Cutaneous epithelial neoplasms can originate from any of the epithelial structures present in the skin and are classified based on the cell of origin and presence or absence of squamous or adnexal differentiation. The subcutaneous tissue lacks epithelial structures. Hence, there are no primary epithelial tumours arising in the subcutis. Cutaneous epithelial tumours can be broadly classified as follows:
• Epithelial tumours without squamous or adnexal differentiation:
• Basal cell tumour.
• Tumours of the epidermis:
• Papilloma.
• Squamous cell carcinoma.
• Adnexal tumours:
• Follicular tumours: different types of follicular tumours can be observed in dogs and cats, some of which cannot be differentiated on cytology. The follicular tumours that will be described in the specific sections of this book include: trichoblastoma, trichoepithelioma, pilomatricoma, and infundibular keratinizing acanthoma. These tumours, besides being the most frequent, may show some cytological features that facilitate their recognition on cytology.
• Sebaceous and modified sebaceous glands tumours: sebaceous adenoma, epithelioma and carcinoma, and perianal gland adenoma, epithelioma and carcinoma.
• Apocrine and modified apocrine glands tumours: sweat gland adenoma and carcinoma, anal sac adenocarcinoma, and ceruminous adenoma and carcinoma.
• Adnexal tumours without further differentiation: clear cell adnexal carcinoma.
Merkel cell tumour will also be described in this section, although this is not strictly an epithelial tumour but a neuroendocrine neoplasm originating from mechanoreceptors present in the epidermis and follicular epithelium.
Cytological diagnosis of cutaneous epithelial lesions
A practical approach to the cytological diagnosis of skin lesions (tumours or non-neoplastic epithelial lesions) should try to answer to the following questions:
• From what type of structure does the lesion originate (e.g. epidermis, sebaceous or sweat glands, hair follicle)?
• Is the lesion benign or malignant?
• Less frequently, is it a primary cutaneous neoplasm or a cutaneous metastasis of another malignancy?
Key cytological features
Some cutaneous epithelial tumours can exhibit an overlap of cellular and morphological features. In these cases, only a sub-classification is possible, leaving a list of main differential diagnoses. Some of the cytological findings that, when present, may help in distinguishing these cutaneous epithelial tumours from each other are as follows:
Table 8.1
| Trichoblastoma (TB) versus basal cell tumour (BC): • Ribbon-like arrangement (TB) • Presence of pink amorphous material associated with the epithelial cells (TB) • Stromal cells (TB) |
| Trichoblastoma (TB) versus trichoepithelioma (TE) and infundibular keratinizing acanthoma (IKA): • Ribbon-like arrangement (TB) • Presence of anucleated squamous epithelial cells (TE: large polygonal squames and/or ghost cells; IKA: large polygonal squames) • Neutrophilic, pyogranulomatous or granulomatous inflammation (TE and IKA) |
| Trichoblastoma (TB) versus sweat gland adenoma (SA): • Ribbon-like arrangement (TB) • Presence of pink amorphous material associated with the epithelial cells (TB) • Tubular arrangement (rarely seen on cytology) (SA) • Columnar epithelial cells (SA) • Possible presence of anucleated squamous epithelial cells (SA) • Cytoplasmic granules of secretory material (SA) |
| Trichoepithelioma (TE) versus infundibular keratinizing acanthoma (IKA): • Progressive maturation of the cells from cuboidal to superficial anucleated squamous epithelial cells (IKA) • Ghost cells (TE) |
| Trichoepithelioma (TE) and infundibular keratinizing acanthoma (IKA) versus pilomatricoma (PM): • Predominance of ghost cells (PM) • Large polytonal anucleated squamous epithelial cells (TE and IKA). |
In other epithelial neoplasms, specific cytological features are present, allowing the identification of the structure of origin and a more detailed diagnosis. For example, amongst the adnexal epithelial tumours, sebaceous and perianal gland neoplasms are those with the more characteristic morphological features that enable the cytologist to reach a definitive diagnosis of the lineage of the tumour.
8.1 Tumours without Squamous or Adnexal Differentiation
Basal cell tumour and basal cell carcinoma
Tumours that originate from the basal cells of the epidermis and do not show squamous or adnexal differentiation.
