Primary orbital melanoma without ocular involvement in a Balinese cat

Abstract

A 6.5-year-old spayed female Balinese cat was diagnosed with a large and locally invasive primary orbital melanoma, without ocular involvement or detectable metastatic disease. Advanced imaging and immunohistochemical studies helped in obtaining the diagnosis. Because of advanced unresectable disease and ensuing poor quality of life, the cat was euthanized.

A 6.5-year-old, spayed female, cream tabby Balinese cat was presented to the University of Illinois Veterinary Teaching Hospital (UIVTH) for evaluation of a large periorbital swelling on the left side, and ongoing weight loss. For 6 wk prior to referral, the cat had been treated for a presumptive abscess. On 3 different occasions, incisions on the soft palate and on the outer periorbital swelling were performed. A 4th premolar tooth had also been extracted. Three courses of oral antibiotics had been administered (amoxicillin, clindamycin, and amoxicillin-clavulanic acid), but they did not result in significant clinical improvement. On the 3rd visit, the cat had a febrile episode (40°C). Plain radiographs of the head did not show evidence of a radiopaque foreign object, or obvious osteolysis. The results of a complete blood (cell) count (CBC) were within reference ranges. The patient was then referred to the UIVTH medical oncology service for further evaluation.

Case description

On presentation to the UIVTH, the patient was thin (2.68 kg), mildly clinically dehydrated, and had normal vital signs. A large and firm periorbital swelling was observed on the left side (Figure 1). The left eye could not be visualized, and a serosanguineous discharge was observed at the palpebral fissure. The cat demonstrated signs of pain upon opening the mouth, had increased upper respiratory noises (stertor), and a serous left nasal discharge. A small ulcerated area was observed in the mouth, at the site of previous 4th premolar excision. At that time, the main differential diagnoses were abscess, neoplasia (orbital lymphoma, squamous cell carcinoma, soft tissue sarcoma, uveal melanoma with orbital extension), and pseudotumor (granulomatous disease, bacterial cellulitis, inflammatory infiltrate).

Figure 1.

Large soft-tissue mass around the left eye of an adult female Balinese cat. The skin incision had been made prior to presentation in an attempt to lance a suspected abscess.

A CBC, serum biochemical profile, and urinalysis (U/A) were performed. The results from the CBC and U/A did not reveal any abnormality, and the only abnormal value on the biochemical panel was a mildly elevated globulin level (56 g/L; reference range 26 to 51 g/L). Three-view thoracic radiographs were obtained (ventrodorsal and left and right laterals) and interpreted as being normal. An abdominal ultrasonographic study failed to reveal any significant finding. The periorbital swelling was also evaluated with ultrasound under sedation. A fine-needle aspiration of the soft tissue swelling was performed, and slides were submitted for cytopathological analysis, which revealed very large, solitary or clustered, spindle-shaped cells containing large round to oval nuclei, many with a large prominent central nucleolus (Figure 2). The cytoplasm was light basophilic, with elongated outlines and black cytoplasmic granules scattered throughout. These cytopathological findings were suggestive of a melanoma.

Figure 2.

Spindle-shaped cells with anisokaryosis, anisocytosis, large prominent nucleoli (arrowheads), and scattered dark cytoplasmic granules (Wright-Giemsa stain). The very dark cell with cytoplasmic vacuoles (thin arrow) is a melanophage. Bar = 20 μm.

The owners were notified of the presumptive diagnosis of orbital melanoma, either primary or secondary to orbital extension from a uveal melanoma, and a poor prognosis was given, owing to the very invasive nature and advanced stage of the neoplasm, and to a markedly decreased quality of life. They nevertheless elected that the cat should have a computerized tomography (CT) scan, in order to further determine local invasion and better assess the potential for surgical resection. The cat was hospitalized and monitored in the intensive care unit overnight, with continuous maintenance IV fluids (lactated Ringer’s) and oxymorphone (Numorphan; Schering Plough Animal Health, Union, New Jersey, USA) injections, 0.07 mg/kg bodyweight (BW) IV, q5h. The CT scan was performed the following morning, when a very large orbital contrast-enhancing mass was identified compressing the left eye and invading into the nasal cavity and nasopharynx (Figure 3). Since the prognosis was very poor, the invasive mass was considered unresectable, and knowing that the quality of life could not be substantially improved, the owners opted for euthanasia. A complete necropsy was declined, but postmortem enucleation and orbital tissue biopsies were allowed.

