Reproductive Pathology Flashcards
ddx for testicular lesions
*tender: torsion, orchitis, epididymitis
*non-tender:
1. hydrocele (transillumination +)
2. varicocele (“bag of worms”)
3. malignancy (testicular cancer, lymphoma)
testicular neoplasms - epidemiology
*Caucasian males between 15-45 years
*risk factors:
-associated with cryptorchidism
-intersex syndromes (androgen insensitivity syndrome; gonadal dysgenesis)
-family history (fathers & sons; 8-10x increased risk)
-increased risk in contralateral testis
testicular neoplasms - pathogenesis
*poorly understood
*precursor lesion = germ cell neoplasia in situ
testicular neoplasms - clinical examples
*painless, solid testicular masses
- seminomas:
-may reach considerable size before diagnosis
-metastases occur first in abdominal lymph nodes
-hematogenous metastases occur late - non-seminomatous tumors (NSGCT):
-may have widespread metastases (liver/lungs)
-absent palpable testicular mass
testicular neoplasms - serum markers
*useful in diagnosis and following therapeutic response
1. alpha fetoprotein (AFP)
2. hCG
testicular neoplasms - treatment
*radical orchiectomy (diagnosis & treatment - presumption of malignancy)
seminoma - overview
*most common germ cell tumor in males
*present with bulky mass:
-soft, well-demarcated, gray-white tumor
-confined to tunica albuginea
seminoma - pathology
*large, uniform cells with distinct borders, abundant clear cytoplasm (fried egg appearance)
*lymphocytic infiltrate present
*few syncytiotrophoblasts release hCG (minimally elevated serum levels)
embryonal carcinoma (testicular neoplasm)
*type of non-seminomatous germ cell tumors
*peak incidence 3rd decade of life
*classic presentation: PAINFUl mass, elevated hCG
*more aggressive than seminoma: vascular-lymphatic invasion is common
*ill-defined, invasive mass; extends through albuginea, epididymis, spermatic cord
*undifferentiated cells forming sheets; frequent component of mixed tumors
yolk sac tumor (testicular neoplasm)
*type of non-seminomatous germ cell tumors
*prepubertal, usually < 3 years of age
*histology:
1. Schiller-Duval bodies = perivascular growth (resemble glomeruli)
2. hyaline globules with elevated alpha-fetoprotein (AFP)
choriocarcinoma (testicular neoplasm)
*type of non-seminomatous germ cell tumors
*highly malignant; widespread metastases (liver, lungs); often associated with hemorrhage
*hCG MARKEDLY ELEVATED
*differentiate into placental trophoblasts:
-cytotrophoblasts = small cuboidal cells
-syncytiotrophoblasts = multinucleated cells
teratoma (testicular neoplasm)
*type of non-seminomatous germ cell tumors
*present any time from infancy to adulthood
*germ cells differentiate along MULTIPLE cell lineages:
-heterogenous collection of differentiated organoid structures
-neural brain tissue, cartilage, skin, thyroid, bronchi, intestine
where is BPH most commonly found in the prostate gland?
central zone (PZ) of prostate
benign prostatic hyperplasia (BPH) - overview
*common cause of prostatic enlargement
*increased frequency progressively with age, reaching 90% by 8th decade of life
benign prostatic hyperplasia (BPH) - pathogenesis
*excessive androgen-dependent growth of stromal and glandular elements:
-dihydrotestosterone (DHT) synthesized by 5-alpha reductase mediates prostatic growth
benign prostatic hyperplasia (BPH) - clinical presentation
*lower urinary tract obstruction sx:
-difficulty in starting urine stream, intermittent interruption of stream while voiding
-urgency, frequency, nocturia
*increased risk of UTI due to incomplete voiding
*may completely obstruct urinary tract
benign prostatic hyperplasia (BPH) - pathology
*well-circumscribed nodules:
-inner periurethral/transition zone
-urethra compressed to slit
-bulge from cut surface
*variable proportion of glands and fibromuscular stroma:
-small to large to cystic glands
-infolding glands produce a papillary architecture
benign prostatic hyperplasia (BPH) - treatment
- 5-alpha reductase inhibitors (finasteride, dutasteride - inhibit DHT formation)
- alpha-1 adrenergic receptor antagonists (tamsulosin, terzosin - relax prostatic smooth muscle)
- surgical techniques for unresponsive cases
prostatic adenocarcinoma - overview
*most common cancer in men
*20% of all male cancers (2nd cause of cancer-related death in men)
*disease of aging; increased incidence after 50 years
prostatic adenocarcinoma - pathogenesis
*androgens: induce expression of pro-growth and pro-survival genes
*inherited genetic factors: increased risk if first-degree relative with prostate cancer
*acquired genetic aberrations
prostatic adenocarcinoma - clinical findings
*most are asymptomatic lesions
*subset detected on digital rectal exam or needle biopsy to investigate increased PSA
prostatic serum antigen (PSA)
*product of normal and neoplastic prostatic epithelium
*increases with age
*serum assay widely used in diagnosis/management of prostate cancer
*limitations: NOT cancer-specific
prostatic adenocarcinoma - treatment
*localized: radical prostatectomy and radiotherapy
*“watchful waiting” approach for older men
*metastatic carcinoma: treated by androgen deprivation
prostatic adenocarcinoma - pathology
*usually located in peripheral zone; does not produce urinary symptoms
*malignant glands may be admixed with benign:
-nucleoli
-perineural invasion
-absent basal cells
-racemase positive
prostatic adenocarcinoma - grading (Gleason Score)
*architecture of glands from multiple (at least 2) zones
*smaller glands = higher score from 1-5
*higher score = worse prognosis
how does HPV transform cells?
*high-risk HPV types express oncoproteins which immortalize epithelial cells:
1. E6: prevents apoptosis (degrades p53); activates telomerase
2. E7: allows progression in cell cycle; binds RB and displaces E2F; blocks p21 and p27
*co-transfection with a mutated RAS gene results in full malignant transformation
HPV oncogenesis
*implicated in the genesis of several cancers:
-benign squamous papillomas (warts)
-squamous cell carcinomas (cervical, anogenitial, oropharynx)
*low risk types = 6 and 11
*high risk types = 16, 18, 31, 33, 35
cervical dysplasia - pathogenesis
*HPV; tropic for immature squamous cells in transformation zone
*squamous intraepithelial lesions (SIL):
-precancerous epithelial changes
-PAP smear = screening (cells scraped from transformation zone)
-determines low-grade vs. high-grade SIL