Following the 1998 World Health Organization (WHO) classification system, all tumours that were previously diagnosed as basal cell tumours were reclassified as either trichoblastomas or sweat gland adenomas. The new classification published by the David-Thompson DVM Foundation (Goldschmidt et al., 2018) has reintroduced this tumour as a separate entity. Due to this, little is known about the true incidence, presentation and clinical behaviour of this tumour nowadays. The clinical information described below goes back to the studies performed before the 1998 WHO classification.
• Basal cell tumour (cats):
• Benign tumour that arises from the basal cells of the epidermis.
• Age: peak incidence between 6 and 13 years old.
• Lesions are well circumscribed, can be alopecic, ulcerated and pigmented.
• Most commonly reported on the head and neck.
• Incomplete excision may result in tumour recurrence.
• It is unknown if this tumour can progress to basal cell carcinoma.
• Basal cell carcinoma:
• Age: peak incidence between 12 and 16 years old.
• Usually appears as a thick plaque. It can be ulcerated and can infiltrate the dermis. It can be pigmented or non-pigmented.
• Low-grade malignancy, thought to be rare in dogs and cats. Surgical excision is generally curative and metastases are very rare but have been reported.
• Infiltrative forms may recur after surgical excision.
• Over-represented feline breed: Ragdoll cat.
Cytological features
• Cellularity is variable, generally moderate.
• Background: variably haemodiluted.
• The aspirates are composed of cuboidal epithelial cells in uniform and cohesive clusters, both seen in benign and malignant forms.
• Nuclei are small to medium sized and round. The chromatin is clumped and nucleoli are not seen.
• The cytoplasm is scant and moderately basophilic, often with indistinct borders. It often contains dark granules (melanin pigment).
• Anisokaryosis and anisocytosis are minimal in benign forms and could become more prominent in carcinomas. The N:C ratio is high.
• Sweat gland adenoma
• Trichoblastoma
• Melanocytic tumour (when containing melanin)
• Basal cell tumours usually lack a significant stroma. The presence of slender spindle cells, especially if numerous, is more typical of trichoblastoma.
• Basal cell tumours are often pigmented and may be confused clinically and microscopically with melanocytic neoplasms.
• In dogs, tumours previously classified as basal cell tumours have now been reclassified as trichoblastomas.
• In cats, tumours previously classified as basal cell tumours that show a focal or multifocal ductal differentiation have been reclassified as aprocrine ductal adenomas.
8.2 Epidermal Tumours
Papilloma
Benign proliferation of the epidermis that can be viral or non-viral in origin.
• Non-viral papilloma (squamous papilloma):
• Age: no known age predisposition, though it is more frequently seen in old dogs.
• Lesions are small, generally 1–5 mm and generally exophytic.
• Most frequently localized on the face, eyelids, feet and conjunctiva.
• It might be triggered by trauma.
• Spontaneous regression is not expected.
• Viral papilloma (wart) (can be exophytic or inverted):
• Exophytic papilloma: uncommon in dogs and rare in cats; single or multiple; frequent on face, ears and extremities.
• Inverted papilloma: rare in dogs, usually younger than 3 years old; multiple and usually on ventral abdomen.
• It can spontaneously regress within 6 weeks to 9 months.
Cytological features
• Cellularity is variable, often adequate.
• Background: variably haemodiluted.
• The aspirates are composed of large squamous epithelial cells that generally exfoliate individually.
• Cells are polygonal and angular with a low N:C ratio.
• Nuclei are round, central to paracentral. They are often large to very large and hyperchromatic. The chromatin is clumped and nucleoli are not seen.
• The cytoplasm is abundant and pale basophilic. Viral papillomas can contain bright fuchsia granulations and/or multiple small clear vacuoles. On histopathology, these cells are known as koilocytes and are typical but not pathognomonic of viral papillomas.
• Small lymphocytes and reactive fibroblasts may be seen in the regression phase.
Further reading
Moore, A.R., Libby, A.L., Khanal, S., Ehrhart, E.J. and Avery, P. (2016) Is this cell hollow? Veterinary Clinical Pathology 45(1), 8–9.
