Pathoma Ch 13, 19 (Female GU and Repro, Skin) Flashcards
What type of hypersensitivity rxn is
(a) Atopic dermatitis
(b) Contact dermatitis
(c) Pemphigus vulgaris
(a) Atopic dermatitis (eczema) = type I, atopy also asthma
(b) Contact dermatitis (ex: nickel allergy, poison ivy) = type IV
(c) Pemphigus vulgaris = type II- Ab against self
Role of hormones in exacerbating acne vulgaris
Hormones stimulate keratin production that blocks hair follicles, also increases sebum production b/c sebaceous glands have androgen receptors
So excess keratin and sebum block the tube and blocked tubes are just waiting to get infected (in this case by Propinibacteirum acnes) that then causes inflammatory response
Mechanism by which the following help tx acne vulgaris
(a) Benzoyl peroxide
(b) Vitamin A derivatives
(a) Benzoyl peroxide = antimicrobial, against Propinibacterium acnes that infected blocked sebaceous gland producing lipases that breaks down sebum and releases proinflammatory fatty acids causing the pustule or nodule formation
(b) Vitamin A reduces keratin production that blocks the follicle, recall vitamin A is key for maintaining specialized epithelium
What are these findings in psoriasis?
(a) Acanthosis
(b) Parakeratosis
(c) Munro microabscesses
Psoriasis findings
(a) Acanthosis = epidermal hyperplasia
(b) Parakeratosis = hyperkeratosis w/ retention of keratinocyte nuclei in the stratum corneum
- so more keratin in upper layer and that keratin keep their nuclei
(c) Munro microabscesses = collection of neutrophils in the stratum corneum
What is Auspitz sign?
Auspitz sign = when scratch a bit of the psoriasis plaque off and you get a punctate hemorrhage
Cause: elongation of dermal papillae w/ thinned epidermis above it => bleeding when scale is picked off 2/2 the exposed BV in the elongated dermal papillae
Why does UVA light aid in the tx of psoriasis?
Psoriasis involves parakeratosis (hyperkeratosis forming the silvery scale) and UVA light can disrupt this keratinocyte proliferation
Histologic finding of lichen planus
Lichen planus = ‘sawtooth appearance’ on histology due to inflammation at the dermal epidermal junction
Chronic hepatitis C is associated w/ what dermatologic finding
Lichen planus- (Ps): pruritic, planar, polygonal, purple plaques
Pemphigus Vulgaris vs. Bullous Pemphigoid
(a) Target of IgG antibody
(b) Ease at which blisters pop
PV
(a) IgG antibody against desmosomes in the stratum spinosum of the epidermis
(b) Thinned epidermis on top of blisters => blisters pop easily (Nikolsky sign)
BP- less clinical severe (not as ‘vulgarrrr’)
(a) IgG against hemidesmosomes that connect stratum basalis to the basement membrane
(b) Entire layer of epidermis on top of blister => blisters are tense and don’t easily pop
Pemphigus Vulgaris vs. Bullous Pemphigoid
(a) Immunofluorescence
(b) Involvement of oral mucosa
PV
(a) IF highlights IgG surrounding keratinocytes in a ‘fish net’ appearance b/c IgG against desmosomes that connect keratinocytes in the stratum spinosum
(b) Involves oral mucosa
BP
(a) IF of IgG along basement membrane in linear pattern
(b) Oral mucosa spared
2 fast clinical ways to differentiate pemphigus vulgaris and bullous pemphigoid
PV (IgG against desmosomes in stratum spinosum) is more clinically severe- involves oral mucosa and blisters easily pop
BV (IgG against hemidesmosomes connecting stratum basalis to basement membrane) less clinically severe- spares oral mucosa and blisters are tense
When does erythema multiforme count as Stevens-Johnson syndrome?
