Reproductive Medicine Pathology

• Risk Factors:
• -multiple sex partners (#1)
• -smoking
• -early sexual intercourse
• -HIV infection

• Pathophysiology:
• -associated with HPV infection
• -HPV 16: E6 inhibits p53
• -HPV 18: E7 inhibits Rb

• Pathology:
• -disordered epithelial growth
• -begins at basal layer of squamo-columnar junction and extends outward
• -koilocytic change (raisinoid nucleus)
• -nuclear atypia
• -increased mitotic activity
• -progressive stepwise from CIN I to CIS

• Classification:
• -cervical intraepithelial neoplasia
• -CIN I: involves < 1/3 of thickness
• -CIN II: involves < 2/3 of thickness
• -CIN III: involves slightly less than the entire thickness
• -Carcinoma in situ (CIS): full thickness

• *may progress to invasive carcinoma if left untreated
• **CIN I often regresses

• Screening:
• -PAP smear can catch cervical dysplasia before it develops into carcinoma
• -low grade (CIN I)
• -high grade (CIN II and CIN III)
• **has not decreased incidence of adenocarcinoma

• Immunization:
• -quadrivalent vaccine (6, 11, 16, 18)
• -6, 11 protect against condylomas
• -16, 18 protect against CIN and carcinoma
• -still need PAP smears (doesn't cover all strains)

• Epidemiology:
• -middle aged women (40-50y)

• Risk Factors:
• -high risk HPV infection
• -smoking
• -immunodeficiency (AIDS-defining illness)

• Presentation:
• -vaginal bleeding (especially post-coital)
• -cervical discharge

• Pathology:
• -squamous cell carcinoma (80%)
• -adenocarcinoma (15%)

• Complications:
• -tumor grows locally and metastasizes late
• -lateral invasion can block ureters (→ hydronephrosis and renal failure)

• Pathophysiology:
• -loss of basalis and scarring
• -result of overaggressive D&C

• Presentation:
• -secondary amenorrhea

• Pathophysiology:
• -bacterial infection (from vagina or intestinal tract) of the endometrium
• -usually due to retained products of conception following delivery/miscarriage/abortion
• -also associated with IUD

• Presentation:
• -fever
• -abnormal uterine bleeding
• -pelvic pain

• Treatment:
• -gentamycin + clindamycin
• -with or without ampicilin

• Pathophysiology:
• -chronic inflammation of the endometrium

• Diagnosis:
• -lymphocytes and plasma cells in endometrium (lymphocytes normally present; plasma cells required for diagnosis)

• Causes:
• -retained products of conception
• -chronic pelvic inflammation (chlamydia)
• -IUD
• -TB

• Presentation:
• -abnormal uterine bleeding
• -pain
• -infertility

• Pathophysiology:
• -non-neoplastic endometrial glands/stroma in abnormal locations outside the uterus
• -most common site of involvement is ovary
• -uterine ligaments, pouch of Douglas, bladder wall, bowel serosa, fallopian tube serosa

• Theories:
• 1. Retrograde menstruation
• 2. Metaplastic theory
• 3. Lymphatic dissemination (lungs)

• Presentation:
• -dysmenorrhea (severe pain during menstruation)
• -painful intercourse
• -infertility
• -menorrhagia
• -dysparenuria

• Pathology:
• -ovaries → chocolate cysts
• -yellow brown, gun powder nodules
• -uterus normal sized

• Complications:
• -increased risk of carcinoma (esp in the ovary)

• Treatment:
• -OCPs
• -NSAIDs
• -Leuprolide
• -danazol

• Pathophysiology:
• -endometrium within the myometrium

• Presentation:
• -menorrhagia
• -dysmenorrhea
• -pelvic pain
• -uterus is enlarged! (vs endometriosis)

• Treatment:
• -hysterectomy

• Risk Factors:
• -obesity
• -anovulatory cycles
• -hormone replacement therapy
• -PCOS
• -granulosa cell tumor

• Pathophysiology:
• -consequence of unopposed estrogen

• Presentation:
• -postmenopausal vaginal bleeding

• Biopsy:
• -too many glands
• -with or without atypia (with atypia → high risk for endometrial carcinoma)

