Download TESTICULAR TUMORS-2016

TESTICULAR TUMORS
TESTICULAR
TUMORS
Department of Pathology
They are divided into two major categories: germ cell
tumors and sex cord-stromal tumors
Approximately 95-98% of testicular tumors arise from germ
cells
Germ cell tumors are subdivided into seminomas and
non-seminomas (NSGCT).
Most germ cell tumors are aggressive cancers capable of
rapid, wide dissemination, although with current therapy
most can be cured.
Sex cord-stromal tumors are generally benign
Medical University of Warsaw
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Germ Cell Tumors (95-98%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
TESTICULAR CANCER (TC)
TESTICULAR CANCER (TC)
TC is an uncommon malignancy,
accounting for 1–2% of all tumours
in men.
However, TC is now the most
common malignancy in young men
(aged 15–34 years) in many
populations worldwide
Typically, the peak age of men with
seminomas is 35–45 years,
compared with 20–30 years for
NSGCT
For unexplained reasons there is a worldwide increase in the
incidence of TC (particularly in white Caucasian populations)
The global incidence of TC has doubled over the past three
decades
There is marked geographical variation in the agestandardized incidence rate for testicular cancer, ranging from
as low as 0.5/100 000 in Egypt to as high as 9.2/100 000 in
Denmark or 9.6/100 000 in Norway
In Europe- the highest IR- the North
In the United States these tumors are much common in whites
than in blacks (ratio 5 : 1)
Whites (6,3/100,000) > Blacks (1,3/100,000)
TESTICULAR TUMORS- epidemiology
What are the Risk Factors for Testicular
Cancer?
Well-established:
Age standardized global incidence of testicular cancer.
(International Agency for Research on Cancer)
TC/GCT- RISK FACTORS
Cryptorchidism (also referred to as
maldescended or undescended testis), which is
associated with approximately 10% of testicular
germ cell tumors, is the most firmly established
risk factor.
There is a three to eight times greater risk of
testicular cancer with cryptorchidism
Cryptorchidism
Intersex syndromes (eg AIS, gonadal dysgenesis)
Personal history
Family history
Race
Cryptorchidism and Testicular Cancer
Cryptorchidism is the failure of descent of one or both
testes into the scrotum.
Normally, the testes descend from the coelomic cavity into the pelvis
by the third month of gestation and then through the inguinal canals
into the scrotum during the last 2 months of intrauterine life.
Several influences, including hormonal abnormalities, intrinsic
testicular abnormalities, and mechanical problems (e.g.,
obstruction of the inguinal canal), may interfere with normal
testicular descent.
In the vast majority of cases the cause of the
cryptorchidism is unknown.
Testicular Cancer - Risk Factors
Cryptorchidism and Testicular Cancer
Personal history
A previous history of testicular GCT is a well established risk
factor for developing testicular cancer in the contralateral
testis.
Individuals with unilateral cryptorchidism are also at
increased risk for the development of cancer in the
contralateral, normally descended testis, suggesting that
Fosså et al.(2005) reported, in a population-based cohort
study involving 29 515 men in the USA, that patients have a
12.4 times greater risk of developing a metachronous
contralateral testicular cancer than the general population.
some intrinsic abnormality, rather than simple failure of
descent, may be responsible for the increased cancer risk.
Testicular Cancer - Risk Factors
Family history
The relative risk of development of these tumors in
fathers and sons of patients with testicular germ
cell tumors is 4 times higher than normal, and is 8
to 10 times higher between brothers.
Testicular Cancer - Risk Factors
Migration studies, especially from Finland, Sweden and
Denmark, where the incidence of testicular cancer is low,
medium and high, respectively, support the hypothesis of
shared genes rather than shared environmental exposures.
The risk of testicular cancer in Finnish men migrating to
Sweden remained low regardless of age of migration (Ekbom
et al.,2003)
the risk of testicular cancer in Danish men migrating to
Sweden remained high (Hemminki K et al. 2002)
Testicular Cancer - Risk Factors
Scrotal trauma
There have been several reports linking trauma to the
testicle or scrotum with testicular cancer, but epidemiological
evidence is inconclusive.
Merzenich et al. concluded, on the basis of their populationbased multicentre case-control study, that there is no
evidence to support the association between scrotal trauma
and testicular cancer (2007, N Engl J Med.)
