Testes

Question 1

Gonad Development

Answer 1

Derived from the PRIMARY SEX CORDS - mesenchymal tissue from the urogenital ridge

At the 6th week of development, the testes are indifferent from the ovaries

Y chromosome contains the SRY GENE which allows the cords to DETACH from the surface and differentiate into LEYDIG and SERTOLI CELLS of the seminiferous tubules

These cells secrete ANTI-MULLERIAN HORMONE which allows the WOLFIAN DUCT (mesonephric duct) to persist as the EPIDiDYMIS and VAS DEFERENS

No Y chromosome, No SRY, no Anti-mullerian = FEMALE (DEFAULT = female)

Question 2

Androgen Insensitivity Syndrome

Answer 2

A congenital defect in the ANDROGEN RECEPTOR

Results in genetically XY males with TESTICULAR FEMINIZATION (pseudohermphroditism)

Male with an external female phenotype (blind-ended vagina, breasts, no axillary or pubic hair), bilateral cryptorchid testis and frequent testicular GERM CELL TUMORS

Raised as females only until they present with amenorrhea or infertility

Question 3

CRYPTORCHIDISM

Answer 3

Undescended testes – FAILURE to descend from retroperitoneum to the scrotum

Usually UNILATERAL, 4% of babies, 0.4% after a year

Most commonly get stuck in the INGUINAL CANAL (48% stop in upper scrotum, 42% in canal itself, 10% get stuck in wall)

Why is this a problem? INCREASED TEMP and SUSCEPTIBILITY TO TRAUMA will cause ATROPHY OF THE UNDESCENDED TESTIS

35x high risk for GERM CELL TUMORS!!!!!! Characteristic histological/gross changes predispose to ABNORMAL PROLIFERATION, including a THICK BM of the seminiferous tubules with LEYDIG and SERTOLI hyperplasia

Uncorrected –> infertility

Question 4

VARICOCELE

Answer 4

Dilation of the pampiniform plexus and STASIS of blood flow

Don’t get good heat exchange between arterial and venous blood –> Testicular temperature RISES –> sperm production DECREASES

Remove abnormal veins and re-wire everything to restore blood flow

Question 5

Normal Cooling System

Answer 5

Need an ideal environment to duplicate DNA and form sperm safely; main way is through cooling system

AIR cooling system –> involves the DARTOS muscle of the scrotum (can expand and contract to adjust the scrotum position based on temperature)

LIQUID cooling system –> Pampiniform plexus –> countercurrent heat exchange between vessels makes it so that VENOUS BLOOD is COOLER than ARTERIAL BLOOD and the testes ONLY RECEIVE COOL BLOOD –> promotes spermatogenesis

Increased temp = DECREASED SPERM PRODUCTION –> workers in hot environments, jock straps, or VARICOCELE

Question 6

TESTICULAR TORSION

Answer 6

Usually in young ATHLETES - but there has to be UNDERLYING ABNORMALITIES PRESENT to predispose the patient

TORSION OF THE SPERMATIC CORD, resulting in cessation of blood supply and possible necrosis if untreated!!!!

Complete –> entire cord, results in hemorrhagic infarction

Incomplete –> torsion is developed over time and can result in ATROPHY or FIBROSIS of the testis

If testis is still viable, then we can AFFIX IT TO THE FLOOR OF THE SCROTUM (called Orchidopexy) to prevent it from happening again

Question 7

ORCHITIS

Answer 7

ORCHITIS –> inflammation of the testes

Caused by GRAM NEGATIVES, SYPHILIS, MUMPS = MOST COMMON!!!!!!, TB, MALAKOPLAKIA

Often presents as a TESTICULAR MASS

Lots of LYMPHOCYTES on biopsy, with VON-HANSEMAN CELLS (Have CALCIUM inclusions called MICHAELIS GUTMAN BODIES)

Question 8

INFERTILITY

Answer 8

Testicular injury – can be secondary to orchitis, cryptorchidism, varicocele, liver cirrhosis (conversion of androgens -> estrogen), diabetes, chemo, radiation, HRT

Primary Testicular Failure –> Don’t know why you’re infertile –> probably due to disorders like KLINEFELTERS (XXY) –> often diagnosed when there is AZOSPERMIA with normal endocrine function –> GET A BIOPSY

Post-Testicular Failure –> mostly iatrogenic and includes vasectomy

Question 9

GERM CELL TUMORS overview

Answer 9

Account for 90% of testicular cancers

Bimodal distribution (young kinds, young adults)

Uncommitted germ cells can develop into a SEMINOMAS which can still differentiate into ANY DIFFERENT TYPE

Can go through the EXTRAEMBRYONIC PATHWAY and become a CHORIOCARCINOMA or YOLK SAC TUMOR

Can go through EMBRYONAL PATHWAY and become a MATURE TERATOMA or an EMBRYONAL CARCINOMA

We can also get neoplasms with multiple cell types (trophoblasts, yolk sac, somatic) –> MIXED GERM CELL TUMORS

Seminomas and Mixed Germ Cell Tumors arise in YOUNGER adults

Extratesticular Germ Cell Tumors (those that are germ cell but appear in the mediastinum, in the middle of the brain, or in the sacrococcygeal area) can occur in infants

Question 10

SEMINOMAS

Answer 10

Most common of the germ cell tumors (40-50%); Usually present in the 30s, almost NEVER PRE-PUBERTY

Produce BULKY MASSES sometimes 10x the size of normal testes

VERY SENSITIVE TO RADIOTHERAPY!!!! 5 year survival = 90%

Question 11

Classic Seminomas

Answer 11

Look HOMOGENOUSLY tan colored and are usually WELL-CIRCUMSCRIBED

LACK NECROSIS OR HEMORRHAGE!!!! (think other cancers if they are present)

