JPC SYSTEMIC PATHOLOGY
Signalment (JPC 2799364): Age and breed unspecified cat
HISTOPATHOLOGIC DESCRIPTION: Subcutis (per contributor): Infiltrating the subcutis and compressing the panniculus carnosus is a 1.0 x 0.8 cm, unencapsulated, multilobulated, moderately cellular neoplasm composed of spindle cells arranged in long interlacing streams and bundles separated by fibromyxomatous matrix. Neoplastic cells have indistinct borders, a small amount of eosinophilic fibrillar cytoplasm, with an oval to elongate nucleus, finely stippled chromatin and1-3 prominent magenta nucleoli. There is moderate anisokaryosis with multifocal single cell necrosis. The mitotic count, averages 1 per 400x HPF. There are multifocally peripheral are perivascular aggregates of macrophages, often-containing blue-gray clumped intracytoplasmic granular material (vaccine material) admixed with aggregates of lymphocytes, and fewer plasma cells and neutrophils. There is rare degeneration and atrophy of subjacent myocytes.
MORPHOLOGIC DIAGNOSIS: Subcutis (per contributor): Vaccine-associated fibrosarcoma, breed unspecified, feline.
CAUSE: Post-vaccination reaction – Rabies or FeLV
SYNONYMS: Feline injection site sarcoma, Postvaccinal fibrosarcomas
Signalment (JPC 2800486): A domestic longhair cat
HISTOPATHOLOGIC DESCRIPTION: Subcutis(per contributor): Within the subcutis there is an 8 x 10 mm nodule with a central pseudocyst containing anastomosing trabeculae composed of eosinophilic lamellated amorphous polymerized fibrin admixed with necrotic debris and areas of drop-out (lytic necrosis). The pseudocyst is rimmed by granulation tissue composed of loosely arranged reactive fibroblasts and small caliber blood vessels lined by reactive endothelial cells that are frequently arranged perpendicular to the surrounding fibrous connective tissue. The pseudocyst is further surrounded by abundant fibrosis, high numbers of large epithelioid macrophages filled with amphophilic granular material (vaccine material), moderate numbers of eosinophils, and nodular perivascular aggregates of lymphocytes. Rarely, there are foreign body and Langhans type multinucleated giant cells.
MORPHOLOGIC DIAGNOSIS: Subcutis: Panniculitis, granulomatous , focally extensive, marked, with central pseudocyst, granulation tissue, and intrahistiocytic vaccine material, domestic longhair, feline.
CONDITION: Post-injection panniculitis; Vaccine-associated granuloma
- Fibrosarcoma most common malignant mesenchymal tumor of cats, 3 forms:
- Non vaccine-associated fibrosarcoma: larger solitary biologically aggressive (more than viral or vaccine induced), commonly in older cats
- Recur multiple times within a period of weeks to months when removed
- Virus-induced from feline sarcoma virus (FeSV): Rare, cause of multicentric fibrosarcoma in cats usually less than 5 years of age
- Retrovirus, requires feline leukemia virus (FeLV) as a helper virus > genetic recombination between viruses > induces multiple simultaneous rapidly growing fibrosarcomas
- Typically locally invasive and metastasize to lung and other sites
- Vaccine-associated sarcoma
- Locally aggressive with a high rate of local recurrence
- Occasionally metastasize, especially to the lungs
- Poor prognosis
- Reported vaccine induced sarcomas include (not limited to):
- Osteosarcoma and chondrosarcoma
- Histiocytic sarcoma (malignant fibrous histiocytoma)
- Overzealous reparative response at postvaccinal site of inflammation or wound healing or both > malignant transformation of mesenchymal cells
- Postvaccinal granulomatous / necrotizing panniculitis possible premalignant lesion
- Epidemiologic studies suggest:
- Increased occurrence at repeated vaccination sites
- FeLV or rabies vaccines; both adjuvant and non- adjuvant vaccines
- Platelet-derived growth factor (PDGF) positive lymphocytes in vaccine-associated sarcomas > secrete PDGF to recruit histiocytes resulting in fibroblastic proliferation
- Vaccine-associated sarcomas are strongly positive for c-jun, a protooncogene that codes for a transcriptional protein (AP-1), which causes cellular proliferation
- Mutation in the p53 gene may play a role in tumor pathogenesis
TYPICAL CLINICAL FINDINGS:
- Average age of cats is 9.6 years, which is younger than cats with nonvaccine-associated fibrosarcoma; no known breed or sex predilection
- Irregularly shaped, firm, multilobular, and are typically larger (greater than 4 cm in diameter) than non-vaccine associated sarcomas
- Post vaccine sites: Interscapular, dorsal neck, shoulder, flank and femoral areas
TYPICAL GROSS FINDINGS:
- Poorly circumscribed neoplasm involving the subcutis and often the underlying musculature and dorsal spinous processes
- Larger tumors often have a central area of necrosis and cavitation on cut surface
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Vaccine-associated sarcomas:
- Neoplastic myofibroblasts
- Neoplastic multinucleated giant cells
