Jack: Hi all and welcome to this lecture
on the epidemiology of testicular cancer.
In this lecture, we have several goals.
We'll review the anatomy of the testis.
We'll review spermatogenesis.
Look at the global burden of testicular cancer,
and trends in testicular cancer.
We also will discuss risk factors,
and prevention in therapy.
So to begin with, we'll give a brief overview
of the anatomy of the testis.
So each testis consists
of approximately 250 lobules separated by fibrous strands.
Each lobule consists of loose connective tissue,
and a network of tubules called seminiferous tubules.
Each seminiferous tubule is lined by a basement membrane
that supports the germinal epithelium.
The germinal epithelium is made
up of primordial germ cells or spermatogonia,
from which sperm arise.
Spermatogonia are sperms, or stem cells,
which proliferate by mitosis.
As spermatogonia move away from the basement membrane,
they undergo miosis
to form immature sperm called spermatids.
Two important cell types, sertoli cells, and leydig cells,
stimulate and regulate the process of spermatogenesis.
Sertoli cells are nurse cells, and secrete estrogen
and other hormones in response to the pituitary hormone,
follicular stimulating hormone, or FSH.
Leydig cells secrete testosterone,
in response to the pituitary hormone, luteinizing hormone,
or LH.
Spermatic angiogenesis involves both mitotic,
and myotic divisions of germinal epithelial cells
under the influence of testosterone and estrogen.
So 95% of all tumors of the testis are germ cell neoplasms.
There are four specific types of germ cell tumors.
Seminomas, embryonal carcinomas, malignant teratomas,
and choriocarcinomas.
These lesions can be combined
into two histologic groups, seminomas and non-seminomas.
So seminomas arise from sertoli or leydig cells,
and they're predominantly occur in young adults.
They're rare during infancy, and they're radio-sensitive.
These have a monotonous histology.
Non-seminomas arise from embryonic cells,
and they're common in infants.
They're not radio-sensitive,
and they have a variable histology.
Embryonal carcinomas have a high AFP,
while malignant teratomas are characterized
by bizarre histology.
Choriocarcinomas are characterized by high HCG values.
50% of all germ cell tumors are seminomas,
and 50% are non-seminomas.
Non-seminomas often represent tumors of mixed histology,
and may include a wide variety of histologic subtypes.
A recent study evaluating the histology
of mixed germ cell tumors reported a strong association
between teratomas, and yolk sac tumors.
So to turn to incidence in prevalence.
During 2012, 55,266 new cases of testicular cancer
were diagnosed globally,
and a little over 10,000 men died of the disease.
The annual incidence of testicular cancer worldwide
has remained stable during the last decade,
at about 1.5 cases per 100,000 men.
However, the incidence rates vary more than 20-fold,
among nations ranging from less than 0.5 per 100,000,
in some Asian and African, or African American populations,
to over 12 per 100,000 in Norway, Denmark, and Switzerland.
The annual mortality of testicular cancer worldwide
has also remained stable during the last decade,
at about 0.3 deaths per 100,000 men.
Mortality rates are highest in nations
of high incidence rates,
and access to therapy is limited.
In 2020, the age-standardized incidence of testicular cancer
was 1.8 per 100,000 men,
and the mortality was 0.22 per 100,000 men.
The annual incidence has steadily increased over time
in some populations, particularly in developed nations.
For example, the incidence more than doubled
in Great Britain during 1975 to 2010.
In the face of rising incidence rates
of testicular cancer, mortality rates are steadily declining
in many populations.
The incidence of testicular cancer among American men
has almost doubled over the last 40 years.
Increases are most pronounced in white males,
though definitive evidence of causation remains elusive.
The age-specific incidence of testicular cancer is distinct
from that of other cancers.
The majority of incidence cases are diagnosed
between the ages of 20 and 40 years,
though a second much smaller peak occurs
after 80 years of age.
An even smaller peak occurs in infants.
Non-seminomas tend to occur prior to age 30,
whereas seminomas show a slightly larger age
of onset pattern.
Within nations, the incidence
of testicular cancer varies markedly by race
with African Americans, and other people of color
exhibiting extremely low rates in comparison
to white populations.
In the US, the incidence of testicular cancer in 2012
was about five times higher among white people,
than African Americans during 1975 to 2010.
Testicular germ cell tumor carrier types are characterized
by neotriploid with chromosome numbers ranging
from 50 to 70, as opposed to the typical diploid, 46.
That is in these germ cell tumors,
there are extra chromosomes.
There's also frequent appearance more than 50% of the time.
There's an isochromosomes of the short arm of chromosome 12,
called i(12p).
That's exhibited here on the slide.
Whereas for chromosome 12, rather than having one short arm,
and one long arm, it has two short arms.
The high chromosome number has been attributed
to the formation of tetraploid carcinoma in situ cells
followed by chromosomal losses that ultimately lead
to tumor forms that are more advanced.
