JPC SYSTEMIC PATHOLOGY
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 on a fine fibrillar stroma. Neoplastic adipocytes have distinct cell borders and a single 60-130 micron clear vacuole that compresses and peripheralizes the nucleus. Nuclei are flattened and hyperchromatic. Anisocytosis is marked depending on the size of the vacuole, but anisokaryosis is minimal. Mitoses are not seen. There are two focal areas of hemorrhage within the neoplasm with associated dark brown to golden globular pigment (hemosiderin).
MORPHOLOGIC DIAGNOSIS: Subcutis: Lipoma, breed not specified, canine.
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 adipocytes with distinct cell borders and a single, clear, 50-80 um cytoplasmic vacuole that compresses and peripheralizes the nucleus. Nuclei are flattened and hyperchromatic. Mitoses are not observed. Multifocally, apocrine glands are mildly ectatic. Skeletal muscle bundles are multifocally mildly atrophied characterized by disorganization of myofibers with paler staining.
MORPHOLOGIC DIAGNOSIS: Haired skin, subcutis: Infiltrative lipoma, breed not specified, canine.
Signalment (JPC #1900656): Age and breed unspecified, dog
HISTORY: A firm subcutaneous mass from the shoulder
HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis, shoulder: 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 solidly cellular or arranged in 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 um) distinct, clear vacuole (lipocyte) or several small (10-15 um) distinct vacuoles (lipoblast). Nuclei are round to oval, vesiculate and occasionally centrally located, with a single prominent magenta nucleolus. Mitoses average 2 per 10 400X HPF. There is marked anisokaryosis and anisocytosis. The center of the neoplastic lobule is necrotic. Multifocally there is mild hemorrhage admixed with few hemosiderin-laden macrophages.
MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis, shoulder (per contributor): Liposarcoma, breed not specified, canine.
- Common benign neoplasm of adipocytes
- 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
- 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
- Uncommon variant of lipoma characterized by intramuscular invasion
- Most common in dogs and horses
- Doberman pinschers, Labrador retrievers, and standard schnauzers may be predisposed (according to one study)
- 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 no metastasize
- Rare malignant tumor of lipocytes
- 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
- May also arise from fat cell precursors in the bone marrow
- A 2011 Veterinary Pathology article classified liposarcomas as one of nine “cutaneous/subcutaneous soft tissue sarcomas;” soft tissue sarcomas are graded (I-III) using a scale which assesses differentiation, mitotic index and degree of necrosis
- A 2016 study of dog liposarcomas found that platelet-derived growth factor receptor-beta (PDGFR-beta) is expressed at a higher level in more mitotically active liposarcomas, suggesting that PDGFR-beta-mediated pathways may have a role in the progression of canine liposarcoma
- PPARs (peroxisome proliferator-activated receptors) are nuclear receptors that are important in adipocyte differentiation; they are also involved in insulin resistance and diabetes
- Three major PPARs:
- PPAR-alpha, PPAR-gamma, PPAR-delta
- PPAR-alpha agonists affect triglyceride and HDL levels; they induce pancreatic acinar cell, testicular Leydig cell and possibly liver tumors in rats
- PPAR-gamma agonists have antimitotic effects on preadipocyte proliferation, while PPAR-delta agonists stimulate proliferation of preadipocytes
- PPAR-gamma agonists have been used in human liposarcoma therapy
- A study of human lipomas and liposarcomas found that:
- PPAR-delta is highly expressed in liposarcoma (versus lipoma) and inhibits leptin expression
- Leptin (an adipose tissue secretory factor or adipokine) is downregulated and appears to inhibit proliferation and migration in liposarcoma compared to lipoma
- PPAR-gamma agonists have been associated with liposarcoma, fibrosarcoma and hemangiosarcoma in rats
- Three major PPARs:
Other Lipocytic tumors:
- Multicentric proliferation of architecturally normal adipose tissue
- Pendulous, fatty skin folds involving the neck and trunk (dog); caudal thighs (cat)
- Histo: Diffuse thickening of the subcutis by mature adipocytes with a small number of primitive mesenchymal cells and lipoblasts
- Characterized by the presence of sparse to moderate amounts of dissecting fibrous connective tissue within a lipoma
- Differential: Fibrotic adipose tissues (end-stage reaction to trauma or severe inflammation)
- Clusters of branching blood vessels within an otherwise typical lipoma
- Differential: Infiltrative hemangioma
- Bands of collagen/branching vessels dissecting well-differentiated adipose tissue
- Scattered islands of well differentiated cartilage within otherwise typical lipoma
Spindle cell lipoma
- Benign rare tumor in dogs, recognized in humans
- Hip, elbow, ventral abdomen, inguinal region, mid-dorsal trunk, forehead
- Well circumscribed, varying between mature adipocytes and spindle cells
- Similar to lipoma, with subtle increased cellularity, and small numbers of individual or clustered lipoblasts; cellular atypia; considered low-grade liposarcomas
- Differentials: Mildly inflamed lipomas, steatitis, fibrolipomas
- Less common variant of liposarcoma, characterized by mucin background
- Differentials: Myxoid variants of other spindle cell malignancies
- Tumor cells vary markedly in size and shape; multinucleated giant cells are common
- Lipoblasts: Marked nuclear variability with hyperchromatism and prominent nucleoli
- Differentials: Histiocytic sarcoma, anaplastic sarcoma with giant cells
Intracranial lipomatous hamartoma
- Mature adipose tissue with varying amounts of intervening fibrous tissue or other mesenchymal elements.