• Epidemiology:
• -most common gynecologic malignancy
• -peak occurrence 55-65 years

• Risk Factors:
• -prolonged use of estrogen without progestins
• -obesity
• -diabetes
• -HTN
• -nulliparity
• -late menopause

• Two Pathways
• 1. Hyperplasia
• -75%
• -avg age 60 years
• -histology shows endometrioid pathology
• 2. Sporadic
• -arises with no evident precursor lesion
• -avg age 70 years
• -histology is serous with papillary structures and psammoma bodies
• -p53 mutations common
• -more aggressive

• Clinical Presentation:
• -vaginal bleeding (postmenopausal bleeding)

"Fibroids"

• Epidemiology:
• -most common tumor in females
• -common in premenopausal women (20-40 years)
• -increased incidence in blacks

• Pathophysiology:
• -benign smooth muscle tumor arising from myometrium
• -related to estrogen exposure
• -increase size with pregnancy
• -decrease size with menoapuse

• Pathology:
• -multiple
• -well defined, white, whorled masses

• Presentation:
• -commonly asymptomatic
• -abnormal uterine bleeding
• -severe bleeding may lead to iron deficiency anemia
• -miscarriage
• -pelvic mass

DOES NOT PROGRESS TO LEIOMYOSARCOMA

• Epidemiology:
• -affect postmenopausal women (70-80 years)
• -increase incidence in blacks

• Pathophysiology:
• -malignant proliferation of smooth muscle of myometrium
• -typically arise de novo!

• Pathology:
• -usually a single lesion
• -bulky, irregularly shaped tumor
• -areas of necrosis and hemorrhage

• Presentation:
• -may protrude from cervix and bleed

• Prognosis:
• -highly aggressive tumor with tendency to recur

• Incidence:
• endometrial > ovarian > cervical
• **worldwide ovarian most common

• Worst Prognosis:
• ovarian > cervical > endometrial

• Pathophysiology:
• -premature atresia of ovarian follicles in women of reproductive age

• Presentation:
• -signs of menopause after puberty but before age 40

• Hormones:
• -↓ estrogen
• -↑ LH
• -↑ FSH

• -pregnancy
• -PCOS
• -obesity
• -HPO axis abnormalities
• -premature ovarian failure
• -hyperprolactinemia
• -thyroid disorders
• -eating disorders
• -Cushing's syndrome
• -adrenal insufficiency

• Epidemiology:
• -affects 5% of women of reproductive age

• Pathophysiology:
• -increased LH production leads to anovulation and therefore no progesterone
• -LH causes hyperandrogenism (increased androgen secretion by theca cells
• -Androgens are converted to estrone peripherally in adipose tissue
• -high levels of androgen inhibit FSH
• -without FSH stimulation granulosa cells don't produce estradiol and oocytes do not mature
• -this leads to cystic degeneration of the follicles

• Pathology:
• -bilaterally enlarged, cystic ovaries

• Clinical Presentation:
• -amenorrhea/oligomenorrhea
• -infertility
• -obesity
• -hirsutism

• Associated with:
• -insulin resistance
• -increased risk of endometrial cancer (increased estrogen without opposing progesterone)

• Hormones:
• -↑ LH
• -↓ FSH
• -↑ testosterone
• -↑ estrogen (from testosterone aromatization)

• Treatment:
• -weight reduction
• -low dose OCPs or medroxyprogesterone (reduce LH and androgenesis)
• -spironolactone (acne and hirsutism)
• -clomiphene (for women who want to get pregnant)
• -metformin (diabetes

• -Follicular cyst
• -Corpus Luteum cyst
• -Theca-lutein cyst
• -Hemorrhagic cyst
• -Dermoid cyst
• -Endometrioid cyst

• Pathophysiology:
• -distention of unruptured graafian follicle
• -may be associated with hyperestrinism and endometrial hyperplasia

Most common ovarian mass in young women

• Pathophysiology:
• -hemorrhage into persistent corpus luteum
• -commonly regresses spontaneously

• Pathophysiology:
• -often bilateral/multiple
• -due to gonadotropin stimulation

