JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

I-N15

SLIDE A

Signalment (JPC #2648402): Age and breed not specified, dog

HISTORY: Dermal mass

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Expanding the subcutis, elevating the overlying epidermis and dermis, and mildly compressing the overlying adnexa is a 11 x 7 mm, well-circumscribed, unencapsulated, paucicellular neoplasm composed of spindle cells arranged in long, interlacing streams and bundles and supported by an abundant, dense collagenous matrix. Neoplastic cells have indistinct cell borders, indistinct to scant amphophilic cytoplasm, a round to elongate nucleus with finely stippled chromatin and indistinct nucleolus. The mitotic rate is less than 1 per 2.37mm². Multifocally within the neoplasm and the directly adjacent subcutis and dermis are low numbers of perivascular lymphocytes and plasma cells.

MORPHOLOGIC DIAGNOSIS: Haired skin: Fibroma, breed unspecified, canine.

SLIDE B

Signalment (JPC #2648388): Age and breed not specified, cat

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Mucosa: Infiltrating and effacing the submucosa, elevating the overlying lamina propria and mucosal epithelium, and extending to deep and lateral margins is a moderately cellular neoplasm composed of spindle cells arranged in irregular, broad, long interlacing streams and bundles and forming “herringbone” patterns on an abundant, dense collagenous matrix. Neoplastic cells have indistinct cell borders, indistinct to scant amphophilic cytoplasm, an oval to elongate nucleus with finely stippled chromatin, and 0-2 nucleoli. There is moderate anisocytosis and anisokaryosis. Mitoses average less than 1 per 2.37mm². Blood vessels within the neoplasm are lined by plump, reactive endothelium. Multifocally within and surrounding the neoplasm are few lymphocytes, plasma cells, mast cells, and scant hemorrhage, fibrin, and edema. Multifocally within the overlying mucosal epithelium, there is moderate marked hyperplasia forming rete ridges with acanthosis, mild intracellular edema, and mild intercellular edema forming prominent intercellular bridging (spongiosis). There are rare transmigrating neutrophils.

MORPHOLOGIC DIAGNOSIS: Mucosa: Fibrosarcoma, breed unspecified, feline.

SLIDE C

Signalment (JPC #4038131): Chesapeake Bay retriever, age unknown

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Expanding the subcutis and mildly compressing overlying adnexa is an unencapsulated, well-demarcated, moderately cellular neoplasm composed of spindle cells arranged in thin streams within a fine, loose, fibrous matrix that surround and separate thick, irregularly shaped bundles of brightly eosinophilic, homogenous, birefringent material (hyalinized collagen). Neoplastic cells have indistinct cell borders, a scant amount of finely fibrillar, eosinophilic cytoplasm, and an elongate central nucleus with finely stippled chromatin and one variably distinct nucleolus. Anisocytosis and anisokaryosis are mild. The mitotic rate is less than 1 per 2.37mm². Admixed with neoplastic cells are low numbers of lymphocytes and plasma cells. Multifocally, there are mildly ectactic apocrine glands lined by attenuated epithelium.

MORPHOLOGIC DIAGNOSIS: Haired skin: Fibroma, keloidal, Chesapeake Bay retriever, canine.

GENERAL DISCUSSION:

Fibroma

Benign tumor of fibroblasts and collagen
Uncommon in all domestic animals

Fibrosarcoma

Common in cats, less common in dogs, rare in other domestic species
Usually low grade malignancy; low metastatic rate but high recurrence rate
May be over-diagnosed as any anaplastic highly cellular spindle cell sarcoma containing collagen is diagnosed as a fibrosarcoma when more specific histiogenesis is not apparent
Graded based on its inclusion in the soft tissue sarcoma group (Dennis, Vet Pathol. 2011, and Mauldin 2016):
- Differentiation score
  - 1 – sarcomas that closely resemble normal adult mesenchymal tissue
  - 2 – sarcomas that histologic type can be determined, but their differentiation is poor
  - 3 – undifferentiated sarcomas
- Mitotic score
  - 1 – 0-9 mitoses per 10 HPF (400x)
  - 2 – 10-19 mitoses per 10 HPF (400x)
  - 3 – >19 mitoses per 10 HPF (400x)
- Tumor necrosis rate
  - 0 – no necrosis
  - 1 – less than or equal to 50%
  - 2 – greater than 50%
    - Total score
      - I – less than or equal to 3
      - II – 4-5
      - III – greater than or equal to 6
    - Dog: Less than 9 is associated with greater survival time
    - Cat: Equal to or less than 5 is associated with greater survival time

