Pathology Flashcards
Bartholin gland
present on each side of vaginal canal
produces mucus-like fluid that drains into lower vestibule
Bartholin cyst
cystic dilation of Bartholin gland
etiology: inflammation and obstruction of gland usually due to UTI or STD –> usually occurs in women of reproductive age
presentation: unilateral painful cystic lesion at lower vestibule adjacent to vaginal canal
Vulvar condyloma
warty neoplasm, often large
Etiology: sexually transmitted; usually due to HPV 6 or 11 (low risk) - condyloma acuminatum or less commonly secondary syphilis (condyloma latum)
Histology: HPV-associated condylomas have koilocytic nuclei (look like raisins)
*Condylomas rarely progress to cancer
Lichen sclerosis
Etiology: Possibly autoimmune, usually seen in postmenopausal women; Thinning of epidermis and fibrosis (sclerosis) of dermis
Presentation: leukoplakia (white patch) with parchment-like vulvar skin
*benign, but can slightly increase risk for squam. cell carcinoma
Lichen simplex chronicus
Hyperplasia of vulvar squamous epithelium
Etiology: chronic irritation/scratching
Presentation: leukoplakia w/ thick vulvar skin
*Benign, NO increase risk of squam. cell carcinoma
Vulvar carcinoma
Rare, carcinoma from squamous epithelium of vulva
Presentation: leukoplakia -> need biopsy to distinguish
Etiology:
- HPV related (HPV 16,18,31,33 - high risk), usually in women of reproductive age
- non-HPV related (long-standing lichen sclerosis), usually elderly women >70yo
Extramammary Paget Disease
Malignant epithelial cells in epidermis of vulva; carcinoma in situ usually with no underlying carcinoma (contrast with Paget of nipple which almost always associated with underlying breast cancer)
Presentation: erythematous, pruritic, ulcerated vulvar skin
Distinguish from melanoma:
Paget cells: PAS+, keratin+, S100-
Melanoma: PAS-, keratin-, S100+
[keratin=intermediate filament in epithelial cells –> carcinoma]
What kind of cells line the vaginal canal?
non-keratinizing squamous epithelium
What are the epithelium of the upper 2/3 and lower 1/3 of the vaginal canal derived from?
upper 2/3: from Mullerian duct (columnar epithelium that is later replaced by squamous epithelium from lower 1/3)
lower 1/3: from urogenital sinus (squamous epithelium)
Vaginal adenosis
focal persistence of columnar epithelium in upper vagina
increased incidence when exposed to DES (diethylstilbestrol) in utero
*Can (rarely) lead to clear cell adenocarcinoma
Clear cell adenocarcinoma of vagina
malignant proliferation of glands w clear cytosol
-Rare complication of DES-associated vaginal adenosis
What complications can arise from DES exposure?
Mother exposed to DES: slight increased risk of breast cancer
Daughter exposed to DES: 1. vaginal adenosis -> clear cell adenocarcinoma, 2. abnormalities of smooth muscle -> abnormal shape of uterus -> increased ectopic pregnancies and fertility problems
Embryonal Rhabdomyosarcoma
Rare. Malignant mesenchymal proliferation of immature skeletal muscle
Presentation: bleeding and “grape-like” mass protruding from vagina or penis of child
Vaginal carcinoma
Carcinoma of squamous epithelium lining vaginal mucosa
Etiology: high-risk HPV (16,18,31,33); precursor lesion is vaginal intraepithelial neoplasia (VAIN) which is dysplastic
Spreads to lymph nodes:
from lower 1/3 of vagina -> superficial inguinal nodes
from upper 2/3 of vagina -> external iliac nodes
What type of cells line the exocervix and the endocervix?
exocervix - nonkeratinizing squamous epithelium
endocervix - single layer of columnar cells
Where does HPV usually infect?
lower genital tract, especially cervical transformation zone
What causes the increased risk associated with high-risk HPV versus low-risk HPV?
