Challenging cases in internal medicine: A dog with an enlarged prostate and bloody preputial discharge

A 5-YEAR-OLD, 114-lb (51.8-kg) neutered male German shepherd was examined because of a three- to four-week history of bloody preputial discharge and prostatomegaly. Initial evaluation by this dog's veterinarian had revealed marked prostatic enlargement on rectal palpation. Cytologic examination of a prostatic wash sample had revealed degenerative neutrophils but no bacteria or neoplastic cells. A two-week course of oral trimethoprim-sulfadiazine had been dispensed. The discharge resolved initially but returned when the antimicrobial therapy was discontinued. The dog was then referred to the University of Georgia College of Veterinary Medicine for further evaluation.

Initial diagnostic procedures

A review of this dog's history revealed that it was born unilaterally cryptorchid and had been castrated at 6 months of age. The testicle removed through an abdominal approach was not submitted for histopathologic examination. The location of the scrotal testicle (right or left side) was not noted.

Table 1: Complete Blood Count Results

The dog was bright, alert, and responsive. Thoracic auscultation revealed an intermittent arrhythmia (consistent with a past diagnosis of atrial premature contractions) with normal lung sounds. Abdominal palpation was unremarkable, and rectal palpation revealed moderate to severe, symmetric prostate enlargement. Additionally, the prostate was nonpainful on palpation, and the median prostatic groove was easily palpable. A blood-tinged, serosanguineous discharge constantly dripped from the dog's prepuce during the examination (and throughout the dog's hospital stay). Occasionally, frank blood was seen in the discharge.

Table 2: Serum Chemistry Profile Results

A complete blood count showed mild hemoconcentration and thrombocytopenia (Table 1). A serum chemistry profile revealed mild azotemia, hypercalcemia, and hypercholesterolemia (Table 2). Complete urinalysis of a urine sample obtained by cystocentesis revealed microscopic hematuria but no bacteria or neoplastic cells (Table 3). The urine was adequately concentrated, suggesting prerenal azotemia. A bacterial culture from this sample produced only light growth of Staphylococcus species (colony count about 2,000/ml). The result indicated a contaminant, so sensitivity and susceptibility testing was not done.

Table 3: Urinalysis Results

An abdominal radiographic examination showed moderate prostatomegaly with no evidence of sublumbar lymph node enlargement (Figure 1). Additionally, mild hepatosplenomegaly was noted. A uniformly enlarged prostate of mostly uniform echotexture was seen on abdominal ultrasonographic examination. One small prostatic cyst was seen dorsal to the urethra (Figure 2). Splenomegaly was noted, but the splenic architecture was of uniform echotexture. The liver and both kidneys appeared to be normal. Despite an extensive evaluation, no evidence of a retained abdominal testicle was found. An ultrasound-guided fine-needle aspiration of the prostate was performed, and microscopic review of this sample revealed only normal prostatic epithelial cells with no evidence of neoplasia or inflammation.

Figure 1: A lateral radiograph of the dog's caudal abdomen obtained on admission revealing marked prostatomegaly (black arrow). The white arrow indicates the cranially displaced urinary bladder.

Initial treatment and further evaluation

Since all physical and laboratory data pointed to a diagnosis of benign prostatic hyperplasia, we decided to further evaluate the possibility of this disease before proceeding with more invasive diagnostic testing. With that in mind, a sample for a baseline testosterone concentration was submitted. While awaiting these results, we instituted antimicrobial therapy with enrofloxacin (5 mg/kg orally b.i.d.) empirically to treat a possible undetected prostatitis. We chose enrofloxacin for its excellent distribution into the prostate gland. We discontinued the antibiotic therapy after one week since the blood-tinged preputial discharge continued despite therapy.

Figure 2: An ultrasonogram obtained on admission. Note the mostly uniform echotexture of the prostatic parenchyma. The white arrow indicates a small cyst in the dorsal prostate.