Figure 3.

Computerized tomography (CT) imaging of a Balinese cat with a large periorbital irregularly contrast-enhancing mass (asterisks), compressing and distorting the left eye, and invading into the left nasal cavity (arrowheads 1) and nasopharynx (arrowhead 2). The round structures in the mouth are the tracheal tube (large) and esophageal stethoscope (small).

Complete histopathologic examination of the left eye showed multiple severe changes, including subacute lens rupture, with anterior and posterior segmental hemorrhage and fibrosis; posterior synechiae; retinal detachment, with outer retinal necrosis and hemorrhage; and subacute central corneal ulceration. These changes were interpreted as traumatic and degenerative in nature, and nonneoplastic. The biopsies of orbital tissue and the third eyelid revealed atypical cells with a modest amount of cytoplasm that appeared highly vacuolated and had poorly defined borders. The nuclei were highly pleomorphic, anisokaryotic, round, and often indented. They had open vesicular chromatin with multiple, variably sized and shaped, large nucleoli. Mitotic figures were common (3 to 4/400× field) and atypical. Individual cell necrosis was also common. This was interpreted as a poorly differentiated sarcoma.

Given the results of cytopathologic and histopathologic characteristics, the periorbital mass was suggestive of an amelanotic melanoma, but because of the poor differentiation, other sarcomas, anaplastic round cell tumors (including lymphoma), and a carcinoma of the third eyelid gland could not be definitively ruled out. Special and immunohistochemical staining was requested to provide a more definitive diagnosis. No melanin granules could be identified with a Warthin-Starry stain. Vimentin immunostain was positive on most of the tumor cells, confirming a mesenchymal cell origin, whereas cytokeratin staining was negative, ruling out an epithelial tumor. Faint cytoplasmic staining was observed in many tumor cells with Melan A immunostain, suggesting a melanocytic origin. The final diagnosis was a poorly differentiated amelanotic melanoma of the orbital tissues, without primary ocular involvement.

Discussion

Orbital and retrobulbar tumors are occasionally observed in cats and dogs, and a variety of histologic types have been described (1–12). They can be characterized as primary, when arising from any tissues that compose and surround the orbit, or secondary when resulting from orbital extension of tumors of the globe or optic nerve, the nasal cavity or paranasal sinuses, the salivary glands, or orbital involvement by systemic neoplasia (1–12).

The most frequently described orbital tumor in cats is squamous cell carcinoma, followed by other carcinomas, lymphoma, melanoma, and various sarcomas (6–8,10). Other sporadically reported types of feline orbital tumors include hemangioma, chondroma, meningioma, plasmacytoma, and osteoma (6,8,9,11,12). A vast majority of cats reported as having orbital tumors, in fact, have secondary orbital extension by primary ocular melanomas, primary sinonasal, oral, or cunjunctival carcinomas, or orbital involvement by systemic or nasal lymphomas (6–8).

In dogs, the most commonly reported orbital tumors are osteosarcomas, various soft-tissue sarcomas and carcinomas, mast cell tumors, meningiomas, lobular adenomas, and multilobular tumors of bone (1–4,7,8). Other types of canine orbital tumors include melanomas, lymphomas, leiomyoma, osteoma, hemangiosarcoma, and retinoblastoma (4,5,7,8). Similar to cats, many canine orbital squamous cell carcinomas and adenocarcinomas described in the literature are actually invasive primary sinonasal tumors with secondary orbital extension (1,4,7,8).

A thorough search of the veterinary literature in English revealed reports on only 5 cats with melanoma in the orbital area without primary ocular involvement (13–15). All 5 cats had malignant melanomas, 4 involving the bulbar conjunctiva (13,15) and 1 originating in the nictitating membrane (14). Four of these 5 cats developed diffuse metastatic disease (14,15). While a definitive diagnosis was not reached, an additional cat was reported to have a presumptive primary melanoma of the upper palpebral cunjunctiva, with orbital infiltration and regional metastases (16). In the case presented here, the tumor was remarkably large and locally aggressive, filling the entire orbit, causing severe traumatic changes to the globe, and invading the caudal nasal cavity and nasopharynx. There was no evidence of primary or secondary ocular involvement, and clinical staging could not demonstrate measurable metastatic disease. The exact origin of the bulky orbital tumor could not be determined.

