Most cutaneous and subcutaneous lesions can be categorised sufficiently to provide meaningful clinical guidance. This lecture will focus on the cytological appearance of some of the more common skin lesions, particularly those which can be diagnosed in practice.

Non-Neoplastic Lesions

Haematoma

An aspirate from a recently formed haematoma has the appearance of blood except that platelets are usually absent. As the lesion starts to organise, the number of macrophages increases and plump fibroblasts may be seen in aspirated fluid. Macrophages may contain phagocytosed red cells or haemoglobin breakdown product in the form of bluish black haemosiderin granules or haematoidin crystals.

Sialocele

Fluid aspirated from a salivary gland cyst may be clear or blood-tinged and is usually quite viscous. It consists primarily of large finely vacuolated mononuclear cells and macrophages (containing either phagocytosed red cells or haematoidin).

Abscess

Cutaneous abscesses are especially common in cats, as result of a bite wounds. Cytology reveals a large number of extremely degenerate neutrophils, many of which may contain intracellular bacteria, often staphylococci or streptococci. Actinomyces spp., Nocardia spp., mycobacteria and certain fungal infections tend to elicit a more mixed pyogranulomatous or granulomatous inflammatory response.

Injection Site Reaction

Aspirates from injection site reactions consist primarily of lymphocytes and reactive macrophages. The macrophages may contain phagocytosed eosinophilic material. Neutrophils and reactive mesenchymal cells (fibroblasts) may be present in low numbers.

Eosinophilic Plaque/Granuloma

Aspirates or impression smears from eosinophilic plaques or granulomas consist of large numbers of eosinophils and neutrophils. Mast cells may also be present in low numbers.

Epidermal Inclusion Cyst or Follicular Cyst

Aspirates from epidermal inclusion or follicular cysts consist almost entirely of keratinised squames and cellular debris. Cholesterol crystals and a few small clusters of normal or dysplastic epithelial cells may also be seen. Rupture of the cyst can induce a secondary pyogranulomatous response.

Neoplastic Lesions

Tumours of Epithelial Origin

 Basal cell tumour: these are almost always benign. Basal cells have scant basophilic cytoplasm which may contain melanin or keratohyaline granules. They tend to exfoliate in compact clusters. Basal cell tumours in which basal cells predominate are also called trichoblastomas. Some basal cell tumours show evidence of sebaceous or follicular differentiation.

 Sebaceous adenoma: sebaceous adenomas are often mistakenly referred to as 'warts'. Sebaceous epithelial cells have a moderate amount of pale finely vacuolated cytoplasm and a small centrally located nucleus.

 Squamous cell carcinoma (SCC): these tend to ulcerate and usually elicit an intense inflammatory response. Cells exfoliate singly or in clusters and may show varying degrees of differentiation. A mixture of intermediate, superficial and anucleated squamous epithelial cells with angular cell borders may be seen in well differentiated tumours. Some epithelial cells may contain other cells, e.g., neutrophils (emperipolesis), and there may be evidence of perinuclear vacuolation. Poorly differentiated SCCs show a more marked degree of anisocytosis and anisokaryosis and cells have a higher nuclear:cytoplasmic ratio. Nuclear chromatin often has a coarse 'moth-eaten' appearance.

 Perianal adenoma: cells aspirated from perianal adenomas exfoliate in clusters and are hepatoid in appearance (i.e., resemble hepatocytes). They have abundant granular pinkish/blue cytoplasm and a round nucleus containing a single centrally located nucleolus. Smaller basophilic reserve cells with a flattened nucleus may be seen between the hepatoid cells. Perianal adenocarcinomas are rarely encountered and tend to show more obvious criteria of malignancy, but some may appear well differentiated and cannot reliably be differentiated from adenomas by cytology.

 Apocrine gland adenocarcinoma of the anal sac: these are malignant and must be differentiated from perianal adenomas. Cells from these tumours usually exfoliate in large sheets or clusters, have a moderate amount of pale basophilic cytoplasm and a round or oval-shaped nucleus. Cytoplasmic margins are poorly defined. Malignant characteristics may be less pronounced than in carcinomas involving other tissues.

Tumours of Mesenchymal Origin

 Lipoma: these are benign mesenchymal tumours. Aspirates have a greasy appearance and consist of numerous fat droplets which can be stained with Sudan red. Adipocytes have abundant clear cytoplasm and a small dark nucleus which is compressed on the periphery of the cell. They may be aspirated either singly or in large clusters. Small blood vessels may also be seen. Liposarcomas are rare tumours. Aspirates consist of plump spindle-shaped mesenchymal cells containing numerous variably sized intracytoplasmic lipid vacuoles. The cells show obvious malignant features.

 Haemangiopericytoma: these occur in dogs and are most frequently located on the limbs. Fine needle aspirates are often quite cellular and consist of plump spindle cells with an oval-shaped nucleus and basophilic cytoplasm which may be vacuolated. Nuclear chromatin has a coarse stippled or reticulated appearance.