One week after our initial evaluation, the baseline testosterone concentration returned as 2,747 pg/ml (reference range for castrated dogs < 50 pg/ml; reference range for cryptorchid dogs 100 to 500 pg/ml; reference range for intact dogs > 1,000 pg/ml). Satisfied that this dog was producing a testosterone concentration adequate to predispose the dog to benign prostatic hyperplasia, we decided to perform a laparoscopic evaluation of the abdomen to attempt to identify an intra-abdominal testicle and obtain a prostatic biopsy sample. Preoperatively, an electrocardiogram showed intermittent atrial premature contractions; however, echocardiography revealed no evidence of heart chamber enlargement or valvular insufficiency.

At laparoscopy, both vasa deferentia were seen, as was the left inguinal ring. A vascular bundle that traversed the left inguinal ring appeared to be thrombosed, but there appeared to be no vas deferens exiting this side. No structures were seen traversing the right inguinal ring. The left vas deferens was followed for about 4 cm from its approximated urethral insertion, where the vas deferens ended abruptly. The right vas deferens was followed about 5 cm from its approximated urethral insertion, at which point a small mass of tissue was identified. This mass was externalized through a trocar site located about 2 cm paramedially to the midprepuce on the right side. It was removed along with about 3 cm of the right vas deferens and submitted for histopathologic examination. The regions of the prostate seen laparoscopically revealed no gross abnormalities; however, only the right lobe of the prostate was isolated (through blunt dissection). Several samples of the prostate were obtained with a Tru-Cut biopsy needle and submitted for histopathologic examination as well.

Anesthetic recovery was normal, and the dog was discharged the next day pending histopathologic examination of both the prostatic biopsy samples and the mass removed from the distal end of the right vas deferens. Carprofen (2.2 mg/kg orally b.i.d. for three days) was dispensed for postoperative pain relief.

Histopathologic examination of the prostatic biopsy samples revealed mild plasmacytic prostatitis with well-differentiated prostatic glands; no evidence of cysts, infection, or neoplasia was noted. The microscopic appearance of the biopsy samples was consistent with benign prostatic hyperplasia. Examination of the right-sided mass at the tip of the vas deferens revealed focal lymphocytic-plasmacytic cellulitis with mineralization and connective tissue. No testicular tissue was seen in this mass.

Given our biopsy confirmation of benign prostatic hyperplasia and prostatitis and lack of evidence of a retained intra-abdominal testicle, we decided to perform provocative testing to further evaluate the presence of retained testicular tissue. We performed a human chorionic gonadotropin (HCG)-response test (Table 4) to support our concern that this dog had viable testicular tissue that was producing the testosterone needed to cause benign prostatic hyperplasia. The response to HCG seen in this patient thus prompted us to resume our search for an undescended intra-abdominal testicle that had evaded laparoscopic exploration or, less likely, an extratesticular source of testosterone.

Table 4: Endocrinologic Testing Results

Definitive diagnosis and treatment

Before we performed an abdominal exploratory, another abdominal ultrasonographic examination was conducted to search for evidence of retained testicular tissue. Again, detailed abdominal ultrasonographic evaluation revealed no findings consistent with retained testicular tissue. However, ultrasonographic evaluation of the subcutaneous tissues cranial to the scrotum on the left side identified tissue consistent with testicular tissue. Firm pressure applied medially to this region caused the testicle to become palpable just cranial to the scrotum, but release of this pressure caused the testicle to return to its deep subcutaneous site, again making it nonpalpable on routine scrotal palpation. With this new information, a castration was performed after the testicle was identified during surgical exploration of the prescrotal subcutaneous tissues on the dog's left side. Gross examination of the testicle revealed the absence of a vas deferens (Figure 3). The dog recovered from the exploratory successfully and was discharged pending histopathologic examination of the testicular tissue.

Figure 3: A normal testicle obtained from a young male dog after routine orchiectomy (left) and the testicle obtained surgically from the patient in this report (right). The white arrows indicate the vas deferens of the normal testicle. The black arrows indicate the absence of a vas deferens in the testicle on the right.

Histopathologic examination of this testicle revealed an interstitial (Leydig) cell tumor along with testicular atrophy and degeneration with aspermia. There was no microscopic evidence of a vas deferens in any section of the testicle evaluated. The epididymis was devoid of sperm, and no evidence of a vas deferens arising from the epididymal tissue was noted.

