JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N03B

SLIDE A

Signalment (JPC Accession #2634082): Age and breed unspecified, dog

HISTORY: This dog had a solitary, slow-growing dermal mass on the head.

HISTOPATHOLOGIC DESCRIPTION: Haired skin, head: Focally expanding the dermis and subcutis, elevating the overlying epidermis, and compressing adjacent adnexa is a 14 mm diameter, densely cellular, unencapsulated, well-demarcated, multilobulated neoplasm composed of polygonal cells arranged in variably sized cords, trabeculae, undulating ribbons, and occasional islands. The cords and trabeculae are separated and surrounded by a dense, often hyalinized collagenous and vascular stroma, while the ribbons are separated by moderately dense fibrovascular to myxomatous stroma. Neoplastic cells have variably distinct cell borders, scant eosinophilic cytoplasm, an oval nucleus with finely stippled chromatin, and one variably distinct nucleolus. Multifocal islands of neoplastic cells have more abundant, finely granular eosinophilic cytoplasm. Neoplastic cells occasionally line small (up to 80 µm) cysts containing flocculent amphophilic material. Anisocytosis and anisokaryosis are mild and there are 2 mitotic figures per 2.37mm². Multifocally within the superficial perivascular dermis, there are low numbers of lymphocytes, fewer plasma cells, and rare macrophages admixed with mild hemorrhage, eosinophilic fibrillar to beaded material (fibrin), and increased clear space (edema).

MORPHOLOGIC DIAGNOSIS: Haired skin, head: Trichoblastoma, breed unspecified, canine

SLIDE B

Signalment (JPC Accession #2015906): Age and breed unspecified, cat

HISTORY: Cystic mass from the neck

HISTOPATHOLOGIC DESCRIPTION: Dermis, neck (per contributor): Expanding the dermis, replacing adnexal structures, and extending to all borders is a densely cellular, well-demarcated, multilobular, unencapsulated neoplasm composed of polygonal cells arranged in variably sized islands and cords which occasionally form thick-walled cysts separated by a moderately dense fibrous stroma. Neoplastic cells are predominantly polygonal, but occasionally are spindle-shaped; neoplastic cells are arranged in trabeculae and have indistinct cell borders, a scant amount of eosinophilic cytoplasm, and a single elongate nucleus with finely stippled chromatin and an indistinct nucleolus. Anisocytosis and anisokaryosis are mild. Neoplastic cells occasionally contain intracytoplasmic dark brown to black granules (melanin). There are 6 mitotic figures per 2.37mm². The center of the cysts contain abundant necrotic cellular debris and melanin pigment (cystic degeneration).

MORPHOLOGIC DIAGNOSIS: Dermis, neck: Trichoblastoma, breed not specified, feline.

GENERAL DISCUSSION:

• Trichoblastomas are benign neoplasms derived from the primitive hair germ of embryonic follicular development
• Common in cats and dogs (poodles, cocker spaniels, mixed breed dogs, Kerry blue terriers, Bichon Frise, Pulis, Bedlington terriers, cockapoos, Shetland sheepdogs and Siberian huskies are predisposed or have reportedly increased rates of occurrence) (Wiener, 2021); occasional in horses; rare in cattle and sheep
• Outdated terminology includes: basal cell tumors (dogs) and spindle cell type of basal cell tumor (cats)

PATHOGENESIS:

• Unknown
• Derived from trichoblastic (primitive hair germ) epithelium

TYPICAL CLINICAL FINDINGS:

• See gross findings

TYPICAL GROSS FINDINGS:

• Dogs
  • Solitary, well-circumscribed, firm, alopecic nodules; dome-shaped or polypoid +/- ulceration; 1-2cm in diameter; freely moveable; +/- pigmentation
  • Site predilection for head, neck, and base of ear
• Cats
  • Solitary, well-circumscribed, firm, dome-shaped; freely moveable; +/- pigmentation
  • Most common on head and cranial half of trunk

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• In general, composed of cuboidal to elongate epithelial cells with indistinct borders, scant basophilic cytoplasm, and a round to oval uniform nucleus; mitotic figures can be frequent; +/- pigmentation due to abundant melanin
• Usually not contiguous with epidermis
• Multiple histologic subtypes, based on pattern of growth, are described, and multiple may be found in a single neoplasm:
  • Ribbon type – most frequently seen in the dog, rare in other species; ribbons, garlands, cords of basaloid epithelial cells; paucicellular fibrous stroma; ribbons are generally two cells wide; rarely associated with the epidermis; may have extensive collagenous matrix which may appear hyalinized; mitoses variable; rare variants: trabeculae of keratinocytes enmeshed in loose fibrous stroma resembling follicular fibrous sheaths
    • Medusoid variant – cords radiate from a central island (occasionally with microcysts of amorphous keratin) of densely packed cells; more abundant eosinophilic cytoplasm; more mucinous stroma
  • Trabecular type – most common variant in cats; lobules and broad trabeculae of basaloid epithelial cells with prominent peripheral palisading and centrally located cells with abundant cytoplasm; connection with the epidermis is focal or absent; sparse intralobular collagenous to mucinous stroma; +/- keratin microcysts
  • Granular type – most frequently seen in dogs; similar to ribbon type; composed of larger cells with finely granular or vacuolated cytoplasm and eccentric nuclei; rare
  • Spindle cell type – most frequently seen in cats; trabeculae and lobules of elongated basal epithelial cells; collagen poor stroma; peripheral palisading is not prominent; broad zone of connection with normal epidermis; +/- melanin in accompanying macrophages or neoplastic cells; rare keratinization
  • Trichoblastoma with outer root sheath (ORS) differentiation – rare; well demarcated; lobules and trabeculae with cystic degeneration; anastomosing cords of small epithelial cells similar to ribbon type merge into islands of cells; markedly vacuolated cytoplasm resembling anagen suprabulbar outer root sheath or pale pink isthmus-type keratinocytes that line cystic zones