 Fibroma/fibrosarcoma: fibromas are relatively rare tumours and are composed of well differentiated spindle cells with an oval nucleus and elongated cytoplasmic tails. Fibrosarcomas are more common, particularly in the cat. Aspirates taken from reactive granulation tissue, fibromas and well differentiated fibrosarcomas may appear remarkably similar making cytological differentiation difficult. Cells from less well differentiated fibrosarcomas are plumper and have a higher nuclear:cytoplasmic ratio. They may be located in an eosinophilic matrix material (collagen). Histology is often required to differentiate fibrosarcomas from other spindle cell tumours.

 Melanoma: cutaneous melanomas occur more frequently in dogs than in cats. Most are benign. Cells from well differentiated melanomas contain numerous fine black- green melanin granules which may obscure nuclear morphology. Conversely, cells from poorly differentiated tumours may contain scant melanin pigment granules and the cells usually have a large nucleus containing several large irregular nucleoli. Anisocytosis and anisokaryosis are usually evident. Amelanotic melanomas are quite rare: with careful examination a few melanin granules can usually be seen in some of the cells.

Discrete Round Cell Tumours

 Canine histiocytoma: histiocytomas are small well circumscribed tumours. Although these tumours are benign, the cells often show a mild to moderate degree of anisocytosis and anisokaryosis. The nuclei are round, oval or indented and the cells have a moderate amount of pale basophilic cytoplasm. Some nuclei may contain one or more poorly defined nucleoli. An increased number of lymphocytes may be seen as the tumour starts to regress. Other histiocytic neoplasms that can involve the skin include cutaneous histiocytosis, systemic histiocytosis and malignant histiocytosis (or histiocytic sarcoma).

 Mast cell tumour (MCT): mast cells contain azurophilic cytoplasmic granules which can obscure nuclear detail (some water-soluble rapid Romanowsky stains may not stain mast cell granules). The presence of mast cells with densely packed cytoplasmic granules and nuclei of uniform size suggests the tumour may be reasonably well differentiated (histology is required to accurately grade mast cell tumours). Cells from more malignant tumours tend to have fewer cytoplasmic granules and a more obvious degree of anisocytosis, anisokaryosis and variation in nuclear:cytoplasmic ratio is evident (toluidine blue can be used to stain the granules in these poorly differentiated cells). Aspirates from most canine MCTs also contain eosinophils. Mesenchymal cells are also frequently observed. MCTs occur less frequently in cats and most solitary lesions are benign. Multiple 'histiocytic-type' MCTs have been reported in young Siamese cats, and often regress spontaneously.

 Extramedullary plasmacytoma: plasmacytomas can involve the skin (especially the digits and ears), oral cavity (gingiva and tongue) of older dogs. They are rare in cats. The cells have a variable amount of dark basophilic cytoplasm and a round eccentrically placed nucleus with a coarse chromatin pattern. A moderate degree of anisocytosis, anisokaryosis and variation in nuclear:cytoplasmic ratio is usually evident and binucleated and/or multinucleated cells may be present (though most plasmacytomas are benign). Pink amorphous material (amyloid) may be intimately associated with the plasmacytoid cells.

 Cutaneous lymphoma: Cutaneous lymphoma can be classified as epitheliotrophic (also known as mycosis fungoides) or non-epitheliotrophic. Epitheliotrophic lymphoma is the more common form, and is usually of T-cell origin. The neoplastic lymphoid cells vary in size, have a variable amount of pale basophilic cytoplasm and a round, indented or convoluted nucleus which may contain visible nucleoli. Occasionally, the neoplastic cells are present in the blood (Sézary syndrome). The non-epitheliotrophic form involves infiltration of the dermis and subcutis with neoplastic B-lymphocytes.

 Canine transmissible venereal tumour (TVT): in the UK, TVTs are usually only seen in dogs imported from temperate climates. The lesions are usually located on the external genitalia or oronasal area and are poorly circumscribed, ulcerated and haemorrhagic. Superficial secondary bacterial infection is common. The cells are large and round with a moderate amount of pale basophilic cytoplasm containing small punctate vacuoles. The nuclei are round with coarse nuclear chromatin and one or two prominent nucleoli. Mitotic figures and a mixed inflammatory cell population may be present.

References

1.  Baker R, Lumsden JH. The skin. In: Baker, R; Lumsden, JH. Colour atlas of cytology of the dog and cat. St. Louis: Mosby Inc, 2000; 39-70.

2.  Raskin RE. Skin and subcutaneous tissues. In: Raskin, RE and Meyer, DJ. eds. Atlas of canine and feline cytology. Philadelphia: WB Saunders Co, 2001; 35-92.

3.  Tyler RD, Cowell RL, Meinkoth JH. Cutaneous and subcutaneous lesions. In: Cowell, RL; Tyler, RD; Meinkoth, JH. Diagnostic cytology and haematology of the dog and cat (second edition). St. Louis: Mosby Inc, 1999; 20-51.