Exam 1 Path Flashcards
Vulvar lesions:
- Cyst located in the posterior aspect of the vaginal introitus
- Painful, warm and erythematous if infected
- Histo: cyst lined with transitional epithelium
Bartholin cyst
Vulvar lesions:
- Post menopausal woman with itchy white plaques of the vulvar and anogenital skin
- Increased risk of TP53+ keratinizing SCC
- Histo: thinning, edematous band, lymphocytic infiltrate
Lichen sclerosus
Vulvar lesions:
- Thickened, reddened vulvar surface caused by habitual rubbing/scratching
- Associated with lichen sclerosus, SCC
- Histo: hyperkeratotic skin with epidermal acanthosis (thickening)
Squamous cell hyperplasia (Lichen Simplex Chronicus)
Vulvar lesions:
- Skin colored exophytic papules and plaques
- Histo: Papillary projections, Koilocytes with prominent perinuclear halos
Condyloma acuminatum (anogenital warts)
*HPV (6, 11)
Vulvar carcinoma: most are SCC
- Age 60 (younger)
- Caused by high risk HPV (16, 18)
- Histo: full thickness atypia
Basaloid/warty SCC (classic VIN)
*contrast with keratinizing SCC
Vulvar carcinoma: most are SCC
- Age 75 (older)
- Caused by chronic irritation (lichen sclerosus or squamous hyperplasia)
- assoc w/ TP53 mutations
- Histo: basal/parabasal atypia +/- keratin pearls
Keratinizing SCC (differentiated VIN)
*contrast with basaloid/warty SCC
Other vulvar neoplasms:
- Solitary, well circumscribed dermal or subcutaneous nodule
- Arise from primitive milk line
- Histo: Benign columnar and myoepithelial cells with apocrine gland differentiation
Papillary hydradenoma
Other vulvar neoplasms:
- Itchy, ill defined, erythematous lesion +/- white crust
- Intraepithelial adenocarcinoma
- Histo: sweat gland and keratinocyte differentiation
Extramammary Paget Disease
Vaginal lesions:
- Reproductive age woman
- Submucosal cyst that arises in lateral vaginal wall
- Can protrude from vaginal orifice
- Histo: cyst with cuboidal lining
Gartner duct cyst (from wolffian/mesonephric duct)
*gartner/mullerian cyst: only difference is histo!
Vaginal lesions:
- Reproductive age woman
- Submucosal cyst that arises in lateral vaginal wall
- Can protrude from vaginal orifice
- Histo: cyst with tubal or endocervical lining
Mullerian cyst (from mullerian/paramesonephric duct)
*gartner/mullerian cyst: only difference is histo!
What exposue?
- Daughter of treated mother develops VAGINAL adenosis
- Eventual clear cell adenocarcinoma of the vagina
Diethylstilbestrol (DES) exposure
Vaginal neoplasm:
- Infant or young girl
- Protruding bulky, polypoid, grape like mass
- Invasion can result in death
- Histo: malignant embryonal rhabdomyoblasts
Vaginal Embryonal Rhabdomyosarcoma (Sarcoma Botryoides)
Vaginal SCC LN spread?
- develops from VAIN (precursor lesion)
- caused by high risk HPV (16,18)
- Located in lower 2/3 of vagina***
SCC in lower 2/3 of vag spreads to inguinal/femoral LNs
Vaginal SCC LN spread?
- develops from VAIN (precursor lesion)
- caused by high risk HPV (16,18)
- Located in upper 1/3 of vagina***
SCC in upper 1/3 of vag spreads to iliac LNs
Cervical neoplasm eitiology:
Most are caused by high risk HPV (16, 18)
E6 viral oncogene function?
Increase telomerase (no division limit) Degrade p53 (tumor suppressor broke)
Cervical neoplasm eitiology:
Most are caused by high risk HPV (16, 18)
E7 viral oncogene function?