Malignant melanoma is well described in cats, the most common primary sites being the eye and the dermis (6,13–15,17–23). While many cases of feline oral melanoma have been reported, the mouth is a much more common primary site of involvement in dogs (15,21–23). Feline malignant melanoma appears to be an aggressive tumor, both locally and with a high rate of dissemination, independent on the primary site of origin (6,15,17–23). While surgery remains the most effective form of therapy (15,17–20,22), a recent report described hypofractionated megavoltage radiation therapy for unresectable oral melanomas in 5 cats (23). Occasionally, feline melanoma cells may be less pigmented, with additional stains being required to confirm the diagnosis (14,19,21). A recent study on 48 cases concluded that Melan A, while being somewhat less sensitive than S100, was a more specific immunostain for poorly pigmented feline melanomas (21). The use of Melan A was helpful to confirm the histopathologic diagnosis of orbital melanoma in the case presented here. It is interesting to notice the discrepancy between the cytopathologic examination, which easily identified cytoplasmic melanin granules (Figure 2), and the histopathologic examination, which required immunostains to better define the cells observed. This difference may stem from a very heterogeneous tumor, with some areas being better differentiated than others.

While abscesses and tumors are the cause of most orbital mass effects, other conditions have been reported and are occasionally encountered (24–33). Many of these reports involve cats with conditions such as orbital cellulitis with Penicillium sp. (24), orbital eosinophilic infiltrate (25), orbital aspergillosis (26), inflammatory retrobulbar pseudotumor (27), and nasal and retrobulbar infection with Pythium insidiosum (28). Reports of canine cases include orbital cryptococcosis (29), orbital cellulitis from Toxocara canis (30), sino-orbital aspergillosis (31), orbital cellulitis from the nasal mite Pneumonyssus caninum (32), orbital mucocele (33), and solitary naso-orbital blastomycosis without systemic involvement at presentation (34).

Biopsy and histopathologic examination remains the only way to definitely diagnose a suspect orbital tumor, but imaging of the orbit is also very useful to determine if a mass is present and to better plan diagnostic or therapeutic intervention. Sectional imaging is far superior to radiography for that purpose (4,33–39). A report describing the use of ultrasonographic studies in 50 dogs with retrobulbar disease demonstrated that a mass effect was identified in 42% of dogs with neoplasia and in 30% of dogs with abscesses (33). Because ultrasonic signals can only travel through fluid and soft-tissues, advanced imaging modalities, such as CT or magnetic resonance imaging (MRI), prove to be much superior for thorough evaluation of the orbital cavity and surrounding bony structures (34–39). In the case presented here, while ultrasonographs showed evidence of a mass effect in the orbit, imaging with contrast-enhanced CT clearly identified a large orbital mass with invasion into the nasal cavity and nasopharynx, and allowed visualization of bone destruction (Figure 3). Surgical resection was thereafter not considered a reasonable option for this cat.

Orbital tumors are best treated with surgical resection, occasionally requiring orbital exenteration for large or invasive tumors (2–4,6–8,10–13,40). With specific radiosensitive tumor types, such as lymphomas, plasmacytomas, and some carcinomas, megavoltage radiation therapy and cytotoxic chemotherapy, alone or in combination depending on subtype and grade, can occasionally be considered first-line therapy (4–6,8). When orbital tumors invade the surrounding structures, surgical excision may need to be followed by radiation therapy, chemotherapy, or both on microscopic disease for improved long-term control (4,7,8,40). The prognosis of treated orbital tumors varies markedly with the type of tumor, the size and invasiveness, the type of therapy, and between studies. Very good survival times and quality of life can be expected with benign and completely excised tumors, but a grave prognosis may accompany unresectable or widely disseminated tumors. The cat reported here was euthanized after confirmation of the diagnosis because of poor quality of life and locally very advanced, incurable disease. CVJ