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Testicular Tumours |
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Testicular tumours are common in early adult
life.
Tumours of the testis are important, as they account for a high proportion of
tumours seen in early adult life; they are particularly significant in those
aged between 20 and 45 years.
The two main groups of testicular tumours are:
germ-cell tumours (97% of all cases), which are derived from the multipotential
germ cells of the testis, arising as teratomas and seminomas; and
sex-cord stromal tumours (3% of all cases), which are derived from the
specialized and non-specialized support cells of the testis.
In the WHO classification a rigorous definition of teratoma is adopted, in that
a teratoma is considered to be composed of somatic differentiated elements
(endoderm, mesoderm, ectoderm). Tumours composed of undifferentiated cells are
termed 'embryonal carcinomas' and are regarded as more primitive than a teratoma.
Tumours with differentiation to extraembryonic tissues (trophoblast and yolk
sac) are not considered conceptually to be teratomas.
In both systems there is a concept of a mixed germ-cell tumour in which several
different patterns of differentiation are seen. In the British classification
the combination of undifferentiated and differentiated teratoma is termed
'malignant teratoma intermediate (MTI)'; this would be regarded as a mixed
tumour in the WHO system (mixed embryonal carcinoma and teratoma). For this
reason, if the WHO system is applied rather than the British, the incidence of
so-called mixed germ-cell tumours is higher.
In the British classification any pure germ-cell tumour that is not a seminoma
is classed as a type of teratoma. Tumours composed of totipotent
undifferentiated cells are regarded as poorly differentiated teratomas, which
are termed 'malignant teratoma undifferentiated' (MTU).
Seminoma may be found in association with other germ-cell elements, forming
mixed germ-cell tumours
Seminoma of the testis is composed of cells resembling spermatogenic tissue
Seminoma of the testis is the most common malignant testicular tumour,
accounting for about 50% of all malignant germ-cell tumours. It is most common
in those aged between 40 and 50 years, characteristically presenting with a
painless, progressive enlargement of one testis; bilateral involvement is rare.
Macroscopically the normal, pale brown testicular tissue is replaced by a
homogeneous creamy white tumour mass. In contrast to other types of germ-cell
tumour, there is no evidence of cyst formation or haemorrhage; necrosis occurs
only in the largest, neglected tumours.
The most common histological type of seminoma is termed classic seminoma.
Histologically these tumours are composed of sheets of regular, tightly packed
cells that have small, dark-staining central nuclei and clear cytoplasm. A
characteristic feature is the presence of fibrous septa, in which numerous
lymphocytes are found. Seminoma shows immunoreactivity for placental alkaline
phosphatase (PLAP).
Other histological variants of seminoma include anaplastic seminoma,} in which
the cells show marked pleomorphism and increased mitotic activity and
spermatocytic seminoma,} which is composed of larger than normal tumour cells
with central, round, dark-staining nuclei and abundant eosinophilic cytoplasm;
some small cells, which resemble spermatocytes, are also present. This variant
tends to occur in patients over the age of 50 years and has a better prognosis
than classic seminoma and anaplastic seminoma.
Seminomas with trophoblastic (human chorionic gonadotrophin-containing) giant
cells} are encountered in 10% of cases, but the biological relevance of the
trophoblastic tissue is uncertain. Such tumours may be associated with increased
blood levels of human chorionic gonadotrophin (HCG) secreted by trophoblast.
Seminoma may be found in association with other germ-cell elements, forming
mixed germ-cell tumours.
Non-seminomatous germ-cell tumours are classified according to their
histological pattern
In the WHO classification the termembryonal carcinoma is used to describe
tumours composed of undifferentiated germ cells, whereas the British system
classifies them as MTU. As noted earlier, there is not an exact parallel, as
definitions of the term 'teratoma' vary, particularly affecting the equivalence
of the term 'mixed tumour'.
Testicular tumours composed entirely of mature somatic elements behave in a
benign fashion
Testicular germ cell tumours composed of fully differentiated somatic tissues
are the least common of the teratoma variants. Usually seen in young children,
these are true teratomas (teratoma differentiated, mature teratoma), with
representatives of all three embryonic layers present; all tissues are well
differentiated and fully matured, so that a wide range (e.g. skin, hair,
cartilage, and bone) can be identified. These mature teratomas almost always
behave in a very benign way, but a thorough histological examination of each
tumour should be made in order to exclude the presence of undifferentiated
tissues.