EM plus oral involvement and fever = SJS
Erythema multiforme
(a) MC association
(b) Other associations
EM
a) MC associated w/ HSV infection
(b) Also seen in SLE, mycoplasma infection (Lymes), drug rxn (PCN, sulfonamides
Explain the three phases of the cycle by which endometrium is hormonally sensitive
- Proliferative phase- growth of endometrium from estrogen signal
- Secretory phase- preparation for implantation- driven by progesterone
- Menstrual phase = Shedding due to loss of progesterone support of endometrium
Serious complication of overaggressive dilation and curretage
Asherman syndrome- if too aggressive may scrape off the basalis (regenerative layer) => secondary amenorheea
Aka don’t get period b/c there is no basalis regenerative layer to regenerate the stratum functionalis which is the layer that sheds
Clinical features of Asherman syndrome
Asherman syndrome presents as secondary amenorrhea (loss of menstruation) due to loss of basalis and scarring
Can arise from overaggressive D&C
-basically concept here is that stratum basalis of the endometrium is needed to regenerate the functionalis layer which is the one that sheds, so if can’t reform functional layer there is nothing to shed = no menses
Clinical features of an anovulatory cycle
(a) When is this commonly seen?
Anovulatory cycle = lack of ovulation, which means lack of progesterone proliferative phase
if have a bunch then estrogen drives proliferation w/o progesterone-secretory phase so the glands eventually outgrow their blood supply and cause abnormal shedding
Histologic diagnostic finding of chronic endometritis
Endometritis = inflammation of endometrial lining, from retained products of conception or chronic PID/IUD/Tb
Histologic finding = plasma cells
-plasma cells necessary for diagnosis of chronic endometritis b/c lymphocytes are normally found in the endometrium (therefore aren’t diagnostic of inflammation)
Endometrial polyp- what is it?
(a) Clinical presentation
(b) Possibly seen as side effect of what drug?
Endometrial polyp = hyplerplastic protrusion of the endometrium
(a) Abnormal uterine bleeding
(b) Possible side effect of Tamoxifen which is an anti-estrogen on the breast but has weak pro-estrogenic effects on the endometrium
Define endometriosis
(a) Most likely mechanism
Endometriosis = endometrial tissue (both glands and stroma) outside of the uterine endometrial lining
(a) Lots of theories, but most likely thought to be due to retrograde menstruation w/ implantation at ectopic site
Clinical presentation of endometriosis
(a) Feared complication of endometriosis
Endometriosis presents as dysmenorrhea = pain during menstruation (b/c endometriosis cycles just like regular endometrial tissue), or pelvic pain, also can cause infertility
(a) Feared complication = infertility but also increased risk of carcinoma at the site of the endometriosis (esp in the ovary)
What is adenomyosis?
Adenomyosis = when endometriosis involves the uterine myometrium
So ectopic endometrial tissue in the myometrium
MC invasive carcinoma of the female genital tract
(a) MC tumor in females
Endometrial carcinoma
(a) Leiomyoma = fibroids
Differentiate the two pathways of endometrial carcinoma: hyperplasia vs. sporadic
(a) RF
(b) Average age
Endometrial carcinoma:
75% hyperplasic where carcinoma arises from endometrial hyplerplasia
(a) RF: estrogen exposure (early menarche, late menopause, nulliparity, obesity)
(b) Average age of 60
25% sporadic- carcinoma arises in atrophic endometrium w/o precursor lesion
(a) RF: age
(b) Average age 75
Name 4 cancers associated w/ psamomma bodies
- papillary carcinoma of the thyroid
- sporadic/papillary serous endometrial carcinoma
- Meningioma
- Mesothelioma
What are leiomyoma?
Leiomyoma = fibroids!!
