Female Reproduction Pathology Review

8/11/2019 Female Reproduction Pathology Review

1/23

Pathology of uterine corpus:

Endometrium

mucosal lining of uterine cavity

hormonally sensitive

Estrogen --> proliferation

progesterone --> preparation for implantation (secretory phase)

loss of progesterone --> menses

Myometrium

s mooth mus cle

proliferative secretory

http://missingli nk.ucsf.edu/lm/IDS_107_Cervix_Ovary_Uterus/homepage.htm

Asherman syndrome:

secondary amenorrhea due toloss of basalis+ scarring

secondary of overaggressive D+C
http://www.google.com/url?q=http%3A%2F%2Fmissinglink.ucsf.edu%2Flm%2FIDS_107_Cervix_Ovary_Uterus%2Fhomepage.htm&sa=D&sntz=1&usg=AFQjCNFEwjx64BADBatKNZGgHy1vSTJ0Dw


2/23

Abnormal Uterine Bleeding: Anovulatory cycle

polymenorrhea: bleeding occurs in intervals 7 days)/ excess ive (>80mL) bleeding - at regular intervasoligomenorrhea:> 35 day cycleMetorrhagia: frequent / irregular intervalsMenometrorrhagia:prolonged/excess ive, frequent, irregulardysfunctional uterine bleeding:anovulatory vs ovulatory

excessive / prolonged estrogen stimulation WITHOUT counteractive effect of progestational phase

Estrogen -- builds up endometrium

built up endometrium (due to E) will breakdown/shed --> irregular bleeding

progesterone -- stabilize endometrium (withdrawal of progesterone --> menses)

most common in menarche + perimenopausal women

Causes:

usually subtle hormone imbalance - no obvious cause

endocrine: thyroid, adrenal, pituitary disorders

functioning ovarian tumor or polycystic ovaries

metabolic disturbance --- obesity

Histology: proliferative glands- secondary to estrogen exposure

no secretory changes

breakdown of stroma (stromal condensation) when estrogen levels diminish

estrogen withdrawal

glandular + stromal breakdown


3/23

Changes induced by exogenous progesterone

seen in women on OCP + in women attempting to control bleeding

undeveloped glands with stromal cells showing enlargement + abundant

eosinophilic cytoplasm (Decidualized stroma)

enlarged stromal cells with more abundant pink cytoplasm (Decidualized)

with inactive glands

Chronic endometritis:

may cause pelvic pain, infertility, bleeding May be due to:

retained products of conception retained IUDs previous instrumentation chronic PID often cause unknown

Histology **plasma cells**

Rx:AB

Endometrial polyps:


4/23

proliferation of endometrial glands + stroma benign -- may contain hyperplasia or carcinoma

increased in patients taking tamoxifen tomaxifen:

antiestrogenic effect on the breast but a weak pro-estrogenic effect on theendometrium

Endometriosis

https://secure.health.utas.edu.au/intranet/cds/pathprac/Files/Cases/Female/Case58/Case58.htm

presence of endometrial glands or stroma in abnormal extra-uterine locations reproductive age F (10%) symptoms:

inferti lity - 30-40% scarring increases risk of ectopic (fallopian tube mucosa)

dysmenorrhea (painful menstruation) cycles with the normal endometrium

Pain: pelvic pain: uterine ligament pain w/ urination: bladder wall

pain w/ defecation: pouch of douglas Sites of involvement:

ovaries, uterine ligaments, rectovaginal septum, cul de sac, pelvic peritoneum, GI, cervix,vagina. fallopian tubes , laparotomy scars
https://www.google.com/url?q=https%3A%2F%2Fsecure.health.utas.edu.au%2Fintranet%2Fcds%2Fpathprac%2FFiles%2FCases%2FFemale%2FCase58%2FCase58.htm&sa=D&sntz=1&usg=AFQjCNF5GxVef4SpooYtuMJJH_v5vfBGcQ


5/23

Theories for development: Metastatic theory:

retrograde menstruation through the fallopian tubes arises directly from the coelomic epithelium

mesothelium of pelvis or abdomen

Gross: white, tan nodule in

cul-de-sac,rectovaginal space,peritoneum

ovary bleeding =chocolate cyst

Complications: scarring --> infertility malignancy can develop

ovary and gynecologic tract rare cases in the intestine

Adenomyosis:

endometrial glands and stroma in the myometrium 20% of uteri removed symptom = pelvic pain


