9. Pathology of the male genital tract

9. Pathology of the male genital tract
PATHOLOGY OF THE MALE GENITAL SYSTEM
DISORDERS OF THE PENIS AND THE MALE URETHRA
Congenital abnormalities of the urethra
Abnormal location of the urethral orifice
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Hypospadias: the meatus is situated on the ventral surface of the penis or in the perineum
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Epispadias: the meatus opens on the dorsal aspect of the penis
Posterior urethral valve
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In the prostatic portion of the urethra
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Connective tissue covered by transitional epithelium bulges into the lumen
Consequence
Outflow obstruction
bilateral hydronephrosis, recurrent urinary tract infections (UTIs)
Urethritis
Pathogenesis
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Gram-neg. bacteria in individuals with abnormal urinary tract (E. coli, Enterobacter, Proteus, etc.)
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Polyresistant nosocomial strains after catheterization, cystoscopy (e.g., Pseudomonas)
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Sexually transmitted: Neisseria gonorrhoeae; Chlamydia trachomatis, and Ureaplasma urealyticum
Gonorrhoea
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2-7 days after exposure: acute purulent urethritis
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Complications: purulent prostatitis, seminal vesiculitis, epididymitis
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Late consequences:
Urethral stricture
UTO
Fibrosis of the prostate
Fibrosis of the epididymis; if bilateral: obstructive azoospermia
Urethritis induced by Chlamydia or Ureaplasma
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Mild mucopurulent urethral discharge
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Complications: acute cystitis; frequently turns into chronic
chronic seminal vesiculitis, prostatitis, epididymitis
Venereal ulceration of the glans penis
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Genital herpes: HSV2, HSV1 (increasing incidence due to practice of oral sex); painful vesicles
ulcer + inguinal
lymphadenitis
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Firm chancre: Treponema pallidum; painless firm ulcer + painless inguinal lymphadenitis; heals with a subtle scar; 2
months later: secondary syphilis: gen. lymph node enlargement, mucocutaneous lesions
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Soft chancre (chancroid): Hemophilus ducreyi; common in Africa and Southeast Asia; painful soft ulcer + painful
inguinal lymphadenitis with central abscesses
Phimosis
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Abnormally small orifice in the foreskin; does not permit the retraction of the foreskin over the glans penis
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Acquired (inflammatory scarring) or congential
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Consequences
Accumulation of secretion and cell debris under the prepuce: balanitis - inflamm. of the glans, posthitis - inflamm.
of the prepuce balanoposthitis
Lower urinary tract obstruction
In adults: disturbed sexual life
Tumors of the penis
Strong association with HPV-infection
Condyloma acuminatum (venereal wart)
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Single or multiple reddish, cauliflowerlike lesions, involving the coronal sulcus, the inner prepuce
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LM: acanthosis, papillomatosis, vacuolation of epithelial cells (koilocytes)
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Benign; however, tends to recur after excision
Squamous cc in situ
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In men usually older than 35 years
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Bowen disease: involves the shaft of the penis and the scrotum; erythroplasia of Queyrat: appears on the glans and
prepuce
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Gross: gray-white or red shiny plaques
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Over the span of years, both can transform into invasive squamous cell cc
Invasive carcinoma of the penis
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Infrequent; peak: around age 65
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Risk factors: HPV 16 and 18; 30 or more sexual partners, chronic irritation, no circumscision, smoking
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Gross: ulcerative or a fungating lesion on the glans or foreskin
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LM: well or moderately diff. squamous cell cc
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Slow course; lymphatic metastases in the inguinal nodes
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5-y-survival rate: 70%
PATHOLOGY OF THE PROSTATE
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Inflammation
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Hyperplasia
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Carcinoma
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9. Pathology of the male genital tract
PROSTATITIS
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Acute
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Chronic
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Granulomatous
Acute prostatitis
Pathogenesis
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Colonization: from direct extension from the urethra (urethritis) or the bladder (cystitis)
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Agents: E. coli, enterococci, gonococci
purulent inflammation
Morphology
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LM: accumulation of ng-s within and around acini
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Large abscesses can develop in gonococcal prostatitis, in diabetics
Clinical features
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Tender and swollen prostate
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Difficulty in micturition with perineal or rectal pain (dysuria)
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Fever
Outcome
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Heals completely or with scarring (insuff. antibiotic th)
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Can turn into chronic prostatitis
Chronic prostatitis
Pathogenesis
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Bacterial: Gram-neg. microorganisms
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Non-bacterial: Ureaplasma or Chlamydia - the most common type of prostatic inflammation
Morphology
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LM: dilated glands filled with ng-s and foamy ma-s, stroma: ly-s, ma-s