Associated with choriocarcinoma and moles

• Pathophysiology:
• -blood vessel rupture in cyst wall
• -cyst grows with increased blood retention
• -usually self resolves

• Pathophysiology:
• -mature teratoma
• -cystic growths filled with various types of tissue such as fat, hair, teeth, bits of bone and cartilage

• Pathophysiology:
• -endometriosis within ovary with cyst formation
• -varies with menstrual cycle
• -"chocolate cyst" when filled with dark reddish-brown blood

• Epidemiology:
• -second most common type of ovarian tumors (15%)-most common in adolescents/women of reproductive age

• Types:
• 1. Dysgerminoma (oocytes)
• 2. Choriocarcinoma (placental tissue)
• 3. Endodermal sinus tumor (yolk sac)
• 4. Teratoma (fetal tissue)
• 5. Embryonal carcinoma (fetal tissue)

• Epidemiology:
• -malignant
• -rare (1% of GCT in females)
• -male counterpart = seminoma (30% of GCT in males)
• -associated with Turner Syndrome

• Pathology:
• -sheets of uniform cells
• -large cells with clear cytoplasm and central nuclei (resemble oocytes)

• Tumor Markers:
• -hCG
• -LDH

• Prognosis/Treatment:
• -good prognosis
• -responds to radiotherapy

• Epidemiology:
• -rare but malignant
• -can develop during or after pregnancy in mother or baby
• -gestational trophoblastic neoplasia

• Pathophysiology:
• -malignancy of trophoblastic tissue
• -chorionic villi are ABSENT
• -small hemorrhagic tumor with hematogenous spread to lungs
• -increased frequency of theca-lutein cysts

• Tumor Markers:
• -hCG

• Prognosis/Treatment:
• -poor response to chemo

• Epidemiology:
• -most common GCT in children

• Pathophysiology:
• -malignant tumor that mimics yolk sac
• -of ovaries (testes in boys) and sacrococcygeal area

• Pathology:
• -yellow, friable solid masses
• -50% have Schiller-Duval bodies (resemble glomeruli)

• Tumor Markers:
• -AFP

• Epidemiology:
• -90% of ovarian GCTs
• -bilateral in 10%
• -benign

• Pathophysiology:
• -contains tissue from 2 or 3 germ layers

• Mature Teratoma
• -"dermoid cyst"
• -mostly benign
• -most common ovarian GCT

• Immature Teratoma
• -aggressively malignant
• -usually neural tissue
• *can also have tumors of tissue in teratoma (most commonly squamous cell carcinoma of skin)

• Struma Ovarii
• -contains functional thyroid tissue
• -can present as hyperthyroidism

• Pathophysiology:
• -malignant tumor composed of large primitive cells

Aggressive with early metastasis

-tumors that arise from surface epithelium or sex cords

• Surface Epithelial Tumor
• 1. Serous Cystadenoma
• 2. Serous Cystadenocarcinoma
• 3. Mucinous Cystadenoma
• 4. Mucinous Cystadenocarcinoma
• 5. Brenner Tumor

• Sex-Cord Stromal Tumor
• 6. Fibromas
• 7. Granulosa Cell Tumor
• 8. Sertoli-Leydig Cell Tumor

• Metastases
• 9. Krukenberg Tumor

• Epidemiology:
• -45% of ovarian tumors
• -benign
• -most commonly in premenopausal women (30-40 years)

• Pathology:
• -frequently bilateral
• -lined with fallopian tube-like epithelium
• -single cyst with flat lining

• Tumor Marker
• -CA-125 (good for monitoring progression, not screening)

• Epidemiology:
• -45% of ovarian tumors
• -malignant
• -more common in postmenopausal women (60-70 years)

• Pathology:
• -frequently bilateral
• -psammoma bodies-complex cyst with a thick, shaggy lining

• Risk Factors:
• -BRCA1, BRCA2, HNPCC
• -significant genetic predisposition makes family history the most important risk factor

• Epidemiology:
• -45% of ovarian tumors
• -benign
• -most commonly in premenopausal women (30-40 years)

• Pathology:
• -multilocular cyst lined by mucus-secreting epithelium
• -intestine like tissue

• Epidemiology
• -45% of ovarian tumors (with serous)
• -malignant
• -most commonly in postmenopausal women (60-70 years)

