Male Reproductive Pathology PDF

Penile Disorders Jason Ryan, MD, MPH Penis Anatomy Three cavernous bodies (“the corpora”) Corpus cavernosa: Two large spongy tissue beds Corpus spongiosusm: Smaller spongy tissue bed Surrounds urethra Penis Anatomy Esseh/Wikipedia Wikipedia/Public Domain...

Penile Disorders Jason Ryan, MD, MPH Penis Anatomy Three cavernous bodies (“the corpora”) Corpus cavernosa: Two large spongy tissue beds Corpus spongiosusm: Smaller spongy tissue bed Surrounds urethra Penis Anatomy Esseh/Wikipedia Wikipedia/Public Domain Penis Anatomy Tunica albuginea Latin: “tunica” = covering, “albuginea” = white White connective tissue surrounding corpus cavernosa Buck’s fascia Covers all three erectile structures Penis Anatomy Mcstrother/Wikipedia Penis Physiology Key structures: arterioles and corpora Flaccid penis: High tone of cavernosal arterioles ↓ inflow of blood Erection (tumescence) Smooth muscle relaxation ↑ blood flow Corpora swell (sinusoids) Compress veins/venules ↓ outflow High inflow/low outflow  ↑intracorporeal pressure Penis Physiology Detumescence Smooth muscle contraction Corpora shrink Venous outflow Peyronie Disease Abnormal tunica albuginea Acquired disorder Likely related to trauma in a susceptible individual Localized fibrosis of tunica albuginea Pain Nodule Abnormal curvature when erect Erectile dysfunction SugarMaple/Wikipedia Peyronie Disease Treatment: Pentoxifylline Phosphodiesterase inhibitor Reduces inflammation Prevents collagen deposition Injection or oral administration Penile Fracture Rupture of tunica albuginea Often associated with urethral damage Caused by blunt trauma Audible snap  pain, swelling, ecchymosis Mcstrother/Wikipedia Priapism Persistent erection Lasting more than 2-4 hours Not due to sexual activity Priapism Types Ischemic Most common type (95% of cases) Lack of outflow  tissue ischemia Non-ischemic “High flow” priapism Fistula between arteries and corpus cavernosum Often follows trauma Ischemic Priapism Etiology Failure of cavernosal outflow Two classic causes: Sickle cell and drugs Sickle cell anemia Veno-occlusion Drugs Block smooth muscle contraction Antipsychotics/antidepressants (trazadone, SSRIs) Alpha blockers (doxazosin, tamsulosin, terazosin, prazosin) Erectile dysfunction drugs Ischemic Priapism Treatment Urologic emergency Hypoxia, acidosis of penile blood occurs May cause permanent erectile dysfunction May leads to penile necrosis Treatments: Corporal aspiration Intracavernosal phenylephrine Surgery Condylomata Acuminata Anogenital Warts STD caused by papillomavirus (6, 11) Soft, tan, cauliflower-like lesions “Verrucous” = warts Also seen vulva, perianal area (rectal bleeding) Treatment: Chemical agents Surgical therapy Does not lead to cancer SOA-AIDS Amsterdam/Wikipedia Condylomata Acuminata Histology Peri-nuclear clear vacuolization (koilocytosis) KGH/Wikipedia Squamous Cell Carcinoma Rare penile malignancy Arises from squamous skin cells Occurs in the glans or shaft Occurs in older men (mean age ~60) Rare in US, Europe Common in Africa, Asia, South America Squamous Cell Carcinoma Risk Factors Uncircumcised penis Circumcision: reduced exposure to carcinogens HPV Infection HPV DNA in 30-50% of cases Types 16 and 18 Smoking Squamous Cell Carcinoma Pre-malignant (in situ) lesions In situ carcinoma (no basement membrane invasion) Bowen disease Gray-white plaque (leukoplakia) on shaft of penis Erythroplasia of Queyrat Dark red lesion on glans of penis Bowen disease of the glans Bowenoid papulosis Multiple, red-brown papules Erectile Dysfunction Inability to achieve/maintain an erection Usually psychological component Associated with many conditions Heart disease HTN Diabetes Obesity Certain medications Smoking Alcoholism and other forms of substance abuse Sleep apnea Phosphodiesterase 5 inhibitors Sildenafil, Vardenafil, Tadalafil PDE5 breaks down cGMP in smooth muscle cells Inhibition  more cGMP  relaxation Improved response to NO NO GMP GTP cGMP PDE5 RELAXATION Smooth Muscle Cell Phosphodiesterase 5 inhibitors Uses Erectile dysfunction (improved blood flow) Pulmonary hypertension (↓PVR) Benign prostatic hyperplasia (BPH) Only tadalafil has FDA approval Phosphodiesterase 5 inhibitors Side Effects Contraindicated in patients taking nitrates Life-threatening hypotension Cannot use with nitroglycerine, isosorbide Headache and flushing Priapism NO GMP GTP cGMP PDE5 RELAXATION Smooth Muscle Cell Phosphodiesterase 5 inhibitors Side Effects Vision problems Temporary blue vision (cyanopia) Only reported with sildenafil Drug cross-reacts with PDE-6 in retina Resolves in hours Scrotal Disorders Jason Ryan, MD, MPH