JPC Systemic Pathology
Integumentary System
September 2022
I-N03 (NP)
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 14mm diameter, densely cellular, unencapsulated, well-demarcated, multilobulated neoplasm composed of basaloid polygonal cells arranged in variably-sized cords, trabeculae, undulating ribbons, garlands, and occasional islands. The cords and trabeculae are separated and surrounded by a dense, often hyalinized collagenous and vascular stroma, while the ribbons and garlands 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 80µm) 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 polygonal to vaguely spindloid; these neoplastic cells form 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. These cells often contain intracytoplasmic black granules (melanin). Mitotic count averages 6 per 2.37mm2. The center of the cysts often contains abundant necrotic neoplastic cells 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 dogs (Kerry blue terrier, Bichon frise, Shetland sheepdogs and Siberian huskies are predisposed) and cats; occasional in horses; rare in cattle and sheep
- Previously termed 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:
- Do not typically metastasize
- Clin path: 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
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 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; poorly collagenous 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:
- Canine trichoblastomas are usually immunoreactive for CK14 (a basal cell marker in the epidermis and hair follicle), likely indicating a follicular stem cell origin; negative immunoreactivity for CAM5.2 (cytokeratin 7 & 8) (Campos, Vet Dermatol 2014)
- Trichoepitheliomas and tricholemmomas also variably express CK14
- IKAs and pilomatricomas, which originate from portions of the hair follicle away from the bulge, are generally CK14 negative
DIFFERENTIAL DIAGNOSIS:
For trabecular trichoblastoma:
- Isthmic tricholemmoma- no peripheral palisading; tricholemmal keratinization
For granular trichoblastoma:
- Bulb type tricholemmoma- has more islands and trabeculae without peripheral displacement of nuclei seen in granular trichoblastoma
- Granular cell basal carcinoma- epidermal contiguity and features of malignancy
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
For trichoblastoma with ORS differentiation (dogs):
- Canine 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 Morgans or pony breeds; may resemble sarcoids or melanomas
- Ruminants: Rare
- Rabbits: Trichoblastoma is the most common cutaneous tumor in pet rabbits (Kok, J Comp Path 2017; Baum, Vet Pathol 2021)
- Virginia opossum: Recent report of a dorsal skin mass (Pope, J Vet Diag Inves 2017)
REFERENCES:
- 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.
- Brannick EM, Newkirk KM, Schaefer DMW. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier: 2022: 390-391.
- 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.
- Goldschmidt MH, Goldschmidt KH. Epithelial and Melanocytic Tumors of the Skin. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Somerset, NJ: John Wiley & Sons, Inc.; 2017: 104-108, 115-118.
- Gross TL, Ihrke PJ, Walder EJ: Epithelial neoplasms and other tumors. In: Gross TL, ed. Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science; 2005: 625-634, 672-677.
- Kok MK, Chambers JK, Ong SM, et. al. Hierarchical Cluster Analysis of Cytokeratins and Stem Cell Expression Profiles of Canine Cutaneous Epithelial Tumors. Vet Pathol. 2018;55(6):821-837.
- Kok MK, Chambers JK, Ushio N, et al. Histopathological and Immunohistochemical Study of Trichoblastoma in the Rabbit. J Comp Pathol. 2017; 157: 126-135.
- 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.
- Pope JP and Donnell RL. Spontaneous neoplasms in captive Virginia opossums (Didelphis virginiana): a retrospective case series (1989-2014) and review of the literature. J Vet Diagn Invest. 2017; 29(3): 331-337.
- 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.
- Welle MM and Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 1210.
- 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.