• Pathology:
• -pseudomyxoma peritonei: intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor ("Jelly Belly")

• Pathology:
• -benign
• -unilateral
• -looks like Bladder
• -solid tumor, pale yellow-tan color
• -appears encapsulated
• -"coffee bean" nuclei

• Pathology:
• -benign tumor of fibroblasts
• -bundles of spindle-shaped fibroblasts

• Meigs' Syndrome
• 1. Ovarian fibroma
• 2. Ascites
• 3. Hydrothorax

Pulling sensation in groin

• Presentation:
• -often produce estrogen
• -Children: precocious puberty
• -Reproductive age: menorrhagia and metrorrhagia
• -Postmenopause: endometrial hyperplasia, postmenopausal uterine bleeding (risk for carcinoma)

• Pathology:
• -Call-Exner bodies: small follicles filled with eosinophilic secretions

• Pathophysiology:
• -Granulosa-Theca cells and Sertoli-Leydig cells have a similar embryonic precursor

• Pathology:
• -composed of sertoli cells that form tubules and Leydig cells inbetween
• -Reinke crystals

• Presentation:
• -may produce androgen
• -associated with hirsutism and virilization

• Pathophysiology:
• -metastatic mucinous tumor that involves both ovaries
• -most commonly due to diffuse type gastric carcinoma

• Pathology:
• -signet ring cells

Krukenberg tumor is usually bilateral, distinguishes from primary mucinous carcinoma of the ovary (usually unilateral)

• Normal Development:
• -squamous epithelium derived from the urogenital sinus lines the lower 2/3 of the vagina
• -columnar epithelium derived from the Mullerian ducts lines the upper 1/3 of the vagina
• -normally squamous epithelium replaces the columnar epithelium

• Pathogenesis:
• -focal persistence of columnar epithelium in the upper 1/3 of the vagina

• Risk Factors:
• -DES exposure in utero

Increased risk for clear cell adenocarcinoma

• Epidemiology:
• -women of reproductive age

• Pathogenesis:
• -cystic dilation of the Bartholin gland (on either side of the vaginal canal, secrete mucus-like fluid)
• -dilation arises due to inflammation and obstruction of the gland

• Presentation:
• -unilateral, painful cystic lesion at the lower vestibule

• Pathophysiology:
• -most commonly due to HPV 6, 11
• -less commonly due to syphilis

• Presentation:
• -warty neoplasm of vulvar skin, often large

Rarely progress to carcinoma

• Epidemiology:
• -postmenopausal women

• Pathophysiology:
• -thinning of the epidermis and fibrosis (sclerosis) of the dermis

• Presentation:
• -white patch (leukoplakia) with parchment like vulvar skin

Benign but slight increased risk for squamous cell carcinoma

• Pathophysiology:
• -associated with chronic irritation and scratching
• -hyperplasia of vulvar squamous epithelium

• Presentation:
• -leukoplakia with thick, leathery skin

Benign, no increased risk of squamous cell carcinoma

• Epidemiology:
• -relatively rare
• -HPV-related: reproductive age women
• -non-HPV related: women > 70 years

• Pathophysiology:
• -may be HPV related (arises from VIN)
• -or non-HPV related (long standing lichen sclerosis)

• Presentation:
• -leukoplakia
• -biopsy needed to distinguish from other causes of leukoplakia

• Pathophysiology:
• -carcinoma in situ (usually no underlying carcinoma)
• -vs Paget disease of the nipple (always underlying carcinoma)

• Presentation:
• -erythematous
• -pruritic
• -ulcers

• Distinguish from Melanoma:
• -Paget Cells: PAS+, keratin+, S100-
• -Melanoma: PAS-, keratin-, S100+

• 1. Squamous Cell Carcinoma
• 2. Clear Cell Adenocarcinoma
• 3. Sarcoma botryoides (Rhadomyosarcoma)

• Pathophysiology:
• -usually secondary to cervical SCC
• -primary VERY rare

• Epidemiology:
• -women who had DES exposure in utero

• Pathology:
• -malignant proliferation of glands with clear cytoplasm

"Embryonal Rhabdomyosarcoma"

