Intranasal mast cell tumor in the dog: A case series

Abstract

The medical records of 4 dogs with histologically confirmed intranasal mast cell tumors (MCTs) were retrospectively evaluated to determine their biological behavior. Information on signalment, presenting clinical signs, tumor grade, treatment administered, and survival times was obtained from the medical record. All 4 patients had high grade tumors and received chemotherapy. Survival times ranged from 27 to 134 days. All 4 dogs showed signs of local or distant disease progression, suggestive of an aggressive behavior of intranasal MCTs.

Mast cell tumors are a commonly diagnosed cutaneous tumor, accounting for 7% to 21% of all canine skin tumors (1,2). These tumors have a range of clinical presentation, varying from benign to malignant behavior. The extent of ancillary diagnostic workup and treatment is predicated on the presence or absence of negative prognostic factors such as histological grade, clinical stage, growth rate, cell proliferation rate, recurrent disease, and the presence of systemic signs (3,4). In some studies, anatomic location has been used as a predictor of the biologic behavior of MCTs in dogs, with tumors in the preputial, scrotal, subungual region, oral cavity, and other mucous membrane sites associated with a higher grade tumor and poorer prognosis (3,4). Visceral MCTs are rare but are associated with systemic signs and carry a guarded prognosis (5,6). There have been few reports discussing mucosal or mucocutaneous MCTs, with most reports focusing on oral, perineal, preputial, and subungual sites. One study investigating MCTs located on the canine muzzle showed a regional metastatic rate of 58% (7). To our knowledge, there have been no reports describing the behavior of intranasal MCTs. The purpose of the study reported here was to retrospectively analyze the biologic behavior and prognosis of dogs with intranasal MCTs. The clinical, diagnostic, and histologic findings associated with a series of 4 dogs diagnosed with intranasal MCTs are described.

Case descriptions

Case 1

A 14-year-old neutered male crossbreed dog (Table 1) was presented to the referring veterinarian for vomiting of unknown cause. Three days prior to presentation the dog was anorexic, polydipsic, and lethargic. Previous clinical signs included noisy inspiratory stertor with nasal discharge.

Table 1.

Case summaries

Case number	Signalment	Presenting clinical signs	Stage	Substage	Histological grade	Overall survival times (days)	Concurrent illnesses
1	14-year-old MN crossbreed dog	Vomiting and inspiratory stertor	T1 N1 M0	b	Grade 3	65	Nil
2	15-year-old MN Maltese cross	Sneezing	T1 N0 M0	a	Undifferentiated round cell tumor	40	Nil
3	12-year-old FS Kelpie cross	Stertorous breathing	T1 N1 M0	a	High grade well-differentiated	27	Grade 3/6 mitral valve murmur
4	13-year-old FS Shetland sheepdog	Sneezing, reverse sneezing, open mouth breathing	T1 N0 M0	b	Grade 3	134	Nil
5	5-year-old ME Kerry blue terrier	Depigmentation of left nares	T1 N1 M0	a	Grade 3	661	Nil

MN — male neutered; FS — female spayed.

Physical examination by the referring veterinarian revealed abdominal discomfort and enlarged mandibular and prescapular lymph nodes. Cytology of a fine-needle aspirate (FNA) from the lymph nodes showed an eosinophilic lymphadenitis. Thoracic and abdominal radiographs showed no significant abnormalities. Blood tests showed a mild decrease in potassium [3.6 mmol/L; reference range (RR): 3.9 to 5.1 mmol/L] and chloride (96 mEq/L; RR: 110 to 124 mEq/L) levels; signs of mild dehydration; and a mature neutrophilia and monocytosis. The patient was treated conservatively with an oral electrolyte solution, dietary modification, and metoclopramide (Metomide; Delvet Pty, Asquith, NSW, Australia), 0.2 mg/kg body weight (BW), IV, q12h, with no improvement, and was subsequently referred to an internal medicine specialist.

Physical examination at the referral hospital revealed persistently enlarged left mandibular lymph nodes. All other findings were unremarkable. An abdominal ultrasound examination revealed no abnormalities. The patient was again managed conservatively for 2 wk using dietary modification and anti-emetics, but there was no clinical improvement.