Inactivates p21 and RB (bypass G1 to S restriction)
Cervical Intraepithelial Neoplasia (CIN):
Mild dysplasia
CIN I / LSIL
more likely to regress, low chance to progress to HSIL
Cervical Intraepithelial Neoplasia (CIN):
Moderate dysplasia
CIN II / HSIL
more likely to persist, low chance to progres to carcinoma
Cervical Intraepithelial Neoplasia (CIN):
Severe dysplasia / Carcinoma in situ
CIN III / HSIL
Concerning observations for on colposcopy
acetowhite areas = concern for dysplasia
abnormal vessels = concern for carcinoma
Pap screening guidelines:
Start?
21-29?
30-65?
>65?
Start at 21
21-29 = q3y
30-65 = q5y
>65 = none if normal previously
HPV vaccination offered to?
boys and girls starting at age 11
Menstrual cycle histo:
tubular glands with pseudostratification and mitotic figures
proliferative phase (estrogen driven)
Menstrual cycle histo:
“piano key” vaculoles
early secretory phase (progesterone driven)
Menstrual cycle histo:
tortuous serrated glands
late secretory phase (progesterone driven)
Menstrual cycle histo:
tight clusters of stromal cells, ischemia and hemorrhage
menses (dec. estrogen and progesterone)
Diagnosis? (endometritis)
- after giving birth, pt has fever, uterine tenderness and abdominal pain due to bacterial infection (GAS, staph)
- Histo: neutrophil infiltration w/ microabscesses
Acute endometritis
*contrast with chronic endometritis (maybe no sxs, plasma cells, later after giving birth)
Diagnosis? (endometritis)
- may be asymptomatic, abn bleeding, abd pain
- many causes (retained fetal products, IUD, chronic PID)
- Histo: plasma cell infiltration
Chronic endometritis
*contrast with acute endometritis (acute symtoms, neutrophils, right after giving birth)
Diagnosis?
- woman with painful menses
- inspection shows “powder burn” lesions and blood filled cysts
- ectopic tissue present in ovaries, pelvis, GI, bladder
- Histo: endometrial glands, endometrial stroma, hemosiderin laden macrophages
Endometriosis
***survival of ectopic tissue driven by inflammation
inflammation => VEGF=> angiogenesis
increased aromatase increases estrogen, proliferation
mutations in tumor suppressor genes
*contrast with adenomyosis (endometrial tissue in myometrium), same clinical presentation
Diagnosis?
- exophytic benign hyperplastic polypoid mass of the endometrium
- woman taking Tamoxifen
Endometrial polyp
*tamoxifen is proestrogenic in endometrium
Type of endometrial hyperplasia?
- glandular crowding w/ NO atypia
- small carcinoma risk
Typical endometrial hyperplasia
*both types caused by chronic unopposed estrogen
Type of endometrial hyperplasia?
- glandular proliferation w/ atypia
- HIGH carcinoma risk
Atypical endometrial hyperplasia
*both types caused by chronic unopposed estrogen
What are these risk factors for?
Obesity PCOS Estrogen replacement tx Tamoxifen tx Estrogen producing tumor (granulosa or thecoma)
Endometrial hyperplasia/ carcinoma
*unopposed estrogen drives proliferation!!!
Secretory products of what tumors can lead to endometrial hyperplasia/carcinoma?
Granulosa cell tumor and Thecoma
*both release estrogen!!!
Endometrial carcinoma:
- Setting of unopposed estrogen
- Mutations in PTEN, PI3K/AKT, MSI
- Indolent course, more favorable prognosis
- Histo: endometrioid morphology
- younger age of onset
Endometrioid carcinoma (Type 1 endometrial carcinoma)
Endometrial carcinoma:
- Setting of endometrial atrophy in African American
- Mutations in TP53
- Aggressive, poor prognosis
- Histo: papillary growth with atypia
- older age of onset
Serous carcinoma of the uterus
Type 2 endometrial carcinoma
Endometrial carcinoma:
- Setting of endometrial atrophy in African American
- Aggressive, poor prognosis
- Histo: malignant glands and stroma
- older age of onset
Malignant Mixed Mullerian Tumor (MMMT)
(Type 2 endometrial carcinoma)
*contrast with adenosarcoma of the uterus (benign glands and malignant stroma)
Diagnosis?
