Testicular Tumours

More than 95% of testicular tumours arise from the germ cells. Of this 95%, about 45% are seminomas and 50% are non-seminomas. The non-germ cell tumours include Leydig's cell tumours, Sertoli's cell tumours and sarcomas.

Testicular tumours are now considered to be the extreme end of the spectrum of a range of testicular conditions which comprise testicular dysgenesis syndrome.¹ It is thought that this syndrome is related to environmental factors,occurring in fetal life.²

On several occassions in this article levels of evidence are given. For an explanation the reader is referred to the article on different levels of evidence or the SIGN guidelines.³

British Testicular Tumour Panel Classification:^3,4

• Seminomas (~45% of total).
• Teratomas (~50% of total) subdivided into:
  • Teratoma differentiated
  • Malignant teratoma intermediate
  • Malignant teratoma undifferentiated
  • Malignant teratoma trophoblastic (choriocarcinoma is the most lethal form and it is the least common at 1% of the non-seminomatous type)
• Yolk sac tumour.

Yolk sac tumours are also known as endodermal sinus tumours and are the most common prepubertal germ cell tumours.They may be benign but they are most often malignant. Most require surgery and chemotherapy because of their aggressive nature but the overall prognosis is excellent.

• They are the most common malignancy in men aged between 20 and 30 years.
• The incidence is increasing but they are still rare. It is 7.5 per 100,000 men in the UK per year representing about 1,400 new cases per year.³
• The peak incidence for teratomas is 25 years and seminomas is 35 years.

Risk Factors

Risk factors include:^3,5,6,7

• Cryptorchidism or testicular maldescent.
• Klinefelter's syndrome.
• Family history.
• Male infertility (increases risk by a factor of three).⁸
• Low birth weight, young maternal age, young paternal age, multiparity, breech delivery.⁹
• Infantile hernia.
• Height - taller men are more at risk of developing germ cell tumours.¹⁰
• Testicular microlithiasis (small intratesticular calcifications seen on ultrasound).¹¹

Of the many factors associated with the risk of developing germ cell tumours of the testis, cryptorchism and malignancy in the contralateral testis are by far the strongest. The risk of cancer developing in the contralateral testicle is 5% but it is said that this should be managed by observation rather than biopsy as results are good if it is caught early. The malignancy risk in men with cryptorchidism is 2 to 4% and the risk in patients with subfertility is 1% or less. This is why if an undescended testis has been left too long and it will be of no value for reproduction it should be excised.

Cryptorchism and low sperm counts are becoming more common and this may account for the rising incidence but there is no obvious explanation for why this should be happening.

Genetic Factors

Many malignancies are due to genetic damage. This genetic damage may be caused in the intrauterine environment for tumours of testis and breast.¹² Virtually all testicular tumours display an abnormality on chromosome 12.^13,14 Up to 20% of men may carry the testicular germ cell tumour 1 (TGCT1) gene on their X chromosome.¹⁵ Possession of this gene may increase risk of testicular malignancy by up to 50 times. It may also be involved in families with a history of cryptorchism and families of men who develop bilateral disease are also more likely to carry this gene.¹⁶

Symptoms

• Painless lump 86%.
• Pain 31%.
• Dragging sensation 29%.
• Recent history of trauma 10%. It is probably the trauma that leads the man to examine himself and find the tumour rather than being the cause of malignant change.
• Hydrocoele.
• Gynaecomastia from βhCG production.
• Metastasis - seminomas metastasise to para-aortic nodes and produce back pain; teratomas undergo blood-borne spread to liver, lung, bone and brain.

• A lump is palpable in 97% of cases.
• Whereas the normal testis is rather delicate and the inflamed testis is very tender, the malignant testis tends to lack the normal level of sensation.
• Lymphatics from the scrotum drain to the inguinal nodes but from the testes they go deeper. Hence, inguinal lymph nodes are unlikely to be enlarged.

• Epididymo-orchitis.
• Torsion.
• Lymphoma.
• Other scrotal lumps, e.g. hydrocoele, haematocoele, epididymal cyst, hernia.
• Infection, e.g. tuberculosis, syphilis, mumps.
• Other non germ cell testicular tumours including Leydig's cell tumours, Sertoli's cell tumours and sarcomas.

Patients should be referred urgently and seen within 2 weeks if malignancy is suspected. (SIGN level of evidence C and NICE referral criteria).