High-risk HPV (16,18,31,33) produce E6 and E7 proteins
E6 destroys p53 –> less regulation of cell cycle
E7 destroys Rb –> E2F can be released and progress cells from G0 to G1
*loss of tumor suppressors -> increase risk for CIN
Cervical intraepithelial neoplasia (CIN)
Characteristics: koilocytic change (raisin nuclei), disordered maturation, nuclear atypia, increased mitotic activity
Grades based on epithelial involvement by immature dysplastic cells
CIN I: WILL PROGRESS to cervical carcinoma
Cervical carcinoma
invasive carcinoma (goes through basement membrane) arising from cervical epithelium
- squamous cell (80%) and adenocarcinoma subtypes
- most common in women 40-50yo (HPV takes 20-30years to develop into carcinoma)
Presentation: vaginal bleeding, especially postcoital, or cervical discharge
Advanced tumors- invade into bladder blocking ureters -> hydronephrosis w/ post-renal failure (most common cause of death)
Risk factors: HPV**, smoking, immunodeficiency
*AIDS-defining illness
What are the characteristics of high-grade dysplastic cells on Pap smear?
hyperchromatic (dark) nuclei, high nuclear to cytosol ratio
What are the limitations of Pap smear?
inadequate sampling -> false negative
more difficult to detect adenocarcinoma (incidence of adenocarcinoma has not decreased significantly)
What HPV types are covered in immunization?
6, 11 (low risk), 16, 18 (high risk)
What are the characteristics of the endometrium and myometrium?
endometrium: mucosal lining of uterine cavity; hormonally sensitive ->
1. growth driven by estrogen (prolif. phase)
2. preparation for implantation driven by progesterone (secretory phase)
3. shedding with loss of progesterone (menstruation)
myometrium: smooth muscle underlying endometrium
Asherman syndrome
Secondary amenorrhea from loss of basalis (stem cells) layer that is result of overaggressive dilation and curettage (D&C)
Acute endometritis
Bacterial infection of endometrium
- usually due to retained products of conception (after delivery or miscarriage)
- Presents with fever, abnormal uterine bleeding and pelvic pain
Chronic endometritis
Chronic inflammation of endometrium characterized by lymphocytes and plasma cells*
Caused by retained products of conception, chronic PID (Chlamydia ex), IUD, TB (granulomas)
Presentation: abnormal bleeding, pain, infertility
How is endometritis treated?
gentamicin + clindamycin w or w/out ampicillin
enodmetrial polyp
well circumscribed hyperplastic protrusion of endometrium
Presents as abnormal bleeding
Can arise as side effect of tamoxifen (weak pro-estrogenic effects on endometrium)
Endometriosis
Endometrial glands and stroma outside of uterine endometrial lining, most commonly affecting ovaries
Etiology: 3 theories
- retrograde menstruation w ectopic implantation
- metaplastic transformation of multipotent cells
- transportation of endometrial tissue via lymphatics
Presentation: dysmenorrhea (menstrual pain)and pelvic pain , dyschezia (pain w/ defecation) - pouch of Douglas, dyspareunia (painful intercourse), infertility
In ovary appears as ‘chocolate cyst’ endometrioma
In soft tissue appears as ‘gun powder’ nodules
Treatment: NSAIDs, OCPs, progestins, GnRH agonists, danazol, laparoscopic removal
Adenomyosis
Endometriosis in myometrium caused by hyperplasia of basal layer of endometrium
Presents with dysmenorrhea, menorrhagia, enlarged soft globular uterus
Treatment: GnRH agonists, hysterectomy
Endometrial hyperplasia
Hyperplasia of endometrial glands relative to stroma
Etiology: unopposed estrogen (obesity, PCOS, estrogen replacement)
Presentation: usually postmenopausal uterine bleeding
Histology: cellular atypia is most important predictor for progression to carcinoma
Endometrial carcinoma
Most common invasive carcinoma of female GU tract
Presentation: postmenopausal bleeding
2 etiologies:
- Endometrial hyperplasia (75%)
- risk factors related to increased estrogen exposure
- age ~60
- histology: endometrioid - Sporadic (25%)
- no evident precursor lesion, p53 mutation common
- aggressive behavior of tumor
- histology: serous papillary structures w psammoma bodies
Leiomyoma (fibroids)
most common tumor in females, higher incidence in African Americans
benign neoplastic proliferation of smooth muscle of myometrium, related to estrogen exposure
Presents: PREmenopausal women
Multiple, well-defined, white, whorled masses -> may distort uterus
*Usually asymptomatic, if presents- symptoms of abnormal uterine bleeding, infertility, pelvic mass
Leiomyosarcoma
Malignant proliferation of myometrium smooth muscle
- Arises de-novo DO NOT arise from leiomyoma (fibroids)
- POSTmenopausal women
- Gross exam: single lesion with necrosis and hemorrhage
Common causes of anovulation
pregnancy PCOS obesity HPO axis abnormalities premature ovarian failure hyperprolactinemia thyroid disorders eating disorders competitive sports Cushing syndrome adrenal insufficiency
Follicular cyst
distention of unruptured graafian follicle, associated with hyperestrogenism, endometrial hyperplasia. most common ovarian mass in young women. Small numbers are common and no clinical significance
Polycystic Ovarian Syndrome (PCOS) aka Stein-Leventhal syndrome
Multiple ovarian follicular cysts from hormone imbalance
Characterized by increased LH and low FSH (LH:FSH >2)
Hyperinsulinemia (increase free testosterone via decreased sex hormone binding globulin) and/or insulin resistance (stimulates theca cells to produce more androgens) may alter hormonal feed back response ->
Increased LH:FSH -> increased androgens from theca -> hirsutism, estrone in adipose negative feedback decreases FSH -> cystic degeneration of follicles + anovulation
Associated with obesity, increases risk of endometrial cancer secondary to unopposed estrogen from repeated anovulatory cycles
Treatment: weight reduction, OCPs, clomiphene citrate (SERM), ketoconazole (anti-androgen), spironolactone (anti-androgen)
Surface epithelial ovarian tumors- what are they derived from and what are the most common subtypes?
