History

A 27-year-old warmblood gelding was evaluated for a history of chronic swelling in the left forelimb extending from the axilla to the coronary band, with small nodules in the perivascular tissue. There were unusually large, tortuous vessels in the entire affected limb with a lack of normal vascular tone (Figure 1). There was no evidence of previous injury or lameness in the left forelimb prior to the development of this lesion.

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Photograph of the front limbs of a 27-year-old warmblood gelding with chronic swelling in the left forelimb extending from the axilla to the coronary band. The left forelimb was up to twice the size of the contralateral limb in some areas, with numerous cord-like structures at the level of the axilla and a large, distended area medially in the axillary region. These distended areas were easily manipulated and compressed on palpation, with redistribution of fluid on compression of the areas.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.01.0007

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Clinical and Gross Findings

On palpation of the left forelimb, vessels were distended by fluid that could be easily shifted proximally and distally with manual compression. Ultrasonography was performed on the entire left forelimb, left axillary region, left pectoral region, and cranial aspect of the thorax to rule out a mass lesion. Three 6-mm-diameter punch biopsy specimens of haired skin overlying the most severely dilated vessels in the affected limb were taken and submitted in formalin to the Animal Health Diagnostic Center at the Cornell University College of Veterinary Medicine.

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Histopathologic Findings

Histologic evaluation of the submitted biopsy specimens revealed variably dilated, tortuous vessels within the deep dermis and extending to the deep margins of the specimens (Figure 2). The vessels were lined by a single layer of plump endothelial cells and were predominantly empty, although a few contained a small amount of blood. Dilated vessels were surrounded by a moderate amount of collagen containing high numbers of fibroblasts. Multifocally in the deep dermis, there were low to occasionally moderate numbers of perivascular lymphocytes and plasma cells with fewer eosinophils and macrophages (Figure 3). Immunostaining of sections for Prospero-related homeobox protein 1 (PROX-1), a marker for endothelial cells, revealed strong intranuclear immunolabeling of endothelial cells (Figure 4). However, immunostaining of sections for CD31, a marker for vascular endothelial cells, did not yield any immunolabeling of endothelial cells. Given these results, a diagnosis of equine cutaneous lymphangioma was made.

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Photomicrograph of a punch biopsy specimen of haired skin. The deep dermis contains variably sized, tortuous vessels mostly filled with empty space and separated by fibrous connective tissue, with aggregates of perivascular inflammatory cells. H&E stain; bar = 1 mm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.01.0007

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Higher-magnification photomicrograph of a skin biopsy specimen. In the deep dermis, vessels with a single layer of lining endothelial cells can be seen, along with fibrous connective tissue stroma and a mixed inflammatory population composed predominantly of lymphocytes and plasma cells with fewer eosinophils and macrophages. H&E stain; bar = 200 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.01.0007

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Photomicrograph of a skin biopsy section following immunostaining for Prospero-related homeobox protein 1 (PROX-1), a marker for endothelial cells. Notice the strong intranuclear immunolabeling of endothelial cells. Bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.01.0007

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: lymphangioma with chronic, multifocal, mild to moderate, lymphoplasmacytic and eosinophilic perivascular dermatitis involving the haired skin of the left forelimb.

Case summary: cutaneous lymphangioma in a horse with secondary peripheral edema and chronic inflammation attributed to accumulation of lymphatic fluid in malformed lymphatic vessels.

Comments

Lymphangiomas are tumor-like proliferations of lymphatic endothelial tissue. They occur primarily in young animals and typically present in locations where the lymphatic system develops primitive lymph sacs, including the jugular and inguinal areas, retroperitoneal areas, and cisterna chyli.¹ Lymphangiomas are rarely reported in horses, but single case reports have been published describing lymphangiomas in the gluteal area of a 3-year-old warmblood mare,² in the abdominal wall and left hind limb of a Standardbred mare,³ in the right forelimb of an adult cross-bred gelding,⁴ in the neck of a 2-year-old Welsh Cob,⁵ and in the inguinal area of a 6-month-old Morgan colt.⁶ Lymphangiomas often represent a recurrent and progressive condition, in part owing to the difficulty in surgical resection of multiple lymphatic vessels.⁷ Previous reports of lymphangiomas have described treatment with surgical excision followed by injection of sclerosing substances or irradiation with cobalt 60 in humans and dogs, respectively.^8,9 In 3 of the previously described cases^3,4,6 of lymphangioma involving the left hind limb, right forelimb, and inguinal area of horses, all animals were ultimately euthanized because of the infeasibility of surgical removal or associated skin lesions, including severe ulceration and secondary infection. In one case, the mass was successfully removed with no evidence of recurrence 3 years after excision.⁵

The terminology in describing lymphangioma is complicated, and the term lymphangiomatosis is sometimes used synonymously to describe lesions similar to lymphangioma. The usage of these terms differs among reports, with some authors¹⁰ believing that the lesions of lymphangiomas are representative of lymphatic malformations rather than true neoplasms, especially when present in young animals, and hence favoring the term lymphangiomatosis over lymphangioma, as the latter implies a neoplastic origin. Separate reports differentiate lymphangioma from lymphangiomatosis by considering lymphangioma a congenital lesion and lymphangiomatosis an acquired lesion.¹¹ Still other reports describe lymphangiomatosis as a multifocal process and differentiate this term from lymphangioma, which is described as a focal process.³

In human medicine, the distinction between these 2 entities is based on distribution, with lymphangiomas described as histologically benign, hamartomatous proliferations of lymphatic vessels and lymphangiomatosis described as the manifestation of multiple lymphangiomas throughout the body.¹² Lymphangiomas tend to occur primarily in children and are believed to represent a congenital developmental defect in which the lymphatic sacs fail to communicate with the venous system or the remainder of the lymphatic system, resulting in deep lymphatic cisterns communicating with ectopic lymphatic vessels.^13,14 These lesions can develop on any cutaneous surface or mucous membrane, but most commonly occur on the head and neck, proximal portions of the extremities, buttocks, and trunk.¹⁴

In humans, lymphangiomas are divided into 3 subtypes on the basis of morphology. The first, cutaneous lymphangioma circumscriptum (also known as lymphangioma simplex or capillary lymphangioma), is characterized by superficial, small, thin-walled lymphatics. The second, cavernous lymphangioma, has deep, large, lymphatic channels. The third, cystic lymphangioma or hygroma, is composed of deep, large, lymphatic spaces.^9,14 Associated conditions reported with lymphangiomas in humans include lymphedema, cellulitis, and bacterial infection.¹⁵ Malignant transformation to lymphangiosarcoma has been rarely reported to occur following irradiation of the site.¹⁶ Treatment of cutaneous lymphangioma circumscriptum has been successful and has used cryotherapy, sclerotherapy, cauterization, and carbon dioxide lasers.^14,16

The authors recognize that the terminology used to describe this lesion has not been adequately standardized in veterinary medicine. Given what is described and defined in the human literature, the focal nature of this lesion, and what has been reported previously in horses, we favor a diagnosis of lymphangioma.

In the current case, excision was not attempted. The gelding’s condition remained stable, and the limb’s appearance remained unchanged 3 months after the initial punch biopsy specimens were obtained. There were a few episodes of dermatitis and ulceration with secondary bacterial infection reported, which responded well to oral treatment with trimethoprim-sulfonamide at the standard dosage for skin infections. Anti-inflammatory doses of glucocorticoids were administered intermittently as needed to control distal limb edema.