Upper gastrointestinal endoscopy revealed fresh ulceration of the mucosa of the esophagus, pyloric antrum, and duodenum. The mucosa of the duodenum also had a cobblestone appearance and certain sections appeared to be edematous. The patient was examined for possible causes of gastric ulceration. A subcutaneous mass on the neck was aspirated and confirmed to be a lipoma. The mandibular lymph nodes were aspirated again and showed large numbers of eosinophils. The patient’s owner confirmed that the dog had not received any ulcerogenic drugs or seen to consume any erosive substances. Histopathology results from the stomach and duodenal biopsies showed a mild gastritis and enteritis with no sign of neoplasia.

A few days after the endoscopy, the patient developed epistaxis from the left nostril and soft tissue swelling around the left eye and lower conjunctiva. Pain was noted on opening the mouth.

Magnetic resonance imaging (MRI) of the nose showed a mass effect with surrounding inflammation occupying a significant portion of the left nasal passage. Repeat aspirates of the mandibular lymph nodes were suggestive, but not definitive, of a metastatic MCT with necrosis. Nasal biopsies demonstrated a granulomatous reaction with an eosinophilic component but no convincing evidence of neoplasia. The dog was treated for eosinophilic rhinitis using prednisolone (Prednisone; Apex Laboratories, Somersby NSW, Australia), 0.6 mg/kg BW, PO, q24h, and gastroprotectants.

Two weeks later the patient developed recurrent swelling of the neck and jaw. The left mandibular lymph node was still enlarged and the patient had developed mild dyspnea.

Repeat nasal biopsies and wedge biopsies of the mandibular lymph node confirmed the presence of a high grade MCT in both sites based on Patnaik grading criteria. Treatment was initiated following a vinblastine (DBL Vinblastine; Aspen Australia, St Leonards NSW, Australia), lomustine (Ceenu; Bristol-Myers Squibb, Noble Park, North Vic, Australia), and prednisolone (Apex Laboratories) chemotherapy protocol (8). Famotidine (Pfizer, Belmont WA, Australia), 0.6 mg/kg BW, PO, q24h, and omeprazole (Gastroshield; Merial Australia Pty, North Ryde, NSW, Australia), 0.6 mg/kg BW, PO, q24h, were also prescribed. After the first cycle of the chemotherapeutic protocol, the patient was switched to single agent lomustine (Bristol-Myers Squibb) for the remaining 3 treatments due to a better initial clinical response to this drug. During this time the patient showed variable responses to treatment with intermittent nasal discharge and dyspnea, a decrease in overall swelling of the mandibular area, and occasional vomiting. Worsening clinical signs were seen when attempts were made to reduce the dose of prednisolone. The patient developed neurological signs including head pressing, pacing, and ataxia, suggestive of brain involvement, and was euthanized 4 mo after diagnosis.

Case 2

A 15-year-old neutered male Maltese cross dog (Table 1) was presented to the referring veterinarian for sneezing and gagging and was treated with doxycycline (Doxycycline; Apex Laboratories) and chlorpheniramine (Iramine; Mavlab Pty, Slacks Creek, QSLD, Australia) with no clinical improvement. Skull radiographs showed a soft tissue opacity in the caudal left nasal cavity. A nasal flush was conducted and 50% of the cells were mast cells. Bacterial and fungal culture was negative. The patient was subsequently referred to an oncologist for further investigation.

Rhinoscopic examination showed increased mucus in the left nasal cavity and a normal right nasal cavity. In-house impression smears from the left cavity mucosa showed an almost pure population of mast cells. While awaiting histopathology results from nasal biopsies, the patient was treated with a single dose of dexamethasone (Dexafort; Intervet/Schering-Plough Animal Health, Bendigo East Vic, Australia), 0.1 mg/kg BW, IV, and chlorpheniramine (Iramine; Mavlab), 0.5 mg/kg BW, IM.

