This page is part of the site called Surgical Pathology of the Canine Male Reproductive Tract by

Table of Contents

Disease of the testis (and of the epididymis)

The two main concerns with disease of the testis (and epididymis) as well as the rest of the reproductive tract are infertility and diseases that cause morbidity or mortality. Infertility is usually the domain of the theriogenologist (therí(on) is Greek for beast and gén(os) is Greek for offspring or sex) and the pathologist can contribute by identifying the underlying reason or diagnosis and the cause. Male infertility is a combination of lack of production of spermatozoa, production of viable spermatozoa, transportation and maturation of spermatozoa and being able to deposit the spermatozoa in the appropriate location mixed with seminal fluid.

Aspermia and Azoospermia

Aspermia is the inability to produce semen. Azoospermia is a lack of spermatozoa in semen. Allen and Longstaffe (1982) reported on 4 azoospermic dogs with spermatogenic arrest, abnormal spermatogenesis and interstitial orchitis. They considered the possibility of an immune mediated reaction. Thus a failure of spermatogenesis was found, and confirmation was by histological evaluation of the seminiferous tubules. Olson (1991) listed causes of azoospermia including gonadal dysfunction, obstructive azoospermia and retrograde ejaculation, Causes of gonadal dysfunction include chromosomal abnormalities, autoimmune disease, orchitis and epididymitis. Olson et al (1992) reported on 18 dogs with azoospermia. One had aplasia of the epididymides, one had a pituitary tumour and one had a Sertoli cell tumour. 5 dogs had no spermatogenesis, and 6 had reduced spermatogenesis. 1 dog had inflammation in the efferent ducts, 3 had inflammation of the epididymides that varied from mild to severe.

Allen WE, Longstaffe JA. (1982). Spermatogenic arrest associated with focal degenerative orchitis in related dogs. J Small Anim Pract 23: 337-343.

Olson PN. (1991). Clinical approach for evaluating dogs with azoospermia or aspermia. Vet Clinics North Amer: Small animal practice. 21: 591-608.

Olson PN, Schultheiss P, Seim HB. (1992) Clinical and laboratory findings associated with actual or suspected azoospermia in dogs: 18 cases (1979). J Amer Vet Med Assoc 201: 478-482.

 

Orchitis

From a pathology point of view, orchitis is inflammation of the testis. Clinically though, orchitis is used to indicate any disease of the scrotal contents, including periorchitis, epididymitis and orchitis itself. Orchitis is, in general, a rare finding.

Macroscopic orchitis is identified clinically as a swollen painfull testis and is usually accompanied by epididymitis and or periorchitis. This is so much so that epididymitis and orchitis is combined as the term epididymoorchitis. True orchitis in dogs is the equivilant of necrotic orchitis of other species. Microscopic orchitis is an incidental finding or seen in dogs with azoospermia. It is an interstitial orchitis usually.

Macroscopic orchitis

Orchitis that is sufficiently severe to cause clinical signs in the testis or scrotal sac, or even systemically is most commonly seen in bacterial infection. It occurs with epididymitis caused by Gram negative organisms such as Eschericha coli and occasionally by Brucells canis and Brucella suis. Instead of the testis being a white pink colour, it is either liquified and white or red black. A dry appearance may indicate testicular necrosis (see testicular necrosis below) and not true orchitis.

It is also found in systemic blastomycosis. Totten et al (2011) reported on 4 clinical cases of blastomycosis where the prostate was involved. They examined 155 dogs with blastomycosis of which 86 were male and 37 were intact. 4 had their testes examined and all blastomycosis. 4 of the dogs had prostatic involvement and diagnosis was on fine needle aspirant cytology. None of the dogs with testicular involvement had evaluation of their prostate.

 

Dogs with Rocky Mountain Spotted Fever are reported to develop orchitis. The vascular changes include vasculitis, disseminated intravascular coagulation and hemorrhage may be present and the reaction one of ischemic injury rather than a true orchitis.

Leishmaniasis is reported to induce orchitis. It can be microscopic only, or cause testicular enlargement (Manna et al 2012)

 

 

James DR, Golovsky G, Thornton JM, Goodchild L, Havlicek M, Martin P, Krockenberger MB, Marriott D, Ahuja V, Malik R, Mor SM. Clinical management of Brucella suis infection in dogs and implications for public health. Aust Vet J. 2017; 95: 19-25

Manna L, Paciello O, Della Morte R, Elio Gravino A. (2012) Detection of Leishmania parasites in the testis of a dog affected by orchitis: case report. Parasites Vectors 2012, 5: 216-220

Ober CP, Spaulding K, Breitschwerdt EB, Malarkey DE, Hegarty BC. (2004) Orchitis in two dogs with Rocky Mountain spotted fever. Vet Radiol Ultrasound. 45(5):458-465.

Serikawa T, Takada H, Kondo Y, Muraguchi T, Yamada J. (1984) Multiplication of Brucella canis in male reproductive organs and detection of autoantibody to spermatozoa in canine brucellosis. Dev Biol Stand. 56:295-305.

Totten AK, Ridgway MD, Debra S. Sauberli DS. (2011) Blastomyces dermatitidis Prostatic and Testicular
Infection in Eight Dogs (1992–2005). J Am Anim Hosp Assoc 2011, 47: 413-418

Microscopic (subclinical) orchitis

Some cases of orchitis are only found as incidental findings on histological evaluation, or during the investigation of infertility (more specifically azoospermia). Diniz et al (2005), in a study on the genital lesions of dogs seropositive for Leishmania spp found 18% of dogs without evidence of exposure to Leishmania has inflammatory lesions.

While the exact cause of microscopic orchitis is unknown, an autoimmune pathogenesis is often suspected. The seminiferous tubule has the blood testis barrier at the level of the Sertoli cell making the spermatocytes, spermatids and spermatozoa outside normal immune survellance. The testis is an immune 'priveledged' region. This is maintained by the blood testis barrier, and the testicular T cells and dendritic cells of the interstitium.. Exposure of antigen from within the seminiferous tubule to the interstitium can potentially cause an autoimmune reaction. While the efferent ductules are most often involved in experimental disease, the testis is also a target.

Any inflammatory reaction within the testis is likely to cause adjacent or generalized tubular degeneration.

Infectious orchitis resulting in microscopic inflammation is reported in leishmaniasis (Diniz et al 2005). The lesion is mutlifocal and lymphocytic and plasmacytic in nature. There was mild to severe degeneration in the affected regions.

Canine distemper virus infects the testis but the changes are restructed to the presence of intranuclear and intracytoplasmic inclusion bodies in the Sertoli cells. There may be testicular degeneration present (McEntee 1990)..

Fritz et al (1976) reported on the finding of an interstitial orchitis in the testis of beagle dogs. 32% of dogs had a lymphocytic interstitial orchitis. Outbred dogs had larger testes than partially inbred animals. 22 of 69 dogs had interstital lymphocytic infiltrates that varied from nodular to diffuse. Adjacent degeneration was found. 14 of the 22 were partially inbred.

Figure : Suppurative orchitis. The outlines of the tubules are visible but they are filled with neutrophils and macrophages.

Figure : Suppurative intratubular orchitis. High magnification of figure above.

 

Diniz SA, Melo MS, Borges AM, Bueno R, Reis BP, Tafuri WL, Nascimento EF, Santos RL. (2005) Genital Lesions Associated with Visceral Leishmaniasis and Shedding of Leishmania sp. in the Semen of Naturally Infected Dogs Vet Pathol 42: 650-658.

Fritz TE, Lombard SA, Tyler SA, Norris WP. (1976) Pathology and familial incidence of orchitis and its relation to thyroiditis in a closed beagle colony. Exp Mol Pathol. 24(2):142-58.

Hayes HM, Tarone RE, Casey HW. (1995). A cohort study of the effects of Vietnam service on testicular pathology of U.S. military working dogs. Mil Med. 160(5):248-255

McEntee K (1990) Reproductive Pathology of Domestic Mammals. p267

Testicular necrosis

Testicular necrosis is where there is death of regions of the testis. It usually affects the whole testis, but in some species (bull and ram) can be a segmental disease. The blood flow to the testis is via a tortuous testicular artery that is part of the pampiniform plexus. By the time the blood reaches the testis, it is barely pulsile and has a lower pressure than normal arterial pressure. A slight change in flow will result in ischemia. This fortunately does not occur very often. Necrosis of the testis is particularly seen in retained (or cryptorchid) testes, and is assumed to occur because of an avascular event, particularly. Torsion of a fully descended testis is virtually unheard of in all species expect for the horse.

  Torsion of the testis can produce venous infarction, with both testis and epididymis becoming hemorrhagic (see below). Death of the testis is an expected sequel. When only the testis is affected, some vascular event apart from torsion should be invoked.  Oedema, inflammation, or anything reducing testicular arterial pressure, increasing venous pressure or slowing blood flow could induce necrosis. Anything that increases intratesticular pressure above testicular venous pressure will obstruct blood flow.

Chemical induced necrosis occurs with the injection into the testis of a chemical sterilent such as EsterilSol (zinc gluconate with arginine). injection of this liquid results in coagulative necrosis of the testis. Occasionally, adverse reactions result is suppurative necrotic orchitis (Forzan et al 2014).

