Liposarcomas in the Dog and Cat

Brian G. Berger, DVM; Kenneth S. Latimer, DVM, PhD; Bruce E. LeRoy, DVM, PhD; Perry J. Bain, DVM, PhD

Class of 2004 (Berger) and Department of Pathology (Latimer, LeRoy, Bain), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388

Introduction

Cutaneous swellings or masses are common complaints that owners cite when presenting a pet for examination by a veterinarian. General causes of cutaneous swellings include hematomas, abscesses, granulomas, hernias, cysts, and neoplasms. Neoplasms commonly originate from one of three basic cell types: round cells, epithelial cells, or mesenchymal cells. Mesenchymal cells constitute bone, muscle, fibrous connective tissue, and adipose tissue. Neoplasms of adipose tissue include lipomas (which are benign fatty tumors) and liposarcomas (which are malignant fatty tumors). This manuscript reviews liposarcomas which are malignant mesenchymal neoplasms originating from adipocytes (fat cells).^1-3

Liposarcoma, Infiltrative Lipoma, and Lipoma

Liposarcomas are rare malignant tumors of white adipose cell lipoblasts.⁴ They are considered a soft tissue neoplasm because of their mesenchymal or connective tissue cell origin. They often arise from the skin and subcutis (Fig. 1).⁵ Liposarcomas occur in older animals, exhibit no gender predilection, and typically arise de novo. Liposarcomas do not originate from pre-existing lipomas.⁵ One published report has suggested a slight gender bias among Brittany Spaniels and Dachsunds.⁵ Most reports indicate that liposarcomas are unlikely to metastasize; however, a few published reports suggest that liposarcomas are aggressive, locally invasive, and commonly metastasize to the lungs, liver, and bone.³ The specific etiology of this neoplasm is unknown, but one dog had a liposarcoma that originated in association with a glass fragment foreign body.⁶

Figure 1. Gross appearance of a liposarcoma invading the muscles of the hind limb and encircling the tibia and fibula (Courtesy of Noah's Arkive, The University of Georgia).

Infiltrative lipomas appear as poorly defined, soft to firm, nodular to diffuse swellings.⁷ They generally enlarge slowly but may exhibit periods of rapid growth.⁸ These neoplasms are not very mobile on palpation because of their infiltrative nature. Infiltrative lipomas also may cause pain, pressure atrophy of muscles, interfere with movement, and result in lameness. Microscopically, infiltrating lipomas (like benign lipomas) are composed of uniform adipocytes, but their invasive nature results in frequent recurrence following surgical excision.

Figure 2. Gross appearance of an infiltrating lipoma from a dog that is dissecting skeletal muscle (Courtesy of Noah's Arkive, The University of Georgia).

Benign lipomas are single or multiple subcutaneous growths of variable size and shape (Fig. 3). These neoplasms usually grow slowly and are well circumscribed.⁷ They often feel soft to spongy on palpation, but may feel more solid due to the presence of fibrous connective tissue, necrosis, or inflammation.⁸ When located in the subcutis, the skin is freely movable over the neoplasm which usually is not attached to underlying fascia and muscle.⁸ Lipomas enlarge by expansion and are noninvasive. Microscopically, they are composed of lobules of well differentiated adipocytes with scattered small blood vessels (Fig. 4).

Figure 3. A small, subcutaneous lipoma on the abdomen of a dog.	Figure 4. Histologic section of a lipoma showing a sheet of well differentiated adipocytes (hematoxylin and eosin stain).

Diagnosis

While simple lipomas are benign in nature, they cannot be distinguished grossly from infiltrative lipomas and liposarcomas. Often the only difference is in the mobility of the skin over the mass.

Histopathologic evaluation is essential in the diagnosis of liposarcoma. Although fine-needle aspiration cytology may be helpful in distinguishing differential diagnoses such as lipoma or abscess, it is of limited value in the diagnosis of liposarcoma.³ Mesenchymal neoplasms do not exfoliate well, thus, cytological evaluation may not be rewarding.

Cytological Appearance

Although mesenchymal neoplasms typically do not exfoliate well, fine-needle aspiration may recover polyhedral cells from liposarcomas. These cells, if present, have a characteristic appearance. The cytoplasm is abundant, lightly basophilic, and contains variably sized, clear vacuoles where lipid is stored (Fig. 5). The nucleus is round and the nucleolus may be prominent. Anisocytosis and anisokaryosis usually can be observed; anisocytosis may be prominent in some cells (Fig. 6).⁹

Figure 5. Malignant lipocytes appear round to polyhedral with vacuolated basophilic cytoplasm, a round nucleus, and occasional prominent nucleoli. A mitotic figure is present (top center) (Wright stain; Courtesy of Noah's Arkive, The University of Georgia).	Figure 6. Malignant lipocyte with marked anisokaryosis and prominent nucleoli (Courtesy of Noah's Arkive, The University of Georgia).

