Canine Cutaneous Histiocytoma

Josh R. Woods, DVM; Kenneth S. Latimer, DVM, PhD; Perry J. Bain DVM, PhD

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

Introduction

Skin tumors are the most commonly diagnosed neoplasms in veterinary medicine.² These neoplasms represent a diverse group of benign and malignant growths arising from a variety of cell types. Determining the origin of cutaneous neoplasms is often challenging, but is of paramount importance in many patients regarding therapeutic considerations.

Cutaneous histiocytoma is classified cytologically as a round cell tumor. Other members of this tumor group in dogs include mast cell tumor, cutaneous lymphoma, transmissible venereal tumor, and plasmacytoma. Treatment and prognosis for the various round cell tumors vary considerable. Therefore, accurate diagnosis is required.

Origin

The name "histiocytoma" implicates a benign neoplasm of monocytic cell lineage, but obscures the exact origin of these neoplastic cells. Histiocytes are mature macrophages that reside in connective tissue.¹² They usually originate from blood monocytes which comprise about 5% of the circulating leukocyte population.

Research indicates that a variety of histiocytic proliferative disorders affect dogs. These include cutaneous and systemic histiocytosis, cutaneous histiocytoma, localized histiocytic sarcoma, and disseminated histiocytic sarcoma.¹

Most evidence indicates that cutaneous histiocytomas are derived from a more specialized population of cells called Langerhans cells.^{6, 8, 9} Langerhans cells are a developmental subset of the antigen presenting cells known as dendritic cells. The development of dendritic cells is well described, and at least three major precursors are known; myeloid series, monocytic series, and a lymphoid series (Fig. 1).¹⁰

Figure 1. Schematic indicating the proposed lineage of Langerhans cell development from myeloid, monocytic, and lymphoid precursor cells.

Incidence

Cancer is one of the major causes of death in dogs.^{3, 7} There is a large amount of clinical information regarding clinical signs, diagnosis, and treatment of canine neoplasia; however, relatively little information exists on the incidence of many types of cancer in this species. It is well accepted that cutaneous neoplasms are among the most commonly observed forms of cancer in dogs. Furthermore, cutaneous histiocytoma has been reported to be the most common presentation of cutaneous neoplasia, and the most commonly observed form of cancer overall.^6,7

Signalment

Canine cutaneous histiocytoma is most commonly observed in young dogs and tumor incidence drops precipitously after three years of age. While this tumor is most commonly observed in young dogs, most studies indicate that it is infrequently observed in older animals. Breeds at risk include Flatcoat Retrievers, English Bulldogs, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers.

Gross Lesions

Cutaneous histiocytomas are generally observed by the practitioner as solitary, red, dome-shaped, sparsely haired nodules that appear rapidly (Fig. 2). They often are ulcerated, but are non-painful. The most common sites of tumor development include the head, pinna, and neck, especially in young dogs.³ More rarely, neoplasms may occur on the trunk and extremities, and frequently involve the feet and toes of older individuals (KSL, personal observation). Rarely, histiocytomas may arise in multiple sites.

The metastatic potential of histiocytomas has not been studied directly, but reports of tumor metastasis are rare. Death due to cutaneous histiocytoma has not been reported. It is generally accepted that this tumor does not readily metastasize, and should be considered benign.

Figure 2. Histiocytomas of the pinna (left) and foot (right) appear as red, raised, sparsely haired masses (Courtesy of Noah's Arkive, University of Georgia).

Diagnosis

Cutaneous histiocytomas may be readily diagnosed using a combination of clinical signs, signalment, and fine-needle aspiration cytology. Rarely, a histopathologic diagnosis may be required. In biopsy sections, histiocytomas are circumscribed, nonencapsulated dermal masses composed of sheets of round cells. Individual cells have a round to reniform nucleus with occasional nucleoli and moderate amounts of cytoplasm(Fig. 3). Increased mitoses, discrete necrosis, and infiltrates of small lymphocytes may be observed. Infrequently, cutaneous histiocytoma may be confused histologically with granulomatous inflammation, poorly granulated mast cell tumors, plasmacytomas, and cutaneous lymphosarcoma.²

Figure 3. Biopsy specimen of a histiocytoma composed of sheets of round cells. Scattered mitoses are present (Hematoxylin and eosin stain, courtesy of Noah's Arkive, University of Georgia).

Cytology

The various round cell tumors of dogs have distinct cytologic characteristics that are presented in Table 1. Additional information can be found in clerkship papers Canine Round Cell Tumors and Mast Cell Disease in Dogs and Cats: An Overview.

Table 1. Cytologic features of round cell neoplasms of dogs.

