Exam 1 Path Flashcards by Brock Wiley

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

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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

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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)

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Vulvar lesions:

Skin colored exophytic papules and plaques
Histo: Papillary projections, Koilocytes with prominent perinuclear halos

Condyloma acuminatum (anogenital warts)

*HPV (6, 11)

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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

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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

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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

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Other vulvar neoplasms:

Itchy, ill defined, erythematous lesion +/- white crust
Intraepithelial adenocarcinoma
Histo: sweat gland and keratinocyte differentiation

Extramammary Paget Disease

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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!

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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!

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What exposue?

Daughter of treated mother develops VAGINAL adenosis
Eventual clear cell adenocarcinoma of the vagina

Diethylstilbestrol (DES) exposure

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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)

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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

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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

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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)

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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)

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Cervical Intraepithelial Neoplasia (CIN):

Mild dysplasia

CIN I / LSIL

more likely to regress, low chance to progress to HSIL

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Cervical Intraepithelial Neoplasia (CIN):

Moderate dysplasia

CIN II / HSIL

more likely to persist, low chance to progres to carcinoma

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Cervical Intraepithelial Neoplasia (CIN):

Severe dysplasia / Carcinoma in situ

CIN III / HSIL

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Concerning observations for on colposcopy

acetowhite areas = concern for dysplasia

abnormal vessels = concern for carcinoma

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Pap screening guidelines:

Start?
21-29?
30-65?
>65?

Start at 21
21-29 = q3y
30-65 = q5y
>65 = none if normal previously

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HPV vaccination offered to?

boys and girls starting at age 11

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Menstrual cycle histo:

tubular glands with pseudostratification and mitotic figures

proliferative phase (estrogen driven)

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Menstrual cycle histo:

“piano key” vaculoles

early secretory phase (progesterone driven)

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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

1. abnormal placental vasculature leads to placental ischemia 2. endothelial dysfunction leads to factor release, causing maternal vasoconstriction (HTN) 3. 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

Exam 1 Path Flashcards

(96 cards)