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Observations on 6,000 testicular tumors revealed the following: Testicular tumors constitute the fourth most common cause of deaths from neoplasia in the
age group of 15-34 years of age. There is a definite geographic, racial, and age
distribution. The cause of testicular tumors is unknown, but cryptorchidism,
trauma, infections, and genetic and endocrine factors appear to play a role in
their development. Germ cell tumors comprise the large majority of testicular
tumors and present one or more of 4 basic histologic patterns: seminoma,
embryonal carcinoma, choriocarcinoma, and teratoma. In 40% the tumors
show admixtures of 2 or more of these basic cell types. Tumors of specialized
gonadal stroma constitute about 6% of testicular tumors and consist of Leydig
cell, Sertoli cell, and granulosa-theca cell tumors, or admixtures of these. The
most important metastatic tumor of the testes is malignant lymphoma,
initially manifested as testicular tumor.
25 YEARS OF
personal experience and the opportunity
to observe over 7,000 testicular tumors registered in the Testicular Tumor Registry of
the American Registry of Pathology, sponsored by the American Urological Association
at the Armed Forces Institute of Pathology.
This discussion will cover the tumors of germ
cell origin and gonadal stromal tumors and
briefly mention some of the other tumors involving this organ.
HIS PRESENTATION IS BASED ON
EPIDEMIOLOGIC
FINDINGS
The incidence rate of testicular tumors in
the United States is 2.1-2.2 per 100,000
males;3 in Ontario, Canada, it is 2.5 per
100,000 males.l3 The U. S. Census Bureau attributed 0.64% of all male cancer deaths to
testicular tumors, while in England the comparable rate was 0.52y0.In the United States
and Canada, in the 15- to 34-year age group,
deaths from testicular tumors account for
11-13% of all cancer deaths, constituting the
fourth most common cause of death from neoplasia in this age group. A doubling of mortality from testicular tumors from 1944-1947
Presented at the Amcrican Cancer Society's National
Conference on Urologic Cancer, Washington, D. C.,
March 29-31, 1973.
From the Genitourinary Pathology Branch, Armed
Forces Institute of Pathology, Washington, D. C.
Address for reprints: F. K. Mostofi. MD, Armed
Forces Institute of Pathology, Washington, D. C. 20306.
Received for publication August 1, 1973.
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TESTICULAR
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than in a normally located testis. Miillerls reported that malignancy in undescended testes
is 10 times greater than in the testes that descended normally. It has been reported that 1
in 80 inguinal testes and 1 in 20 abdominal
testes will become malignant.10J9 It must be
remembered, however, that such studies are of
selected groups, e.g., hospital patients and soldiers, and may not be applicable to the general population. Attention should also be
called to the fact that a tumor may occasionally develop in a normally descended testis of
a patient with a contralateral undescended
testis.
Five factors may be operative in increased
incidence of testicular tumors in cryptorchid
testes: abnormal germ cells, elevated temperature, interference with blood supply, endocrine disturbances, and gonadal dysgenesis.
There is, however, no conclusive evidence as
to which of these factors is responsible for the
high incidence of tumors in such testes.
B. Age
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D. Infection
Many patients with testicular tumors have a
history of orchitis of some type, particularly
mumps. It is quite possible that a viral infection of the germ cell may trigger carcinogenesis.
E. Endocrine Abnormalities
A number of factors suggest a strong endocrine role in testicular tumors:16 (a) Induction
of teratomas in fowl by injection of zinc salts
occurs only during pituitary gonadotropin secretion; (b) the peak incidence in testicular
tumors in man is in the period of high androgenic activity; (c) gonadotropins and/or estrogens are produced by a number of testicular
tumors; (d) a number of patients with such tumors show elevation of pituitary gonadotropins, which persists even after orchiectomy; (e)
in tissue culture, androsterone accelerates
growth of certain tumors; and (f) the type of
tumor encountered in the testis varies with
the stage of maturation of the testis.
Testicular tumors are almost entirely limited to 3 age periods: infancy, late adolescence-young adulthood (20-35 years), and 50
years and over.16 The histologic pattern and
behavior of the tumor differ with each period.