Testicular torsion Testicle rotates in scrotum Twists spermatic cord Forms at deep inguinal ring Wikipedia/Public Domain Travels through inguinal canal Enters scrotum through superficial inguinal ring Ends at testes Carries arteries, veins, ductus deferens Testicular torsion Scrotal ligament Secures testis to scrotum Limits movement in scrotum Wikipedia/Public Domain Abnormal function may lead to torsion Allows testes to twist Testicular torsion Compression of thin-walled venous outflow Continued inflow through arteries (thick walled) Engorgement of testicle Hemorrhagic infarction Kalumet/Wikipedia Testicular torsion Neonatal form (rare) Occurs in first 30 days after birth Testes not yet attached to scrotum “Adult” form Boys 12-18 years old Often caused by anatomic defect Lack of attachment testicle to scrotum “Bell clapper deformity:” tunica vaginalis covers cord Increased mobility of testicle in scrotum Testicular torsion Clinical Features Painful, swollen testicle Absent cremaster reflex Stroking inner thigh Normal response: contraction of cremaster muscle Pulls ipsilateral scrotum/testis up Kalumet/Wikipedia Testicular torsion May lead to infertility Treatment: urgent surgery Detorsion (manual or surgical) Orchiopexy (fixation of testicle) Testicle removal (if nonviable) Must treat contralateral testis Kalumet/Wikipedia Varicocele Dilatation of pampiniform plexus of spermatic veins Wikipedia/Public Domain Varicocele Caused by obstruction to outflow of venous blood More common on left Left spermatic vein  left renal (long course) Compressed between aorta and superior mesenteric artery “Nutcracker effect” Right vein drains directly to IVC Associated with renal cell carcinoma Invades renal vein Varicocele Scrotal pain and swelling Dilated veins = “Bag of worms” More swelling with: Valsalva Standing Fisch12/Wikipedia Diagnosed by ultrasound Can cause infertility ↑ temperature Poor blood flow Schomynv /Wikipedia Varicocele Treatment Surgery (varicocelectomy) Isolate dilated/abnormal veins Redirect blood flow to normal veins Embolization Interventional radiology procedure Catheter inserted into dilated/abnormal veins Coil or sclerosants used to clot off veins Hydrocele Accumulation of fluid in tunica vaginalis Small, fluid-filled sac attached to testicle Scrotal swelling Transilluminates with light Differentiates from solid mass (i.e. tumor) Hydrocele Newborn form Incomplete closure of processus vaginalis “Communicating hydrocele” Peritoneal fluid collects in tunica vaginalis Usually resolve spontaneously by 1 year of age Adult form “Noncommunicating hydrocele” Often idiopathic May be 2° to infection, torsion, trauma May become bloody (“hemotocele”) Hydrocele Spermatocele Large epididymal cyst Usually at head (top) of epididymis Wikipedia/Public Domain Usually asymptomatic Detected on physical exam Mass at top of testicle Separate from testis Can diagnosis with ultrasound KDS444 /Wikipedia Cryptorchidism “Hidden testes” Usually due to undescended testes Abdominal Inguinal canal Can be unilateral/bilateral Cryptorchidism Complications Low sperm counts ↑ temperature effects on Sertoli cells ↑ risk of germ cell tumors Inguinal hernias Testicular torsion Cryptorchidism Treatment Testes may descend on their own Usually occurs by 6 months of age Orchiopexy Surgical placement of the testis in scrotum Sperm counts usually become normal Testicular Tumors Jason Ryan, MD, MPH Testicular Malignancy Many similarities to ovarian malignancies Key difference: no common epithelial cancers Two main categories: Germ cell tumors Sex cord-stromal tumors Wikipedia/Public Domain Testicular Tumors Germ cell tumors Seminoma and Non-seminomas Embryonal carcinoma, Yolk Sac tumor Choriocarcinoma, teratoma Non-germ cell tumors Leydig cell tumor Sertoli cell tumor Lymphoma Mikael Häggström/Wikipedia Testicular Tumors Usually present as painless, testicular mass Do not transilluminate Often evaluated with ultrasound If cancer suspected: orchiectomy Usually not biopsied Risk of tumor seeding Into scrotum or spread to inguinal nodes Germ Cell Tumors Most common type (95%) of testicular malignancy Usually occur in young men 15-34 years old Key risk factors: Cryptorchidism Kleinfelter syndrome Malcolm Gin/Wikipedia Germ Cell Tumors Always malignant (capable of metastasis) Often a mix of subtypes Highly curable 5-year survival ~95% Seminoma Most common germ cell tumor Same characteristics as dysgerminoma in females Seminoma much more common Dysgerminoma: rare ovarian cancer Wikipedia/Public Domain Seminoma Homogenous mass Grey-white appearing No hemorrhage or necrosis May produce β-hCG Tumor marker