Pathology in Practice

Terry M. Jacobs 1Park Pet Hospital, 7378 N Teutonia Ave, Milwaukee, WI 53209.

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F. Yvonne Schulman 2Marshfield Labs, Veterinary Services, 1000 N Oak Ave, Marshfield, WI 54449.

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History and Clinical Findings

A 9-year-old 6.8-kg (14.96-lb) neutered male domestic shorthair cat was evaluated because of a progressively enlarging mass that encompassed the caudomedial region of the left brachium. The cat had a history of mild lameness of the left forelimb of approximately 1 year's duration, and the mass had been apparent for 8 months. The cat's vaccination status was current; vaccine administration involved the left flank area. On physical examination, the cat had non-weight-bearing lameness of the left forelimb with massive, firm to gelatinous, nonpainful swelling of the soft tissues caudal and medial to the shoulder joint with extension down to the elbow joint. Results of a CBC, serum biochemical analysis, and assessment of serum thyroxine concentration were unremarkable; a coagulation profile revealed no abnormalities. The cat tested negative for circulating FeLV antigen and anti-FIV antibody. Radiography of the left forelimb revealed lytic lesions of the humeral head and glenoid process of the scapula as well as severe soft tissue swelling; results of 3-view thoracic radiography did not indicate any evidence of metastasis. Left forelimb amputation including the scapula was performed.

Gross Findings

An 8.5 × 6.5 × 4.0-cm, off-white to gray, glistening, multiloculated soft tissue mass was attached to the caudomedial aspect of the shoulder joint. Amber-colored mucoid fluid was contained within variably sized cavities dispersed throughout the mass (Figure 1)

Figure 1—
Figure 1—

Photograph of the amputated left forelimb of a 9-year-old domestic shorthair cat. The cat was evaluated because of a mass that encompassed the caudomedial region of the left brachium and had been progressively enlarging over a period of 8 months. Notice the multiloculated soft tissue mass with cavities containing amber fluid attached to the caudomedial aspect of the shoulder joint.

Citation: Journal of the American Veterinary Medical Association 255, 7; 10.2460/javma.255.7.797

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →

Histopathologic Findings

A portion of the left forelimb including the proximal portion of the humerus and the entire scapula was fixed in neutral-buffered 10% formalin. Sections of the mass with attached soft tissues and affected bone were routinely processed for histologic examination. The mass was composed of spindle-shaped to stellate to occasionally round cells that were arranged in streams or haphazardly and separated by small to moderate amounts of myxomatous to loosely arranged collagenous matrix (Figure 2) The cells had infiltrated and expanded the subcutis and had abutted, infiltrated, and partially effaced the proximal portion of the humerus and ventral aspect of the scapula. Neoplastic cells had an irregularly oval nucleus, stippled chromatin, usually a single (occasionally 2 or more) small- to medium-sized nucleolus, a small to moderate amount of cytoplasm, and indistinct cell margins. Scattered neoplastic cells were expanded by multiple, small, clear, discrete lipid-type cytoplasmic vacuoles that indented the nucleus (Figure 3); occasionally, a single, large, clear, discrete vacuole indented and peripheralized the nucleus, creating a signet ring appearance. The mitotic count was low (< 1/10 hpf [total area examined, 2.37 mm2]). Within the tumor, there were large cavitary lesions, corresponding to the loculated areas noted grossly. Osteolysis and peripheral lymphoid aggre-gates were present. The tumor appeared completely excised. Recognizable lymph node tissue was not identified grossly or histologically.

Figure 2—
Figure 2—

Photomicrograph of an Alcian blue-stained section of the excised tumor in Figure 1. The neoplasm is composed of spindle-shaped to stellate to occasionally round cells arranged in streams or haphazardly and separated by small to moderate amounts of myxomatous matrix. Occasional cells (arrows) are distended by discrete, lipid-type vacuoles. Alcian blue stain; bar = 200 μm.

