Testicular Tumours

• Divided into germ cell and nongerminal (derived from the stroma or sex cord)
• 95% are germ cell tumours
• Most are highly aggressive that are capable of wide disseminated spread
• Most nongerminal tumours are benign but they can produce steroids leading to endocrinologic syndromes

 

Germ cell tumours

 

• Most commonly affect the 15 to 34 year old age group
• Germ cell tumours are;
  • Seminomas
  • Speramatocytic seminomas
  • Embryonal carcinoma
  • Yolk sac tumour
  • Choriocarcinoma
  • Teratoma

 

• In about 60% of patients there is a mixed of two or more histological patterns in the tumour
• Most tumours in this group originate from intratubular germ cell neoplasia (ITGCN)
• ITGCN  progresses to invasive germ cell tumour in 50% of cases over 5 years
• It is encountered with high frequency in the following conditions;
  • Cryptorchidism
  • Prior germ cell tumours
  • Strong family history of germ cell tumour
  • Androgen insensitivity syndrome
  • Gonadal dysgenesis syndrome
• ITGCN is seen adjacent to all adult germ cell tumours with exception of seminomas, epidermoid and dermoid cysts
• It is also rarely seen in paediatric tumours
• It is identified it is treated with low dose radiotherapy which destroys the germ cells but maintains androgen production of the Leydig cells

 

• Neoplastic germ cells may differentiate alone gonadal lines to become a seminoma or it may transform into a totipotential cell which may give rise to a nonseminomatous tumour.
• Such a nonseminomatous tumour may remain undifferentiated to form a embryonal carcinoma
• Or it may differentiate along extraembryonic lines into a yolk sac tumour of choriocarcinoma
• Teratomas result from differentiation of the embryonal carcinoma along the lines of all three germ cell layers

 

• Clinically the most important distinction to make is between seminomas and nonseminomatous tumours

 

Pathogenesis

 

• Predisposing influences in developing germ cell tumours;
  • Cryptorchidism – 10% are associated with undescended testes. The higher the testes are (intra-abdominal vs inguinal) the greater the risk
  • Testicular dysgenesis – highest risk with testicular feminisation. Also Klinefelter syndrome
  • Genetic factors – sibs of affected individuals have a ten times higher risk of developing testicular cancers

 

Seminomas

• Most common germinal cancer tumour – 50%
• Peak occurs in the thirties
• An identical tumour arises in the ovary called dysgerminoma
• Morphology
  • Produce bulky masses sometimes 10 times the size of the normal testes
  • Usually homogenous, grey, lobulated and not associated with haemorrhage or necrosis
  • In more than half of cases the whole testis is replaced
  • Generally the tunica albuginea is not penetrated but extension to the epididymis, spermatic cord or scrotal sac occurs
  • Microscopically the uniform sheets of cells are divided into poorly demarcated lobules
  • The classical seminoma cell is large and round and has a distinct cell membrane, a clear cytoplasm and a large central nucleus with two prominent nucleoli
  • Classically they do not contain AFP or HCG but stain positively for placental alkaline phosphatase
  • In about 15% of seminomas there is also syncytiotrophoblasts – in this case they do produce small amounts of HCG

 

Spermatocytic Seminoma

• Uncommon – 1% of all testicular germ cell neoplasms
• Affected individuals are generally over 65
• It is a slow growing tumour which rarely metastases
• Morphology
  • Larger than seminomas with a pale grey, soft cut surface often with mucoid cysts
  • They consist of a mixed cell population of medium sized, small and giant cells
  • The name come from the fact that in some of the medium sized cells the chromatin is similar to that seen in the meiotic phase of non-neoplastic spermatocytes

 

Embryonal Carcinoma

• Occur mostly in the 20-30 age group
• They are more aggressive than seminomas
• Morphology
  • Smaller than a seminoma and doesn’t generally replace the entire testes
  • It is generally poorly demarcated and associated with foci of haemorrhage or necrosis
  • It can extend through the tunica albuginea into the epididymis or cord
  • Histologically the tumour shows sheets of undifferentiated cells as well as primitive glandular structures
  • The cells are anaplastic with hyperchromatic nuclei

 

 

 

Yolk sac Tumour

• Also called infantile embryonal carcinoma or endodermal sinus tumour
• It is the most common testicular tumour in children below the age of 3 and in this age group it has a very good prognosis
• In adults the pure form is rare instead it is frequently found in combination with embryonal carcinoma
• Morphology
  • Nonencapsulated tumour with a homogenous, yellow, mucinous appearance
  • Microscopically consists of a reticular network of cuboidal or elongated cells which may form papillary structures or cords
  • In 50% of tumours structures resembling endodermal sinuses may be seen (Schiller-Duval bodies) these consist of a mesodermal core with a central capillary and a parietal layer of cells resembling primitive glomeruli
  • Staining with AFP is characteristic

 

Choriocarcinoma

• Highly malignant
• Composed of both cytotrophoblastic and syncytiotrophoblastic cells
• Identical tumours may occur in the ovary or placenta
• Rare – less than 1% of all germ cell tumours
• Can also occur with a mixed pattern
• Morphology
  • Generally small, often causing no testicular enlargement
  • Because they are rapidly growing they may outgrow their blood supply and sometime the primary testicular focus is replaced by a small fibrous scar leaving only widespread metastases
  • Haemorrhage and necrosis are common
  • Syncytiotrophoblasts produce HCG

