Path of female GT & endometrium: Gupta

Question 1

Describe common uterine neoplasms, including important clinical features, and relate pathological features to prognosis.

Answer 1

Endometrial carcinoma type I (80% of cases)- found in pts aged 55-65 w/ unopposed estrogen, obesity, DM, HTN. Endometrioid morphology. Hyperplastic precursor. PTEN, MSI (microsatellite instability) mutations. Indolent. Spreads via lymph. Good prognosis.

Endometrial Carcinoma type II (20% of cases)- pts aged 65-75 w/ uterine atrophy. Serous (high grade), clear cell, mixed mullerian tumor (MMT) morphology. Serous endometrial intraepithelial carcinoma precursor. TP53 mutation. Aggressive intraperitoneal and lymph spread. Bad prognosis.

Serous Carcinoma- P53 positive nuclear stain. May be associated with extensive peritoneal dz. Always grade 3, irrespective of histology.

Malignant Mixed Mullerian Tumors- Epithelial and stromal components appear to be derived from same cell. Poor prognosis.

Leiomyomas- SM tumors. Uterine leios perhaps most common tumor in women. Do NOT transform to malignancy. Risk of Fe deficiency anemia. Surgical excision is curative.

Leiomyosarcoma- Bad news. Hemorrhagic, necrotic, nuclear atypia.

Question 2

Discuss the relationship of endometrial carcinoma to hereditary non-polyposis colorectal carcinoma (HNPCC).

Answer 2

Endometrial carcinoma is the most common invasive cancer of the female genital tract.
Defects involving DNA mismatch repair genes are prevalent in endometrial carcinomas in women from families with HNPCC.

Question 3

Define endometrial hyperplasia and discuss its etiology, classification, and prognosis.

Answer 3

Endometrial hyperplasia is divided into 4 categories, as follows:
Simple w/o atypia- mild glandular crowding, cystic glandular dilation
Complex w/o atypia- back to back glands, crowding
Simple w/ atypia (neoplasia)- nuclear features of atypia
Complex w/ atypia (neoplasia)- nuclear features of atypia

Important cause of abnormal bleeding and frequent precursor to endometrial carcinoma. Associated with prolonged estrogenic stimulation of endometrium unopposed by progesterone.

PTEN tumor suppressor inactivation found in endometrial hyperplasia and carcinoma.

Question 4

Compare and contrast the pathology of adenomyosis with endometriosis.

Answer 4

Endometriosis is endometrial tissue found outside the uterus.
Adenomyosis is endometrium found buried in the myometrium within the uterine wall.

Endometriosis almost always contains functioning endometrium, which undergoes cyclic bleeding. Adenomyosis does NOT.

3 features of endometriosis: (must have all 3 for Dx)
endometrial glands
endometrial stroma
hemosiderin pigment

Question 5

Features of herpes infection

Answer 5

• “below the belt” usually HSV-2 which establishes latent infection in LS ganglia
• in order of most frequent involvement: cervix, vagina, vulva
• start as red papules; progress to vesicles; then painful coalescent ulcers
• worst consequence is transfer to child during birth, so if active infection will do C-section
• 3 M’s for cytology:
  1. Margination (of chromatin due to accumulated viral particles),
  2. Molding (of the nucleus), and
  3. Multinucleation

Question 6

Features of molluscum infection

Answer 6

• molluscum is a poxvirus, common in kids age 2-12 (transmitted via direct contact or fomites), STI in adults
• appearance is distinct: always (yes always) looks like a pink erupting volcano out of skin, with bright pink eosinophilic inclusions

Question 7

Features of herpes candida

Answer 7

• shish-kabobing appearance; the pseudohyphae spear the cells
• extremely common and results during microbial disturbance, which can be caused by DM, Abx, pregnancy, other conditions

Question 8

Features of trichomonas vaginalis infection

Answer 8

• a protozoan
• [sometimes will see] strawberry cervix results from dilated vessels; asx or frothy yellow vaginal discharge, vulvovaginal discomfort, and dyspareunia
• look for little red viral inclusions

Question 9

Features of gardnerella vaginalis infection

Answer 9

• Gram neg bacillus, main cause of bacterial vaginosis
• thin, green-gray malodorous discharge (fishy)
• LOTS of bacteria on sample among the cervical squamous cells can end up covering cells, these are called Clue cells

Question 10

Features of chlamydia trachomatis infection

Answer 10

• Gram negative IC (ovoid) bacterium
• mainly causes infection of the cervix (cervicitis), and also a cause of pelvic inflammatory disease (PID)
• problem with PID is that it can become an ascending infection and cause tuboovarian abscesses
• non-specific histology, but you can stain for inclusion bodies

