Treatment of Cutaneous Lymphosarcoma

By | 2012-10-23

Glucocorticoids remain the mainstay of treatment of cutaneous T cell-rich, B cell lymphoma. Tumor regression is typically noted following the systemic administration of dexamethasone (0.02-0.2 mg/kg IV, IM or PO q24h) or prednisolone (1-2 mg/kg PO q24h). In these authors’ experience, dexamethasone proves more effective than prednisolone in treating lymphosarcoma. Once cutaneous lesions have regressed in size and number, the glucocorticosteroid dose can be gradually tapered. However, a rapid decrease or discontinuation of glucocorticosteroid administration may result in recurrence of cutaneous lesions. Relapses are anecdotally reported to be sometimes more refractory to treatment. Long-term maintenance therapy may be required in these cases. These authors prefer to use a dose of 0.04 mg/kg of dexamethasone (approximately 20 mg for an average-size horse) once daily until significant regression of tumors has occurred; the dose then is reduced to 0.02 mg/kg daily and then to every 48 hours. Intralesional injections of betamethasone or triamcinolone can also be performed with success; this may be impractical when presented with a large number of cutaneous lesions. Topical application of corticosteroid preparations may result in clinical improvement in cases with ulceration; however, results of its use have not been reported. In addition to im-munosuppression, laminitis is a potential side effect of corticosteroid administration.

Exogenous progestins may demonstrate an antiproliferative effect on lymphosarcoma tumors. The exact mechanism of action has not been determined; however, it is believed to be due to the presence of progesterone receptors, which have been demonstrated on both neoplastic and normal equine lymphoid tissues. Progestogens also have glucocorticoid-like activity, which may also account for the response observed in some cases of lymphosarcoma. In one study, progesterone receptors were identified on 67% of the subcutaneous lymphosarcoma tumors that were evaluated (primarily representing T cell-rich, B cell tumors). In the mare diagnosed with simultaneous cutaneous histiolymphocytic lymphosarcoma and a granulosatheca cell ovarian tumor, partial regression of the skin lesions occurred following a ten-day course of the synthetic progestin, altrenogest (0.044 mg/kg q24h PO). A temporary response was also observed after unilateral ovariectomy. The ovarian tumor stained positive for estradiol and led the authors to believe it was estrogen-secreting. The authors speculated that the steroid hormones secreted by the ovarian tumor may have influenced growth of the T cell-rich, B cell tumors by leading to low progesterone concentrations. Anecdotal reports of tumor regression during pregnancy also exist. In one mare with cutaneous T cell lymphosarcoma, regression of nodules was noted after surgical excision, a single intralesional injection of betamethasone (0.04 mg/kg), and an 8-day course of the oral progestogen, megestrol acetate (0.2 mg/kg q24h). Surgical excision may be efficacious in cases in which a single or a small number of cutaneous nodules exists.

The administration of autologous tumor cell vaccines may benefit horses with cutaneous lymphosarcoma. In one report, tumor regression was achieved by using a combination of low-dose cyclophosphamide and autologous tumor cells infected with vaccinia virus. Cyclophosphamide is thought to potentiate the immune response by decreasing suppressor T cell activity. Infection of tumor cells with the vaccinia virus was performed to augment the host antitumor immune response. The treatment protocol included intravenous administration of cyclophosphamide (300 mg/m2) via a jugular catheter over a period of 2 to 3 minutes on days 1 and 36. Immunization with tumor-cell vaccine was performed on days 4 and 21. Response to immunostimulation was confirmed by development of a delayed-type hypersensitivity response to autologous tumor cells injected intradermally in the horse. Potential side effects of cyclophosphamide administration in other species include immunosuppression, enterocolitis, myelosuppression, and hemorrhagic cystitis. No side effects were noted in the horse in this report.

Treatment of epitheliotropic (cutaneous T cell lymphosarcoma) in horses remains speculative because of a paucity of reported cases. Surgical excision of small lesions may be curative. Retinoids and vitamin A analogs inhibit malignant lymphocyte proliferation in human and canine patients with epitheliotropic lymphosarcoma. No reports of the use of retinoids in horses have been published. However, these authors noted no gross or histologic improvement in treating one case of equine epitheliotropic lymphosarcoma with retinoid cream. Side effects included local erythema and signs of irritation after repeated applications.

Investigations as to the effectiveness of radiation therapy and systemic chemotherapy in the management of equine cutaneous lymphosarcoma are needed. Local therapy that consists of intralesional injection of cutaneous nodules with cisplatin has been used successfully in horses with a small number of lesions. Combination chemotherapy that consists of cytosine arabinoside, chlorambucil or cyclophosphamide, prednisone, and vincristine has been reported for use in horses with multicentric lymphosarcoma, as has L-asparaginase.