- Macrophages often contain an intracytoplasmic granular to crystalline gray-brown to bluish vaccine material
- Necrotic core with micro- or macro-cavitations surrounded by neoplastic cells
- Prominent peripheral lymphoid aggregates with high proportion of T cells
- Differentiates vaccine-associated from non vaccine-associated sarcomas
- Accentuated peripheral vascularity
- Tumors are often contiguous with granulation tissue
- Vaccine reaction:
- Perivascular aggregates of predominately lymphocytes and eosinophils arranged around a central core of caseous necrosis
- Macrophages with gray-brown (amphophilic) to bluish vaccine material granular vaccine substance
- Spindle cells, giant cells, histiocytoid cells and cells with myofibroblastic features
- Similar to fibroblasts; subplasmalemmal dense attachment of plaques and thin cytoplasmic actin myofilaments
ADDITIONAL DIAGNOSTIC TESTS:
- Histochemical stains/ Immunohistochemistry:
- Vimentin positive
- Smooth muscle actin positive
- COX-2 negative
- Masson’s trichrome highlights collagen
- Electron probe x-ray microanalysis to identify intra histiocytic adjuvant (aluminum)
- Cytology: Abundant large, plump spindle cell individually arranged and in aggregates associated with pink, collagenous material with occasional multinucleated giant cells
- Primary or metastatic neoplasm: Cutaneous lymphomas at injection sites (CLIS)
- Inflammatory: Granuloma, abscess, foreign body reaction
- Immune mediated: Post vaccine reaction
- Non vaccine-associated fibrosarcoma: No peripheral lymphocytes / macrophages
- Giant cell tumor of tendon sheath: Nuclear pleomorphism, abnormal mitoses
- Hemangiopericytoma: Concentric whorls of spindle cells around capillaries; occurs almost exclusively in dogs
- Keloidal vaccine-associated fibrosarcoma: Thick bands of hyalinized collagen
- Leiomyosarcoma: Often retain cigar shaped nucleus
- Liposarcoma: Lipocytes, pleomorphic, +/- scant collagen
- Myxosarcoma: Spindloid to stellate cells separated by mucinous material
- Myofibroblastic sarcoma
- Nerve sheath tumors
- Feline intraocular tumors
- Most common types: melanomas, primary ocular sarcomas, optic nerve meningiomas, malignant lymphomas
- Feline post-traumatic ocular sarcoma (FPTOS
- Second most common primary feline ocular neoplasm
- Unique to cats (few reports in rabbits) recognized following a period of dormancy (average 5 years)
- Eyes subjected to trauma, especially penetrating injury, prone to develop pleomorphic spindle cell sarcomas that efface the globe
- Locally invasive (hallmark feature) malignant neoplasm
- Initially spindle cells line and efface the uveal tract, extending to the sclera and optic nerve, ultimately diffusely filling the globe
- Inclination to “line the globe” is a repeatable feature that can be used to distinguish primary ocular sarcoma from rare metastatic sarcomas
- Similar morphologic features to feline vaccine-induced sarcomas fibrosarcomas, but have a mixed epithelial-mesenchymal phenotype, suggesting lens epithelial origin
- Feline restrictive orbital myofibroblastic sarcoma (FROMS), previously feline orbital pseudotumor, is a progressive, invasive, sclerosing orbital tumor resembling a low-grade myofibroblastic sarcoma
- Affected cats typically have a history of restricted mobility of the globe & eyelids with secondary corneal disease
- Characterized by infiltration of neoplastic spindle cells in the orbit, eyelids, and periorbital skin and soft tissues, with collagen deposition and a few perivascular lymphocytes
- IHC: Positive for vimentin, S-100 and smooth muscle actin
- Often no discrete mass; spreads along fascial planes; often concurrent involvement of contralateral eye and/or oral cavity
- Dogs: Immune-mediated dermatoses with focal mononuclear vasculitis and ischemic atrophy of surrounding follicles
- Post rabies vaccine panniculitis (poodle patch), cell-poor vasculitis with follicular atrophy and lymphocytic panniculitis is associated with rabies vaccine
- Rabies vaccine–associated panniculitis can present like lupus panniculitis
- Microchip associated fibrosarcoma (one case report)
- Ferrets: Preferential development of fibrosarcomas in areas routinely used for vaccine administration; similar histologic, immunohistochemical, and ultrastructural features as those in feline vaccine-associated sarcomas
- Horse: Injection-site eosinophilic granulomas, progressive (1-3 days post vaccination) nodules with necrotic cores, response to the use of silicone-coated hypodermic needles (form of delayed hypersensitivity)
- Rats: Malignant fibrous histiocytomas at injection sites, experimentally induced in rats associated with chronic inflammation
- Rabbits: Intraocular tumors are variably pleomorphic, poorly differentiated, invasive, intraocular spindle cell neoplasms associated with lens capsular fragments
- Closely resemble feline post-traumatic ocular sarcomas
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