• Epidemiology:
• -very rare
• -usually child (<5 years)

• Pathophysiology:
• -malignant mesenchymal proliferation of immature skeletal muscle

• Presentation:
• -bleeding and grape-like mass that protrudes from the vagina or penis of a child

• Pathology:
• -cytoplasmic cross-striations
• -IF positive for desmin and myogenin

• Pathophysiology:
• -usually related to high-risk HPV
• -precursor lesion VAIN

• Lymph Node Spread
• -lower 2/3 of vagina (UGS) → inguinal nodes
• -upper 1/3 of vagina (Mullerian Duct) → regional iliac nodes

• Nipple:
• -Paget's Disease
• -Breast abscess

• Lactiferous Sinus:
• -intraductal papilloma
• -breast abscess
• -mastitis

• Major Duct:
• -fibrocystic change
• -ductal cancer

• Terminal Duct:
• -tubular carcinoma

• Lobules:
• -lobular carcinoma
• -sclerosing adenosis

• Stroma:
• -Fibroadenoma
• -Phyllodes tumor

• 1. Fibroadenoma
• 2. Intraductal Papilloma
• 3. Phyllodes Tumor

• Epidemiology:
• -most common tumor in those < 35 years

• Pathophysiology:
• -tumor of fibrous tissue and glands
• -estrogen sensitive (increase size and tenderness)

• Pathology:
• -small, mobile, firm mass
• -sharp edges

• Prognosis:
• -no increased risk of carcinoma

• Epidemiology:
• -typically premenopausal women

• Pathology:
• -small projection that grows into lactiferous ducts
• -typically beneath areola
• -lined by both epithelium and myoepithelial cells

• Presentation:
• -bloody nipple discharge

• Prognosis:
• -slight (1.5-2x) increase risk for carcinoma

• Must distinguish from Papillary Carcinoma!!!
• -risk increases with age (commonly in postmenopausal women)
• -lacks myoepithelial cell layer

• Epidemiology:
• -most common in 6th decade (postmenopausal women)

• Pathophysiology:
• -fibroadenoma-like tumor with overgrowth of fibrous component

• Pathology:
• -large bulky mass of connective tissue and cysts
• -"leaf like" projections

• Prognosis:
• -some may become malignant

• Epidemiology:
• -most common cause of "breast lumps" from age 25 to menopause

• Pathophysiology:
• -thought to be hormone mediated
• -cysts of glands/ducts stretch connective tissue leading to fibrosis

• Pathology:
• -cysts have a blue dome appearance on gross exam

• Presentation:
• -premenstrual breast pain
• -multiple lesions
• -often bilateral
• -fluctuation in size of mass

• Histologic Types:
• 1. Fibrosis:
• -hyperplasia of breast stroma

• 2. Cystic:
• -fluid filled
• -blue dome
• -ductal dilation

• 3. Sclerosing Adenosis:
• -increased acini and intralobular fissures
• -calcifications
• -often confused with cancer
• -slight increased risk of cancer (2x)

• 4. Epithelial Hyperplasia/Apocrine hyperplasia
• -increase in number of epithelial cell layers in terminal duct lobule
• -increased risk of carcinoma with atypical cells (5x)
• -occurs in women > 30 years old

• 1. Acute Mastitis
• 2. Periductal Mastitis
• 3. Mammary Duct Ectasia
• 4. Fat Necrosis

• Epidemiology:
• -associated with breast feeding (fissures develop in nipple allowing microbe entry)

• Pathophysiology:
• -most common organism = S. aureus

• Presentation:
• -erythematous breast
• -purulent nipple discharge
• -may develop abscess (can lead to a mass)

• Treatment:
• -continued drainage (breast feeding)
• -antibiotics (dicloxacillin)

• Pathophysiology:
• -inflammation of subareolar ducts
• -usually seen in smokers: lactiferous ducts surrounded by highly specialized epithelium that is dependent on vitamin A
• -vitamin A deficiency leads to squamous metaplasia → duct blockage and inflammation

• Presentation:
• -subareolar mass
• -nipple retraction

• Epidemiology:
• -rare
• -classically arises in multiparous, postmenopausal women