Citation: Journal of the American Veterinary Medical Association 255, 7; 10.2460/javma.255.7.797

Figure 3—
Figure 3—

Photomicrographs of a section of the excised tumor in Figure 1. A—Notice the neoplastic cell (arrow), which is expanded by multiple, clear, discrete lipid-type cytoplasmic vacuoles that indent the nucleus. H&E stain; bar = 60 μm. B—One of the neoplastic cells has a single, large, clear, discrete vacuole that indents and pushes the nucleus to the side, thereby creating a signet ring appearance. H&E stain; bar = 60 μm.

Citation: Journal of the American Veterinary Medical Association 255, 7; 10.2460/javma.255.7.797

In addition to routine histologic evaluation, sections of the mass underwent staining with special stains (Alcian blue and oil red O stains for paraffin-embedded tissue) and immunohistochemical analysis for S-100 protein. In Alcian blue-stained sections, the extracellular matrix stained blue (Figure 2), consistent with myxomatous matrix. The cytoplasmic vacuoles did not stain with Alcian blue or oil red O stain in the paraffin-embedded tissue (frozen tissue samples were not available, and formalin-fixed wet tissue samples were no longer available when the special staining was performed). Immunohistochemically, neoplastic cells tested negative for S-100 protein.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: histologically low-grade myxoid liposarcoma with osteolysis of the proximal portion of the left humerus and ventral aspect of the left scapula in a cat.

Comments

The cat of the present report had a slowly progressive forelimb tumor that originated in the soft tissues caudomedial to the left shoulder joint and invaded the humerus and scapula. The clinical findings were strongly suggestive of neoplasia, and the gross appearance of a multiloculated mass with mucoid fluid was consistent with a soft tissue sarcoma. Examination of a fine-needle aspirate specimen of the mass, which was not performed in this case, may have provided information to help support the diagnosis of sarcoma, but differentiation of neoplastic mesenchymal cells from reactive fibroblasts in cytologic preparations can be difficult or impossible.

Histologically, the tumor in the cat of the present report was a mesenchymal neoplasm with myxoid matrix and cytoplasmic vacuoles. Both myxoid liposarcomas and myxofibrosaromas can have cytoplasmic vacuoles, but in liposarcomas, the vacuoles indent the nuclei of neoplastic cells, as was seen in this tumor. Although the vacuoles did not stain with oil red O stain, lipid is usually lost during routine tissue processing and the result of oil red O staining of paraffin-embedded tissue sections is often negative. Oil red O stain works optimally on frozen sections, which were not available in the case described in the present report. Oil red O staining can also be performed on formalin-fixed, non-paraffin-embedded tissue sections, but formalin-fixed wet tissue samples were no longer available when the special staining was undertaken. The vacuoles did not stain with Alcian blue stain at a pH of 2.5, indicating that they did not contain myxoid material composed of glycosaminoglycans.

In veterinary medicine, poorly differentiated sarcomas that produce a myxoid matrix are often called myxosarcomas, which are purported to be of fibroblastic origin.1,2 In human medicine, myxosarcomas include myxoid liposarcoma and myxofibrosarcoma, previously referred to as myxoid malignant fibrous histiocytoma. Myxofibrosarcomas are malignant neoplasms composed of spindle-shaped fibroblasts, myofibroblasts, round histiocytic cells, and undifferentiated cells with myxomatous matrix, and have at least some areas of pleomorphism with no evidence of differentiation to another cell line.3,4 Typically, mitoses are easy to find3 and curvilinear or plexiform blood vessels are often present.3,4 The absence of pleomorphism and presence of lipoblasts with a signet ring appearance (wherein clear cytoplasmic vacuoles indent or push the nucleus to the periphery) ruled out myxofibrosarcoma in the case described in the present report.