A grossly necrotic testis has a black or brown black colour, and the cut surface is often dry.

When testicular necrosis is identified, it is important to determine the underlying cause.

Figure : Testicular necrosis; this dog had epididymitis and periorchitis. The testis is black and dry, has coagulation necrosis and periorchitis.

Figure : Testicular necrosis; dog has seminoma (black well circumscribed mass) and adjacent testis is necrotic.

Histologically the necotic testis is usually a simple coagulation necrosis. When there is torsion, there may be diffuse haemorrhage throughout the interstitium. Some cases have viable tubules directly beneath the tunica albuginea as the blood flow to the tunic is separate to that of the testicular parenchyma, or at least the vessels beneath the tunic are not affected as are those in the parenchyma.

Figure : Testicular necrosis with interstital hemorrhage from torsion and venous infarction.

Figure : Testicular parenchymal necrosis with viable tunica albuginea

 Figure : Testicular necrosis - coagulative type.

Forzán MJ, Garde E, Pérez GE, Vanderstichel RV.Necrosuppurative orchitis and scrotal necrotizing dermatitis following intratesticular administration of zinc gluconate neutralized with arginine (EsterilSol) in 2 mixed-breed dogs. Vet Pathol 2014; 51: 820-823

Testicular torsion (torsion of the spermatic cord)

Torsion (from the latin word meaning 'wringing pain') of the spermatic cord is commonly called testicular torsion. It is a periodic event in dogs, and is usually seen in cryptorchid testes as there is sufficient laxity of the gubernaculum to allow the twist. In a normally descended testis, the attachment of the vaginal tunic precudes a twist form occurring. Zymet (1975) and Young (1979) report torsion of the testis in descended testes.

Testicular torsion may be identified clinically as an 'acute abdomen'. Many are silent and the remains of a small degenerate gonad remains. Torsion is more likely to occur in those testes that contain testicular tumours.

The acutely twisted gonad becomes red black and swollen, as would be expected in venous infarction.

Most published accounts of testicular torsion are individual case reports, but most cases are recognized and surgically corrected.

Figure : Testicular torsion; retained testis with a Sertoli cell tumour.

Hulse DA. (1973) Intrascrotal torsion of the testicle in a dog. Vet Med Small Anim Clin. 68(6):658-659.

Laing EJ, Harari J, Smith CW. (1983) Spermatic cord torsion and Sertoli cell tumor in a dog. J Am Vet Med Assoc. 183(8):879-881

Pearson H, Kelly DF. (1975) Testicular torsion in the dog: a review of 13 cases. Vet Rec. 97(11):200-204

Pinto CR, Paccamonti DL, Partington B, McFadden K. (2001) Theriogenology question of the month. Torsion of the spermatic cord. J Am Vet Med Assoc. 219(10):1343-1345.

Pollock WB. (1981) Spermatic cord torsion in a dog. Mod Vet Pract. Mar;62(3):216.

Young AC. (1979) Two cases of intrascrotal torsion of a normal testicle. J Small Anim Pract. 20(4):229-231.

Zymet CL (1975) Intrascrotal testicular torsion in a sexually agressive dog. Vet Med Small Anim Clin 70(11):1330-1331

 

Testicular rupture

Pressure sufficient to overcome the ability of the tunica albuginea to contain the testicular parenchyma will result in rupture. Local blunt force trauma could do this, but it is a rare event. The outcome of testicular rupture is twofold. There will be severe trauma and the formation of a hematocele, and inflammation will occur. Rupture and exposure of the germinal cells, that are outside the blood testis barrier, as well as altering the environment and therefore the antiinflammatory properties of the testis, will induce a foreign body type reaction (granulomatous) and immune mechanisms will be mediated to induce a further reaction. This is particularly the case in postpubertal animals.

Some dogs find attacking the genitals of other animals particularly effective in asserting their dominance and the recipients of these attacks may have severe injuries including penetrating and crushing wounds.

Polyorchia

Polyorchia is a very rare condition where a dog has more than 2 testes.

Tamminen et al (2012) reported on one dog with 2 right testes - one scrotal and one cryptorchid - that shared the same deferent duct.

 

Tamminen TM, Leinonen MR , Ka H Andersson M. (2012) A Polyorchid Dog. Reprod Dom Anim 2012, 47: e26-e28

Small testes

Anorchia - No testis,

The failure to find one or both testes in the scrotum becomes a clinical challenge. If there results of endocrinological testing indicate functional testicular tissue , the first condition to exclude is cryptorchidism (also called retained testis). Surgery to remove the retained structure will hopefully reveal a testicular structure, and there will be no need for histological examination. On occasion, pathologists get involved when the deferent duct is found on exploratory surgery but there is no testis. The major possibilities therefore become

• Previous surgical removal

• Testicular hypoplasia

• Testicular atrophy/necrosis

• Testicular aplasia

Previous surgical removal

When there has been previous surgical removal, the end of the deferent duct can be found, and usually the ductus is well developed and at a size commensurate with the size of the ductus at the age of castration or removal. No epididymal tissues or embryonic remnants should be present.

Testicular atrophy/necrosis

The retained testis is hypoplastic, virtually by definition, as the raised temperature compared to scrotal testes prevents spermatogenesis. Further details are listed below under cryptorchidism. Testes retained in the abdomen, despite their hypoplastic nature, also undergo a process of degeneration and they will atrophy. The process is a degenerative one, the histological appearance is that of degeneration, but the macroscopic change is atrophy - this is the convention used to define these particular terms as they apply to the testis. For further information about testicular degeneration, see the section below.

The process of degeneration of a retained testis is thought to mirror the degenerative changes of a scrotal testis, although the lack of spermatogenesis or spermatic arrest already exists. Tubules shrink in size, the basement membranes become wavy, and with time, the Sertoli cells disappear so that all that remains is an outline of the previous tubule. The epididymis remains as a hypoplastic tube, but over time, it too may 'fade'and only a vestige remains. This usually occurs after the testis becomes completely degenerate. On occasion, the testis suffers a severe process where it dies, and the necrosis is assumed to be a vascular event. Torsion of the retained testis can occur and both testis and epididymis will be affected.

Figure : Retained testicular remnant with fibrous tissue surrounding mineralised foci and adjacent epididymal remnant (below)

Figure : Retained testis and epididymis. Coiled portion of deferent duct near epididymal head.

Testicular hypoplasia

Not only is the retained testis hypoplastic, but the amount of testicular tissue can be greatly reduced. As with degeneration of a retained testis, extreme hypoplasia may be to the state that the tissue is only microscopic. A thorough search of the tissue is required to find testicular tissue.The range of changes is illustrated in the section on the diseases of the male cat. The frequency of this is much less than in cats.

Testicular aplasia

Aplasia of the testis is extremely rare, and should only be made when all tissue has been examined thoroughly to exclude advanced degenerative or necrotic changes.

Cryptorchidism (Retained testes)

Cryptorchidism is a disorder of sexual development (DSD) and I moved this section to the pages refering to DSD. It is an DSD categorised as XY SRY+ with testes and normal phenotype and retained testes. See the website of canine DSD

Testicular hypoplasia

Testicular hypoplasia is a disorder of sexual development (DSD) and I moved this section to the pages refering to DSD. It is an DSD categorised as XY SRY+ with testes and normal phenotype, See the website of canine DSD.

Testicular atrophy – degeneration.

Testicular atrophy is when the testis becomes smaller in size. It is a macroscopic term, whereas the corresponding microscopic change is degeneration. It is difficult to differentiate atrophy from hypoplasia, and a knowledge that the testis became smaller is important.

Testicular atrophy-degeneration is very common. Ortega-Pacheco et al (2006) reported 48 cases in 318 stray dogs in Mexico.

Pathogenesis

Mainenance of the seminiferous epithelium requires a close intergration of pituitary hormones, systemic and local environments, and of the crosstalk between germ cell, Sertoli cell and interstitial endocrine cell. Injury to any one of these ill upset the equilibrium necessary for normal spermatogenesis.

The causes of testicular atrophy – degeneration are legion. Here are some of the known causes, and some are discussed further below.

• heat

  • high environmental temperature

  • fever

  • epididymitis and orchitis

  • scrotal dermatitis

  • scrotal edema

  • periorchitis

• radiation (for cancer therapy)

• poor health and debility

• advancing age.

• hormones

  • estrogen

  • Sertoli cell tumours

• drugs

  • chemotherapy

 

A study of testicular degeneration following raising scrotal temperature by 3degrees C for 48hr was done by Henning et al (2014) There were minimal degenerative changes histologically and no significant change in spermatozoa, so perhaps the canine testis is more resistant than other species.

Mild degenerative changes occur in dogs with aging. James and Heywood (1979) reported seeing incomplete spermatogenesis in older dogs, and up to 6% of dogs over 7 years are affected. Lowseth et al (1990) examined beagle dogs of varying ages from 3 to 14. They noted that there was a relative decrease in the percentage of germ cells, a relative increase in the tubular luminal size and a decrease in the volume of the Sertoli cells. Interstitial endocrine cell volume decreased also.