There's a number of risk factors for testicular cancer.
One is cryptorchidism, or MDT, or maldescended testes.
In this case, the testicle lies
above the external inguinal ring, either
within the inguinal canal, or within the abdomen.
This is non-palpable in the anesthetized patient,
and the abnormality can be unilateral, or bilateral.
MDT is associated with a 2 to 4-fold increase
in the risk of testicular cancer,
with a population attributable risk of 10%.
Some studies have reported a relative risk
for testicular cancer associated with MDT in the range
of 5 to 10-fold.
And MDT prevalence has increased
in Denmark over the last 40 years.
There are striking differences
in testicular cancer incidents between Denmark and Finland,
despite their geographic proximity.
Recently, two large studies
have demonstrated large differences
between the two countries in the prevalence
of MDT at birth, and at three months of age.
Genetic lifestyle and environmental factors may be involved
in the etiology of MDT, and testicular cancer.
MDT can be treated by orchiopexy before the age of 10 years,
and rapid detection of MDT,
and timely surgical correction is essential
in lowering the risk of developing testicular cancer.
There also is a possible role of high endogenous estrogens
during gestation in the risk of testicular cancer.
Firstborn males may be at higher risk,
and fraternal twins may be
at higher risk than identical twins.
Males with a female co-twin may also be
at higher risk of testicular cancer,
though evidence is inconsistent for all of these cases.
Mumps can also lead to a higher rate of testicular cancer.
Mumps is a contagious disease of childhood,
and young adulthood, and it is spread by contact
with respiratory secretions.
Vaccinations do exist, and common symptoms are swelling
of salivary glands, orchitis, and epididymitis in males.
In a 1987 case control study, it was found
that mumps infection raises...
There are those with mumps infection
have a 5.8 times greater chance
of developing testicular cancer than those without mumps.
Other risk factors include in utero exposure
to diethylstilbestrol which we discussed
in a previous lecture.
While there's insufficient evidence to show that exposure
to DES in utero is a risk factor for testicular cancer,
it has been found
that there was a nonsignificant 3-fold increase in risk
in men exposed to DES in utero in one study.
However, this study only involves seven cases
of testicular cancer in the DES-exposed group.
There also potentially are maternal risk factors,
including late, or early age of pregnancy, prematurity,
low birth weight, congenital malformations,
and exposure to tobacco and alcohol
though evidence is inconsistent.
Occupational lifestyle, socioeconomic,
and other risk factors have demonstrated mixed associations
with testicular cancer.
Hormonal imbalance, that is high estrogens and low androgens
in various life stages may initiate testicular cancer.
Lifestyle and occupational exposures occurring later
in life may play a role in promoting the disease,
although they're not likely involved in cancer initiation.
In a case controlled study of non-seminoma testicular cancer
involving 163 cases, and 292 healthy controls, it was found
that marijuana use doubled the risk of testicular cancer,
but cocaine use reduced the risk,
suggesting that more studies are important.
We also see that testicular teratomas and yolk sac tumors
of prepubertal boys are rare.
The annual rate is 1.2 per million.
Though testicular teratomas are usually benign,
and curable by orchidectomy.
Yolk sac tumors typically show aneuploidy,
often tetraploidy, and have invasive malignant potential,
thus requiring combination therapy.
Again, mentioning that these tumors are related
to abnormal numbers of chromosomes.
That tetraploidy means having four copies
of the chromosome set as opposed to the typical two.
The identification and monitoring of individuals
with carcinoma in situ can lead to early detection
of testicular cancer, which is key to successful treatment.
It is possible that detection of testicular cancer
could eventually be aided by the identification of CIS
in younger adolescent males, since all cases of CIS
of the testis eventually progressed to cancer.
Thus mitigating the factors that cause carcinoma in situ
in preventing the progression of the CIS to invasive cancer,
may help in reducing testicular cancer incidents,
and increasing survival rates.
At present, surgical testicular biopsy
is the most common method
of diagnosing testicular carcinoma in situ.
Because of its invasive nature, biopsy is not suitable
as a screening tool,
and there are several new noninvasive technologies,
including scrotal ultrasonography,
and the analysis of semen for carcinoma in situ cells.
Due to the difficulty of diagnosing carcinoma in situ,
in apparently healthy men, it is not possible
to obtain a valid estimate of the prevalence of CIS
in the general population at this time.
Finally, treatment of testicular cancer usually
involves surgery, usually orchiectomy,
and retroperitoneal lymph node dissection,
depending on the stage of the cancer.
After surgery, the patient usually undergoes radiation
and, or chemotherapy.
And advances in treatment have led to an increase
in the five-year survival for testicular cancer,
during the last 30 years, from 63% to 90%.
Current research on testicular cancer treatment, focuses
on individualizing therapy for specific patients,
so that survival is not compromised.