What are the Risk Factors for Testicular
Cancer?
No association:
Vasectomy
Maternal smoking
Scrotal trauma
TESTICULAR TUMORS
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Most testicular tumors in postpubertal males arise from the in situ lesion
intratubular germ cell neoplasia (ITGCN).
This lesion is present in conditions associated with a high risk of
developing germ cell tumors (e.g., cryptorchidism, dysgenetic gonads).
These in situ lesions can be found in grossly “normal” testicular tissue
adjacent to germ cell tumors in virtually all cases.
From: http://www.wikiwand.com/en/Intratubular_germ_cell_neoplasia
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Seminoma
Seminoma - morphology
Ss are the most common type of germ cell tumor, making
up about 50% of these tumors
MA: Seminomas produce bulky masses, sometimes ten times
the size of the normal testis. The typical seminoma has a
homogeneous, gray-white, lobulated cut surface, usually
devoid of hemorrhage or necrosis.
the peak incidence is the third decade and they almost
never occur in infants.
an identical tumor in the ovary - dysgerminoma
Ss contain an isochromosome 12p, and express OCT3/4
and NANOG.
Approximately 25% of ss have c-KIT activating mutations.
Seminoma of the testis appears as a fairly well-circumscribed, pale, fleshy, homogeneous mass.
Seminoma - morphology
MI (low magnification): the typical seminoma is composed of
sheets of uniform cells divided into poorly demarcated lobules
by delicate septa of fibrous tissue containing a moderate
amount of lymphocytes.
Seminoma - morphology
MI (higher magnification): the cell is large and round to
polyhedral and has a distinct cell membrane; a clear or wateryappearing cytoplasm; and a large, central nucleus with one or
two prominent nucleoli. Mitoses vary in frequency. The
cytoplasm contains varying amounts of glycogen.
Seminoma – L.m. shows clear seminoma cells divided into poorly demarcated lobules by delicate septa.
Mi. examination reveals large cells with distinct cell borders, pale nuclei, prominent nucleoli, and a sparse lymphocytic infiltrate.
Seminoma - morphology
Seminoma cells are diffusely positive for: c-KIT (CD117),
OCT4, and placental alkaline phosphatase (PLAP), with
sometimes scattered keratin-positive cells.
Seminoma - morphology
Approximately 15% of seminomas contain
syncytiotrophoblasts. In this subset of patients, serum human
chorionic gonadotropin (hCG) levels are elevated, though not
to the extent seen in patients with choriocarcinoma.
hCG (+)
Spermatocytic Seminoma
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma is a distinctive tumor both clinically
and histologically.
Spermatocytic seminoma is an uncommon tumor,
representing 1% to 2% of all testicular germ cell neoplasms.
The age of involvement is much later than for most
testicular tumors: generally over the age of 65 years.
In contrast to classic seminoma, it is a slow-growing tumor
that does not produce metastases,
The prognosis is excellent.
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Spermatocytic Seminoma - morphology
Grossly, spermatocytic seminoma tends to have a soft, pale
gray, cut surface that sometimes reveal mucoid cysts.
Gross appearance of spermatocytic seminoma.
A large tumor of myxoid appearance bulges on the cut surface.
Spermatocytic Seminoma - morphology
SS. contain three cell populations, all intermixed:
(1) medium-sized cells, the most numerous, containing a round nucleus
and eosinophilic cytoplasm;
(2) smaller cells with a narrow rim of eosinophilic cytoplasm
(3) scattered giant cells, either uninucleate or multinucleate.
Spermatocytic seminoma showing admixture of medium-sized cells (predominating), giant cells, and small
lymphocyte-like cells
Embryonal carcinoma
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinomas occur mostly in the 20- to 30-year
age group
These tumors are more aggressive than seminomas
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Embryonal carcinoma - morphology
Embryonal carcinoma - morphology
Grossly, the tumor is smaller than seminoma and usually
does not replace the entire testis. On cut surfaces the mass
is often variegated, poorly demarcated at the margins, and
punctuated by foci of hemorrhage or necrosis
Histologically the cells grow in alveolar or tubular patterns, sometimes
with papillary convolutions. The neoplastic cells have an epithelial
appearance, are large and anaplastic, and have hyperchromatic nuclei with
prominent nucleoli. The cell borders are usually indistinct, and there is
considerable variation in cell and nuclear size and shape. Mitotic figures and
tumor giant cells are frequently seen.