• Diagnosis is usually confirmed by ultrasound.
• Tissue histology can follow an inguinal orchidectomy.
• Disease can be staged by thoraco-abdominal CT scanning.
• Tumour markers are useful in staging and assessing response to treatment.
• Alpha-fetoprotein (αFP) is produced by yolk sac elements but not produced by seminomas.
• Beta-human chorionic gonadotrophin (βhCG) is produced by trophoblastic elements and so may be elevated levels in both teratomas and seminomas.
• LDH should be measured.
• Tumour markers are present in 75% of teratomas.³

Royal Marsden staging of testicular tumours:⁴

• Stage I - disease confined to the testis.
• Stage IM - as Stage I but with tumour markers rising after operation.
• Stage II - para-aortic lymph node involvement with further division into Stage IIA with nodes <2 cm in diameter, Stage IIB with nodes 2-5 cm and Stage IIC with nodes >5 cm in diameter.
• Stage III - the disease has spread above the diaphragm with further subdivision into A, B and C as for Stage II.
• Stage IV - extra lymphatic metastases.
• Stage L1 - <3 lung metastases.
• Stage L2 - >3 lung metastases but all <2 cm diameter.
• Stage L3 - >3 lung metastases with 1 or more >2 cm in diameter.
• Stage H+ - liver metastases.

This is slightly different from the system used by SIGN and the Royal College of Radiologists in that they add a Stage D to para-aortic nodes. 5 to 10 cms is grade C and over 10 cms is grade D.

Management is dependent on type of tumour and stage (see SIGN guidelines for individual treatment recommendations.) The treatment of advanced testicular germ cell tumors with combination chemotherapy is based on risk stratification (good, intermediate, or poor prognosis) according to pretreatment clinical features of prognostic value. Approximately 90% of patients classified as having a good prognosis achieve a durable complete remission with treatment.¹⁷ Even metastatic disease should be seen as potentially curable.¹⁸ When treating young adults with a highly curable disease, possible long-term toxicity of treatment is an important consideration.¹⁹

Seminomas

Seminomas are radiosensitive:

• Removal of primary tumour by inguinal orchidectomy.
• Stage I and II disease treated by inguinal orchidectomy plus radiotherapy to ipsilateral abdominal and pelvic nodes or surveillance .
• Stage IIC and beyond are treated with chemotherapy (often cisplatin, etoposide and bleomycin).
• Tumour markers are less reliable.

Teratomas

Teratomas are not radiosensitive:

• Removal of primary tumour by inguinal orchidectomy.
• Chemotherapy for any who relapse or have metastasis at presentation (cisplatin, bleomycin and etoposide is standard regime).
• Surveillance.
• Tumour markers.

Where retroperitoneal lymph nodes remain enlarged after surgery and chemotherapy, their surgical removal is usual. This is a major operation but a laparoscopic approach may be welcome. However, NICE recommends that the advantages of laparoscopy are not proven and it should be reserved for specialist centres involved in trials.²⁰

Other

• Counselling and support organisations.
• Fertility issues and sperm storage (semen quality is reduced after orchidectomy and samples should be taken before surgery).²¹
• Testicular prosthesis should be offered to all patients (SIGN evidence level C).

• Detect relapse.
• Monitor and treat toxicity.
• Detect contralateral cancers.
• Longer-term follow-up for metastatic teratomas.
• Stage I teratomas and seminomas may be discharged after 5 years' follow-up.
• If there is relapse, salvage chemotherapy is curative in 25% of cases.³

• 5% of men with testicular cancer have carcinoma in situ of the opposite testicle.
• Infertility may precede treatment or result from it.
• Treatment toxicity of radiotherapy.
• Treatment toxicity of chemotherapy.
• Short-term (e.g. neutropaenia, nausea and vomiting, alopecia, fatigue and sepsis).
• Long-term (e.g. lung damage with bleomycin, nerve, hearing and renal damage with cisplatin, avascular necrosis).

Dependent on stage, tumour type and presence of low, medium or high levels of markers.³

• Seminoma is highly curable when detected early. The 5-year survival is around 95% with Stage I disease and 85 to 90% with Stage 2 disease.
• For non-seminomatous germ cell tumours, the results are less favourable, with a 5-year survival rate of 86% for Stage I disease. The corresponding survival rate for teratocarcinomas is only 70%.
• Choriocarcinoma has a dismal prognosis, with nearly no patients surviving 5 years after their presentation. Choriocarcinomas have the worst prognosis of any of the testicular malignancies.

Routine ultrasound to detect early cases does not fit the criteria required of a screening technique.⁷ Public information campaigns have encouraged men to check themselves in the shower (SIGN evidence level C).

They tend to be rather different in biological and pathological terms from the picture in adults. In a series from India²² the mean age at presentation was 6.7 months (range 1 to 18 months) with the mass having been noted at birth in 3 infants. Serum AFP was elevated preoperatively in only one case. The report was of 5 cases, showing how rare is the condition. There had been 20 cases of testicular cancer in children over 12 years, of which only 5 (25%) were teratomas. At the time of writing, all these children were doing well with no evidence of residual or recurrent disease at a mean follow-up of 4.7 years (range 4 months to 11 years). In view of the high incidence of non-malignant tumours, the recent tendency has been to perform testicular-sparing surgery.²³