Most common type of ovarian tumor
Derived from coelomic epithelium that lines ovary - embryologically produces lining of fallopian tube (serous cells), endometrium and endocervix (mucinous cells)
Common subtypes: Cystadenomas Cystadenocarcinomas Endometriod tumors Brenner tumors
They often present late with vague symptoms: pain and fullness or signs of compression - urinary frequency
Poor prognosis of surface epithelial carcinoma and tend to spread locally, especially peritoneum
(CA-125 marker to monitor treatment response)
Cystadenomas
Benign tumors
composed of single cyst with simple flat lining - contain serous (most common) or mucinous epithelium and fluid
-commonly in PREmenopausal women (30-40yo
Cystadenocarcinomas
Malignant tumors
- Serous cystadenocarcinoma - most common ovarian neoplasm, freq bilateral, psammoma bodies
- Mucinous - pseudomyxoma peritonei-intraperitoneal accumulation of mucinous material from ovarian or appendical tumor
- composed of multiple complex cysts with thick shaggy lining
- commonly in POSTmenopausal women (60-70yo)
BRCA1 mutation carries increased risk for what kind of carcinomas in the female GU tract?
serous carcinoma of ovary and fallopian tube
Endometrioid tumors
Usually malignant
composed of endometrial-like glands, may arise from endometriosis
15% associated with an independent endometrial carcinoma (endometriod type)
Brenner tumors
Usually benign, composed of urothelium (bladder-like epithelium)
Solid tumor is pale yellow and appears encapsulated. ‘coffee bean’ nuclei on H&E
Germ cell tumors
2nd most common type of ovarian tumor
-usually women of reproductive age
Subtypes:
- Fetal tissue- cystic teratoma and embryonal carcinoma
- Oocytes (germ cell) - dysgerminoma
- Yolk sac - endodermal sinus tumor
- Placental tissue - choriocarcinoma
Cystic teratoma (dermoid cyst)
Most common ovarian tumor in women 20-30yo
Cystic mass with elements from all 3 germ layers (bilateral 10% of time)
Can present with pain secondary to ovarian enlargement
Benign, but presence of immature tissue (neural) or somatic malignancy (tumor w/in teratoma, usually squamous cell carcinoma of skin) –> malignant potential
Struma ovarii
Cystic teratoma comprised mostly of thyroid tissue –> hyperthyroidism presentation
Dysgerminoma
Most common in adolescents
Malignant tumor composed of large cells with clear cytosol and central nuclei; Seminoma is counterpart in males
Good prognosis, responds to RT
Serum LDH may be elevated
Endodermal sinus tumor (yolk sac tumor)
Aggressive tumor in ovaries or testes and sacrococcygeal area in kids
Most common germ cell tumor in children
Yellow, friable (hemorrhagic) solid mass
Histo: Schiller-Duval bodies (resemble glomeruli)
AFP= tumor marker
Choriocarcinoma
Rare, can develop during or after pregnancy in mom or baby/
Malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts; mimics placental tissue but villi absent
Small, hemorrhagic tumor with early hematogenous spread -> to lung
Presentation: shortness of breat, hemoptysis and *High beta-hCG is characteristic –> may lead to thecal cysts in ovaries
Granulosa-theca cell tumor
Malignant sex cord-stromal tumor, neoplastic proliferation of granulosa and theca cells (usually don’t metastasize)
- Presents with signs of excess estrogen
- Predominantly women in 50s - endometrial hyperplasia with postmenopausal bleeding
- prior to puberty can cause precocious puberty
- reproductive age- menorrhagia or metrorrhagia
Histology: Call-Exner bodies (granulosa cells arranged around collections of eosinophilic fluid, resembles primordial follicles)
Sertoli-Leydig cell tumor
Sex cord-stromal tumor of ovary
- composed of sertoli cells and Leydig cells with characteristic Reinke crystals
May produce androgen -> virilization
Fibroma
Benign ovarian tumor of fibroblasts
Bundles of spindle-shaped fibroblasts
Associated with Meigs syndrome: triad of ovarian fibroma, ascites and hydrothorax.
