Cervix, Vagina, and Vulva

Question 1

Answer 1

Microglandular hyperplasia

Sometimes can have this cribriform architecture, but has no cytologic atypia and is non-infiltrative of the stroma (no desmoplasia).

Question 2

Answer 2

Nabothian cysts

Pronounced dilatation of endocervical glands.

Benign.

Question 3

Answer 3

Mesonephric remnants with mesonephric hyperplasia

Developmental remnants of the Wolffian duct, occasionally found in the deep cervical stroma.

Bland cytology and dense “bubble gum” luiminal contens are characteristic.

Calretinin, AR, and GATA3 are positive. p16 shows a focal/wild-type pattern.

Question 4

Answer 4

Arias-Stella reaction

Cervical epithelial response to progesterone.

Results in clear cell change and nuclear enlargement. Not to be confused with a neoplasm!!!

Question 5

Answer 5

Prostatic ectopia

Infiltrative-appearing glands in the cervical stroma, but with minimal cytologic atypia and a clear basal cell layer.

IHC for PSA, PSAP, and 34betaE12 will clear this up.

Question 6

Answer 6

Cervical intraepithelial neoplasma, grade 1 (CIN1)

Question 7

Answer 7

Cervical intraepithelial neoplasma, grade 2 (CIN2)

Question 8

Answer 8

Cervical intraepithelial neoplasma, grade 3 (CIN3)

Question 9

Answer 9

Invasive squamous cell carcinoma of the cervix

Note the paradoxical maturation of the invasive component.

Question 10

Answer 10

Warty squamous cell carcinoma

So-called “warty” because it shows prominent cytologic features of HPV infection.

Behaves less aggressively than other SCCs.

Question 11

Answer 11

Lymphoepithelioma-like carcinoma

Type of SCC with synscytial sheets and islands of undifferentiated epithelioid cells with eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli in a lymphoid stroma.

Question 12

Answer 12

Cervical adenocarcinoma in-situ

HPV-associated glandular lesion (usually HPV16 or 18). Often seen in conjunction with LSIL or HSIL.

Characterized by loss of cytoplasmic mucin, cellular stratification, cellular crowding, nuclear enlargement, atypia, and apical mitoses and apoptoses.

Can have numerous subtypes: Endocervical, endometrial, gastric, or intestinal, with glandular, papillary, or cribriform architecture.

Requires complete excision.

Question 13

Answer 13

Microinvasive cervical adenocarcinoma

FIGO definition: Invades less than 3mm from the basement membrane of the adjacent epithelial surface and extends less than 7mm in greatest lateral extent.

Question 14

Answer 14

Gastric-type adenocarcinoma

aka Minimal deviation adenocarcinoma
aka Adenoma malignum

HPV-negative type of cervical adenocarcinoma.

Rare type of cervical adenocarcinoma, so bland that it may not be recognized on curettage or cytology.

Diagnosis rests on the presence of deep infiltration, perivascular/perineural invasion, and stromal reaction.

Question 15

Answer 15

Stratified mucin-producing intraepithelial lesion (SMILE)
aka gastric-type adenocarcinoma in-situ

Question 16

Answer 16

Invasive stratified mucin-producing intraepithelial lesion (iSMILE)

Question 17

Answer 17

Lobular endocervical glandular hyperplasia (LEGH)

Question 18

Answer 18

Atypical lobular endocervical glandular hyperplasia (aLEGH)

Premalignant lesion to gastric-type cervical adenocarcinoma

Question 19

Answer 19

Well-differentiated villoglandular adenocarcinoma

Somewhat overlapping morphologic features between endometrioid and cervical adenocarcinoma, but considered a subtype of endometrioid.

Exophytic growth pattern with glandular and villous elements, minimal nuclear pleomorphism, and a low mitotic rate. Reminiscent of a villous adenoma of the intestinal tract.

Tends to affect younger women and has a favorable prognosis.

Question 20

Answer 20

Clear cell cervical adenocarcinoma

Associated with in utero exposure to diethylstilbestrol.

Clear cells with hobnail morphology are observed in solid, papillary, and tubular arrangements (often called “tubulocystic”). Except. . . note that the cells aren’t always clear. In fact, often they aren’t. This makes serous carcinoma a key differential.

The presence of this tumor in the cervix should prompt a search for a primary tumor of the ovary, endometrium, or vagina, which are sites where this entity is much more common.

IHC: HNF1b+, AMACR diffusely +, ER/PR negative, CEA negative, TP53 negative

Note: Most other cervical adenocarcinomas are CEA positive.

Molecular: Associated with mutations in the Hippo pathway (50% of cases), especially the recurrent WWTR1 p.S89W variant (20% of cases). Also can carry POLE mutations or be associated with Lynch syndrome.

Question 21

Answer 21

Mesonephric adenocarcinoma

Derived from mesonephric (Wolffian) remnants.

Can exhibit a variety of glandular patterns, including tubular, ductal, cribriform, papillary, and solid.

IHC: GATA3+, CD10+ (luminal), HNF1b+ (50%), ER/PR negative, AMACR negative

Question 22

Answer 22

Endocervical adenocarcinoma, usual (cervical) type

Question 23

Answer 23

Differentiated vulvar intraepithelial neoplasia

A widened epithelium with atypical parakeratosis and elongated rete ridges is seen. Nuclear atypia, premature keratinisation and cobblestone appearance are apparent. Elongated rete ridges, a deep squamous eddy, nuclear atypia, and parakeratosis can be identified under low magnification. Under higher magnification, macronucleoli can be seen. Angulated nuclei, individual cell keratinisation and cobblestone appearance can be better appreciated.

May be very subtle, with only basal atypia and acanthosis, but maintenance of overall maturation.

TP53 may be overexpressed in only the basal layer in dVIN, but be lost as cells mature and lose p53 expression.