Testicular tumours are quite frequent in the canine species, accounting for 90% of the tumours which affect the male genital apparatus and 15-20% of all tumours in the dog, second only to skin neoplasms. The mean age at diagnosis is 9 to 11 years old, with a range between 2 and 19 years; the age of onset is earlier (7 years old) in Boxers. Despite the clinical relevance of testicular tumours, given their potential local invasiveness and their capacity of inducing diseases in other organ systems (the so-called paraneoplastic syndromes), knowledge about the incidence of these tumours and the risk factors for their development are still insufficient. This said, an incidence of 0.91% has been reported.
The factors predisposing to testicular tumours in the dog are genetic, hereditary and environmental. The breeds at greater risk are the Boxer, Chihuahua, German Shepherd, Weimaraner, miniature and standard Poodle, miniature Schnauzer, Shetland Sheepdog, Siberian Husky and Yorkshire Terrier, while the breeds at lower risk are the Dachshund, Beagle, Labrador Retriever and mongrels. Testicular tumours are more frequent (by 9-14 times) in testes which have not descended correctly into the scrotal sac (ectopic testes or cryptorchidism), compared to testicles in the scrotum.
Testicular tumours may be unilateral or bilateral, the latter being found in 45% of cases, and may involve one or more types of cell lines. The presence of two or more cell lines is found in 11-35% of cases.
Testicular tumours may be primary or metastatic. According to the World Health Organization, primary tumours may be classified as stromal cell tumours (Sertoli cell tumour and Leydig cell tumour), germ cell tumours (seminoma, teratoma, embryonal carcinoma and gonadoblastoma), and extremely rare tumours of the mesothelium (mesothelioma), vessel walls (haemangioma), lymphatic system (lymphosarcoma) and fibroconnective tissue (fibroma).
The most commonly found tumours are Sertoli cell tumour, seminoma and Leydig cell adenoma (interstitioma, interstitial cell tumour), although, as previously mentioned, it is often possible to find two or more types of tumours coexisting.
Sertoli cell tumour
Sertoli cell tumour is found more commonly in older subjects, at a mean age of 7 to 10 years old, although the reported range is extremely variable being between 2.5 and 16 years. Sertoli cell tumour is diagnosed with a greater frequency in the case of cryptorchidism. In fact, it seems that the incidence of this tumour in cryptorchid subjects is around 20 times greater than in subjects in which both testicles have descended normally into the scrotum. Sertoli cell tumour is unilateral in around 90% of cases. It has been reported that Boxers and Weimaraners have a greater predisposition to this tumour, while a particular syndrome has been described in the miniature Schnauzer, consisting of cryptorchidism and Sertoli cell tumour associated with cystic endometrial hyperplasia or pyometra of the masculine uterus (utricle) of intersexual subjects.
Macroscopically, the Sertoli cell tumour is characterized by extremely variably sized masses, ranging in diameter from less than 1 cm to over 10 cm, which are compact and lobulated, with various connective tissue septa. The nodules are often white/greyish in colour, sometimes with haemorrhagic or cystic areas.
The malignancy of these tumours is usually rather low (2-6%), with metastases spreading mostly to regional lymph nodes (iliac, sub-lumbar and inguinal) and mesenteric and para-aortic lymph nodes, but also to the spleen, liver, lungs and pancreas.
The Sertoli cell tumour may be oestrogen-secreting (more frequently in undescended testes than in scrotal testes) and is responsible for the so-called paraneoplastic feminisation syndrome, reported in around 17% of scrotal testicles, in 50% of inguinal testicles and in 70% of intra-abdominal testicles. The syndrome is characterized by gynaecomastia, with or without galactorrhoea, attraction of males, atrophy of the contralateral testis, and a pendulous prepuce. Cutaneous disorders are often present, with bilateral symmetrical alopecia which often progresses from the posterior areas of the thighs and from the perineum to the flanks, abdomen, thorax and neck. Cutaneous hyperpigmentation, hair coat colour abnormalities, keratinisation and comedones may also be present. There may also be a localised dermatitis between the preputial ostium and the scrotum (linear preputial dermatosis), with erythema, hyperpigmentation and comedones; this is considered by some as a pathognomonic sign of oestrogen-secreting testicular neoplasms. Keratinisation of the internal surface of the prepuce, similar to that found in the vagina of bitches in oestrus, may be present, and cytology of the exfoliated cells can be used to confirm the state of hyperoestrogenism. The prostate is often involved, with the development of squamous metaplasia.
