Penile Amputation and Scrotal Urethrostomy Followed by Chemotherapy in a Dog with Penile Hemangiosarcoma

Introduction

Reported penile neoplasms include squamous cell carcinoma, mast cell tumor, extramedullary plasmacytoma, transmissible venereal tumor, papilloma, lymphoma, fibroma, hemangiosarcoma (HSA), mesenchymal chondrosarcoma, osteosarcoma, and glomangioma. Of those, transmissible venereal tumor is the most common penile tumor in dogs. Little information exists in the literature regarding penile HSA, which includes one single case report with focus on the imaging diagnosis and no discussion on survival time.¹ This report describes the surgical outcome, chemotherapy, and patient follow up of a standard poodle diagnosed with penile HSA that underwent penile amputation and scrotal urethrostomy surgery followed by chemotherapy with doxorubicin.

Case Report

A 7 yr old castrated male standard poodle weighing 25 kg was referred to The Veterinary Teaching Hospital, University of Illinois with a 5 day history of hematuria and dysuria. He initially presented to the referring veterinarian with a swollen penis and dribbling urine. At the referring veterinarian, results of a complete blood cell count (CBC) and serum biochemical profile were within normal limits. A urine reagent strip indicated 3+ blood on a free-flow sample. Few bacteria were seen in the urine sediment. The clinical signs did not improve after a 5 day course of amoxicillin trihydrate/clavulanate potassium^a (22 mg/kg per os [PO] q 12 hr), and at that point he started to drip blood from his prepuce. The patient was then referred for further diagnostics and treatment.

At the time of referral, the patient was bright, alert, and responsive with a body condition score of 3 out of 9. Slightly tacky mucous membranes and sinus tachycardia were noted. Dehydration was estimated to be 6%. The bladder was moderately distended but soft and nonpainful on palpation. A moderate amount of urine with blood dribbled intermittently from the prepuce during initial evaluation. When voluntary urination was observed, the patient produced a stream of bloody urine with several blood clots. After urination, the bladder was still palpably distended. A 2.5 cm, firm swelling was palpable within the prepuce preventing the penis from being exteriorized normally. Rectal examination and rectal palpation of the prostate were normal.

An 18-gauge IV catheter^b was placed in the left cephalic vein to administer a crystalloid fluid bolus^c (30 mL/kg) followed by a constant rate infusion at 20 mL/kg/hr. A urine sample was collected via cystocentesis and submitted for urinalysis. Blood was collected for a blood gas analysis^d, CBC, serum biochemical profile, and coagulation profile. The lactate concentration was 3.1 mmol/L (reference range, 0.43–0.93 mmol/L), no other abnormalities were noted on blood gas. The CBC and serum biochemical profile results revealed no abnormalities. The urinalysis revealed a specific gravity of 1.038, pH of 5.5, a trace amount of protein, and 40–60 red blood cells/high-power field. Prothrombin time, activated partial thromboplastin time, D-dimers, and fibrinogen were within normal limits.

An abdominal-focused assessment with ultrasonography (US) for trauma was performed to evaluate the presence of fluid in the abdominal cavity, which was negative. Lateral and ventrodorsal abdominal radiographs were performed revealing a soft-tissue swelling of the distal prepuce and lysis of the cranial margin of the os penis. A complete abdominal US, including imaging the prepuce and penis, was performed, showing an irregular and mixed echogenic mass surrounded by fluid with areas of mineralization in the distal aspect of the penis. The remainder of the exam was unremarkable. A thoracic-focused assessment with US for trauma was performed, showing no evidence of pleural effusion, pericardial effusion, or heart masses. Thoracic radiographs were normal.

The patient was sedated with hydromorphone^e (0.3 mg/kg), dexmedetomidine^f (3 μg/kg), and atropine^g (0.44 mg/kg) to help better examine the penis and to place a urinary catheter. After sedation, the penis was easily exteriorized and a large blood clot was removed from the prepuce revealing an ulcerated/necrotic mass that was actively hemorrhaging (Figure 1). Pressure was applied to the mass and epinephrine^h was dripped onto the mass to help control hemorrhage. After bleeding was controlled, an 8-French urinary catheter was placed and connected to a closed urine collection system. An abdominal pressure wrap, which encompassed the cranial penis and prepuce, was placed to avoid trauma and further bleeding.