in 15% cases Syncytiotrophoblast tissue in tumor Placental alkaline phosphatase Old marker Poor sensitivity Treatment Surgery +/- chemo/radiation Ed Uthman/Wikipedia Seminoma Histology: undifferentiated germ cells Nests of large cells with clear cytoplasm Central nuclei “Fried egg” appearance Nephron/Wikipedia Embryonal Carcinoma Non-seminoma Germ Cell Tumor Usually occurs as component of mixed tumor Pure embryonal carcinoma rare (2% testicular GCTs) Key distinctions from seminoma: Mass with hemorrhage and necrosis Painful May have syncytiotrophoblast tissue Secretes β-hCG Yolk Sac Tumor Endodermal Sinus Tumor Most common GCT children 60 years old Testicular mass may be presenting complaint Extragonadal GCT Extragonadal Germ Cell Tumors Occur in males and females Arise in midline locations Adults: Anterior mediastinum most common Children: Sacrococcygeal and intracranial most common Many types Seminomas/dysgerminomas Teratomas Failure of germ cell migration Prostate Jason Ryan, MD, MPH Prostate Round gland a base of bladder Anterior to rectum Palpation on digital rectal exam Encircles urethra Produces prostatic fluid Stimulated by androgens Wikipedia/Public Domain Acute Prostatitis Acute inflammation of the prostate Usually bacterial Older man Similar organisms to cystitis E. coli most common Also proteus, pseudomonas Sexually-active, younger men Neisseria gonorrhoeae Chlamydia trachomatis Image courtesy Wikipedia/Public Domain Acute Prostatitis Symptoms Fevers, chills, malaise Dysuria, frequency Cloudy urine Digital rectal exam: Prostate edematous/enlarged (“boggy”) Exquisitely tender Workup: Urine analysis (WBC) and culture Chronic Prostatitis Chronic bacterial prostatitis Chronic/recurrent prostatitis symptoms Evidence of bacterial infection Chronic abacterial prostatitis Symptoms of prostatitis (pain, difficulty voiding) May present as chronic pelvic and low back pain Sometimes blood in semen No bacteria identified Etiology unclear BPH Benign Prostatic Hyperplasia Age-related condition Common in men >50 Hyperplasia of stromal and epithelial cells Results in partial or complete urinary obstruction Not a premalignant condition Wikipedia/Public Domain BPH Symptoms Hesitancy (cannot start urine stream) Frequency (incomplete voiding) Dribbling Bladder may hypertrophy Rarely may cause complete obstruction Bladder distention Hydronephrosis Increased risk of UTIs BPH Histology “Nodular” hyperplasia Transitional zone Urethra compressed into “slit” Wikipedia/Public Domain BPH Treatment Growth driven by dihydrotestosterone (DHT) Treatment: 5α-reductase inhibitors (Finasteride) Slow onset symptom relief 5-α reductase Dihydrotestosterone Testosterone (DHT) BPH Treatment α1-blockers Smooth muscle relaxation Tamsulosin: Uroselective (α1A not α1B - no hypotension) PDE-5 inhibitors Also cause smooth muscle relaxation Tadalafil Surgery Transurethral resection of the prostate (TURP) Prostate Adenocarcinoma Most common form of cancer in men 2nd most deadly (lung) Occurs in older men (>50) More common among African Americans Prostate Adenocarcinoma Occur in peripheral zone of prostate Classically posterior lobe Wikipedia/Public Domain Prostate Adenocarcinoma Usually asymptomatic (rarely causes dysuria) Often felt as nodule on digital rectal exam Screening with PSA Diagnosis: prostate biopsy Transrectal biopsy Often with transrectal ultrasound (TRUS) guidance BruceBlaus/Wikipedia - BruceBlaus/Wikipedia - PSA Prostate-specific antigen Androgen-regulated substance found in semen Produced by normal and malignant prostate tissue Elevated in BPH and prostate cancer Can be used for screening (controversial) 0-4 ng/mL: Normal 4-10 ng/mL: Elevated >10 ng/mL: Highly suspicious for cancer Free PSA Most PSA bound to protease inhibitors in blood: Antichymotrypsin Macroglobulin Can measure % free versus bound PSA Prostate cancer produces more bound PSA ↑ total PSA with ↓ % free PSA Prostate Cancer Grading Prognosis based on stage and grade Stage: Extent of tumor growth/spread Grade: Gleason system Score done by pathologist based on biopsy findings Based on well- versus poorly-differentiated cells Nephron /Wikipedia Metastasis Hematogenous spread to spine May cause back pain and ↑ alkaline phosphatase Osteoblastic lesions Deposition of new bone Contrast with osteolytic (breakdown) Prostate CA: classic osteoblastic lesion Myeloma: classic osteolytic disease James Heilman, MD /Wikipedia James Heilman, MD /Wikipedia Prostate Cancer Treatment Surgery Flutamide Competitive inhibitor of androgen receptors Leuprolide GnRH analog IM or SQ continuous (not pulsatile) therapy Suppresses pituitary FSH/LH release