Case of the month #8
by Nazare Pinto Nazaré Pinto da Cunha (DipECVCP)
A 19-year-old crossbreed neutered female dog was presented for evaluation of a sudden onset of a left mandibular, non-adherent mass of soft consistency. On ultrasound, the mass was heterogeneous and lobulated. A fine-needle non-aspiration cytology was performed to further characterization.
What is your diagnosis?
Fig 1 A-C – Cytology image of a mass on the mandibular region. MGG, 20-60x
The cytological exam reveals a high cellularity sample consisting mainly of a fusiform cell population arranged in non-cohesive to poorly cohesive clusters. These cells have a scant to moderate amount of slightly granular basophilic cytoplasm, with indistinct cell borders and rare small sized intracytoplasmic vacuoles. The nucleus is oval, peripheral, with finely stippled chromatin containing 1-3 prominent nucleoli of various shapes and sizes. Signs of atypia were moderate, with anisocytosis and anisocaryosis, rare macrocytosis and atypical mitosis.
Malignant neoplasia, suspicion of mesenchymal tumor or amelanotic melanoma.
The coverslip was removed from the pre-stained slides and immunocytochemistry (ICC) for SOX-10 with fast-red chromogen and Melan-A with DAB chromogen was performed on the two available MGG smears.
Melan-A revealed a faint to moderate cytoplasmic staining in circa 60-70% of the cell population, while SOX 10 had a strong and robust nuclear staining in circa 90% of the neoplastic cells.
These findings were considered consistent with a melanocytic origin of the neoplastic cells, hence the diagnosis of amelanotic malignant melanoma.
Fig.2 Upper row – A MGG stained slide (left image) was subject to ICC analysis with Melan-A (right image), which reveals a faint to moderate cytoplasmic staining in circa 60-70% of the cell population; DAB chromogen, 40x. Lower row – On another MGG stained slide (left image) ICC with SOX 10 revealed a strong and robust nuclear staining in circa 90% of the cells; Fast red Chromogen, 60x.
Malignant melanoma (MM) is one of the most frequently documented malignant tumors in the oral cavity in dogs older than 10 years of age. It has a high metastatic potential and local invasiveness. Amelanotic forms are reported to have a more aggressive behaviour.
Diagnosing melanomas can be a challenge because the degree of pigmentation can be variable, ranging from highly pigmented to completely amelanotic forms. In these cases, immunostaining can help define the origin of the cell population, allowing an estimate of the prognosis and therapeutic plan.
The current gold standard immunohistochemistry (IHC) protocol for amelanotic malignant melanoma in dogs includes a panel of markers composed of antibodies against Melan-A, PNL2, TRP-1,TRP-2. Recently, in dogs, SOX-10 has also been found to be expressed in melanocytes of dermal and mucosal origin, myoepithelial cells of apocrine and mammary glands, basal cells of meibomian glands and dermal nerves, as well as in Schwann cells and autonomic ganglia. SOX-10 is reported to have a sensitivity of 100% and a specificity of 90% for the distinction of oral malignant melanoma vs oral soft tissue sarcoma. Because it is not a specific antibody, SOX-10 shouldn’t be used as a single marker to confirm melanocytic origin and/or to differentiate from soft tissue sarcomas, emphasizing the importance of incorporating Melan-A and/or additional markers depending on the morphologic characteristics of the cells.
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