Clinical features
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Difficulty in micturition + low back pain
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Disturbed ejaculation
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Harbours foci of infection, causing arthritis, myositis, neuritis, iritis
Outcome
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Acinar atrophy, stromal fibrosis
Granulomatous prostatitis
Pathogenesis
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Secretions escape into the stroma and elicite inflammation
Morphology
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Destructed acini, surrounded by epitheloid cells, giant cells, ly-s, plasma cells + dense fibrosis
Clinical features
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Disturbed micturition
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”Stony hard” prostate by palpation because of marked fibrosis
clinically simulates prostatic cc
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Dg.: biopsy of the prostate
NODULAR HYPERPLASIA
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Very common, the incidence increases with age: up to 70% of men by age 60 years
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The nodules arise from the inner portions of the prostate (central zone [close to the bladder]), periurethral zone)
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Compression of the prostatic urethra
obstruction of the urinary flow
Pathogenesis
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A relative increase in the level of estrogens that occurs with aging may facilitate the growth promoting effect of
dihydrotestosterone (castrated boys do not develop NH when they age)
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DHT increases the production of fibroblast growth factor-7 by stromal cells
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FGF-7 inhibits apoptosis of glandular epithelial cells and stimulates stromal cell proliferation
nodular overgrowth of
the glands and the fibromuscular tissue
Morphology
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Gross: nodular enlargement (60-100 g; normal: 20 g), the nodules have no capsule
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LM: hyperplasia of glands and stromal fibroblasts and smooth muscle cells
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Glands are lined by an inner secretory columnar layer and an outer layer of basal cells (positive with high molecular
weight cytokeratins)
Mechanic consequences of urethra obstruction
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Bladder: detrusor muscle hypertrophy (first concentric, then dilative
residual urine), diverticula
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Bilateral ureterectasis, pyelectasis, and hydronephrosis
Infectious consequences of urethra obstruction
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Infection of residual urine in the bladder: acute cystitis
ascending pyelonephritis
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Recurrent infectious episodes + urinary tract obstruction: chronic pyelonephritis
Clinical features
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Difficulty in micturition: delay in starting to pass urine; poor, intermittent stream, dribbling at the end of micturition
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If there is cystitis: frequency, lower abdominal pain, dysuria, hematuria
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If there is bilateral hydronephrosis: azotemia, chronic renal insufficiency + renal hypertension
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Emergency situation: acute complete obstruction
painful distension of the urinary bladder
risk of bladder
rupture, acute postrenal uremia
Therapy
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Pharmacologic: inhibition of DHT and/or relaxation of smooth muscles by blocking alpha adrenergic receptors
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Surgical: transurethral resection
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9. Pathology of the male genital tract
PROSTATE CARCINOMA (PCC)
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The most common non-skin malignancy in males in the developed countries
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Peak: between the ages 65 and 75 years
Pathogenesis
Androgens, diet, hereditary factors, and acquired somatic mutations have roles
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The tumor cells express androgen-receptors (ARs); growth of the tumor is inhibited by androgen deprivation and
administration of estrogens
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Race: rare in Asians who live in Asia; common in Caucasians (particularly in Scandinavia) and Afro-Americans
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ARs with shorter glutamine repeats (common in Afro-Americans) are more sensitive to androgens, whereas ARs with
more numerous repeats (common in Asians) are less sensitive
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Diet: increased fat and/or meat consumption
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Family history (germline mutations): 2x risk in a man with a father or brother who developed PCC
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Acquired mutations: creation of TPRSS2-ETS fusion gene, activation of the oncogenic pathway PI3K/AKT signaling
pathway, and inactivation of the tumor suppressor gene PTEN
Morphology
Gross
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PCCs arise multifocally in the peripheral posterior zone of the prostate, facilitating palpation during rectal digital
examination
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Appear as multifocal firm, grayish-yellowish masses
LM
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Precursor lesion: prostatic intraepithelial neoplasia (PIN): cytologic atypia in glands, but the outer basal layer of cells
is retained
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The invasive cancers are adenocarcinomas: the atypical glands are lined by a single layer of epithelium
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Gleason score system of grading: combination of very well (score 1); well (score 2); moderately (score 3); poorly
(score 4); very poorly (score 5) differentiated patterns. Example: adenocarcinoma of prostate, Gleason score: 2+4= 6
Spread
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Continuously: involvement of the entire prostate
the seminal vesicles
the bladder neck
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Lymphatic metastases in nodes below the bifurcation of the common iliac arteries