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology: clusters of small cuboidal epithelial cells that lack prominent cytologic features of malignancy; +/- pink matrix and spindle cells (collagenous stroma); cannot be distinguished from other tumors of basilar epithelium cytologically
• Granular trichoblastoma- cytoplasm of individualized cells appears abundant and finely granular
• AI: In one study, a machine-based-learning-algorithm for automated diagnosis was able to diagnose canine trichoblastomas with 98% accuracy (Fragoso-Garcia, 2023)
• Ki67 index did not correlate with patient variables for trichoblastomas in recent study (Firsching, 2022)
• Trichoblastomas previously reported to be variably immunoreactive for CK 14; found to be negative in control (trichoblastoma) tissue in comparative study of rabbit cheek tumors (Murphy, 2023)

DIFFERENTIAL DIAGNOSIS:

For trabecular trichoblastoma:

• Isthmic tricholemmoma- no peripheral palisading; tricholemmal keratinization
• Merkel cell carcinoma: lack peripheral palisading; immunoreactive for CK20, chromogranin A, synaptophysin, and NSE

For granular cell trichoblastoma:

• Bulb type tricholemmoma- lack eccentric nuclei
• Granular basal cell carcinoma- epidermal contiguity and features of malignancy

Ribbon or medusoid trichoblastoma

• Merkel cell carcinoma: can have cord-like pattern; immunoreactive for CK20, chromogranin A, synaptophysin, and NSE

For spindle cell trichoblastoma:

• Solid-cystic apocrine ductular adenoma - can have some spindling, but usually not as much as spindle cell trichoblastoma; ductal differentiation with intracellular vacuoles and lack of papillary mesenchymal bodies
• Basal cell carcinoma: due to the broad connection of spindle trichoblastomas to the overlying epidermis, BCC should be considered; however, BCC is more plaque-like, with a higher mitotic rate, and a more abundant and cellular stroma

For trichoblastoma with ORS differentiation (dogs):

• Canine solid-cystic apocrine ductular adenoma (I-N07A) - tubular structures lined by double row of cells; gradual keratinization with keratohyaline granules and lamellations of keratin

COMPARATIVE PATHOLOGY:

• Cats: Trichoblastomas are common, but true incidence is difficult to estimate as they were previously called basal cell tumors
• Horses: Occasional to rare; more common in Morgan horses or pony breeds; may resemble sarcoids or melanomas
• Ruminants: Rare
• Rabbits: Trichoblastoma is the most common cutaneous tumor in pet rabbits (Baum, 2021); most often reported on the head and neck but can occur in many locations (Rätsep, 2024)
  • Malignant trichoblastoma with sarcomatous stroma reported in one 10 year old rabbit (Mineshige, 2022)
• Humans: Adamantinoid trichoblastomas histologically similar to ameloblastomas but may be a variant of trichoblastoma (Murphy, 2023)
  • Ectopic odontogenic tumors in rabbit cheeks hypothesized to also be variant of trichoblastoma

REFERENCES:

1. Baum, B. Not Just Adenocarcinoma- Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits (Oryctolagus cuniculus): A Review. Vet Pathol. 2021;58(5):890-900.
2. Brannick EM, Newkirk KM, Schaefer DMW. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Elsevier: 2022:390-391.
3. Delaney MA, Treuting PM, Rothenburger JL. Lagomorpha. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:486.
4. Firsching TH, Dietert K, Bartel A, Doherr MG, Gruber AD. Dependence of the Ki67 Labelling Indes of Selected Canine Tumors on Patient Age, Sex and Tumor Size. J Comp Pathol. 2022;193:1-8.
5. Fisher DJ. Cutaneous and subcutaneous lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020:92-93.
6. Fragoso-Garcia M, Wilm F, Bertram CA, Merz S, Schmidt A, Donovan T , Fuchs-Baumgartinger A, Bartel A, Marzahl C, Diehl L, Puget C, Maier A, Aubreville M , Breininger K, Klopfleisch R. Automated diagnosis of 7 canine skin tumors using machine learning on H&E-stained whole slide images. Vet Pathol. 2023;60(6)8:65–875.
7. Hill FI, Tse MPY, Ferguson AD, Mills SW, Sandy JR, Ganta CK, Cino-Ozuna AG, Elsohaby I. Neoplastic and non-neoplastic lesions in biopsy samples from pet rabbits in Hong Kong: a retrospective analysis, 2019-2022. J Vet Diagn Invest. 2024:36(5):701–710.
8. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 714-716.
9. Mineshige T, Kamiie J, Ishikawa M, Shirota K. Malignant Trichoblastoma with Sarcomatous Stroma in a Rabbit. J Comp Pathol. 2022;199:109-113.
10. Murphy BG, Swan E, Affolter V, Ayala S, Jennings S, Cartoceti A, LaDouceur EEB. Odontogenic-like neoplasms of the rabbit cheek: pathological features and comparison to cutaneous trichoblastoma and jaw-associated ameloblastoma. Vet Pathol. 2023;60(2) 178–184.
11. Raskin RE and Conrado FO. Integumentary System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:70-71.
12. Rätsep E, Ludwig L, Dobromylskyj M. Orofacial masses in domestic rabbits: a retrospective review of 120 cases from 2 institutions, 2000–2023. J Vet Diagn Invest. 2024;36(5) 724–729.
13. Welle MM and Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Elsevier; 2022:1210.
14. Wiener DJ. Histologic features of hair follicle neoplasms and cysts in dogs and cats: a diagnostic guide. J Vet Diagn Invest. 2021 May;33(3):479-497.

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