- endometrioid carcinoma + colorectal/ovarian cancer
- AD inheritance
- mut in mismatch repair gene (MLH1 or MSH2) leading to microsatellite instability (MSI)
Lynch Syndrome
*MSI + unopposed estrogen increases risk for endometrial hyperplasia/carcinoma
Diagnosis?
Endometrial tumor composed of benign glands and malignant stroma
Adenosarcoma
*contrast with MMMT (malignant glands AND stroma)
Diagnosis?
- Malignant endometrial stroma
- Invades myometrium +/- lymph/vascular
- Histo: small blue cell tumor
- JAZF1 mutation
Low Grade Endometrial Stromal Sarcoma
*differentiate from endometrial adenosarcoma and MMMT (mixed tumors)
Diagnosis?
- Benign smooth muscle tumor of the uterus
- White circumscribed nodules
- MED12 mutation
Leiomyoma
Diagnosis?
- Malignant smooth muscle tumor of the uterus
- Bulky fleshy mass
- Aggreessive with likelihood of metz
- Histo: atypia, mitoses, necrosis
Leiomyosarcoma
Fallopian tube lesions:
Paratubal cyst derived from mullerian remnants near fimbriae
Hydatid cyst of Morgagni
Fallopian tube lesions:
Benign tumor of mesothelial origin
Adenomatoid tumor
Diagnosis?
- Hyperandrogenism (inc testosterone, hirsutism)
- Hormonal imbalance (high LH, low FSH)
- Insulin resistance
- Polycystic ovaries
PCOS
*increased risk of endometrial hyperplasia/carcinoma
Epithelial ovarian tumors:
Papillary growth pattern, cystic with tubal-like epithelium
Low grade serous tumor of the ovary
Epithelial ovarian tumors:
- Solid tumor with marked atypia
- p53 mutation
- BRCA1/2 mutations (breast cancer risk/assoc.)***
High grade serous tumor of the ovary
***BRCA1/2 mutations predispose to breast cancer!!!
Epithelial ovarian tumors:
- Tumor of columnar epithelium, cystic lesion filled with mucinous fluid
- Unilateral, malignant
- KRAS mutation
Ovarian mucinous tumor
Epithelial ovarian tumors:
- Endometrial tissue can be precursor lesion
- Carcinoma
Endometrioid ovarian tumor
Epithelial ovarian tumors:
- Histo: large epithelial cells with clear cytoplasm
- Carcinoma
Clear cell ovarian tumor
*NOT associated with DES, that is for clear cell carcinoma of the VAGINA
Epithelial ovarian tumors:
- Tumor comprised of urothelial-type transitional epithelium
- Benign (unilateral)
Brenner tumor (ovarian transitional cell tumor)
Germ cell ovarian tumor:
-comprised of mature tissues from all embryonic layers (hair, teeth, muscle, fat, etc.)
