AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENT SYSTEM

October 2013

I-N13

 

SLIDE A

SIGNALMENT (AFIP #3007635):  7-year-old male neutered German Shepherd Dog

 

HISTORY:  2.5 x 2.5 cm firm mass on lateral aspect of left elbow

 

HISTOPATHOLOGIC DESCRIPTION:  Subcutaneous tissue (per contributor):  Expanding the subcutis and elevating the overlying dermis and epidermis is a 1 x 2 cm, unencapsulated, well-circumscribed, multilobulated neoplasm composed of spindle cells arranged in short interlacing streams and bundles, that often form whorls around capillaries and collagen.  In some areas the neoplastic cells are closely packed and separated by a small amount of collagenous matrix (Antoni A-like pattern).  In other areas, neoplastic cells are more widely separated and surrounded by a pale, loose, amphophilic matrix (Antoni B-like pattern).  There are occasional variably sized clefts partially separating neoplastic cells.  The neoplastic cells have variably distinct cell borders, scant eosinophilic fibrillar cytoplasm, and round to elongate nuclei with finely stippled chromatin and 1 to 2 variably distinct nucleoli.  The mitotic rate is less than 1 per 10 HPF.  Neoplastic cells occasionally form multinucleated cells. Multifocally there are few macrophages that contain an intracytoplasmic, brown globular pigment (hemosiderin), lymphocytes, plasma cells, and scattered hemorrhage.

 

MORPHOLOGIC DIAGNOSIS:  Subcutaneous tissue (per contributor): Peripheral nerve sheath tumor of the skin and subcutis, breed unspecified, canine.

 

SLIDE B

SIGNALMENT (AFIP #2923392):  Ten-year-old Belgian Malinois (military working dog)

 

HISTORY (AFIP #2923392):  This dog presented with a pedunculated mass on the left thigh.  At necropsy there were multiple nodules in the lungs which histologically were sites of metastasis.

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin, left thigh (per contributor):  Extending to cut borders is a multilobulated, infiltrative neoplasm composed of spindle cells arranged in short streams and interlacing bundles that occasionally whorl around vessels and are separated by a fibromyxomatous matrix. There are densely cellular areas (Antoni-A-like pattern) and more loosely arranged areas (Antoni-B-like pattern) with a storiform pattern. Neoplastic cells have variably distinct borders, small amounts of eosinophilic fibrillar cytoplasm, oval to elongate nuclei with finely stippled chromatin, and 1 to 3 distinct nucleoli. Mitotic figures average 2 per HPF. There is moderate anisokaryosis and anisocytosis and occasional binucleate neoplastic cells. Multifocally, there are stacked parallel rows of palisading nuclei (Verocay bodies). There is multifocal coagulative necrosis. There is a focally extensive ulcer with a serocellular crust composed of eosinophilic cellular and karyorrhectic debris (necrosis), fibrin, hemorrhage, and large numbers of degenerate neutrophils, and numerous superficial basophilic cocci.  Blood vessels subjacent to the ulcer often contain fibrin thrombi.

 

MORPHOLOGIC DIAGNOSIS:  Haired skin, left thigh (per contributor):  Malignant peripheral nerve sheath tumor of the skin and subcutis, Belgian Malinois, canine.

 

GENERAL DISCUSSION:

·         The WHO classification of peripheral nerve sheath tumor of the skin and subcutis (dogs), formerly called canine cutaneous spindle cell sarcoma, is a general term that includes neoplasms split into two categories:

·         Benign PNST of the skin and subcutis

·         Neurofibroma – when composed of Schwann cells and perineural cells

·         Schwannoma – when cells are solely of Schwann cell origin

·         Malignant PNST of the skin and subcutis

·         Neurofibrosarcoma – when composed of Schwann cells and perineural cells

·         Malignant schwannoma – when cells are solely of Schwann cell origin

·         Perivascular wall tumor (PWT), formerly termed canine hemangiopericytoma, is a new term which has been proposed for histologically similar tumors that originate from various cells of the vascular wall to include: hemangiopericytoma, angiomyeloma, angioleiomyosarcoma, myopericytoma, angiofibroblastoma and angiofibroma

·         Other articles propose lumping PWT and PNST into broad soft tissue sarcoma category as all are graded similarly and carry the same prognosis

·         Common in dogs, rare in cats

·         Growth rate is slow; metastasis is rare

 

TYPICAL CLINICAL FINDINGS: 

·         Fleshy to firm lobulated subcutaneous or dermal mass

·         Primarily located on the head, neck, tail, or distal limbs (especially stifle and elbow)

·         Range from 2.0 to 5.0 cm in diameter; sometimes much larger

·         Overlying skin is often alopecic, ulcerated, and hyperpigmented

·         Complete excision is difficult, and recurrence at the site of excision is common with tumors becoming more aggressive with each subsequent resection

 

TYPICAL GROSS FINDINGS:

·         Cut surface is cream colored, often lobulated, and may appear fatty

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

·         Well circumscribed with low cellularity

·         Spindle to ovoid cells with small amounts of eosinophilic cytoplasm

·         Areas of densely packed neoplastic spindle cells in short interlacing streams and bundles (Antoni A-like pattern) intermixed with areas of loosely packed haphazardly arranged neoplastic cells (Antoni B-like pattern)

·         Stacked parallel rows of palisading nuclei (Verocay bodies)

·         Neoplastic spindle cells often whorl around capillaries and or collagen

·         Variation in cellular density, clefting, and lipid laden macrophages

·         Graded according to soft tissue sarcoma scale based on degree of differentiation, degree of necrosis and mitotic rate (see below)

