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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