Gyne Flashcards
List four non-molar gestational trophoblastic lesions
Placental site nodule
Epithelioid trophoblastic tumor
Placental site trophoblastic tumor
Gestational choriocarcinoma
What is the karyotype of a partial mole?
69XXY (or XYY, or XXX)- triploid
What is the pathogenesis of a partial mole?
Diandric triploidy: fertilization of a normal oocyte by two spermatozoa or single sperm that duplicates itself.
Two paternal and one maternal haploid set of DNA
What is the karyotype and pathogenesis of a complete mole?
Diandric diploidy: two paternal sets of chromosomes, no maternal DNA.
= 46XX (usually) or XY
What is persistent gestational trophoblastic disease and what are the pathologic differential diagnoses?
Plateau or continued rise in beta-hcg after evacuation of a molar (or normal) pregnancy;
Pathologically corresponds to:
Persistent mole with no invasion
Invasive mole
choriocarcinoma
What is the risk of progression to choriocarcinoma in a Partial Mole and a Complete Mole?
Partial: <1%
CHM: 2 - 5%
What is the pattern of p57 staining in partial and complete moles?
What is the internal positive control?
p57 staining is paternally imprinted (silenced) - expressed only in the maternal genome - in the villous STROMA and CYTOTROPHOBLAST.
Therefore:
p57 staining absent in Complete mole
p57 staining present in Partial mole
Positive INTERNAL CONTROL is the maternal tissue: decidua.
Intermediate trophoblast islands are fetal tissue but still retain some staining due to incomplete imprinting even in complete mole.
What is the immunoprofile of Primary Extramammary Paget disease of the vulva? (at least two immunos and two special stains)
What would you use to differentiate it from Secondary extramammary paget disease?
Primary Extramammary Paget disease Positive: CK7 & LMWCK (Cam 5.2); GATA3; GCDFP-15 CEA, mucicarmine, PAS-D, Alcian Blue (CK20-, p63/p40-, CDX2-, SOX10-) MUC1+ MUC5+
Secondary Paget, urothelial:
CK7+, CK20+, GATA3+, p63/p40+;
(GCDFP15-, CDX2-, SOX10-)
Secondary Paget, anorectal:
CK20+, CDX2+
(GATA3-, CK7-, SOX10-, GCDFP15-)
MUC2+
Quick Reference: 46.
List 4 types of metaplasia that can be found in the cervix.
Squamous
Tubal
Tuboendometrioid (replacing cervical glands; endometriosis has the conspicuous stroma and hemosiderin)
Gastric/pyloric
What is the immunoprofile of endometriosis?
Positive:
ER/PR
Pax-2
Bcl-2
Stroma: CD10+, CD34- (opposite of cervical stromal cells)
Negative/patchy:
p16
Cervical stromal cells: CD10-, CD34+
What immunos could you use to differentiate tunnel clusters from adenoma malignum?
Tunnel clusters: ER/PR +; p53 wild type; low ki67; p16 negative
Adenoma malignum: loss of ER/PR, p53 overexpression, high Ki67.
List precursors of endometrial endometrioid carcinoma according to the latest WHO.
Endometrial hyperplasia without atypia
Atypical endometrial hyperplasia / endometrial intraepithelial neoplasia (AEH/EIN)
What is the pathway mutated in EIN and list the key genes involved.
PI3K/AKT pathway
Genes:
PTEN (seen in hyperplasia)
MLH1
KRAS (key to EIN)
PIK3CA (40% of endometrioid carcinomas)
ARID1a is important for transition from atypical hyperplasia to EIN)
What are the essential diagnostic criteria for nonatypical endometrial hyperplasia?
- Increased endometrial gland–to–stroma ratio;
- tubular, branching, and/or cystically dilated glands resembling proliferative endometrium;
- uniform distribution of nuclear features across submitted tissue.
NB: criteria above are from WHO.
Nucci: characterized by increase in amount of glands at scanning magnification, in which glands occupy >50% of the area (gland to stroma ratio >1)
- stratification and polarity maintained
What are the essential and desirable diagnostic criteria for EIN?
Essential: morphologically defined endometrial changes with crowded glandular architecture and altered epithelial cytology, distinct from the surrounding endometrium and/or entrapped non-neoplastic glands.
Desirable: loss of immunoreactivity for PTEN, PAX2, or mismatch repair proteins.
List the classification of intraepithelial lesions of the vulva.
What are their staining patterns for p16 and p53?
