Repro-Endo: Male Repro Pathology

Question 1

• Opening of the Urethra on the Inferior (Ventral) surface of Penis due to failure to close the Urethral folds
• Most common malformation of the Urethral groove
• Due to Failure of the Urethral folds to close
• A/w Father and previous male sibling w/ disease
• A/w Monozygotic twins and insufficient hCG by single placenta
• A/w Ventral curvature of penis –> Chordee

Answer 1

Hypospadias

Question 2

• Opening of Urethra on the Superiror (Dorsal) surface of Penis
• Abnormal positioning / Defect of the Genital tubercle
• A/w Bladder extrophy –> opening of the anterior wall of the Abdomen leading to Bladder exposure

Answer 2

Epispadias

Question 3

• Benign, Warty growth on Genital skin
• HPV 6 or HPV 11
• Characterized by Koilocytic change –> “Raisen” appearing nuclei

Answer 3

Condyloma Acuminatum

Question 4

• Necrotizing granulomatous inflammation of the Inguinal Lymphatics and Lymph nodes
• STDs a/w Chlamydia trachomatis (L1 -L3)
  
  • Mucosal surface entering
  • Obligate intracellular organism
• Eventually heals w/ fibrosis
• Perianal involvement may result in Rectal stricture

Answer 4

Lymphogranuloma Venereum

Question 5

• Malignant proliferation of Squamous cells of the Penile skin
• Circumcision protects against SCC
• SCC of Penis is most common cancer
• Men 40 - 70 y.o.
• A/w High risk HPV 16, 18, and HPV 31, 33
  
  • ​Smoking tobacco may act as cocarcinogens / HPV
• Lack of Circumcision - Foreskin is Nidus for inflammation and irritation = Greatest Risk Factor
• Bowen Disease and Erythroplasia of Queyrat
• Metastasizes to Inguinal and Iliac nodes

Answer 5

Penile Squamous Cell Carcinoma

Question 6

• In situ Carcinoma of the Penis Shaft or Scrotom that presents w/ Leukoplakia (White plaque on the shaft of the Penis)
• > 35 y.o.
• HPV 16
• Precursor for Invasive SCC (~10%)
• A/w other types of Visceral Cancer

Answer 6

Bowen disease

Question 7

• In situ Carcinoma of the Glans of the Penis (Mucosal Surface) that presents as Erythroplakia
• Precursor for Invasive SCC of Penis
• HPV 16

Answer 7

Erythroplasia of Queyrat

Question 8

• In situ Carcinoma that presents as
• *Multiple Reddish-brown Papules**
• Seen in younger patients (40s) relative to Bowen disease and Erythroplasia of Queyrat
• HPV 16
• DOES NOT progress to invasive Carcinoma

Answer 8

Bowenoid papulosis

Question 9

• Failure of the Testicle to descend –> Scrotal sac
• Normally develop in abdomen and “descend” into the scrotal sac as Fetus grows Mullerian Inhibitory substance (MIS) is responsible for Transabdominal phase, Androgens and hCG - Inguinoscrotal phase
• Most common congenital male reproductive abnormality
• 30% Premature and 5% Full term Male infants
• A/w Androgen Insensivitivy Syn., Kallman syndrome, Cystic Fibrosis
• Resolve spontaneously (mostly), hCG therapy
• GnRH w/ Orchiopexy is Sx < 2 y.o.
• A/w Testicular atrophy and Infertility
• Increased risk of Seminoma (5-10x)

Answer 9

Cryptorchidism

Question 10

• Inflammation of the Testicle
  
  • Chlamydia trachomatis (serotypes D-K)
  • Neisseria gonorrhoeae
  • Increased risk of sterility
  • Libido is not affected because Leydig cells are spared

Answer 10

Orchitis of Young Adults < 35 y.o.

Tx: Ceftriaxone + Doxycycline

Question 11

• Inflammation of the Testicle
  
  • Escherichia coli
  • Pseudomonas
  • A/w Urinary tract infection
  • Pathogens spread to Reproductive tract

Answer 11

Orchitis of Older Adults > 35 y.o.

Tx: Ciprofloxacin Extended Release

Question 12

• Inflammation of the Testicle
  
  • Mumps virus
  • Increased risk of Infertility
  • Testicular inflammation is usually not seen in Children < 10 y.o.

