Squamous Cell Carcinoma of the Penis with Pulmonary Metastasis and Paraneoplastic Hypertrophic Osteopathy in a Dog
ABSTRACT
Squamous cell carcinoma of the penis was diagnosed by incisional biopsy of a penile mass in a 12 yr old intact male beagle dog presenting with hemorrhagic discharge from the prepuce. Penile amputation, orchiectomy with scrotal ablation, and scrotal urethrostomy were performed. Hypertrophic osteopathy secondary to pulmonary metastatic disease occurred 10 mo after the surgery. Palliative treatment with piroxicam was administered and led to complete resolution of the clinical signs of the pain. Sixteen months following surgery, the dog presented with significant dyspnea and anorexia and was euthanized due to poor prognosis. This case report describes a rare penile tumor, squamous cell carcinoma. Consequent paraneoplastic hypertrophic osteopathy and its palliative treatment are also reviewed.
Introduction
A 12 yr old male intact beagle dog was referred to Instituto Nacional de Protecao Animal, Rio de Jeneiro, Brazil, for evaluation of a large exophytic mass on the penis. The dog had presented to the referring veterinarian with a 1-mo history of hemorrhagic discharge from the prepuce. Coming from an enzootic area for transmissible venereal tumors, the patient had previously been treated empirically with three weekly doses of vincristinea (0.75 mg/m2, IV bolus). No response was observed to vincristine therapy, prompting referral for further evaluation.
Case Report
On initial physical examination, a painful and friable, broad-based, 5-cm long mass was observed, involving the entire length of the glans penis (Figure 1). The mass appeared to originate from the penile mucosa. The right testis was enlarged and firm on palpation. No palpable lymphadenopathy was detected, and there were no additional findings on physical exam.
Citation: Journal of the American Animal Hospital Association 53, 5; 10.5326/JAAHA-MS-6425
An incisional biopsy was performed, and histopathological analysis revealed a moderately differentiated squamous cell carcinoma (SCC). Clinical staging included a complete blood cell count, a serum biochemistry profile, abdominal ultrasound, and three-view thoracic radiographs. All results were found to be within normal limits.
Penile amputation, orchiectomy with scrotal ablation, and scrotal urethrostomy were performed, and recovery was uneventful. Histopathologic evaluation of the penile mass confirmed the diagnosis of intermediate-grade SCC. Complete surgical margins were achieved. Two inguinal lymph nodes that were resected and submitted for staging purposes were determined to be free of neoplastic cells. Microscopic examination of the right testicle revealed a mass of 1-cm diameter, consistent with an interstitial cell tumor (Leydig cell tumor).
Initial recovery was uneventful, and the patient was reevaluated at 3-mo intervals by physical examination, complete blood cell count, serum biochemistry profile, urinalysis, abdominal ultrasound, and thoracic radiographs. The first three reevaluations failed to demonstrate local recurrence or metastatic dissemination of the disease.
Ten months following surgery, the patient presented with edema and pain of all metacarpal and metatarsal areas and reluctance to walk. Survey radiographs of both forelimbs identified a proliferative periosteal reaction of the distal radius and metacarpal bones, suggestive of hypertrophic osteopathy (HO). (Figure 2) Thoracic radiographs revealed a large, 7-cm diameter, soft tissue density in the right cranial lung lobe. The owners declined definitive therapy or additional diagnostics, and the dog was administered piroxicamb (0.3 mg/kg [0.14 mg/lb], per os once daily) for palliation of pain. Clinical signs of bone pain and lameness gradually resolved over the following 4 wk. The patient was asymptomatic upon reevaluation 1 mo later, despite both the lung mass and periosteal proliferative lesions appearing unchanged on repeat radiographs. Administration of oral piroxicam was continued at the dose previously prescribed.
Citation: Journal of the American Animal Hospital Association 53, 5; 10.5326/JAAHA-MS-6425
Sixteen months following surgery, the dog presented with acute signs of dyspnea and anorexia. Lameness, edema, or pain could not be detected on physical examination, and the lung mass still appeared unchanged on radiographs. The owners elected to euthanize the dog. Necropsy was declined, but consent for a fine-needle aspiration of the lung mass was granted. Cytological examination of the aspirate was consistent with SCC, presumably metastatic from the original penile neoplasia, although primary pulmonary SCC could not be ruled out.