Sprague, W. and Thrall, M.A. (2001) Recurrent skin mass from the digit of a dog. Veterinary Clinical Pathology 30(4), 189–192.
Squamous cell carcinoma (SCC)
Malignant tumour arising in the epidermis, with cells showing a variable degree of differentiation to keratinocytes.
• Common tumour in domestic animals. It accounts for approximately 5% of the skin tumours in dogs and 15% in cats.
• Age: 6–13 years in dogs and 9–14 years in cats.
• Usually solitary lesion, but multiple SCCs can occur. Masses are often alopecic, erythematous and ulcerated.
• Preferred anatomical sites:
• Dogs: nail bed, scrotum, lips, ventral trunk and legs.
• Cats: nasal planum, eyelids and pinnae.
• In cats, predisposing factors include chronic sun exposure (solar-induced form), light pigmentation of the skin and lack of hair.
• Cutaneous SCC is locally invasive and destructive but generally with a low metastatic rate. The highest metastatic tendency is observed in digit SCC in dogs.
• Metastases usually occur to the draining lymph node and rarely to other organs.
Cytological features
• Cellularity is variable, generally medium-high.
• Background: variably haemodiluted, pale basophilic and finely granular (proteinaceous).
• The aspirates are composed of numerous squamous epithelial cells at variable degrees of differentiation.
• Well-differentiated SCC exfoliates polygonal squamous epithelial cells with a relatively low N:C ratio and heavy cytoplasmic keratinization. These cells usually occur individually or in groups. Bizarre cells can be present.
• Nuclei are round, central to paracentral. The chromatin is clumped or coarsely stippled. Nucleoli are usually poorly visible.
• The cytoplasm is moderate to abundant, dense, pale to moderately basophilic, with angular borders. It occasionally contains small, clear vacuoles in the perinuclear area.
• Asynchronous nuclear to cytoplasmic maturation can be observed.
• Poorly differentiated SCC usually exfoliates a population of squamous epithelial cells that are less keratinized. Neoplastic cells are cuboidal and have a high N:C ratio. They are often in cohesive clusters, which may be disorganized. Cell crowding and nuclear moulding can be observed.
• Nuclei are round, central to paracentral. The chromatin is finely clumped to coarsely stippled and multiple prominent nucleoli are often seen.
• The cytoplasm is scant to moderate, moderately basophilic.
• Mitoses may be found.
• Irregularly shaped cells may be observed (e.g. tadpole cells).
• A prominent neutrophilic inflammation is often present, as a result of the ulceration that frequently accompanies these lesions.
• Neutrophils can be found within the cytoplasm of the neoplastic cells. This phenomenon is known as emperipolesis.
Variants
Some of the variants listed below can be recognized on cytology (e.g. spindle cell variant) or their cytological presentation has been described in literature (acantholytic variant). The others require histopathology for recognition.
• Acantholytic squamous cell carcinoma:
• Cytologically, this variant is characterized by a heterogeneous population of round to spindle-shaped cells that exfoliate individually or in small clusters.
• Nuclei are round with finely stippled to hyperchromatic chromatin.
• The cytoplasm is amphophilic and finely vacuolated.
• Spindle cell squamous cell carcinoma:
• Rare variant of poorly differentiated SCC.
• Cells vary from polygonal to spindle shaped.
• Spindle-shaped cells have round to oval nuclei and two cytoplasmic tails that project away from each side of the nucleus.
• The cytoplasm is dense, pale to moderately basophilic and often has well-defined margins.
• A transition from the spindle-shaped cells and the more classical polygonal cells usually helps in the diagnosis.
• Verrucous and papillary variants:
• Rare variants.
• Cytologically they are not distinguishable from the more classical form of SCC.
In cats, a multicentric form of squamous cell carcinoma in situ has been described. The neoplastic cells are confined to the epidermis and do not invade through the basement membrane. This form is characterized by the presence of multifocal plaques or verrucous lesions that can occur at any site and with no relationship to sun exposure.
