Feline lymphomas can affect various body parts of a cat beyond just the lymph nodes, known as extranodal lymphomas. The specific location impacted by the lymphoma can influence the behavior and management of the tumors (11). Extranodal lymphomas include those found in places other than the digestive system, chest cavity, lymph nodes, or multiple areas. These sites encompass lymphomas in the kidneys, nose/paranasal area, central nervous system, eyes, larynx, and skin (16). Among nasal and nasopharyngeal lymphomas, 82% are categorized as nasal lymphoma, 10% as nasopharyngeal lymphoma, and 8% involve both nasal and nasopharyngeal tissues (7).

Clinical signs of nasal lymphoma include purulent or mucoid nasal discharge, facial deformities, epistaxis, and sneezing (5). Other initial clinical signs encompass stertorous breathing, anorexia, dyspnea, buphthalmos, and epiphora (5).

Treatment options for nasopharyngeal lymphoma comprise radiation therapy (RT), chemotherapy, surgical debulking, and any combination of the above (13). Lymphoid neoplasia not only responds to chemotherapy, but also responds to radiation. Localized forms particularly respond well to RT (5). Definitive RT (DRT) and stereotactic RT (SRT) are known treatment modalities for feline nasal and nasopharyngeal lymphoma (13,15). Additionally, previous studies have indicated that a coarsely fractionated protocol is as effective as a definitive protocol for feline nasal lymphoma (3). Nasal cavity tumors are predominantly treated with radiation, although adjunctive surgery benefits some patients (18). According to other previous reports in canine, RT followed by surgical excision of nasal cavity tumors can increase disease-free interval in nasal tumors (18). However, treatment involving surgical debulking and RT for feline nasopharyngeal lymphoma has not been reported yet.

Hypofractionated RT (HRT) is employed as a palliative treatment, whereas multifractionated RT is utilized as a definitive treatment (12). The goal of HRT is to enhance the patient’s quality of life by alleviating clinical symptoms. HRT, differing from curative intent (definitive) therapy, aims not to eliminate malignancy but to improve symptoms, contrasting with the goal of returning the patient to a disease-free state (17). Some owners select hypofractionated radiotherapy due to the cost and burden of frequent veterinary hospital visits (12). However, there was no significant difference in survival time between HRT and multifractionated RT protocols for feline nasal lymphoma (5).

This case report aims to describe successful treatment of a feline nasopharyngeal lymphoma using hypofractionated radiation therapy combined with surgical debulking.

A 3-year-old, spayed female, Russian blue weighing 4.3 kg was presented for dyspnea, nasal discharge, and stertorous breathing. There were no remarkable findings in the blood test. Plain thoracic radiography was not remarkable. Computed tomography (CT) was performed to differentiate upper airway tract disorders.

Contrast-enhanced CT revealed the presence of an iso-attenuating mass measuring 10.0 × 7.9 × 15.6 mm, with mild homogeneous contrast enhancement occupying the rostral nasopharynx (Fig. 1A, B). There was no evidence of invasion into surrounding bone structures adjacent to the mass. Differential diagnosis for the mass included nasopharyngeal polyp and malignant tumor. Left retropharyngeal lymph node enlargement with homogeneous contrast enhancement was confirmed. No specific findings were noted in adjacent lymph nodes, including the submandibular lymph node. On differential diagnosis of the lymph node, reactive lymphadenopathy was considered. However, the possibility of metastasis of neoplasia could not be ruled out.

Figure 1. Computed tomography (CT) images of axial and sagittal planes before hypofractionated radiation therapy following surgical debulking (A, B) or at 27 months after RT (C, D). (A, B) Contrast-enhanced CT images revealing iso-attenuating mass (*) with mild homogenous contrast enhancement, occupying the rostral nasopharynx. (C, D) No tumor identified in the nasopharynx at 27 months after RT. The patient was confirmed to have achieved a complete response.

