Testicular tumors

1. Testicular Tumors

2. Germ cell tumors (95%) and sex cord-stromal tumors
Germ cell tumors are subdivided into seminomas and
nonseminomas. Most germ cell tumors are aggressive cancers
capable of rapid, wide dissemination.

3. Pathologic Classification of
Common Testicular Tumors
Germ Cell Tumors
Seminomatous tumors
 Seminoma
 Spermatocytic seminoma
Nonseminomatous tumors
 Embryonal carcinoma
 Yolk sac (endodermal sinus) tumor
 Choriocarcinoma
 Teratoma
Sex Cord-Stromal Tumors
 Leydig cell tumor
 Sertoli cell tumor

4. Germ Cell Tumors
 In the 15- to 34-year age group, testicular germ cell tumors
constitute the most common tumor of men and cause
approximately 10% of all cancer deaths.

5. Environmental Factors.
 Incidence of testicular germ cell tumors in Finland is about
two times lower than in Sweden
 Testicular germ cell tumors are associated with a spectrum of
disorders collectively known as testicular dysgenesis
syndrome (TDS).

6.  Cryptorchidism,hypospadias, and poor sperm quality.
 It has been proposed that these conditions are increased by in utero
exposures to pesticides and nonsteroidal estrogens.
 The most important association is with cryptorchidism, which is seen
with approximately 10% of testicular germ cell tumors.

7.  Klinefelter syndrome is associated with a greatly increased
risk (50 times normal) for development of mediastinal germ
cell tumors, but these patients do not develop testicular
tumors.

8. Genetic Factors.
 Strong familial predisposition
 Relative risk of these tumors is four times higher than normal
 Several genetic loci have been linked to familial germ cell
tumor risk, including the genes encoding the ligand for the
receptor tyrosine kinase KIT and BAK, which you will recall is
an important inducer of apoptotic cell death

9. Pathogenesis.
 Most testicular germ cell tumors originate from a precursor
lesion called intratubular germ cell neoplasia (ITGCN).
 The exceptions to this rule are pediatric yolk sac tumors and
teratomas, and adult spermatocytic seminomas.

10. ITGCN
Is believed to arise in utero and stay dormant until puberty, after which it may progress to
seminoma or nonseminomatous tumors.
lesion consists of atypical primordial germ cells with large nuclei and clear cytoplasm,
which are
about twice the size of normal germ cells.
These cells retain the expression of the transcription factors OCT3/4 and NANOG, which
are important in maintenance of pluripotent stem cells.
ITGCN shares some of the genetic alterations that are found in germ cell tumors. One that
is
particularly important is the reduplication of the short arm of chromosome 12 (12p) in the
form of an isochromosomei(12p), a cytogenetic alteration that is invariably found in
invasive germ cell tumors regardless of histological type.
Activating mutations in the gene encoding the KIT receptor tyrosine kinase, which may be
present in seminomas,are also freqeuntly present in ITGCN.
About 50% of individuals with ITGCN develop invasive germ cell tumors within five years
after diagnosis, and it may be that practicallyall patients with ITGCN will eventually develop
invasive tumors.

11. Seminoma
 Seminomas are the most common type of germ cell tumor,
making up about 50% of these tumors
 The peak incidence is the third decade and they almost never
occur in infants.
 An identical tumor arises in the ovary, where it
is called dysgerminoma
 Seminomas contain isochromosome12p and express OCT3/4
and NANOG.
 Approximately 25% of these tumors have KIT activating
mutations. KIT amplification and KIT overexpression
through other unknown mechanisms have also been
reported.

12. Microscopic examination reveals large cells with distinct cell
borders, pale nuclei, prominent nucleoli, and a sparse
lymphocytic infiltrate.

13. Spermatocytic
Seminoma
Medium-sized cells,
the most numerous,
containing a
roundnucleus and
eosinophilic (2)
smaller cells with a
narrow rim of
eosinophilic cytoplasm
resembling secondary
spermatocytes; and (3)
scattered giant cells,
either uninucleate or
multinucleate.

14. Embryonal Carcinoma
Embryonal carcinoma shows sheets of undifferentiated cells
as well as primitive glandular differentiation. The nuclei are large and
hyperchromatic.

15. Yolk Sac Tumor
Lacelike (reticular) network of
medium-sized cuboidal or
flattened cells. In addition,
papillary structures, solid cords
of cells,and a multitude of other
less common patterns may be
found. Inapproximately 50% of
tumors, structures resembling
endodermal
sinuses (Schiller-Duval bodies)

16. Choriocarcinoma
shows cytotrophoblastic
cells (arrowhead)
with central nuclei and
syncytiotrophoblastic cells
(arrow) with multiple dark
nuclei embedded in
eosinophilic cytoplasm.
Hemorrhage and necrosis
are seen in the upper right
field.