• Pathophysiology:
• -inflammation with dilation (ectasia) of the subareolar ducts

• Presentation:
• -periareolar mass
• -green-brown nipple discharge
• -plasma cells seen on bx

• Epidemiology:
• -forms after trauma (50% may not report trauma)

• Presentation:
• -benign, usually painless lump
• -calcification on mammography

• Epidemiology:
• -occurs in males

• Pathophysiology:
• -hyperestrogenism (cirrhosis, testicular tumor, puberty, old age)
• -Klinefelter's syndrome
• -Drugs (estrogen, marijuana, heroin, psychoactive drugs)

• "Some Drugs Create Awkward Knockers"
• -Spironolactone
• -Digitalis
• -Cimetidine
• -Alcohol
• -Ketoconazole

• Epidemiology:
• -common post-menopause
• -second most common cause of cancer mortality in women

• Risk Factors:
• -increased estrogen exposure
• -increased total number of menstrual cycles
• -older age at first live birth
• -obesity (increased estrogen due to peripheral adipose conversion)
• -BRCA1/2

• Pathophysiology:
• -usually arise from terminal duct lobular unit
• -usually located in upper outer quadrant of breast

• Molecular Factors:
• -overexpression of estrogen/progesterone receptors or Her2/Neu is common
• -affect therapy and prognosis

• Prognosis:
• -axillary LN metastasis is the most important prognostic factor (usually caught before peripheral metastasis)

• Noninvasive Types:
• 1. Ductal Carcinoma In Situ
• 2. Comedocarcinoma (subtype of DCIS)
• 3. Lobular Carcinoma In Situ

• Invasive Types:
• 1. Invasive Ductal Carcinoma
• 2. Invasive Lobular Carcinoma
• 3. Medullary Carcinoma
• 4. Inflammatory Carcinoma
• 5. Paget's Disease

• Characteristics:
• -fills ductal lumen
• -arises from ductal hyperplasia
• -no invasion of basement membrane

• Presentation:
• -often detected as calcification on mammography (biopsy often needed to distinguish between malignant and benign calcifications)
• -doesn't usually produce a mass

• Histologic Types:
• 1. Comedo type
• 2. Paget disease of the breast

Subtype of DCIS

• Characteristics:
• -ductal, caseous necrosis
• -dystrophic calcification at the center of ducts

• Pathophysiology:
• -DCIS that extends up the ducts to involve the skin of the nipple

• Paget Cells
• -large cells in epidermis with clear halo

• Presentation:
• -nipple ulceration and erythema
• -almost always associated with underlying carcinoma (vs. Paget's in the vulva)

• Pathophysiology:
• -malignant proliferation of lobules with no invasion of basement membrane
• -dyscohesive cells (due to lack of E cadherin)

• Presentation:
• -does not produce a mass or calcifications
• -usually discovered incidentally on biopsy
• -often multifocal and bilateral

• Treatment:
• -tamoxifen (reduce risk of subsequent carcinoma)
• -close follow up

Currently seen as more of a risk factor than a malignancy

• Epidemiology:
• -most common type of invasive carcinoma (>80%)

• Presentation:
• -firm, fibrous, "rock hard" mass with sharp margins
• -detected by mammography (>1cm) or on physical exam (>2cm)

• Pathology:
• -small, glandular duct-like cells
• -duct-like structures with desmoplastic stroma

• Subtypes:
• 1. Tubular: well differentiated, relatively good prognosis
• 2. Mucinous: "tumor cells floating in a pool of mucus", older women (>70), good prognosis
• 3. Medullary carcinoma
• 4. Inflammatory carcinoma

• Epidemiology:
• -increased incidence in BRCA1 carriers

• Pathology:
• -fleshy, cellular
• -well-circumscribed mass
• -lymphocytic infiltrate (plasma cells)
• -mimic fibroadenoma

• Prognosis:
• -relatively good

• Presentation:
• -inflamed swollen breast
• -no discrete mass
• **can be mistaken for acute mastitis
• -Peau d'orange (skin resembles orange peel)

