Vulvar, Vaginal, Cervical, Uterine and Endometrial Pathology Flashcards
What is a Bartholin cyst?
At what ages might they present?
What is the presentation?
Cyst of the Bartholin gland (2 in vagina) that produces an acute inflammation due to infection. They are lined by transitional or squamous epithelium and can become large (up to 3-4 cm) in diameter.
They can present at any age.
Pain and local discomfort.
What is the gross morphology of Lichen Sclerosis?
What can it increase the risk for?
What is the pathogenesis?
Smooth, white plaques or macules that, in time, may enlarge and coalesce to produce a certain a “poreclain” or “parchment” surface. If it affects the entire vulva, the labia can become atrophic and agglutinated and the vaginal orifice constricts.
Very slight increased risk for SCC of the vulva.
Uncertain pathogenesis, but it is thought to have some kind of autoimmune connection.
What causes squamous cell hyperplasia?
What is the presentation (mostly morphological)?
When might it be seen?
Rubbing and itching to relieve pruritis.
May present as leukoplakia and epidermal thickening and hyperkeratosis.
Might be seen at the margins of vulvar cancers, but it itself is not pre-malignant.
What causes condyloma acuminatum?
What is the morphological and gross appearance?
Are they pre-malignant?
Low oncogenic risk HPV (types 6 and 11).
Papillary, exophytic, tree-like cores of stroma covered by thickened squamous epithelium.
NOT pre-malignant.
What are the 2 types of squamous cell carcinoma of the vulva?
What age group is most common?
Basaloid and warty carcinomas: related to infection with HPV-16 most commonly (30% of cases). They are less common and occur at younger ages.
Keratinizing SCC: unrelated to HPV infection (70% of cases). More common and occur in older women.
> 60 y/o (2/3 of cases)
What is classic vulvar intraepithelial neoplasia (VIN)?
When do they occur?
What is a risk factor?
In which patients are complications more concerning?
In situ precursor lesions of basaloid and warty carcinomas.
Reproductive age women.
HPV infection.
Risk of progression to invasive carcinoma is higher in women >45 y/o who are immunosuppressed (peak age is 60 y/o).
What is differentiated vulvar intraepithelial neoplasia (VIN simplex)? Patients with which 2 underlying processes does it occur with?
What is the peak age of occurrence?
What mutation can be in high frequency in these neoplasms?
The precursor lesion for vulvar keratinizing SCC in patients with long-standing lichen sclerosus or squamous cell hyperplasia (no relation to HPV).
Peak age is 70 y/o.
TP53
What is papillary hidradenoma?
What is the morphology?
A sharply circumscribed nodule and may be confused with carcinoma as it is able to ulcerate.
Histologically identical to intraductal papilloma of the breast.
What is the presentation of extra-mammary Paget disease?
How is it different than Paget disease of the nipple?
Pruritic, red, crusted area on the labia majora.
Vulvar Paget is not typically associated with underlying cancer and is confined to epidermis of skin (100% of breast Paget’s is associated with malignancy).
What is uterus didelphys?
A double uterus that accompanies a septate/double vagina.
What is vaginal adenosis?
The vagina maintains its glandular epithelium into adulthood instead of transforming into squamous epithelium. During embryological development, the vaginal epithelium is columnar.
What is a Gartner cyst?
Common lesions along the lateral walls of the vagina and are derived from the mesonephric (Wolffian) ducts.
They are 1-2 cm fluid-filled cysts in the submucosa.
What is the clinical presentation of embryonal rhabdomyosarcoma?
What are the histological features?
What is the prognosis?
Polypoid, rounded, bulky masses that appear as grape-like clusters in the vagina in kids <5 y/o.
Oval nuclei with small protrusions of of cytoplasm from one end (tennis racket looking).
Tumors tend to cause death by invasion into the peritoneum or obstructing the urinary tract. Conservative surgery coupled with chemo offer the best hope if detected early.
What is the “transformation zone” of the cervix? What is the significance?