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The patient was hospitalized in the intensive care unit with IV crystalloid fluids^c at 32 mL/hr with 16 mEq/L of potassium chlorideⁱ added. A constant rate infusion of fentanyl^j (3 μg/kg/hr), lidocaine^k (25 μg/kg/min), and ketamine^l (3 μg/kg/min), and one dose of cefazolin^m (20 mg/kg IV) were administered to control pain and secondary bacterial infection.

The day after presentation, a fine-needle aspirate and an impression smear were obtained from the mass and submitted for cytology. An incisional biopsy was performed under sedation for histopathology in case the results of the cytology were nondiagnostic (the sample was ultimately not submitted due to the owner's decision to go to surgery based on the cytology results). A mattress suture pattern with 3-0 nylonⁿ was placed following the biopsy to close the ulcerated surface of the mass in attempt to control the active hemorrhage. The pressure wrap and urinary catheter were removed once bleeding was controlled.

The sample was diagnosed as a sarcoma on cytology based on the presence of several individualized and aggregated mesenchymal cells with multiple characteristics of malignancy. Cells were large with deeply basophilic rounded to wispy cytoplasm and an ovoid nucleus that was eccentrically placed in the rounded cells and centrally located in other cells. Many cells contained several punctate, clear, cytoplasmic vacuoles. Eosinophilic product was observed within low numbers of cells. Malignant characteristics included multinucleation, anisocytosis, anisokaryosis, and multiple prominent variably sized nucleoli (Figure 2). Based on cellular morphology, HSA and fibrosarcoma were considered likely differential diagnoses. Osteosarcoma was also considered due to the presence of mesenchymal cells with ovoid, eccentrically placed nuclei and the radiographic evidence of osteolysis of the os penis. Cells were tested for alkaline phosphatase activity by incubating unstained slides in a colorimetric phosphatase substrate. The neoplastic cells were negative for alkaline phosphatase, which eliminated osteosarcoma arising from the os penis as a differential diagnosis.

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Based on the cytology, a penile amputation with scrotal urethrostomy was performed. The patient was induced with fentanyl IV (3 μg/kg) and propofol^o IV (4 mg/kg), and anesthesia was maintained with isoflurane^p in O₂. Fentanyl was administered at a constant rate infusion at 5 μg/kg/hr during the procedure. Bupivicaine^q (2 mg/kg) and preservative-free morphine^r (0.1 mg/kg) were administered for epidural analgesia.

Methylene blue dye^s (0.1 mL) was injected in the penile mucosa close to the ulcerated mass to help locate the sentinel lymph node. A fusiform incision was made around the prepuce and penis. The penis and prepuce were dissected from the body wall from cranial to caudal. Penile and preputial vessels were either cauterized or ligated with 3-0 poliglecaprone 25^t. Uptake of dye was observed during surgery in the superficial inguinal lymph nodes, which were excised with blunt dissection. The incision was extended caudally to include the scrotum. The retractor penis muscle was transected and the penis was amputated. Once the penis and associated prepuce were removed, the tunica albuginea was apposed with 3-0 poliglecaprone 25. The subcutaneous tissue and skin cranial to the planned urethrostomy site were closed in two layers with 2-0 polydioxanone^u in the subcutaneous tissue and 3-0 poliglecaprone 25 intradermal. The urethra was catheterized with a 10-French red rubber catheter placed retrograde into the proximal segment and into the bladder. A scrotal urethrostomy was then performed with the urethra incised on midline over the catheter and the urethral mucosa was sutured to the skin using 4-0 polyglactin 910^v. Simple interrupted sutures were placed in the most caudal and cranial aspects of the urethrostomy site. The lateral aspects were closed in two simple continuous patterns.

The patient recovered well from anesthesia and was moved to the intensive care unit. Crystalloid fluids^c (5 mL/kg/hr) and fentanyl (3 μg/kg/hr) were continued. His incision site was monitored for suture dehiscence and for obstruction of the urethrostomy. No complications were noted during hospitalization and he was discharged the day after surgery with amoxicillin trihydrate/clavulanate potassium (20 mg/kg PO q12 hr), carprofen^w (2 mg/kg PO q12 hr), and tramadol^x (4 mg/kg PO q12 hr). A fentanyl patch^y (3 μg/kg/hr transdermally) was applied to the skin.

