Nasal lymphoma – a summary

Lymphoma is the most common tumour in cats and represents about 90% of all feline haematopoietic malignancies (Teske et al, 2002).

Nasal lymphoma is an uncommon manifestation of feline lymphoma, with a reported incidence of fewer than 1% of all feline tumours (Haney et al, 2009). However, nasal lymphoma is the second most common extranodal lymphoma in the species, after alimentary lymphoma (Taylor et al, 2009).

In humans, the nasal cavities and paranasal sinuses are rarely affected by primary extranodal lymphoma. More common primary extranodal sites of lymphomas include the liver, soft tissue, dura and bone (Cheung et al, 1998). In comparison, lymphoma is the most common tumour of the feline nasal cavity and represents half of all nasal neoplasia, followed by adenocarcinoma, squamous cell carcinoma and fibrosarcoma (Mukaratirwa et al, 2001). It is the second most common cause of chronic nasal disease in cats after chronic rhinitis, followed by foreign bodies, stenosis and nasal polyps (Henderson et al, 2004).

The aetiology of nasal lymphoma in cats is unknown; human associations between Epstein-Barr virus infection and nasal lymphoma have been reported (Ho et al, 1990).

In cats, FeLV has been associated with increased risk of developing lymphoma; however, the incidence of FeLV has decreased in the past few decades and most cats with nasal lymphoma are FeLV-negative (Teske et al, 2002). The association between FeLV and feline nasal lymphoma is not known, but the incidence of FeLV in this type of tumour is lower than 10% (Stützer et al, 2011).

Environmental exposure to tobacco smoke has been found to be a risk factor for nasal tumours in dogs (Reif et al, 1998), but most canine nasal tumours are carcinomas. This has not been proven for nasal tumours in cats, but an increased risk of lymphoma in cats exposed to tobacco smoke has been reported (Bertone et al, 2002).

Presentation and diagnosis

Cats usually present with upper respiratory stridor, sneezing, nasal discharge, epistaxis, epiphora and facial pain or deformation. As with feline patients, epistaxis, facial swelling and nasal obstruction are common clinical signs of nasal lymphoma in human patients; headache is also frequently reported (Chalastras et al, 2007).

The time between initial clinical signs and diagnosis is usually longer for nasal lymphoma compared to other forms of lymphoma. This is due to the early clinical signs of nasal lymphoma being mild and easily confused with acute or chronic viral infections.

Definitive diagnosis requires a tissue biopsy. Rhinoscopy can be used to visualise the best area for collection of the biopsy sample, although blind nasal biopsy has been reported to be as successful as guided biopsy in obtaining a diagnosis of nasal neoplasia in dogs (Harris et al, 2014). In the authors’ experiences, nasal blind biopsy in cats is a reliable and straightforward way to obtain tissue, following confirmation of a nasal mass. It is commonly performed at their institution.

CT and MRI are both useful tools to diagnose nasal disease and investigate the extent of the tumour (Figures 1 to 3). MRI is more expensive and requires longer anaesthesia time compared to CT, but is the more sensitive technique in detecting neoplastic soft tissue invasion (for example, into the brain) and in visualising small accumulations of fluid. Conversely, CT is probably superior for investigating neoplastic bone involvement (Drees et al, 2009).

Accurate staging of both the disease and patient is necessary before treatment. In addition to advanced imaging of the nasal cavity, this will ideally involve haematology, biochemistry and urinalysis, FeLV and FIV tests, radiography of the chest and abdominal ultrasound. Alternatively, a full-body CT scan could investigate the extension of the nasal mass, for staging purposes and radiotherapy planning at the same time. The only disadvantage of this is the need for an abdominal ultrasound to collect a guided fine-needle aspiration biopsy, in the event any abnormalities are found on the CT scan.

Nasal lymphoma carries a fair to good prognosis, with the median survival time (MST) reported to range from 12 months to 30 months (Haney et al, 2009; Sfiligoi et al, 2007). It is often a localised disease, with 37% of patient death (or euthanasia) due to local recurrence and only 10% to 17% due to systemic disease. The kidneys appear to be a frequent site for distant disease development (Haney et al, 2009; Sfiligoi et al, 2007; Taylor et al, 2009).

Treatment

Treatment is based on radiotherapy (Figures 2 to 5), chemotherapy or both; however, it is unclear which approach is more effective (Haney et al, 2009).

One study found the longest MST of 955 days was obtained with a combination of both. Different radiotherapy protocols were used, with most patients receiving radiotherapy combined with chemotherapy either daily or every other day (Sfiligoi et al, 2007).

A larger study found an MST of 536 days, with little difference between patients receiving radiotherapy, chemotherapy or both (Haney et al, 2009). The optimal treatment for feline nasal lymphoma, therefore, has yet to be established.

It seems reasonable to think radiotherapy could be the preferred treatment for stage I nasal lymphoma, where the tumour is confined to the nose; however, due to the risk of distant recurrence, the addition of chemotherapy could be beneficial. Alternative approaches could be to treat the nasal lymphoma with radiotherapy first, only using chemotherapy in case of distant recurrence, or to start with a multi-agent chemotherapy protocol, with radiation therapy to the nose if no response is achieved or when progression develops.

No gold standard treatment exists for feline nasal lymphoma, so a case-by-case approach is normally established for each patient.

The response rate for either chemotherapy or radiotherapy are reported to be between 66% and 75%. Response to treatment is probably the best positive prognostic factor and patients that respond either to chemotherapy or radiotherapy seem to achieve the longest survival.

One study found patients that achieved complete response survived significantly longer (MST 749 days) compared to patients that responded only partially (54 days; Taylor et al, 2009).

Different radiotherapy protocols have been reported, with the main two being coarsely fractionated weekly protocols (three weeks to four weeks) or a 10-fraction to 12-fraction Monday-Wednesday-Friday regimen, but no survival advantage between these approaches has been found (Haney et al, 2009).

However, the total dose of radiotherapy delivered to the patient has been found to correlate positively with survival; patients that received more than 32 Gray achieved a better outcome (Haney et al, 2009).

Negative prognostic factors reported are anaemia, anorexia and invasion of the cribriform plate on CT (Haney et al, 2009). The prognostic significance of immunophenotype in extranodal feline lymphoma has not been clearly established; however, most feline nasal lymphomas are of B cell origin (about 70%; Mukaratirwa et al, 2001). Direct comparison in survival, or response to treatment, between the two phenotypes could be challenging and, as yet, has not been documented.

Conclusion

Nasal lymphoma in cats is treatable, with a high response rate and long survival time – particularly with a multimodal therapeutic approach. No standard protocol exists for treatment; it is often based on the institution and/or oncologist’s experience and preference.

In the authors’ institution, treatment is tailored to each patient, considering extension of the disease, anaesthesia risks, concomitant diseases, affordability and owner preference.