JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N18B

Slide A

Signalment (JPC # 1647900): Age and breed unspecified, dog

HISTORY: A slow growing soft subcutaneous mass

HISTOPATHOLOGIC DESCRIPTION: Haired skin, subcutis: Expanding the subcutis and compressing the underlying skeletal muscle is a 1.5 cm diameter, well-circumscribed, partially encapsulated, moderately cellular neoplasm composed of mature adipocytes arranged in indistinct lobules on a fine fibrovascular stroma. Neoplastic adipocytes have distinct cell borders and a single, 60-130 µm, clear vacuole (lipid) that compresses and peripheralizes a flattened and hyperchromatic nucleus. Anisocytosis is marked depending on vacuole size and anisokaryosis is minimal. Mitoses are not seen. There is multifocal hemorrhage, fibrin, and edema.

MORPHOLOGIC DIAGNOSIS: Subcutis: Lipoma, breed not specified, canine.

Slide B

Signalment (JPC # 1958368): Age and breed unspecified, dog

HISTORY: A large, soft, subcutaneous mass

HISTOPATHOLOGIC DESCRIPTION: Haired skin, subcutis, and panniculus carnosus: Expanding the subcutis; elevating the overlying dermis and epidermis; widely separating adnexa; and separating, surrounding, and replacing skeletal muscle bundles is a poorly circumscribed, infiltrative neoplasm composed of densely packed, mature adipocytes with distinct cell borders and a single, clear, 50-80 µm, cytoplasmic vacuole that compresses and peripheralizes a flattened and hyperchromatic nucleus. Mitoses are not observed. Skeletal muscle fibers are often either replaced or are shrunken with angular margins (atrophy) or swollen with pale, vacuolated sarcoplasm (degeneration). Multifocally, apocrine glands are mildly ectatic.

MORPHOLOGIC DIAGNOSIS: Haired skin, subcutis: Infiltrative lipoma, breed not specified, canine.

Slide C

Signalment (JPC #1900656): Age and breed unspecified, dog

HISTORY: A firm subcutaneous mass from the shoulder

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Effacing the subcutis, elevating the overlying dermis, and extending to the deep margins is an infiltrative, unencapsulated, multilobulated neoplasm composed of polygonal to spindle cells that are arranged in solidly cellular areas or short streams separated by a fine fibrovascular stroma. Neoplastic cells have indistinct cell borders and a moderate amount of eosinophilic cytoplasm that often contains one large (up to 80 µm), distinct, clear vacuole (lipocyte) or several small (10-15 µm), distinct vacuoles (lipoblast). Nuclei are round to oval, vesiculate, and occasionally centrally located with up to 4 prominent magenta nucleoli. Mitoses average 2 per 2.37mm². There is marked anisokaryosis and anisocytosis. The center of the neoplastic lobule, affecting approximately 30% of this section, is characterized by loss of differential staining with retention of architecture (coagulative necrosis). Multifocally there is mild hemorrhage, fibrin, and edema admixed with few hemosiderin-laden macrophages.

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis, shoulder (per contributor): Liposarcoma, breed not specified, canine.

SYNONYMS: Soft tissue sarcoma favor liposarcoma

GENERAL DISCUSSION:

Lipoma

• Common benign neoplasm of adipocytes (also known as lipocytes)
• Reported more frequently in cocker spaniels, dachshunds, Weimaraners, Doberman pinschers, miniature schnauzers, labrador retrievers and small terriers
  • Higher incidence in obese female and middle-aged to older dogs and cats
• Common sites include the subcutis of the thorax, abdomen, proximal limbs, and brisket; often multiple; reports of canine primary cardiac/pericardial lipomas
• Intramuscular lipomas of the thigh region of dogs: Usually occur between the fascial planes of the semitendinosus and the semimembranosus muscles, are not infiltrative, and have an excellent prognosis following surgical excision
• Occasionally, hemangiosarcomas/mast cell tumors arise from lipomas, suggesting that lipomas may provide a beneficial environment for tumor development

Infiltrative Lipoma

• Uncommon variant of lipoma characterized by intramuscular invasion
• Most common in dogs and horses
  • Doberman pinschers, Labrador retrievers, and standard schnauzers may be predisposed
• Common sites include the subcutis of the extremities, thorax, and neck
• Usually occur in middle-aged dogs
• Not associated with obesity
• Locally invasive, and often recur following incomplete excision
• Usually do not metastasize
• May rarely undergo malignant transformation to liposarcoma (Kim, 2025).

Liposarcoma

• Rare malignant tumor of lipocytes; may also arise from fat cell precursors in the bone marrow
• Locally invasive and may recur, but rarely metastasize
• Common sites include the subcutis of the ventral thorax, abdomen and proximal limbs; have also been reported in mammary gland of dogs
• Dachshunds, Shetland sheepdogs and Brittany spaniels are predisposed
  • Usually occur in older dogs

PATHOGENESIS:

• Not definitively known

TYPICAL GROSS FINDINGS:

Lipoma

• Well-circumscribed, soft, white to yellow neoplasms not attached to adjacent tissue

Infiltrative Lipoma

• Soft, poorly circumscribed, deep subcutaneous masses attached to the surrounding tissue; may cause pain or interfere with limb function

Liposarcoma

• Poorly circumscribed, firm, gray-white neoplasms

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Necrosis, hemorrhage, and fibrosis can occur in any of these neoplasms especially if they are large or traumatized

Lipoma

• Well-circumscribed proliferation of well-differentiated adipocytes
  • Indistinguishable from normal fat except for compression of adjacent tissue and a fine capsule which separates tumor from normal adipose tissue
  • Some contain cartilage, bone, collagen or blood vessels