The area of the cervix where the columnar epithelium abuts the squamous epithelium. It is most common area of malignant transformation.
What are endocervical polyps?
What do they look like histologically?
What is their significance?
Benign exophytic growths that arise within the endocervical canal.
Composed of loose fibromyxomatous stroma covered by mucous-secreting endocervical glands and include inflammation.
They may cause irregular vaginal “spotting”. They can be removed or curettaged.
The ability of HPV to act as a carcinogen depends on what?
Viral proteins E6 and E7, which interfere with the activity of TSGs in HPV-16.
What is CIN I, CIN II and CIN III?
What “grade” is associated with each?
What is the morphologic feature of each?
CIN I: mild dysplasia, LSIL, koilocytic atypia
CIN II: moderate dysplasia, HSIL, progressive atypia and expansion of the immature basal cellsa bove the lower 1/3 of epithelial thickness
CIN III: severe dysplasia, HSIL, diffuse atypia, loss of maturation, and expansion of immature basal cells to the epithelial surface
What is the diagnosis of squamous intraepithelial lesions (SILs) based on? (4)
Indentification of nuclear atypia characterized by nuclear enlargement, hyperchromasia (dark staining), coarse chromatin granules and variation in nuclear size/shape.
LSILs have what kind of viral activity/cell changes?
High level of viral replication, but only mild alteration of growth in affected cells.
What is the progression of LSIL?
Most do not progress directly to invasive carcinoma and usually regress, so it is not treated like a pre-malignant lesion.
HSILs have what kind of viral activity/cell changes?
Dysregulation of cell cycle by HPV leads to increased cell proliferation, decreased/arrested epithelial maturation and lower rate of viral replication.
+Ki67 in cervical dysplasia =
Abnormal expansion of proliferating cells from basal location.
CIN II.
Average age of cervical carcinoma in the US:
Types of carcinoma (3)
45 y/o (cervix - 40, endometrium - 50, ovary - 60)
SCC (80%)
Adenocarcinoma (15%)
Mixed adenosquamous or neuroendocrine (5%) - worst prognosis and shorter progression
Which LNs does cervical cancer metastasize to? (2)
What are the distant mets? (4)
What causes the death?
Primary pelvic nodes first, then para-aortic nodes (non-palpable).
Lung, other LNs, liver and bone.
Complications related to local tumor invasion rather than the mets.
Risk of metastasis of invasive cancers of the vulva is linked to: (3)
Size of primary tumor (<2 cm - 90% 5 year survival)
Depth of invasion
Lymphatic involvement
Describe the histological changes in the uterus during the following phases:
Proliferative phase
Early secretory phase
Late secretory phase
Menses
Proliferative phase: mitoses (rapid growth)
Early secretory phase: subnuclear vacuoles
Late secretory phase: stromal cell hypertrophy,
increased cytoplasmic eosinophilia (predecidual change)
Menses: stromal breakdown
What is dysfunctional uterine bleeding (DUB)?
What are 2 possible causes?
A clinical term for uterine bleeding that lacks an underlying organic (structural) problem.
Anovulatory cycle (most common)
Inadequate luteal phase
What can cause an anovulatory cycle? (3)
Endocrine disorders
Metabolic dysfunctions
Ovarian lesions (failure of ovulation caused excessive endometrial stimulation by unopposed estrogen).
What is the presentation of inadequate luteal phase?
Infertility with either increased bleeding or amenorrhea.
What can cause abnormal uterine bleeding in pre-puberty ages?
Precocious puberty (hypothalamic, pituitary or thyroid origin)
What can cause abnormal uterine bleeding in adolescent ages? (2)
Anovulatory cycle
Coagulation disorders
What can cause abnormal uterine bleeding in reproductive aged women? (3)
Complications of pregnancy
Anatomic lesions
DUB - anovulatory cycle, inadequate luteal phase (ovarian bleeding)
What can cause abnormal uterine bleeding in preimenopausal women? (2)
DUB - anovulatory cycle
Anatomic lesions
What can cause abnormal uterine bleeding in postmenopausal? (2)
Endometrial atrophy
Anatomic lesions
What is the cause of acute endometriosis?