Mature cystic teratoma
Germ cell ovarian tumor:
- prepubertal female or young woman
- malignant immature neuroepithelium
Immature malignant teratoma
Germ cell ovarian tumor:
- comprised of one tissue type
- mature thyroid tissue => hyperthyroidism
- or carcinoid tumor (flushing, diarrhea, hypotension)
Monodermal (specialized) teratoma
Germ cell ovarian tumor:
- ovarian counterpart to testicular seminoma
- KIT mutation
Dysgerminoma
Germ cell ovarian tumor:
- Tumor cells secrete alpha-fetoprotein
- Schiller-Duval body (glomerulus-like structure) on histo
Yolk sac tumor
Germ cell ovarian tumor:
- Malignant trophoblastic tumor
- High B-hCG levels
- Widespread metz common
- assoc w/ complete mole
- chemotherapy has high cure rate
Choriocarcinoma
Ovarian sex cord stromal tumors:
- “coffee bean” nuclei on histo
- release estrogen (endometrial hyperplasia risk)
- stain positive for inhibin
Granulosa cell tumor
- hormonally active tumors are yellow, increased risk for endometrial hyperplasia (adults)
- hyperestrogenism can cause precocious puberty in juvenile tumor
Ovarian sex cord stromal tumors:
- benign tumor of fibroblasts and theca cells
- release estrogen (endometrial hyperplasia risk)
Fibrothecoma (fibroma + thecoma)
*can also exist as individual parts
Diagnosis?***
Ascites
Pleural effusion
Benign ovarian tumor (fibroma most common)
Meigs Syndrome***
Ovarian sex cord stromal tumor:
- Secretes testosterone (defeminization, virilization)
- DICER1 mutation
Sertoli-Leydig cell tumor
*sertoli cells and leydig cells on histo
Metastatic tumor to the ovary:
- mucin rich “signet ring” cells on histo
- Metz from GI tract (colon or stomach)
- Bilateral metz
Krukenberb tumor
Metastatic tumor to the ovary:
- Mucinous ascites (jelly belly)
- Metz from appendiceal mucinous tumor
- Acellular mucin on histo
Pseudomyxoma peritonei
Diagnosis?
- abdominal pain and bleeding 6-8 weeks after LMP
- # 1 risk factor is PID from chlamydia/gonorrhea infection
Ectopic pregnancy
- fetal implantation outside uterus (fallopian tube most common)
- rupture can lead to severe pain and hemorrhagic shock
Diagnosis?
- New onset HTN and proteinuria in pregnancy
- HA and visual changes
Preeclampsia
+seizure = eclampsia
Preeclampsia/eclampsia pathogenesis
- abnormal placental vasculature leads to placental ischemia
- endothelial dysfunction leads to factor release, causing maternal vasoconstriction (HTN)
- resultant hypercoagulable state (fibrin thrombi)
The following are pathological findings for what disease process?
- Infant: abnormal decidual vessels (placental infarcts)
- Mother: fibrinoid necrosis, fibrin thrombi in organs
Preeclampsia/eclampsia
Diagnosis?
Hemolysis, microangiopathic anemia (schistocytes)
Elevated liver enzymes
Low platelets
HELLP syndrome
Gestational trophoblastic disease: findings for Complete Molar Pregnancy 1. Fetal parts? 2. villi involvement? 3.genetic derivation? 4. choriocarcinoma/invasive mole risk?
- multi-cystic mass lesion with “snow storm” US
- cystic swelling of chorionic villi
- abnormally elevated B-hCG
- NO fetal parts
- abnormal villi SURROUND specimen
- Paternally derived (46 XX)
- risk for both choriocarcinoma/ invasive mole
*also p57 negative
Gestational trophoblastic disease: findings for Partial Molar Pregnancy 1. Fetal parts? 2. villi involvement? 3.genetic derivation? 4. choriocarcinoma/invasive mole risk?
- multi-cystic mass lesion with malformed fetus on US
- cystic swelling of chorionic villi
- abnormally elevated B-hCG
- YES fetal parts
- abnormal villi involve small part of specimen
- Maternally and Paternally derived (69 XXX or XXY)
- low risk for invasive mole
*also p57 positive
Gestational trophoblastic disease:
- malignant tumor of INTERMEDIATE trophoblasts
- uterine mass following normal pregnancy or spontaneous abortion
- elevated B-hCG
Placental site trophoblastic tumor
Inflammatory disorders of the breast:
Diagnosis?
- red erythematous breast in breastfeeding mother
- caused by S. aureus (abscess) or GAS (cellulitis)
- infection is secondary to tissue damage
Acute bacterial mastitis
Inflammatory disorders of the breast:
Diagnosis?
- subareolar mass
- smoker (relative vit A deficiency)
- inverted nipple
- keratinizing squamous metaplasia causes duct blockage and abscess formation
Squamous metaplasia of the lactiferous ducts (SMOLD)
Inflammatory disorders of the breast:
Diagnosis?
