The female genital tract Flashcards
What diseases are specific to the vulva?
1) bartholin cyst
2) lichen sclerosus
3) squamous cell hyperplasia or lichen simplex chronicus
What does lichen sclerosus look like?
smooth white plaques that in time coalesce
What happens in lichen sclerosus when the entire vulva is affected?
the labia becomes atrophic and stiffened and the vaginal orifice is constricted
What group of women does lichen sclerosus more commonly occur in?
post menopausal women
What does lichen sclerosus look like on histology?
1) thinned epidermis with disappearance of rete pegs
2) dermal fibrosis with a scan perivascular mononuclear infiltrate
Is lichen sclerosus pre malignant?
NO!
What is the histology seen with squamous cell hyperplasia or lichen simplex chronicus?
1) marked epithelial thickening
2) expansion of the stratum granulosm
3) significant surface hyperkeratosis
Does squamous cell hyperplase or lichen simplex chronicus increase your predisposition to cancer?
NO!
What is a benign tumor of the vulva?
condyloma acuminatum
What are the malignant tumors of the vulva?
1) vulvar intraepithelial neoplasia and vulvar carcinoma
2) extra mammary paget disease
3) malignant melanoma
What is the cause of condyloma cuminatum?
1) sexually transmitted
2) HPV 6 and 11
What is the gross apperance of condyloma cuminatum?
1) verrocous
2) multifocal
3) looks like cauliflower and can be mistaken for laryngeal papiloma
What is the most common type of vulvar carcinoma?
squamous carcinoma
What squamous cell carcinoma is most related to high risk HPV infections?
basolid and warty carcinomas
VIN —–> SCC
What squamous cell carcinoma is not related to HPV?
keratinizing SCC
What cells do HPV infect?
immature basal cells
What cells does HPV replicate in?
1) squamous cells
2) results in a cytopathic effect “kolicytic atypia”
What is the progression of vulvar intraepithelial neoplasia (VIN) cause basaloid or warty carcinomas?
1) HPV infection
2) low grade dysplasia
3) moderate dysplasia
4) severe dysplasia (carcinoma in situ)
5) invasive squamous carcinoma
What causes non-HPV related VIN and what does it lead to?
probably caused by chronic irritation in the elderly. leads to keratinizing squamous carcinomas
What does extramammary pagets disease look like clinically?
1) pruritic
2) red
3) crusted
4) sharply demarcated
5) on the labia majora
What does extra mammary pagets disease look like on histology?
large tumor cells with a clear halo
What do patients with extra mammary pagets disease also have?
all have an underlying breast carcinoma
What product caused benign vaginal lesions in some babies?
DES - diethylstilbestrol
What are the tumors of the vagina?
1) vaginal intraepithelial neoplasia
2) squamous cell carcinoma
3) embryonal rhabdomyosarcoma
What is the most common malignant neoplasm of the vagina?
metastasis from the cervix
What is embryonal rhabdomyosarcoma also called and who does it occur in?
1) sarcoma botryoides
2) infants less than 5
What does embryonal rhabdomyosarcoma look like clinically?
1) polyploid, round bulk mass
2) protrudes out of vagina
3) bag of grapes
What does embryonal Rhabdomyosarcoma look like on histology?
1) small cells with oval nuclei
2) small protrusions of cytoplasm
3) striations within the cytoplasm
What is the more recent terminology for cervical intraepithelial neoplasia?
1) CIN I - mild
2) CIN II - moderate
3) CIN III - severe
What terminology are clinical decisions based on for CIN?
1) CIN I - low grade
2) CIN II and III - high grade
What are the characteristics of an SIL or squamous intraepithelial lesion?
1) nuclear atypia
2) enlargement
3) hyperchromasia (dark)
4) variation in nuclear size
What is koliocytosis?
1) involves mature squamous cells
2) bi nucleation and cytoplasmic halos
What are the differences in atypia found in the different stages of CIN?
1) CIN I - atypia in lower 1/3 of epithelium
2) CIN II - atypia 2/3 of epithelium
3) CIN III - full thickness atypia (Carcinoma in situ)
What is p16?
1) a gene that encodes for cyclin kinase inhibitor
What does cyclin kinase inhibitor do?
it is a cell cycle regulatory protein which inhibits the cell cycle
What is wrong with p16 in cells with HPV?
There is an over expression of p16 (cyclin kinase inhibitor)
What do ALL high grade squamous intraepithelial lesions have?
HPV 16 and HPV 18 infections
What are the recommendations for pap screening?
1) first pap - 21 y/o or within 3 years of onset of sexual activity and after on an anual basis
2) after age 30 - with 3 normal results - screened every 2-3 years
What are the two types of cervical carcinoma and how common are they respectively?
