L16- gynecological and breast malignancies

gestational trophoblastic diseases (GTD)

• molar preg

• malignant gestational trophoblastic neoplasia (GTN)

gestation

• preg/ther period the time btwn conception and birth

trophoblasts

cells that help form a layer around dev embryo adn eventually become a major part of the placenta (and procuce hCG)

GTD

• disorders related to abnormal proliferation of placental trophopblasts

molar preg

• aka hydatiform mole (HM)- MC form

• premalignant condiiton

• occurs after abberrant fertilization btwn egg and sperm

• abnormal proliferation of placental trophoblst causes a cystic tumor to form

• arises from gestaritional and not maternal tissu

• partial or complete molar preg

  • more common in females at extremem s of materal age (<20 or >35)

  • risk of GTN

partial molar preg

• triploid (XXX,XXY, or XYY) usuallu from fertilization of a normal ovumm by two sperm

• fetus present- cardiac activity may be detected

• almost always results in intrauterine death early in the pregnancy- often misdx as an incomplete or missed abortion

• hCG levels generlaly LOWER compared to complete molar preg

complete molar preg

• diploid- most cases due to fert of an ovum by single sperm that then duplicates its DNA and maternal chrom are lost

• no fetus is present

• marked elevation of hCG compared to partial molar preg

• higher risk of gestational trophoblastic neoplasia compared to partial molar preg

molar preg- manifestations

• initial missed period and positive preg test

• most cases dev vaginal bleeding in first trimester

• uterine size greater than gestational age in complete molar

  • picked up on physical exam or US

  • due to large volumes of molar tissue and retained blood

• n/v

  • thought to be related to high hCG levels

• sx tend to be more severe in complete

  • hyperthyroidism and preecmlampsia can dev if preg gets to second semester (rare)

molar preg- dx findings

• consider in any reproductive age female with abnormal vaginal bleeding

• serum hCG

  • elevated and usually higher than with normal preg of same gestational age

  • levels often >50,000-100,000mlU/mL

• transvaginal US

  • complete- no fetus/amniotic fluid+ hetero mass with anechoic spaces, SNOWSTORM appearance or (swiss cheese/cluster of grapes)

  • partial- fetus present but often growth restricted + enlarged placenta with cystic spaces

molar preg- dx

• made clinically and then confirmed on histology after uterine evacuation

• for partial with + fetus/cardiac activity, follow with serial hCG/US until a normal/viable preg is suled out

molar preg- tx; surgery

• surgical uterine evacuation (dilation and evacuation- D&E) = MC

• hysterectomy is alternative esp in those who have completed childbearing

molar preg- tx; post op serial hCG measurements

• weekly checks until levels are undetectable OR documented to be plateauing/rising

• mUST use reliable contraception during this time

molar preg- tx; prophylactic chemo

• only considered in cases of complete molar preg of post op hCG unavailable and high risk of GTN (age >40, hCG >100,000, uterine size greater than gestational age)

• NOT indicated in cases treated with hysterectomy

gestational trophoblastic neoplasia (GTN)

• group of malignant neoplasms consisting of bnromal proliferation of trophoblastic tissue

• may follow a molar (more common) OR nonmolar pregnancy (term/preterm, preg loss, tubal preg)

  • trophoblastic tissue that is retianed in the uterus becomes cancerous

GTN types

• invasive mole (only occurs after molar preg)

• choriocarcinoma (aggressive)

• placental site trophoblastic tumor (PSTT)

• epitheloid trophoblastic tumor (ETT)

GTN RF

• prior to molar preg, advanced maternal age, asian/american indian ancestry

• MC sites of metastatic disease are the lungs and vagina

GTN- manifestations

• elevated hCG (either during post-op surveillance of molar preg or after nonmolar)

• hyperthyroidism- tachy, tremor

• ovarian theca lutein cysts

• hyperemesis

• abnormal uterine bleeding OR amenorrhea

• pelvic pain

• sx of mets

  • dyspnea, chest pain, cough, hemoptysis, vaginal bleeding/discharge

GTN- dx findings

• serum hCG

  • greater degree of elevation in cases fo invasive mole and choriocarcinoma

  • PSTT and ETT have lower levels

• TVUS

  • initial imaging of choice- typically shows a poorly defined intrauterine masss + vascular flow on doppler

• CXR

  • obtain baseline to eval for lung mets

• clinical dx made based on hCG after preg with US showing changes of GTN

GTN- tx

• tissue dx NOT required prior to tx

  • biopsy not pursued due to risk of sig hemorrhage

• tx depends on low risk vs high risk and whether pt desirres future childbearing