Surgical access to the nasopharynx was obtained through a longitudinal incision in the soft palate, where surgical debulking of the mass and biopsy retrieval were performed (Fig. 2). Nasopharyngeal lymphoma was confirmed through immunohistopathologic diagnosis. An immunohistochemical diagnosis confirmed CD3–/CD79a+ B-cell lymphoma. The biopsy revealed an incomplete margin. After 24 days of surgery, a CT simulation was performed for radiation therapy planning. The cat was anesthetized and positioned in sternal recumbency, facing headfirst in a dorsoventral direction with forelimbs positioned caudally. To maintain this position, a vacuum-lock cushion (Vac-LokTM, CIVCO Medical Solutions), a base plate (MT-20100CF, CIVCO Medical Solutions), a custom upper jaw support bridge, a bite block (made from thermoplastic pellets, CIVCO Medical Solutions), and a thermoplastic mask (Uni-frame^®, CIVCO Medical Solutions) were used for cranial immobilization of the patient. An intravenous injection of iodinated contrast medium (Omnipaque^TM 300 mgI/mL, GE Healthcare, Princeton, NJ, USA) at a rate of 3.0 mL/kg was given. Images without contrast and with contrast were captured using a 160-slice multidetector CT scanner (Toshiba Aquilion^TM prime, Cannon Medical Systems, Otawara, Japan) at a slice thickness of 1 mm. Subsequently, images taken after the contrast was administered were transferred to a radiation treatment-planning system (Elekta Monaco, Stockholm, Sweden). The gross tumor volume (GTV) was defined as the area of the tumor visualized on plain and contrast enhanced CT images (19). After surgical debulking, no visible mass was observed. Thus, the GTV was not contoured. Clinical target volume (CTV) was contoured with a 3 mm margin from the previous visible mass area, considering peritumoral edema and/or microscopic tumor infiltration. It was performed by a veterinarian with four years of experience in veterinary radiation oncology. Subsequently, the planning target volume (PTV) was contoured with a 5 mm margin from the CTV. The dose was planned to the 95% isodose line with the CTV receiving 100% of the dose and the PTV receiving 95% of the dose (Fig. 3). Organs at risk (OARs) included the brainstem, bilateral eyes and lenses, brain, optic chiasm, and optic nerves (Table 1).

Table 1 . Mean radiation dose details for organs at risk for feline nasopharyngeal lymphoma.

	Volume (cm3)	Mean dose (min-maximum dose) (Gy)
Brain	26.45	5.24 (0.76-30.05)
Optic chiasm	0.09	17.49 (13.16-22.88)
Optic nerve	0.16	13.38 (4.37-24.74)
Lt. eye	4.81	5.41 (0.63-21.22)
Lt. lens	0.69	4.41 (1.65-9.03)
Rt. eye	4.94	5.78 (1.00-19.61)
Rt. lens	0.73	5.58 (3.32-8.23)
Skin	396.09	4.94 (0.02-39.20)

Figure 2. (A) Nasopharynx was approached surgically via a longitudinal incision in the soft palate. (B) Surgical debulking of the nasopharyngeal mass was performed and biopsy sample was obtained.

Figure 3. Transverse plane (A) and sagittal plane (B) of the dose distribution and dose-volume histogram (C) of the patient.

HRT was performed using a 6-MV Synergy linear accelerator (Elekta, Stockholm, Sweden) equipped with a multi-leaf collimator and cone-beam CT. The prescribed treatment involved a total of 36-gray (Gy) delivered in fractions of 6-Gy per week. To ensure accurate positioning, a vacuum-lock cushion, a custom upper jaw support bridge, a bite block, and a thermoplastic mask were used along with kilovoltage cone-beam CT-based image guidance. Before the procedure, the patient received premedication with glycopyrrolate (Mobinulinj^®, Myungmoon pharm, Korea; 0.01 mg/kg, SC) followed by anesthesia induction using propofol (Prepole MCT^®, Daewon pharm, Korea; 6 mg/kg, IV) and maintenance with isoflurane. To ensure accuracy of dose distribution, quality assurance was conducted using a PTW two-dimensional array (PTW Freiburg GmbH, Germany). The measurement involved a minimum of 95% gamma analysis with criteria set at 3% dose difference and 3 mm distance to evaluate the relative dose. No adverse effects of RT were observed (Veterinary radiation therapy oncology group [VRTOG]) (6).

Follow-up CT examination was performed after 27 months of irradiation. The patient was confirmed to have achieved a complete response (Fig. 1C, D). There were no chronic complications related to irradiation. The patient is still alive for 40 months without recurrence.