presentation: “pulling” sensation in groin
Krukenberg tumor
Metastatic mucinous tumor involving both ovaries
Usually due to metastatic gastric carcinoma (diffuse type)
See mucin secreting signet ring cells
Ectopic pregnancy
Implantation of fertilized ovum at site other than uterine wall
Most commonly site is ampulla of fallopian tube
Presentation: pain w or w/out bleeding, hx of amenorrhea, lower-than expected rise in hCG, sudden lower abdominal pain
Confirm w US
Risk factors- scarring of fallopian tube: Hx of infertility Salpingitis (PID) Ruptured appendix Prior tubal surgery
Major complications: hematosalpinx (bleeding into fallopian tube) and rupture
Spontaneous abortion
Miscarriage before 20 weeks
Presentation: vaginal bleeding, cramping, passage of fetal tissues
Usually due to chromosomal anomalies, also hypercoagulable states (ex SLE antiphospholipid syndrome), infection, teratogens
polyhydramnios
Too much amniotic fluid (>1.5-2L)
Associated with fetal malformations (inability to swallow amniotic fluid)
- esophageal/duodenal atresia
- anencephaly
Associated with maternal diabetes, fetal anemia, multi gestations
oligohydramnios
Vasa previa
Fetal vessels run over or near cervical os
May result in vessel rupture, exsanguination, fetal death
Presents: triad of membrane rupture, painless vag bleeding, fetal bradycardia ( fetal vessels travel unprotected by Wharton jelly)
Placenta previa
Attachment of placenta to lower uterine segment over or
Placental abruption
Prematureseparation of placenta from uterine wall
Presentation: abrupt painful bleeding in 3rd trimester; possible DIC, maternal shock, fetal distress. Life threatening to mom and fetus
Risk factors:
Trauma, HTN, smoking, preeclampsia, cocaine abuse
Placenta accreta/ increta/ precreta
Defective decidual layer -> abnormal attachment of placenta
Presentation: usually detected early on US
No separation of placenta after delivery -> postpartum bleeding -> can cause Sheehan syndrome
Risk factors: prior C-section, inflammation, placenta previa
3 types based on depth:
- placenta accreta - attaches to myometrium w/out penetrating it (most common)
- placenta increta - placenta penetrates into myometrium
- placenta precreta - placenta penetrates through myometrium and into serosa, can cause attachment to rectum or bladder
Preeclampsia
Pregnancy induced HTN (may cause HA and vision changes), proteinuria and edema
- usually in 3rd trimester (if less than 20 weeks suggest molar pregnancy)
- abnormalities of spiral arteries (maternal-fetal vascular interface) in placenta; resolves w delivery
Risk factors:
pre-existing HTN, diabetes, chronic renal disease, autoimmune disorders
Complications:
placental abruption, coagulopathy, renal failure, uteroplacental insufficiency, eclampsia
Treatment: antihypertensives, IV magnesium sulfate (prevent seizure), definitive treatment is delivery of baby
Retained placental tissue
may cause postpartum hemorrhage, increases risk of infection
Eclampsia
Preeclampsia + seizures
Maternal death due to stroke, intracranial hemorrhage or ARDS
Treatment: IV magnesium sulfate, antihypertensives, immediate delivery
HELLP syndrome
Hemolysis, Elevated Liver enzymes, Low Platelets
Severe preeclampsia manifestation with thrombotic microangiopaty involving liver –>
Blood smear shows schistocytes
Can lead to hepatic hematomas -> rupture -> severe hypotension
Treatment: immediate delivery
Sudden infant death syndrome (SIDS)
death of healthy infant (1mo-1yr) w/out obvious cause
usually during sleep
Risk factors: sleeping on stomach, second hand smoke, prematurity
Gestational HTN (pregnancy-induced HTN)
BP>140/90mmHg after 20th week gestation when no pre-existing HTN
No proteinuria or end-organ damage
Treatment: antihypertensives (alpha-methyldopa, labetalol, hydralazine, nifedipine); deliver at 37-39 wks
Hydatidiform mole
abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts
Associated with theca-lutein cysts, hyperemesis gravidarum, hyperhtyroidism
Treatment: dilation and curettage and methotrexate. Monitor beta-hCG
Partial mole
Genetics: 69XXX, 69XXY, 69XYY
Components: 2 sperm +1egg
fetal parts: Yes
hCG: elevated
Uterine size: ~normal
Convert to choriocarcinoma: rare
Risk of complications: low risk of malignancy
Symptoms: vaginal bleeding, abdominal pain
Imaging: fetal parts
villous edema: some villi hydropic, some normal
Trophoblastic proliferation: focal proliferation around villi
Complete mole
Genetics: 46XX, 46XY
Components: enucleated egg+ single sperm that duplicates or 2 sperm
fetal parts: no
hCG: very high!
