Rose E. Raskin1, DVM, PhD, DACVP; Alan H. Rebar2
Follicular Cyst
These cysts are found in a third to a half of the nonneoplastic noninflammatory tumor-like lesions removed in dogs and cats, respectively. The cyst occurs most frequently in middle to older aged dogs. They may be single or multiple, firm to fluctuant, with a smooth, round, well circumscribed appearance. These are often located on the dorsum and extremities. The cyst lining arises from well differentiated stratified squamous epithelium often associated with adnexal structures. Keratin bars, squames, or other keratinocytes predominate on cytology. Degradation of cells within the cyst may lead to the formation of cholesterol crystals which appear as negative stained, irregularly notched, rectangular plates best seen against the amorphous basophilic cellular debris of the background. The behavior of these masses is benign, but rupture of the cyst wall can induce localized pyogranulomatous cellulitis with evidence of acute and/or chronic hemorrhage. When this occurs, neutrophils and macrophages may be frequent.
Mucocele or Sialocele
Duct rupture related to trauma or infection leads to an accumulation of saliva within the subcutaneous tissues. The presence of a fluctuant mass containing clear to bloody fluid with string-like features suggests a salivary gland duct rupture. The cytologic specimen often stains uniformly purple from the high protein content. The background may contain scattered, pale basophilic, amorphous material, consistent with saliva. The fluid is often bloody with evidence of both acute and chronic hemorrhage. Erythrophagocytosis is common and occasional yellow rhomboid crystals may be seen. These are termed hematoidin crystals and are associated with chronic hemorrhage. The nucleated cell population consists predominately of highly vacuolated macrophages displaying active phagocytosis. Distinction between these cells and secretory glandular tissue may be difficult, especially when cells are individualized and nonphagocytic. Nondegenerate neutrophils are common.
Nodular Panniculitis/Steatitis
This condition may have an infectious or noninfectious etiology. Causes of noninfectious panniculitis include trauma, foreign bodies, vaccination reactions, immune-mediated conditions, drug reactions, pancreatic conditions, nutritional deficiencies, and idiopathic. The condition appears in the cat and dog as solitary or multiple, firm to fluctuant, raised, well demarcated lesions. These may ooze an oily yellow-brown fluid. Sites of prevalence involve the dorsal trunk, neck, and proximal limbs. Cytologically, nondegenerate neutrophils and macrophages predominate against a vacuolated background composed of adipose tissue. Small lymphocytes and plasma may be numerous, especially in lesions induced by vaccination reactions. Frequently, macrophages present with abundant foamy cytoplasm or as giant multinucleated forms. When chronic, evidence of fibrosis is indicated by the presence of plump fusiform cells with nuclear immaturity. The fibrosis may be so extensive as to suggest a mesenchymal neoplasm. Multiple lesions are often associated with systemic disease in young dogs. Dachshunds and poodles may be predisposed to this form of the disease.
Dermatophytosis
The lesions vary from alopecia, broken hair shafts, crusts, scales, and erythema to raised nodules on the head, feet, and tail of dogs and cats. Cytologic specimens reveal a pyogranulomatous inflammation with degenerate neutrophils and large epithelioid macrophages. Arthrospores and hyphae are associated with hair shafts that are best visualized using clearing agents with plucked hairs. Arthrospores are occasionally present as oval to round lightly basophilic structures having a thin clear halo and measuring 2 x 2-3 um. They may be seen extracellularly or within neutrophils and macrophages and associated with hair or keratin.
Squamous Cell Carcinoma
This is a common tumor occurring as solitary or multiple proliferative or ulcerative masses. It is most common on the limbs of dogs and thinly haired areas of the pinnae or face of cats. Cytologically, purulent inflammation often accompanies immature or dysplastic squamous epithelium. Bacterial sepsis may occur if the surface has eroded. Characteristic tadpole shape and keratinized blue-green cytoplasm may be helpful criteria in determining the cell of origin. Squames and highly keratinized nucleated squamous epithelium are frequent in well-differentiated tumors corresponding to the keratin pearls seen histologically. Cellular and nuclear pleomorphism is marked. Perinuclear vacuolation may be present. The neoplastic epithelium may appear as individual cells or as adherent sheets of cells.