A study on nasopharyngeal disorders in cats has revealed that 49%, 28%, 23% are diagnosed with lymphoma, inflammatory polyps located dorsal to the soft palate, and other diseases including squamous cell carcinoma, adenocarcinoma, lymphoplasmacytic rhinitis/pharyngitis, rhabdomyosarcoma, spindle cell carcinoma, and melanoma, respectively (1). Nasal lymphoma typically affects middle-aged to older cats, with mean ages of 8.9 and 11.4 years (7,15), while nasopharyngeal polyps are more common in young cats, with cases reported in an age range of 3 months to 15 years (14). The most common clinical signs observed at the time of diagnosis are nasal discharge (84%), sneezing (68.4%), and increased respiratory noises (68.4%) in cats. Other commonly reported clinical signs include ocular discharge (52.6%), weight loss (42.1%), and facial deformity (31.6%) (15). Various diagnostic methods such as endoscopy, CT scan, skull radiographs, oral examination, digital palpation of the soft palate, and nasopharyngeal biopsy or their combination have been used to diagnose nasopharyngeal masses (1). Biopsy is considered the definitive method for diagnosing nasal lymphoma (7). Clinical stage of the disease plays a crucial role in determining prognosis and treatment for most cancers in cats (11). According to Mooney and Hayes’ staging system (9), the lymphoma stage significantly impacts treatment response (10). For cats with extranodal lymphoma confirmed to have stage 1 disease in an accessible site, localized therapies such as radiation therapy or surgery can offer palliative, therapeutic, and potentially curative outcomes (11). Recent studies have indicated that radiation therapy followed by surgical debulking of nasal cavity masses in dogs can extend their disease-free interval (18). In the present case, the patient presented with dyspnea, nasal discharge, and stertorous breathing. A surgical approach was taken to remove the nasopharyngeal mass identified in the CT scan. Immunohistochemical examination of the excised mass confirmed nasopharyngeal lymphoma, with an incomplete margin.

DRT is a usual treatment for feline nasal lymphoma. A total of 39-48 Gy is delivered at 3-Gy per fraction (15). In SRT, a total of 18-20 Gy is administered for feline nasal and nasopharyngeal lymphoma (13). The HRT protocol involves weekly fractionated doses of 6.0-8.1 Gy (median, 8.0 Gy) at two to six doses for a total dose of 16-36 Gy (median, 32 Gy) (4). Lymphocytes are sensitive to radiation, suggesting that localized forms of nasal lymphoma will respond well to treatment with RT (5). Coarsely fractionated protocols might be as effective as definitive protocols for feline nasal lymphoma (3). In the present case, the patient received a total of 36 Gy of radiation therapy delivered in 6 fractions following the HRT protocol.

In a previous report, of 32 feline nasal lymphomas treated with HRT alone, 41% achieved a complete response, 53% achieved a partial response, and 6% achieved stable disease, resulting in an overall response rate of 94% (19). According to previous reports, chemotherapy alone yielded median survival time (MST) ranging from 3.3 months to 11.9 months (5), while radiation therapy alone resulted in an overall survival time of 15 months to 30 months (13). Survival time following treatment with both chemotherapy and radiation ranged from 5.8 months to 31.4 months (8,15). Cats treated with prednisolone alone had an MST of 11 days to 33 days (2).

Negative prognostic factors include anemia, anorexia, and destruction of the cribriform plate (15). Cats that exhibit a complete response to treatment and cats receiving a total radiation dose of 32 Gy or higher tend to live much longer (5). In the present case, during a follow-up period of 27 months, a complete response was observed after application of HRT with a total radiation dose of 36-Gy, confirming a positive prognosis (5).

Acute complications are defined as side effects observed within one month of RT while late complications are defined as side effects observed from 6 months post-RT to death (4). HRT as a palliative measure can increase the incidence for severe late side effects (4). Commonly reported acute side effects include mucositis/pharyngitis, conjunctivitis, and rhinitis (15). All these problems could be managed medically and resolved in an acceptable period (15). Late complications include cataract (observed in 20.5% of cats), poliosis at the irradiation site (12.8%), atrophy of the entire eyeball, osteochondroma at the irradiation site, chronic ocular discharge, fistula between nasal and oral cavities, and blepharospasm (4). Cataracts have been found to be the most common late side effects. However, they are not severe as they are acceptable to owners (4). The present case did not show any acute or chronic side effects.

This case describes the response and prognosis of nasopharyngeal lymphoma in a cat treated with hypofractionated RT following surgical debulking. Complete response was achieved. No complications related to RT were identified. Therefore, hypofractionated RT after surgical debulking could be considered as a treatment option for nasopharyngeal lymphoma in cats.

This work was supported by the research grant of the Gyeongsang National University in 2023.

The authors have no conflicting interests.