Diseases of the testis and penis Flashcards
Overview of progression of spermatogenesis
primary spermatocytes (diploid) → secondary spermatocytes (haploid) → spermatids → spermatozoa
Spermiogenesis
process of cytodifferentiation by which spermatids become spermatozoa
Leydig cells
Produce testosterone in response to pituitary luteinizing hormone
Cryptorchidism
Congenital maldescent of one (75% of cases) or both (25%) testes
Vast majority are idiopathic (? hormonal or mechanical factors)
Contralateral testes may also regress and result in infertility
Undescended testes have 10-40 fold increased risk of developing cancer
- Risk increased in contralateral testis as well (to less extent)
- Surgery may not reduce risk
When does histologic evidence of atrophy begin with cryptorchidism and what does that look like?
Begins as early as 2 years of age
- Arrest in germ cell development
- Thickening of basement membrane and hyperplasia of Leydig cells
- Eventual “hyaline” replacement
Other causes of testicular atrophy (not due to cryptorchidism)
A. Atherosclerosis B. Inflammation C. Malnutrition D. Hypopituitarism E. Hormone therapy (prostate cancer) F. Klinefelter’s Syndrome
Causes of male infertility
A. Congenital abnormalities (e.g. cryptorchidism, immotile cilia syndrome, anorchia, absent vas)
B. Acquired abnormalities
- Torsion and infarction
- traumatic/mechanical or vascular - Varicocele – dilatation and tortuosity of veins in pampiniform plexus
- Obstruction
- Inflammation
C. Hormonal abnormalities (FSH, LH or GnRH deficiencies)
D. Klinefelter’s Syndrome (Sclerosing tubular degeneration)
- 47 XXY most common
- Tubular sclerosis with absence of elastic fibers
- Leydig cell nodules
- Elevated FSH/LH and decreased testosterone
Inflammatory diseases of testis / epididymis
Nonspecific epididymitis and orchitis
Mumps orchitis
Tuberculus orchitis
Syphilis
Nonspecific epididymitis and orchitis
Inflammatory disease of testis/epididymis
Usually due to direct extension from urinary tract (vas deferens or lymphatics) and tends to effect epididymis first with subsequent orchitis
In children – usually associated with urinary tract malformations (gm neg rods)
In sexually active adults – Chlamydia trachomatis, N. gonorrhoeae
Elderly – enterobacteria
Acute inflammation – may develop abscesses
Mumps orchitis
Inflammatory disease of testis/epididymis
Can occur in pubertal or adult males who acquire mumps (30%)
Usually subsequent to parotid involvement
Unilateral in 70% of cases
Mononuclear inflammatory infiltrate with interstitial edema +/- neutrophils
Infertility uncommon
Tuberculus orchitis
Inflammatory disease of testis/epididymis
Almost always begins in epididymis with spread to testes
Usually part of systemic disease
Caseating granulomas
Syphilis
Inflammatory disease of testis/epididymis
Almost always involves testes first
Congenital or acquired
Diffuse mononuclear interstitial inflammation rich in plasma cells
Obliterative endarteritis
+/- gummas
What is the most common kind of testicular tumor?
Germ cell tumor (95%)
Germ cell tumors
Malignant germ cells may reflect spermatocytic differentation (seminoma) or totipotential cells (embryonal carcinomas) which can then transcend along various lines of intraembryonic (teratoma) or extraembryonic
(choriocarcinoma, yolk sac tumor) differentiation
Can form pure tumor types (“pure” seminoma or embryonal carcinoma) or mixtures of tumor types
Metastases can be of different type than primary
Tend to occur in young men (15-35 years) – painless testicular enlargement
Predisposing factors: cryptorchidism, genetic factors, testicular dysgenesis
Types of Germ cell tumors
Seminoma Spermatocytic seminoma Embryonal carcinoma Yolk sac tumor Choriocarcinoma Teratoma Mixed GCT’s
Seminoma
Most common (30% - 50% of all GCT’s)
Gross – homogeneous “fish flesh” appearance
Microscopic – uniform population of large, polygonal cells with distinct cell membrane, cleared cytoplasm and central nucleus with prominent nucleolus
-fibrous septa with lymphocytic infiltration or granulomatous
reaction
- may be “anaplastic” with high mitotic counts (uncommon)
- can have syncytiotrophoblastic giant cells – produce hCG
Spermatocytic seminoma
(1-2% of GCT’s)
Clinically and histologically distinct from seminoma
Effects older men (>65 years)
Slow growing – rarely metastasizes
Mixture of cells resembling primary and secondary spermatocytes in myxoid stroma
Embryonal carcinoma
More common in mixed GCT’s (seen in >40% of GCT’s) than as pure embryonal (~3% of GCT’s)
More aggressive than seminomas
Usually found as small tumors in testes but has high potential for extension through tunica albuginea and into spermatic cord
Large, hyperchromatic, pleomorphic nuclei and indistinct
cytoplasm – mitoses frequent
Glandular, trabecular, papillary arrangements
Yolk sac tumor
Most common testicular tumor of infants and children
Often part of mixed tumor in adults
Characteristic loose or maze-like network of cells on thin
fibrovascular cords or microcystic / myxomatous
Cells accumulate and secrete alpha - fetoprotein
Choriocarcinoma
Very rare in pure form (0.3% of GCT’s)
Seen in ~7% of mixed GCT’s
Placental differentiation – syncytiotrophoblast and
cytotrophoblast
Aggressive, often metastasize
Produce human chorionic gonadotropin – useful as marker
Teratoma
May occur at any age (40% of testicular tumors in infants, 2-3% of adult GCT’s)
good prognosis in children, variable in adult (considered
malignant)
Common component of mixed tumors (~45%)
Mature
- heterogeneous differentiated elements including any combination of neural tissue; muscle; cartilage; bronchial, intestinal, squamous epithelium, etc. within loose stroma
Immature
- incompletely differentiated elements of the three germ cell layers
- embryonic elements
May have malignant transformation in any of the germ layers
What percent of germ cell tumors are mixed?
60%
Sex-cord-stromal tumors
NOT a germ cell tumor
Leydig cell (2% of testicular tumors)
a. May produce hormones (androgen, estrogen) – gynecomastia, precocious puberty
b. Characteristic granular eosinophilic cytoplasm & intracytoplasmic crystals
c. 90% are benign
Sertoli cell tumors – uncommon
What is the most common testicular tumor in someone over 60?
Lymphoma
Condyloma acuminatum
“Genital wart” composed of papillary projections of connective tissue covered with thickened hyperplastic epithelium
Koilocytes – epithelial cells with atypical crinkled nuclei and large perinuclear halo – a characteristic of human papilloma virus infection (most often types 6 and 11)
Verrucous carcinoma
A “giant condyloma” with the tendency for local invasion
Rarely, if ever, metastasizes
Carcinoma in situ (CIS) of the penis
Bowen’s disease – squamous CIS involving skin of genital region
- 5-10% of cases will progress to invasive squamous carcinoma
- associated with visceral cancers
Erythroplasia of Queyrat – squamous CIS involving mucosal surfaces of glans penis in noncircumsized men
- also can progress to invasive carcinoma
Squamous carcinoma of the penis
Rare in U.S. due to hygiene practices (0.3-0.6% of all male malignancies)
Significant health problem in areas of the world where good genital hygiene not practiced
Largely a disease of elderly (peak incidence ~ age 80)
Blacks affected more than whites by almost 2:1
HPV types 16 and 18 have been implicated
Major prognostic factors include grade and stage
