JPC SYSTEMIC PATHOLOGY
SLIDE A Signalment (JPC #2648402): Age and breed not specified, dog
HISTORY: Dermal mass
HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Expanding the subcutis and elevating the overlying epidermis and dermis is a 9 x 6 mm, well-circumscribed, unencapsulated, sparsely cellular neoplasm composed of spindle cells arranged in long, thick, interlacing streams and bundles and supported by an abundant collagenous matrix. Neoplastic cells have indistinct cell borders and cytoplasm, an oval to elongate nucleus with finely stippled chromatin and a variably distinct nucleolus. The mitotic rate is less than 1 per 10 hpf. Multifocally within the neoplasm and adjacent dermis are few lymphocytes, plasma cells, and mast cells. Multifocally, within the superficial dermis, collagen fibers are mildly separated by amphophilic, beaded to fibrillar mucin and mildly ectactic apocrine glands are lined by attenuated epithelium.
MORPHOLOGIC DIAGNOSIS: Haired skin: Fibroma, breed unspecified, canine.
Signalment (JPC #2648388): Age and breed not specified, cat
HISTOPATHOLOGIC DESCRIPTION: Mucosa: Infiltrating and effacing the subepithelial connective tissue, elevating the overlying epithelium, and extending to deep and lateral margins is a moderately cellular neoplasm composed of spindle cells arranged in irregular, broad, interlacing streams and bundles to form a “herringbone” pattern supported on an abundant collagenous matrix. Neoplastic cells have indistinct cell borders and cytoplasm, an oval to elongate nucleus with finely stippled chromatin, and an indistinct nucleolus. There is moderate anisokaryosis. Mitoses are less than 1 per 10 hpf. 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 hemorrhage.
MORPHOLOGIC DIAGNOSIS: Mucosa: Fibrosarcoma, breed unspecified, feline.
strong>Signalment (JPC #4038131): Chesapeake Bay retriever, age unknown
HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Expanding the dermis and subcuticular tissue and elevating the overlying epidermis is an unencapsulated, well demarcated, moderately cellular, neoplasm consisting of spindle cells arranged in thin streams surrounding and separating thick bundles of brightly eosinophilic homogenous birefringent material (hyalinized collagen) within a fine fibrovascular stroma. Neoplastic cells have indistinct cell borders, a scant amount of finely fibrillar eosinophilic cytoplasm and an elongate central nucleus with finely stippled chromatin and indistinct nucleoli. Anisocytosis and anisokaryosis are mild. The mitotic rate is less than 1 per 10 HPF. Admixed with neoplastic cells are a small number of lymphocytes and plasma cells.
MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Fibroma, keloidal, dermal, Chesapeake Bay retriever, canine
- Benign tumor of fibroblasts and collagen
- Uncommon in all domestic animals
- Usually low grade malignancy; low metastatic rate but high recurrence rate
- Graded based on its inclusion in the soft tissue sarcoma group:
- 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
- Common in dogs and cats, but uncommon in other domestic species
- 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
- Only mitotic index is significant as a predictor of tumor behavior
- Dog: Less than 9 is associated with greater survival time
- Cat: Less than 6 is associated with greater survival time
- Fibromas and fibrosarcomas can originate from any location, but fibrosarcomas usually originate from the subcutis
- Feline fibrosarcomas occur in three forms
- Multicentric feline sarcomavirus (FeSV) associated fibrosarcoma: Occurs in cats less than 5 years old and is associated with feline leukemia virus (FeLV) positivity
- Solitary fibrosarcoma: Occurs in older cats; resemble canine forms; not virus related
- Post-vaccination fibrosarcoma: Occurs in younger cats (median age of 8 years); at site of previous vaccination; biologically aggressive
- 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
TYPICAL CLINICAL FINDINGS:
- More common in middle aged to older animals
- Boxers, Doberman pinschers, and golden retrievers have higher incidences
- Flanks and limbs
- Occurs most commonly in older animals
- Most common malignant mesenchymal tumor in cats
- Trunk and limbs
TYPICAL GROSS FINDINGS:
- Solitary, soft to rubbery to firm, well-circumscribed, round, ovoid, dome-shaped, polypoid, or penduculated mass from 1 to 50 cm in diameter
- 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
- Soft to firm, poorly-circumscribed, infiltrative masses from 1 to 15 cm in diameter
- Ulceration and alopecia are common in the overlying epidermis
- Keloid fibroma
- May be dermal or subcuticular
- Nodular or plaque-like
- Keloid fibrosarcoma
- Invasive, nodular subcutaneous tumors
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- 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
- Unencapsulated and locally invasive
- Interlacing and intersecting bundles of immature fibroblastic cells; “herringbone” pattern
- Variable pleomorphism, mitotic rate and amount of collagen
- Multinucleated cells with 2 to 3 nuclei are common
- Highly cellular
- Keloid fibroma
- Streams of thick hyalinized collagen fibers surrounded by fascicles of closely packed plump cells
- Lesions are more cellular at the periphery than at the center
- Rare mitoses
- Keloid fibrosarcoma
- Superficial portion may be indistinguishable from a keloid fibroma
- Deep portion composed of closely packed, interlacing fascicles of fusiform cells supported by a small amount of fibrovascular stroma in which thick hyalinized collagen fibers have been entrapped
- Low mitotic index; mild anisocytosis and anisokaryosis
ADDITIONAL DIAGNOSTIC TESTS:
- Masson’s trichrome or van Gieson to identify collagen vs. smooth muscle
- Vimentin positive, otherwise diagnosis of exclusion
- Monocyte markers (lysozyme, MAC 387, CD18, CD11a, and CD 68) may help differentiate malignant histiocytoma from fibrosarcoma
- Current research indicates fibrosarcomas can be differentiated from peripheral nerve sheath tumors by the use of marker genes in their transciptome
- Seven of these gene products, known to be specifically expressed in neuroectodermal tissues, had higher expression levels in PNSTs: FMN2, KIF1B, GLI1, ROBO1, NMUR2, DOK4 and HMG20B; conversely, eight genes associated with carcinogenesis had higher expression in fibrosarcomas: FHL2, PLAGL1, FNBP1L, BAG2, HK1, CSK and Cox5A
- Use of S100, laminin and PGP 9.5 for the diagnosis of PNSTs has been challenged, since both PNSTs and fibrosarcomas showed similar expression of these proteins
- A combination of the markers GLI1 and CLEC3B differentiated PNSTs from fibrosarcomas with a sensitivity of 89% and a specificity of 87%.