From a haematological point of view, there may be transient or progressive atrophy of the hematopoietic bone marrow (myelosuppression). Transient bone marrow suppression is characterized by leucocytosis and granulocytopoiesis, while the progressive form is characterized by leucocytopenia, thrombocytopenia and severe non-regenerative anaemia. In this latter case patients may have pale mucous membranes or haemorrhagic petechiae, epistaxis, haematuria, melaena or haematemesis. The spermogram may also show frequent alterations.
These signs are not, however, always related to a real increase of blood oestrogens or only related to such a state; it has been reported that some subjects with Sertoli cell tumour and feminisation syndrome do not have alterations in the concentration of oestrogens in the blood, but rather an increase of inhibin and a reduction of the gonadotropins, luteinising hormone (LH) and follicular stimulating hormone (FSH), thus indicating the extreme complexity of the hormonal basis of this syndrome.
Seminoma
Seminoma is frequently unilateral (prevalently involving the right testicle), the median age of onset is 10 to 11 years old, and it mostly affects (more than 70% of cases) scrotal testes. The breeds with an apparent greater predisposition are the German Shepherd and the Boxer. The malignancy of this tumour is low, although metastases to regional lymph nodes, abdominal or thoracic organs, the brain and eyes have been reported. Despite this low, although possible, potential for distant metastases (6-10% of cases), local invasion is more frequent (15-20% of cases). The hormone-secreting nature of this tumour has not been confirmed, however paraneoplastic syndromes which have resolved following bilateral orchidectomy have been described. The syndrome is characterized by progressive, non-pruriginous alopecia with hyperpigmentation of the trunk, prostatic diseases and non-insulin dependent diabetes mellitus.
Macroscopically, the shape and size of the tumour are quite variable. The diameter varies between 1 to 10 cm, and the tumour is a homogeneous, lobulated mass, typically cream-coloured on the cut surface. The lesions, which may be focal or diffuse, have a flaccid or semi-firm consistency.
Leydig cell tumour
Leydig cell tumour, or interstitial cell tumour, affects older dogs (mean age, 10 years old), there is no specific breed predisposition, and it almost exclusively affects scrotal testes (99%). It is a benign tumour, which rarely metastasises. In 40% of cases it affects both testes. It is usually not diagnosed clinically but is a frequent, incidental autopsy finding.
Macroscopically, the Leydig cell tumour is characterized by small masses, usually under 1 cm in diameter, which normally do not distort the shape of the testicles. The neoformations are yellow to brown, soft, and well circumscribed. Haemorrhages and cystic areas are frequent.
Leydig cell tumour is a hormone-secreting tumour and, therefore, has the potential to cause paraneoplastic syndromes due to excessive secretion of both oestrogen and androgens. The clinical presentation of these syndromes depends on the prevailing hormonal status. In the case of hyperandrogenism, prostatic diseases, perianal adenomas, perineal hernias, anal gland or tail hyperplasia can be found.
Teratoma
Teratoma is relatively frequent in humans, but extremely rare in the canine species. The tumour originates from tissues belonging to several germ cell layers (ectoderm, mesoderm and endoderm). Probably deriving from the partial differentiation, without organization, of multipotent germ cells, these tumours can be of considerable size, be cystic or polycystic, and contain hair, mucus, bones and other structures. Teratomas are usually benign.
DIAGNOSIS
In many subjects testicular tumours are asymptomatic, the tumour may pass unrecognized and then be an incidental finding during clinical examination. In other cases the owner notices an increase in the volume of one testicle, with consequent scrotal asymmetry (Fig. 1), or, in the case of breeding dogs, a decrease in fertility. Finally, the dog may undergo a clinical examination because of signs caused by a paraneoplastic syndrome.
The clinical investigation, with the signalment (elderly dog, eventual breed predisposition, site of testes), an accurate clinical history and a careful general physical examination, is the first step in making a suspected diagnosis of a testicular tumour. The history can provide information on symptoms linked to prostate disorders, on behavioural alterations during micturition and/or defecation, and a possible decrease in fertility.