• Pathophysiology:
• -tumor cells block lymphatic drainage

• Prognosis:
• -very poor
• -50% survival at 5 years

• Pathology:
• -grows in a single file pattern (Indian file)
• -no duct formation due to lack of E cadherin
• -may have signet-ring morphology

• Presentation:
• -often multiple lesions and bilateral

• Presentation:
• -dyuria
• -frequency
• -urgency
• -fever and chills
• -low back pain
• -prostate tender and boggy on DRE
• Acute (bacterial)
• -Young adults (C. trachomatis, N. gonorrhea)
• -Older adults (E. coli, Pseudomonas)

Chronic (abacterial)

• Epidemiology:
• -age-related change
• -common in men > 50 years

• Pathophysiology:
• -hyperplasia (NOT hypertrophy) of prostate gland
• -related to DHT (causes hyperplasia)

• Pathology:
• -nodular enlargement of periurethral (lateral and middle) lobes → compress the urethra

• Presentation:
• -increased frequency of urination
• -nocturia
• -difficulty starting and stopping stream
• -dysuria
• -increased PSA

• Complications:
• -distention and hypertrophy of bladder
• -hydronephrosis
• -UTI

• Prognosis:
• -NOT considered premalignant

• Treatment:
• 1. α1-antagonists (terazosin, tamsulosin)
• -relaxation of smooth muscle
• -also lowers BP
• 2. 5a-reductase inhibitor (finasteride)
• -takes months to work
• -also used for male pattern baldness
• -AE: gynecomastia, sexual dysfunction

• Epidemiology:
• -common in men > 50 years
• -most common cancer in men

• Risk Factors:
• -age
• -race (African Americans > Caucasians > Asians)
• -diet high in saturated fats

• Pathophysiology:
• -usually arises in the peripheral, posterior region of the prostate (rarely urinary sx early on)

• Presentation:
• -most often clinically silent

• Screening:
• -increased total PSA (>10)
• -decreased free PSA
• -needle core bx (invasive glands, prominent nucleoli)

• Gleason Grading System
• -based on architecture alone
• -assess multiple regions (pick two most common presentations and add scores: 2-10)

• Metastases:
• -spread to lumbar spine and pelvis is common (osteoblastic mets → lower back pain and ↑Alk Phos)

• Treatment:
• -prostatectomy for localized disease
• -GnRH analogs (leuprolide)
• -Androgen Receptor Antagonist (Flutamide)

Undescended testicle

• Epidemiology:
• -most common congenital male reproductive abnormality
• -1% of male infants
• -increased risk with prematurity

• Pathophysiology:
• -normally testicles develop in the abdomen and then descend into the scrotum

• Hormones:
• -can have normal testosterone (Leydig cells unaffected by temperature)
• -↓ inhibin
• -↑ FSH
• -↑ LH
• -↓ testosterone in bilateral (normal in unilateral)

• Complications:
• -testicular atrophy
• -infertility (increased temperature)
• -increased risk for seminoma (GCT)

• Treatment:
• -usually resolve spontaneously
• -orchioplexy before 2 years if not

Inflammation of the testicle

• Young Adults:
• -Chlamydia trachomatis (D-K)
• -Neisseria gonorrhea
• -increased risk of sterility
• -libido not affected (Leydig cells spared)

• Older Adults:
• -E. Coli
• -Pseudomonas
• -UTI pathogens spread into reproductive tract

• Teenage Males:
• -Mumps virus
• -increased risk for infertility
• -testicular inflammation usually absent in children < 10

• Autoimmune orchitis:
• -granulomas of seminiferous tubules
• -distinguish from TB

• Pathophysiology:
• -twisting of the spermatic cord
• -thin walled veins become obstructed by arterial flow remains intact (blood can get in but can't get out)
• -usually due to congenital failure of testes to attach to inner lining of scrotum (by processus vaginalis)

• Presentation:
• -sudden testicular pain
• -absent cremasteric reflex

• Epidemiology:
• -most common cause of scrotal enlargement in males

• Pathophysiology:
• -dilated veins in pampiniform plexus
• -result of increased venous pressure (impaired drainage)
• -usually left testicle (increased resistance of flow from left gonadal vein drainage into left renal vein)