- Uncommon, reported in human, dog, mice, rats, ducks, single report in horse, pig, humpback whale; generally asymptomatic unless compressing adjacent neuroparenchyma.
TYPICAL GROSS FINDINGS:
- Well-circumscribed, soft, white to yellow neoplasms not attached to adjacent tissue
- Soft, poorly circumscribed, deep subcutaneous masses attached to the surrounding tissue; may cause pain or interfere with limb function
- 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
- Well-circumscribed proliferation of well-differentiated adipocytes
- Indistinguishable from normal fat except for a fine capsule which separates tumor from normal adipose tissue and compression of adjacent tissue
- Some contain cartilage, bone, collagen or blood vessels
- Infiltrative lipoma: Well-differentiated adipocytes that invade muscle, fascia and occasionally bone
- Densely cellular, infiltrative; round to spindle cells with cytoplasm containing variably sized vacuoles and central nucleus (lipoblasts) mixed with lipocytes
- May display anisokaryosis, multinucleated cells and mitoses
- Three subtypes
- Well-differentiated liposarcoma: Resemble normal adipocytes with a single clear fat vacuole and a peripheral nucleus admixed with lipoblasts
- Pleomorphic liposarcoma: Anaplastic with large bizarre multinucleated cells; only a few cells contain fat vacuoles
- Myxoid liposarcoma: Scattered lipoblasts with abundant stromal mucin
- Round cell variant: Neoplastic cell morphology is more round with abundant binucleate to multinucleate cells
- Myxoid liposarcoma (round cell variant): Populations of myxoid and round cells. Analogous to high-grade myxoid liposarcoma in humans.
ADDITIONAL DIAGNOSTIC TESTS:
- Liposarcoma: higher mitotic rate correlated with lower FGF2 and higher PDGFR-beta expression
- Liposarcoma: Like in humans, in dogs MDM2 expression is inversely correlated with grade (high MDM2 expression in grade I tumors), and is expressed frequently in canine well-differentiated and dedifferentiated liposarcomas but rarely in myxoid or pleomorphic liposarcomas; unlike humans, CDK4 has shown no histotype or grade correlation.
- Vimentin positive; may be S-100 positive
- Stains for lipid on frozen tissue sections (i.e. Oil-red-O, osmium, Sudan black)
- Normal subcutaneous adipose tissue: Must consider if sample is from FNA
- Hibernomas: 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
- Lipomas occur in all species
- Bovine: Rare; Most often located in internal organs
- Dog: Reports of primary cardiac/pericardial lipomas
- Horse: Pedunculated lipomas develop in the mesentery and cause intestinal strangulation
- Case reports:
- Snakes: One report showed 8 of 33 soft tissue masses studied were lipoma; this study was the first report of lipoma in a ribbon snake, and of angiolipoma in a black-headed bython and corn snakes
- Rhesus macacque: lipomatosis with self-strangulating lipoma
- 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
- Reports: Bovine nasal cavity, neck, tail base
- Pet rabbits
- Case reports:
- Metastatic pleomorphic liposarcoma in a South African fur seal
- Metastatic pleomorphic liposarcoma in a pig
- Myxoid liposarcoma round cell variant in a Japanese macaque
- Avallone G, Pellegrino V, Roccabianca P, Lepri E, Crippa L, Beha G, De Tolla L, Sarli G. Tyrosine kinase receptor expression in canine liposarcoma. Vet Pathol 2016 Oct 3. pii: 0300985816671379. [Epub ahead of print]
- Avallone G, Roccabianca P, Crippa L, Lepri E, Brunetti B, Bernardini C, Forni M, Olandese A, Sarli G. Histological classification and immunohistochemical evaluation of MDM2 and CDK4 expression in canine liposarcoma. Vet Pathol. 2016: 53(4)773-780.
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- Deitz J, Heckers KO, Aupperle H, Pees M. Cutaneous and subcutaneous soft tissue tumours in snakes: A retrospective study. J Comp Path. 2016;155(1):76-87.
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