Benign neoplastic proliferation of smooth muscle arising from myometrium
Give three ways to differentiate leiomyoma from leiomyosaroma
Leiomyoma (benign fibroid): usually multiple, well-defined, white whorled masses
-related to estrogen exposure => seen in premenopausal F
Leiomyosarcoma = malignant prolif of endometrial smooth muscle
- single lesion w/ area of necrosis and hemorrhage (not multiple white whorled masses)
- seen in postmenopausal F (60-70)
MC clinical feature of leiomyoma
MC clinical feature of fibroids = nothing! Super common and majority are asymptomatic, but if symptomatic: AUB (abnormal uterine bleeding), infertility, pelvic mass
Precursor lesion to leiomyosarcoma
Trick question!!!! There is no precursor lesion, these malignant proliferation of smooth muscle of the endometrium arise DE NOVO
-Be careful: leiomyosarcoma do NOT arise from leiomyomas (fibroids)
How are HPV strains risk stratified?
Determine risk of HPV strain by DNA sequencing
Risk meaning risk of progression to carcinoma
Low risk (form condylomas not carcinoma) = HPV 6,11 High risk = 16,18,31,33
Clinical presentation of lichen sclerosis
(a) Benign?
Lichen sclerosis = parchment/paper thin epidermis w/ fibrosis/sclerosis of dermis
Presents as white patch (leukoplakia) w/ parchment-like vulvar skin
-2/2 age, seen in postmenopausal
(a) Benign but is associated w/ slightly increased risk of vulvar carcinoma (b/c of chronic inflammation)
Condyloma 2/2 HPV vs. 2/2 secondary syphilis
Condyloma accuminatum = cauliflower, wart-like from HPV 6 and 11 (low risk strains)
Condyloma latum (less commonly) = flat papules from secondary syphilis
Lichen sclerosis vs. lichen simplex
(a) Clinical presentation
(b) Association w/ squamous cell carcinoma
Lichen sclerosis
(a) Leukoplakia (white patch) w/ parchment-like vulvar skin in postmenopausal F
(b) Benign in itself but carries slight association w/ vulvar carcinoma b/c of chronic inflammation
Lichen simplex chronicus
(a) Hyplerplasia of vulvar squamous epithelium => leukoplakia (also white plaque) but which thick, leathery vulvar skin
- itchy
(b) Benign, no increased risk or association w/ squamous cell carcinoma
2 risk factors for vulvar carcinoma
Vulvar carcinoma relatively rare (cervical MC)
- HPV strains 16,18,31,33 (high risk strains)- start as VIN precursor lesion characterized by koilocytic change
- Long standing lichen sclerosis in postmenopausal F 2/2 chronic inflammation
How to distinguish extramammary Paget disease from melanoma
Immunohistochemical stain
Paget cells: positive for PAS (marks mucus) and keratin (int filament of epithelial cells), but negative for S100
Melanoma: positive for S100 (melanoma tumor marker…) while negative for PAS and keratin
Composition of the vagina
Vagina = fibromuscular canal lined by non-keratinized stratified squamous epithelium that leads to the cervix
Embryologic origin of the vagina
(a) Type of epithelium
(b) Lymphatic drainage
Upper 2/3 of vagina from the Mullerian (paramesonephric) duct
(a) Starts as columnar epithelium, replaced by squamous cells from bottom 1/3
(b) Drains to regional iliac nodes
Lower 1/3 of vagina from the urogenital sinus
(a) Stratified squamous, grows up to replace the columnar above it
(b) Drains to inguinal nodes
Adenosis
(a) Mechanism
(b) RF
Adenosis = focal persistence of columnar epithelium in the upper vagina
(a) Upper 2/3 of vagina from paramesonephric duct starts as columnar, then usually replaced by squamous from lower 1/3, but if not replaced = adenosis
(b) RF: diethylstilbesterol exposure in utero
DES exposure association
Diethylstilbesterol exposure:
- increased incidence of adenosis (persistence of columnar epithelium in upper vagina)
- increased incidence of clear cell adenocarcinoma = malignant proliferation of glands w/ clear cytoplasm
Distinguishing feature of extramammary Paget disease and Paget disease of the nipple
Extramammary pagets disease = malignant ep cells in the epidermis of the vulva, only in the vulva (carcinoma in situ) usually w/ no underlying carcinoma
While Paget disease of the nipple (also malig cells in epidermis but this time in the nipple) is almost always associated w/ underlying carcinoma
Grape like mass protruding from vagina or penis of child
Embryonal rhabdomyosarcoma (rhabdomyo- smooth muscle, sarcoma- malignant mesenchymal proliferation) = malignant mesenchymal proliferation of immature skeletal muscle
Characteristic cell = rhabdomyoblast (immature skeletal muscle cell) that stains positive for desmin and myogen
Precursor lesion to vaginal carcinoma
VAIN = vaginal intraepithelial neoplasia from high risk HPV strains (16,18,31,33)
Why are HIV pts at increased risk of HPV?