Answer 12

Orchitis of Teenage Males

Question 13

• Testicular Inflammation
  
  • Characterized by Granulomas involving the Seminiferous tubules

Answer 13

Autoimmune Orchitis

Question 14

• Sudden Testicular pain w/ Absent Cremasteric reflex
• Twisting of the Spermatic cord, Violent, Physical Trauma
• 12 - 18 y.o. Males
• Thin-walled veins become obstructed leading to congestion and Hemorrhagic infarction
• Usually due to congenital failure of Testes to attach to the Inner lining of the Scrotum (via the Processus Vaginalis)
• Thick artery wraps around vein –> Blood in but not out
• 1/3 Resolve spontaneously
• Sx is imperative w/in 12 hours if it does not Resolve

Answer 14

Testicular Torsion

Question 15

• Dilation of the Spermatic vein due to Impaired drainage
• Presents as scrotal swelling w/ a “bag of worms” appearance
• 15 - 25 y.o. Males
• Usually Left Sided Scrotal enlargement
• Left testicular vein drains into the Left renal vein, while the Right testicular vein drains directly into the IVC
• A/w Left-sided Renal cell carcinoma: RCC often invades the Renal vein
• A/w a Large percentage of Infertile males
• Dx: Ultrasound
• Tx: Varicocelectomy, Embolization by Interventional Radiologist

Answer 15

Variococele

Question 16

• Scrotal Swelling that can be Transilluminated
• Fluid collection w/in the Tunica vaginalis (FAILS TO CLOSE)
  
  • Tunica vaginalis is a serous membrane that covers the Testicle as well as the Internal surface of the Scrotum
• A/w Incomplete closure of the Processus Vaginals
• -> Communication w/ the Peritoneal cavity (infants) or Blockage of Lymphatic drainage (adults)
• A/w Indirect Inguinal Hernia

Answer 16

Hydrocele

Question 17

• Arise from Germ cells or Sex cord-stroma
• 15 - 35 y.o.
• Whites > Blacks
• Presents as a Unilateral, Firm, Painless Testicular mass that CANNOT be Transilluminated
• NOT BIOPSID! –> risk of Seeding the Scrotum
• Removed via Radical Orchiectomy
• Most are Malignant Germ cell Tumors (Seminoma 40%)
• A/w Cryptorchid testicle, Androgen insensitivity syndrome, Klinefelter syndrome (XXY), Peutz-Jeghers syndrome, Inguinal hernia, Mumps orchitis

Answer 17

Basics of Testicular Tumors

Question 18

• Most common type of Testicular tumor (>95%)
• 15 - 40 y.o.s
• Risk factors: Cryptorchidism and Klinefelter syndrome
• (2) Types
  
  • Seminoma - highly responsive to radiotherapy, metastasize late, excellent prognossis
  • Nonseminoma - variable response to Tx and often metastasize early

Answer 18

Germ Cell Tumors

Question 19

• Malignant tumor comprised of Large cells w/ Clear cytoplasm and Central ‘Prominant’ nuclei (resemble spermatogonia), Stroma has a prominent lymphocytic infiltrate
• Forms a Homogeneous mass w/ no Hemorrhage or Necrosis
• Lymphatic metastasis before Hematogenous (lungs)
• Most common tumor (40%)
• Rare case produces β-hCG (10%)
• Resembles Ovarian dysgerminoma
• Good prognosis; Responds to Radiotherapy (Radiosensitive)

Answer 19

Germ Cell - Seminoma

Question 20

• Malignant tumor comprised of Immature, Primitive cells that MAY produce Glands
• 20 - 25 y.o.
• Bulky tumor w/ Hemorrhagic mass and Necrosis
• Aggressive w/ early Hematogenous spread before Lymphatic
• Chemotherapy may result in differentiation into another type of germ cell tumor (e.g. Teratoma)
• Increased AFP or β-hCG may be present (90% cases)

Answer 20

Embryonal Carcinoma

Question 21

• Malignant tumor that resembles Yolk sac elements
• Most common Testicular Tumor in Children (<4 y.o.)
• Schiller-Duval bodies (Glomerulus-like structures) are seen on Histology - “Glomeruloid-like structure”
• Increasesd AFP, elevated in all cases!
• Good prognosis

Answer 21

Yok sac Tumor

(Endodermal sinus)

Question 22

• Malignant Tumor of Trophoblastic Tissue: Syncytiotrophoblast and Cytotrophoblasts (placenta-like tissue, BUT the Vili are absent)
• 20 - 30 y.o.
• Spreads early via blood (Hematogenous) –> Lungs
• β-hCG is elevated –> Hyperthyroidism or Gynecomastia
• α-subunit of hCG is similar to that of FSH, LH, and TSH
• increased hCG in call cases

Answer 22

Choriocarcinoma

Question 23

• Tumor composed of Mature Fetal tissue derived from Two or Three embryonic layers
  
  • Derivatives of Ectoderm, Endoderm, Mesoderm
  • If Mixed w/ Embryonal carcinoma –> “Teratocarcinoma”
• Malingnant in Males of All Ages
  
  • ​Benign in Children, Malignant in Adults (SCC)
• Bening in Females
• AFP or β-hCG may be increased (50% of cases)

