A challenging case: Conjunctival lymphoma in a cat

A 10-year-old 12-lb (5.5-kg) female spayed domestic shorthaired cat was presented to Colorado State University's Veterinary Medical Center for evaluation of a protruding nictitating membrane of the right eye. The cat's eye had not improved with topical gentamicin ophthalmic drops (1 drop b.i.d.) prescribed two weeks earlier by the referring veterinarian.

The right eye had been blind and the cornea had been cloudy since birth. The cat had no history of other medical problems, and its vaccination status was current.

Vital Stats

FIRST PRESENTATION

Physical and ophthalmic examinations

The results of a Schirmer tear test and tonometry were normal in both eyes, and there was no corneal staining with fluorescein dye in either eye.

The right eye had scarring and edema of the entire cornea, so the internal ocular structures could not be evaluated. The bulbar and nictitating membrane conjunctiva were moderately hyperemic, and the nictitating membrane protruded and covered about half the cornea. Retropulsion of the right globe was severely limited compared with the left eye. The cat appeared to be in pain.

The remainder of the physical examination findings were normal, and no enlarged lymph nodes were detected on palpation.

Presumptive diagnosis

We suspected that a right retrobulbar mass was present and recommended ophthalmic ultrasonography to further evaluate the eye. The owner failed to take the cat to the imaging appointment the next day.

SECOND PRESENTATION

The owner returned with the cat two months later. The right eye was extremely exophthalmic (Figure 1), the conjunctiva had severe chemosis and hyperemia, the eyelids were markedly swollen, and lagophthalmos was present. The conjunctiva was so swollen it covered most of the cornea and precluded corneal evaluation. The cat appeared to be in pain and resisted eyelid manipulation.

Figure 1

Differential diagnoses

Our two differential diagnoses were an extensive retrobulbar mass that was causing venous stasis in the eyelids and conjunctiva leading to swelling or a primary eyelid or conjunctival inflammatory or cellular infiltrate.

Cytologic evaluation of a fine-needle aspirate of the conjunctiva suggested an infiltrative lymphoma (Figure 2). Tropicamide, a topical anesthetic, was administered in both eyes, and orbital ultrasonography was performed to determine the extent of the lesion. The ultrasonographic examination revealed a mass that involved the right globe and the orbit (Figure 3). The mass was hypoechoic and irregularly shaped but had a definitive rounded region with hyperechoic edges and several anechoic cavitated regions. These findings suggested a neoplasm invading the ocular tissues. No abnormalities were identified on ultrasonographic examination of the left eye.

Figure 2

Given the extensive nature of the lesion, the cat's pain, and the owner's financial constraints, in addition to the fact that the eye was blind, immediate exenteration of the orbit was recommended. However, the owner did not return with the cat until three weeks later, reporting the mass had bled profusely several times during the previous three weeks. An exenteration was planned to remove the eye and the contents of the orbit.

Figure 3

Surgery

The cat had lost 4.4 lb (2 kg) since the initial examination and was weak. A complete blood count (CBC) and serum chemistry profile before surgery revealed that the cat was severely anemic (packed cell volume [PCV] = 11%, reference range = 30% to 46%) and that the anemia was mildly regenerative (reticulocytes = 17,520/μl, reference range = 0 to 5,000/μl; nucleated red blood cells = 0.1 x 103/μl, reference value = 0 x 103/μl). The anemia presented an anesthetic and surgical risk, but because of the severity of the ocular lesion and the possibility that the anemia was due to the profuse bleeding from the mass, immediate surgery was deemed necessary.

Blood typing was performed, and the cat was given one unit of type A whole blood. Preanesthetic drugs included hydromorphone and glycopyrrolate given subcutaneously. Anesthesia was induced with intravenous propofol and midazolam, and the cat was intubated and anesthesia was maintained with inhalation oxygen and isoflurane. During surgery, the cat was given a constant-rate infusion of fentanyl for analgesia.

The exenteration was performed by using a transpalpebral approach. A tarsorrhaphy was performed by using 4-0 Dermalon (Syneture), and a No. 15 scalpel blade was used to incise the skin 5 mm from the eyelid edge in an elliptical fashion to allow for smooth skin apposition at closure. The orbital contents were removed by dissection with tenotomy scissors, which were kept as close to the bones of the orbit as possible. The medial and lateral orbital ligaments were transected, and the nictitating membrane was completely removed. The dissection was continued around the eye and mass until the optic nerve was encountered. The nerve was then transected, and the tissue was completely removed.