17. Teratoma
Immature teratoma
showing primitive cell
also showing rosette
formation.

18. Mature teratoma
Mature cartilage, glands lined
by mature epithelium, and
mature glial tissue.

19.  Stage I: tumor confined to the testis, epididymis, or spermatic
 cord
 • Stage II: distant spread confined to retroperitoneal
 nodes below the diaphragm
 • Stage III: metastases outside the retroperitoneal nodes
 or above the diaphragm

20. Biomarkers.
 Germ cell tumors of the testis often secrete polypeptide
hormones and certain enzymes that can be detected in blood
by sensitive assays. Such biologic markers include HCG,
AFP, and lactate dehydrogenase, which are valuable in the
diagnosis and management of testicular cancer. The
elevation of lactate dehydrogenase correlates with the mass
of tumor cells, and provides a tool to assess tumor burden.
 Marked elevation of serum AFP or HCG levels are produced
by yolk sac tumor and choriocarcinoma elements,
respectively. Both of these markers are elevated in more than
80% of individuals with NSGCT at the time of diagnosis.

21. Tumors of Sex Cord-Gonadal
Stroma
 Leydig Cell Tumors
 Sertoli Cell Tumors
 Gonadoblastoma

22.  Circumscribed nodules, usually less than 5 cm in diameter.
Distinctive golden brown, homogeneous cut surface.
 Histologically, neoplastic cells have an appearance that is similar to
their normal counterparts. They are large in size and have round or
polygonal cell outlines, abundant granular eosinophilic cytoplasm, and
a round central nucleus.
 The cytoplasm contains lipid droplets, vacuoles, or lipofuscin pigment,
and, most characteristically, rod-shaped crystalloids of Reinke, which
are seen in about 25% of the tumors. Approximately 10% of the
tumors in adults are invasive and produce metastases; most are
benign.

24. Sertoli Cell Tumors
 hormonally silent and present as a testicular mass. These
neoplasms appear as firm, small nodules with a
homogeneous gray-white to yellow cut surface.
 Histologically the tumor cells are arranged in distinctive
trabeculae that tend to form cordlike structures and tubules.
 Most Sertoli cell tumors are benign, but approximately 10%
pursue a malignant course.

26. Gonadoblastoma
 Comprised of a mixture of germ cells and gonadal stromal
elements that almost always arise in gonads with some form
of testicular Dysgenesis.
 In some cases the germ cell component becomes malignant,
giving rise to seminoma.

27. Testicular Lymphoma
 Non–Hodgkin lymphomas account for 5% of testicular
neoplasms, and are the most common form of testicular
neoplasms in men older than age 60 years.
 Diffuse large B-cell lymphoma, Burkitt lymphoma,and EBV-
positive extranodal NK/T cell lymphoma, Lymphoblastic
lymphoma.
 Testicular lymphomas have a higher propensity
for central nervous system involvement than do similar tumors
arising at other sites.

28.  Which one of the following is not used as a tumor marker in
testicular tumours?
 A. AFP
 B. LDH
 C. HCG
 D. CEA

30.  which of the following statements about testicular cancer is false ?
 a. a testicular mass in a male of age greater than or equal to 50 years
of age should be regarded as lymphoma unless proved otherwise .
 b. GCTs are 4 or 5 times more common in whites than in african-
american males
 c. The incidence of the testicular GCTs has been decreasing lately
 d. Cryporchidism is associated with a several fold higher risk of GCT
 e. Inguinal cryptorchid testis are at a higher risk than abdominal
cryptorchid testis

31.  involvement of nodes in germ cell tumor of testes belongs to
which stage ?
 a. I A
 b. I B
 c. II A
 d. III

32.  A 30-year-old man has had a feeling of heaviness in his left testis for the
past 6 months. Physical examination reveals enlargement of the left
testis, while the right testis appears normal. There is a palpable left
inguinal lymph node. An ultrasound reveals a 4 cm solid mass within the
body of the left testis. Laboratory findings included a serum beta-HCG of
5 IU/L and alpha-fetoprotein of 2 ng/mL. The left testis is removed and
with gross examination on sectioning reveals a firm, lobulated light tan
mass without hemorrhage or necrosis. He receives radiation therapy.
 Which of the following neoplasms is he most likely to have?
 A Choriocarcinoma
 B Embryonal carcinoma
 C Seminoma
 D Yolk sac tumor
 E Leydig cell tumor