For example, no seminomas have been reported in infants; embryonal carcinoma and
teratoma are the most common tumors of infants and children. Their morphological features are somewhat different, and their prognosis is much better than corresponding
tumors in adults. Seminoma, embryonal carcinoma, teratoma, and teratocarcinoma are common in young adults, but seminoma is more
frequent in patients in the fourth decade,
while spermatocytic seminoma and malignant
lymphoma occur in the older age group.
F. Genetic Factors
A high incidence of testicular tumors has
been reported in brothers, identical twins,
monozygous twins, and other members of the
same family. Miiller18 reported that in about
16% of the cases on which sufficient information was available there was a history of malignant disease in the nearest family. There
is also a high incidence of a second testicular
tumor in a patient with a testicular tumor.
C. Trauma
Many patients with testicular tumor give a
history of trauma, and Fergusons reported
that 11% of the 527 testicular tumors had
such a history. Experimental evidence also
suggests a relationship between tumor and
trauma. Trauma is considered a factor in zinc
or copper-induced testicular tumors and in experimental induction of such tumors by transplantation of the genital ridge.m.21 A heavy
and dragging tumorous testis may be susceptible to trauma, and aggravation of an existing
tumor by trauma may facilitate spread of the
tumor.
G. Abnormal Testes
The high incidence of testicular tumors in
dysgenetic testes would seem to suggest that
such testes are genetically abnormal, but
whether such testes are dysgenetic has not
been settled.
CANCERNovember 1973
1188
PATHOLOGIC
FEATURES
Other papers emphasize the fact that as yet
there is no clinically reliable classification of
testicular tumors and the urologist must depend on clinical stage and on histologic appearance of the tumor. Biopsy, generally
accepted for other sites, is absolutely contraindicated in testicular tumors. If a tumor is
suspected, the testis must be removed in toto.
From the pathologists point of view, it is esTABLE1. Pathologic Classification of Testicular
Tumors
~
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FIG. 2. Anaplastic
seminoma showing
moderate anaplasia of
cells and increased mitotic activity. At least
four mitotic figures
are seen (H & E. x250;
AFIP Neg. 5182).
ble amount of eosinophilic cytoplasm. Scattered in this sea are two other cell types, the
very small lymphocyte-like cells and the huge
mononuclear cells. The cells have a spherical
basophilic glassy nucleus surrounded by a distinct rim of eosinophilic cytoplasm. Giant
cells are usually mononuclear but occasionally
may be binucleated or multinucleated. The
nuclei are spherical, ovoid, or indented and
surrounded by a considerable amont of eosinophilic cytoplasm.
Masson15 called attention to the filamentous
or spireme-like arrangement of the chromatin
in the nuclei of intermediate and large cells
similar to that present in the meiotic phase of
normal primary spermatocytes. T h e chromatin also occurs in regular clumps, and the nuclear membrane is irregularly thickened. Moderate numbers of mitotic figures may be seen
in some fields, and some of these figures are
abnormal.
Typical seminoma has an excellent prognosis and, properly treated, should have a
95-96% 5-year survival. Spermatocytic seminoma also seems to have good prognosis. In
our experience, most of the seminomas that
metastasize and terminate fatally belong to
the category of anaplastic seminoma.
Seminoma usually spreads by the lymphatic
route. In our material, at autopsy, the most
No. 5
TESTICULAR
TUMORS Mostofi
1191
FIG.3. Spermatocytic
seminoma. In contrast
to Figs. 1 and 2, in this
tumor three cell types
are identified: large
cells, intermediate
cells, and small darkstaining cells (AFIP
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Vol. 32
FIG. 4. Embryonal
carcinoma of the testis. The tumor forms
glandular and tubular
structures (AFIP Neg.
73-5737; x 210).
(46%), bones of the trunk (21%), and gastrointestinal tract (18%). I n 96 7' of autopsy
cases the metastatic lesions are embryonal carcinomas. In 8% there are also associated areas
FIG. 5. Embryonal
carcinoma compared
to seminoma. Carcinoma cells (right) are
larger, more pleomorphic, and have an
a m p h o p h y l i c cytoplasm a n d a large
vesicular nucleus with
prominent nucleolus.
The cells form acini.
Seminoma cells (left)
are smaller and have
vacuolated cytoplasm
and small nucleus.