6/23

Endometrial carcinoma most common invasive cancer of the female genital tract in US post-menopausal (55-65)

presents as post-menopausal bleeding(must do an endometrial biopsy) endometrial biopsy & curettage

two types type I: hyperplasia type II: sporadic pathway

preneoplastic / neoplastic lesions precurs or

s imple hyperplas ia complex hyperplasia simple atypical hyperplasia (rare) complex atypical hyperplasia alternative endometrial intraepithelial neoplasia (EIN) for precursor lesions

Endometrial carcinoma type I/II carcinoma

Type 1 -75% type 2

increase in the gland: stroma ratio associated with prolonged estrogen

stimulation of the endometrium obesity late menopause polycytic ovarian disease functioning ovarian tumors prolonged estrogen administration

Genetic alterations: inactivation of the PTEN (TSG)

Histologic types: serous:

high cytologic atypia/ mitosis/papillary

clear cells

carcinosarcoma (malignant mixedmullerian tumor - MMMT)


7/23

http://ww w .w ebpathology.com/image.asp?n=15&Case=569

combined sarcoma carti lage / bone/

rhabdomyoblasts + carcinoma (metaplastic) aggressive 5yr 25-30% survival F > 60

high grade generally > aggressive than type 1

55-65 65-75

unopposed es trogenobesityHTNDM

atrophythin

endometriod morphology serous , clear cell, carcinosarcoma, MMMT

hyperplas ia endometrial intraepithelial carcinoma (rare)

PTEN, PIK3CA, KRAS, MSI, B-catenin P53, aneuploidy, PIK3CA

less aggress ive -- spread via lymphatics aggress ive -- intraperitoneal / lymphatic spread

incidence = 85% incidence = 15%

Histologic grade: grade 1: well differentiated (< 5% solid) grade 2: moderately differentiated (5-50% solid) grade 3: poorly differentiated (>50% solid)

Prognosis: most are stage 1 (confined to the uterus) > 90% survival grade III - stage I ~75% 5yr survival

survival drops to 50% for stage II/III

Mesenchymal tumors- uterus
http://www.google.com/url?q=http%3A%2F%2Fwww.webpathology.com%2Fimage.asp%3Fn%3D15%26Case%3D569&sa=D&sntz=1&usg=AFQjCNFrMJ1I0XGz2aOSoGDJ5LWM6o1GVghttp://www.google.com/url?q=http%3A%2F%2Fwww.webpathology.com%2Fimage.asp%3Fn%3D15%26Case%3D569&sa=D&sntz=1&usg=AFQjCNFrMJ1I0XGz2aOSoGDJ5LWM6o1GVg


8/23

smooth muscle tumor endometrial stromal tumor

leiomyoma leiomyosarcoma

endometrial stromal nodule endometrial stromal sarcoma

Leiomyoma - fibroid

very common (increased incidence in AA) 75% are reproductive age F

Symptoms: abnormal bleeding / urinary fq fq cause of spontaneous abortion + infertility Malignant change = very rare

not regarded as a precursor to leiomyosarcoma Rx:

myomectomy hysterectomy uterine artery embolization GnRH agonists: continuous stimulation = inhibitory --> hypoestrogen state

used to shrink fibroid prior to Sx Pathology

well circumscribed, white, tan, firm mass size: range - microscopic --> 20 cm often multiple enlarged during pregnancy / shrink post menopause (E sensitive)


9/23

location: intram ural submucosal subserosal +/- broad ligamanet / cervix

Histology: smooth muscle cells no significant cytologic atypia - few/no mitoses

leiomyosarcoma:

malignant smooth muscle tumor peak incidence 40-60 aggressive malignancy with frequent lung mets gross:

bulky, fleshy mass, not well circumscribed, hemorrhage Histologic criteria:

mitotic activity cytology (nuclear) atypia necrosis/hemorrhage

Gestational + Placental disorders spontaneous abortions

ectopic pregnancy abnormalities in placental implantation placent previa placental accreta/incretia/percretia

placental infections pre-eclampsia / eclampsia gestational trophoblastic disease

Ectopic Pregnancy:


10/23

implantation of the products of gestation in any site outside the normal intrauterine location occurrence:

1/150 pregnancies symptoms

severe abdominal pain about 6 wks after last menstrual period Predisposing conditions:

prior peritubal scarring(chronic salpingitis) adhesions (appendicitis, endometriosis, prior surgery) location

fallopian tube (90%) abdominal cavity, intrauterine portion of the fallopian tube, ovary (rare)

histologic: chorionic villi + trophoblastic cells

may see only trophoblastic cells only

abnormalities in placental implantation:


11/23

Placental previa Placenta Accreta placenta increta

placental implants in the lower uterinesegment or cervix and may result inbleeding

3rd tr imester painlessbleeding often requires C-section

partial or completeabsence of deciduawith adherence of the placental villoustissue directly to the myometrium

failure of the placenta to separate fromthe myometrium is a cause ofpostpartum bleeding (life-threatening)

often rq hysterectomy

placenta dissectingthrough themyometrium

Placental infections:

bacterial: acute chorioamnionitis + acute villitis opaque membrane (normal = translucent) acute inflammation in the chorionic membrane extending --> amnion

TORCH + syphilis + TB + rubella + CMV + HSV --> chronic villitis


12/23

Gestational trophoblastic disease:tumor/ tumor-like conditions characterized by a proliferation of placental tissue

hydatiform mole: complete/ partial / invasive choriocarcinoma placental site trophoblastic tumor

Hydatidiform Molar Pregnancies

US incidence is 1 / 1000 2000 pregnancies. 7-10 times higher in Asia than in North America and Europe.

Patients with > four pregnancies and increased number of abortions are at high risk >50% are complete moles. 25-43% partial moles.

complete partial

genetics empty ovum + 2 sperm (46) normal ovum + 2 sperm (69)

fetal tissue none present

villous edema most some

trophoblastic proliferation diffuse, circumfrentialproliferation around hydrophic

villi

focal proliferation aroundhydrophic villi

choriocarcinoma risk 2-3% minimal

Clinical symptoms: Uterus larger than expected for date of gestation


13/23

passage of grape-like masses High HCG level that expected for date of gestation Often diagnosed in the first trimester today

Fetal heart sounds absent Snow storm appearance on ultrasound

Complete Mole

Histologic Features

Enlarged and dilated villi with central cistern formation (cavitations) Circumferential trophoblastic proliferation

atypia Early complete mole can be a diagnostic challenge as the proliferation is not as well

developed

Partial mole

karyotype: triploid 69, XXY or tetraploid 92, XXXY +/- fetal parts some vi ll i are edematous trophoblastic proliferation - not as marked as that of a complete mole

Rx: D&C + BHCG monitoring

Px: molar pregnancies have ~10% chance of persis tent moles/invasive mole complete molar pregnancies have 2.5% risk of subsequent choriocarcinoma ***note:

choriocarcinomas arising from gestational pathway - respond to chemo ones that arise from germ cell pathway do not!

partial moles increased risk of persistent molar disease/minimal risk of subsequent choriocarcinoma


14/23

post ovulation: corpus luteum secretes progesterone --> prepares endometrium for possible implantation(secretory phase)

PCOS: (Stein-leventhal syndrome)


15/23

3-6% reproductive aged F obese young inferti le oligomenorrhea hirsutism +/- DM (insulin R)

numerous cystic foll icles oligomenorrhea persistent anovulation, hirsutism, obseity

Pathophys: unclear increased secretion of LH --> excessive androgen production (theca cells) --(Aromatase)->

estrone estrone negative feedback on FSH --> cystic degeneration of follicles high estrone levels --> risk of endometrial carcinoma

LH:FSH > 2

Ovarian cancer:

3% of all cancers US- F 1/70 american women lifetime incidence

risk increases with age 3/100,000 F


16/23

pariety + OCP = protective more deaths than cervical/endometrial cancer clinical:

abdominal distention, ascites, pan complications --> rupture / torsion urinary or GI symptoms No well-validated screening

Genetic risk factors: About 5-10% patients have a first degree relative with ovarian cancer

Compared to a 1-2% risk for the general population women who have relative with ovarian cancer have a 9.4% risk Women who inheri t the BRCA1 or BRCA2 have a 15-40% absolute risk

estimated risk by age 70 -- 20-60% BRCA still explain < 1/3 familial ovarian cancers Usually serous carcinoma and display p53 dysregulation.