Histology –> LARGE NEST of tTUMOR CELLS separated by FIBROUS STROMA of LYMPHOCYTES

DISTINCT POLYGONAL BORDERS

Question 12

Spermatic Seminomas

Answer 12

SIgnificantly less common (4-7% of seminomas)

Occur EXCLUSIVELY IN OLDER MALES

These are TERMINALLY DIFFERENTIATED so they WONT appear in mixed cell tumors

NEVER outside of the testes

Grossly look similar to classic

Histology –> PLEOMORPHIC; looks scary, but since it’s a tumor of the SPERMATOGENIC PROCESS then the neoplastic cells are MORE IMMATURE! Mortality rate is NOT bad, prognosis is EXCELLENT (slow growing, no mets)

Question 13

EMBRYONAL CARCINOMA

Answer 13

2nd most common germ cell tumor (15-35%)

MORE AGGRESSIVE THAN SEMINOMAS!

Requires CHEMO + RADIATION

Not seen before puberty, usually occurs between 20-25 years old

90% of patients will be cured if the lesion is LOCALIZED, but only 50% if disseminated

Grossly –> SMALLER than seminomas and VERY HEMORRHAGIC AND NECROTIC (direct contrast to seminomas)

Histology –> HIGH CELLULARITY, SYNCYTIAL APPEARANCE; Cells grow in ALEVEOLAR or TUBULAR PATTERNS with OCCASIONAL PAPILLARY CONVULTIONS

Higher magnification shows PSAMMOMA BODIES (round collection of calcium) within the papillary projection

Question 14

Seminomas VS Embronal Carcinomas

Answer 14

SEMINOMAS –> Larger, no structural patterns, NO HEMORRHAGE/NECROSIS, distinct cell borders (polygonal), KERATIN -, PLAP +, CD117+, CD30 -

Embryonal –> tubular, papillary, alveolar, SMALLER; HEMORRHAGE AND NECROSIS BOTH PRESENT; syncitial appearance; KERATIN+, PLAP+ CD117 - , CD 30+

Question 15

TERATOMAS

Answer 15

Somewhat different than those in the ovaries

In ovaries, remember that “adult” tissue is BENIGN

IN TESTES, REGARDLESS OF MATURITY IT IS MALIGNANT!!!!!!!!!

No age distribution

Constitute 50% of testicular germ cell tumors in CHILDREN!!! Only 5% in adult

Question 16

YOLK SAC TUMORS

Answer 16

In embryogenesis, the yolk sac is formed and disappears within 21 days

Serves as a NUTRITIONAL SOURCE FOR DEVELOPMENT -> vessels within it connect to the developing FETAL vasculature

Tumors of this origin MIMIC HISTOLOGY OF THE YOLK SAC in the early embryonic stages as it transitions from the sac to the fetal placenta

Usually in the infant it is in EXTRA-TESTICULAR locations –> GOOD prognosis

MOST COMMON TESTICULAR TUMOR IN KIDS UP TO 3 YEARS OLD

When it occurs in ADULTS, it is part of a MIXED GERM CELL TUMOR (similar prognosis to EMBRYONAL carcinoma)

Histology –> patterns (polyvesicular, papillary, embryoid bodies, hyaline globules, glomeruloid bodies, eosinophilic globules)

Question 17

TESTICULAR CHORIOCARCINOMA

Answer 17

VERY AGGRESSIVE TUMOR

Generally HIGHLY MALIGNANT TUMOR and FREQUENTLY METASTASIZE TO THE BRAIN!

Lance Armstrong!!!!

These tumors often show a PROLIFERATION OF CYTOTROPHOBLASTS or SYNCTIOTROPHOBLASTS at the interface between normal and neoplastic tissue (DARK on stain)

Question 18

MIXED GERM CELL TUMORS

Answer 18

Mixture of any and all of the ones talked about except SPERMATOCYIC SEMINOMA (remember?!?! It’s already terminally differentiated!)

Prognosis is DETERMINED by the HIGHEST-GRADE NEOPLASM PRESENT

60% of all testicular tumors are mixed

Question 19

STROMAL or SEX CORD TUMORS –> LEYDIG

Answer 19

LEYDIG CELL –> More common, hormonally active, and thus easier to spot because of symptoms

Can arise at any age, mostly between 20-60

Testicular SWELLING is most common presentation (like most)

GYNECOMASTIA man boobs

PRECOCIOUS PUBERTY

Question 20

STROMAL or SEX CORD TUMORS –> SERTOLI

Answer 20

Extremely RARE; present as a testicular mass……….

CAN OCCUR COMBINED WIth LEYDIG

Question 21

What is unique about sex cord tumors?

Answer 21

ALMOST ALWAYS BENIGN AND WELL-CIRCUMSCRIBED!!!!!!!!

Question 22

Testicular LYMPHOMAS

Answer 22

Testicular cancers are generally NOT primary, especially in OLDER MEN

Aggresive NHL accounts for 5% of all testicular cancers, and is the MOST COMMON TESTICULAR NEOPLASM OVER THE AGE OF 60

By the time of detection, the disease is already disseminated

FREQUENCY = Diffuse large B Cell > Burkitt > NK/T cell lymphoma

patients with these tumors have a HIGHER INCIDENCE IN CNS INVOLVEMENT!!!!!!

Question 23

Leydig and Sertoli

Answer 23

LEYDIG = TESTOSTERONE (respond to LH)

SERTOLI = SUPPORTING (respond to FSH)