1) squamous cell carcinoma - 80%
2) adenocarcinoma - 15%
What is an immediate precursor to squamous cell carcinoma?
CIN III (HSIL)
What is endometriosis?
presence of endometrial tissue outside the uterus
What are the most common sites of endometriosis?
1) ovaries
2) uterine ligaments
3) rectovaginal septum
4) cul de sac
5) pelvic peritoneum
What is the clinical presentation of endometriosis?
1) infertility
2) dysmenorrhea (painful menses)
3) pelvic pain
4) women of reproductive age
What can endometriosis give rise to?
carcinoma
What are the two theories on how endometriosis occurs?
1) metastatic theory
2) metaplastic theory
What is the main thought behind metastatic theory and what is some proof behind it?
1) retrograde menstration
2) proof - shed of endometrium in peritoneal fluid, high incidence in women with retrograde flow
What is the main thought behind metaplastic theory and what is some proof behind it?
1) endometrium could arise from epithelial lining of pelvic peritoneum or mullerian remnant tissue
2) proof - endometriosis in men and females with turner syndrome
What two things are present on histological diagnosis of endometriosis?
1) endometrial glands
2) endometrial stroma
What causes endometrial hyperplasia?
1) due to prolonged estrogen stimulation
2) increased number of glands
What are the 4 categories of endometrial hyperplasia?
1) simple without atypia
2) simple with atypia
3) complex wtithout atypia
4) complex with atypia
What category of endometrial hyperplasia is most likely to progress to carcinoma?
complex with atypia: 23-48%
Who is most likely to get endometrial carcinoma?
1) post menopausal women (55-65)
2) post menopausal bleeding
What have mutations of PTEN tumor supressor gene been associated with?
1) endometrioid carcinomas
2) endometrial hyperplasia
What is the most common type of endometrial carcinoma?
endometrioid adenocarcinoma
What are the associations with endometriod type carcinoma?
1) estrogen
2) age 55-65
3) hyperplasia
What are the associations with non-endometrioid carcinoma?
1) older females: 65-75
2) p53 mutations
3) poor prognosis
4) not related to estrogen
5) includes serous, clear cell and mixed mullerian tumors
What are the benign and malignant tumors of the myometrium?
1) benign - leiomyomas
2) malignant - leiomyosarcomas
What is a leiomyoma?
1) most common benign tumor in women
2) originates from smooth muscle
3) most of the women are child bearing age
What is the gross appearance of a leiomyoma?
1) sharply circumscribed
2) round
3) firm
4) gray-white
What is the histological apperance of a leiomyoma?
1) bundles of smooth muscle cells
2) uniform in size and shape
3) rare mitotic figures
Who is most susceptible to a leiomyosarcoma?
1) equally common before and after menopause
2) peak age 40-60
What is the prognosis of leiomyosarcoma?
1) tendency to metastasize
2) 5 year survival of 40%
What is the gross appearance of a leiomyosarcoma?
1) bulky, fleshy masses invading the uterine wall
2) polypoid masses that project into the uterine lumen
What is the histology of a leiomyosarcoma?
1) bundles of smooth muscle cells with pleiomorphic and abundant mitotic figures
2) enlarged and irregular nucleus
What are the non-neoplastic/functional cysts of the ovaries?
1) follicle and luteal cysts
2) polycystic ovaries and stromal hyperthecosis
What are tumors of the ovaries?
1) surface epithelium tumors
2) sex cord stromal tumors
3) germ cell tumors
4) metastatic tumors
How common are cystic follices in the ovaries?
so common they are basically normal
What are cystic ovarian follicles?
1) originate in unruptured graafian follicles or in follicles that have ruptured and immediately sealed
2) usually multiple
2) up to 2cm in size
What is polycystic ovaries and stromal hyperthecosis?
1) numerous cystic follicles often associated with oligomenorrhea
2) high levels of LH (anovulation, hyperandrogenism)
3) persistent amenorrhea, obesity, hirsutism and rarely virilism
What is hirsutism?
presence of excessive terminal hair in androgen-dependent areas of a womans body
Why is ovarian cancer so bad?
only 3% of all female cancer BUT detected when they have metastasized and account for a very high number of deaths
What are 3 types of tumors of the surface epithelium of the ovary?
1) serous tumor
2) mucinous tumor
3) endometroid tumor
What are risk factors for serous epithelial tumor of the ovary?
1) nulliparity
2) family history
3) mutations - BRACA1 and BRACA2
What mutations are associated with malignant serous carcinoma of the ovary?
1) low grade - KRAS, BRAF
2) high grade (de novo) - p53, BRACA 1/2
What are risk factors for mucinous epithelial ovarian tumors?