Which agents? (2)
Where is the inflammation limited?
What is the treatment?
Bacterial infections that arise after delivery or miscarraige.
Grp. A hemolytic strep., staphylococci.
Limited to the stroma and is nonspecific.
Removal of retained gestational fragments and abx.
Which disorders can cause chronic endometriosis? (4)
PID
Retained gestational tissue, postpartum or post-abortion
IUD
Tb
What is needed on biopsy to diagnose chronic endometriosis?
Plasma cells in the stroma (not found in normal endometrium)
What is the definition of endometriosis?
Presence of “ectopic” endometrial tissue at a site outside of the uterus.
What are the 3 most common sites of involvement of endometriosis (listed in order)?
- Ovaries
- Uterine ligaments
- Rectovaginal system
Cul de sac Pelvic peritoneum Lower GI Mucosa of lower GU Laparotomy scars
Which 4 symptoms are typical of endometriosis?
Infertility, dyspareunia, dysmenorrhea and pelvic pain
Regurgitation theory of endometriosis
Regurgitation theory: endometrial tissue implants at ectopic sites via retrograde flow of menstrual endometrium.
What molecular changes occur in endometriosis? (2)
Release of proinflammatory cytokines: PGE2, IL-1b, TNFa, IL-6, IL-8, etc.
Increased estrogen production from endometriotic stromal cells.
What is the morphology of ovarian hemorrhages in endometriosis?
“Chocolate cysts” = endometriomas
What is atypical endometriosis?
Likely a precursor to endometriosis-related ovarian carcinoma.
What is adenomyosis?
What are the symptoms? (3)
Presence of endometrial tissue in the uterine wall. Exists in approx. 20% of uteri.
Irregular and heavy menses, colicky dysmenorrhea and pelvic pain in the premestrual period.
What is endometrial hyperplasia?
What causes it? What are associated conditions? (4)
A cause of abnormal bleeding and a frequent precursor to the most common type of endometrial carcinoma.
Prolonged estrogenic stimulation of the endometrium (unopposed estrogen most common).
- obesity
- menopause
- polycystic ovarian syndrome
- estrogen replacement therapy
What is the morphological description of endometrial hyperplasia?
Increased number of glands relative to the stroma, often seen as crowded glands with abnormal shapes.
What are the 2 WHO divisions of endometrial hyperplasia?
Which one is associated with an increased risk for endometrial carcinoma?
Non-atypical and atypical hyperplasia, based on nuclear atypia.
Atypical hyperplasia is associated with an increased risk of endometrial carcinoma.
What is the major mutated gene associated with endometrial hyperplasia?
PTEN tumor suppressor gene (in approx. 20% of patients)
Most common invasive cancer of the female genital tract:
Endometrial carcinoma
Type I endometrial carcinoma (endometriod carcinoma)
Age
Underlying conditions (4)
Morphology
Precursor lesion
Mutated genes/abnormalties (4)
Behavior and manner of spread
Age: 55-65 y/o
Underlying conditions: unopposed estrogen, obesity, HTN, DM
Morphology: endometriod
Precursor lesion: hyperplasia
Mutated genes/abnormalties: *PI3K/AKT, PTEN, ARID1A, KRAS
Behavior and manner of spread: indolent and spreads via lymphatics
Type II endomentrial carcinoma (serous carcinoma)
Age
Underlying conditions (2)
Morphology (2)
Precursor lesion
Mutated genes/abnormalties (3)
Behavior and manner of spread
Age: 65-75 y/o
Underlying conditions: atrophy, thin physique
Morphology: serous, clear cells
Precursor lesion: serous endometrial intraepithelial carcinoma
Mutated genes/abnormalties: TP53, PI3K, PP2A
Behavior and manner of spread: aggressive, spreads via intraperitoneal and lymphatics
What is the most common tumor in women?
What are they composed of? How many?
