Conference 19 - 2015 Case: 03 20160330

Signalment:

Domestic cat, 5 years and 8 months old, male, castrated. (Felis silvestris catus).The cat was brought to the clinic with hypotension and icteric mucous

membranes. All lymph nodes were slightly prominent. Radiograph showed an enlarged, pendulous abdomen with hepatomegaly and severe splenomegaly. The ultrasound examination revealed that the liver is covered with hypo echoic, nodule-like structures. The visible mesenteric lymph nodes were enlarged. Laboratory tests: Coagulation time was significantly prolonged. Liver-associated values were as well significantly altered. Because of poor prognosis the animal was euthanized.

Gross Description:

Right eye: Buphthalmos. A brownish, 0.5 cm mass is present laterally on the sclera.

Liver: Diffusely severely enlarged, with disseminated white-green and black, up to 5mm nodules which are multifocally slightly raised and show central necrosis.

Spleen: Diffusely severely enlarged. Multifocally are up to 4 cm nodules present that are dark red and slightly firm.

Histopathologic Description:

Liver: Ex-tending to all cut borders, infiltrating the sinusoids and disrupting the architecture of the hepatocellular cords, there is a diffuse, densely cellular, non-demarcated and non-encapsulated neoplasm consisting of neoplastic cells that are arranged in sheets and vague packets. The cells are round to polygonal, up to 25 μm in diameter with moderately distinct cell borders and abundant basophilic, finely granular cytoplasm that multifocally contains brownish pigment (melanin). The cells contain a round to oval, central nucleus with finely vesicular chromatin and mostly one prominent, basophilic nucleolus. There are abundant multinucleated, up to 100 μm giant cells with up to 8 nuclei. Anisokaryosis and anisocytosis are severe. Mitoses range from 3 to 6 per 400x HPF. The neoplastic cells are in large numbers present in almost all blood vessels and lymphatics (vascular invasion, Figure 3). Multifocally there are large areas of necrosis, surrounded by hemorrhage, edema and an inflammatory infiltrate consisting mostly of degenerate neutrophils, macrophages and some lymphocytes and plasma cells. The adjacent hepatocytes are rounded, have an eosinophilic and vacuolated cytoplasm (degeneration). Single cell necrosis is present. Multifocally bile plugs are present in the canaliculi and yellow to brown pigment in the hepatocytes (cholestasis). There is diffuse congestion present.

Masson-Fontana: Many of the neoplastic cells contain variable amounts of intra-cytoplasmatic, agyrophilic, granular material (melanin).

Immunohistochemistry: The neoplastic cells stain positive with -Ç-ÿMelan A and -Ç-ÿPNL-2 (Melanoma).

Morphologic Diagnosis:

Liver: Melanoma, metastatic

Lab Results:

(See Table 1, next page)

Condition:

Metastatic melanoma

Contributor Comment:

The present case describes a rare case of metastatic conjunctival melanoma in the liver and spleen of an adult spayed, domestic shorthair cat, presented because of jaundice and an enlarged, pendulous abdomen. The hematology, blood chemistry and co-agulation values were severely abnormal (see Table 1). The primary tumor was found in the eye as a small conjunctival, brownish nodule. In the clinic, because of the exclusive conjunctival involvement and no evidence of iridial or corneal involvement, the mass was diagnosed as a conjunctival melanoma. This mass was not clinically relevant and was surgically removed before the clinical symptoms occurred.

Malignant melanomas are generally tumors of older animals; however, they have been reported in juvenile animals of many species.² They are common in the dog and uncommon in other domestic species. In cats, they are uncommon and occur mainly in older cats showing no sex predisposition. Malignant melanomas can be composed of a variety of cell morphologies including spindle cells, epithelioid cells, a mixture of spindle cells and epithelioid cells, singet-ring cells or balloon cells. In addition they can be heavily pigmented or amelanotic.³ The present metastatic mass in liver and spleen is considered as an epithelioid type and is pigmented. Metastasis occurs commonly with spread via lymphatics to regional lymph nodes and lungs. It is not uncommon for malignant melanomas to spread to other body sites, including unusual locations such as the brain, heart and spleen.³

Ocular melanoma in cats occurs in a variety of sites. The vast majority of feline ocular melanomas arise diffusely from the anterior uvea (iris, ciliary body).⁵Conjunctival melanomas in dogs and cats are in general rare.³ One study reported in a comparison study of 19 feline ocular melanomas that 16 were intraocular, while only three were conjunctival.⁴ In another study by Schobert et al. (2010), in 13 cases of conjunctival melanoma in cats with adequate follow-up information, only three reported metastasis (14%). Of those three cases, two had metastasized to the submandibular lymph nodes, while in the third case, an abdominal mass was detected.⁵ Interesting about our case is that two abdominal organs (liver, spleen) were severely infiltrated and that the neoplastic cells were present in the lymphatics and blood vessels diffusely within the spleen and liver.

JPC Diagnosis:

Liver: Metastatic melanoma.

Conference Comment:

The most common location for feline conjunctival melanoma is on the bulbar conjunctiva with extension into the orbital tissues, and abundant pigmentation is seen in the majority of tumors. The presence of multinucleated tumor cells is common and may explain the presence of multinucleated neoplastic cells in the metastatic disease in the liver in this case. Conjunctival melanoma in cats has a poorer long term prognosis than the same neoplasm in dogs.⁵ In general, melanomas are less common in cats than dogs but the eye is the most common site, and melanoma is the most common intraocular neoplasm in cats. Non-ocular melanomas occur in cats as well but are considered rare and metastasis was present in 30% of cases in one study.¹ In general non-ocular melanoma is a disease of older cats, with the exception of auricular melanoma which occurs in a significantly younger population.¹ Non-ocular me-lanomas often occur on the head of cats and have a similar distribution as squamous cell carcinoma. Amelanotic melanomas in cats carry a poorer prognosis and are often negative for Melan A but most are positive for S100.¹

This was a challenging case for conference participants with the majority diagnosing this lesion as histiocytic sarcoma due in large part to the presence of multinucleated cells. Cholestasis, as seen in this case, is also a common feature of hepatic histiocytic sarcoma. The moderator commented this is an unusual case and he had not previously seen a case like this one. Additional features described and discussed included vascular thrombosis and, interestingly, rare mitoses were noted in hepatocytes in the absence of regenerative nodules. The moderator pointed out the collar of connective tissue surrounding the central vein, which is a normal feature in the feline liver that distinguishes it from other species. The areas of hepatocyte necrosis and loss surrounding the central vein are presumed secondary to hypoxia from obstruction of sinusoids by tumor emboli. The excellent gross image and the laboratory data provided by the contributor greatly enhanced the learning / teaching value of this case.

References:

1. Chamel G, Abadie J, Albaric O, Labrut S. Non-ocular melanomas in cats: a retrospective study of 30 cases. J Feline Med Surg. 2016; Jan 14(E pub):1-7.

2. Ginn PE, Mansell JEKL, Rakich PM. Skin and appendages. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. 5th ed. Vol 1. Philadelphia, PA: Elsevier Saunders; 2007:760.

3. Meuten DJ. Tumors in Domestic Animals. 4th ed. Iowa State Press; 2002.

4. Patnaik AK, Mooney S. Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms. Vet Pathol. 1988; 25: 105-112.

5. Schobert CS, Labelle P, Dubielzig RR. Feline conjunctival melanoma: histo-pathological characteristics and clinical outcomes. Veterinary Ophthalmology. 2010;