Infiltrative lipoma

• Well-differentiated adipocytes that invade muscle, fascia, and occasionally bone

Liposarcoma

• Densely cellular, infiltrative; round to spindle cells with variably sized intracytoplasmic vacuoles and a central nucleus (lipoblasts) mixed with lipocytes
• May display anisokaryosis and multinucleated cells; mitotic figures are usually infrequent
• Three subtypes
  • Well-differentiated liposarcoma: Resemble normal adipocytes with a single clear fat vacuole and a peripheral nucleus admixed with lipoblasts
  • Anaplastic/pleomorphic liposarcoma: Anaplastic with large bizarre tumor giant cells; only a few cells contain fat vacuoles and neoplastic cells bear little resemblance to adipocytes
  • Myxoid liposarcoma: Scattered lipoblasts with prominent mucinous ground substance

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology: Oily appearance on aspiration, lipomas typically contain clusters of adipocytes, few spindle cells and bare nuclei, can be washed off during the alcohol fixative portion of staining; liposarcomas have increased nuclear pleomorphism with mitotic figures possible, often free lipid and fewer well differentiated adipocytes
• Immunohistochemistry
• Vimentin positive; may be S-100 positive
• Histochemistry: Stains for lipid on frozen tissue sections include Oil-red-O, osmium, and Sudan black

DIFFERENTIAL DIAGNOSIS:

Histologic and/or gross differentials:

• Normal subcutaneous adipose tissue: Must consider if sample is from FNA
• Hibernomas (I-N14): Soft, brown tumor of brown adipose tissue; neoplastic cells have tiny cytoplasmic lipid droplets; occurs most commonly in the subcutis of the dorsal thorax and the axilla of rodents and wild mammals
• Myelolipoma: Adipocytes are combined with myeloid elements; primarily in the liver of domestic cats and wild cats such as cheetahs, spleen of dogs, and the adrenal gland of nonhuman primates and cattle
• Myxosarcoma: Absence of lipid vacuoles aids in differentiating from liposarcoma; spindle to stellate neoplastic cells
• Balloon cell melanoma: Brown cytoplasmic granules and IHC + for melanocytic markers (MelanA Red)
• Anaplastic sebaceous carcinoma: Arranged in nests and lobules

Other Lipocytic tumors:

• Uncommon variants may also have components of collagenous stroma (fibrolipoma), cartilage (chondrolipoma), or blood vessels (angiolipoma) that are mixed with adipose
• Osteoliposarcoma: malignant mesenchymoma that contains liposarcomatous and osteosarcomatous tissue; reported in a dog

COMPARATIVE PATHOLOGY:

• Lipomas occur in all species
  • Bovine: Rare; Most often located in internal organs
  • Horse: Pedunculated lipomas develop in the mesentery and cause intestinal strangulation
  • Owl monkeys: strangulating lipoma reported as a cause of acute GI disease (Hensel et al, 2024).
  • Birds: lipomas have been reported as a cause of beak neoplasia in multiple avian species (Barrantes Murillo et al, 2025).
  • Most common external neoplasm diagnosed in guinea pigs (Dobromylskyj et al, 2023).
• Infiltrative lipoma: Rare reports in horses, cattle, and cats
• Liposarcomas: Rare in all species
  • In cats, have been associated with vaccination sites and retrovirus infection
  • Renal liposarcomas in research rats
  • Recent report of a lingual liposarcoma arising from an infiltrative lipoma in a dog; contrasts current thought that lipomas do not undergo malignant transformation (Kim et al, 2025).

Lipomatosis in cattle: Infrequently, congenital infiltrative lipomatosis is seen in calves and can infiltrative into the subcutis, deeper musculature, and skeleton (Caliskan et al, 2024).

REFERENCES:

1. Barrantes Murillo DF, Berrocal A, Bell C, Rissi DR, Craig LE, Graham EA, Brinker EJ, Negrão Watanabe TT. Oral fibrolipoma in dogs: Retrospective case series study and comparative review. Vet Pathol. 2025;62(1):31-36. 
2. Barrantes Murillo DF, Berrocal A, Stranahan LW, Brinker EJ, Craig LE, Negrão Watanabe TT. Beak neoplasia in avian species: description of nine cases. J Comp Pathol. 2025;221:35-39.
3. Brannick EM, Newkirk KM, Schaefer DMW. Neoplasia and tumor biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:387.
4. Caliskan N, Vandekerckhove A, Forrez E, Rolly E, Strubbe M, Roels S. Two cases of congenital lipomatosis in calves. J Comp Pathol. 2024;211:52-56. 
5. Dobromylskyj MJ, Hederer R, Smith KC. Lumpy, bumpy guinea pigs: a retrospective study of 619 biopsy samples of externally palpable masses submitted from pet guinea pigs for histopathology. J Comp Pathol. 2023;203:13-18.
6. Fisher DJ. Cutaneous and subcutaneous lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020:96.
7. Hensel ME, Rodrigues-Hoffmann A, Dray BK, Wilkerson GK, Baze WB, Sulkosky S, Hodo CL. Gastrointestinal tract pathology of the owl monkey (Aotus spp.). Vet Pathol. 2024;61(2):316-323.
8. Kim TU, Huh C, Yim JH, Kim WJ, Baek SM, Park JK. Lingual liposarcoma transitioning from an infiltrative lipoma in a dog. J Comp Pathol. 2025;221:31-34.
9. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. New York, NY: Elsevier, Inc.; 2016:726.
10. Raskin RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:92-93.
11. Valentine BA. Skeletal muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1016.
12. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1209-1219.

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