Embryonal carcinoma showing solid nodular cut surface with numerous areas of necrosis and hemorrhage
Embryonal carcinoma - morphology
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Embryonal carcinomas share some markers with
seminomas such as OCT 3/4 and PLAP,
but differ by being positive for cytokeratin and
CD30, and
negative for c-KIT (CD117)
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Yolk Sac Tumor
(endodermal sinus tumor)
Yolk sac tumor is of interest because it is the most
common testicular tumor in infants and children
up to 3 years of age
In this age group it has a very good prognosis.
In adults the pure form of this tumor is rare; instead,
yolk sac elements frequently occur in
combination with embryonal carcinoma
Yolk Sac Tumor - morphology
Yolk Sac Tumor - morphology
Grossly, the tumor is nonencapsulated, and on cross-section it
presents a homogeneous, yellow-white, mucinous appearance.
Yolk Sac Tumor - morphology
MI: characteristic on mi. examination is a lacelike (reticular) network of
medium-sized cuboidal or flattened cells. In addition, papillary structures,
solid cords of cells may be found. In approximately 50% of tumors, structures
resembling endodermal sinuses (Schiller-Duval bodies) may be seen; these
consist of a mesodermal core with a central capillary and a visceral and
parietal layer of cells resembling primitive glomeruli.
Yolk sac carcinoma. A, Low-power photomicrograph demonstrating
areas of loosely textured, microcystic tissue and a papillary structure
resembling a developing glomerulus. B, Higher power photomicrograph
demonstrating characteristic hyaline droplets within the microcystic areas
of the tumor. α-fetoprotein is present within the droplets
Yolk Sac Tumor - morphology
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Present within and outside the cytoplasm are
eosinophilic, hyaline-like globules in which αfetoprotein (AFP) and α1-antitrypsin can be
demonstrated by immunocytochemical
staining.
The presence of AFP in the tumor cells is highly
characteristic, and it underscores their
differentiation into yolk sac cells.
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Choriocarcinoma - morphology
Choriocarcinoma
Choriocarcinoma is a highly malignant form of
testicular tumor.
In its "pure" form choriocarcinoma is rare,
constituting less than 1% of all germ cell
tumors.
Often they cause no testicular enlargement and are
detected only as a small palpable nodule. Typically, these
tumors are small, rarely larger than 5 cm in diameter.
Hemorrhage and necrosis are extremely common.
Gross appearance of pure choriocarcinoma.
The strikingly hemorrhagic appearance is characteristic of this tumor type
Choriocarcinoma - morphology
Choriocarcinoma - morphology
Histologically the tumors contain two cell types. The
syncytiotrophoblastic cells are large and have many
irregular or lobular hyperchromatic nuclei and an abundant
eosinophilic vacuolated cytoplasm. hCG can be readily
demonstrated in the cytoplasm. The cytotrophoblastic cells
are more regular and tend to be polygonal, with distinct
borders and clear cytoplasm; they grow in cords or masses
and have a single, fairly uniform nucleus.
Choriocarcinoma shows clear
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.
Teratoma
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
The designation teratoma refers to a group of complex
testicular tumors having various cellular or organoid
components reminiscent of normal derivatives from
more than one germ layer.
Pure forms of teratoma are fairly common in infants and
children, second in frequency only to yolk sac tumors.
In adults, pure teratomas are rare, constituting 2% to 3% of
germ cell tumors.
However, the frequency of teratomas mixed with other
germ cell tumors is approximately 45%.
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Teratoma - morphology
Grossly, teratomas are usually large, ranging from 5 to 10
cm in diameter. Because they are composed of various
tissues, the gross appearance is heterogeneous with solid,
sometimes cartilaginous, and cystic areas. Hemorrhage
and necrosis usually indicate admixture with embryonal
carcinoma, choriocarcinoma, or both.
Teratoma - morphology
Teratomas are composed of a heterogeneous,
helter-skelter collection of differentiated cells or
organoid structures, such as neural tissue, muscle
bundles, islands of cartilage, clusters of squamous
epithelium, structures reminiscent of thyroid gland,
bronchial or bronchiolar epithelium, and bits of
intestinal wall or brain substance, all embedded in
a fibrous or myxoid stroma.
Elements may be mature (resembling various
adult tissues) or immature (sharing histologic
features with fetal or embryonal tissue).