Freshman summarized the drugs that are known to affect infertility. They include

• Steroidal compounds (methyltestosterone, Estrodiol, diethylstilbestrol, KABI1774, betamethasone, prednisolone)

• Contraceptive compounds: tamoxifen citrate, gossypol.

• Chemotherapeutic agents: Busulfan, Chlorambucil, Cisplatin, cyclophosphamide, methotrexate, vincristine.

• Miscellaneous drugs: anticholinergics, barbiturates, chlorpromozine, diazepam, digoxin, levodopa, phenytoid, primidone, propranolol, thiazine diuretics, verapamil.

 

 

Freshman JL. (1989) Drugs affecting fertility in the male dog. Current Veterinary Therapy X, Small Animal Practice. WB Saunders Toronto. p1225

Henning H, Masal C, Herr A, Wolf K, Urhausen C, Beineke A, Beyerbach M, Kramer S, Gunzel-Apel A-R. (2014) Effect of Short-Term Scrotal Hyperthermia on Spermatological Parameters, Testicular Blood Flow and Gonadal Tissue in Dogs. Reprod Dom Anim 2014, 49: 145-157

James RW, Heywood R. (1979) Age-related variations in the testes and prostate of beagle dogs. Toxicology. 12(3):273-279.

Lowseth LA, Gerlach RF, Gillett NA, Muggenburg BA. (1990) Age related changes in the prostate and testes of the beagle dog. Vet Pathol 27: 347-353.

McEntee (1990) Reproductive Pathology of Domestic Mammals. p258-263

Ortega-Pacheco A, Rodríguez-Buenfil JC, Segura-Correa1 JC, Bolio-Gonzalez ME, Jiménez-Coello M and Linde Forsberg C. (2006) Pathological Conditions of the Reproductive Organs of Male Stray Dogs in the Tropics: Prevalence, Risk Factors, Morphological Findings and Testosterone Concentrations. Reprod Dom Anim 41 :429-437

 

Macroscopic changes

The convention in reproductive pathology is to call a reduction in size of the testis, atrophy. This is a term used to describe a macroscopically small testis that once was larger.

In mild forms of atrophy/degeneration, the testis looses its tone but this cannot be determined with certainty at necropsy as the testis autolysises rapidly and loses tone as a consequence. There can be considerable histological evidence of degeneration but little detectible change grossly and as a consequence, macroscopic evaluation is not very sensitive.

Typically, an atrophic testis has a normally sized epididymis so the proportions change. When there is advanced atrophy, the capsule of the testis is white, thick and the testicular vessels in the tunica albuginea are less obvious or missing. On cut section, an atrophic testis may be a red brown colour, or could contain bands of or diffuse white areas of fibrosis. Mineralization can also occur, often beginning at the mediastinum and extending outward. While there may be a segmental change visible in the testes of other species, I am unaware of any macroscopically visible segmental change.

Microscopic changes

Degeneration is a microscopic change, and a process.

Many of the early microscopic changes of degeneration are similar to autolytic change.

Figure : Autolytic changes to seminiferous tubules are simular to early degenerative change including vacuolation of Sertoli cells, undulation of the basement membrane, and slouging of germ cells.

The earliest stages of degeneration are seen as spermatogenic arrest, and increased single cell death of the germinal cells. Spermatid desquamation, multinucleated spermatid giant cells and vacuolation of Sertoli cells are early changes. Spermatocytes are often also involved and eventually, no spermatogenesis may be visible, so that the tubules are lined by Sertoli cells only. In the early phases, the tubules reduce in diameter and the basement membranes become undulating or wavy. With progressively severe degeneration, Sertoli cells die, and when this occurs, all that remains is an outline of the basement membranes. Interstitial endocrine cells often remain, but as there is constant cross talk between interstitial endocrine cells, Sertoli cells and spermatocytes, loss of one group will eventually result in loss of all. Interstitial endocrine cells may appear to be more numerous in some instances, but this is not an absolute increase in cells, but rather a relative increase as the area that is tubules is reduced. Interstitial endocrine cells can contain lipochrome pigment and this may become more obvious.

Figure : Testicular degeneration. There is vacuolation of the wall of the seminiferous tubule, and a lack of spermatogenesis.

Figure : Testicular degeneration. There is spermatogenic arrest at the spermatocyte stage - spermatids are not present. There is also vacuolatioin of the Sertoli cells, but this may be artifactual.

Figure : Testicular degeneration. There are multinucleated spermatid within the lumen of the tubule.

Figure : Testicular degeneration. There is spermatogenic arrest at the primary spermatocyte stage.

Figure : Advanced testicular degeneration with tubules lined only bby Sertoli cells. Vessels have prominant walls, and interstitial endocrine cells are more obvious.

Figure : Advanced testicular degeneration - higher magnification of figure above.

In some individuals, there are groups of seminiferous tubules that are degenerate and others that are not. It is said that this segmental histological lesion may have a vascular basis, with arterioles in the affected areas appearing to have a thicker wall.

Large testes

Testicular dissymmetry is a common clinical presentation. Because neoplasia is so common, the natural tendency for clinicians is to assume that the larger testis is abnormal and potentially contains a neoplasm. The larger testis may be presented for examination. Consideration for testicular dissymmetry should be given for another possibility - unilateral testicular atrophy. A combination of changes may be operative, and should be considered when the larger testis is grossly 'normal'. One may be smaller, and the other larger. Neoplasia is a common cause of testicular enlargement, and some testicular neoplasms cause testicular atrophy of the contralateral testis. Testicular hypertrophy is seldom considered though. The list of conditions causing testicular enlargement therefore include

• neoplasia (primary)

• neoplasia (secondary)

• hypertrophy

• orchitis

• cystic rete testis

• rete cysts

• spermatocele

Compensatory hypertrophy

The testis is capable of hypertrophy. This enlargement is not dramatic. The basis is believed to be a greater stimulation of interstitial endocrine cells and Sertoli cells by the hormones of pituitary origin (LH and FSH) that are not inhibited in a negative feedback system.

 

In general, compensatory hypertrophy occurs to its maximal with unilateral castration or even testicular retention from birth. When beagle dogs were hemicastrated at 16 weeks of age, the remaining testis was 125% larger than age matched controls. (Tsutsui et al 2004). Luteinizing hormone and testosterone concentration were significantly higher than control dogs. Despite this, there was no commensorate increase in daily sperm output so that although the semen volume is normal, the concentration of spermatozoa is reduced.. Adult castration does not apparently appear to result in hypertrophy (Tha et al 1982) - so the presence of hypertrophy indicated a unilateral lesion before puberty. My personal impression is that there are hypertrophic changes after puberty.

The hypertrophic testis is more bulbous than normal, and this is difficult to appreciate by anyone who is not familiar with the normal testis. Histologically, the seminiferous tubules are larger in diameter and the lumen is wider.

Taha MA, Noakes DE, Allen WE. (1982) Hemicastration and castration in the beagle dog; the effect on libido, plasma testosterone concentrations, seminal characteristics and testicular function. J Sm Anim Pract 23: 279-285. as quoted by Tsutsui et al (2004).

Tsutsui T, Kurita A, Kirihara N, Hori T, Kawakamie E. (2004). Testicular compensatory hypertrophy related to hemicastration in prepubertal dogs. J Vet Med Sci 66: 1021-1025.

Hyperplasia of testicular elements

Hyperplasia of testicular elements is an unusual finding. Despite a greater number of particular elements, hyperplasia does not cause enlargement of the testis. It is a microscopic finding usually. There is no known link with neoplasia.

Interstitial cell hyperplasia

In testicular hypoplasia (see above), the interstitial endocrine cells apear to be more numerous and are said to be hyperplastic. It is generally believed that this is a relative change and that the absolute number are not increased.

Focal nodular hyperplasia is recognised, but the conundrum is that the deliniation of nodular hyperplasia and focal interstitial cell tumour. This argument occurs with any endocrine tissue especially. Panels of people decide that a set size is the deliniation, but this is arbitary. Until laser dissection and capture, and an appropriate marker of neoplasia becomes available, this argument will continue. McEntee (1990), in the spirit of being arbitary, chose to call those that were macroscopically visible as neoplasia and those that were microscopic only to be nodular hyperplasia.

Sertoli cell hyperplasia

Hyperplasia of Sertoli cells is seen in two main circumstances. Nodules of Sertoli cell cells are sometimes seen in retained (cryptorchid) testes and are assumed to be a hyperplastic rather than neoplastic change. Given the predisposition of retained testes to develop Sertoli cell tumours, this may be a forerunner of neoplasia.

McEntee (1990) reports seeing hyperplasia of Sertoli cells in the lumen of seminiferous tubules in old dogs and some has feminisation. There is one case of this at the University of Guelph.

Figure : Focal Sertoli cell hyperplasia. Photo compliments of Dr J Caswell.

Figure : Focal Sertoli cell hyperplasia. Photo compliments of Dr J Caswell.