Recheck examination of this dog seven weeks after the castration revealed a markedly smaller prostate on rectal palpation compared with previous examinations. Additionally, the preputial discharge had resolved. Repeat abdominal radiographs confirmed the absence of prostatomegaly noted on previous examinations (Figure 4).

Figure 4: A lateral radiograph of the caudal abdomen taken seven weeks after castration. The black arrow indicates a much smaller prostate compared with presurgical radiographs (Figure 1). The white arrow indicates the urinary bladder.

Discussion

Benign prostatic hyperplasia

Benign prostatic hyperplasia is a common, spontaneous, age-related condition in sexually intact male dogs. The condition increases in frequency with age, and nearly 95% of intact male dogs are affected by 9 years of age.1 Mild inflammatory changes in the prostate are commonly associated, without bacteria.2 Benign prostatic hyperplasia commonly causes no clinical signs in affected animals; however, if the prostate gland is markedly enlarged, a dog may experience constipation, tenesmus, or thin stools secondary to dorsal prostatic compression of the rectum.1-4 Also, intermittent, clear to light-yellow to hemorrhagic urethral discharge may occur in some dogs. Although signs consistent with urethral compression such as dysuria or stranguria are common in affected men, they are rarely present in dogs.1 At the time of initial presentation, this dog may have had a staphylococcal prostatitis, but this was not confirmed. Confirmation would have required quantitative culture of prostatic fluid obtained by aspiration, ejaculation, or prostatic massage. It is evident that antimicrobial therapy did not eliminate the urethral discharge, while castration did.

The pathophysiology of benign prostatic hyperplasia is not completely understood, but dihydrotestosterone, which is irreversibly converted from testosterone by the action of 5α-reductase in prostatic epithelial cells, is accepted as a key hormone in stimulating enhancement of prostate growth.1,4,5 Other hormones (estrogen, prolactin, growth hormone) have been implicated in its pathophysiology as well.1,4 The dog in this report had circulating testosterone concentrations well within the ranges expected for intact dogs despite its castrated status. However, there are conflicting reports regarding serum testosterone concentrations in cryptorchid dogs. One group of researchers reported no significant difference in serum testosterone concentrations between unilaterally cryptorchid dogs and normal control dogs.6 In contrast, another group of researchers7 reported a tendency for lower serum testosterone concentrations in unilaterally and bilaterally cryptorchid dogs during sexual development as compared with normal age-matched dogs both before and after administration of a luteinizing hormone-releasing hormone analogue.8 Blood testosterone concentrations may help differentiate among intact, castrated, and bilaterally cryptorchid dogs (Table 5).9

Table 5: Testosterone Concentrations in Normal Intact Dogs and Dogs with Common Testicular Disorders*

Diagnosing benign prostatic hyperplasia involves noting typical clinical signs and detecting prostatic enlargement by palpation and abdominal imaging. Palpating the dog in this report revealed an enlarged, symmetric, and nonpainful prostate, which is consistent with benign prostatic hyperplasia. Complete blood count and serum chemistry profile findings are typically unaffected by uncomplicated hyperplasia, while urinalysis results may be normal, or may reveal hematuria without pyuria or bacteriuria.1,3,4 The mild azotemia noted in this dog was not present on subsequent examinations. We suspected a prerenal cause such as subclinical dehydration or a high-protein meal rather than a renal azotemia since the urine specific gravity was 1.032.10 The mild thrombocytopenia and hepatosplenomegaly were considered clinically insignificant in this dog; however, potential exposure to tick-borne pathogens was not determined serologically. The hypercholesterolemia was likely associated with postprandial hypercholesterolemia, as these samples were obtained when the dog was not fasted. The mild hypercalcemia noted on initial examination was considered consistent with the mild hemoconcentration and was not present in subsequent serum chemistry profile results. The results of all other diagnostic tests (abdominal radiography and ultrasonography, prostatic biopsy and fine-needle aspiration, and prostatic fluid cytology) were deemed consistent with a diagnosis of benign prostatic hyperplasia.