• methotrexate ± D&C for those who desire future childbearing

• hysterectomy ± chemo for high risk pts or those who do NOT desire furutre childbearing

whoch type of moalr preg os often misdx as a missed/incomplete abortion

partial molar preg

vulvar cancer- eti

• majority= squamous cell carcinoma (SCC)

  • other types- BCCm melanoma, sarcoma

• pathways

  • HPV associated

  • HPV independent

• HPV 16 and 33

• HPV independent causes are due to chronic inflammatory or autoimmune processes

  • vulvar dystrophy or lichen sclerosus (disease causing chronic vulvar pruritis)

vulvar cancer- presentation

• avg age of dx= mid 60s

• localized plaque, nodule, or mass

  • most on labia majora

  • labia minora, perineum, clitoris less common

  • typically firm adn white/red/skin colored

  • ulcerated or friable surface

• pruritis often present

• less common

  • bleeding

  • pain

  • dysuria

  • enlarged lymph nodes

vulvar cancer- mgmt

• dx made through biopsy of lesion(s)

• colposcopy may be necessary to eval fro subclinical lesions

• staging depends on tumor size, extension

• tx

  • primarily surgical excision of lesion ± lymph noces

  • chemo and rad considered in some cases depending on stagem pt factors, and risk recurrence

vaginal cancer- eti

• primary vaginal cancer= rare

• lesions are more often metastatic from endometrial/cervical/ovarian/breast primary

• cases of primary vaginal cancer are typically SCC

  • other- melanoma, sarcoma, adenocarcinoma

• MC due to HPV

  • 16 and 18

vaginal cancer- presentation

• avg age of dx is 60yo

• vaginal bleeding most common sy

  • postmenopausal or postcoital

• many pts are asx

• vaginal mass, discharge, or urinary/GI sx may be noted

• pelvic pain usually absent unless disease extends beyond vagina

• mass, plaque, or ulcer ion exam

  • posterior wall of upper one third of vagina= MC SITE

  • MOVE speculum during exam and inspect during removal top ensure entire area visualized

vaginal cancer- mgmt

• cytology specimen shoudl be taken during initial exam

• biopsy to confirm dx

  • done in office or under anesthesia

• colposcopy may be necessary to eval for subclinical lesions

• chest and skeletal xrays fro staging

• CT/MRI can help with tx planning

  • tumor may extend to other pelvic structures (bladder, rectum, urethra)

• surgical excision ± rad fro most pts

  • chemo for more advanced disease

vulvar squamous intraepithelial lesions (SIL)

• previously vulvar intraepithelial neoplasia (VIN)

• VIN 1/2/3 vs LSIL or HISL documentaiton

• 45-50yo

• HPV = MC

• asx- occ pruritis or dysuria

• biopsy ± coploscopy to confirm

• LSIL- benignm no tx needed unless sx

• HSIL- excision vs ablation or topical imiquimod

vaginal squamous intraepithelial lesions

• squamous cell atypia without invasion

• VaIN 1/2/3 vs LSIL or HSIL doc

• 40-60yo

• HPV = MC

• asx- occ spotting or discharge

• picked up on pap

• LSIL- surveillance, spontaneous regression

• HSIL- excision or ablation

intraepithelial neoplasia (CIN)

• premalignant condition of the cervix

• low of high grade (LSIH/HSIL)

• 25-35yo

• HPV= MC

  • LSIL- subtype 6 and 11

  • HSIL- subtype 16 and 18 most prev

• RF

  • smoking

  • immunosupp

  • multipel sex partners

  • intercourse at young age

  • inad screening

cervical cancer screenign

• average risk

  • pts with cervix who are

    • asx

    • immunocompetent

    • hx of normal screenigns

    • USPSTF guidelines apply

• high rosk

  • pts with HIV ro immunosuppression

    • soli dor organ transplant

    • stem cell transplant

    • SLE

    • IBD/rheum on CURRENT immunosupressives

    • testign hsoudl include cytology

    • annual exam with insepction

    • lifelong screening

adequate negative prior cervical screening

• no hx CIN2+ fro past 25years AND

• two consecutive neg HPV tests in past 10years with most recent in past 5 years OR

• two consecutive neagtive co test within past 10 years with most recent in past 5 years OR

• three consecutive negative pap tests in past 10 years with most recent in past 3 years

pap smear cytology

five component

• specimen type: conventionl smear (pap), liquis base dprep, other

• specimen adequacy: satisfactory/unsat for eval

• general categorization: neg for intraepithelial lesio/mal (NILM) or + epithelial cell abnormality