Testicular neoplasia

In general, testicular neoplasia in dogs is very common. The literature contains many case reports or series, and there has been much done to compare testicular neoplasia in dogs to those in human males. Sertoli cell tumour, seminoma and interstitial cell tumours are the most common. Most authors suggest this order is in decreasing prevalence. Interestingly, Sertoli cell tumours and seminomas are similar in prevalence and interstitial cells tumors were much less. In the YB database there are 733 of these three and interstitial cell tumours were most common at 268, seminomas were second at 263 and Sertoli cell tumours least at 202. McEntee (1990) reports seeing 640 testicular tumours of which 235 were seminomas, 223 were Sertoli cell tumours, 175 interstitial cell tumours and 7 others. Grieco et al (2008) examined the testes of 232 dogs and found 62 dogs had 110 testicular tumours. 55 were interstitial cell tumours, 46 were seminomas and 9 were Sertoli cell tumours. Nødtvedt et al (2010) examined 345 testicular tumors from a registry of 14,401 (2.4%) and found that 33% were Interstitial cell tumours, 26% were Sertoli cell tumours and 34 % were seminomas.

All species have a similar range of primary testicular neoplasms, including sex cord/stroma tumors (interstitial cell tumors, Sertoli cell tumors), germ cell tumors (seminoma, teratoma), and epithelial tumors (rete adenoma and carcinoma). The classification of neoplasms used here is as outlined by Kennedy et al (1998)

The vast majority of testicular neoplasms are benign - metastatic tumours are rare and unfortunately have no distinguishing feature apart from the presence of metastasis.

Neoplasms of dogs are accompanied by hormonal changes and feminisation - especially the Sertoli cell tumour and occasionally the interstitial cell tumour. These same tumours are particularly seen in crytorchid testes.

Grieco V, E. Riccardi E, G.F. Greppi GF, F. Teruzzi F, V. Iermanò V and M. Finazzi M (2008) Canine Testicular Tumours: a Study on 232 Dogs. J Comp Pathol 138: 86-89

Hayes HM, Pendergrass TW. (1976) Canine testicular tumors :epidemiologic features of 410 dogs. Internat J Cancer 18: 482-487.

Herron MA, (1982) Tumors of the canine genital system. J Amer Anim Hosp Assoc 19: 981-994.

Benazzi C, Sarli G, Preziosi R, Marcato PS. (1995) Laminin expression in testicular tumours of the dog. J Comp Path 112: 141-150.Reifinger M (1988) Statistische untersuchungen zum Vorkommen von hodentumoren bei haussaugetieren. J Vet Med A 35: 63-72.

Peters MAJ, de Long FH, Teerds KJ, Rooij DG, Dieleman SJ, van Sluijs FJ. (2000) Ageing, testicular tumours and pituitary-testis axis in dogs. J Endocrinol 166: 153-161.

Nødtvedt A, Gamlem H, Gunnes G, Grotmol T, Indrebø I, Moe L. (2010) Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry. Vet Comp Oncol 2011 9: 45-54

Sex cord - stromal (gonadostromal) tumours

Neoplasms with a phenotype resembling the cells that originate from stroma or sex cords of the primitive gonad include the interstitial cell tumour and Sertoli cell tumour.

Interstitial cell tumour

Interstitial (Leydig) cell tumours are almost all very well differentiated tumours and their macroscopic and histologic features are so characteristic that they are usually easy to recognize. These tumours are almost always benign - there is one case report of a metastatic interstital cell tumour (Canadas et al 2016), there is anecdotal accounts of them. There is one in the YB database.

Interstitial tumours may be hormonally active. Both androgenic and estrogenic effects may be seen.

Peters et al (2000) examined 14 dogs with interstitial cell tumours and found 2 with feminization. These had a greater concentration of estrodiol and inhibin like immunoreactivity than did dogs without feminisation. Their testosterone and LH concentrations, however, were lower than normal. Their FSH concentration was normal suggesting the inhibin was not active (not dimeric).

Miscke et al (2002) examined 20 dogs with interstitial cell tumours and found one dog that had feminisation. They measured estradiol and testosterone concentrations and calculated the testosterone/estradiol ratio. They found no difference to normal values. The dog with feminisation had a high testosterone/estradiol ratio.

Canadas et al (2016) reported a case of metastatic interstitial cell tumor. Metastases were to the skin. All tumors were inhibin alpha and calretinin positive.

There is no apparent association between cryptorchidism and the development of interstitial cell tumours.

As with the other neoplasms, interstitial cells stain positively for calretinin.

 

Canadas A, Romão P, Gärtner F. Multiple Cutaneous Metastasis of a Malignant Leydig Cell Tumour in a Dog. J Comp Pathol. 2016; 155(2-3):181-184.

Mischke R, Meurer D, Hoppen H-O, Ueberschar S, Hewicker-Trautwein M. (2002) Blood plasma concentrations of estradiol-17B, testosterone and testosterone/oestradiol ratio in dogs with neoplastic and degenerative testicular diseases. Res Vet Sci 73: 267-272.

Peters MAJ, de Long FH, Teerds KJ, Rooij DG, Dieleman SJ, van Sluijs FJ. (2000) Ageing, testicular tumours and pituitary-testis axis in dogs. J Endocrinol 166: 153-161.

Radi ZA, Miller DL.(2005) Immunohistochemical expression of calretinin in canine testicular tumours and normal canine testicular tissue. Res Vet Sci. 79(2):125-129.

Macroscopic appearance

As with any mass derived from endocrine tissue, there will be an argument about whether a particular lesion is focal or nodular hyperplasia or neoplasia. Most would agree that the large masses are neoplastic, but using an arbitary size on differentiating these runs counter to the transformation theory of neoplasia. From a pragmatic point of view, it makes no difference prognostically. Interstitial cell tumours are well circumscribed expansile and non invasive neoplasms that have a tan colour. The presence of many vascular channels, and in some, lakes of blood or haemorrhage means they may have large red to black regions throughout. Many are incidental lesions discovered when the testis is routinely cut at surgery or necropsy. Some are large enough to cause testicular enlargement.

Figure : Interstitial cell tumour. The adjacent testis is atrophic .

Figure : Metastatic interstitial cell tumour. Multiple yellow tan nodules were present throughout the parenchyma and capsule of this testis (YB141530).

.Microscopic features

The histological appearance of the neoplastic cells in interstitial cell tumours is characteristic. The neoplasms are very well differentiated and the neoplastic cells resemble normal interstitial endocrine cells. There are 3 main patterns listed in Kennedy et al (1998) - the solid-diffuse, cystic-vascular and pseudoadenomatous patterns but in each the neoplastic cells are the same - with only their arrangement and relationship to the vessels varying. There is no prognostic difference with this division into different patterns. The cells are arranged in variably sized clusters or sheets that are surrounded by or are surrounding blood filled spaces. They tend to form a typical endocrine pattern of fine packeting, and the cells are polygonal with abundant cytoplasm. This may be vacuolated with microvesicles of lipid or with cytoplasmic clearing. Some cells may contain fine brown lipofuscin granules. Nuclei are usually uniform in size and round. Mitoses are exceedingly rare even in metastatic tumours. Intranuclear cytoplasmic inclusions may be found in the nuclei (Sanford et al 1987).

 

Figure : Interstitial cell tumours. Solid-diffuse pattern with cells packeted in a typical endocrine arrangement.

Figure : Interstitial cell tumours. Packeting and anisokaryosis.

Figure : Interstitial cell tumours. Pseudoadenomatous pattern.

Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S (1998). Histological Classification of Tumors of the Genital System of Domestic Animals. World Health Organisation International Histological classification of Tumours of Domestic Animals. Armed Forces Institute of Pathology and Americal Registry of Pathology Washington DC.

Sanford SE, Miller RB, Hoover DM. (1987) A light and electron microscopical study of intranuclear cytoplasmic invaginations in interstitial cell tumours of dogs. J Comp Pathol. 97(6): 629-635.

Immunohistochemistry

Reference

AE1/AE3

Vimentin

S100

melanin A

Inhibin

OCT4

CD30

AFP

PLAP

Calretinin

PGP 9.5

KIT

E cadherin

NSE

GATA-4

Hwang et al (2007)

0/1

0/1

0/1

0/1

1/1

0/1

Owston, Ramos-Vara (2007)

1/1

1/1

0/1

0/1

0/1

0/1

0/1

1/1

Ramos-Vara, Miller (2009)

27/28

Canadas et al (2016)

1/1

1/1

PLAP = Placental alkaline phosphatase, OCT, AFP = alpha fetoprotein,

Canadas A, Romão P, Gärtner F. Multiple Cutaneous Metastasis of a Malignant Leydig Cell Tumour in a Dog. J Comp Pathol. 2016; 155(2-3):181-184.

Hwang D-N, Yhee J-Y, Yu C-H, Lyoo Y-S, Sur J-H (2007) Immunohistochemical analysis of canine testicular tumors. ACVP/ASVP meeting abstract, Vet Pathol 44: 751

Owston MA, Ramos-Vara (2007) Histologic and immunohistochemical characteristics of a testicular mixed germ cell sex cord stromal tumor and a Leydig cell tumor in a dog. ACVP/ASVP meeting abstract, Vet Pathol 44: 751

Owston MA, Ramos-Vara (2007) Histologic and immunohistochemical characteristics of a testicular mixed germ cell sex cord stromal tumor and a Leydig cell tumor in a dog. Vet Pathol 44: 936-943.