Teratoma - morphology
Teratoma - morphology
Teratoma - morphology
Mixed tumors
In the child, differentiated mature teratomas usually
follow a benign course.
In the postpubertal male all teratomas are regarded
as malignant, capable of metastatic behavior
whether the elements are mature or immature.
Consequently, it is not critical to detect
immaturity in a testicular teratoma of a
postpubertal male.
About 60% of testicular tumors are composed
of more than one of the "pure" patterns.
Common mixtures include: teratoma, embryonal
carcinoma, and yolk sac tumor; seminoma with
embryonal carcinoma; and embryonal carcinoma
with teratoma (teratocarcinoma).
In most instances the prognosis is worsened by the
inclusion of the more aggressive element.
Testicular tumors – clinical stages
Stage I: tumor confined to the testis, epididymis, or spermatic cord
Stage II: distant spread confined to retroperitoneal nodes below the
Testicular tumors
Seminoma, which is extremely radiosensitive and tends to
remain localized for long periods, has the best prognosis. More
than 95% of patients with stage I and II disease can be cured.
diaphragm
Stage III: metastases outside the retroperitoneal nodes or above the
Among NSGCTs, the histologic subtype does not influence the
diaphragm
prognosis significantly, and hence these are treated as a group.
The therapy and prognosis of testicular tumors depend largely
on clinical stage and on the histologic type.
Approximately 90% of patients with NSGCTs can achieve complete
remission with aggressive chemotherapy, and most can be cured.
Pure choriocarcinoma has a poor prognosis.
Testicular tumors
From a therapeutic viewpoint:
seminomas are extremely radiosensitive,
whereas NSGCTs are relatively radioresistant
The prognosis of many NSGCTs has improved
dramatically with the introduction of platinumbased chemotherapy regimens.
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Sertoli cell tumor
Leydig Cell Tumors
They may elaborate androgens and in some cases both
androgens and estrogens, and even corticosteroids.
They may arise at any age, although most cases occur
between 20 and 60 years of age.
As with other testicular tumors, the most common presenting
feature is testicular swelling, but in some patients
gynecomastia may be the first symptom.
In children, hormonal effects, manifested primarily as sexual
precocity, are the dominating features.
Leydig cell tumor - morphology
MA: These neoplasms form circumscribed nodules, usually
less than 5 cm in diameter. They have a distinctive golden
brown, homogeneous cut surface.
Gross appearance of Leydig cell tumor. This tumor, occurring in a child, is solid, well
circumscribed, and dark brown.
Leydig cell tumor - morphology
Leydig cell tumor - morphology
Histologically, neoplastic Leydig cells usually are remarkably similar to
their normal counterparts in that they are large and round or polygonal,
and they have an abundant granular eosinophilic cytoplasm with a round
central nucleus. The cytoplasm frequently contains lipid granules,
vacuoles, or lipofuscin pigment, and, most characteristically, rod-shaped
crystalloids of Reinke occur in about 25% of the tumors.
crystalloids of Reinke
Sertoli Cell Tumors
TESTICULAR TUMORS
Pathologic Classification of Common Testicular Tumors
Germ Cell Tumors (95%)
Seminomatous tumors:
Seminoma
Spermatocytic seminoma
Non-seminomatous tumors
Embryonal carcinoma
Yolk sac (endodermal sinus) tumor
Choriocarcinoma
Teratoma
Sex Cord-Stromal Tumors
Leydig cell tumor
Most Sertoli cell tumors are hormonally silent and present as
a testicular mass.
Grossly, 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 occasional tumors
(∼10%) pursue a malignant course.
Sertoli cell tumor
Testicular Cancer and Early Detection
What are the Symptoms of Testicular Cancer?
Painless enlargement of the testis is a characteristic
feature of TC
Pain or discomfort in a testicle or the scrotum
Feeling of heaviness in the scrotum
Dull ache in the lower abdomen or groin
Buildup of fluid in the scrotum
Breast tenderness or growth
Lower back pain, chest pain may be symptoms of
advanced cancer
Can often be detected early
Many men find the cancer during a self-examination
Doctors recommend that men ages 15 to 55 perform a
monthly self-examination
Testicular Cancer and Early Detection
Men who notice a lump, hardness, enlargement, pain or any
other change in one or both of their testicles should
….see their doctor as soon as possible