Neoplasms included in this group originate from different cell lines, but have been historically grouped all together as they share similar cytological features. Round cell tumours include:
• Mast cell tumour (MCT).
• Cutaneous histiocytoma.
• Plasma cell tumour.
• Transmissible venereal tumour (TVT).
• Cutaneous lymphoma.
Cytological diagnosis of cutaneous round cell tumours
Aspiration from round cell tumours usually harvests high numbers of cells. These cells are discrete, round to oval shaped, hence the name. Although round cells do not cluster together or produce extracellular matrix, in very thick and hypercellular aspirates they may give the impression of forming organized structures. In this case, it is important to look at their arrangement in the thinnest areas of the slides.
Each of the round cell tumours listed above has additional specific morphological features that facilitate their recognition on cytology. The ability to differentiate cytologically different round cell tumours is clinically important, as the biological behaviour of these neoplasms and the therapeutic options differ significantly. As an example, cutaneous histiocytoma often undergoes spontaneous regression, whereas mast cell tumour is generally approached with wide surgical excision and may have malignant potential. The morphology of these tumours will be described in detail in this chapter.
10.1 Canine mast cell tumour (canine MCT)
Neoplasia of mast cells.
• Common neoplasm of the dog, accounting for approximately 21% of canine skin tumours.
• Age: mostly occurs in adult and old animals, with an average of approximately 9 years. However, it can be observed in dogs of any age, including puppies.
• Cutaneous mast cell tumour (MCT) is the most common form, followed by subcutaneous MCT. The differentiation between the two is based on clinical and histological examination.
• Cutaneous MCT: can develop anywhere in the body. Macroscopically, it ranges from nodular rashes to diffuse swellings or, most commonly, hairless raised erythematous solid lesions. Masses can be ulcerated. Multiple forms can also occur, especially in Boxer, Boston Terrier, Golden Retriever and Pug.
• Subcutaneous MCT: arises in the subcutaneous adipose tissue and presents as soft, fleshy masses. Legs, back and thorax are the most common sites.
• Variable biological behaviour: this mostly depends on histological grading (for cutaneous MCT), proliferation indexes (e.g. Ki67), c-Kit mutation and Kit receptor expression. High‐grade cutaneous MCTs have an aggressive behaviour, with metastases starting from regional lymph nodes and often progressing to the spleen and liver in advanced stages. Peripheral blood involvement may also occur (mastocytaemia).
• MCTs in the oral mucosa or muzzle usually are more aggressive.
• As a general rule, subcutaneous MCTs tend to be less aggressive than cutaneous forms.
• Local and/or systemic paraneoplastic signs may be observed and are linked to the release of histamine, heparin and proteases contained within the mast cell granules. Local signs include oedema, ulceration and swelling at the primary tumour site, and possibly delayed wound healing and local coagulation abnormalities. The most common systemic effects are gastrointestinal signs and include vomiting, GI haemorrhage, anorexia and abdominal pain. Acute anaphylactic reactions are rare.
• Over-represented canine breeds: Boxer, Labrador Retriever, Golden Retriever, Shar Pei, Bulldog, Boston Terrier, Staffordshire Bull Terrier, Fox Terriers, Weimaraner, Cocker Spaniel, Rhodesian Ridgeback, Dachshund, Australian Cattle Dog, Beagle, Schnauzer and Pug.
Cytological features
• Cellularity is variable, often high.
• Background: often clear, variably haemodiluted and with free purple granules from disrupted mast cells. It may contain collagen fibrils.
• Cells are round with a moderate N:C ratio.
• Nuclei are often obscured by the granules, especially in well-differentiated forms. When visible, they are medium sized, round to oval, mostly paracentral, with uniform to slightly clumped chromatin and variably visible nucleoli.
• The cytoplasm is moderate in amount and clear to pale basophilic. Rarely, an increased basophilia can be observed in high-grade tumours.
• In well granulated forms, the cytoplasm contains numerous thick purple granules, usually evenly distributed within the cell.
• In poorly granulated forms, granules are reduced in numbers and are usually finer. In these cases they may be polarized to one side of the nucleus or may form clumps.
• Occasionally, neoplastic cells can display erythrophagia.
• Cytological features of atypia are prominent in high-grade forms. These include karyomegaly, variable anisokaryosis and anisocytosis, bi- and/or multinucleation. Mitotic figures can be observed.
• A concurrent eosinophilic inflammation is often present. Eosinophils are attracted by the chemokines contained in the mast cell granules.
• Reactive fibroblasts are frequently seen. They may exhibit variable cytological pleomorphism and may contain eosinophilic/pink granules.
• Collagen fibrils may also be present.
• Mast cell rich inflammatory lesion (e.g. insect bite reaction)
• Round cell tumour of other origin (in poorly granulated forms or Diff-Quik slides)
• Histopathology is always required to differentiate between cutaneous and subcutaneous forms and, in the case of a cutaneous MCT, for histopathological grading, which has been reported to have a prognostic significance. The most widely used grading systems are the three-tier Patnaik and the two-tier Kiupel systems. Nowadays, most anatomical pathologists apply both grading systems to all canine cutaneous mast cell tumours. The Patnaik system designates MCTs as grade I (low), II (intermediate), or III (high), based on depth of invasion, cell and nuclear morphology and mitotic count. The Kiupel system designates MCTs as low-grade or high-grade based on mitotic count, presence of multinucleation, bizarre nuclei and karyomegaly.