Not b/c they’re more sexually active…but b/c they’re immunocompetent and HPV is usually eradicated by acute inflammation
-its only persistent infection that => CIN
How does HPV increased risk of cancer?
High risk HPV strains have DNA genes that code for E6 and E7
E6 destroys p53 while E7 destroys Rb (both tsgs)
CIN
(a) Dysplasia vs. carcinoma
(b) CIS vs. invasive carcinoma
CIN = cervical intraepithelial neoplasia
(a) Dysplasia is reversible, while carcinoma is not
(b) CIS has not invaded basement membrane, invasive carcinoma has
MC presentation of cervical carcinoma
(a) Age group
Cervical carcinoma (a) average age 40-50 p/w vaginal bleeding, especially post-coital bleeding
Why may advanced cervical carcinoma cause hydronephrosis?
Advanced tumors often invade thru the anterior uterine wall into the bladder which can block the ureters => hydronephrosis
Can cause postrenal failure which is a common cause of death in advanced cervical carcinoma
2 subtypes of cervical carcinoma
(a) Relationship to HPV infection
Cervical carcinoma: 85% squamous cell, 15% adnocarcinoma
(a) BOTH are related to HPV!!! Not just squamous cell
What strains does the HPV vaccine cover for?
(a) If we have a vaccine why do we still need screening?
HPV covers 6,11 (condyloma) and 16,18 (high risk
(a) B/c vaccine only covers a few of the strains
- doesn’t cover high risk 31,33
2 limitations of pap smear screening
Limitations
- False negative if don’t get cells from the transformation zone
- Limited efficacy for adenocarcinoma- only 15% of cervical carcinomas, but also possible and associated w/ HPV infection
What are follicular cysts?
(a) Normal number?
Most females have a few follicular cysts when ovarian follicles degenerate, no clinical significant when just a few
(a) But when becomes multiple 2/2 hormonal imbalance = PCOS
Characteristic lab finding in PCOS
PCOS: elevated LH, specifically LH:FSH > 2
High LH induces excess androgen production from theca cells => hirsuitism
Also these pts tend to be obese, so androgen –> estrone peripherally which inhibits FSH
PCOS- increased risk of what malignancy?
PCOS: high levels of circulating estrone b/c elevated androgen from theca cells (high LH primary problem) leaves lots of androgen for peripheral adipose conversion => high estrone
High estrogen = increased risk of endometrial carcinoma
3 cell types of the ovary
3 cell types (aka 3 types of tumors that can arise from the ovary)
- Surface epithelium => serous and mucinous epithelial tumors (MC, 70%, also sadly poor prognosis)
- The oocyte! => germ cell tumor
- Supporting cells = granulosa cells, theca cells, fibroblasts = sex cord stroma => sex cord stromal tumors
How to differentiate the 2 MC subtypes of ovarian surface epithelial tumors
Ovary has three types of cells (surface epithelium, germ cells, sex cord stroma)- MC tumors are from surface epithelium and MC of those are serous and mucinous
Can differentiate by the fluid inside!
Watery fluid = serous tumor
Mucus-like fluid = mucinous tumor
What specific cancers does BRCA1 mutation increase risk for?
