AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENT SYSTEM

October 2019

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 10 x 6 mm, well-circumscribed, unencapsulated, sparsely cellular 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 and cytoplasm and an elongate nucleus with finely stippled chromatin and an indistinct nucleolus. The mitotic rate is less than 1 per 10 40x HPF. Multifocally within the neoplasm and the directly adjacent subcutis and dermis are low numbers of perivascular lymphocytes and plasma cells. Multifocally within the superficial dermis there are low numbers of often perivascular lymphocytes and plasma cells; collagen fibers are mildly separated by amphophilic, beaded to fibrillar mucin; and apocrine glands are mildly ectactic and lined by attenuated epithelium.

 

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 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, long interlacing streams and bundles and forming “herringbone” patterns supported on an abundant, dense collagenous matrix. Neoplastic cells have indistinct cell borders and 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 10 40x 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 scant hemorrhage, fibrin, and edema. Multifocally within mucosal keratinocytes, there is both intracellular (edema) and extracellular (spongiosis) clear space.

 

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

 

 

SLIDE C

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

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Expanding the deep dermis and subcutis, elevating the overlying dermis and epidermis, 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 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 10 40x HPF. 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 and subcutis: Fibroma, keloidal, dermal, Chesapeake Bay retriever, canine

 

GENERAL DISCUSSION:

·      Fibroma

·      Benign tumor of fibroblasts and collagen

·      Uncommon in all domestic animals

·      Fibrosarcoma

·      Common in dogs and cats, but uncommon 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

·      Only the mitotic index is significant as a predictor of tumor behavior

·      Dog: Less than 9 is associated with greater survival time

·      Cat: Equal to or less than 5 is associated with greater survival time

·      Keloidal fibroma/fibrosarcoma is considered a histologic subtype

·      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)

·      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 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:

·      Horse: Sarcoids (locally aggressive, non-metastatic, fibroblastic skin tumor associated with trauma, association with BPV1/2 is currently controversial; I-N17)

·      Rabbit: Viral-induced Shope fibroma (Rabbit fibroma virus; a Leporipoxvirus transmitted by fleas and mosquitoes); fibrosarcoma

·      Neon Tetra: Single case of a cutaneous ossifying fibroma

·      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

 

REFERENCES:

1.    Dennis MM, McSporran KD, Bacon NJ, Schulman FY, Foster RA, Powers BE. Prognostic factors for cutaneous and subcutaneous soft tissue sarcomas in dogs. Vet Pathol. 2011;48:73-84.

2.    Gross TL, Ihrke PJ, Walder EJ, et al. Fibrous tumors. In: Gross TL, Ihrke PJ, Walder EJ, et al. eds. Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science Ltd; 2005:716-734.

3.    Hargis AM, Myers S. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1065, 1109, 1754.

4.    Hendrick MJ. Mesenchymal Tumors of the Skin and Soft Tissues. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: John Wiley & Sons, Inc; 2017:143-5, 147-8, 152.

5.    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; 2016:523, 616, 722-6.

6.    Murphy B, Imai DM. Cutaneous Ossifying Fibroma in a Neon Tetra (Paracheirodon innesi). J Comp Path. 2016;155:272-275.

7.    Newkirk KM, Brannick EM, Kusewitt DF. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:312.

8.    Raskin RE. Skin and Subcutaneous Tissues. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 3rd ed. St. Louis, MO: Elsevier; 2016:66-68.

9.    Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:27, 35, 44, 424.


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