Treatment of benign prostatic hyperplasia is required only when clinical signs warrant, as was the case with the dog in this report. The most effective treatment is castration, which decreases prostate size by 50% within three weeks postoperatively and by 70% within nine weeks.1,4 In this dog, the prostate size was reduced and the clinical signs were completely alleviated by seven weeks after surgery. Several medical options (e.g. diethylstilbestrol, progestins, flutamide, finasteride, tamoxifen citrate) are available for breeding animals or those with inherent anesthetic risks, but none are as effective (physiologically or cost-wise) as castration, and the use of some of these drugs is associated with side effects.1-5

Cryptorchidism

Cryptorchidism is a developmental defect in which complete descent of one or both testes into the scrotum does not occur. The incidence of cryptorchidism has been reported to be 1% to 15% of adult dogs.11 Normally, the testes should descend to the scrotum by 10 to 14 days after birth with both testicles completely within the scrotum by 8 weeks of age. However, some authors think that cryptorchidism cannot be diagnosed until dogs are 6 months of age.12 About 75% of affected dogs are unilaterally cryptorchid, with the right testicle being retained almost twice as often as the left.11 The cryptorchid testis is smaller than the scrotal testis because of the absence of spermatogonia. However, Sertoli and Leydig cells remain, and androgen synthesis is unimpaired11; such was the case with the dog in this report. A retrospective study identified 14 breeds with a significantly higher risk of cryptorchidism and eight breeds with a significantly lower risk of cryptorchidism; German shepherds were on neither of these lists.13

Dogs with cryptorchid testes are reported to have an increased risk of developing testicular neoplasia.11,12,14 Dogs with abdominal testes tend to develop Sertoli cell tumors as a result of the abdominal temperature causing loss of all tubule cells except the Sertoli cells. Conversely, dogs with inguinal testes tend to develop seminomas as a result of transitional inguinal canal temperature, which appears to stimulate neoplastic growth of the spermatogenic cell line. Because temperature does not affect interstitial cells, the incidence of interstitial cell tumors (as seen in this dog) is not thought to be related to cryptorchidism.11 The interstitial cell tumor found in this dog was considered clinically insignificant, as these tumors are hormonally silent and almost always benign.11 Also, the absence of intra-abdominal lymphadenopathy on ultrasonographic examination and surgical exploration of this dog's abdomen lessened our concern of tumor metastasis. Sertoli cell tumors account for about 60% and seminomas for 40% of tumors in cryptorchid testes.14

Cryptorchidism is diagnosed by careful inspection and palpation. Abdominal testicles are difficult to identify by palpation unless diseased and swollen. In the dog in this report, scrotal palpation was normal, and firm medial pressure in the prescrotal subcutaneous tissues while the dog was in dorsal recumbency was required to palpate this testicle. It is postulated that the dog was effectively vasectomized at the time of its original abdominal exploration, complicating proper identification and removal of the remaining testicle at the time of laparoscopic exploration; this finding was supported by gross and histopathologic examination results postcastration.

Treatment of affected dogs is typically limited to castration, and the breeding of affected individuals is discouraged because of the hereditary nature of this disease. Gonadotropins (HCG, gonadotropin-releasing hormone) and androgens (testosterone) have been used with mixed results to treat unilateral and bilateral cryptorchidism.11 Surgical placement of the retained testes into the scrotum (orchiopexy) is considered unethical in veterinary medicine as it allows the possibility of mating (thus, perpetuating the trait) and does not remove the possible development of undesirable sequelae such as testicular neoplasia or torsion.

Although not done by this dog's original veterinarian, histopathologic examination of all intra-abdominal testicles removed surgically or with a laparoscope is recommended15 to evaluate for any testicular neoplasia and to confirm removal of testicular tissue.

John K. Sessions, DVM

Jeanne A. Barsanti, DVM, MS, DACVIM

Department of Small Animal Medicine and Surgery

College of Veterinary Medicine

University of Georgia

Athens, GA 30602

REFERENCES

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