Answer 23

Teratoma

Question 24

• Germ cell tumors are usually mixed
• Prognosis is based on Worst component

Answer 24

Mixed Germ Cell Tumors

Question 25

• Tumors that resemble Sex cord-stromal tissues of the Testicle
• Usually benign
• Leydic cell tumor –> Androgens –> Precocious puberty in Children or Gynecomatia in Adults
• Sertoli cell tumor –> comprised of Tubules –> usually Clinically Silent

Answer 25

Sex Cord-Stromal Tumors

Question 26

• Most common cause of Testicular mass in
• *Males > 60 y.o.**
• Bilateral (Both Testes)
• Usually Diffuse Large β-cell Type
• No Tumor Markers
• Prognosis is Poor

Answer 26

Malignant Lymphoma

Question 27

• Acute inflammation of the Prostate
• Intraprostate Reflux of Urine from Posterior urethra or Urinary bladder
• A/w Acute cystitis
• Usually due to Bacteria
  
  • **Chlamydia trachomatis and Neisseria gonorrhoeae
• -> Young Adults (< 35 y.o.)**
  
  • **Escherichia coli and Pseudomonas
• -> Older Adults (> 35 y.o.)**
• Dysuria w/ Fever and Chills
• Prostate is Tender and Boggy on Digital Rectal Exam
• Prostatic secrtions show WBCs –> Bacteria

Answer 27

Acute Prostatitis

Question 28

• Chronic inflammation of the Prostate
• Dysuria w/ Pelvic or Lower Back Pain
• Common in Bicycle riders
  (Seat compression on the Prostate)
• Prostatic secretions show WBCs –> Negative cultures
  
  • Abacterial

Answer 28

Chronic Prostatitis

Question 29

• Hyperplasia of Prostatic Stroma and Glands
• Age-related change (Men > 60 y.o.)
• NO increased risk for Cancer
• A/w Dihydrotestosterone (DHT)
  
  • 5α-reductase (Stromal cells) converts Testosterone –> DHT in Stromal cells
  • DHT –> Androgen receptor of Stromal and Epithelial cells –> Hyperplastic nodules
• Transitional (Glandular hyperplasia) and Central Periurethral zone (Stromal hyperplasia) of the Prostate
• Starting / Stoping urine stream and Dribbling
• Impaired bladder empything –> Infections and Hydronephrosis –> Postrenal Azotemia –> Renal Failure
• Hypertrophy of Bladder Smooth muscle –> Diverticula
• Microscopic Hematuria, Nocturia, Dysuria
• PSA (prostate-specific-antigen) often elevated

Answer 29

Benign Prostatic Hyperplasia

(BPH)

Question 30

Treatment for Benign Prostatic Hyperplasia

Tx for BPH

Answer 30

• Avoid Caffeine or Foods that exacerbate symptoms
• α₁-antagonist (Terazosin to relax Smooth muslce)
  
  • Relaxes vascular Smooth Muscle Lower BP
  • α₁-antagonist (Tamsulosin) are used in Normotensive Individuals to avoid α_1B effects on Blood vessels
• 5α-reductase inhibitor
  
  • Blocks conversion of Tesosterone –> DHT
  • Takes months to produce results
  • Useful for Male pattern baldness
  • S/E Gynecomastia and Sexual Dysfunction
  • Saw Palmetto

Question 31

• Malignant proliferation of Prostatic Glands
• Most common cancer in Men (2nd most cancer-death)
• Age, Race (Black > White >> Asian), Diets in High Sat. Fat
• Most often Clinically silent
  
  • Arises in the Peripheral-Posterior region –> No urinary symptoms early on
• Screening begins at age 50 y.o. w/ DRE and PSA
• Normal serum PSA increases w/ age due to BPH (>10)
• Decreased % free-PSA is suggestive of cancer

Answer 31

Prostate Adenocarcinoma

Question 32

How do you Dx Prostate Adenocarcinoma?

Answer 32

• Prostatic biopsy is required to confirm the presence of Carcinoma
• Small, Invasive glands w/ prominant nucleoli
• Gleason grading system is based on Architecture alone and not by Nuclear atypia
  
  • Two areas (1-5) are added to score (2-10)
  • Higher = Worse prognosis
• Spread to Lumbar spine is common
• -> Osteoblastic metastases
• -> Lower Back Pain –> Increased Serum Alkaline Phosphatase and Prostatic Acid Phosphate (PAP)

Question 33

Testicular Tumor Markers?

Answer 33

• α-Fetoprotein (AFP)
  
  • Yolk sac (enodermal sinus) tumor origin
• Human chorionic gonadotropin (hCG)
  
  • Choriocarcinoma
• Lactate Dehydrogenase
  
  • Nonspecific cancer enzyme
  • Degree of elevation correlates w/ Tumor mass

Question 34

Follicle-stimulating Hormone (FSH) in Male repro?

Answer 34

• Stimulates Spermatogenesis in the S