2/24 Cancers of Male Repro Tract - Corbett Flashcards
male devpt timeline and events
gonads and repro tracts are indifferent until wk7
- SRY- → female path of devpt
- SRY+ → male path of devpt, gonad → testis (spermatogonia, Sertoli cells, Leydig cells)
- Leydig cells: testosterone → support growth of mesonephric ducts
- some testosterone → DHT : supports devpt of external genitalia (prostate gland, penis, scrotum)
- Sertoli cells: antiMullerian hormone → regression of paramesonephric ducts
cryptorchidism
incomplete descent of testis from abd to scrotum
- uncorrected? assoc w tubular atrophy and sterility
- 3-5x risk for testicular cancer (arises from foci of intratubular germ cell neoplasia within atrophic tubules)
orchiopexy reduces risk of sterility and cancer
testicular torsion
acute onset of unilateral scrotal pain w assoc n/v
- abd pain, fever
- scrotal swelling, pain with palp, loss of cremasteric reflex
dx: scrotal ultrasound
rx: surgical exploration, detorsion, bilat orchidopexy
testicular tumor risk factors
- familiar risk w germ cell tumors : 8-10x in brothers
- genetic disorders
- testicular dysgenesis syndrome
- Kleinfelter Syndrome
- cryptorchidism
- racial factors
- higher in Caucasians
- AfAm present with higher grade disease
testicular tumors
clinical pres
nodule or painless swelling
- ache in lower abd or scrotum
- acute pain
- metastatic disease
- gynecomastia )assoc with hCG, germ cell tumors, Leydig cell tumors)
testicular tumors
breakdown
95% germ cell tumors
- “embryo-like”
- spermatocytic seminoma
- teratoma (non-seminoma)
- “placenta-like”
- yolk sac
- embryonal carcinoma
- choriocarcinoma
*exception: OLDER MEN - testicular mass - most likely diffuse large B cell lymphoma
- rapid growing, 30% BCL6 overexp
**exception: INFANTS/YOUNG CHILDREN - testicular tumor - most likely yolk sac tumor (elevated serum AFP)
- 16-18mo: pure YST
- 25-35y: YST in mixed GCT (rare in adults)
*
testicular germ cell neoplasia in situ
precursor lesion
precursor lesion
- seen in 90-100% testes adjacent to GCT
- assoc with gonadal dysgenesis, androgen insensitivity syndrome, infertility, cryptorchidism, contralat tests if prior test tumor
50% → germ cell tumor in 5y
seminoma
most common type of GCT (50%)
peak in 30s, almost never in infants
uniform tumor cells with abundant clear cytoplasm, distinct cell border, large central nuclei w prominent nucleoli
- PLAP+
- OCT3/4+
- CD117+ (ckit overexpression in 25%)
- cytokeratin -
excellent prognosis bc usually stay confined to testis
spermatocytic seminoma
v rare
older pt (mean 54yr)
doesn’t arise from ITGCN, not assoc with cryptorchidism
no serum tumor markers (AFR, hCG, LDH)
no race predilection in contrast to other GCT
embryonal carcinoma
second most common GCT
poorest prognosis of all GCTs
- more aggressive than seminomas
- serum alphaAFP and HCG can be elevated
- features:
- freq extend through tunica albuiginea
- poorly demarcated
- cells grow in alveolar or tubular patterns
choriocarcinoma
- pure choriocarcinoma: v rare, most aggressive
- often small nodule, almost always with hematogenous spread to lungs/liver
- marked elevation in serum hCG
recall:
testicular/ovarian tumors having syncytiotrophoblasts…
produce beta-hCG!!!
teratoma
tumor with mature or immature somatic tissue from more than one germ layer
peaks: under4y, 20s-40s
- pediatric: benign
- postpubertal: all malignant
mature tissue with hair, cartlage, bone/teeth, muscle and nerve, squamous cells
testicular neoplasm
MUST KNOW
biopsy is absolutely contraindicated bc
- leaves inguinal portion of spermatic cord intact → may alter lymphatic drainage of testis
- increases risk of local recurrence
- might lead to pelvic or inguinal lymph node metastasis
tx: radical inguinal orchiectomy (removal of tumor bearing testis and spermatic cord to level of internal inguinal ring)
seminoma vs NSCCT
testicular tumors summary
prostate gland
four distinct zones
- peripheral
- central
- transitional
- periurethral
proliferative lesions are different in each region:
- hyperplasias: TZ
- more likely to cause obstruction
- carcinomas: PZ
- not as likely to cause obstruction
glands are lined by two layers of cells
- (cell growth in response to androgens)
- basal layer of low cuboidal epi
- layer of columnar secretory cells
glands separated by fibromuscular stroma
BPH
benign prostatic hypertrophy
most common benign prostatic disease in men over 50
nodular hyperplasia of prostatic stromal and epithelial cells in periurethral region
- formation of discrete nodules
- NOT PREMALIGNANT
- can cause urethral obstruction
pathogenesis
-
stromal cells: DHT (main prostatic androgen) → binds to nuclear androgen receptor
- more potent than testosterone
- higher affinity for AR
- DHT binding to AR → FGF synthesis → stromal proliferation
*DHT production requires 5alpha reductase activity (test → DHT)
- DHT inhibitors can reduce prostate size, lower PSA levels
adenocarcinoma of prostate
most common form of cancer in men
- risks: family history, age, race (AfAm), BRCA2
pathogenesis: most early prostate cancers are androgen- and androgen_receptor-dependent
- AR polymorphisms and mutations can play a role in racial predisp
- 70% in peripheral zone
- microscopy shows pleomorphic cells, single layer glands, no secretions
- malignant gland lacks basal cells
5alpha reductase deficiency
