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The male reproductive system includes the testes with their related duct systems, the prostate and the penis. These organs are responsible for the production, storage and periodic emission of the male gametes, spermatozoa, as well as the production of male sex hormones, principally testosterone. The organs of this system are prone to the full range of pathological conditions seen in other organ systems. However, clinically, the most important pathological conditions are inflammation (mainly caused by infection) and tumours.
Inflammation of the testis (orchitis) may result from viral infections, for example mumps; the testis may also be the site of a gumma in the tertiary stage of syphilis (see Fig. 5.11 ). Other bacterial infections usually arise as a complication of infection of the lower urinary tract or following surgical instrumentation. A non-infective cause of testicular inflammation is granulomatous orchitis , which may follow an episode of trauma to the testis. Focal granulomatous inflammation, known as sperm granulomas , may also occur because of sperm retention, for example after vasectomy. Venous infarction of the testis owing to torsion is an important cause of testicular pain in childhood and young adulthood and is illustrated in Fig. 19.1 .
The most important pathological lesions of the testes are tumours, most of which are derived from germ cells; a system of classification is shown in Table 19.1 and examples are illustrated in Figs 19.3 to 19.7 .
|Tumour type||WHO (2016) classification|
|Germ cell tumours derived from GCNIS|| Seminoma
Teratoma (post pubertal type)
Yolk sac tumour (endodermal sinus tumour)Choriocarcinoma
|Germ cell tumours not derived from GCNIS|| Spermatocytic tumour
Pre pubertal teratomas, e.g. epidermoid cyst
|Combination of two or more of any type||Mixed germ cell tumour|
Like the testis, the epididymis may become infected by pyogenic bacteria, associated with lower urinary tract infection and/or surgical instrumentation. When infection occurs, usually both the testis and epididymis are involved, a condition known as acute epididymo-orchitis . The epididymis is occasionally the site of disseminated tuberculous infection, tuberculous epididymitis , usually secondary to active pulmonary or renal tuberculosis.
Testicular tumours may arise in any of the normal components of the testis, but by far the most common are the germ cell tumours , thought to be derived from multipotential germ cells of the seminiferous tubules. Most testicular germ cell tumours are thought to arise from a pre-malignant change in the cells lining the seminiferous tubules known by the term germ cell neoplasia in situ (GCNIS) . Foci of GCNIS are commonly found in the testis adjacent to tumours. These (with the exception of the rare spermatocytic tumour) are highly malignant tumours in young men, which may be cured by a combination of surgery and modern chemotherapy regimens. Most countries now use the current World Health Organization (WHO) classification to subtype tumours. Approximately two-thirds of testicular tumours contain elements of two or more different tumour types, for example seminoma plus embryonal carcinoma . There are some similarities between testicular and ovarian germ cell tumours, but it should be remembered that most ovarian germ cell tumours are mature teratomas (dermoid cysts) and behave in a benign fashion, whereas most germ cell tumours in males are malignant.
Testicular germ cell tumours can be broadly divided into two main groups and this is an important distinction as the two groups are treated differently:
Seminoma: This tumour type consists of malignant cells resembling the normal cells lining the seminiferous tubules ( Fig. 19.3 ).
Non-seminomatous germ cell tumours: This group includes a variety of tumours that exhibit differentiation towards embryonal or extra-embryonal structures ( Figs 19.4 to 19.6 )
In the current WHO classification, tumours are divided into those derived from GCNIS and those not derived from GCNIS. Only the main subtypes are shown in Table 19.1 . A small proportion of testicular tumours arise from the other cells in the testes, for example Leydig cell tumours and Sertoli cell tumours; the majority of these tumours are benign but they may secrete inappropriate sex hormones. In older men, the most common tumour of the testis is lymphoma , usually in association with lymphoma at other sites in the body. Rarely, a testicular mass may be the first indication of lymphoma. Testicular lymphomas are almost always non-Hodgkin diffuse large B cell lymphomas (see Ch. 16 ).
E epididymis N neoplastic germ cells S Sertoli cells T testis
C cartilage D Schiller–Duval body E epithelial structure G glandular structures M primitive mesenchyme R reticular pattern S septum T tubular structures
The prostate gland ( E-Fig. 19.5 H ) undergoes benign nodular hyperplasia (hypertrophy) in almost all men from middle age onwards, probably because of an alteration in hormone balance. This important lesion, shown in Fig. 19.8 , produces obstruction to bladder outflow as a result of pressure on the prostatic urethra; in turn, the obstruction may produce pressure effects on the proximal conducting system of the urinary tract, leading to hydroureter and hydronephrosis with pressure atrophy of the renal parenchyma. Prostatic hyperplasia also predisposes to infection and stone formation.