- inflammation and dilation of the subareolar ducts
- palpable periareolar mass
- thick white (or brown-green) nipple secretion
- multiparous postmenopausal women
- histo markers for chronic inflammation (plasma cells)
Duct ectasia
Inflammatory disorders of the breast:
Diagnosis?
- mass with abnormal calcification on mammogram (due to saponification)
- history of trauma
- necrotic fat and calcifications seen on biopsy
Fat necrosis of breast
Inflammatory disorders of the breast:
Diagnosis?
- granulomatous inflammation in the breast
- systemic granulomatous disease (sarcoid, GPA, TB)
Granulomatous mastitis
Benign epithelial breast lesion prognosis:
cystic change
fibrosis
adenosis
*fibrocystic changes
Non-proliferative changes, no increased risk of invasive carcinoma
these are fibrocystic changes
Benign epithelial breast lesion prognosis:
epithelial hyperplasia sclerosing adenosis complex sclerosing lesion intraductal papilloma gynecomastia
Proliferative changes w/o atypia, 2x increased risk of invasive carcinoma
Benign epithelial breast lesion prognosis:
atypical ductal hyperplasia
atypical lobular hyperplasia
Proliferative changes w/ atypia, 5x increased risk of invasive carcinoma
Inflammatory disorders of the breast:
Diagnosis?
- palpable breast mass with lymphocytic infiltrate
- associatted with autoimmune dz (T1DM, autoimmune thyroid dz)
Lymphocytic mastopathy
Benign epithelial breast tumors:
- tumor of fibrous tissue and glands
- well circumscribed mobile mass distorts ducts
- estrogen sensitive
- MED12 mutation
Fibroadenoma of breast
Benign epithelial breast tumors:
- fibroadenoma-like tumor
- papillary “leaf like” projections on biopsy
- higher cellularity, mitoses, pleomorphism than fibroadenoma (therefore higher risk of malignancy)
- MED12 mutation
Phylloodes tumor
Male breast cancer associations (invasive ductal carcinoma)
BRCA2 mutation and Kleinfelter (XXY)
Greatest risk factor for developing breast carcinoma
lifetime estrogen exposure
Familial ER+ luminal breast cancers are associated with
BRCA2 mutation
*sporadic assoc. w/ PIK3A or TP53
Familial HER2+ breast cancers are associated with
TP53 mutation, Li Fraumeni syndrome
*SBLA = sarcoma, breast, leukemia, adrenal gland
Familial TNBC are associated with
BRCA1 mutation
*sporadic due to TP53 mutation
ER+ breast cancer prognosis and tx
best prognosis, low risk of metz
Tx with tamoxifen
HER2+ breast cancer prognosis and tx
moderate prognosis, bimodal risk of metz (early and late)
Tx with trastuzumab
TNBC prognosis
worst prognosis, likely early metz
Breast neoplasm diagnosis:
- palpable mass with calcification on mammo
- confined to ductal system
- central necrosis of tumor
- may present with inflammation at the nipple
DCIS (comedo type due to necrosis)
*inflammation at the nipple = Paget disease of the nipple and is indicative of underlying DCIS that has invaded the skin (HER2+)
Breast neoplasm diagnosis:
- no palpable mass, incidental finding
- bilateral
- loss of E-cadherin (discohesive, linear growth pattern of lobular tissue)
- most commonly ER+ and PR+
LCIS
*E-cadherin loss = CDH1 mutation, therefore diffuse type gastric cancer assoc.
Special type breast cancers:
- TNBC subtype with better prognosis
- BRCA1 assoc.
- Tumor has lymphocyte and plasma cell infiltrate
Medullary pattern carcinomas
Special type breast cancers:
- soft, rubbery
- malignant cells floating in mucus
Mucinous (colloid) carcinoma
Special type breast cancers:
- dimpling of the skin of the breast (peau d’ orange)
- tumor observed in dermal lymphatics
- poor prognosis
Inflammatory carcinoma of the breast
Most useful staging metric for breast cancer
Node involvement (N), migration to sentinel nodes worsens prognosis
*most important prognostic metric is metz (M), but since metz are not common at dx, N is more useful