- Breast
- Ovarian serous carcinoma (malignant surface epithelial cell of serous epithelium)
- Serous carcinoma of the fallopian tumor
So means not only b/l mastectomy but b/l salpingo-oophorectomy for elective procedure (remove both ovaries and the fallopian tubes)
CA-125
Serum marker for surface epithelium tumors of the ovary
MC ovarian tumor
(a) 2nd MC
MC ovarian tumor = surface epithelial tumor (from the surface epithelium of the ovary) aka carcinoma (70%)
(a) 2nd MC = germ cell tumors (15%)
Leaves just sex-cord stromal tumors made of the supportive tissue of the ovary
Ovarian tumor most expected by age
(a) 15-30
(b) 30-40
(c) 50-60
(a) F of reproductive age- suspect germ cell tumor
(b) Early adulthood- suspect benign surface epithelial tumor
(c) 50-60- malignant surface epithelial tumor
Surface epithelial MC overall (70%) but not really seen in 15-20s so then think germ cell tumors (15%)
MC germ cell tumor
(a) Overall in females
(b) Malignant
(c) In children
MC germ cell tumor
(a) Overall = cystic teratoma = fetal tissue derived from 2-3 embryologic layers
(b) MC malignant germ cell tumor = dysgerminoma (from oocytes aka germ cells)
(c) In children (aka an ovarian mass in a 5 yr old) = endodermal sinus tumor which is from the yolk sac tissue
What is a cystic teratoma?
(a) Percent b/l
Cystic teratoma = cystic tumor composed of fetal tissue derived from 2 to 3 embryologic layers
This is the weird one that contains skin, hair, bone, teeth, cartilage, gut, thyroid (ew freaky, can even be struma ovarii that is primarily thyroid tissue and presents w/ hyperthyroidism)
(a) 10% b/l
2 features that increase the malignant potential of a cystic teratoma
Cystic teratomas are benign, but malignant potential indicated by
- presence of immature tissue w/in the teratoma- usually immature neural tissue
- somatic malignancy w/in the tumor (aka some of the tumor tissue is malignant)- usually squamous cell carcinoma of skin component w/in the tumor
Germ cell tumor w/
(a) Skin, hair bone, teeth etc
(b) Elevated AFP
(c) Elevated LDH
(d) Elevated beta-hCG
(a) Tissue from 2-3 embryologic layers = cystic teratoma
(b) Elevated AFP = endodermal sinus tumor (from yolk sac tissue)
(c) Elevated LDH = dysgerminoma (from oocytes aka germ cells)
(d) Elevated beta-hCG = choriocarcinoma (aka placental tissue which makes beta-hCG in the first place)
Male counterpart of dysgerminoma
Dysgermina comes from the germ cells, in F its from the oocytes
In males from the testes = seminoma and is relatively common germ cell tumor
Germ cell tumor w/ early hematogenous spread
Choriocarcinoma has early hematogeous spread b/c its from placental tissue (and entire purpose of placental tissue is to invade BVs)
What is the MC sex cord-stromal tumor?
MC sex cord-stromal tumor = Granulosa-theca cell tumor = neoplastic proliferation of both granulosa and theca cells
Presents w/ signs of estrogen excess
Presentation of granulosa-theca cell tumors
Present w/ signs of estrogen excess
Prior to puberty- precocious puberty
Reproductive age- menorrhagia or metrorrhagia
Postmenopause (MC setting) = endometrial hyperplasia w/ abnormal uterine bleeding
Triad of features seen w/ ovarian mass in Meigs syndrome
Meigs syndrome = triad of ovarian mass (MC fibroma = benign sex cord-stromal tumor of fibroblasts) w/ pleural effusion and ascites
Something to do w/ the lymphatic drainage but mechanism poorly understood
What is pseudomyxoma peritonei?