- Squamous intraepithelial lesions, HPV-associated, of the vulva (also known as usual VIN); low-grade VIN1 and high grade VIN2-3.
p16 block positive, p53 wild-type - Vulvar intraepithelial neoplasia, HPV-independent (also known as dVIN);
p16 negative, p53 abnormal (null or diffuse)
How do you differentiate LSIL from HSIL (semi-quantitatively) in the Vulva?
Atypia: involves lower 1/3 vs at least 1/2 to full-thickness;
Define primary Paget of the vulva.
What is the immunoprofile of primary vulvar Paget disease?
Primary Paget: in situ adenocarcinoma of the vulvar skin, with or without underlying invasive adenocarcinoma. Secondary involvement of vulvar skin by carcinoma of rectal, bladder or cervical origin is designated “secondary Paget disease.”
POSITIVE: ER/PR (HER2 less common) CK7 (distinguishes from HPV-independent HSIL & melanoma) EMA CAM5.2 (LMWCK) CEA GATA3 !!! p16+/- PAS (for mucin) mucicarmine
NEGATIVE: melanoma markers uroplakin-3 CDX2 CK20
How do you grade dVIN?
it is not graded!
How many lymph nodes are normally examined in a vulvar specimen, and what are the designated “regional” nodes?
6
Regional nodes = inguinal and femoral
How do you measure tumor thickness and depth of invasion in vulvar carcinoma?
Thickness: mm from the surface of the tumor or, if there is surface keratinization, from the bottom of the granular layer to the deepest point of tumor. Not used in staging, but used when the tumor is exophytic, surface ulcerated, or no adjacent epithelial-stromal junction, preventing measurement of depth of invasion.
Depth of invasion: in mm, from the epithelial-stromal junction of the adjacent, most superficial dermal papilla to the deepest point of invasion.
Alternative method: from BM of adjacent deepest dysplastic rete to the deepest point of invasion (tends to downstage).
What are the strongest predictors of overall progression-free survival in vulvar carcinoma?
Tumor Stage
Lymph node status
Which has better prognosis - HPV-associated or HPV-independent vulvar carcinoma?
HPV-associated.
What are the 3 abnormal patterns of p53 expression (specifically from Vulvar CAP protocol)
- Block: uniformly strong, continuous basal cell nuclear overepression; cytoplasmic blush ok.
- Null: lack of nuclear or cytoplasmic expression;
- Abnormal cytoplasmic: diffusely to contiguously moderate to strongly positive while the nuclei are negative or variably stained.
What are the main morphologic “types” of uVIN vs dVIN?
uVIN = Rare. younger. Warty or basaloid types. often multifocal. Less common (20%)
dVIN = Keratinizing
older; assoc. LSC; unifocal; more common (80%)
What immunoprofile can you use to differentiate between endometrial endometrioid adenocarcinoma vs cervical endometrioid adenocarcinoma?
ENDOMETRIAL ENDOMETRIOID:
ER/PR : positive
p16 : negative
Vimentin : positive
CERVICAL ENDOMETRIOID:
ER/PR : negative
p16: positive
Vimentin : negative
Both are positive for PAX8
CEA can be positive in cervix adenoCa but it is really nonspecific.
What is the immunoprofile of clear cell adenocarcinoma of the cervix / endometrium?
POSITIVE
Napsin
HNF-1B
PAX8
NEGATIVE
ER/PR
WT1
p53 wild type
How do you differentiate between serous carcinoma of the ovary vs uterus?
Uterus: PAX8+ ER/PR 50% p53 DIFFUSE OR NULL p16 diffuse strong very high ki67 ****Wt1 negative
Ovary: PAX8+ ER/PR 50% P53 abnormal in high-grade ****Wt1 postiive
What are the two major non-neoplastic causes of leukoplakia?
lichen sclerosus
squamous cell hyperplasia (a.k.a. lichen simplex chronicus)
Robbins p. 990
what is the pathogenesis of lichen sclerosus?
autoimmune
Robbins p. 990
list causes of dysfunctional uterine bleeding.
chronic endometritis endometrial polyps submucosal leiomyomas endometrial neoplasms hormonal disturbances.
List 4 causes of chronic endometritis
IUD
Pelvic inflammatory disease
Tuberculosis
Retained products of conception
List three “types” of endometriosis
Superficial peritoneal endometriosis
ovarian endometriosis
deep infiltrating endometriosis
Robbins p. 1004
List 4 theories for the pathogenesis/distribution of endometriosis.
Regurgitation
Metaplasia
Metastasis
Stem cell
List 2 ovarian carcinomas associated with endometriosis.