• Presentation:
• -scrotal enlargement
• -bag of worms appearance

• Complications:
• -infertility (increased temperature)
• -associated with L sided renal cell carcinoma

• Treatment:
• -varicocelectomy
• -embolization

Fluid collection in the tunica vaginalis

• Pathophysiology:
• -associated with incomplete closure of the processus vaginalis leading to communication with peritoneal cavity (infants)
• -blockage of lymphatics (adults)

• Presentation:
• -scrotal swelling
• -can be transilluminated (vs tumor)

Dilated epididymal duct

Testicular mass that can be transilluminated (vs. tumor)

• ~95% of all testicular tumors
• -most often malignant
• -can present as mixed germ cell tumors
• -usually occur btwn 15-40 years of age

• Risk Factors:
• -crytorchidism
• -Klinefelter syndrome

• Presentation:
• -testicular mass that does not illuminated

• Types:
• 1. Seminoma (55%, radioresponsive, metastasize late, excellent prognosis)

• Non-seminoma (45%, variable response to tx, mets early)
• 2. Yolk Sac (Endodermal sinus)
• 3. Choriocarcinoma
• 4. Teratoma
• 5. Embryonal Carcinoma

• Epidemiology:
• -most common testicular tumor
• -mostly males age 15-35
• -resembles ovarian dysgerminoma

• Presentation:
• -painless, homogenous testicular enlargement

• Pathology:
• -malignant
• -large cells in lobules with watery cytoplasm and "fried" egg appearance
• -no hemorrhage or necrosis

• Tumor Markers:
• -↑ placental alkaline phosphatase (PLAP)
• -rare cases produce b-hCG

• Epidemiology:
• -most common testicular tumor in children

• Pathology:
• -yellow, mucinous
• -Schiller-Duval bodies (resemble glomeruli)

• Tumor Markers:
• -↑AFP

• Pathology:
• -malignant
• -disordered syncytiotrophoblastic and cytotrophoblastic elements (absent villi)
• -spreads early by blood (lungs)

• Tumor Markers:
• -↑ β-hCG
• -subunit of hCG is similar to FSH, LH and TSH → gynecomastia and hyperthyroidism

• Pathophysiology:
• -composed of mature fetal tissue derived from 2 to 3 embryonic layers
• -MALIGNANT in males (as opposed to females)
• -benign in children

• Tumor Markers:
• -↑ AFP/ ↑ β-hCG in 50%

• Pathophysiology:
• -malignant
• -painful
• -aggressive with early hematogenous spread
• -pure embryonal carcinoma is rare (usually mixed)

• Pathology:
• -often glandular/papillary morphology

• Tumor Markers:
• -Pure: ↑ hCG, normal AFP
• -Mixed: ↑ AFP

• Prognosis:
• -worse than seminoma
• -chemotherapy may result in differentiation into another type of GCT

• Sex Cord-Stromal Tumors
• 1. Leydig cell tumor
• 2. Steroli cell tumor

Testicular Lymphoma

• Presentation:
• -produce androgen
• → gynecomastia in men
• → precocious puberty in boys

• Pathology:
• -golden brown color
• -Reinke crystals

• Presentation:
• -usually clinically silent

• Pathology:
• -composed of tubules

• Epidemiology:
• -most common cause of a testicular mass in males > 60 years old

• Pathophysiology:
• -not a primary cancer, arises from lymphoma metastasis to testes

• Pathology:
• -often bilateral
• -diffuse large B cell type

• Prognosis:
• -aggressive

• Epidemiology:
• -more common in Asia, Africa, South America

• Risk Factors:
• -high risk HPV-lack of circumcision

• Precursor Lesions
• 1. Bowen Disease:
• -in situ carcinoma on shaft or scrotum
• -leukoplakia
• 2. Erythroplasia of Queyrat
• -in situ carcinoma on the glans
• -erythroplakia
• 3. Bowenoid papulosis
• -multiple reddish papules
• -seen in younger patients
• -does not progress to invasive carcinoma

Bent penis due to acquired fibrous tissue formation

Painful sustained erection not associated with sexual stimulation or desire

• Associated with:
• -trauma
• -SCD
• -medications (anticoagulants, PDE5 inhibitors, antidepressants, α-blockers, cocaine)