T-cell lymphoma of the tympanic bulla in a feline leukemia virus-negative cat

Abstract

This report constitutes the first description of a T-cell lymphoma of the tympanic bulla in a cat. This feline leukemia virus (FeLV)-negative cat originally presented with signs referable to middle ear disease; it deteriorated rapidly after definitive diagnosis. Lymphoma of the middle ear is extremely rare in all species.

An 8 year-old, spayed female Persian cat with a previous history of chronic ear infections was presented to the University of Illinois Veterinary Teaching Hospital (UIVTH) for anisocoria (right eye [OD] miotic, left eye [OS] normal), head tilt, and loss of balance of 1 week's duration. Prior to the cat being admitted to the UIVTH, the referring veterinarian had determined by using a commercially available enzyme linked immunosorbent assay (ELISA) that the cat's feline leukemia virus (FeLV) status was negative and had instituted symptomatic therapy with oral prednisone (Prednisone; Watson Laboratories, Corona, California, USA), 10 mg, PO, q24h. A rapid and significant, but transient, clinical improvement in the cat's head tilt and ability to ambulate resulted. However, upon recurrence of vestibular signs, the cat was referred to the UIVTH for further evaluation.

On initial presentation, the cat was found to be in good body condition, weighing 3.6 kg. All vitals signs were within normal limits. A linear corneal ulcer involving the OD was identified and believed to be secondary to exposure keratitis. On otoscopic examination, the right tympanic membrane was ruptured and could not be visualized, but the left one appeared normal. A neurologic examination identified several right-sided deficits, including right head tilt, circling to the right, right facial paralysis, OD loss of corneal reflex, OD prolapsed third eyelid, and OD miosis. A horizontal nystagmus at rest became rotary following up-and-down head motions. No conscious proprioceptive deficits or long tract abnormalities were identified. All spinal reflexes tested were within normal limits. Given the history of chronic ear infections and in conjunction with the clinical findings, a presumptive diagnosis of otitis media was made. Other differential diagnoses included non- neoplastic brainstem lesions (ischemic, inflammatory), nasopharyngeal polyps, Horner's syndrome, or tumors involving the middle ear or brainstem.

Initial diagnostic testing included a complete blood cell (CBC) count, a serum chemistry panel, and a systolic blood pressure measurement. No abnormalities were identified on the CBC count. Elevated total protein (97 g/L; reference range, 58 to 80 g/L), secondary to hyperglobulinemia (63 g/L; reference range, 26 to 51 g/L), was identified on the serum chemistry panel. Systolic blood pressure was normal at 130 mm Hg. Prior to advanced imaging, the cat was hospitalized in the intensive care unit, given IV fluids at maintenance rate (lactated Ringer's, with 20 mEq/L of potassium chloride), and had artificial tears placed in both eyes, q8h. Additionally, to alleviate some of the discomfort associated with severe vestibular disease, the cat was administered the antihistamine meclizine (Meclizine HCl; Geneva Pharmaceuticals, Broomfield, Colorado, USA), 12.5 mg, PO, q24h.

A computerized tomography (CT) of the tympanic bullae was performed on the 2nd d of hospitalization. Abnormal findings consistent with fluid, soft tissue opacity, or both, were identified in both bullae, with more severe changes on the right side (Figure 1). No bony abnormalities were appreciated within the bullae. With the identification of middle ear disease and in conjunction with the lateralizing vestibular clinical signs, exploratory bulla osteotomy on the right side was performed on day 4 of hospitalization. While approaching the right bulla ventrally during surgery, an enlarged right submandibular lymph node was observed, removed, and submitted for histopathologic analysis. A soft-tissue mass occupying the lateral and medial compartments of the right bulla was identified. Biopsy samples were obtained through curettage of the bulla cavity and submitted for culture and histopathologic examination. A Penrose drain was placed in the bulla, and the cat recovered uneventfully from surgery.

Figure 1. Computerized tomography imaging of a cat with T-cell lymphoma of the right tympanic bulla. Soft-tissue or fluid density is observed in the right middle ear (arrowhead); less severe findings are seen in the contralateral bulla.

Histopathologic evaluation of biopsies, from both the lymph node and bulla, indicated a large cell lymphoma. Immunohistochemical testing revealed the lymphoma to be of T-cell origin, as determined by strong cytoplasmic CD3 staining (T-cell marker) of the neoplastic lymphocytes of the bulla and lymph node. Bacterial culture revealed no growth. Treatment options were discussed and included megavoltage radiation therapy of the bullae and submandibular area, in conjunction with systemic chemotherapy. Initiation of radiation and chemotherapy was planned to follow complete surgical site tissue healing. The Penrose drain was removed on day 6, and the patient was discharged on day 7 with oral meclizine, amoxicillin-clavulanic acid (Clavamox; Smithkline Beecham Pharmaceuticals, Philadelphia, Pennsylvania, USA), 62.5 mg, PO, q24h, and artificial tears. A 10-day recheck visit was scheduled to assess surgical site wound healing and to initiate definitive therapy for the lymphoma.