Clear Cell
Endometrioid
List the squamous epithelial mimics, precusors and neoplasms of the uterine cervix according to the WHO.
mimics:
- Squamous metaplasia
- atrophy of the uterine cervix
Precursors and neoplasms:
- condyloma acuminata of the uterine cervix
- squamous intraepithelial neoplasia of the uterine cervix
- squamous cell carcinoma, HPV-associated of the uterine cervix
- squamous cell carcinoma, HPV-independent of the uterine cervix
- squamous cell carcinoma, NOS (no access to HPV testing or p16)
List benign glandular tumors of the uterine cervix according to the WHO.
Edocervical polyp
Mullerian papilloma of the uterine cervix
Nabothian cyst
Tunnel clusters
microglandular hyperplasia
Lobular endocervical glandular hyperplasia
Diffuse laminar endocervical hyperplasia
Mesonephric remnants and hyperplasia
Arias-Stella reaction of the uterine cervix
Endocervicosis of the uterine cervix
Tuboendometrioid metaplasia
Ectopic prostate
List the classification of adenocarcinomas of the uterine cervix according to the WHO.
Adenocarcinoma in situ, HPV-associated, of the uterine cervix
Adenocarcinoma, HPV-associated of the uterine cervix
Adenocarcinoma in situ, HPV-independent, of the uterine cervix
Adenocarcinoma, HPV-independent, gastric type
Adenocarcinoma, HPV-independent, clear cell type
Adenocarcinoma, HPV-independent, mesonephric type
Other adenocarcinomas of the uterine cervix
List the histologic types of HPV-associated adenocarcinoma of the uterine cervix
Usual type: <50% mucin (vast majority of cases are this type)
- has a villoglandular variant
(purely exophytic villoglandular conveys excellent prognosis)
Mucinous type: ~10% of endocervix adenocarcinomas; >50% of cells with intracytoplasmic mucin
subtypes:
- Mucinous NOS
- signet ring cell
- intestinal adenocarcinoma: goblet cells >50%
- stratified mucin-producing carcinoma (with a SMILE component).
list causes (ddx) of atypical endometrial cells
NB: this explains why “Atypical endometrial cells, favour neoplasia, is not a category”
Endometrial polyps
IUD
Endometritis
Endometrial hyperplasia
= all benign conditions that mimic endometrial adenocarcinoma.
But the risk of carcinoma with the finding of atypical endometrial cells is high, so endometrial/endocervical sampling is recommended.
What is the causative/etiological agent most commonly associated with small cell neuroendocrine carcinoma of the cervix?
HPV-18
What is the pattern-based classification of HPV-associated adenocarcinoma of the uterine cervix?
Silva system: classifies adenoca of the cervix as A, B or C based on pattern of invasion.
A: non-destructive invasion (well-demarcated, no LVI) - conservative management
B: Early/focally destructive invasion (focally desmoplastic, can have LVI, no solid)
C: Diffusely destructive invasion (solid, desmoplastic, fills a 4x field, can have LVI);
- hysterectomy, lymphadenectomy and rads!
Significance: prognostic indicator of recurrence, lymph node metastases and survival.
List reasons why a morphologically HPV-associated carcinoma of the uterine cervix may be p16 negative.
95% of cases show block-like/every cell staining.
rare cases:
- methlyation inactivation of CDKN2A/p16
- old or poorly-preserved tissue
- if negative for mRNA chromogenic ISH, may be positive for an HPV subtype not covered by the assay.
List important prognostic factors in HPV-associated adenocarcinoma of the uterine cervix.
WHO: Stage is the most important prognostic variable.
other factors:
Invasive pattern (pattern C, micropapillary is worse)
LVI
age of patient
KRAS and PIK3CA mutations associated with invasive patterns and prognosis.
Which is worse prognosis, HPV-associated or independent adenocarcinoma of the cervix?
WHO: HPV-associated are associated with significantly better disease-free and disease-specific survival than their HPV-independent counterparts
What is the molecular alteration is most often seen in mesonephric carcinoma of the uterine cervix?
What are mesonephric remnants?
KRAS
Wolffian duct that fails to regress
P16 negative, p53 wild type, HPV negative
Positive for PAX8, CD10, GATA3, TTF1, Calretinin
List positive immunohistochemical and special stains in primary Paget’s disease of the vulva.
CK7+, EMA+, CAM5.2+
CEA+
GCDFP15+
GATA3+
NB: should be negative for uroplakin, CDX2, CK20. Also negative for melanoma markers.