Ramos-Vara JA, Miller MA (2009) Immunohistochemical Evaluation of GATA-4 in Canine Testicular Tumors. Vet Pathol 48: 493-496.

Sertoli cell tumour

Sertoli cell tumours are one of the most common and well known testicular tumours, especially because of their propensity to induce a feminization syndrome. They arise especially in cryptorchid testes and those in the abdomen are more likely to be affected. Metastatic disease occurs, but it is rare. There are 2 metastatic tumours out of 202 in the YB database

Sertoli cell tumours are mostly found when there are lesions associated with hormonal secretion by the tumour, and when they cause testicular and or scrotal enlargement. While most authors do not measure the volume of testicular tumours, there is a suggestion that the secondary effects are related to the size of the neoplasm, and as such, tumours in cryptorchid testes are likely to achieve a large size, and are more likely to be associated with secondary effects.

Hormone production by Sertoli cell tumours, because of the feminisation seen clinically, was assumed to be the result of estrogen production but many dogs with feminisation do not have a significantly increased estradiol concentration. Even so, Peters et al (2000) examined 13 dogs with Sertoli cell tumours and 8 had feminisation. Affected dogs, as a group, had higher estrodiol and inhibin like immunoreactivity than in normal dogs and dogs with tumours but without clinical signs. Testosterone, FSH and LH concentrations were lower than normal. Miscke et al (2002) examined 6 dogs with Sertoli cell tumours. Feminisation was seen in 5 dogs. All 6 dogs had significantly higher estradiol concentrations than normal dogs. Intraabdominal tumours had the highest concentrations. Testosterone concentration was lowest in this group also. Dreimanis et al (2012) evaluated preputial cytology as an indicator of estrogen secreting testicular tumors and found that 10 of 45 dogs had an serum estrogen concentration of greater than 40 pmol/L. So it is clear that some Sertoli cell tumours are responsible for estrogen production. The increased concentration in inhibin like reactivity is believed to be responsible in the others. Inhibin is normally part of the negative feedback system so that it inhibits the release of pituitary gonadotropin (especially LH and FSH). This lowers testosterone secretion by interstitial cells and alters the testosterone estradiol ratio.

The feminizing effects of some Sertoli cell tumours includes the presence of gynecomastia, attraction of affected dogs to other male dogs, alopecia, and hyperpigmentation, and testicular atrophy. Dogs can develop prostatic disease from prostatic hyperplasia, and from squamous metaplasia of the prostatic epithelium. There may be development of a pancytopaenia that is poorly responsive. As part of this, thrombocytopenia may result in bleeding tendencies. About one half of Sertoli cell tumours have feminisation (Weaver (1983). These effects are reversed when the offending neoplasm is removed. The pathophysiology of oestrogen induced toxicosis of the bone marrow is not known (Sontas et al 2009)

Sertoli cell tumours can produce other hormones. Fadok et al (1986) reported on a dog with hyperprogesteronemia in a dog with a Sertoli cell tumours..

Urinary obstruction is a rare complication of a Sertoli cell tumour. Jacobs et al (1988) reported on 2 dogs with enlarged

Sertoli cells of immature dogs express anti Mullerian hormone, but this expression is lost in post pubertal dogs. It expression is consistently present in Sertoli cell tumours (Banco et al 2012)

Metastasis of Sertoli cell tumours is reported, and there are no cytological features to indicate those likely to metastasise. Metastasis, when present, are often to the spermatic cord but some are to the local lymph node or beyond (Coffin et al 1952, McNeil and Weaver, 1980) .Weaver (1983) reported on 67 cases with Sertoli cell tumours and 4 had confirmed or suspected metastasis.

As with all other testicular neoplasms, Sertoli cell tumours stain for calretinin

U. Dreimanis, K. Vargmar, T. Falk, M. Cigut and L. Toresson (2012) Evaluation of preputial cytology in diagnosing oestrogen producing testicular tumours in dogs J Sm Anim Pract 2012, 53: 536–541

Radi ZA, Miller DL.(2005) Immunohistochemical expression of calretinin in canine testicular tumours and normal canine testicular tissue. Res Vet Sci. 79(2):125-129.

Macroscopic findings

Sertoli cell tumours are usually recognised when they are large enough to cause testicular enlargement. They are usually expansile and well demarcated tumours that are solid and some contain a variable number of cystic spaces. The neoplasm is usually white in colour, but some are red or red brown. They are often hard to cut, and do not appreciably bulge on cut section. Beams or trabeculae of fibrous tissue are usually prominent and abundant.

 

Figure : Solid Sertoli cell tumour.

Figure : Mostly solid Sertoli cell tumour with some cystic regions. Tissue is fixed in formalin

Figure : Mostly cystic Sertoli cell tumour, same tumour as Fig above. Tissue is fixed in formalin

Figure : Bilateral Sertoli cell tumours in bilateral abdominal cryptorchid testis of the same dog.

Microscopic findings

The histological appearance of most Sertoli cell tumours is very characteristic. They are the well differentiated tumours. The cystic regions are more problematic and some have been mistaken for epithelial neoplasms.

Well differentiated solid Sertoli cell tumours are composed of beams of mature fibrous tissue with abundant collagen - some are so collagenous that they appear to be hyalinized. Between these beams are tubular structures of varying size. Some are smaller than normal seminiferous tubules and most are larger. These contain mature Sertoli cells that are elongate or even spindle shaped with the cells bridging from one side to the other. Larger tubules may have a lumen - so that the largest ones appear as cystic structures. Individual cells have well defined cytoplasmic boundaries, a pale or clear fibrilar cytoplasm and an open oval nucleus. Most have only occasional mitosis. The more anaplastic tumours tend to form larger diffusely arranged sheets of cells with a haphazard arrangement and marked anisocytosis. Regions of necrosis may be present.

 

There are isolated reports of Sertoli cell tumours containing structures within tubules that resemble the Call-Exner bodies, structures more often seen in granulosa cell tumours (Bazzo et al 2002)

Figure : Sertoli cell tumour - solid type with typical tubular structures and septae of fibrous tissue.

Figure : Sertoli cell tumour - higher magnification of above fig.

Figure : Sertoli cell tumour, cystic type.

Figure : Sertoli cell tumour, higher magnification of Fig above.

 

Bazzo R, Sarli G, Mandrioli L, Marcato PS (2002) Sertoli cell timour with Call-Exner-like bodies in a dog. J Vet Med A 49: 535-537.

Brodey RS, Martin JE. (1958) Sertoli cell neoplasms in the dog: the clinicopathological and endocrinological findings in 37 dogs. J Amer Vet Med Assoc 133: 249-257.

Coffin DL, Munson TO, Scully RE (1952) Functional Sertoli cell tumour with metastasis in a dog. J Amer Vet Med Assoc 352-358

Dreimanis U, Vargmar K, Falk T, Cigut M L, Toresson L (2012) Evaluation of preputial cytology in diagnosing oestrogen producing testicular tumours in dogs. J Sm Anim Pract 2012, 53: 536–541

Fadok VA, Lothrop CD, Coulson P. (1986) Hyperprogesteronemia associated with Sertoli cell tunor and alopecia in a dog. J Amer Vet Med Assoc 188: 1058-1059.

Jacobs G, Barsanti J, Prasse K, Selcer B. (1988) Colliculus seminalis as a cause of a urethral filling defect in two dogs with Sertoli cell testicular neoplasms. J Amer Vet Med Assoc 192: 1748-1750.

McNeil PE, Weaver AD. (1980) Massive scrotal swelling in two unusual cases of canine Sertoli cell tumour. Vet Rec 106: 144-146.

Mischke R, Meurer D, Hoppen H-O, Ueberschar S, Hewicker-Trautwein M. (2002) Blood plasma concentrations of estradiol-17B, testosterone and testosterone/oestradiol ratio in dogs with neoplastic and degenerative testicular diseases. Res Vet Sci 73: 267-272.

Peters MAJ, de Long FH, Teerds KJ, Rooij DG, Dieleman SJ, van Sluijs FJ. (2000) Ageing, testicular tumours and pituitary-testis axis in dogs. J Endocrinol 166: 153-161.von Bomhard D, Pukkavesa C, Haenichen T (1978) The Ultrastructure of testicular tumours in the dog: III Sertoli cells and Sertoli cell Tumours and general conclusions. J Comp Path 88: 67-73.

Radi ZA, Miller DL.(2005) Immunohistochemical expression of calretinin in canine testicular tumours and normal canine testicular tissue. Res Vet Sci. 79(2):125-129.

Sontas HB, Dokuzeylu B, Turna O, Ekici H. (2009) Estrogen-induced myelotoxicity in dogs: a review. Canadian vet J 50: 1054-1058

Weaver AD. (1983) Survey with follow-up of 67 dogs with testicular sertoli cell tumours. Vet Rec 113: 105-107.