Uterine leiomyomas (fibroids)
Smooth muscle neoplasms that may occur singly, but are usually multiple.
What is the gross appearance of a uterine leiomyoma?
What is the morphological appearance?
Firm and white.
Well-differentiated, regular, spindle-shaped smooth muscle cells associated with hyalinization.
What is a leiomyosarcoma?
What do they arise from?
What is the most common age range?
What is the prognosis?
An uncommon malignancy of the uterus.
Arise from the myometrium or endometrium stromal precursor cells (not fibroids!)
40-60 y/o
Poor - generally reoccur post-op and metastasize. Low 5-year survival rate.
What are the 2 distinctive growth patterns of leiomyosarcomas?
What feature is seen on biopsy?
- Bulky, fleshy masses that invade the uterine wall.
- Polypoid masses that project into the uterine lumen.
Lots of mitoses (>10 mitotic figures per hpf)
Suppurative salpingitis
Inflammation of the fallopian tubes by any pyogenic organism, though Gonorrhea (most common) and Chlamydia are responsible for majority of cases.
Psammoma bodies are seen in…
Type II endometrial carcinoma (serous-type)
Seen in most serous tumors.
What is a malignant mixed mullerian tumor?
Which component metastasizes?
Prognosis?
An endometrial adenocarcinomas with a premalignant mesenchyma; component. It is a carcinosarcoma.
Only the epithelial component metastasizes.
Poor - highly aggressive.
Most common primary lesions of the fallopian tube (minus endometriosis):
What do they consist of?
How is it different from a hydatid of Morgagni?
Paratubal cysts
Clear serous fluid
Hydatid of Morgagni is a larger variety found near the fimbriae or broad ligaments.
What is an adenomatoid tumor? Where does it occur? (2)
A benign tumor of the fallopian tube that can occur subserosally on the tube or sometimes in the mesosalpinx.
Follicle cyst
Luteal cyst
Follicle cyst - very common. Originate from unruptured graafian follicles or in follicles that ruptured and are immediately sealed.
Luteal cyst - present in normal ovaries of women of reproductive age. Lined by a rim of bright yellow tissue containgin luteinized granulosa cells.
5 clinical features of polycistic ovarian syndrome (PCOS)
Hyperandrogenism Menstrual abnormalities Polycystic ovaries Chronic anovulation Decreased fertility
Kruckenburg tumor definition:
What is the morphology?
A classic metastatic GI carcinoma, characterized by BL mets.
Mucin-producing, signet-ring cancer cells (gastric origin).
What is a pseudomyxoma peritonei?
Mets in the ovary from an appendiceal tumor.
“Powder burn” =
Endometriosis
Spontaneous abortion occurs by…
Week 20, most commonly by week 12.
Twin-twin transfusion syndrome
A complication of a twin pregnancy. Monochorionic twins have anastomoses that connect the circulations of both babies. If changes in pressure occur, one baby may become overperfused at the expense of the other. It can lead to death of one or both fetuses.
Placenta previa
The placenta implants in the lower uterine segment or cervix, often leading to serious third trimester bleeding.
Characteristic symptoms of pre-eclampsia: (3)
How is the placenta implicated?
What are the principle physiologic aberrations? (3)
HTN, edema and proteinuria.
Uncertain, but pre-eclampsia develops shortly after delivery of the placenta.
- Abnormal placental vasculature - failed remodeling of maternal vessels.
- Endothelial dysfunction and imbalance of angiogenic and anti-angiogenic factors
- Coagulation abnormalities
Eclampsia is..
Pre-eclampsia + convulsions and coma (CNS changes)
What morphological changes occur in pre-eclampsia in the following organs:
Placenta
Liver
Kidney
Placenta: infarcts, exaggerated ischemic changes, retroplacental hematomas, abnormal decidual vessels.
Liver: irregular, focal, subcapsular and intraparenchymal hemorrhages.
Kidney: swelling of endothelial glomerular cells.
Hydatidiform mole is concerning due to…
Their increased risk for persistent trophoblastic disease (invasive mole) or choriocarcinoma.