Invasive carcinoma of the prostate is a common and important malignant tumour in men and is illustrated in Fig. 19.10 . Carcinoma of the prostate may be associated with dysplasia of the glandular epithelium. This has been named prostatic intraepithelial neoplasia (PIN) and is shown in Fig. 19.9 . The prognosis of carcinoma of the prostate can be predicted by careful grading and staging. Staging takes into consideration the size (volume) of the tumour, the degree of spread within the prostate, extension beyond the prostate and lymph node and distant metastases. Perineural and vascular invasion also contributes to assessment of prognosis. Some of these features may only be determined in radical prostatectomy specimens whereas others can be assessed on core biopsies. Imaging is also important for the detection of distant metastases, for example to bone. Small foci of low-grade tumour that are not palpable may be found in prostates removed for benign hyperplasia. Most of these tumours progress too slowly for them to cause clinically significant disease in elderly patients and, for this reason, are often called latent carcinomas .
A acinus C corpora amylacea Ca immature cartilage D high-grade PIN E normal epithelium Em embryonal carcinoma H hyperplastic prostate nodule M fibromuscular connective tissue N compressed peripheral glands P papillary fold Sem seminoma
Screening for disease is dependent on the principle that early detection increases cure rate and reduces morbidity and/or mortality. Screening is, by definition, applied to large numbers of healthy individuals. Blood testing for prostate-specific antigen (PSA) has been available for several years, but, as yet, there is no national government-funded screening programme as there is for breast carcinoma. Although the test is cheap and has minimal side effects, the benefits of applying it to large numbers of asymptomatic men have yet to be demonstrated. The test has a significant false positive rate, thus triggering prostatic biopsies, a more expensive test with more potential side effects, in healthy men. It is also likely that the test would detect many cases of indolent, low-grade carcinoma that would be unlikely to cause appreciable problems during the lifespan of the individual. However, in clinical practice, many men are screened for prostate cancer on an individual basis, usually because they themselves have requested the test.
B benign glands E basal epithelial cell M small malignant glands S sheets of malignant cells T islands of squamous cell carcinoma
The most important pathological lesion of the penis is squamous cell carcinoma ( Fig. 19.11 ), which is usually preceded by squamous dysplasia similar to that in the vulva (see Fig. 17.3 ) known as penile intraepithelial neoplasia PeIN (human papillomavirus (HPV) associated lesions) or differentiated PeIN (non–HPV associated lesions). Genital wart or condyloma acuminatum also occurs on the penis and is caused by infection with certain types of HPV, as in the lower genital tract in the female. Phimosis is a common clinical condition that can be caused by an inflammatory and fibrosing condition of the foreskin termed balanitis xerotica obliterans , similar to lichen sclerosus in women (see Fig. 17.1 ).
|Testis||Torsion||Necrosis of tissue with extensive congestion and haemorrhage due to venous infarction||19.1|
|Epididymo-orchitis||Acute inflammation, similar to acute inflammation in other tissues||Like 3.4|
|Germ cell neoplasia in situ||Malignant germ cells within seminiferous tubules, usually as a single layer around the basement membrane with the Sertoli cells pushed inwards||19.2|
|Seminoma||Sheets of large, undifferentiated cells separated by delicate fibrous septa usually with a lymphocytic infiltrate in the septa||19.3|
|Teratoma||Tumour consists of mixtures of fetal tissues, e.g. cartilage, primitive mesenchyme, epithelial structures, bone, etc.||19.4|
|Embryonal carcinoma|| Large malignant cells forming gland-like structures, solid sheets, tubular structures and papillary structures
Often large necrotic areas
|Yolk sac tumour|| Primitive germ cells resembling yolk sac structures
Various patterns including reticular (microcystic), Schiller–Duval bodies, hyaline cytoplasmic globules
|Choriocarcinoma||Alternating layers of syncytiotrophoblast and cytotrophoblast with haemorrhage||17.16|
|Mixed germ cell tumour||Consists of a mixture of one or more different germ cell tumours||19.7|
|Prostate||Benign hyperplasia||Nodular enlargement of glandular and stromal elements of the prostate gland; usually affects the transitional and para-urethral components||19.8|
|High grade prostatic intraepithelial neoplasia||Highly atypical cells similar to those seen in invasive carcinoma but confined within prostatic acini||19.9|
|Adenocarcinoma||Malignant cells invading the prostate as glands, cribriform structures or sheets||19.10|
|Penis||Balanitis xerotica obliterans||Hyalinisation of the subepithelial collagen of the foreskin with an underlying band of inflammation||Like 17.1|
|Squamous cell carcinoma (SCC)||Similar to SCC of vulva: invasion of underlying tissue by nests of atypical squamous cells, often with formation of keratin pearls.HPV related and non-related types.||19.11|
Which of the following tumours is NOT associated with the precursor lesion in the seminiferous tubules shown in the above image? Select ONE correct answer.
Yolk sac tumour
A 92-year-old man develops a well differentiated squamous cell carcinoma of the penis with adjacent differentiated penile intraepithelial neoplasia. Which of the following non-neoplastic conditions is associated with this type of dysplasia?
Balanitis xerotica obliterans
Herpes simplex virus