The general clinical examination can reveal dermatological alterations which are possibly hormone-based, or disorders affecting the perineal region. In the presence of metastatic lesions, signs related to functional alterations of the specific organs involved may be identified.
The clinical examination, with inspection, but especially with palpation of the scrotal area, may detect asymmetry of the two testes, with alterations in their size, shape and consistency, usually in the absence of pain, which may raise the suspicion of a neoplastic disease (Figs. 2 and 3). Testicular asymmetry is more evident when the increase in size of the neoplastic testicle is combined with hypertrophy/atrophy of the contralateral testicle.
Ultrasonography is a useful and non-invasive technique for the detection of alterations in testicular structure and also enables investigation of ectopic or cryptic testes that cannot always be explored by palpation as well masses not detectable by palpation. Furthermore, it can show alterations in echostructure (disappearance of the mediastinum testis) and echogenicity (hypo- or hyperechoic areas) caused by the presence of cystic, necrotic or haemorrhagic areas. These areas of different echogenicity may be surrounded by a well-defined, hyperechoic capsule. Ultrasonography cannot, however, differentiate between the various types of testicular tumours.
Routine blood tests may give indications on the overall health of the animal and, in particular, on the functioning of the bone marrow. Hormonal assays do not always have a decisive role, as various studies have reported contrasting results. Evaluation of the testosterone/oestradiol ratio seems more useful than the absolute value of oestradiol, although definite data on this issue are still lacking.
Cytology is extremely useful, not only for the diagnosis of the tumour but also in order to identify the histotype. The procedure is minimally invasive and not painful, carried out by freehand needle aspiration in the case of masses easily identifiable by palpation, or with an ultrasound-guided technique. It is worth recalling that should more than one tumour be contemporaneously present, this technique may not give an exhaustive final diagnosis which can, instead, be made from histological studies of biopsy samples or post-orchidectomy. The final diagnosis relies exclusively on histology.
In the case of suspected systemic involvement by metastases, additional instrumental examinations are necessary (computed tomography and nuclear magnetic resonance imaging), so as to define the clinical status of the patient, to make the diagnosis more precise and to choose the best treatment possible.
THERAPY AND PROGNOSIS
In most cases treatment is based on the surgical removal of the testes (orchidectomy ororchiectomy), plus scrotal exeresis, should the scrotum also be involved. The removal of both testicles is usually suggested, unless dealing with breeding dogs of high genetic value. Bilateral orchidectomy is to be preferred because of the frequency of testicular tumours which involve both gonads, but also because in unilateral forms the contralateral testis is often atrophic and has lost its function. Post-operative inspection of the cut surface of the testicles may show macroscopic alterations, such as the disappearance of the mediastinum testis (Fig. 4) and the presence of haemorrhagic and/or necrotic or cystic areas.
In highly valuable breeding dogs unilateral orchidectomy causes a compensatory hypertrophy, which is evident starting from 3 months after the removal of the neoplastic testicle.
In the absence of metastases and/or severe bone marrow involvement, surgery is curative and the prognosis favourable. Both the dermatological syndrome and prostatic disease resolve spontaneously within a few weeks of surgery, and myelosuppression, if in its initial stages, resolves within a few months. The development of progressive bone marrow hypoplasia is a negative prognostic factor. The lack of resolution of a feminisation syndrome after bilateral orchidectomy suggests that the tumour has already spread hormone-secreting metastases; in such cases the prognosis is poor. In all cases myelosuppression requires supportive therapy with blood transfusions. In the case of aggressive neoplasms, chemotherapy and radiotherapy are necessary.
Suggested readings
- Nielsen SW, Kennedy PC. In Moulton JE: Tumors in Domestic Animals. 1990 University of California
- Maclachland NJ, Kennedy PC. In Meuten DJ: Tumors in domestic animals. 2002 Iowa State Press
- Masserdotti C. Tumori testicolari del cane: diagnostica citologica e correlazioni istopatologiche. Veterinaria, 2000; 14(1): 57-63
- SD Johnston, MV, R Kustritz, PNS Olson. Canine and Feline Theriogenology. Saunders edition, 2001.