• interpretation/result: NILM, non neoplastic cellulat variations, reactive cellular chages, organisms, other

• adjunctive testing

pap smear cytology- results

epithelial cell abnormalities

• ASC-US: asytp aquam cells of undetermined sig (MC)

• SCC: majority of cervical cancers

pap smear- mgmt

• APP by the ASCCP

• based on pts immediate five year risk of dev CIN 3/AIS/cancer

• fpr most pts ≥25

  • CIN1: observation is typically recommended

  • CIN 2: tx often recommended- excision or ablation

  • CIN3: tx with excision or ablation

  • cervical cancer: surgery or rad ± chemo

pap smear- mgmt excisional procedures

• LEEP

• cold knife cone

• laser cone biopsy

pts under 26 should be offered HPV vaccine if not already received

pap smear- mgmt ablation procedures

• cryptherapy

• laser ablation

• thermoablation

pts under 26 should be offered HPV vaccine if not already received

endometrial hyperplasia

• overgrowth of endometrium

  • often due to excess unopposed estrogen

  • without atypia (benign/nonneoplastic)

  • with atypia (EIN/noeoplastic disease)

  • can progress to /coexist with endometrial CA

endometrial hyperplasia- epi and rf

epi

• perimenopause

• early menopause

RF:

• advancing age

• unopposed estrogen

• tamoxifen

• late menopause

• nulliparity

• PCOS

• ibesity

• diabetes

endometrial hyperplasia- s/sx

• AUB

• abnormal pap (AGC)

• pelvic exam/labs otherwise normal

endometrial hyperplasia- imaging

• US may show thickened endometrium (can be nonspecific in absence of AUB or premenopause)

endometrial hyperplasia- dx

• histologic based on endometrial bx

• D&C

• hysterectomy

endometrial hyperplasia- tx

• EH without atypia- progestin therapy

  • LNG IUD preferred

  • PO megestrol acetate

  • can give COCa od premenopausal

• EH with atypia- hysterectomy

  • progestin therapy for those wishing to preserve fertility

endometrial cancer- epi adn eti

• MC gynecologic malignancy in high income countries

• epi: most cases >55yo

• RF: same as EH

endometrial cancer- S/sx

• AUB

• abnormal pap

• enlarged uterus in advanced disease

• incidental finsdigns on imaging/hysterectomy

endometrial cancer- imaging

• risk of cancer increase as endometrial thickness approaches 20mm on US

endometrial cancer- dx

• histological based on endometrial bx, D&C, or hysterectomy specimen

• eval adnexal mass in those without obvrious source of excess estroge

  • rule out estrogen producing tumor

• genetic testing for lynch syndrome

• staging is done surgically via TAH BSO and lymphadenectomy

endometrial cancer- tx

• surgery ± rad or chemo

ovarian cancer

• mc cause of gynecologic cancer death in US

• epi: avg risk at dx 63yo

• RF:

  • increasign age

  • late menopause

  • nulliparity

  • endometriosis

  • hereditary ovarian cancer syndromes

• protective factors:

  • parity

  • brastfeeding

  • oral contraceptives

  • IUD

  • tubal ligation

ovarian cancer- s/sx

• presentation can be acute or subacute (MC)

• majority of cases are stage III at dx

ovarian cancer- acute sx

• ascites

• pleural effusion

• bowel obstruction

• venous thromboembolism

ovarian cancer- subacute

• bloating/distention

• urinary freq

• nausea

• anorexia

• early satiety

• pelvic/abdominal pain

• vaginal bleeding

ovarian cancer- imaging

• initial pelvic US (or CT if presentation is acute)- shoes adnexal mass

• CT/MRI for further eval and or staging

ovarian cancer- labs

• baseline CA125

ovarian cancer- dx

• histologic often based on tissue obtained during surgery

  • can do image- guided pleural/omental biopsy or paracentesis/ thoracentesis as alternative

  • image guided biopsy of ovary NOT recommended

ovarian cancer- tx

• refer to gyn onc for surgery/chemo

ductal carcinoma

• malignant cells within mammary ductal system

• in situ (DCIS) accounts for 25% of ALL breast cancer cases

• infiltrating ductal carcinoma = MC INVASIVE breast cancer of cases

• more than 90% of DCIS cases are picked up ONLY on routine mamograms

lobar carcinoma

• malignant cells within lobules of breast

• infiltrating lobular carcinoma = second most common type of INVASIVE breast cancer