1) smoking
2) KRAS mutations
What is the histology of mucinous epithelial ovarian tumors?
tall columnar epithelial cells with apical cilia
What mutations are associated with endometriod tumors of the ovary?
1) PTEN tumor suppressor gene
2) KRAS and b-catenin oncogenes
3) micro satellite instability
What is present in the serum of most patients with serous and endometrioid carcinomas and why is it not good for screening?
1) CA-125
2) can be elevated with non-specific irritation
What is the most common germ cell tumor?
teratoma
What are the contents of a teratoma?
1) wall of cyst - squamous epithelium with hair shafts and sebaceous glands
2) cyst contents - hair, bone, cartilage, brain
What is dyserminoma and whatis its prognosis?
1) ovarian counterpart of seminoma of testis
2) large polyhedral tumor cells with central round nucleus, with surrounding lymphocytes
3) responsive to chemo - 80% survival
What is an endodermal sinus (yolk sac) tumor?
1) rare
2) rich in alpha fetoprotein and alpha 1 antitrypsin
3) schiller-duval body - central blood vessel surrounded by germ cells
What is a chriocarcinoma?
1) very aggressive but rare
2) exist mostly in combo with other germ cell tumors
3) identical to placental choriocarcinoma
4) high blood levels of hCG
What happens with a granulosa theca cell tumors in young females vs adult females?
1) young females - precocious puberty
2) adult females - endometrial hyperplasia, cystic disease of the breast
What are the characteristics of a granulosa theca cell tumors?
1) elevated inhibin serum levels
2) usually unilateral
3) yellow cut surface - lipids
4) call-exner body - gland like structure filled with central acidophilic
What are fibromas, thecomas and fibrothecomas?
1) fibromas - tumors composed of fibroblast
2) thecomas - plump spindle cells with lipids
What are the characteristics of fibroma, thecoma and fibrothecomas?
1) unilateral (90%)
2) majority are hormonally inactive and benign
3) pelvic mass + ascites + hydrothorax = meig’s syndrome
What is a sertoli-leyding cell tumors (androblastomas)?
1) produce masculinization due to androgen production - atrophy of breasts, amenorrhea, sterility and loss of hair
2) progress to virilization (hirsutism) - male distribution of hair, hypertrophy of clitoris and voice changes
What does a sertoli-leyding cell tumor look like grossly?
solid, golden yellow (lipid)
What does a sertoli-leyding cell tumor look like on histology?
tubules composed of sertoli cells or leydig cells
What are the gestational trophoblastic diseases?
1) hydatidiform mole
2) invasive mole
3) tumors
a) choriocarcinoma
b) placental site trophoblastic tumor
What is a hydatidiform mole?
1) cystic swelling of the chorionic villi
What age groups are hydatidiform moles most common?
1) teens
2) 40-50
What is a complete hydatidiform mole?
1) fertilization of an egg that has lost its chromosomes - genetic material is parenterally derived
2) 46 XX (90%)
3) 10% fertilization of an egg by two sperm
4) not usually fetal parts
5) small risk of choriocarcinoma
What is a partial hydatidiform mole?
1) fertilization of an egg with two sperm
2) triploid karyotype (69 XXY)
3) tetrapolyd (92, XXXY)
4) more often fetal parts
5) no risk of choriocarcinoma
What does a complete mole show on histology?
1) show abnormalities that involve all or most of the villous tissue
2) enlarged chorionic villi and proliferation of trophoblast that involves the entire circumference of the villi
What does a partial mole show on histology?
1) abnormalities involve only a portion of the villi
What is p57KIP2?
a gene that is maternally transcribed but paternally imprinted and shows expression in maternal decidual tissue and cytotrophoblast and stromal cells when maternal genetic material is present
Is p57 expressed in hydatidiform moles?
1) complete mole = negative p57
2) partial mole = positive p57 (has maternally derived tissue)
What are the treatments for hydatidiform moles?
1) curettage
2) monitor serum concentrations of HCG (6 months to a year)
What is an invasive mole?
1) mole that penetrates or perforates uterine wall
2) persistent elevated serum HCG
3) treat with chemotherapy
What is a choriocarcinoma?
1) malignant neoplasm of trophoblastic cells derived from a previously normal or abnormal pregnancy
Where do choriocarcinomas arise from?
1) 50% - hydatidiform moles
2) 25% - previous abortions
3) 22% - normal pregnancy
What is seen on histology with choriocarcinomas?
1) does not contain chorionic villi - contains syncytiotrophoblast and cytotrophoblast
2) invades myometrium, has a rapid growth
3) metastasis to lung, vagina, brain, liver and kidney
What is the treatment for choriocarcinoma?
1) chemotherapy - 100% remission
2) high cure rate