Two days following discharge from the UIVTH, the cat's right eye worsened progressively to severe exophthalmos and discomfort, ultimately resulting in corneal rupture 48 h later. Therapeutic options were discussed (tarsorraphy, enucleation), but a decision was made to euthanize the cat; necropsy was not performed.

Lymphoma is the most common feline neoplasia (1). In the last 15 y, the overall incidence of feline lymphoma has decreased, and the relative frequency of different anatomical forms has changed. These shifts in the incidence and locations of feline lymphoma may be due, in part, to the use of commercial vaccines to prevent infection with feline leukemia virus, a biologic carcinogen responsible for the development of feline lymphoma (1). Although feline lymphoma may arise from virtually any organ, recent studies report intestinal lymphoma as the most common anatomical form of the disease, occurring predominantly in older, FeLV-negative cats (1).

Diseases affecting the feline tympanic bulla are rare. Of the disorders reported, inflammatory nasopharyngeal polyps are frequently diagnosed with clinical signs suggestive of nasopharyngeal pathology (2). While nasopharyngeal polyps are well-recognized inflammatory lesions affecting predominantly young cats, reports of neoplasia involving middle ear structures are scarce and poorly described (3,4,5). In a study of 19 cats treated with tympanic bulla osteotomies, 11 ears had surgery for otitis media, 7 for inflammatory polyps, and 4 for middle-ear neoplasia (3). Of the 4 cats with neoplasia in the tympanic bulla, 3 had carcinomas, and only 1 was diagnosed with lymphoma (3). One additional case of feline lymphoma involving the middle ear had been described briefly in a textbook (4). Neither of the existing 2 reports of feline lymphoma involving the tympanic bulla characterized the immunophenotype of the malignant lymphocyte population (3,4).

Primary neoplasia of the tympanic bulla is equally rare in the dog; most reports discuss invasion of the bulla through the tympanic membrane by predominantly epithelial tumors arising from the external ear canal. A study of 11 dogs diagnosed with middle ear tumors described 1 papilloma, 2 basal cell tumors, 3 adenocarcinomas of the ceruminous glands, 2 papillary adenomas, 2 sebaceous adenocarcinomas, and an anaplastic neoplasia, but no lymphoma (6).

The historical presentation of middle ear tumors in humans is often chronic and mimics clinical signs of therapy-resistant otitis (7). While rarely diagnosed, carcinomas are the most common malignant tumors of the human middle ear, accounting for 75% to 90% of all tumors involving this anatomic site (7). Hodgkin's and non-Hodgkin's lymphomas arising from the middle ear are even more unusual, with less than 20 reported cases (7,8). Although malignant transformation of epithelial structures is better recognized, the presence of lymphoid tissue within the epithelial layers of the middle ear explains the occasional genesis of lymphoid malignancies from this area (7). Organized lymphoid structures, such as mucosa-associated lymphoid tissue (MALT), have also been described recently in the middle ears of children between 1 mo to 7 y of age, with greater MALT proliferation and development in pediatric patients having concurrent otitis media (9). Adults and neonates do not appear to have MALT in the tympanic bulla (9). Given the diagnosis of T-cell lymphoma in this cat, it is unlikely that the malignant lymphoid population arose from MALT of the middle ear, MALT being of a B-cell immunophenotype (10).

Maximally effective therapy for lymphoma requires the use of multiagent chemotherapy protocols with lymphotoxic drugs, such as prednisone, vincristine, L-asparaginase, doxorubicin, and cyclophosphamide (1). In this case, the transient improvement in vestibular signs demonstrated by the cat may have been attributable to malignant lymphocyte apoptosis, secondary to single-agent prednisone administration. Alternatively, the clinical response to prednisone therapy may have been due purely to a reduction in peritumoral inflammation, without any cytotoxic effects to the primary lymphoid malignancy. It is generally recommended that the use, especially longterm, of single-agent prednisone be avoided for lymphoma if multiagent protocols are to be used afterwards. Although poorly documented, the risk of inducing a multidrug resistance phenotype has been speculated in the dog, and the same could be possible in cats (11). The potential precipitation of early multidrug resistance could limit the subsequent cytotoxic effects of frequently used chemotherapeutic agents, such as vincristine and doxorubicin, resulting in shorter remission and overall survival times.

When lymphoma is strictly localized to 1 organ or to regional lymph nodes, surgery may be considered as an effective local treatment modality (1). Additionally, given the exquisite radiosensitivity of malignant lymphocytes, the use of radiation therapy is considered an excellent therapeutic option for the control of local disease (1). Lymphoma tends to be a systemic disease and, although therapies such as surgery and radiation therapy possess clear merit in the treatment and control of local disease, the adjunctive administration of systemic chemotherapy is generally warranted. While surgery remains important, at least for obtaining diagnostic samples in such a case, a patient with lymphoma confined to the middle ear would potentially have a good long-term prognosis when treated with radiation therapy combined to systemic chemotherapy (8,9). The proposed plan, for the cat reported here, was to treat with megavoltage radiation therapy (Cobalt-60) and follow-up with systemic chemotherapy, but the rapidly progressive condition associated with OD, combined with significant discomfort, prompted the owners to opt for euthanasia. CVJ