Question 11

Clinical features, sequelae, and 2 main causes of pelvic inflammatory disease (PID)

Answer 11

• pelvic pain, adnexal tenderness, fever, vaginal discharge
• can ascend to fimbriae and cause acute salpingitis (tubes fill with pus) and chronic salpingitis (plicae scar and fuse)
• Neisseria gonorrhea and Chlamydia trachomatis

Question 12

Fitz-Hugh-Curtis syndrome

Answer 12

adhesions to the liver and peritoneum caused as a result of ascended PID/infection

Question 13

Bartholin cyst

Answer 13

• obstruction of the Bartholin glands in the vulva
• anything from secretions to squamous cells can cause obstruction
• can affect all ages
• can become large and painful

Question 14

Lichen sclerosis

Answer 14

• white plaques of the skin overlying the vulva
• atrophy of the skin/thinning of the epidermis; then sclerosis of superficial skin, chronic inflammation of deeper skin, and stenosis of the vagina
• ddx includes SCC and LSC

Question 15

Lichen simplex chronicus

Answer 15

• thickened epidermis from some irritating process

- with chronic inflammation

Question 16

Condyloma accuminatum

Answer 16

• benign warts (pedunculated verrucae, also described as velvety) often caused by HPV 6 + 11
• 3 features of the viropathic effect within the cells:
  1. koilocytosis - halo forms around the nucleus
  2. raisinoid nuclei
  3. binucleation of cells
  (also looking for mitotic figures; would be a tip-off that this is more than benign warts)

Question 17

Vulvular intraepithelial neoplasia (VIN)

Answer 17

• neoplasm of the epithelial cells of the vulvular skin (not as common as cervix)
• younger patients - will usually be associated with HPV 16, non-keratinizing
• usually found in older women (60s) and these patients will usually be keratinizing and not associated with HPV
• VIN can progress to SCC

Question 18

Squamous cell carcinoma (SCC) of the female genital tract

Answer 18

• will see homogenous cells throughout the whole epidermis, that all resemble the cells that normally belong in the basal layer, instead of normal matured layers of cells
• in situ = hasn’t busted through the basement membrane
• invasive = busted through the basement membrane
• Can be HPV pos or neg; HPV+ assoc’d with strains 16 and 18; HV neg will have keratin pearls

Question 19

Paget’s disease of vulva

Answer 19

• intraepithelial proliferation of malignant cells (adenocarcinoma), but not typically assoc’d with underlying cancer and is confined to epidermis of vulvular skin
• malignant cells have abundant clear cytoplasm (ddx - melanoma!) and will stain positive for keratin (CK7)

Question 20

Cancer of the vagina

Answer 20

• called VANE: Vaginal Intraepithelial Neoplasia, can also progress to SCC
• virtually all primary carcinomas of the vagina are SCCs assoc’d with high risk HPVs

Question 21

Sarcoma botryoides

Answer 21

• uncommon vaginal tumor made of malignant embryonal rhabdomyoblasts (an embryonal rhabdomyosarcoma) that resembles a cluster of grapes
• tend to invade locally
• cause death by invasion into the peritoneal cavity or obstruction of urinary tract

Question 22

Cervical cancer

Answer 22

• HPV 16 accounts for 90% and is favored by SCC
• HPV 18 accounts for 10% and is favored by adenocarcinomas
• HPV 16 and 18 are so oncogenic because they can integrate into host DNA and, if not cleared by the immune system, will produce lots of E6 (inh. p53) and E7 (inh. RB)
• most of these lesions will clear on their own, especially in young women and yes even the high risk HPVs
• most deaths come from local tumor invasion (not distant meta, i.e., ureteral obstruction, pyelonephritis, and uremia

Question 23

Squamous Lesion Terminology:

• stages of dysplasia
• stages of CIN
• squamous intraepithelial lesion (SIL)

Answer 23

• dysplasia: mild, mod, severe, carcinoma in situ
• CIN: I, II, III
• SIL: low-grade, high-grade
• 10% of LSIL progress to HSIL, 10% of HSIL progress to carcinoma

Question 24

Stains associated with HPV infection

Answer 24

• Ki-67 – stains keratin, brown nuclear staining

- p16 – it’s upregulated in high-risk HPV infected cells

Question 25

Cervical adenocarcinoma

Answer 25

• 2nd most common tumor type behind SCC
• can be caused by HPV (esp 18)
• causes glands of malignant cells that are different from normal cells in that they have less mucin and more elongated nuclei; glands also get weird and appear back-to-back with little stroma in between
• if lesion is 3mm risk is 10%