Discussion
The case reported here is unique in that it describes two uncommon oncologic entities, penile SCC and paraneoplastic HO. Although SCC occurs frequently in dogs, to the authors’ knowledge, its location on the penis has been reported only once. Wakui et al. reported a dog with penile SCC and a testicular epidermoid cyst. The dog was treated by penile amputation and orchiectomy and was eventually lost to follow-up at 9 mo. Metastatic disease had not been detected.1
Squamous cell carcinoma most commonly affects the oral cavity, the skin, and the nail bed. It accounts for 5% of all cutaneous tumors in dogs. Local behavior and metastatic potential of canine SCC is known to vary depending on the location.2 Those arising from the skin of the flank and ventral abdomen tend to be locally aggressive with a low metastatic rate, while the metastatic potential of nail bed SCC has been reported to vary from 10% to 29%.3 In the oral cavity, location may also dictate behavior and prognosis. Tumors located in the rostral mandible and maxilla may be detected earlier than those in the caudal oral cavity and may therefore be more amenable to complete surgical excision. They are also expected to have a lower metastatic rate. In contrast, SCCs arising in the tonsils or at the base of the tongue tend to be locally aggressive and highly metastatic.4
Transmissible venereal tumor is the most common penile tumor in dogs. Other primary penile tumors are very rare. Tumors affecting penile soft tissues include fibrosarcoma, lymphoma, hemangiosarcoma, adenocarcinoma, mast cell tumor, SCC, and squamous papilloma.5–7 One case of metastatic carcinoma to the penis has also been reported.8
Hypertrophic osteopathy, also known as pulmonary hypertrophic osteopathy, hypertrophic osteoarthropathy, and acropachy, is an uncommon paraneoplastic syndrome reported to occur in animals and humans.9 This painful disorder is characterized by periosteal new bone formation at the distal end of long bones. The most common causes are primary or metastatic lung tumors of various histologic classifications.10 Isolated reports described renal carcinomas, prostatic carcinoma, nephroblastoma, and bladder rhabdomyosarcoma, without intrathoracic metastatic disease, as possible causes of paraneoplastic HO.10–12 Infectious (bacterial endocarditis), parasitic diseases (Spirocerca lupi, Dirofilaria immitis), and right-to-left shunting patent ductus arteriosus have also been associated with HO in dogs.10–13
The specific mechanisms that lead to HO are not completely understood. The etiologies suspected to play a role in the development of HO include: hormonal (growth hormone, adrenocorticotropic hormone, melanocyte-stimulating hormone, calcitonin, and gastrin), growth factors (platelet-derived growth factor and vascular endothelial growth factor), and increased vagal tone to the limbs.10,14–18 Clinical remission may be obtained with a combination of surgical removal of the lung lesion, systemic chemotherapy, and unilateral intrathoracic vagotomy. In such cases, resolution of clinical signs, (pain and edema on the limbs) can also be accompanied with improvement of radiographic lesions.18–20
In the case reported here, although improvements of the lung or the bone lesions were not detected radiographically, treatment with piroxicam resolved the clinical signs of pain and consequent lameness associated with HO. The dog remained active and free of clinically detected pain or edema until euthanasia was requested 6 mo later.
Multiple studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for both prevention and treatment of cancer.22 While inhibition of cyclooxygenases (COXs), COX-1 and COX-2, is the primary mechanism of action of NSAIDs, COX-independent effects against tumors have also been proposed.23 Up-regulation of COX-2 in tumors is associated with increased growth rate, angiogenesis, cell motility, metastatic potential, resistance to apoptosis, and suppression of the host immune response.24,25 Modulation of COX-2 activity is one among many ways in which NSAIDs interfere with cancer growth and metastasis. Piroxicam is a NSAID, which has been shown in dogs to preferentially inhibit the inducible COX-1.25 Since inflammation is not a described histological feature of HO, the clinical benefit from piroxicam in our patient may have been purely analgesic.
Conclusion
To the author’s knowledge, this is the first case report of hypertrophic osteopathy resulting from pulmonary metastasis secondary to a penile squamous cell carcinoma in a dog.
Friable mass involving most of the glans penis.
Antero-posterior view of the distal radius, carpal, and metacarpal bones, showing periosteal proliferation perpendicular to the long axis of the bones.
Contributor Notes