Immunohistochemistry

Reference

AE1/AE3

Vimentin

S100

melanin A

Inhibin

OCT4

CD30

AFP

PLAP

Calretinin

PGP 9.5

KIT

E cadherin

NSE

GATA 4

AMH

Hwang et al (2007)

5/5

5/5

0/5

0/5

5/5

0/5

Doxsee et al 2006

0/6

6/6

6/6

0/6

3/6

Ramos-Vara, Miller 2009

21/21

Yu et al 2009

14/15

0/15

0/15

8/15

6/15

10/15

Banco et al 2010

7/21

21/21

13/21

Banco et al 2012

24/24

PLAP = Placental alkaline phosphatase, OCT, AFP = alpha fetoprotein,

B. Banco B, Giudice C, Veronesi MC, Gerosa E, Grieco V. (2010) An Immunohistochemical Study of Normal and Neoplastic Canine Sertoli Cells. J Comp Path 143: 239-247

B. Banco B, M. C. Veronesi MC, C. Giudice C, A. Rota A V. Grieco V. (2012) Immunohistochemical Evaluation of the Expression of Anti-Mullerian Hormone in Mature, Immature and Neoplastic Canine Sertoli Cells. J Comp Path 2012 146: 18-24.

Doxsee AL, Yager JA, Best SJ, Foster RA. (2006) Extratesticular interstitial and Sertoli cell tumors in previously neutered dogs and cats: A report of 17 cases. Canadian Vet J. 47: 763-766.

Hwang D-N, Yhee J-Y, Yu C-H, Lyoo Y-S, Sur J-H (2007) Immunohistochemical analysis of canine testicular tumors. ACVP/ASVP meeting abstract, Vet Pathol 44: 751

Owston MA, Ramos-Vara (2007) Histologic and immunohistochemical characteristics of a testicular mixed germ cell sex cord stromal tumor and a Leydig cell tumor in a dog. ACVP/ASVP meeting abstract, Vet Pathol 44: 751

Owston MA, Ramos-Vara (2007) Histologic and immunohistochemical characteristics of a testicular mixed germ cell sex cord stromal tumor and a Leydig cell tumor in a dog. Vet Pathol 44: 936-943.

Ramos-Vara JA, Miller MA (2009) Immunohistochemical Evaluation of GATA-4 in Canine Testicular Tumors. Vet Pathol 48: 493-496.

Yu C-H, Hwang D-N, Yhee JY, KimJH, Im K-S, Nho W-G, Lyoo Y-S, Sur J-H, (2009) Comparative immunohistochemical characterization of canine seminomas and Sertoli cell tumors J Vet Sci 10: 1-7

Germ cell tumors

Neoplasms of the testis categorized as germ cell tumours have a phenotype indicating they originated from the primordial germ cells that originated in the yolk sac and migrated to the gonad. They become spermatogonia. These cells have an amazing degree of pluripotency, being able to differentiate to any tissue in the body. When they form tissues of all different embryonic types (ectoderm (including neuroectoderm), mesoderm, and endoderm) they are called teratomas. Seminomas are very common in dogs - they are a more primitive and poorly differentiated type of neoplasm. Other types are rarely reported - like seminoma with neuroectodermal differentiation (Saegusa et al (2011). Other germ cell neoplasms, such as yolk sac tumours, endodermal sinus tumours, embryonal sinus tumours, embryonal carcinomas and choriocarcinomas, have not been reported.

Seminoma

Seminomas are very common in dogs, and, although there are differences between various surveys, have the same prevalence as interstitial cell tumours (see above). They cause testicular enlargement as the main clinical sign..

Seminomas have 2 main patterns - an intratubular type that is often microscopic and found incidentally, and a diffuse type. It is assumed that they begin as intratubular neoplasms that expand to form the diffuse type. Older dogs are more likely to be affected, and there is an increased prevalence in cryptorchid testis, especially those that are inguinally retained.

The vast majority of dogs with seminomas do not have altered concentrations of hormones like estradiol, testosterone, FSH or LH (Peters et al 2000, Mische et al 2002). There is only one report of a dog with a seminoma that had hyperestrogenism. (Kim and Kim 2005). Taniyama et al (2001) stained normal testes and testes with tumours with inhibin alpha, betaB, Beta A and 3bets-hydroxysteroid dehydrogenase. Seminomas did not stain for these.

Little is known of their pathogenesis.

The lymphocytes present either diffusely, or in clusters within the tumours are mostly cytotoxic type T cells (CD3+, annd CD8+), except where follicles are formed - where the cells are of the B cell (CD21) lineage. CD18+, CD11c cells (dendritic or antigen presenting cells) were present and much more numerous than monocytes and macrophages. Most leucocytes were positive for both MHC1 and MHC-II . Many of the neoplastic cells were MHC-1 positive, suggesting that there is an immune reaction to the neoplastic cells. Regulatory T cells (Tregs), identified by the presence of Foxp3, are also present in low numbers, and especially in the diffuse seminoma rather than the intratubular type.

Murakami et al (2001) examined normal testis and cells of common testicular neoplasms for cyclin expression. Spermatogonia and primary spermatocytes expressed cyclin A, but not D1, D2 or E. Thirteen or 14 seminomas (2 of 11 Sertoli cell tumours but not interstitial cell tumours expressed cyclin A), suggesting they represent arrested development at those stages.

Benazzi et al (1995) examined laminin expression to examine the distribution of basement membranes. They were present around intratubular but not diffuse seminomas. Loss of basement membranes was correlated to increases in the proliferative activity of cells as measured using mitotic index, PCNA and Ki67 activity.

Inoue and Wada (2000) examined testicular tumours for p53 and p21 expression. Seminomas had an intense p53 and p21 nuclear protein staining whereas Sertoli cell tumours had a moderate or intense staining and interstitial cell tumours had no staining. There was weak staining of spermatocytes in normal tubules.

Peters et al (2003) examined testis and testicular tumours for insulin like growth factor expression, IGF receptor expression, IGF binding proteins and the expression of steroidal hormones and enzymes including IGF1, IGF2, IGF1R, IGF2R, IGFBP2, 4 and 5, and androgen receptor, 5 alpha reductase and aromatase. Seminomas had a lower expression of IGFBP1, IGF-I, and 5alpha-reductase type I, and aromatase.

Radi and Miller (2005) examined calretinin expression in normal testes and in testicular tumours. All tumours expressed calretinin.

Grieco et al (2007) examined 43 seminomas and stained them with PAS and human placental alkaline phosphatase (PLAP) so as to classify them according to the human scheme as classical seminoma (20 cases, PAS and HPAP positiive) and 23 as spermatocytic seminoma (23 cases, PAS and PLAP negative).

Lucas et al (2012) reported on a dog with metastatic seminoma

 

Benazzi C, Sarli G, Preziosi R, Marcato PS. (1995) Laminin expression in testicular tumours of the dog. J Comp Pathol. 112(2):141-150.

Grieco V, Rondena M, Romussi S, Stefanello D, Finazzi M. (2004) Immunohistochemical characterization of the leucocytic infiltrate associated with canine seminomas. J Comp Pathol 130(4):278-84.

Grieco V, Riccardia E,Rondenaa M,Ciampia V, Finazzia M. (2007) Classical and Spermatocytic Seminoma in the Dog: Histochemical and Immunohistochemical Findings. J Comp Path 137: 41-46

Inoue M, Wada N. (2000) Immunohistochemical detection of p53 and p21 proteins in canine testicular tumours.Vet Rec.25;146(13):370-372.

Kim O, Kim KS. (2005) Seminoma with hyperesterogenemia in a Yorkshire Terrier. J Vet Med Sci. 67(1):121-123.

Kim JH, Chon SK, Im KS, Kim NH, Cho KW, Sur JH (2013) Infiltrating Foxp3+ Regulatory T cells and Histopathological Features in Canine Classical and Spermatocytic Seminomas. Reprod Dom Anim 2013, 48: 218-222.

Lucas X, Rodenas C, Cuello C, Gil MA, Parrilla I, Soler M, Belda E, Agut A (2012). Unusual Systemic Metastases of Malignant Seminoma in a Dog. Reprod Dom Anim 2012, 47: 59–61

Mischke R, Meurer D, Hoppen H-O, Ueberschar S, Hewicker-Trautwein M. (2002) Blood plasma concentrations of estradiol-17B, testosterone and testosterone/oestradiol ratio in dogs with neoplastic and degenerative testicular diseases. Res Vet Sci 73: 267-272.

Murakami Y, Tateyama S, Uchida K, Yamaguchi R. (2001) Immunohistochemical analysis of cyclins in canine normal testes and testicular tumors. J Vet Med Sci. 63(8):909-912.

Peters MAJ, de Long FH, Teerds KJ, Rooij DG, Dieleman SJ, van Sluijs FJ. (2000) Ageing, testicular tumours and pituitary-testis axis in dogs. J Endocrinol 166: 153-161.

Peters MA, Mol JA, van Wolferen ME, Oosterlaken-Dijksterhuis MA, Teerds KJ, van Sluijs FJ. (2003) Expression of the insulin-like growth factor (IGF) system and steroidogenic enzymes in canine testis tumors.Reprod Biol Endocrinol.14;1:22.