Uterine size: much larger for date of gestation
Convert to choriocarcinoma: 2%
Risk of complications: 15-20% malignant trophoblastic disease
Symptoms: 1st trimester bleeding, enlarged uterus, hyperemesis, pre-eclampsia, hyperthyroidism
Imaging: “honeycombed” uterus or “clusters of grapes”/ “snowstorm” on US
villous edema: almost all villi are hydropic
Trophoblastic proliferation: diffuse, circumferential proliferation around villi
Hyposadias
Opening of urethra on inferior surface (ventral side) due to failure of urethral folds to fuse
Epispadias
(very rare) opening on uretra on superior (dorsal) surface of penis due to abnormal positioning of the genital tubercle
Associated with exstrophy of bladder (complete exposure of bladder wall)
Lymphogranuloma venereum
necrotizing inflammation of inguinal lymphatics and lymph nodes
Etiology: STDs caused by Chlamydia trachomatis (L1-L3 serotypes)
Eventually heals w fibrosis, perianal involvement may cause rectal stricture
Squamous cell carcinoma of the penis
risk factors: high risk HPV (16,18,31,33), lack of circumcision and improperly maintained foreskin
-More common in Asia, Africa and S. America
Precursor in situ lesions:
1. Bowen disease - in situ carcinoma of penile shaft, presents as leukoplakia
- Erythroplasia of Queyrat - in situ carcinoma on glans presenting with erythroplakia
- Bowenoid papulosis - in situ carcinoma presenting with reddish papules, seen in younger patients (40s), does NOT progress to carcinoma
Cryptorchidism
Failure of testicle to descend into scrotal sac
-impaired spermatogenesis (sperm develop best at
Orchitis
Inflammation of testicle
Causes:
1. young adults- C. trachomatis (D-K serotypes) or N. gonorrhoeae. Increased risk of sterility, but libido spared since Leydig unaffected
- older adults - E. coli and Pseudomonas. UTI spread into repro tract
- teenage males -> Mumps virus, increased risk for infertility (mumps also causes parotitis, meningitis, pancreatitis)
- Autoimmune - granumolas involving seminiferous tubules
Peyronie disease
Abnormal curvature of penis due to fibrous plaque within tunica albuginea
Associated w erectile dysfunction
Priapism
painful erection >4 hours
Associated with trauma, sickle cell disease (sickled RBCs get stuck), meds (sildenafil, trazodone)
Treat with corporal aspiration, intracavernosal phenylephrine or surgical decompression to prevent ischemia
varicocele
dilation of spermatic vein due to impaired drainage gives ‘bag of worms’ appearance
- usually L sided, associated with L sided RCC since often invades L renal vein
- seen in many infertile males (warm blood piles up)
testicular torsion
twisting of spermatic cord -> veins become obstructed -> congestion and hemorrhagic infarction
- usually congenital failure of testes to attach inner lining of scrotum via processus vaginalis
- presents as sudden testicular pain and absent cremasteric reflex
congenital hydrocele
common cause of scrotal swelling in infants due to incomplete obliteration of proccessus vaginalis
-transilluminating swelling
acquired hydrocele
benign scrotal fluid collection usually secondary to infection, trauma, tumor
-transilluminating
-if bloody: hematocele
spermatocele
cyst due to dilated epididymal duct or rete testis
paratesticular fluctuant nodule
extragonadal germ cell tumors
arise in midline locations
Adults- retroperitoneum, mediastinum, pineal and supraseller regions
Infants and young kids- sacrococcygeal teratomas most common
Testicular germ cell tumors
~95% of testicular tumors
- Seminomas (55% of cases, good prognosis)
- Non-seminomas (45% of cases, variable response and metastasize early): embryonal carcinoma, yolk sac (endodermal sinus) tumor, choriocarcinoma, teratoma
- usually young men (15-40yr)
- risk factors: cryptorchidism, Klinefelter syndrome