Three days after surgery, the patient presented through the emergency service reportedly straining to urinate. On physical examination all vital signs were normal. The patient was panting and showed abdominal discomfort on palpation. The urinary bladder was large and unable to be expressed. The penile amputation site was healing well and the urethrostomy site had mild erythema and swelling. A urinary catheter was passed without any resistance and his bladder was emptied. He was prescribed diazepam^z (5 mg PO q12 hr) for muscle relaxation. The urinary catheter was removed within 12 hr of placement, and the patient was hospitalized for 2 additional days to ensure that he was able to urinate. The patient was able to urinate normally during the hospitalization and was sent home with diazepam (5 mg PO q 12 hr).

The mass was submitted for histopathology, and its margins were inked and evaluated by a board-certified pathologist. The results revealed that the mass was infiltrating the submucosa, poorly circumscribed, unencapsulated, moderately cellular, and neoplastic. The neoplastic cells were arranged in variably sized, blood-filled, anastomosing, irregular vascular channels, wrapping around dense collagen bundles. Adjacent to the mass there was a focally extensive area of lytic necrosis characterized by eosinophilic cellular and basophilic karyorrhectic debris, intact and degenerate neutrophils, fibrin, edema, and hemorrhage. The penile mucosa and corresponding preputial mucosa were mildly hyperplastic. The sentinel lymph node showed changes consistent with chronic draining hemorrhage. The histological diagnosis was an intermediate-grade HSA with complete excision.

Sixteen days after surgery, the patient was presented to the oncology service of the Veterinary Teaching Hospital, University of Illinois for follow-up treatment. A CBC, serum biochemical profile, thoracic radiographs, and abdominal US were performed. No evidence of metastases was noted on either thoracic radiographs or abdominal US. Hematology and serum biochemical results were unremarkable. The surgical site was well healed and chemotherapy with doxorubicin^aa was initiated. The patient was treated at 30 mg/m² IV doxorubicin q 3 wk for five doses. Prior to each treatment, a CBC and electrocardiogram were evaluated and were normal. Repeat imaging of the thorax and abdomen at 49 days was declined by the owner. Thoracic radiographs (three views) and abdominal US were performed at the last chemotherapy treatment (105 days) and showed no evidence of metastasis. Full staging (i.e., a CBC, serum biochemical profile, three-view thoracic radiographs, and abdominal US) was performed 56 days following chemotherapy (161 days after diagnosis). CBC results revealed a mild thrombocytopenia (125 × 10⁹/L; reference range 200–900 × 10⁹/L). Biochemical profile results were within normal limits. Three-view thoracic radiographs were normal. On abdominal US, a rounded, anechoic mass with a central hyperechoic region was identified in the retroperitoneal space caudal to the left kidney. The mass measured 35.8 mm in diameter. Fine-needle aspirate revealed a few atypical mesenchymal cells. Computed tomography of the abdomen to further characterize the mass was declined by the owner and exploratory surgery was performed.

The patient was induced with IV fentanyl (3 μg/kg) and propofol (4 mg/kg), and anesthesia was maintained with isoflurane in O₂. Fentanyl was administered at a rate of 5 μg/kg/hr during the procedure. The liver, intestines, kidneys, and adrenal glands appeared grossly normal. The spleen was enlarged but of normal contour and texture. A mass resembling a hematoma surrounded by fat was seen in the left perirenal region. The mass was resected and submitted for histopathology, which showed focal fibrosis with edema, acute hemorrhage, and granulation tissue. No neoplastic cells were identified.

After 205 days from the initial diagnosis of HSA, the dog presented to a local emergency clinic recumbent, minimally responsive, and with pale mucous membranes. Abdominocentesis revealed nonclotting blood. The patient was euthanized with a presumptive diagnosis of hemoabdomen secondary to HSA. No necropsy was performed.

