Cutaneous Squamous Cell Carcinoma with Mucinous Metaplasia in Dogs

Background : Squamous cell carcinoma (SCC) is one of the most common malignant skin tumors in domestic animals. Histologically, they are characterized by a proliferation of neoplastic keratinocytes with varied keratin production. Some SCCs have peculiar histological characteristics that permit them to be classified into uncommon to rare histological subtypes, reported in animals and humans. However, according to the authors' knowledge, the mucin-producing subtype described in humans has not yet been reported in animals. In this study, we report the occurrence of two mucin-producing SCCs in dogs, a histological presentation similar to that seen in cutaneous SCCs with mucinous metaplasia in humans. Cases : Two dogs, a 5-year-old Yorkshire female and a 17-year-old Dachshund male, had a skin nodule near the tail and on the right eyelid. The nodules varied from 1 to 5 cm in diameter, were firm and covered with skin and hair. The cut surface was firm and white. Histological findings were compatible with squamous cell carcinoma, characterized by a neoplastic proliferation of keratinocytes originating in the epidermis and infiltrating the dermis. The keratinocytes were arranged in islands and occasional anastomosed cords, supported by a fibrous stroma. The formation of pearls varied from moderate to sparse. The nuclear and cellular pleomorphism was accentuated in case two and moderate in case one. Mitosis figures ranged from two to five in a high magnification field. Within the neoplasm, there were large vacuolated neoplastic cells with slightly fibrillar intracytoplasmic basophilic content. This content has been rarely observed in an extracellular medium. The presence of mucin was confirmed by positive Alcian Blue (AA) staining. In immunohistochemistry (IHC), tumor cells showed strong immunostaining for pancitokeratin, and in areas with marked mucin deposition, immunostaining was predominantly moderate to weak. No tumor cells were immunostained for CD34 and Blc-2 antibodies. Compared to AA and Harris' hematoxylin, it was possible to demonstrate the presence of mucin in the cytoplasm of neoplastic keratinocytes using IHC. No vascular or lymphatic invasion by neoplastic cells was observed. The average cell proliferation index assessed by counting the nucleolar argyrophilic organizing regions (AgNOR) was 3.4 in case 1 and 4.5 in case 2. Discussion : Although the SCC routinely does not present a diagnostic challenge in veterinary practice, the histological presentation of the reported cases does not fit the current classification available in veterinary medicine. The histological presentation observed in these two dogs is similar to that described for cutaneous SCCs with mucinous metaplasia in humans, and so far not described in animals. The observation of intracytoplasmic mucin in humans is an essential finding for the diagnosis of SCC with mucin metaplasia. In the present cases, we observed a slightly basophilic amorphous substance in the cytoplasm of proliferated neoplastic keratinocytes, which stained strongly in blue when applied the Alcian Blue (AA) histochemical technique. This observation became more evident when using IHC counterstained with AA and Harris hematoxylin . In the histological analysis, the absence of an adenoid growth pattern or glandular formation amid neoplastic proliferation ruled out the possibility of a mucinous adenocarcinoma or a mucoepidermoid carcinoma. In addition, we could rule out a follicular neoplasia, including keratinizing infundibular acanthoma due to the absence of a central pore and the absence of immunostaining for CD34 and Bcl-2. These immunohistochemical findings, together with histological findings, reinforce the diagnosis of SCC with mucinous metaplasia in our dogs.