- can present as mixed germ cell tumor
- Ddx for painless testicular mass that doesn’t transilluminate is cancer
Seminoma
Malignant, painless, homogenous testicular enlargement
- most common testicular tumor, most common in 30s, never in infancy
- large cells in lobules with clear cytoplasm and ‘fried egg’ appearance (resembles dysgerminoma in ovary)
- increased placental ALP
- responds to RT, late metastasis, very good prognosis
Embryonal carcinoma
malignant, hemorrhagic mass with necrosis; painful; worse prognosis than seminoma- aggressive with early spread
- glandular/papillary morphology, usually mixed with other tumor types
- chemo can cause differentiation into other germ cell tumors
- may have increased hCG and normal AFP levels when pure, increased AFP if mixed
Yolk sac (endodermal sinus) tumors
malignant tumor that resembles yolk sac elements- yellow, mucinous
-most common testicular tumor in children
Choriocarcinoma
malignant tumor of syncytiotrophoblasts (produces hCG) and cytotrophoblasts (placenta like with absent villI)
- high hCG
- spreads early via blood –> lungs and brain, may present with ‘hemorrhagic stroke’
- may produce gynecomastia, symptoms of hyperthyroidism (hCG structurally similar to LH, FSH, TSH)
Teratomas
Unlike in females, mature teratoma in adult males may be malignant! Benign in children
Increased hCG and/or AFP in 50% cases
Sex cord-stromal tumors
~5% of all testicular tumors, mostly benign
Leydig cell tumor
produces androgen -> precocious puberty in children or gynecomastia in adults
-Characteristic Reinke crystals (eosinophilic cytoplasmic inclusions)
Sertoli cell tumor
Androblastoma from sex cord stroma, comprised of tubules and clinically silent
Testicular lymphoma
most common in older men. bilateral masses
- not a primary cancer-> arises from metastatic lymphoma to testes, usually diffuse large B cell
- aggressive
Acute prostatitis
-usually bacterial: 1. young adults STDs: chlamydia and gonorrhoeae, 2. old (UTIs): E. coli and Pseudomonas
- presents with dysuria, fever and chills
- prostate tender on DRE
- prostatic secretions show WBCs and bacteria on culture
Chronic prostatitis
- chronic inflammation, usually abacterial
- dysuria with pelvic or low back pain
- secretios show WBCs with negative culture
Benign prostatic hyperplasia (BPH)
hyperplasia of prostatic stroma and glands -> smooth, elastic, firm nodular enlargement (since no hypertrophy, just hyperplasia) of periurethral lobes (lateral and middle)
- common in men >50yr
- NOT precursor to cancer
- related to DHT -> acts on androgen receptors of stromal and epithelial cells -> hyperplastic nodules
Clinical features:
- problems starting and stopping urine stream
- dysuria
- increased frequency of urination
- free PSA elevated
Complications: impaired bladder emptying increases risk for UTIs, hydronephrosis, hypertrophy of bladder wall
Treatment:
-alpha1 antagonists: terazosin (if also have HTN), tamsulosin (in normotensive patients) -> relax smooth muscle
- PDE-5 inhibitors
- 5a-reductase inhibitors (finasteride) -> blocks conversion to DHT but takes months to produce results
Prostate adenocarcinoma
malignant proliferation of prostatic glands, usually arises in posterior lobe (peripheral zone)
- common in men >50
- diagnosed by increased total PSA, decreased fraction of free PSA (tumor produces bound PSA) and needle core biopsy
- Prostatic acid phosphatase (PAP) also good tumor marker
- Osteoblastic mets in bone may develop late -> presents with low back pain and increased serum ALP and PSA
Treatment: prostatectomy for localized disease; advanced disease treated with hormone suppression: continuous GnRH analogs (leuprolide), Flutamide competitive inhibitor at androgen receptor
What are the 2 layers of epithelium that line the lobules and ducts of the breast?