Basal Cell Tumor
Found commonly in dogs and cats as typically a single, firm, elevated, well demarcated round intradermal mass that may be ulcerated or cystic. Many tumors appear pigmented due to abundant melanin. Tumors in cats may be cystic. They are located mostly about the head with frequent occurrence on the neck and limbs. Cytologically, basal cells are small cells characterized by high nuclear to cytoplasmic ratios, monomorphic nuclei, and deeply basophilic cytoplasm. They may be arranged as clusters or in row formation.
Perianal Gland Adenoma
The tumor may be single or multiple occurring generally near the anus, but may also be found on the tail, perineum, prepuce, thigh, and along the dorsal or ventral midline. Initially they grossly appear as smooth, raised round lesions which become lobulated and ulcerated as they enlarge. The tumor arises from modified sebaceous gland epithelium. Cytologically, sheets of mature round hepatoid cells predominate characterized by abundant finely granular pinkish-blue cytoplasm. Nuclei resemble those of normal hepatocytes appearing round with an often single or multiple, prominent, nucleolus. A low number of smaller basophilic reserve cells having a high nuclear to cytoplasmic ratio may also be present, but these lack features of cellular pleomorphism.
Fibrosarcoma
In young cats this tumor may be caused by the feline sarcoma virus and may be multiple. In older dogs and cats, tumors are solitary with a predilection for the limbs, trunk, and head. They are poorly circumscribed and sometimes ulcerated. Cytologically, fibrosarcoma consists of abundant numbers of large plump cells occurring individualized or in aggregates. Multinucleated giant cells may be present occasionally. Nuclear pleomorphism may be marked compared with the benign counterpart. Cells are less uniform and generally have high nuclear to cytoplasmic ratios.
Canine Hemangiopericytoma
This is a common tumor generally considered to affect dogs only. These are often solitary tumors with a predilection for the joints of the limbs, but are found commonly on the thorax and abdomen. They are firm to soft, multilobulated, and often well circumscribed. Cytologically, preparations are moderately cellular. Plump spindle cells may be individualized or arranged in bundles, sometimes found adherent to the surface of capillaries. Nuclei are ovoid, with one or more prominent central nucleoli. Multinucleated cells are occasionally seen. Associated with cells may be a pink amorphous collagenous stroma. The cytoplasm is basophilic and may contain numerous small discrete vacuoles. Lymphoid cells have been found in approximately 10% of cases.
Lipoma
This is the most common connective tissue tumor in dogs. The tumor may be single or multiple, occurring mostly on the trunk and proximal limbs. These are dome-shaped, well circumscribed, soft, often freely moveable masses within the subcutis which can grow slowly becoming quite large. Cytologically, unstained slides appear wet with glistening droplets that do not dry completely. Lipid may be best demonstrated with water-soluble new methylene blue and a fat stain (oil-red-O). When stained with alcohol-based Romanowsky stains, lipid is dissolved leaving slides often void of cells. When present, intact adipocytes have abundant clear cytoplasm with a small compressed nucleus to one side of the cell.
Hemangiosarcoma
This is a malignant infiltrative mass of the dermis or subcutis. Lesions are raised, poorly circumscribed, ulcerated, and hemorrhagic. Cytologically, slide preparations are of low cellularity with numerous blood cells within the background. Evidence of hemorrhage with hemosiderin-laden macrophages may be present. Neoplastic cells are pleomorphic ranging from large spindle to stellate. Cytoplasm is basophilic, having indistinct cell borders and occasional punctate vacuolation. Cells have high nuclear to cytoplasmic ratios, oval nuclei with coarse chromatin and prominent multiple nucleoli.
Melanoma
This is a common tumor of dogs and an uncommon tumor of cats. Older animals are usually affected as are those with dark skin pigmentation. Gross features differ for benign and malignant forms. Benign tumors are mostly dark brown to black, circumscribed, raised, dome-shaped masses covered by smooth hairless skin. Malignant tumors are variably pigmented, infiltrative, frequently ulcerated and inflamed. Cytologically, cells are pleomorphic ranging from epithelioid to fusiform, or occasionally as discrete round cells. In well-differentiated tumors, nuclei may be masked by numerous fine black-green cytoplasmic granules. Poorly differentiated tumors may contain few or no cytoplasmic granules. Nuclei in benign forms are small and uniform compared with characteristics of anisocytosis, anisokaryosis, coarse chromatin, and prominent nucleoli seen in the malignant melanomas. Prognosis depends on tumor site of origin and histologic characteristics. Benign skin tumors frequently have a good prognosis. Malignant forms arise more often from the nail bed, lip and other oral mucocutaneous junctions in dogs. The latter forms carry a guarded or poor prognosis related to frequent recurrence and metastasis.