Further reading
Gradi, F., Monteriro, L.N., Fernandes, T.R., Salgado, B.S. and Rocha, N.S. (2011) What is your diagnosis? Cutaneous mass in the mammary region of a dog. Veterinary Clinical Pathology 40, 101–102.
8.3 Follicular Tumours
Trichoblastoma
Benign tumour that derives or shows differentiation to the primitive hair germ cells.
• Common tumour in dogs and fairly common in cats.
• Age in dogs: 4–10 years old.
• In dogs it generally presents as a solitary, firm and alopecic mass, polipoid or dome-shaped. In cats, masses are usually solitary and dome-shaped.
• In dogs, it more frequently occurs on the head, neck and at the base of the ears. In cats, it most frequently occurs on the head and cranial half of the trunk.
• Trichoblastoma carries a good prognosis; the malignant counterpart of trichoblastoma has never been described in dogs and cats, but it is rarely reported in people.
Cytological features
• Cellularity is variable from low to high.
• Background: clear to lightly basophilic. Haemodilution is possible.
• Neoplastic cells are cuboidal and are arranged in variably sized cohesive and uniform clusters. Palisade arrangement is common.
• Nuclei are small to medium sized, with clumped chromatin and inconspicuous nucleoli.
• The cytoplasm is scant and lightly to moderately basophilic. It can contain a variable amount of melanin pigment.
• Anisokaryosis and anisocytosis are minimal.
• Cells can be associated with a small amount of extracellular pink amorphous material (possible basement membrane).
• Low to numeorus slender spindle cells can be found, often individually scattered in the background (stromal cells).
Variants
• Ribbon and medusoid variants:
• Both variants are common in dogs and rare in cats.
• Cells are arranged in branching, winding and radiating columns (ribbons), generally two cells in width. The cell cords radiate from a central island in the medusoid type.
• Cells are uniform and cuboidal. Cytoplasm is more abundant in the ribbon type.
• Granular cell variant:
• Uncommon form in dogs and rare in cats.
• Cells are individualized, medium to large and round to polygonal.
• Nuclei are oval, eccentric, with smooth chromatin and an inconspicuous nucleolus.
• The cytoplasm is abundant, has distinct borders and contains light purple granules.
• Variable numbers of cuboidal epithelial cells may be present.
• Solid/cystic variant:
• Reported rarely in dogs.
• Masses are often multilobular. Lobules can have a central cyst delineated by small keratinocytes. Cysts contain pale basophilic proteinaceous material or black necrotic material.
• Melanocytes may be present amongst the epithelial cells.
• Trabecular variant:
• Multilobulated tumour, common in cats and rare in dogs.
• Cells at the periphery of the tumour are in palisades and cuboidal. Cells in the centre of the neoplasm have slightly more cytoplasm.
• Melanocytes can be found amongst the neoplastic cells, singly or in small groups.
• Spindle cell variant:
• This variant is more common in cats and rare in dogs.
• Cells are uniform, elongated and occur individually and in variably sized cohesive clusters.
• Nuclei are small and cigar-shaped, with coarse chromatin and 1–2 small prominent nucleoli.
• The cytoplasm is pale basophilic, elongated and with inconspicuous cell margins.
• Basal cell tumour (cats)
• Sweat gland adenoma
• Sebaceous epithelioma (though sebocytes are usually seen)
• Melanocytoma (when trichoblastoma is heavily pigmented)
• Granular cell tumour (for the granular cell variant. However, granular cell tumour in skin is very rare in dogs and cats)
Further reading
Adedeji, A.O., Affolter, V.K. and Christopher, M.M. (2017) Cytological features of cutaneous follicular tumours and cysts in dogs. Veterinary Clinical Pathology 43(2), 143–150.
Asakawa, M.G., Lewis, S.M., Buckles, E.L. and Stokol, T. (2015) What is your diagnosis? Cutaneous mass in a dog. Veterinary Clinical Pathology 44(4), 607–608.
Emanuelli, M.P. and Bohn, A.A. (2014) What is your diagnosis? Dermal mass in a dog. Veterinary Clinical Pathology 43(2), 285–286.
Trichoepithelioma
Follicular tumour that shows differentiation to all three segments of the hairfollicle: infundibulum, isthmus and inferior segment. |  |
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