 

Teratomas

• A group of complex tumours having cellular or organoid components resembling normal derivatives from more than one germ layer
• More common in children than adults (in adults constitute 3% of all germ cell tumours)
• They are often found combined with other histological types
• In children pure forms of teratoma behave relatively benignly
• In the postpubertal male all teratomas are regarded as malignant and capable of metastases regardless of whether the elements are mature or immature
• Morphology
  • Large, heterogeneous, solid, sometimes with cartilaginous and cystic areas
  • Haemorrhage or necrosis generally indicates a mixture with embryonal carcinoma or choriocarcinoma
  • Can contain;
    • Neural tissue
    • Muscle bundles
    • Cartilage
    • Squamous epithelium
    • Structures reminiscent of thyroid gland
    • Bronchial or bronchiolar epithelium
    • Intestinal wall
    • Brain substance
  • The dermoid cysts and epidermoid cysts that are common in the ovary are rare in the testes
  • Rarely within the teratoma there may be malignant transformation in one or more of the derivatives of the germ cell layers and may result in a squamous cell carcinoma or adenocarcinoma.
  • The importance of recognising these non-germ cell malignancies derived from teratomas is that if they spread out of the testes they are resistant to chemotherapy

 

Mixed tumours

• Account for 60% of testicular tumours
• Carry a worse prognosis
• Common combinations include;
  • Teratoma, embryonal carcinoma and yolk sac tumour
  • Seminoma with embryonal carcinoma
  • Embyronal carcinoma and teratoma

 

Clinical features of testicular tumours

• Clinically testicular tumours are segregated into two broad categories; seminomas and nonseminomatous germ cell tumours (NSGCT)
• NSGCT as well as including tumours of a single cell type also includes those of a mixed phenotype
• Determines therapy
• Presentation is generally with a painless mass
• All testicular masses should be considered malignancy until proven otherwise
• As biopsy can result in tumour spillage into the scrotal skin, the standard management of a solid testicular mass is radical orchiectomy based on the presumption of malignancy

 

Mode of spread

• Lymphatic spread is common to all forms of testicular tumour
• Retroperitoneal para-aortic nodes are the first to be involved with further spread occurring to the  mediastinal and subclavian nodes
• Haematogenous spread commonly occurs to the lungs. Liver, brain and bones may also be involved
• Histologically the metastases may differ from the tumour of origin as they are derived from totipotent cells

 

Clinical difference between seminomas and NSGCT

 

 

Three clinical stages of testicular tumours;

• Stage I – confined to testis, epididymis or spermatic cord
• Stage II – distant spread confined to retroperitoneal nodes below the diaphragm
• Stage III – metastases outside the retroperitoneal nodes or above the diaphragm
• Stages II and III are further subdivided into early or advanced

 

Germ cell tumours after secrete polypeptide hormones and detectable enzymes, including;

• a-fetoprotein (AFP) – associated with yolk sac tumour
• Human chorionic gonadotrophin (HCG) – choriocarcinoma tumours
• Placental alkaline phosphatase
• Placental lactogen
• Lactate dehydrogenase (also produced by skeletal and cardiac muscle)
• Elevated levels of these markers are most often seen in nonseminomatous tumours

 

• Seminomas have the best prognosis – 95% of patients with Stage I or II disease can be cured
• Among the nonseminomatous tumours, they all have a similar prognosis so are treated as a group. 90% can be cured with chemotherapy
• Pure choriocarcinoma has the worst prognosis

 

Tumours of the Sex cord/gonadal stroma

 

• Include;
  • Leydig cell tumours derived from the stroma
  • Sertolic cell tumours derived from the sex cord

 

Leydig (Intersitial) cell tumours

• Can produce androgens, oestrogens or corticosteroids
• Occur between 20 and 60
• Most common presenting feature is testicular swelling
• Gynecomastia may present
• In children hormonal abnormalities such as sexual precocity can dominate
• Morphology
  • Form well circumscribed nodules of a characteristic golden brown colour with an homogeneous cut surface
  • Most are benign but 10% metastasise

 

Sertoli cell tumours (Androblastomas)

• May be composed entirely of Sertoli cells or may contain some granulosa cells
• May produce endocrinologic changes by producing oestrogens and testosterones but not usually enough to cause precocious masculinisation or feminisation
• May present with gynecomastia
• Morphology
  • Small, homogenous, white/yellow nodules
  • Form cordlike structures resembling immature seminiferous tubules
  • Mostly benign – 10% metastasise

 

Gonadoblastoma

• Rare tumours containing a mixture of germ cells and gonadal stromal element
• Almost always arising in dysgenetic gonads
• The germ cell component may become malignant giving rise to an invasive seminoma

 

Testicular lymphoma

• Accounts for 5% of testicular neoplasms
• Most common form of testicular neoplasm in men over 60
• In most cases disseminated disease has already occurred by the time of detection of testicular mass
• Histologically it is generally a diffuse large cell lymphoma
• Prognosis is very poor