Fibrosarcomas of the mandible and maxilla in dogs: Golden retrievers are over-represented; histologically appear low-grade with moderate to low cellularity, but aggressively infiltrate adjacent normal tissue; this is the third most common oral malignancy in dogs (behind squamous cell carcinoma and melanoma)
Fibrosarcomas in cutaneous sites of previous vaccination have been reported
Oral fibrosarcoma in cats: Uncommon, but second most common oral malignancy in cats (behind squamous cell carcinoma); bone invasion is common

PATHOGENESIS:

Trauma may predispose to development of keloidal fibroma/fibrosarcoma
Feline fibrosarcomas occur in three forms:

Virus-induced (multicentric fibrosarcoma): Rare; occurs in cats less than 5 years old and is associated with coinfection with feline sarcoma virus (FeSV) and feline leukemia virus (FeLV); metastasize
- FeSV is a replication-defective virus that requires FeLV
- Genetic recombination of the two viruses → produces an acutely transforming virus → induces multiple rapidly growing fibrosarcomas
- Rapid clinical course is pathognomonic
Solitary fibrosarcoma: More common; occurs in older cats; resemble canine forms; not virus related
Injection-site associated (formerly post-vaccinal, I-N16): Occurs in younger cats than those affected with spontaneous fibrosarcoma (median age of 8 years); occurs at site of previous vaccination; biologically aggressive

Canine fibrosarcoma, or other mesenchymal neoplasms, can develop in association with granuloma formation secondary to infection with Spirocerca lupi (D-P10), typically within the esophagus

TYPICAL CLINICAL FINDINGS:

Fibroma

More common in middle aged to older animals
Rhodesian ridgebacks, Doberman pinschers, and boxers are predisposed
Limbs and head most common sites in the dog

Fibrosarcoma

Occurs most commonly in older animals
Most common malignant mesenchymal tumor in cats
Trunk and limbs most common sites

TYPICAL GROSS FINDINGS:

Fibroma/Keloidal fibroma

Solitary, soft to rubbery to firm, well-circumscribed, round, ovoid, dome-shaped, polypoid, or penduculated mass from 1 to 50 cm in diameter
Grey to white on cut surface
Alopecia common; may be hyperpigmented; large tumors may be ulcerated due to self-trauma

Fibromyxoma: Fibroma which contains a substantial amount of mucinous or myxomatous matrix in addition to collagen
Myxoma (myxofibroma): Rare cutaneous neoplasm which arises from fibroblasts or multipotential mesenchymal cells and contains an abundant glycosaminoglycan (GAG) stroma

Solitary, infiltrative, soft mass; poorly circumscribed
Pale on cut surface and exudes a clear, viscous fluid

Fibrosarcoma/Keloidal Fibrosarcoma

Soft to firm, poorly-circumscribed, infiltrative masses from 1 to 15 cm in diameter
Gray-white, glistening on cut surface
+/- Ulceration and alopecia (more common in large tumors)
Golden retrievers and Doberman pinschers appear to be at increased risk

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Fibroma

Well-circumscribed, unencapsulated, dermal or subcutaneous nodule
Long interlacing and streaming bundles of collagen
Low mitotic rate
Low cellularity
Normal structures are displaced, not invaded

Fibrosarcoma

Unencapsulated and locally invasive
Interlacing and intersecting bundles of immature fibroblastic cells; “herringbone” pattern
Variable pleomorphism, mitotic rate, and amount of collagen
Multinucleated giant cells may be present
Highly cellular

Keloidal fibroma

Streams of thick hyalinized collagen fibers surrounded by fascicles of closely packed plump fibroblastic cells
More cellular than fibroma
Mitotic figures rarely observed

Keloidal fibrosarcoma

As described for keloidal fibroma, but with local infiltration, increased cellularity, nuclear pleomorphism, and mitotic activity
Low mitotic index

ADDITIONAL DIAGNOSTIC TESTS:

IHC: Vimentin positive, otherwise diagnosis of exclusion
Histochemistry: Masson’s trichrome or Verhoeff-van Gieson to identify collagen vs. smooth muscle (to differentiate from leiomyosarcoma)
Cytology:

Fibroma: Spindle to fusiform cells individually or in small clusters; lightly basophilic cytoplasm forming tails on either side of the nucleus; cells may be embedded in an amorphous pink matrix
Fibrosarcoma: Abundant large, plump spindle cells individually or in aggregates often embedded in an amorphous pink matrix; +/- multinucleated cells; nuclear pleomorphism
Keloidal fibroma/fibrosarcoma: Abundant dense, hyalinized bright magenta bands of matrix associated with plump fibroblasts with minimal inflammation

DIFFERENTIAL DIAGNOSIS (histologic lesions):