Histologic classification of primary ovarian surface epithelial tumors / site of origin serous: fallopian tube / surface epithelial lining

cystadenoma/adenofibroma 70% borderline 10% CA 20-25%

endometrioid: endometriosis

clear cell:endometriosis mucinous:unclear primary

About 10-15% of ovarian tumors; May be combined with other types tumors (serous tumor), teratoma, sex cord stromal tumors. Mean age 51-54

transitional (Urothelial)- poss ible walthard nests

benign - cystadenoma

single cyst w/ simpleflat lining (30-40)

borderline: low malignant potential,atypical proliferating*proliferation - no stromal invasion*

malignant:stromal invasion

serous - 70% Serous Borderline Tumor - 15%

Histology: Proliferation of epithelialcells, but no invasionSynonyms:

Serous borderline tumor (SBT) Serous tumor of low malignantpotential (SLMP)

Atypical proliferating s erous tumor(APST)

low metastatic potential ifconfined to the ovary, may progressover many years

Serous Carcinoma: 5%40-50% of all ovarian malignanciesMean age 56 (45-65)67% BilateralStage distribution:

I: 14% confined to the ovary II: 7% confined to the pelvis III: 63% in the peri toneum

IV: 16% distant metastasis

Size-microscopic to over 20 cmSolid and cystic confluent areas

BRCA1: increased risk serouscarcinoma ovary/fallopian tube

Microscopic


17/23

Destructive stromal invasion

Mucinouscystadenoma 80%

benign: 2-5% bilatlargest ovarian tumorsmulti/uni-cystic

single layer ofcolumnar cells w/ lotsof intracellular mucin(endocervical or GI)

Mucinous borderline 15% increases epithel ial

proliferation w/o destructivestromal invasion

Mucinous Carcinoma 5-10%

5% present stage II+ 5% bilateral gross:large tumors

(15-30cm), multiloculatedcysts w/ mucin

hemorrhage, necrosis, solid+/- papillary areas

http://www.webpathology.com/image.asp?n=14&Case=526

Ovary: Endometrioid Carcinoma

Often (15%-20% of cases) co-exist with endometriosis. Frequent mutations in thePTEN tumor suppressor geneand in the KRAS and -catenin

oncogenes. 40% are bilateral. About 15%-30% are accompanied by a synchronous carcinoma in the endometrium

Microscopic: Resemble endometrioid carcinoma of the uterine corpus

glands and nests of cells invading the ovarian stroma Grade identical to endometrial carcinoma May find adjacent endometriosis

Clear Cell Tumors of the Ovary
http://www.google.com/url?q=http%3A%2F%2Fwww.webpathology.com%2Fimage.asp%3Fn%3D14%26Case%3D526&sa=D&sntz=1&usg=AFQjCNERKdkOapH2WHfYCWxr8kQt4k2ZHQ


18/23

Benign and borderline variants are rare, most are carcinomas Similar histology to clear cell carcinomas of the endometrium

clear cytoplasm Frequently arise in endometriosis Frequently admixed with endometrioid carcinomas

Transitional Cell Tumors

Epithelial elements histologically resembling urothelium May arise from benign Walthards Nests

Vast Majority are benign Brenner tumor uncommon borderline and malignant Brenner tumors

Benign Brenner Tumor

Common incidental finding (microscopic size to several cm) about 4-5% of all benign ovariantumors.

7-8% Bilateral Microscopically:

Mature urothelial-like cells arranged in solid or cystic within a fibromatous stroma


19/23

Associations : mucinous cystic tumors serous cystadenoma dermoid cys t

Metastatic Tumors to the Ovary ~5% of ovarian tumors Non-ovarian primary may present after ovarian met Metastatic mucinous carcinomas are more common than primary ovarian mucinous carcinomas Krukenburg tumor

metastatic mucin-produing signet-ring cell carcinoma typically gastric origin

Common tumors metastasizing --> ovary GYN tract: Tube, endometrium, cervix.

GI tract: Colon, appendix, stomach, pancreas, hepatobill iary tree.

Breast.

Lung. Melanom a.

GU tract: Bladder and kidney. Sarcoma.

Pseudomyxoma Peritonei

Clinical term indicating the presence of mucinous material in the peritoneum (jelly belly)surrounded by fibrous tissue.

almost all are metastatic tumors rather than primary tumors (GI tract, appendix) Generally regarded as malignant, but may have a protracted clinical course.