The cells are in lobules, and there are
scattered lym hocytes
(AFIP Neg. !3-5148;
x 210).
No. 5
yolk sac tumor, endodermal sinus tumor, adenocarcinoma of the infantile testis, juvenile
embryonal carcinoma, etc., and constitutes the
most common testicular tumor of infants and
children. It occurs in adults but usually as a
part of a teratocarcinoma. It is also the variant of embryonal carcinoma that is found in
the ovary.
i. Gross features: It has a homogeneous yellowish, mucinous appearance.
ii. Histologic features: T h e principal histologic pattern consists of anastomosing glandular and ductal structures lined by low columnar, cuboidal, or flat epithelium (Fig. 6).
These may form papillary structures, rows and
columns of cells, or solid areas. T h e large,
irregularly shaped nuclei have a variable chromatin distribution and one or more prominent nucleoli. T h e cytoplasm is usually vacuolated, and the cell borders are indistinct.
The cytoplasm contains considerable amounts
of fat, often refractile, as well as glycogen.
Fine or coarse vacuolization of the cells is
present. Some of these vacuoles coalesce to
form larger vacuoles that seem to merge with
the host vascular spaces.
T h e stroma varies in amount and ranges
from fibrous to cellular to primitive mesenchyme. Frequently it is difficult to distinguish
between stroma and the epithelial elements.
TESTICULAR
TUMORSMostofi
1193
Vascular invasion is not an infrequent finding, but while its presence suggests poor prognosis, a fatal outcome is not necessarily indicated. Careful examination of these tumors
will reveal some teratoid structures in almost
every tumor, usually consisting of a duct lined
by tall columnar epithelium, a nest of cartilage, or an epidermal cyst. In contrast to adult
embryonal carcinoma, which has a grave prognosis, infantile embryonal carcinoma has a 5year mortality of only SO%, and almost all
deaths occur within the first 18 months.16
In a number of embryonal carcinomas, organoid structures are seen that resemble embryos of 1-2 weeks gestation. They may be
spherical, lobular, or cylindrical. They usually
measure less than 1 mm in diameter and consist of a disc, a cavity, and a tubular form surrounded by loose mesenchyme in which syncytiotrophoblastic and cytotrophoblastic cells
may be seen. The disc consists of a single row
of large cells resembling epithelial cells. The
cavity, which simulates an amniotic cavity, is
lined by flattened epithelial cells. The tubular
structures resemble entoderm. Such structures
are found not only in embryonal carcinomas
but in teratocarcinomas also.
Since embryoid bodies are a stage in the development of embryonal carcinoma and since
they have a wide variation in morphological
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*
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FIG.8. Teratoma of
the testis showing
cystic spaces, some of
which are lined by
columnar epithelium
and others by squamous cells. Note islands
of cartilage (AFIP Neg.
73-4925; ~22).
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TESTICULAR
TUMORSMostofi
C. Other Tumors
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2. Auopardi, J. G., Mostofi, F. K.,and Theiss. E. A.:
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the human testis. A m . J . Pathol. 38:207-225, 1961.
3. Clarke, B. G.: The relative frequency and age incidence of principal urological diseases. J . Urol. 98:
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4. Clemmesen, J.: A doubling of morbidity from testis carcinoma in Copenhagen, 1943-1962. ~~t~ Pathof.
&ficrobiol. Stand. 72:34&349, 1968.
5. Dixon, F. J., and Moore, R. A.: Tumors of the
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TESTICULAR
TUMORS Mostofi
31b and 32. Washington, D. C., Armed Forces Institute of Pathology, 1952.
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8. Ferguson, J. D.: Tumours of the testis. Br. J . Urol.
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9. Friedman, N. B., and Moore, R. A.: Tumors of
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10. Gilbert, J. B., asd Hamilton, J. B.: Studies in
malignant testis tumors-incidence and nature of tumors in ectopic testes. Surg. Gynecol. Obstet.
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11. Grumet, R. F., and MacMahon, B.: Trends in
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12. Howden, P. F.: Carcinoma of the testicle. N . 2.
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13. MacKay, E. N., and Sellers, A. H.: A statistical
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1938-1961. Can. Med. Assoc. J . 94889-899, 1966.
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