Radi ZA, Miller DL.(2005) Immunohistochemical expression of calretinin in canine testicular tumours and normal canine testicular tissue. Res Vet Sci. 79(2):125-129.

Taniyama H, Hirayama K, Nakada K, Numagami K, Yaosaka N, Kagawa Y, Izumisawa Y, Nakade T, Tanaka Y, Watanabe G, Taya K.(2001) Immunohistochemical detection of inhibin-alpha, -betaB, and -betaA chains and 3beta-hydroxysteroid dehydrogenase in canine testicular tumors and normal testes. Vet Pathol. 38(6):661-666

Prognosis

The majority of seminomas are benign and metastatic seminomas are very rare. While their histological appearance is, based on first principles, that of a malignant neoplasm (see below) very few metastasise. When they do metastasise, they spread to the spermatic cord and then throughout the body. The eye and brain can be affected (HogenEsch et al 1987).

McDonald et al (1988) report on 4 dogs that had metastatic seminoma with regional metastasis. All dogs received radiotherapy and all except 1 had a long survival (37-57 months) with the 4th dog dying of transitional cell carcinoma and renal failure. The survival time of dogs not given treatment is not known.

HogenEsch H, Whiteley HE, Vicini DS, Helper LC. (1987) Seminoma with metastases in the eyes and the brain in a dog. Vet Pathol 24: 278-280.

McDonald RK, Walker M, Legendre AM, vanEe RT, Gompf RE. (1988) Radiotherapy of metastatic seminoma in the dog. Case reports. J Vet Intern Med. 2(2):103-107.

Macroscopic findings

Testicular seminomas have a characteristic appearance in the dog. They are usually found when they cause testicular enlargement, so they form an intratesticular mass. This mass usually well circumscribed. It is white and homogenous, rarely having obvious necrosis or hemorrhage when it is small. There is no obvious septation, although some can be multilobular. They typically are soft and do not bulge on cut section.

.

Figure : Intratesticular seminoma in a dog. The mass is white, homogenous and soft.

Microscopic findings

The histological appearance of cells in seminomas, be they intratubular or diffuse in pattern are identical and resemble the spermatocytic seminomas of humans. (Looijenga et al 1994, Maiolino et al 2004) .

The lesions are infiltrative, but often relatively well circumscribed. They are composed of large round cells and they have a characteristic feature of having clusters of lymphocytes near vessels. These lymphocytes are mostly CD8+ T suppressor types (Grieco et al 2004). The neoplastic cells are large round cells with a small amount of clear cytoplasm, a large round nucleus, and prominent mucleoli. Anizokaryosis is 2 fold, bi- and multinucleate cells are common and mitoses are up to10pHPF.

Figure : Testicular seminoma, subgross. The mass is homogenous and has many lymphoid aggregates throughout (dark foci).

Figure : Intatubular seminoma.

Figure : Diffuse seminoma with lymphoid aggregates.

Figure : Canine testicular seminoma

Grieco V, Rondena M, Romussi S, Stefanello D, Finazzi M. (2004) Immunohistochemical characterization of the leucocytic infiltrate associated with canine seminomas. J Comp Pathol 130(4):278-84.

Looijenga LH, Olie RA, Van der Gaag I, van Sluijs FJ, Matoska J, Ploem-Zaaiger J, Knepfle C, Ostgerhuis JW. (1994) Seminomas of the canine testis. Counterpart of spermatocytic seminoma in men? Lab Invest 74: 490-496

Maiolino P, Restucci B, Papparella S, Paciello O, De Vico G. (2004) Correlation of nuclear morphometric features with animal and human World Health Organization international histological classifications of canine spontaneous seminomas. Vet Pathol 41: 608-611.

Immunohistochemistry

Reference

AE1/AE3

Vimentin

S100

melanin A

Inhibin alpha

OCT4

CD30

AFP

PLAP

Calretinin

PGP 9.5

KIT

E cadherin

NSE

GATA 4

Hwang et al (2007)

2/9

1/9

0/9

0/9

1/9

0/9

Owston and Ramos-Vara (2007)

1/1

1/1

0/1

1/1

1/1

1/1

0/1

0/1

Ramos-Vara, Miller (2009)

0/24

Yu et al 2009

5/20

9/20

0/20

0/20

8/20

4/20

20/20

PLAP = Placental alkaline phosphatase, OCT, AFP = alpha fetoprotein,

Hwang D-N, Yhee J-Y, Yu C-H, Lyoo Y-S, Sur J-H (2007) Immunohistochemical analysis of canine testicular tumors. ACVP/ASVP meeting abstract, Vet Pathol 44: 751

Owston MA, Ramos-Vara (2007) Histologic and immunohistochemical characteristics of a testicular mixed germ cell sex cord stromal tumor and a Leydig cell tumor in a dog. ACVP/ASVP meeting abstract, Vet Pathol 44: 751

Owston MA, Ramos-Vara (2007) Histologic and immunohistochemical characteristics of a testicular mixed germ cell sex cord stromal tumor and a Leydig cell tumor in a dog. Vet Pathol 44: 936-943.

Ramos-Vara JA, Miller MA (2009) Immunohistochemical Evaluation of GATA-4 in Canine Testicular Tumors. Vet Pathol 48: 493-496.

Yu C-H, Hwang D-N, Yhee JY, KimJH, Im K-S, Nho W-G, Lyoo Y-S, Sur J-H, (2009) Comparative immunohistochemical characterization of canine seminomas and Sertoli cell tumors J Vet Sci 10: 1-7

Seminoma with neuroectodermal differentiation

Saegusa et al (2011) reported on a dog with a cryptorchid testis and 2 nodules. One was a Sertoli cell tumor, and the other was a seminoma with regions of focal primitive neuroectodermal differentiation including rosettes and immunoreactivity for S100, NSE, synaptophysin and neurofilaments.

Saegusa Y, Hayashi H, Taniai E, Imaoka M, Ohishi T,Wang L, Mitsumori K, Shibutan M. (2011) Spermatocytic seminoma with neuroectodermal differentiation and Sertoli cell tumor in a dog. Vet Pathol 2011, 48: 1024-1028.

Teratoma

Mixed Germ cell - Sex cord stromal cells

These tumours are not commonly reported (Turk et al 1981, Reis-Filho et al 2004, Ortega-Pacheco et al 2006) ). There is one series reported by Patnaik and Mostofi (1993). In this series of 16 affected dogs, 7 were predominantly germ cell tumours and 11 were predominantly Sertoli cell tumours. The features of each component is identical to that described above for each. It is easy to imagine that many mixed tumours are diagnosed as the predominant cell type, especially when most surgical specimens are not widely sampled. There are no specific features to separate these from other testicular tumours.

Banco et al (2015) reported on their immunohistochemistry

There are 7 cases in the YB database.

Figure : Mixed germ cell - gonadal stromal tumour with feature of seminoma and Sertoli cell tumour.

Figure : Mixed germ cell - gonadal stromal tumour with both seminoma and Sertoli cell components.

Reference

AE1/AE3

Vimentin

S100

melanin A

Inhibin alpha

AMH

Desmin

PLAP

Calretinin

PGP 9.5

KIT

E cadherin

NSE

GATA 4

Banco et al (2015) (ScST)

6 of 13

all

all

all

all

8 of 13

all

Banco et al (2015) GC

7 of 13

8 of 13

 

Banco B, Giudice C, Ghisleni G, Romussi S, Behar DK, Grieco V. Immunohistochemical study of mixed germ cell sex cord stromal tumours in 13 canine testes. J Comp Pathol 2015; 152: 182-187

Ortega-Pacheco A, Rodríguez-Buenfil JC, Segura-Correa1 JC, Bolio-Gonzalez ME, Jiménez-Coello M and Linde Forsberg C. (2006) Pathological Conditions of the Reproductive Organs of Male Stray Dogs in the Tropics: Prevalence, Risk Factors, Morphological Findings and Testosterone Concentrations. Reprod Dom Anim 41 :429-437

Patnaik AK, Mostofi FK. (1993) A clinicopathologic, histologic, and immunohistochemical study of mixed germ cell-stromal tumors of the testis in 16 dogs. Vet Pathol 30: 287-295.

Reis-Filho JS, Ricardo S, Gartner F, Schmitt FC. (2004) Bilateral gonadoblastomas in a dog with mixed gonadal dysgenesis. J Comp Pathol. 130(2-3):229-233.

Turk JR, Turk MA, Gallina AM. (1981) A canine testicular tumor resembling gonadoblastom a.Vet Pathol. 18(2):201-207

Extratesticular testicular tumours in previously neutered dogs

Although it is rare, primary testicular tumours may be found in previously neutered dogs (Robinson, 1973, Doxsee et al 2006). Robinson (1973) reports a single case of a dog with a Sertoli cell tumour - the dog had feminisation. Doxsee et al (2006) report twelve cases and there are anicdotal reports of this having been seen around the world. Of the 12 the the series, dogs, 11 had Sertoli cell tumours and one had an interstitial cell tumour. One of the dogs with the Sertoli cell tumours had feminisation. All dogs were castrated as juveniles, and developed neoplasia later in life, either in the spermatic cord, at the site of the prescrotal incision or in the scrotal skin. Excision was curative. It is assumed that the neoplasms arose from testicular tissue implanted after the testis as inadvertantly incised during castration. The presence of ectopic tissue developing neoplasia was also a possibility. Most of the neoplasms were small (about 1.5 cm diameter, but the largest was 5.5cm. Histologically they were identical to Sertoli cell tumours of the testis as described above.

