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Flashcards in Diseases of the testis and penis Deck (28):
1

Overview of progression of spermatogenesis

primary spermatocytes (diploid) → secondary spermatocytes (haploid) → spermatids → spermatozoa

2

Spermiogenesis

process of cytodifferentiation by which spermatids become spermatozoa

3

Leydig cells

Produce testosterone in response to pituitary luteinizing hormone

4

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
1. Risk increased in contralateral testis as well (to less extent)
2. Surgery may not reduce risk

5

When does histologic evidence of atrophy begin with cryptorchidism and what does that look like?

Begins as early as 2 years of age
1. Arrest in germ cell development
2. Thickening of basement membrane and hyperplasia of Leydig cells
3. Eventual “hyaline” replacement

6

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

7

Causes of male infertility

A. Congenital abnormalities (e.g. cryptorchidism, immotile cilia syndrome, anorchia, absent vas)

B. Acquired abnormalities
1. Torsion and infarction
- traumatic/mechanical or vascular
2. Varicocele – dilatation and tortuosity of veins in pampiniform plexus
3. Obstruction
4. Inflammation

C. Hormonal abnormalities (FSH, LH or GnRH deficiencies)

D. Klinefelter’s Syndrome (Sclerosing tubular degeneration)
1. 47 XXY most common
2. Tubular sclerosis with absence of elastic fibers
3. Leydig cell nodules
4. Elevated FSH/LH and decreased testosterone

8

Inflammatory diseases of testis / epididymis

Nonspecific epididymitis and orchitis
Mumps orchitis
Tuberculus orchitis
Syphilis

9

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

10

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

11

Tuberculus orchitis

Inflammatory disease of testis/epididymis

Almost always begins in epididymis with spread to testes

Usually part of systemic disease

Caseating granulomas

12

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

13

What is the most common kind of testicular tumor?

Germ cell tumor (95%)

14

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

15

Types of Germ cell tumors

Seminoma
Spermatocytic seminoma
Embryonal carcinoma
Yolk sac tumor
Choriocarcinoma
Teratoma
Mixed GCT’s

16

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

17

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

18

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

19

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

20

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

21

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

22

What percent of germ cell tumors are mixed?

60%

23

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

24

What is the most common testicular tumor in someone over 60?

Lymphoma

25

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)

26

Verrucous carcinoma

A “giant condyloma” with the tendency for local invasion

Rarely, if ever, metastasizes

27

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

28

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