Germ-cell tumours containing undifferentiated elements are common as pure
tumours, or mixed with other elements
Some testicular germ-cell tumours contain sheets of immature cells in solid,
tubular or papillary patterns. When in a pure form these tumours are termed 'MTU'
(British) or 'embryonal carcinoma' (WHO). These tumours tend to occur in those
between the ages of 20 and 30 years.
Macroscopically these tumours tend to have a variegated appearance, with fleshy
and necrotic areas. Histologically, cells are pleomorphic and there are
typically many mitoses.
In other germ-cell tumours, undifferentiated elements are seen in association
with differentiated somatic elements. These would be considered mixed germ-cell
tumours in the WHO classification, but are MTI in the British system.
Macroscopically these lesions have both solid and cystic areas, as well as areas
of necrosis centred on the undifferentiated elements. Germ-cell tumours composed
predominantly of undifferentiated cells often also contain yolk-sac tumour or
trophoblastic tissue.
Yolk-sac tumour is a form of highly malignant germ-cell tumour and secretes
alpha fetoprotein
One of the extraembryonic elements that may develop in a germ-cell tumour is
differentiation to resemble embryonic yolk sac (also called 'endodermal sinus
tumour'). This may be present in a pure form, particularly in children in the
first 3 years of life, but is more often encountered as a component of a mixed
germ-cell tumour, most commonly mixed with undifferentiated cells.
Yolk-sac elements have characteristic histological appearances, forming solid,
papillary and microcystic patterns. This type of germ-cell tumour can also be
identified by immunohistochemical detection of alpha fetoprotein (AFP), which is
also secreted into the blood and can be detected as a tumour marker.
These tumours are highly malignant and spread rapidly. When trophoblastic or
yolk-sac elements are seen in association with other elements, they confer a
worse prognosis.
Trophoblastic germ-cell tumours are highly malignant and secrete HCG}.
Testicular germ-cell tumours that are composed of trophoblast (choriocarcinoma
in the WHO classification, malignant teratoma trophoblastic in the British
system) contain recognizable syncytiotrophoblast and cytotrophoblast, as would
be seen in placental tissue. Tumours may be entirely composed of trophoblastic
tissue, or trophoblast may be seen as part of a mixed germ-cell tumour. This
element can be identified by immunohistochemical detection of HCG, which may
also be detected in the blood as a tumour marker.
Although seminomas may contain trophoblastic giant cells, this does not make
them mixed tumours, and the biological significance of their presence is
uncertain.
Seminomas tend to spread to nodes, whereas non-seminomatous germ cell tumours
tend to spread via the bloodstream
Seminomatous tumours tend to spread to lymph nodes in the iliac and para-aortic
groups, bloodstream spread being a late feature. In contrast, non-seminomatous
germ-cell tumours tend to spread via the bloodstream at an early stage, and in
some tumours (particularly trophoblastic germ-cell tumours) there may be
widespread metastases before the patient becomes aware of any particular
testicular enlargement. Metastatic disease may be widespread, but the lung is a
particularly common site. Nodal spread also occurs.
Prognosis in germ-cell tumours is related to histological type, as well as to
tumour stage. The prognosis in testicular teratoma has improved greatly since
the use of cytotoxic chemotherapy. In general, germ-cell tumours containing
trophoblastic, yolk sac and undifferentiated elements have the worst prognosis.
Sex-cord and stromal tumours of the testis are less common than germ-cell
tumours
Tumours may be derived from the non-germ-cell components of the testis (the
interstitial Leydig cells and the Sertoli cells), but these are much less common
than germ-cell tumours and account for about 5% of all cases. The testis may
also be a site for development of primary lymphoma.
Leydig-cell tumours (also termed interstitial cell tumours) may occur at any age
from childhood to late adult life. In childhood, tumours may cause precocious
development of secondary sexual characteristics; in adults they often cause loss
of libido and gynaecomastia, reflecting secretion of either testosterone or
oestrogen, or both. Macroscopically, tumours appear circumscribed and are
yellow. They are composed of cells that resemble normal Leydig cells. Although
the majority of tumours are benign, tumours over 5 cm in diameter, and those
with mitoses, may behave in a malignant fashion.
Sertoli-cell tumours (also called 'androblastoma') may arise at all ages,
including infancy, but have a peak incidence in the fourth decade. Typically,
tumours are well circumscribed and are composed of cells resembling the normal
Sertoli cells of the tubules. Most lesions are benign, but tumours with many
mitoses may behave in a malignant fashion.
Primary lymphoma of the testis is mainly seen after the age of 50 years. Tumours
are generally high-grade non-Hodgkin's lymphomas.
Spread of other tumours to the testis may be seen, particularly acute leukaemias. |
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