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Hematogeneous metastases: to the spine, pelvis, and ribs; to the lungs
Clinical presentation
Prostate specific antigen
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Normal acini produce a protein, termed prostate specific antigen (PSA), which liquifies the semen
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Tumor cells also elaborate PSA
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Elevation in serum PSA level is of value in the diagnosis of prostate carcinoma (normal up to 4 ng/L, suspicious
above 10 ng/L, almost sure >20 ng/L)
Non-metastatic, clinically localized prostate cancer
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Difficulty of micturition, urinary retention; urinary tract infection
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Raised PSA on screening
Metastatic disease
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Back pain from vertebral metastases + pathologic bone fracture
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Anaemia + uraemia because of urinary tract obstruction
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High levels of serum PSA
Dg.: ultrasound-guided transrectal biopsy
Prognosis
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Non-metastatic prostate cancer: radical prostatectomy or radiotherapy + anti-testosterone blockade: favourable
outcome
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Metastatic disease: worse outcome; anti-testosterone th + radioth - response can be achieved in a few individuals
NON-TUMOROUS DISORDERS OF THE SPERMATIC CORD AND THE TESTIS
Twisting of the spermatic cord
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Torsion and subsequent hemorrhagic necrosis of the testis because of venous obstruction
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Most common in 10-to-25 year-olds
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Acute dramatic testicular pain; requires immediate surgery to save the testicle
Varicocele
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Varicosity of the pampiniform venous plexus within the spermatic cord
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Frequent in young men; more common on the left side (the left internal spermatic vein empties into the renal vein, the
right internal spermatic vein drains directly the inferior vena cava)
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Consequence: the intrascrotal temperature raises
a reduction in the rate of spermiogenesis
oligospermia in the
semen
danger of infertility
Hydrocele
Serous fluid accumulates in the tunica vaginalis
Causes
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Right sided HF
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Blockade of lymphatic drainage of scrotum
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Epididymo-orchitis
Cryptorchidism
A failure of descent of testis; affects 1% of 1-y-old boys
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Undescended testis may be abdominal, in the inguinal canal or at the external inguinal ring
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Mainly unilateral; affects the right testis more frequently; association with other urological abnormalities and/or
inguinal hernias
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Consequences
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9. Pathology of the male genital tract
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The malpositioned testis undergoes atrophy; the contralateral, descended testis can also display histological
signs of atrophy
Bilateral and some unilateral cases
infertility
Risk of testicular cancer
Testicular inflammation (orchitis)
Acute orchitis
Pathogenesis
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Result of urethritis, cystitis, or seminal vesiculitis
spread along the vas deferens and epididymis
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Under age 35: Neisseria gonorrhoeae, Ureaplasma, Chlamydia
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Older patients: Gram-neg. bacteria
Morphology
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Acute purulent epididymo-orchitis
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Large destructive abscesses may develop
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Healing: by scar formation
Clinical features
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Painful, enlarged, firm testis
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Fever
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Orchiectomy may be necessary
Chronic orchitis
Pathogenesis
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If acute orchitis is not treated or inadequately treated
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Mumps-virus induced orchitis after puberty
Morphology
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One or both testes may be involved in a focal or diffuse fashion
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LM: interstitial ly-c infiltrates and fibrosis, tubular hyalinization
Outcome
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Testicular atrophy; bilateral involvement
infertility
Granulomatous orchitis
Uncommon, in middle-aged males
Pathogenesis: autoimmune mechanism is suspected
Morphology
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Gross: the testis is enlarged, the tunica albuginea is thickened
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LM: intratubular inflammation composed of epitheloid cells, multinucleated giant cells, ly-s, pl-s
Clinical features
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Painless to moderately tender testicular mass of sudden onset
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Simulates tumor or tbc
fibrosis
Male infertility
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Infertile couple: no success during a 12-month period of wished gestation
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Male partner disease is present in 25-40% of the couples
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Evaluation reveals azoospermic or oligospermic (< 20 M sperms/ml) ejaculate [normospermic more than 40 M
sperms/ml]
Testicular biopsy from azoospermic men
4 conditions
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Normal spermatogenesis
Bilateral posttesticular obstruction, commonly due to previous gonorrhea
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Germ cell aplasia (Sertoli cell only sy)
Congenital or acquired; FSH
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Maturation arrest
The spermatogenic process abruptly fails to progress one of the early stages of maturation
Causes: varicocele, mumps orchitis, exposure to lead or petroleum, etc.
