The Male Reproductive Structures

Malignant Testicular Pathology

Testicular malignancies include primary testicular germ cell tumours, non-germ cell tumours, metastases, lymphoma and adrenal rest tumours.

Primary testicular malignancy comprises approximately 1% of malignancies in men, with an incidence of 3 : 100,000 per annum. This peaks between the age of 15 and 45 years, where it accounts for approximately 9% of deaths from malignant disease. The most publicised risk factor is cryptorchidism, which appears to be a factor in 10% of primary testicular malignancy. This increased risk persists after orchidopexy and includes an increased risk of malignancy in the normal contralateral testis in males with unilateral cryptorchidism. Other reported associations include mumps orchitis, testicular microlithiasis, infective orchitis and infertility. The risk of developing a further malignancy in the contralateral testis several years after initial treatment of testicular malignancy is 500 to 700 times the incidence in the normal population. At present there is no common policy regarding screening any of the at-risk populations, although there is an emerging consensus regarding microlithiasis, suggesting that routine surveillance is not indicated unless the patient has other associated risk factors. Interestingly, there is an unexplained rising incidence and geographical variation to testicular malignancy. An incidence of 8 : 100,000 is reported in Denmark compared with 2 : 100,000 in Israel.

Testicular tumours usually present with a painless, unilateral, scrotal mass noticed by the patient on self-examination. Approximately 10% present with acute pain thought to be caused by haemorrhage. A small group present with metastases from an undeclared primary mass, which may be demonstrated by US when still clinically impalpable. In this setting the reported negative predictive value of 100% for excluding testicular malignancy is reassuring but should be considered in the light of a recent report of US-negative intratubular germ cell neoplasms discovered at orchiectomy in patients with the rare presentation of paraneoplastic meningitis.

Approximately 95% of primary testicular tumours are of germ cell origin, the remainder arising from Leydig, Sertoli or theca cells that comprise the gonadal stroma. Most germ cell tumours are of single histological type and are seminomas. In order of frequency, other histological types comprise embryonal tumours, yolk sac tumours and teratomas. Approximately 40% of tumours are of mixed cellularity. The peak incidence of seminoma is in the fourth and fifth decades, while the incidence of other germ cell tumours peak approximately a decade earlier. All testicular tumours are rare in childhood where yolk sac tumours, followed by teratomas, are the most common. Seminomas are generally extremely radiosensitive; they are associated with high levels of alpha-fetoprotein (AFP) but less often with human chorionic gonadotrophin (hCG). Teratomas respond well to a number of chemotherapeutic agents and are associated with elevated AFP and hCG. They are characteristically less responsive to radiotherapy.

The differentiation of seminoma from the other histological types is important clinically but despite some variation in the ‘textbook’ appearances, there are generally insufficient features to make the distinction using direct imaging or Doppler features. Seminomas are characteristically hyporeflective compared with the surrounding parenchyma and are well defined and homogeneous ( Fig. 33.2 ). They may also be apparently multifocal on presentation. The typical embryonal cell tumour is less homogeneous and well defined, while teratomas are of mixed reflectivity and more likely than seminoma to contain cystic spaces and calcifications ( Fig. 33.3 ).

Increased tumour flow on Doppler sonography is common but not invariable and in practice this cannot be used to differentiate neoplastic from non-neoplastic, benign from malignant or one cell type from another.

Staging Testicular Malignancy

Testicular tumours extend into the surrounding testicular parenchyma and from the mediastinum testis to the epididymis. The lymphatics accompany the venous drainage to retroperitoneal nodes at the level of the renal hila. The local inguinal nodes are not typically involved unless there has been invasion of the scrotal wall. Current best practice suggests the use of CT to assess the retroperitoneal and mediastinal lymph nodes. MRI of the retroperitoneum is feasible but, as yet, has not been widely adopted owing to cost and, instead, serves a role in selected patients in whom repeat CT examinations may be undesirable due to radiation dose or previous contrast medium reactions or in those patients where CT is inconclusive. ¹⁸ F-Fluorodeoxyglucose positron-emission tomography (FDG PET) or FDG-PET/CT examinations do not form part of the diagnostic algorithm for initial staging but may be helpful in the evaluation of residual disease after chemotherapy ( Figs 33.4 and 33.5 ).

Computed Tomography

Although a chest radiograph will demonstrate the larger pulmonary and mediastinal metastases, CT reliably demonstrates pulmonary lesions of 3 to 4 mm in diameter. These are frequently peripheral (subpleural and basal—in line with maximal ventilation and perfusion) but no lung segment is exempt. In the relatively younger age group susceptible to testicular malignancy, pulmonary lesions that may mimic lung metastases, such as old granulomata, are not common. Nevertheless, care should be taken before assuming that a lung lesion is a metastasis, especially in the absence of mediastinal lymphadenopathy. Mediastinal deposits are less common than pulmonary metastases, but care should be taken in the subcarinal region. It is debatable whether iodinated intravenous contrast enhancement should be used routinely; however, close attention should be paid to the mediastinum at soft-tissue settings. Unexpected lesions in the hila or mediastinum with absent tumour markers, favourable histology and a normal retroperitoneum should raise the possibility of coincidental disease such as sarcoidosis. Current guidelines indicate that supraclavicular lymph nodes should be assessed by means of physical examination rather than CT.

Abdominopelvic CT offers a sensitivity of up to 93% in determining involvement of the retroperitoneal nodes, with potential for understaging identified more commonly in stage 1 and 2 disease. There are known pitfalls in the evaluation of the aortic chain due to issues such as underfilled bowel loops and anomalous venous anatomy. Nevertheless, the spread of testicular malignancy is predictable. Left-sided lesions spread to the upper left para-aortic chain closer to the left renal vein than the aortic bifurcation ( Fig. 33.6 ). Metastases from right-sided lesions tend to be situated slightly more caudal and are usually seen in the anterior interaortocaval recess ( Fig. 33.7 ). Right-sided lesions may, however, be situated at a more superior level and, when located just posterior to the third part of the duodenum, can prove problematical to the surgeon should resection of a residual mass be required.

Only when nodal disease is well established on the ipsilateral side does crossover to the contralateral side and inferior spread to the inguinal nodes occur. Isolated contralateral lymphadenopathy should be viewed with extreme suspicion. Isolated pelvic disease is slightly more common but still rare in uncomplicated testicular tumours. Naturally, it can occur where there has been previous testicular maldescent or scrotal involvement. The whole pelvis should be examined at initial staging, but it is controversial whether this needs to be undertaken at follow-up in straightforward cases; radiation dose is a consideration in these usually young patients. Other examinations such as brain or spinal CT, bone scan or liver US should be performed if there is suspicion of metastases to these organs.

The accurate staging of testicular malignancy is important and can influence treatment options with radiotherapy or chemotherapy and the follow-up surveillance period. The radiological findings should be considered with other diagnostic features such as cell type and tumour markers. If staging uncertainty persists, a limited repeated CT study at a short time interval of 6 to 12 weeks can often resolve the matter. Any lung nodules or para-aortic nodes may have enlarged in the interim and involvement can be assumed.