luminal cell layer- inner cell layer, responsible for milk production in lobules
myoepithelial cell layer- outer cell layer lining ducts and lobules, contractile fxn propels milk
Acute mastitis
Bacterial infection of breast, usually Staph aureus
- associated with fissures in nipple- breast feeding usually
- presents as erythematous breast w purulent nipple discharge; may progress to abscess
Treatmet: drainage (continued feeding), antibiotics (dicloxacillin)
Periductal mastitis
inflammation of subareolar ducts (highly specialized epithelia dependent on vitamin A)
- common in smokers (vitamin A deficiency)
- > squamous metaplasia of lactiferous ducts blocks duct and causes inflammation
-presents as subareolar mass w nipple retraction (myofibroblasts contract)
Mammary duct ectasia
Inflammation with dilation (ectasia) of subareolar ducts
-rare, usually in multiparous postmenopausal women
**green-brown nipple discharge and periareolar mass
-plasma cells seen on biopsy
Fat necrosis of breast
benign, usually painless lump, usually blunt trauma related (50% do not report trauma)
-abnormal calcifications on mammogram
Biopsy shows necrotic fat and giant cells
Proliferative breast disease
Most common cause of ‘breast lumps’ from 25-menopause.
-presents w pre-menstrual breast pain and multiple lesions, usually bilateral in upper outer quadrant. Fluctuates size
NO increased risk for invasive carcinoma:
- Fibrosis- hyperplasia of breast stroma
- cystic change - fluid filled, blue dome. ductal dilation
- apocrine metaplasia (abundant eosinophilic cytosol)
- 5-2x increased risk for invasive carcinoma:
- Ductal hyperplasia
- sclerosing adenosis: associated with calcification and often mistaken for cancer
Atypical hyperplasia -> 5x increased risk
Intraductal papilloma
benign papillary growth into large duct, slight increase risk for cancer
- fibrovascular projections lined by epithelial (luminal) AND myoepithelial cells (normal cell layers)
- presents as bloody nipple discharge in PREmenopausal woman
- must be distinguished from papillary CARCINOMA: no myoepithelial cells, usually POSTmenopausal woman
Fibroadenoma
Most common benign neoplasm of breast in premenopausal women
- small, mobile, firm mass with well-circumscribed edges
- estrogen sensitive-> grows during pregnancy and pain during menstrual cycle
- benign with NO increased risk of carcinoma
Phyllodes tumor
Fibroadenoma-like tumor with overgrowth of fibrous component
Large, bulky mass with ‘leaf-like’ projections on biopsy
- most common in postmenopausal women (50s)
- can be malignant
Breast cancer risk factors
increased estrogen exposure
- F»M
- Age
- Early menarche/late menopause
- obesity (adipose converts androgens to estrone)
- atypical hyperplasia
- 1st degree relative with breast cancer (BRCA1/2 mutations)
- African American ethnicity (increases risk of triple negative breast cancer)
Ductal carcinoma in situ (DCIS)
Malignant proliferation of cells in ducts (fills lumen) with NO invasion of basement membrane
- often detected as calcification on mammography, does NOT usually produce mass
- Biopsy calcification to distinguish difference between malignant and benign
Comedo type DCIS
subtype of DCIS
- high-grade cells with necrosis and dystrophic calcification in center of ducts
Paget disease of breast
DCIS or invasive breast cancer that extends up to ducts to involve skin of the nipple
Presentation: nipple ulceration and erythema
-almost always associated with underlying carcinoma
Paget cells= large cells in epidermis with clear halo
Invasive ductal carcinoma
Most common type of invasive carcinoma in breast, most invasive breast cancer
- presents as firm, fibrous ‘rock-hard’ mass with sharp margins, detected by physical exam (>2cm) or mammography (1cm or larger)
- Advanced tumors may result in dimpling of skin or retraction of nipple
- biopsy usually shows duct-like structures in desmoplastic stroma
Tubular carcinoma
subtype of invasive ductal carcinoma
- well-differentiated tubules that lack myoepithelial cells
- good prognosis
Mucinous carcinoma
subtype of invasive ductal carcinoma
- carcinoma w abundant extracellular mucin ‘tumor cells floating in a mucus pool’
- older women (70yrs)
- relatively good prognosis
Medullary carcinoma
subtype of invasive ductal carcinoma
- large, high-grade cells growing in sheets with associated lymphocytes and plasma cells
- grow as well-circumscribed mass that can mimic fibroadenoma on mammography
- good prognosis
- increased incidence in BRCA1
Inflammatory carcinoma
subtype of invasive ductal carcinoma
- carcinoma in dermal lymphatics