- The proposed fibrosarcoma markers FHL2-Ex4 and FHL2-Ex9 failed to separate PNSTs and fibrosarcomas (sensitivity 50%, specificity 88%).
DIFFERENTIAL DIAGNOSIS (histologic lesions):
- Collagen nevus: Less cellular than fibromas; displace rather than incorporate adnexa
- Dermatofibroma: Spindle cells in short streams with variable amounts of well- differentiated collagen bundles
- Nodular dermal fibrosis: Less nuclear to cytoplasmic ratio than fibroma; proliferates among normal dermal structures
- Nodular dermatofibrosis of German shepherd dogs: Associated with renal cysts, renal adenocarcinoma and uterine leiomyoma; lesions are not limited to the superficial dermis; multiple cutaneous nodules; inherited autosomal dominant genetic defect caused by a tumor suppressor gene (FCLN or Birt-Hogg-Dube gene) located on chromosome 5 which encodes the protein folliculin
- Peripheral nerve sheath tumor: Whorls, short interlacing streams
- Collagenous hamartoma: Proliferation will be in the superficial dermis elevating epidermis with distortion or loss of adnexa
- Granulation tissue: Numerous small caliber vessels perpendicular to the epidermal or mucosal surface
- Hypertrophic scar: Will usually have remnants of hair follicles or inflammation
- Keloidal fibroma: Collagen bundles are hyalinized, markedly thickened and irregular, and surrounded by proliferating fibrocytes
- Fibrosarcoma of the oral cavity in golden retrievers and large breed dogs: Histologically benign; grows rapidly and invades the maxilla and mandible; frequently recurs after surgery; submucosa is diffusely infiltrated by densely cellular sheets of pleomorphic fusiform fibroblasts arranged in interwoven bundles with variable, but often relatively small, amounts of collagen; mitotic rate is high in high-grad tumors; multinucleate giant cells (+/-)
- Malignant peripheral nerve sheath tumor: More complex structure with whorls and neuroid structure
- Feline post-vaccine fibrosarcoma: Necrotic center; peripheral lymphohistiocytic inflammation; macrophages containing intracytoplasmic brown-gray vaccine material
- Leiomyosarcoma: Minimal collagenous stroma and abundant cytoplasm with perinuclear vacuoles
- Keloidal fibrosarcoma: Keloidal fibromas rarely progress to keloidal fibrosarcomas; dermal portion of neoplasm resembles keloidal fibroma, but subcutaneous portion may develop invasive growth characterized by closely packed, interlacing bundles of spindle cells accompanied by a fibrovascular stroma with entrapped large hyalinized collagen fibers; mild anisokaryosis; mitotic index of 1 to 2
- Inflammatory myofibroblastic tumor (IMT): Discrete neoplasm composed of a interweaving streams and bundles of bland fusiform myofibroblastic cells and variable numbers of lymphocytes, plasma cells, and histiocytes; all spindle cells are positive for vimentin and calponin and a subset of spindle cells are positive for muscle actin and desmin
- Feline restrictive orbital myofibroblastic sarcoma (FROMS): Dense, moderately cellular infiltrate of neoplastic spindle cells; moderate collagenous matrix; non-discrete mass; orbit, eyelids, periorbital skin and soft tissues; collagen deposition leads to entrapment and restricted mobility of the eyelids and orbital tissues
- Horse: Sarcoids (locally aggressive, non-metastatic fibroblastic skin tumor associated with trauma and BPV1/2)
- Rabbit: Viral-induced Shope fibroma (Rabbit fibroma virus; a Leporipoxvirus transmitted by fleas and mosquitoes); fibrosarcoma
- Llama: Cutaneous and mucocutaneous fibroma/fibropapilloma was most common neoplasm in 2007 study from Oregon State University; fibrosarcoma
- Gerbil: Fibroma
- Angelfish: Lip fibroma
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