Discussion

To the authors' knowledge, this case report is the second published report of HSA of the penis in a dog and the first report to describe the outcome of the surgery, chemotherapy, and patient follow up. The first reported case of penile HSA was in a 12 yr old castrated male Labrador retriever that had a 2 day history of dysuria and stranguria with no observed urine stream. In that report, abdominal radiographs showed osteolysis of the distal third of the os penis with no evidence of associated periosteal reaction or soft-tissue swelling. A urethrogram was performed and showed an oval filling defect in the distal penile urethra at the level of the os penis. A penile amputation and scrotal urethrostomy were performed. The histologic diagnosis of the penile mass was HSA.¹ No details about treatment, follow-up information, or survival were provided.

HSA is a malignant neoplasm of vascular endothelial cells with an aggressive biological behavior and a poor prognosis. The overall prevalence for all forms of HSA is reported to be 0.3–2% of all tumors in dogs.^2,3 That type of neoplasm can affect any tissue in the body, and the three most commonly reported primary sites are the spleen (28–50%), right atrium and auricle (3–50%), and skin or subcutaneous tissue (13%).³ Other primary sites include liver, kidney, bladder, prostate, peritoneum, lung, pulmonary artery, aorta, muscle, bone, oral cavity, tongue, vertebral body, and central nervous system.^2–6 Little information exists in the literature regarding penile HSA, making prognostication difficult.

In the patient described in this report, a diagnosis of sarcoma was made based on cytology of a fine-needle aspirate. Cytology offers the advantage of rapid turnaround time, low morbidity, no need for sedation or special equipment, and minimal risks of complication. Limitations of cytology include possible low cellularity and difficulty in specifying tumor subtype, which makes it less accurate than histopathology. Differential diagnoses for sarcoma on this particular cytology were HSA, fibrosarcoma, and osteosarcoma. Staining the cells for alkaline phosphatase activity was performed to rule out osteosarcoma. Detection of intracellular alkaline phosphatase within the neoplastic cells of a sarcoma is a rapid and simple test, which is 100% sensitive and 89% specific for diagnosing osteosarcoma.⁷ In this case report, the neoplastic cells were negative for alkaline phosphates, effectively eliminating osteosarcoma as a diagnosis.

Due to the location of the mass, radical excision was elected to improve the likelihood of attaining clean margins. That procedure entails resection of the penis, prepuce, and in some cases, the adjacent scrotal tissue. After amputation, the penile mass and associated prepuce were submitted for histopathology and an intermediate-grade HSA was diagnosed.

Accurate identification of the lymph node receiving drainage from a tumor site is of utmost importance. The first lymph node receiving drainage from a specific region of the body is referred to as the sentinel lymph node. Localization and excision of the sentinel lymph node has become the standard of care in humans. Methylene blue dye was injected into the penile mucosa to locate the sentinel lymph node in this case. That technique was previously used in a study involving five dogs, and identification of the sentinel lymph node for excision was achieved in 98% of the injection sites.^8–10 The sentinel lymph node was also submitted for histopathology and revealed draining hemorrhage but no evidence of neoplasia.

A scrotal urethrostomy was performed after amputation. Common complications of urethrostomy involve urine dribbling, skin scalding, cystitis, and stricture formation. Three days after surgery, the patient described in this report presented to the emergency service with inability to empty his bladder. A urinary catheter was easily passed and normal urine was produced. Medical options offered to the owner were to perform either a urethroscopy or a contrast urethrogram to rule out the presence of intra- or extraluminal obstruction but those were declined.

Due to the lack of data regarding penile HSA it is difficult to compare or estimate survival after surgery alone versus surgery and chemotherapy. Survival times for dogs with splenic HSA are typically less than two to three months after splenectomy alone.^11–13 A modest survival benefit from the addition of adjuvant doxorubicin-based chemotherapy with a median survival of 6–9 months if no visceral spread is detected at the time of splenectomy has been reported.^14,15 The median survival time in dogs with subcutaneous HSA varied from 172 to 242 days when treated with either surgery alone or surgery and doxorubicin, respectively, but it can go as high as 1,189 days.^3,4,14,16 Tumor location had no effect on outcome.¹⁷

The dog in this report was euthanized 205 days after original diagnosis of HSA, which is consistent with the median survival reported for dogs with subcutaneous HSA treated with surgery and chemotherapy. Although it is not possible to draw significant conclusions from one case, it is likely that the surgery and chemotherapy were instrumental in prolonging this dog's survival.