20/23

Germ Cell Tumors

Teratoma, seminoma, yolk sac, choriocarcinoma, embryonal, mixed type

mature cystic teratomas:

46 xx -- usually reproductive years (but seen all ages 2-80) 27-40% of all ovarian tumors

58% of all benign tumors (almost all benign) mos t form a mas s

Variety of cells from all three germ cell layers: endoderm, mesoderm, ectoderm. Skin and sebaceous glands, hair shafts, bone, cartilage, gastrointestinal epithelium,

bronchial epithelium , thyroid, neural tiss ue.

Skin only dermoid cyst Monodermal teratoma-composed of only one cell type such as thyroid

Teratoma with Secondary Malignant Transformation ~1.5%. usually post-menopausal women,

Squamous cell carcinoma, melanoma, thyroid, adenocarcinoma, carcinoid, skin adnexaltumors, basal cell carcinoma, thyroid carcinoma, chondrosarcoma, etc

Immature Teratoma contains a variable amount of immature, embryonal-type (generally immature neuroectodermal) tissue.

1-2 weeks of gestation-germ cell tumor. 2-8 weeks embryonal. >8 weeks fetal .

Generally seen in patients less than 40, peak incidence of 14-19 years. Raised HCG and AFP levels. Treatm ent

Rapidly growing tumor - graded by amount of immature elements grade I, stage I surgery. > stage I , or higher histologic grade or very large tumors are given chemotherapy


21/23

Mature cystic teratoma- majority and are benign young adult to middle age Multiple different types of cells.

Malignancy Malignant transformation older patients, rare. Immature teratoma younger patients, immature neuroepithelium.

Dysgerminoma

primitive germ cell tumor. +/- elevated Serum LDH His tology:

Proliferation of primitive germ cells large cells w/ clear cytoplasm and central nuclei Lymphocytes and macrophages. Identical to a testicular seminoma.

Respond to chemotherapy and radiation therapy. Stage - significant factor.

yolk sac

#2 malignant tumor of germ cell origin Derived from differentiation of malignant germ cells along the extra-embryonic yolk sac lineage. rich in -fetoprotein. Characteristic feature

glomeruloid-like structure composed of central blood vessel enveloped by germ cells within aspace lined by germ cells (Schiller-Duval body).

Identical morphology to testicular counterpart.

choriocarcinomaNon-gestational

Trophoblastic differentiation within a germ cell tumor. Strict definition of combination of cytotrophoblast and syncytiotrophoblasts (NO villi)

Secrete -HCG


22/23

Less favorable outcome than gestational choriocarcinoma- which is chemo sensitive. Rx: Cytoreductive surgery followed by chemotherapy.

embryonal

Least differentiated form with large, highly atypical cells Highly malignant aggressive malignancy

Treated with chemotherapy

Sex cord stromal tumors

granulosa cell tumor

call-exner bodies

Adult Granulosa Cell Tumors >95% of granulosa cell tumors Middle aged to postmenopausal women Average size 12.5 cm - Commonly encapsulated.

Sectioned surface is yellow to tan withvarious amounts of solid and cysticareas.

Hemorrhage is common

Generally regarded as malignant but low risk formetastasis May show metastasis years after

diagnosis 10-year survival is about 85% may have late > 10 year recurrences and

metastasis

Histopathology Small round cells with scant cytoplasm, and

round to oval nucleus (coffee bean) withlongitudinal grooves.

Variety of patterns microfoll icular insular, moire silk (water silk),

trabecular, diffuse. Call-Exner body gland-like structure filled with

eosinophilic material. Mitotic rate rarely exceeds 1-2 per 10 hpf.

Call-Exner bodies and grooved, coffee bean nuclei Secrete estrogen-may be associated with

endometrial hyperplasia. Inhibin product of granulosa cells.


23/23

Juvenile type granulosa cell tumor 5% of all granulosa cell tumors Firs t 30 yrs Almost always stage I

Less than 5% bi lateral 2% have extraovarian spread. Vast majority are benign.

Associated with precocious puberty.

fibromas, trhecoma, fibrothecoma Composed of plump spindle cells (fibroma) withlipid droplets cells within the cells (thecoma).

Unilateral: 90%. Hormonally inactive Gros sly:

White tan mass. His tology:

Well-differentiated fibroblasts withinterspersed collagen.

Thecoma-fibroma group Generally have a favorable prognosis Association with Meigs syndrome

Ovarian tumor Hydrothorax right side. Ascites

sertoli-leydig cell tumorandroblastoma

Composed of Sertoli cells tubules that resemble testisLeydig cells and primitive gonadal stroma

May see Reinke crystals

Female Reproduction Pathology Review

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