 

ADDITIONAL DIAGNOSTIC TESTS: 

·         PNSTs in dogs:

·         Neural tumors express vimentin, S-100 protein, myelin basic protein, neuron-specific enolase, and GFAP

·         Occasionally, S-100 protein, GFAP, or LEU 7 marker can be used to distinguish between schwannomas and neurofibroma/sarcomas

·         On electron microscopy: Thickened basal lamina around PNST tumor cells can be demonstrated with IHC for laminin and collagen IV, both basement membrane proteins

·         Desmin has been used to distinguish PNST from PWTs, however a more recent study found Olig2 and NGFR were more accurate, but inconsistencies were identified with each stain

 

DIFFERENTIAL DIAGNOSIS: 

·         Fibroma – are less cellular, lack palisading and whorling

·         Fibrosarcoma – have more mitotic activity and atypical mitoses; lack palisading and whorling

·         Spindle cell lipoma – have admixed adipose tissue

·         Dermatofibroma – have ragged margins and entrapped pre-existing dermal collagen bundles

 

COMPARATIVE PATHOLOGY:

·         PNSTs in cats: Regardless of the histological subset, feline PNST have the potential for local recurrence but none have been documented to metastasize

·         There are three distinct types which are distinguished histologically as:

1.    Benign tumors with Antoni A areas that are S-100 and GFAP positive

2.    Benign tumors that lack Antoni A areas and are S-100 positive and GFAP negative

3.    Tumors with features of malignancy such as a mitotic index greater than or equal to 4, nuclear atypia, tumor necrosis, and areas of high cellularity which are S-100 positive and variably positive for GFAP

·         Bovine:  Subcutis, heart, and brachial plexus; Schwannomas are most common; all bovine PNSTs were positive for S100 and CNPase in one study

·         Equine:  Eyelids; Schwannomas are most common; all positive for S100, laminin, and GFAP

·         Tasmanian devil: Devil facial tumor disease (DFTD) is a neoplasm of schwann cell origin; all DFTDs express periaxin

 

REFERENCES: 

1.  Avallone G, Hembold P, Caniatti M, Stefanello D, Nayak RC, Roccabianca P. The spectrum of canine cutaneous perivascular wall tumors: morphologic, phenotypic and clinical characterization.  Vet Pathol 2007;44:607-620.

2.  Bogaert L, Van Heerden M, De Cock HEV, Martens A, Chiers K. Molecular and immunohistochemical distinction of equine sarcoid from schwannoma. Vet Pathol 2011;48(3):737-741.

3.  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.

4.  Ginn PE, Mansell JEKL, Raich PM. The skin and appendages. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. 5th ed. Philadelphia, PA: Elsevier; 2007:762-763.

5.  Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Neural and perineural tumors. In: Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science; 2005:786-796.

6.  Hendrick MJ, Mahaffey EA, Moore FM, Vos JH, Walder EJ.  WHO Histological Classification of Mesenchymal Tumors of Skin and Soft Tissue of Domestic Animals, Vol II, 2nd ed. In:  Schulman FY, ed. Armed Forces Institute of Pathology, American Registry of Pathology, and The World Health Organization Collaborating Center, Washington, D.C.;1998:26-27, 32.

7.  Klopfleisch R, Meyer A, Lenze D, Hummel M, Gruber AD. Canine cutaneous peripheral nerve sheath tumours versus fibrosarcomas can be differentiated by neuroectodermal marker genes in their transcriptome. J Comp Pathol. 2013;148:197-205.

8.  Kreiss A, Tovar C, Obendorf DL, Dun K, Woods GM. A murine xenograft model for a transmissible cancer in Tasmanian devils. Vet Pathol 2011;48:475-481.

9.  Nielsen AB, Jensen HE, Leifsson PS. Immunohistochemistry for 2’,3’-cyclic nucleotide-3’-phosphohydrolase in 63 bovine peripheral nerve sheath tumors. Vet Pathol. 2011;48(4):796-802.

10.  Palmieri C, Avallone G, Cimini M, Roccabianca P, Stefanello D, Della Salda L.  Use of electron microscopy to classify canine perivascular wall tumors. Vet Pathol 2012;50(2):226-233.

11.  Schoniger S, Valentine BA, Fernandez CJ, Summers BA. Cutaneous schwannomas in 22 horses. Vet Pathol 2011;48:433-442.

12.  Schulman FY, Johnson TO, Facemire PR, Fanburg-Smith JC. Feline peripheral nerve sheath tumors: histologic, immunohistochemical, and clinicopathologic correlation (59 tumors in 53 cats).  Vet Pathol 2009;46:1166-1180.

13.  Suzuki S, Uchida K, Nakayama H. The effects of tumor location on diagnostic criteria for canine malignant peripheral nerve sheath tumors (MPNSTs) and the markers for distinction between canine MPNSTs and canine perivascular wall tumors. Vet Pathol. 2013;0:1-15.

14. Tovar C, Obendorf D, Murchison EP, Papenfuss AT, Kreiss A, Woods GM. Tumor-specific diagnostic marker for transmissible facial tumors of Tasmanian devils: immunohistochemistry studies. Vet Pathol 2011;48(6):1195-1203.

15.  Zachary, JF. The integument. In: McGavin MD, Zachary JF, ed. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, Missouri: Mosby; 2012: 867-868.

 

 

Reed 2013

 

 

 

 

 

 

 

 

 

 

 

                           Grading system for cutaneous and subcutaneous soft tissue sarcomas

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                           Dennis MM, et. al. Vet Pathol 2011;48:73-84.

 


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