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Tubular hyalinization and peritubular fibrosis
Causes: trauma, alcoholism, diabetes, irradiation
Testicular biopsy from oligospermic men
4 conditions
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Spermatogenic hypoplasia
Spermatogenic cells are present in reduced numbers.
Causes: idiopathic, malnutrition, antecedent febrile illness, varicocele, insecticides, chemotherapy. May respond
to clomiphen citrate
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Incomplete maturation arrest
Causes: varicocele, mumps orchitis, exposure to lead or petroleum, etc.
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Focal peritubular fibrosis and tubular hyalinization
Causes: trauma, alcoholism, diabetes, irradiation
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Sloughing of immature germ cells
Sertoli cells and spermatogonia appear normal, the spermatocytes have sloughed into the lumen.
Causes: varicocele, mumps orchitis, etc.
Treatment option: in vitro fertilization
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Mature spermatids (if any) in the biopsy specimen can be selectively isolated and injected into oocytes;
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9. Pathology of the male genital tract
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preembryos are transferred to the cavity of uterine corpus where they implant
2010: Nobel prize for IVF: Robert Edward, Cambridge, UK; the gynecologist Patrick Steptoe, inventor of
embryotransfer, died earlier
TESTICULAR TUMORS
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95% of testicular tumors arise from the germinal (seminiferus) epithelium, termed germ cell tumors
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Malignant (exception: dermoid cyst in childhood)
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Occur with increased frequencies in association with undescended testis
General features
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Present with Insidious painless enlargement of the testis
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Lymphatic metastases: in nodes along the aorta and mediastinum
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Hematogeneous metastases: lungs, followed by liver, brain, and bones
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Treatment: radical orchiectomy + postoperative therapy (radiation, chemotherapy)
Histogenesis
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Precursor: intratubular germ cell tumor (ITGCT)
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Occurs in utero, but remains dormant untill puberty, malignant transformation in adulthood
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ITGCT cells give rise to seminoma or transform into a totipotential neoplastic cell ( e.g., embryonal carcinoma)
capable of further differentiation
Seminomas
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Most frequent germ cell tumors, mainly at about age 40
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Gross: well-demarcated homogeneous, lobulated bulky mass (sometimes ten times the size of the normal testis; the
tunica albuginea is saved
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LM: the seminoma cells have clear, glycogen containing cytoplasm; the nucleus has a prominent nucleolus;
lymphocytes in the stroma
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Remain confined to the testis for long intervals; produce lymphatic metastases; hematogeneous metastases occur
late
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Radiosensitive; the overall prognosis is good
Non-seminomatous germ cell tumors
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Highly malignant tumors, peak: about 30 y of age
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Gross: infiltrative tumors with necrosis + hemorrhage
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LM
Composed of a single histologic type: embryonal cc, choriocc (serum marker: hCG), yolk sac cc (serum
marker: alfa-fetoprotein), teratoma
Mixed: contain more than one element, most common: embryonal cc + teratoma + yolk sac cc
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At dg.: lymph node and lung metastases
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Prognosis: chemotherapy achieves remission in the majority of cases
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Pure choriocc: particularly agressive, extensive hematogeneous metastases can be present even with small primary
lesion – the prognosis is dismal
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