• compared to ductal carcinoma, more liekly to-

  • be bilateral adn estrogen receptor (ER) positive

  • occur in older females (≥55)

  • grow in target like configuration around normal breast ducts vs forming a solid mass

  • metastasize later ans spread to less common locations (peritoneum, meninges, GI tract)

what is the most freq dx malignancy and leading cause of cancer death in females worldwide

breast cancer

breast CA s/sx

• abnormal mammogram

• firm, immobile, single breast mass with irregualr borders

• axillary adenopathy in locoregional disease

• back/leg pain (bone mets), abdominal pain/jaundice (liver mets), SOB/cough (lung mets)

breast cancer imaging

• mammogram- soft tissue mass or density , microcalcifications

• breast US- helpful to dist benign vs malignant + hypoechogenicity, calcifications, shadowing

• breast MRI- screening in high risk cases + irregular margins and rim enhancement

breast CA- dx

• malignant epithelial cells on biopsy (ductal, lobular, mixed are the most common types)

• eval for mets- may include bone scan, MRI/CT of abdomen/chest, or PET scan

• tets for estrogen (ER) adn progesterone (PR) receptors adn human epidermal growth factor 2

  • helps determine tx and prognosis

• discuss option of genetic eval to determine personal/family risk of breast/other malignancies

key criteria for genetic risk eval - breast CA

• personal hx dx≤65

• triple neg breast CA
  personal/fhx of ovaria, male, metastatic prostate, or exocrine pancreatic CA

staging- tumor size

• T1- <2cm

• T2- 2-5cm

• T3- >5cm

• T4- extends to skin or chest wall

staging- lymph nodes

• N0- no lymph node metastasis

• N1- metastasis to ipsilateral, movable, axillary LN

• N2- metastasis to ipsilateral fixed, axillary, or IM LN

• N3- mestastasis to infraclavicular/supraclvicular LN, or to axillary and IM LN

staging- metastasis

M0- no distant metastasis

MI- distant metastasis

breast CA- tx

surgery

• lumpectomy- breast conservation

• simple/total mastectomy- complete removal of entire breast and underlying fascia of pectoralis major muscle

• modified radical mastectomy- simple mastectomy alogn with removal of axillary lymph nodes

radiation

• post op therapy indicated for those high risk of recurrence

systemic therapy

• chemo- kills cancer cells

• selective estrogen receptor modulator (SERM)- estrogen antagonist, used in ER- receptor + cases (tamoxifen)

• aromatase inhibitors (AI)- endocrine tx for hormone receptor + cases (anastrozole, letrozole)

• trastuzumab- antiHER2 agent

pagets disease of the breast

• less common form of breast cancer

• peak incidence age 50-60

pagets disease of the breast- s/sx

• unilateral scaly, raw, vesicular/ulcerated lesion beginning on the nipple and spreads to areola

• occ bloody discharge

• pain/burning/pruritis are common and may precede lesion- follow closely

• underlying reast cancer present in 85%of cases ± breast mass or abnormal mamm

pagets disease of the breast- dx

• nipple biopsy (punch or wedge) + malignant intraepithelial adenocarcinoma cells (paget cells)

• mamm to eval for underlying mass- breast bx if abnomral

• breast MRI of mamm is normal

pagets disease of the breast- tx

• if underlying cancer, follow appropriate tx (surgery, rad, chemo)

• if NO underlying cancer identified, still concern fro ccult malignancy, recommend resection og nipple-areolar complex followed by whole breast rad

inflammatory breast cancer

• rare, aggressive form of breast cancer- often presents as advances disease

• avg age 59

• in US, more common in black vs white females

inflammatory breast cancer- s/sx

• rapidly growing breast lump with a tender, firm, or enlarged breast

• skin over breast is warm, pink/red and thickened with peau d’orange appearance

  • will often receive abx for presumed mastitis which will provide no benefit

• nipple may be flattened with crusting, blistering, or retraction

• swelling or pain form lymph node involvement (most cases) adn or mets (1/3 of cases)

inflammatory breast cancer- eval

• mamm + US of breast and regional LN

• core needle bx

• chest/pelvis (CAP) CT and bone scan to check for mets

inflammatory breast cancer- dx

• rapid onset of breast erythema, edema, and or peau d’orange ± underlying palpable mass

• duration od sx no more than 6 months

• erythema occupying at least 1/3 of breast

• pathologic confirmation of invasive carcinoma

inflammatory breast cancer- tx

• non-metastatic- chemo followed by surgery or rad

• metastatic- chemo ± rad

what is the most likely presentation of ductal carcinoma in situ (DCIS)

abnormal mamm