PNI
Neoadjuvant therapy
Additional findings: condyloma, VIN, dVIN, LSC
P16 immunohistochemistry
pTNM Staging (AJCC 8th):
pT1 Size of tumour (< / > 2cm) and depth of stromal invasion
pT2 Invasion into lower uretha / periurethal structures
pT3 Upper urethra / vagina / bladder / rectum
NB: no pT4
Sentinel Lymph Nodes in Breast
sn (ITC) = < 0.2mm or < 200 cells
sn (mi) > 0.2mm and < 2mm
macrometastasis >2mm
macro: size of largest deposit and ENE
Microinvasive Breast Carcinoma
Invasive carcinoma <1mm in size outside interlobar stroma
Usually arises in a field of DCIS
Can be single or multiple
Staged as pT1mi
Grading of Breast Cancer
Histologic grading is based on the Nottingham Score / Modified Bloom & Richardson Score
Tubule formation (1 - 3 points):
> 75% (1 point)
10 - 75% (2 points)
< 10% (3 points)
Nuclear pleomorphism (1 - 3 points):
Small, regular, uniform, similar to normal ductal epithelial cells, 2 - 3x RBC (1 point)
Moderate increase in size / variability (2 points)
Large nuclei, marked variation, often vesicular chromatin with prominent nucleoli (3 points)
Mitotic count (1 - 3 points)
Per 10 HPF, score dependent on microscopic field area
Total score
3 - 5 points: grade 1
6 - 7 points: grade 2
8 - 9 points: grade 3





