Flashcards in Path of female GT & endometrium: Gupta Deck (25)
Describe common uterine neoplasms, including important clinical features, and relate pathological features to prognosis.
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.
Discuss the relationship of endometrial carcinoma to hereditary non-polyposis colorectal carcinoma (HNPCC).
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.
Define endometrial hyperplasia and discuss its etiology, classification, and prognosis.
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.
Compare and contrast the pathology of adenomyosis with endometriosis.
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)
Features of herpes infection
- "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
Features of molluscum infection
- 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
Features of herpes candida
- 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
Features of trichomonas vaginalis infection
- 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
Features of gardnerella vaginalis infection
- 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
Features of chlamydia trachomatis infection
- 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
Clinical features, sequelae, and 2 main causes of pelvic inflammatory disease (PID)
- 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
adhesions to the liver and peritoneum caused as a result of ascended PID/infection
- 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
- 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
Lichen simplex chronicus
- thickened epidermis from some irritating process
- with chronic inflammation
- 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)
Vulvular intraepithelial neoplasia (VIN)
- 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
Squamous cell carcinoma (SCC) of the female genital tract
- 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
Paget's disease of vulva
- 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)
Cancer of the vagina
- 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
- 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
- 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
Squamous Lesion Terminology:
- stages of dysplasia
- stages of CIN
- squamous intraepithelial lesion (SIL)
- 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
Stains associated with HPV infection
- Ki-67 -- stains keratin, brown nuclear staining
- p16 -- it's upregulated in high-risk HPV infected cells