- presents as inflamed- erythematous, peau d’ orange- swollen breast (tumor blocks lymphatics)
- no discrete mass, can be mistaken for mastitis
- very poor prognosis
Lobular carcinoma in situ (LCIS)
malignant proliferation of cells in lobules without basement membrane proliferation
- no mass or calcifications -> found incidentally on biopsy
- lacks E-cadherin
- multifocal and bilateral
- treat with tamoxifen to reduce risk of carcinoma, close follow-up
Invasive lobular carcinoma
invasive, orderly row of cells ‘Indian file’ due to lack of E-cadherin expression (no duct formation)
- usually multifocal and bilateral
- may show signet-ring morphology
Prognostic and predictive factors of breast cancer
Metastasis is most important factor, but since most present before metastasis –> axillary lymph node spread is most USEFUL factor
Predictive factors to treatment response:
Estrogen receptor (ER)
Progesterone receptor (PR)
HER2/neu gene amplification
ER and PR (+) –> antiestrogenic agents (tamoxifen)
HER2/neu (+)–> trastuzumab (Herceptin)
BRCA1 and BRCA2 mutations
BRCA1 mutation associated with breast and ovarian (serous, also in fallopian tubes) carcinoma
BRCA2 also associated with breast carcinoma in males
Male breast cancer
very rare
- subareolar mass in older males, may produce discharge
- most common is invasive ductal carcinoma
Associated with BRCA2 and Klinefelter syndrome
Klinefelter syndrome
47, XXY [male]
Testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution, mild intellectual disability
- usually diagnosed in puberty, common cause of hypogonadism in infertility work up (azoospermia)
Primary testicular failure:
hyalinization and fibrosis of seminiferous tubules -> decreased inhibin -> high FSH
Leydig disfunction -> decreased testosterone -> increased LH -> increased estrogen
Turner syndrome
45, XO [female] resulting from mitotic or meiotic error; can be complete monosomy (45 XO) or mosaicism (45XO/46XX)
- short stature (untreated)
- ovarian dysgenesis (streak ovary)
- shield chest
- bicuspid aortic valve
- preductal coarctation (femoral high LH, FSH
- cystic hygromas (lymphatic malformations) usually on neck- painless doughy mass that transluminates
Double Y males
XYY
Phenotypically normal, very tall
Random nondisjunction event (paternal meiosis II)
-normal fertility, associated with severe acne, learning disability, autism spectrum disorders
True hermaphroditism
46 XX or 47 XXY
Also called ovotesticular disorder of sex development
-Both ovarian and testicular tissue present; ambiguous genitalia
What are the relative testosterone and LH levels with defective androgen receptor?
Testosterone: high
LH: high
What are the relative testosterone and LH levels with testosterone secreting tumor or exogenous steroids?
Testosterone: high
LH: low
What are the relative testosterone and LH levels with primary hypogonadism?
Testosterone: low
LH: high
What are the relative testosterone and LH levels with hypogonadotropic hypogonadism?
Testosterone: low
LH: low
Female pseudo-hermaphrodite (XX)
ovaries present but external genitalia are virilized or ambiguous
-excessive/inappropriate exposure to androgenic steroids during early gestation (congenital adrenal hyperplasia, exogenous androgens during pregnancy)
Male pseudo-hermaphrodite (XY)
testes present but external genitalia are female or ambiguous
most commonly caused by androgen insensitivity syndrome (testicular feminization)
Aromatase deficiency
Inability to synthesize estrogen from androgens
- masculinization of female infants (ambiguous genitalia)
- increased testosterone and androstenedione
- can present with maternal virilization during pregnancy since androgens cross the placenta
Androgen insensitivity syndrome (46XY)
Defect in androgen receptor -> normal appearing female; female external genitalia with scant sexual hair, rudimentary vagina
- uterus and fallopian absent
- patients develop testes (found in labia majora; surgically removed to prevent malignancy)
- increased testosterone, estrogen and LH
5alpha reductase deficiency
AR, sex limited to genetic males 46XY
Inability to convert testosterone to DHT
-normal internal genitalia, ambiguous external genitalia until puberty when increased testosterone causes increased growth of external genitalia
- Testosterone/estrogen levels normal
- LH normal or elevated
Kallmann syndrome
Failure to complete puberty
-hypogonadotropic hypogonadism -> defective migration of GnRH cells and formation of olfactory bulb
- anosmia (no sense of smell)
- decreased GnRH, FSH, LH, testosterone
- infertility (low sperm in males, amenorrhea in females)