Meticulous hemostasis was maintained to minimize any additional blood loss. To prevent excess indentation of the orbit and to optimize the cat's appearance after surgery, sutures were placed across the orbital rim (from rim to rim) using 4-0 Dermalon in a continuous pattern. The subcutaneous tissue was closed with 4-0 Dexon S (Syneture) in a simple continuous pattern, and the skin was closed with 4-0 Dermalon in a simple interrupted pattern (Figure 4). Another unit of whole blood was given during the surgery, and at surgical completion, the cat's PCV was 17%.

Figure 4

The cat's recovery from anesthesia was uneventful, and it was released to the owner that day. For pain management, the cat was given oral buprenorphine (0.12 mg/kg sublingually b.i.d. for three days). A two-week postoperative reevaluation with suture removal was scheduled.

HISTOLOGIC EVALUATION

Histologic evaluation of the orbital contents confirmed a diagnosis of conjunctival lymphoma (Figures 5 & 6). Since the tumor was extensive, it was difficult to determine whether it originated in the orbit or the conjunctiva. The initial clinical presentation was consistent with a conjunctival tumor: a relatively slow progression and protrusion of the nictitating membrane and no forward globe displacement.1

Figure 5

The mass was composed of neoplastic lymphocytes, completely obscuring the periorbital tissue and extraocular muscles. These cells also invaded the conjunctiva and eyelids and completely filled the shrunken globe. The cells had scant cytoplasm and round nuclei with densely stippled chromatin and a single prominent nucleolus and were arranged as diffuse sheets among a fibrovascular stroma. The conjunctiva was also infiltrated by lymphocytes, plasma cells, and neutrophils, and there were areas of necrosis and hemorrhage. The orbital tissue was completely invaded by neoplastic lymphocytes. No Reed-Sternberg cells—large abnormal lymphocytes that may contain more than one large pale nucleus with a prominent nucleolus and that indicate Hodgkin-like lymphoma—were seen.

Figure 6

Immunohistochemical staining demonstrated that the cells were negative for CD3 T lymphocyte receptor and positive for CD79a B lymphocyte receptor, confirming the mass was a B-cell lymphoma.

The diagnosis was non-Hodgkin-like, apparent primary conjunctival lymphoma. The histologic examination results indicated that neoplastic cells remained in the orbit, so the chance of mass recurrence was high.

TWO- AND FOUR-WEEK POSTOPERATIVE RECHECKS

At a recheck examination two weeks after surgery, the owner reported that the cat was eating and was alert and playful. Repeat blood tests revealed normal serum chemistry values and a normal PCV (32%). The cat still had reticulocytosis (reticulocytes = 22,620/μl) and increased nucleated red blood cells (0.1 x 103/μl), suggesting that the anemia had been due to blood loss and that erythrocyte production was sufficient.

Since the tumor had been removed and the cat was doing well, treatment options for the lymphoma were discussed with the owner. It was recommended that a thorough check for metastases and testing for feline leukemia virus (FeLV) infection be done before definitive treatment plans were made. Two weeks later, FeLV and feline immunodeficiency virus (FIV) tests were done and the results were negative. Orbital palpation revealed a swollen area, which could have been a regrowth of the mass. Additional ultrasonographic and radiographic examinations were recommended.

SIX-WEEK POSTOPERATIVE EVALUATION

Six weeks after surgery, orbital ultrasonography (Figure 7) showed a soft tissue mass measuring 29.5 mm in diameter. This mass was evaluated with color flow Doppler ultrasound and appeared to be well-vascularized (Figure 8). Cytologic examination of a fine-needle aspirate of the submandibular lymph nodes did not reveal neoplastic cells. Thoracic and abdominal radiographic examination results were normal. Abdominal ultrasonography revealed that the cat had hepatomegaly, splenomegaly, and possible degenerative changes in both kidneys; however, cytologic evaluation of fine-needle aspirates of the spleen and liver failed to show any neoplastic cells.

Figure 7

Since there was no evidence of systemic neoplasia, localized radiation therapy was recommended to treat the lesion recurrence. Because of financial constraints, the owner elected to monitor for tumor progression.

Figure 8

FOLLOW-UP

At a recheck examination three months after surgery, the cat was doing well, but the enlarged area was still present in the right orbit. The right submandibular lymph node was not enlarged. A repeat ultrasonographic examination of the orbit demonstrated that the mass had not changed in size or shape since the last examination. Thus, the owner elected to continue to monitor the cat's health rather than pursue radiation therapy.

A year and a half after the exenteration, the cat continues to do well. The cause of the lymphoma remains unknown. It is also unknown whether the previous blindness of unknown pathogenesis in the eye and the onset of the neoplasm are associated.