Canine Histiocytoma
This is a very common benign rapidly growing tumor of mostly young dogs. The tumor appears as a small solitary, well circumscribed, dome-shaped, red ulcerated, hairless mass. It occurs commonly on the head, especially ear pinna, as well as on the hindlimbs, feet, and trunk. Cytologically, cells have round to indented nuclei with fine chromatin and indistinct nucleoli. Cells exhibit minimal anisocytosis and anisokaryosis. The cytoplasm is abundant and clear to lightly basophilic with indistinct cell borders. A variable number of small well-differentiated lymphocytes are common in regressing lesions.
Mast Cell Tumor
Tumors in dogs are generally solitary, nonencapsulated and highly infiltrative into dermis and subcutis. Mast cell tumors in cats are usually solitary, well circumscribed, dermal masses that occur on the head, neck, and limbs. Multiple masses are common in young Siamese cats. Mast cell tumors in cats are common also in visceral organs, spleen, and liver. Cytologically, tumor cells may vary in the degree of granularity with some cells having numerous distinct metachromatic stained granules while others contain moderate numbers of granules or few to no cytoplasmic granules. In less differentiated forms, anisokaryosis, coarse chromatin, and prominent nucleoli may be present along with a poorly granulated cytoplasm. Giant binucleated cells are more commonly found in poorly differentiated forms. Eosinophils are more numerous in canine tumors than feline tumors.
Plasmacytoma
This tumor is infrequent in dogs and rare in cats. They present as mostly solitary, well circumscribed masses often on the digits, ears, and mouth. Cytologically, aspirates are moderately to markedly cellular. Individual cells have variable amounts of basophilic cytoplasm in which borders are discrete. Anisocytosis and anisokaryosis are prominent features. Nuclei are round to oval with fine to moderately coarse chromatin and indistinct nucleoli. The nuclei are often eccentrically placed and frequently binucleated. Multinucleated cells may be present. Amorphous eosinophilic material, representative of amyloid is seen in less than 10% of plasmacytomas. Prognosis is generally good, but local recurrences may be common.
Cutaneous Lymphoma
The disease may occur primarily in the skin or rarely as a manifestation of generalized lymphoma. It is more common in older dogs and cats. Lesions are solitary to multiple in the form of nodules, plaques, ulcers, erythroderma, or exfoliative dermatitis in the form of excessive scaling. Pruritus may be common. Epitheliotropic lymphoma is characterized by neoplastic T-lymphocyte infiltrates of the epidermis and adnexa. Focal collections of the neoplastic cells, termed Pautrier microabscesses, are sometimes formed within the epidermis. B- or T-lymphocytes are presumed involved in the infiltration of the dermis and subcutis with nonepitheliotropic lymphomas. Lymphocytes range in size from small to large with round, indented, or convoluted nuclei. Nucleoli may be prominent. Cytoplasm is scant to moderate and lightly basophilic. Uniformity of the lymphoid population without significant inflammation or plasma cell infiltration is suggestive of cutaneous lymphoma. Prognosis is poor as the disease rapidly progresses necessitating euthanasia.
References
1. Baker R, Lumsden JH. Colour Atlas of Cytology of the Dog and Cat: Mosby, St. Louis; 2000
2. Cowell RL, Tyler RD, Meinkoth JH. Diagnostic Cytology and Hematology of the Dog and Cat: Mosby, St. Louis; 2nd Ed. 1999
3. Radin MJ, Wellman ML. Interpretation of Canine and Feline Cytology: Ralston Purina Company Clinical Handbook Series. The Gloyd Group, Inc, Wilmington, DE; 2001
4. Raskin RE, Meyer DJ (eds). Atlas of Canine and Feline Cytology: WB Saunders Co, Philadelphia; 2001