Complete mole is caused by…
Karyotype?
Fertilization of an egg that has lost its female chromosomes - genetic material is completely paternal.
90% are 46,XX
Partial mole is caused by…
Karyotype?
Fertilization of an egg with 2 sperm.
69,XXY (triploid most common), sometimes 92,XXXy (tetraploid).
Continuous elevation of hCG might suggest…
A persistent or invasive mole
What is an invasive mole?
What is done to help medically?
A mole that penetrates or even perforates the uterine wall. hCG always elevated.
They respond well to chemo, but might result in uterine rupture and require a hysterectomy.
Choriocarcinoma definition:
What is a common presentation?
A malignant neoplasm of trophoblastic cells and can be from a previously normal or abnormal pregnancy (moles, abortions, or normal). It is rapidly invasive and metastasizes quickly, but it easily treated with chemo.
Irregular vaginal spotting of bloody, brown fluid.
Placental site trophoblastic tumor (PSTT) is a malignancy of which cells specifically?
Where does it invade?
Prognosis?
Intermediate trophoblasts (extravillous trophoblasts).
Infiltrates the endomyometrium.
Excellent prognosis.
What are 3 diseases/conditions associated with PCOS? (3)
Obesity
T2DM
Early atherosclerosis
Hirsutism, paldness and acne may occur in which disease?
PCOS
When are ovarian tumors most common?
Are they often highly symptomatic?
What is the laterality?
45-65 y/o
Although they have distinctive features and can be hormonally active, they only become symptomatic until they reach a larger size
BL tumors
What symptoms are common in patients with large ovarian tumors?
Abdominal pain, urinary and GI symptoms (ascites maybe) due to compression by the tumor or cancer invasion.
3 serous epithelial-stromal ovarian tumors
Serous
Mucinous
Endometrioid
3 germ cell ovarian tumors
Teratoma
Dysgerminoma
Yolk sac tumor
4 sex cord-stromal tumors
Granulosa tumors
Fibromas/Thecomas
Sertoli-Leydig cell tumors
Leydig cell tumor gonadoblastoma
3 risk factors for developing malignant serous ovarian tumors
What might reduce the risk?
Nulliparity (never/few births)
+ FMH
Heretible mutations - BRCA1 and BRCA2
OCs and tubal ligation might reduce risk
How are mucinous ovarian tumors unique compared to other ovarian tumors? (2)
What mutation is consistent in these tumors?
The surface of the ovary is rarely involved
Very rarely are they BL
KRAS proto-oncogene mutation
High-stage ovarian cancers have often spread by the time of diagnosis, so how do they present? (2)
Where do they metastasize? (4)
Cachexia and peritoneal disease (ascites, omental cake).
Liver, lungs, GI, opposite ovary
What is the use of CA-125?
To monitor recurrence/progression of ovarian cancers
What are the 3 categories of ovarian teratomas?
How common are they? (%)
Mature (benign), immature (malignant) or monodermal/highly specialized.
15-20%
What is a dermoid cyst?
What age group is most common?
A benign cystic teratoma of the ovary lined by skin-like structures.
Young women during reproductive years
What is Meigs syndrome?
What tumors is it most often seen with?
“The triad of benign ovarian tumor with ascites and pleural effusion (right sided) that resolves after tumor resection”
Most often seen in ovarian fibromas
Which Muellerian tumors metastasize to the ovary? (4)
Uterus
Fallopian tube
Opposite ovary
Pelvic peritoneum
Which extra-Mullerian tumors metastasize to the ovary? (5)
Stomach Breast Colon Pancreas Biliary tract
-basically GI + breast
Ovarian torsions can cause…
What ages/times is it most common?
What else is often involved?
If the diagnosis is delayed, what can occur as a result?
Acute lower abdominal pain
Reproductive age (mean is 28 y/o) and a second peak is post-menopause
Tube is often involved
If delated, vascular compromise of adenxa and subsequent infarction can ensue