Myxoid liposarcomas are characterized by small, uniform, spindle-shaped to stellate cells with myxoid matrix, variable numbers of lipoblasts containing clear cytoplasmic vacuoles that indent or push the nucleus to the periphery (so-called signet ring cells), arborizing vasculature, and generally a low mitotic count.5–8 Many cells have few or no cytoplasmic lipid droplets, and detection of lipid-filled vacuoles within the cytoplasm of the neoplastic cells may require painstaking histologic examination. Although the tumor in the cat of the present report lacked a distinct arborizing vascular component, the other histologic features of this tumor (ie, a mesenchymal neoplasm with uniform neoplastic cell nuclei, low mitotic count, myxoid matrix, and discrete intracytoplasmic vacuoles that indent and peripheralize neoplastic cell nuclei) were consistent with myxoid liposarcoma. The mild atypia and low mitotic count in this tumor are histologic features typically associated with low-grade tumors. In myxoid liposarcomas in humans, the lipoblasts are often, but not invariably, positive for S-100 protein.7,9 The presence of S-100 protein in liposarcomas in cats has not been reported, to our knowledge. The tumor in the cat of the present report and the previously described feline myxoid liposarcoma10 tested negative for S-100 protein.

Liposarcomas are less common in domestic animals than in humans, and only a few published case reports10–15 describe this type of tumor in cats. Liposarcomas are thought to originate from lipoblasts and not from malignant transformation of lipomas, and specific causes are not known. Liposarcoma in a kitten that also had lymphoma and was infected with FeLV has been reported.11 There are also 2 individual case reports12,15 of cats with liposarcomas that developed at body sites where vaccinations had been administered; in a large case series16 of 392 cats with soft tissue sarcomas at potential injection sites, 5 liposarcomas were identified, but overall, the documented evidence for virus- or vaccine-induced liposarcomas is weak.

Liposarcoma is a type of soft tissue sarcoma.17 In dogs, liposarcomas are uncommon and usually develop in middle-aged to old individuals as firm, poorly circumscribed masses in the subcutis along the ventral aspects of the abdomen, thorax, and limbs but have also been identified in other primary locations such as bone and inside the peritoneal cavity.17 Liposarcomas in dogs are locally invasive and tend to recur but have a low incidence of metastasis.18,19 Metastatic sites may include the lungs, liver, and bones.18,19 Because so few cases of liposarcoma in cats have been reported, the data available are inadequate to predict biologic behavior of these tumors or determine the optimal treatment approach. It is noteworthy that several of the case reports11–15 of liposarcoma in cats describe aggressive local growth as well as distant metastasis.

In veterinary medicine, liposarcomas have been classified as well differentiated, myxoid, or pleomorphic.8,20 In a recent study,21 dedifferentiated liposarcoma and evidence of genetic abnormalities similar to those found in human liposarcomas were identified in dogs. In another study19 of 56 dogs with liposarcoma, there was no correlation of histologic subtype with survival time; however, metastases were more common in dogs with the pleomorphic form. To our knowledge, myxoid liposarcoma in only 1 cat has been reported.10 In that case,10 the tumor affected the proximal portion of the humerus of an elderly cat, and amputation resulted in a disease-free interval of > 10 months.

In humans, liposarcomas account for at least 20% of all soft tissue sarcomas in adults and are most commonly found in the thigh region and retroperitoneum. Prognosis varies with histologic subtype. Well-differentiated (paucicellular) myxoid liposarcoma in humans is considered a low-grade tumor and is associated with a 5-year survival rate of 90%, whereas round cell (poorly differentiated) liposarcoma has a worse outcome.22

In cats, myxoid liposarcoma does not appear to be a well-recognized or well-documented tumor, but it should be included as a differential diagnosis for mesenchymal neoplasms with myxomatous matrix. The case described in the present report and the sole previously reported case of myxoid liposarcoma in a cat10 bear striking similarities in that both tumors involved the proximal portion of a humerus, developed in an FeLV- and FIV-negative cat, were not associated with inflammation or known sites of vaccination, and were histologically classified as low grade. Moreover, amputation of the affected forelimb in both cases led to prolonged disease-free intervals. The cat of the present report received no adjunct treatment and had no local tumor recurrence or evidence of distant metastasis 40 months after amputation of the left forelimb. Identification of more cases is needed to further characterize this uncommon tumor in cats.

References

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