(a) MC cause
Pseudomyxoma peritonei = clinical condition of tons of mucus in the peritoneum due to a mucinous tumor (adenocarcinoma)
(a) MC from mucinous tumor of the appendix, usually w/ mets to the ovary
Define spontaneous abortion
(a) MC cause
Spontaneous abortion = miscarriage before 20 weeks
(a) Chromosomal anomalies
Typical presentation of ectopic pregnancy
(a) Why is this a surgical emergency?
Ectopic pregnancy: p/w lower quadrant abdominal pain a few weeks after a missed period
(a) Surgical emergency b/c can bleed into fallopian tube (hematosalpinx) and rupture the tube!
Placenta previa vs. placenta accreta
Placenta previa = placenta overlying cervical os, usually requires C-section
Placenta accreta = placenta implanted into myometrium, usually requires hysterectomy b/c can’t remove the placenta
Clinical consequence of placenta accreta
Hysterectomy :-( b/c placenta won’t deliver and mom just keeps bleeding
What type of necrosis may be seen in the placenta due to preeclampsia?
Fibrinoid necrosis = necrosis of BV due to malignant HTN
Physiology of HELLP syndrome
HELLP = presentation of preeclampsia w/ thrombotic microangiopathy involving the liver
So hemolysis of RBC as schistocytes rushing past microthrombi, elevated liver enzymes b/c of hepatocyte dysfunction, low plts b/c they’re used up in the cots
Definition of SIDS
(a) RF
Death of healthy infant from 1 mo to 1 year
RF: sleeping on stomach, cig smoke exposure, prematurity
What is a hydatidiform mole?
(a) Clinical features of mother
Hydatidiform mole = abnormal conception characterized by swollen and edematous villi w/ proliferation of trophoblasts
-either normal egg fertilized by 2 sperm (partial mole) or empty ovum fertilized by two sperm or sperm that duplicates (complete mole)
(a) Clinically: uterus much larger than expected, beta-hCG much higher than expected for date of gestation (b/c its all just placental tissue)
Prenatal care detection of hydatidiform mole- ultrasound finding
US founding = absent fetal heart sounds, classic ‘snowstorm’ appearance of the edematous villi
Tx of molar pregnancy
(a) F/u
Hydatidiform mole requires suction currettage
(a) F/u w/ beta-hCG monitoring to ensure adequate mole removal and screen for development of choriocarcinoma
Differentiate the two pathways of choriocarcinomas
(a) Which is more responsive to chemotherapy
Choriocarcinoma (tumor of placental tissue) can arise from
- Gestational pathway- aka hydatidiform mole or abnormal placental tissue
(a) Good reponse to chemo - Can arise from germ cell pathway (as germ cell tumor)
(a) Poor response to chemo
Partial vs. Complete Mole
(a) Number of chromosomes
(b) Presence of fetal tissue
(c) Prevalence of villous edema
Partial
(a) 69 chromosomes (1 egg w/ 2 sperm)
(b) Fetal tissue is present (egg wasn’t empty, not completely molar)
(c) Some villi are hydropic while some normal are also present
Complete
(a) 46 chrom (empty ovum w/ 2 sperm or duplicated sperm)
(b) No fetal tissue (it’s completely molar!!)
(c) Most villi are hydropic (edematous/full of water)
Partial vs. complete mole
(a) Number of chromosomes
(b) Trophoblastic proliferation
(c) Risk for choriocarcinoma
Partial
(a) 69
(b) Focal trophoblastic proliferation present around hydropic (edematous) villi
(c) Minimal risk of choriocarcinoma
Complete mole
(a) 46 chromosomes (empty ovum)
(b) Diffuse, circumferential proliferation around hydropic villi
(c) 2-3% (higher) risk of choriocarcinoma
Partial vs. complete mole
(a) Which has higher b-hCG
(b) Which carries higher risk of choriocarcinoma
(a) Complete mole has higher beta-hCG b/c more proliferation of trophoblastic tissue
(b) Complete mole carries a higher risk (2-3%) of choriocarcinoma