Doxsee AL, Yager JA, Best SJ, Foster RA. (2006) Extratesticular interstitial and Sertoli cell tumors in previously neutered dogs and cats: A report of 17 cases. Canadian Vet J. 47: 763-766.

Meichner K, Montgomery SA, Borst LB, Murphy KM, Grindem CB. Pathology in Practice. J Amer Vet Med Assoc 2016; 249:

 

Robinson RR (1973). A Sertoli cell tumor in ectopic testicular tissue. Mod Vet Pract 54 (11): 69.

Neoplasms of the collecting system (including the rete)

This section is restricted to neoplasms only. If we choose to use the term 'tumour' as a swelling, then tumours can also be cysts! Cysts of the testis are described below.

Rete neoplasms

The collecting ducts of the testis include the rete testis and efferent ductules. Neoplasms of these ductules are epithelial in type, so epithelial tumors of the testis are believed to be derived from these. Neoplasms with an phenotype resembling epithelial tissue can also be part of a teratoma (or teratocarcinoma) and occasionally, cystic Sertoli cell tumours can have an epithelial appearance. It is important to perform multiple sections to exclude teratome and to do immunohistochemistry for various cytokeratins to positively identify the neoplastic cells as epithelial.

The one case reported in detail (Radi et al 2004) was of a mucinous phenotype. Their neoplasms (it was a bilateral disease in the affected dog) was both cytokeratin and vimentin positive, and stained for carcinoembryonic antigen and for neurone specific enolase. It was S100 negative.

Radi ZA, Miller DL, Hines ME 2nd. (2004) Rete testis mucinous adenocarcinoma in a dog. Vet Pathol. 41(1):75-78

Miscellaneous primary neoplasms

The presence of cells from a wide range of tissue types means that neoplasia of those cells can result in an almost infinite range of neoplasms. This reported in case reports or other sites are indicated below.

Hemangioma/hemangiosarcoma

Clarke (1979) found a testicular hemangiosarcoma in an older dog. The testis was retained in the abdomen. McEntee (1990) reports seeing 2 cases in dogs. One was metastatic.

Clarke RE (1979) A new method to repair a peroneal hernia in a dog caused by hemangiosarcoma in a retained testicle. Aust Vet Pract 9: 71-73. as cited by McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic press. p298.

McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic press. p298

Histiocytic sarcoma

Several of these neoplasms has been seen, although none have been reported in the refereed literature.

Leiomyoma

Leiomyomas of the tunica albuginea of the testis is reported - see tumours of the tunics

Mast cell tumour

There is a mention of a dog with a mast cell tumour of the testis in a study of cytology of testicular neoplasia (Masserdotti et al 2005)

Masserdotti C, Bonfanti U, De Lorenzi D, Tranquillo M, Zanetti O. (2005) Cytologic features of testicular tumours in dog. J Vet Med A Physiol Pathol Clin Med.52(7):339-346

Osteosarcoma

Patnaik (1990) reported a case of primary osteosarcoma in the testis of a dog.

Patnaik AK (1990) Canine extraskeletal osteosarcoma and chondrosarcoma: a clinicopathologic study of 14 cases. Vet Pathol. 27(1):46-55.

Peripheral nerve sheath tumour (schwannoma, neurofibroma)

Rothwell et al (1986) reported on a dog with a schwannoma of the testis. It was a solitary lesion in the testis, and presumably arose from a testicular nerve.

Rothwell TLW, Papadimitriou JM, Middleton DJ. (1986) Schwannoma in the testis of a dog. Vet Pathol 23(5):629-631

Tumours metastatic to the testis

Testes are not routinely examined in animals with metastatic neoplasia, and, if a metastatic disease is present and the testis is found to have a metastasis, mention is made in the report, but an electronic literature search is unlikely to find it. One might expect the most likely candidate would be lymphoma. Melanoma and transitional cell carcinoma are both sufficiently widespread to involve the testis.

Lymphoma

Nieto et al (1989) found one case of lymphoma with involvement of the testis of a dog. McEntee (1990) reports seeing lymphoma in the testis of a dog.

Nieto JM, Pizarro M, Balaguer LM, Romano J. (1989) Canine testicular tumors in descended and cryptorchid testes. Dtsch Tierarztl Wochenschr. 96(4):186-189

McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic

Non-neoplastic masses and cysts of testis

Testicular spermatocele and spermatic granuloma

A spermatocele is a cavity filled with spermatozoa. Small spermatoceles are dilated tubules such as the straight seminiferous tubule (also called the tubuli recti), or rete testis. Those cavities that are not lined by epithelium are where spermatozoa leak into the interstitium. These cavities quickly incite an inflammatory response and become spermatic granulomas. Spermatoceles and spermatic granulomas are unusual in the testis as a primary lesion as most are secondary to orchitis, needle biopsy or trauma.

Cysts of the testis

Cysts within the testis, lined by epithelium and with a central cavity filled with fluid, can be derived from the the rete testis, a network of ducts or from remnants of mesonephric tubules called the efferent ductules.mesonephric ductules have ciliated epithelium and this is a major differentiating factor. Ortega-Pacheco et al (2006) reports finding a testicular cyst but no further details were given.

Ortega-Pacheco A, Rodríguez-Buenfil JC, Segura-Correa1 JC, Bolio-Gonzalez ME, Jiménez-Coello M and Linde Forsberg C. (2006) Pathological Conditions of the Reproductive Organs of Male Stray Dogs in the Tropics: Prevalence, Risk Factors, Morphological Findings and Testosterone Concentrations. Reprod Dom Anim 41 :429-437

Cystic rete testis

A cystic rete testis is different to other cysts in that it is a cystic dilation of the rete tubules secondary to obstruction of fluid outflow. It can be secondary to segmental aplasia of the mesonephric duct or spermatic granuloma of the epididymal head. Most cases would be missed or not deemed significant, especially if the primary lesion was identified. Typically, the mediastinum of the testis is affected so the testis has a large central cavity. This is reported in the fox, but there are no detailed descriptions in the domestic dog. There is one case in the YB database (YB135534).

Figure : Cystic rete testis in a dog.

Efferent ductule cyst

Cysts of the efferent ductules are true cysts, as they have an epithelial lining and a central cavity filled with fluid. These are different to cystic rete testis, a condition where there is cystic dilation of all of the rete testis from obstruction to outflow as would occur in segmental aplasia of the epididymis or spermatic granuloma of the epididymal head (see above).They are lined by ciliated epithelium, a distinguishing feature from a 'rete cyst'.

Wakui et al (1997) provides a detailed description of an efferent ductule cyst in a dog. It was located within the testis where the rete testis exits the testis.

Rete testis cyst

There are 2 cases in the YB database (YB116854 and 127115). In both cases, cysts were filled with a clear fluid, and were lined by a single layer of nonciliated epithelium. One dog had testicular atrophy and fibrosis that likely contributed to cyst formation by obstructing ducts. The other was an incidental finding.

Figure : Rete cyst in the testicular parenchyma of a dog.

Figure : Histology of a rete cyst of the testis with an epithelial lining and seminiferous tubules below.

Epidermoid cyst

There is a report of an epidermoid cyst (Wakui et al 1992) within the testis of a dog. It was composed of a wall resembling the epidermis and a lumen filled with keratin. It was suspected to be a monophasic teratoma.

Wakui S, Furusato M, Nomura Y, Iimori M, Kano Y, Aizawa S, Ushigome S. (1992) Testicular epidermoid cyst and penile squamous cell carcinoma in a dog. Vet Pathol. 29(6):543-545

'>Cystic interstitial cell tumour

One of the differential diagnoses of cystic rete testis is a rete cyst. Cystic interstitial cell tumour can, on rare occasions, be cystic and confused with a true cyst. Somewhere in the cystic cavity will be neoplastic cells. There will be no epithelium so if a cystic structure is found and histologically there is no epithelial wall, examination of the formalin fixed tissue will be necessary to identify the origin of the 'cyst' or, more correctly, the pseudocyst.

Figure : Cystic interstitial cell tumour in a dog.

Parasites of the testis

Brookins et al (2009) reports on a stray dog that was castrated at an animal shelter and the testis was found to be heavily infected with intermediate stage of a pentastomid Porocephalus crotali. The dog had widespread peritoneal infestation with this intermediate stage.

Brookins MD, Wellehan JFX, Roberts JF, Allison K, Curran SS, Childress AL, Greiner EC (2009) Massive Visceral Pentastomiasis Caused by Porocephalus crotali in a Dog. Vet Pathol 2009 46: 460-463.

 

Disease of the efferent ductules

The efferent ductules are the tubules that link the rete testis to the epididymal duct. Diseases, such as spermatic granuloma of the epididymal head, and cysts of the ducts are to be found under disease of the epididymis (non inflammatory) below.