Histological Appearance

Most literature concerning liposarcomas mentions three variants of the neoplasm. These variants are designated well differentiated, pleomorphic, and myxoid.

Well-differentiated liposarcomas are composed of round to polygonal cells arranged in sheets with little or no collagenous stroma (Fig. 7). The majority of cells resemble mature adipocytes with a single clear fat vacuole and a peripherally located nucleus. Other cells in the histologic section often exhibit anisokaryosis and anisocytosis. The cytoplasm is abundant and contains variably-sized, lipid filled vacuoles.⁸

Figure 7. Histologic section of a liposarcoma. Malignant lipocytes exhibit anisocytosis, anisokaryosis, and contain variably sized, lipid-filled vacuoles (hematoxylin and eosin stain).

Pleomorphic liposarcomas contains cells of variable morphology mixed with large multinucleated cells. Intracytoplasmic fat vacuoles are also present, albeit in a small percentage of cells. These vacuoles are helpful in the diagnosis of this variant.⁸

Myxoid liposarcomas stain positively with Alcian blue and resemble myxosarcomas. These neoplasms contain a "bubbly," mucoid stroma composed of spindle cells, lipocytes, and lipoblasts. The presence of lipid-filled vacuoles differentiates this form of liposarcoma from a myxosarcoma.⁸

Histologic Staining Techniques to Demonstrate Lipid

Frozen sections of lipomatous neoplasms can be stained with Sudan III or oil red O to demonstrate lipid. ¹⁰ Lipid-filled vacuoles will appear orange to red. Alternatively, formalin fixed tissue can be immersed in osmium tetroxide and then processed routinely. Lipid will appear black in these tissue sections. .

Electron Microscopy

The ultrastructural features of liposarcoma have been described.¹⁰ Neoplastic lipocytes may display various stages of differentiation. These neoplastic cells usually have a round to oval nucleus with finely granular chromatin that is condensed toward the periphery. A Golgi complex, ribosomes, and rough endoplasmic reticulum (RER) generally are present. Lysosomes and microtubules may be observed occasionally. Single lipid inclusions usually were present and were located toward one side of the cell.¹⁰

Treatment and Prognosis

Liposarcoma is categorized as a soft tissue sarcoma. The locally aggressive nature of this neoplasm requires aggressive surgical resection, which often results in long-term remission or cure. The identification and evaluation of resection margins is of utmost importance in appropriate case management.¹¹ Radiation therapy may induce remission of incompletely resected neoplasms.¹¹

Prognosis is based on the size, location, grade, histologic type of neoplasm; response to previous treatment; and adequacy of surgical margins.¹¹ Size and location of a liposarcoma are prognostic only in that they directly affect the surgeon's ability to completely resect the neplasm.¹¹

References

1. Morrison WB: Cancer in Dogs and Cats: Medical and Surgical Management , 2nd ed. Jackson Hole , Teton NewMedia, 2002, pp. 479-80.

2. Morris J, Dobson J: Small Animal Oncology, 1st ed. Oxford, Blackwell Science, 2001, pp. 69-76.

3. Withrow SJ, MacEwen EG: Small Animal Clinical Oncology, 3rd ed. Philadelphia, W.B. Saunders Co., 2001, pp.286-295.

4. Messick JB, Radin MJ: Cytologic, histologic, and ultrastructural characteristics of a canine myxoid liposarcoma. Vet Pathol 26:520-522, 1989.

5. Strafuss AC, Bozarth A: Liposarcoma in Dogs. J Am Animal Hosp Assoc 9:183-187,1973.

6. McCarthy PE, Hedlund CS, Veazy RS, Prescott-Mathews J, Cho DY: Liposarcoma associated with a glass foreign body in a dog. J Am Vet Med Assoc 209:612-614, 1996.

7. Ogilvie GK, Moore AS: Managing the Veterinary Cancer Patient. Trenton, Vet Learning Systems, 1995, pp. 486-487.

8. Moulton JE: Tumors in Domestic Animals, 3rd ed. University of California Press, Berkeley, 1990, pp.31-33, 98.

9. Baker R, Lumsden JH: Color Atlas of Cytology of the Dog and Cat, 1st ed. St. Louis, Mosby, pp. 47-48, 66.

10. Doster AR, Tomlinson MJ, Mahaffey EA, Jordan CW: Canine liposarcoma. Vet Pathol 23:84-87, 1986.

11. Dernell WS, Withrow SJ, Kuntz CA, Powers BE: Principles of treatment for soft tissue sarcoma. Clin Tech Small Animal Pract 13:59-64, 1998.

Acknowledgement

The image "Hey Diddle Diddle" by Monica Van der Weer is from the web site The Art of Monica Van der Weer and is used with permission of the artist.

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