The fine-needle cytologic characteristics of canine cutaneous histiocytoma have been well described and usually are diagnostic (Fig. 4).⁶ Histiocytoma cells have an eccentric, oval to reniform nucleus with occasional nuclear clefts. The chromatin pattern is finely granular and nucleoli are inconspicuous. Cells that contain nuclear clefts are sometimes referred to as "butt cells" because of their characteristic morphology (Fig. 5). The cytoplasm is abundant, lightly basophilic, and lacks vacuoles or granules.

Figure 4. Fine-needle aspirate of a histiocytoma containing cells with a round to oval nucleus and moderately abundant blue cytoplasm that lacks vacuoles and granules. A binucleated cell and mitotic figure are present (Wright stain, courtesy of Noah's Arkive, University of Georgia).	Figure 5. Histiocytoma cell with a nuclear cleft and typical butt cell morphology.

Treatment and Prognosis

Most cutaneous histiocytomas regress spontaneously regardless of the course of treatment pursued.^{6, 9} Regression of the tumor has been correlated with infiltration of T- lymphocytes. This has been hypothesized to be a CD-8 T-cell mediated phenomenon based on the infiltration of this cellular subset and expression of major histocompatability complex class II antigens.⁶

Initial surgical excision usually is curative; however, a second surgical excision may be necessary for complete cure on rare occasions.^{1, 6} Due to the high rate of surgical cure and the probability of spontaneous regression, few studies have been done addressing alternate forms of therapy. Infection of ulcerated lesions on the surface of the neoplasm is probably the primary indication for surgical intervention.

Summary

Cutaneous histiocytomas are benign round cell tumors of Langerhans cell origin. Neoplasms are seen predominantly in young dogs, but can occur in older dogs. These neoplasms usually appear as small, red, raised, sparsely haired nodules that often have an ulcerated surface. They are observed most commonly on the head and neck, but may occur on the trunk and limbs, including the feet and toes. Diagnosis can generally be sufficiently made on the basis of history, signalment, and fine-needle aspiration cytology. In some instances, histopathology may be required for a definitive diagnosis. Most histiocytomas regress spontaneously without treatment; however, surgical excision is usually curative. These neoplasms rarely metastasize and the prognosis for non-recurrence is excellent.

References

1. Affolter VK, Moore P.F. 2000. Canine cutaneous and systemic histiocytosis: Reactive histiocytosis of dermal dendritic cells. Am J Dermatopathol 22:40-48.

2. Aiello SE, Mays A (eds). 1998. Tumors with histiocytic differentiation. Merck Veterinary Manual, 8th ed. Merck & Co., Inc, Whitehouse Station, NJ, pp. 708-709.

3. Bonnett BN, Egenvall A, Olson P. 1997. Mortality in insured Swedish dogs: Rates and causes of death in various breeds. Vet Rec 141:40-44.

4. Dee ONT, Dorn CR, Luis OH. 1969. Morphologic and biologic characteristics of the canine cutaneous histiocytoma. Cancer Res 29:83-92.

5. Dobson JM, Samuel S, Milstein H, Rogers K, Wood JLN. 2002. Canine neoplasia in the UK: Estimates of incidence rates from a population of insured dogs. J Small Animal Pract 43:240-246.

6. Kipar A, Baumgartner W, Kremmer E, Frese K, Weiss E. 1998. Expression of major histocompatibility complex class II antigen in neoplastic cells of canine cutaneous histiocytoma. Vet Immunol Immunopathol. 62:1-13.

7. Michell AR. 1999. Longevity of British breeds of dog and its relationships with sex, size, cardiovascular variables and disease. Vet Rec 145:628-629.

8. Moore PF. 1986. Characterization of cytoplasmic lysozyme immunoreactivity as a histiocytic marker in normal canine tissues. Vet Pathol 23:763-769.

9. Moore PF, Schrenzel MD, Affolter VK, Olivry T, Naydan D. 1996. Canine cutaneous histiocytoma is an epidermotropic Langerhans cell histiocytosis that expresses CD1 and specific beta 2-integrin molecules. Am J Pathol 148:1699-1707.

10. Peters JH, Gieseler R, Thiele B, Steinbach F. 1996. Dendritic cells from ontogenetic orphans to myelomonocytic descendants. Immunol Today 17:273-278.

11. Shortman K, Caux C. 1997 Dendritic cell development: Multiple pathways to natures adjuvants. Stem Cells 15:409-419.

12. Tizard IR 2000. The organs of the immune system. Vet Immunol 6:69-83.

Acknowledgement

"Colorful Greyhound 1" by Julie Neidlinger is from her Lone Prarie Art Works web site.

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