• As discussed above, the accurate grading of MCTs remains pertinent to the histopathology. However, based on a study by Camus et al. (2016), a cutaneous MCT is defined as high-grade on cytology when cells are either poorly granulated or when at least two of the four following findings are observed: (i) mitotic figures; (ii) binucleated or multinucleated cells; (iii) nuclear pleomorphism; and (iv) > 50% anisokaryosis. Claimed sensitivity and specificity of this cytological grading scheme are 88% and 94%, respectively.
• Certain Romanowsky-type dyes (e.g. Diff-Quik) sometimes fail to stain mast cell granules. However, also in these cases, it should always be possible to find a few intracytoplasmic granules in some of the cells upon careful observation of the slide.
Reference and further reading
Blackwood, L., Murphy, S., Buracco, P., De Vos, J.P., De Fornel-Thibaud, P., Hirschberger, J., Kessler, M., Pastor, J., Ponce, P., Savary-Bataille, K. et al. (2012) European consensus document on mast cell tumours in dogs and cats. Veterinary Comparative Oncology 10(3), 1–29.
Camus, M.S., Priest, H.L and Koehler, J.W. (2016) Cytologic criteria for mast cell tumor grading in dogs with evaluation of clinical outcome. Veterinary Pathology 53(6), 117–1123.
Hergt, F., Von Bomhard, W. and Kent, S. (2016) Use of a 2-tier histologic grading system for canine cutaneous mast cell tumors on cytology specimens. Veterinary Clinical Pathology, 45(3), 477–483.
Scarpa, F., Sabattini, S. and Bettini, G. (2016) Cytological grading of canine cutaneous mast cell tumours. Veterinary Comparative Oncology 14(3), 245–251.
10.2 Feline mast Cell Tumour (feline MCT)
Neoplasia of mast cells.
• Common neoplasm accounting for approximately 7% and 21% of all feline skin tumours, according to previous European and American studies, respectively. Visceral forms are much more common than in dogs and account for up to 50% of all feline mast cell tumours (MCTs).
• Age: adult cats are more frequently affected, with an average of approximately 10 years. However, it can be observed in cats of any age. No sex predisposition reported.
• It can develop anywhere in the body, with preference for head (especially in young animals), neck, trunk and legs.
• It usually presents as a single firm tan papule, plaque or discrete nodule in the skin or subcutis. Overlying epidermis is usually pink and alopecic, but it may be ulcerated. Approximately 20% of cats present with multiple lesions.
• Mastocytaemia is uncommon.
• Cutaneous mast cell tumour is generally a benign neoplasm in cats, but up to 22% of cases may show an aggressive behaviour.
• Over-represented feline breeds: Siamese, Burmese, Russian Blue, Ragdoll, Maine Coon, Oriental and Havana cat.
Cytological features
• Cellularity is variable, often high.
• Background: often clear, variably haemodiluted. It often contains free purple granules derived from the disruption of the mast cells during the smearing.
• Neoplastic mast cells are round with a moderate N:C ratio.
• Nuclei are often obscured by the granules. When visible, they are round to oval, mostly paracentral, with uniform to slightly clumped chromatin and variably visible nucleoli.
• The cytoplasm is clear or lightly basophilic, moderate to abundant and commonly contains numerous fine purple/magenta granules. Granules are often finer than in dogs. In poorly granulated forms, granules may be present in very low numbers and/or may have a patchy distribution.
• Cytological pleomorphism is variable and is more prominent in the pleomorphic variant. Anisocytosis and anisokaryosis can be moderate to marked and binucleation and/or multinucleation are often observed. Mitotic figures can be seen in variable numbers.
• Occasionally, neoplastic cells can display erythrophagia.
• Eosinophils are also present, but with a lower frequency than in canine MCT. Low numbers of small lymphocytes can also be observed.
• Reactive fibroblasts and collagen fibrils are rarely present.
Variants
Histologically, feline MCTs can be subclassified in different forms. In the literature, the terminology is not standardized and there is inconsistency between studies. The following is the classification of feline cutaneous MCTs suggested by Kiupel (2016) in the latest edition of Meuten’s Tumors in Domestic Animals.
• Well-differentiated form:
• Most common form of feline MCT.
• Neoplastic cells show little pleomorphism and resemble normal mast cells.
• Eosinophilic infiltrates are rare or absent.
• Small lymphocytes are often found.
• Pleomorphic form:
• Uncommon form of feline MCT.
• As per name, the cellular pleomorphism in this form is often prominent. Cytomegalic cells can be seen and anisokaryosis and anisocytosis can be marked. Multinucleated cells and cells with bizarre nuclei are observed.
• Cell pleomorphism and nuclear atypia do not seem to correlate with a malignant behaviour.
• Numerous eosinophils are often present.
• Atypical (histiocytic) form:
• Rare form of feline MCT.
• Seen mostly in young cats as multiple nodular lesions.
• Associated with a benign clinical course or spontaneous regression.
• Siamese cats may be predisposed.
• Cytologically, neoplastic mast cells resemble histiocytes. They are large, polygonal to round, with lightly basophilic cytoplasm lacking the typical intracytoplasmic granules. Nuclei are large, round, often indented and paracentral. Mitotic activity is low.
• Small lymphocytes are frequently present.
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