Fibroma

Focal sclerosis (scar): Decreased numbers of fibroblasts interspersed between increased numbers of thick, hyalinized, mature collagen fibers
Dermatofibroma (collagenous nevus): Spindle cells in short streams with variable amounts of well-differentiated collagen bundles
Nodular dermatofibrosis of German shepherd dogs: Paraneoplastic syndrome associated with renal cysts, renal adenocarcinoma, and/or uterine leiomyoma; multiple cutaneous nodules; inherited autosomal dominant genetic defect
Peripheral nerve sheath tumor (PNST, I-N13): Whorls, short interlacing streams; palisades (S100, NSE, GFAP positive)
Collagenous hamartoma: Focal, nodular areas of excessive dermal collagen in a haphazard arrangement; few fibroblasts; entrap adnexa
Myxoma (myxofibroma): Rare cutaneous neoplasm which arises from fibroblasts or multipotential mesenchymal cells and contains an abundant glycosaminoglycan (GAG) stroma (alcian blue stain)
Canine maxillary well-differentiated fibrosarcoma: Histologically benign, biologically malignant; grows rapidly and invades the maxilla and mandible; frequently recurs after surgery; well differentiated fibrocytes and fibroblasts in an extensive fibrous matrix; infiltrative; rare mitoses and nuclear pleomorphism; golden retrievers and other large breed dogs predisposed

Fibrosarcoma

Malignant peripheral nerve sheath tumor (I-N13): More complex with whorls and neuroid structure
Feline injection-site (post-vaccine) fibrosarcoma (I-N16): Necrotic center; peripheral lymphohistiocytic inflammation; macrophages contain intracytoplasmic brown-gray vaccine material
Leiomyosarcoma: Long spindle cells with cigar-shaped nuclei and abundant pale eosinophilic cytoplasm forming whorls and interlacing bundles; nuclear pleomorphism (desmin and smooth muscle actin positive)
Myxosarcoma: Rare cutaneous neoplasm which arises from fibroblasts or multipotential mesenchymal cells and contains an abundant glycosaminoglycan (GAG) stroma (alcian blue stain)

COMPARATIVE PATHOLOGY:

Horses: Sarcoids (locally aggressive, non-metastatic, fibroblastic skin tumor associated with trauma, association with BPV1/2 is currently controversial; I-N17)
Rabbits: Viral-induced Shope fibroma (Rabbit fibroma virus; a Leporipoxvirus transmitted by fleas and mosquitoes); widespread in wild cottontail rabbits (reservoir host) in Canada and eastern US; usually benign in wildlife; firm, flattened tumors of legs and feet, sometimes periorbital, muzzle and perineal regions
Hares: Hare fibroma virus, closely related to rabbit fibroma virus and myxoma virus; affects European hares; arise on ears and legs, but then regress;
Small rodents: Hepatic fibrosarcoma has been associated with hepatic infection with Cysticercus fasciolaris (D-P22), the strobilicercus (larval) form of the feline cestode (tapeworm) Taenia taeniformis
Pet and aviary birds:
1. Fibromas reported in the oral cavity, but typically found, although infrequently, in the skin and subcutaneous tissue of the sternum, extremities, neck, and head; not reported in upper respiratory tract
2. Fibrosarcomas are the most common beak tumor; common in budgerigars and cockatiels; other common tumors of the integument include face and limbs; also seen in the nasal infraorbital sinuses, syrinx small intestine, liver, spleen, air sacs, cloaca, heart, lungs, and bone medullary space; abundant mitotic figures; typically locally invasive, rarely metastasize, with a high rate of recurrence
Cervids: Cutaneous fibroma most commonly reported in roe deer, white-tailed deer, European moose, and others; due to fibroma viruses (family Papillomaviridae); tumor may regress; most numerous on the head and neck, to include oral mucosa and legs; evidence of cytopathic effect
Gray squirrels: Fibromas or fibromatosis due to squirrel fibroma virus (Leporipoxviridae); transmission likely due to biting arthropods; potentially fatal- systemic disease results in multiple pulmonary nodules or renomegaly
Snakes: Fibromas reported in the oral cavity; fibrosarcomas most commonly reported (Colubrids and Viperids)
Walleye: Viral-induced Walleye dermal sarcoma (Walleye dermal sarcoma virus; a type C retrovirus in the genus Epsilonretrovirus); induces dermal sarcomas (seasonal lesions – peak in late autumn and regress in spring)
Guinea Pig: Fibromas and leiomyomas most common uterine tumors.
Dwarf Hamsters: Recent report of an atypical fibroma with evidence of a neuroectodermal phenotype in two hamsters (J Comp Path, 2019)
Leatherback Sea Turtle: Recent report of a pulmonary fibromyxoid sarcoma with possible association with Chelonid alphaherpesvirus 5 (J Comp Path, 2019)

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