DISCUSSION

Lymphomas, the most common tumors in domestic cats,2 are solid tumors composed of neoplastic cells of lymphocytic lineage.1 Lymphoma is often more difficult to diagnose in cats than in dogs because in dogs, multicentric distribution and generalized lymphadenopathy are common, while lymphoma in cats usually involves internal structures such as the alimentary tract,3-5 thymus,3 and mediastinum.6 Solitary lymph node involvement has been reported in cats as well, and most commonly involves lymph nodes of the head and face.5 In cats, ocular lymphomas have been reported in the anterior uvea,5 orbit,7 and conjunctiva.8,9

Conjunctival lymphomas are relatively rare, extranodal neoplasms that have been reported in people,10 horses,11 and cats.8,9 They probably arise from the mucosa-associated lymphoid tissue present in the conjunctiva, which would be consistent with the B-cell immunophenotype of this cat's lymphoma. Conjunctival lymphoma has the best prognosis of any ocular adnexal lymphomas. In a retrospective study, only 36 of 117 (31%) patients with conjunctival lymphoid infiltration already had or eventually developed systemic lymphoma.10 The study suggested that the tumor's location when the disease was first identified was prognostic for the development of systemic lymphoma and that patients with tumors initially arising from extra-limbal sites (e.g. fornix or midbulbar) were less likely to develop systemic lymphoma.10 However, too few reported cases of this tumor exist to determine whether tumor location is a prognostic indicator in cats.

Immunocompromised pets and people

In people, conjunctival lymphoma occurs with increased frequency in immunodeficient individuals and may be associated with viral infections or may be familial.1 Lymphoma in cats is often associated with viremia or latent FeLV infection12; however, as testing for FeLV infection and vaccinations have increased, the incidence of FeLV-positive lymphoma has decreased.13 In the alimentary and mediastinal forms of feline lymphoma, FeLV infection worsens the prognosis for long-term survival and response to chemotherapy.14 However, the association between FeLV infection and conjunctival lymphoma in cats is unknown. In both of the reported cases of conjunctival lymphoma and in the cat presented here, the FeLV test results were negative. Two of the three cats survived long-term (> 1 year),9 while the remaining one was lost to follow-up.8 FIV infection increases the incidence of lymphoma but is thought to play an indirect role in its tumorigenesis.13

Immunophenotyping

Immunophenotyping is being performed in cases of lymphoma in many species to provide prognostic information,6,15 and these tumors have been classified according to cytochemical and immunologic markers.14 Immunophenotyping is more readily available for lymphoid tumors in dogs than in cats, and it is generally considered to be less useful as a prognostic indicator in cats.6,16 Lymphoid tumors arise from T and B lymphocytes17 and from natural killer cells.14,17 As in this case, feline lymphoma is most often the B-cell type.15,18

Non-Hodgkin vs. Hodgkin-like lymphoma

Another possible prognostic indictor is the classification of the initial tumor as either non-Hodgkin or Hodgkin-like lymphoma.1 In cats, both Hodgkin-like9 and non-Hodgkin lymphomas have been reported in the conjunctiva, but to our knowledge, only one report of each disease has been published.9,12 The tumor in the cat reported here appears to be most similar to conjunctival B-cell lymphoma (non-Hodgkin lymphoma)8 because it consisted primarily of B cells and lacked Reed-Sternberg cells.19 Non-Hodgkin lymphoma arises from monoclonal expansion of either T or B lymphocytes, and in people, most are B cell in origin.1 In people, a diagnosis of Hodgkin lymphoma generally carries a better prognosis for long-term survival than does a diagnosis of non-Hodgkin lymphoma.1 This better prognosis appears to be the same in cats19; however, there are so few known cases of conjunctival lymphoma in cats that such a conclusion cannot be made.

Treatment

Treatment protocols for feline lymphoma are determined after disease staging. Staging involves performing a CBC, a serum chemistry profile, a urinalysis, FeLV and FIV testing, a lymph node or organ biopsy, bone marrow aspiration, and thoracic and abdominal radiography.13,20 Additional tests might include thoracic and abdominal ultrasonography and computed tomography.

Chemotherapy is the treatment of choice for most forms of systemic lymphoma. Effective chemotherapeutic agents include cyclophosphamide, vincristine sulfate, and prednisolone. Cytosine arabinoside and lomustine have also been used with some success.13,20 Lymphoma cells are radiation-sensitive, and radiation therapy, which was recommended in this case, can be an effective treatment for the localized forms of lymphoma.

Juliet R. Gionfriddo, DVM, MS

Fiona Tancredi-Ballugera, DVM

Department of Clinical Sciences

College of Veterinary Medicine & Biomedical Sciences

Colorado State University

Fort Collins, CO 80538.

David Gardiner, DVM

E.J. Ehrhart, DVM, PhD

Department of Microbiology Immunology and Pathology

College of Veterinary Medicine & Biomedical Sciences

Colorado State University

Fort Collins, CO 80538.

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