The histopathologic diagnosis was an undifferentiated round cell tumor, most likely a MCT. The patient commenced a vinblastine, lomustine, and prednisolone chemotherapy protocol (8). Half way through the second cycle, the patient developed multiple masses in the liver, ascites, and a neck mass which was aspirated and showed poorly differentiated mast cells. The patient was subsequently euthanized 40 d after diagnosis.

Case 3

A 12-year-old neutered female Kelpie cross dog (Table 1) was presented to the referring veterinarian with a history of progressive stertorous breathing and snoring while asleep. The dog was treated with cephalexin (Cephalexin; Apex Laboratories) and antihistamines and showed slight improvement, but clinical signs recurred when the medication was discontinued. A computed tomography (CT) scan of the head revealed a nasopharyngeal mass extending into the nasal cavity and markedly enlarged, contrast-enhancing retropharyngeal lymph nodes. The dog was subsequently referred to an oncologist. Physical examination at the referral hospital revealed enlarged left mandibular and left prescapular lymph nodes. Fine-needle aspirate cytology of the mass revealed a round cell population with large numbers of cytoplasmic granules. The histopathologic diagnosis from nasal tissue biopsies was a high grade MCT. The patient was treated with imatinib (Glivec; Novartis Australia, North Ryde, NSW, Australia) for a month before being euthanized due to local progression of the disease.

Case 4

A 13-year-old neutered female Shetland sheepdog (Table 1) was presented to the referring veterinarian with a history of increased sneezing, reverse sneezing, throat clearing, and open-mouthed breathing. Rhinoscopic examination revealed a hemorrhagic mass in the right nasal cavity and histopathologic examination of nasal tissue biopsies resulted in a diagnosis of a high grade MCT. The patient was prescribed doxycycline and prednisolone and was subsequently referred to an oncologist for chemotherapy. The patient commenced a prednisolone, vinblastine, and lomustine chemotherapy protocol (8). Clinical examination at the final treatment reported minimal airflow through the right nostril with dried blood visible at the right nares, suggestive of tumor recurrence. Four days later the patient developed seizures which were suspected to be secondary to tumor involvement of the brain. The patient was euthanized 134 d after diagnosis.

Discussion

Primary tumors of the sinonasal cavity account for 1% to 2% of all neoplasms in dogs (9). Of these neoplasms, about 80% have histologic characteristics of malignancy with adenocarcinomas being the most common, followed by squamous cell carcinomas, chondrosarcomas, and undifferentiated (anaplastic) carcinomas (10). Less frequently diagnosed sinonasal malignancies include hemangiosarcoma (11), transmissible venereal tumor, melanoma, leiomyosarcoma, neuroendocrine carcinomas, and round cell tumors (9,12). Little information exists on the biological behavior, prognostic factors, and recommended treatment for these less commonly occurring sinonasal neoplasms.

The average age of dogs diagnosed with sinonasal tumors is 10 y with medium to large breed male dogs more commonly affected (9). It is speculated that dolicocephalic breeds may be at a higher risk for developing sinonasal cancer (13,14). This is not a finding in the present study, with only 1 of 4 patients being dolicocephalic. Two of the 4 patients in this case series were male and all 4 patients were 12 y or older at presentation. None of the breeds in this study are reported to be predisposed to developing cutaneous MCTs (15).

Clinical signs in our patients overlapped with those seen in other intranasal diseases. These included intermittent and progressive unilateral epistaxis, mucopurulent nasal discharge, sneezing, difficulty breathing, and ocular discharge (9,11,16). One patient in our series also presented for vomiting, which was subsequently diagnosed as secondary to gastric ulceration. This was suspected to be a paraneoplastic syndrome secondary to the MCT, due to increased circulating histamine levels and stimulation of the gastric H2 receptors.

Mast cell tumors involving mucocutaneous areas have been described as having a grave prognosis (3,7,17). Results of the present study suggest that dogs with intranasal MCTs frequently have aggressive disease with 3 of the 4 cases diagnosed on histopathology with a high grade MCT and the remaining case being described as anaplastic with a high mitotic index. Despite the variation and lack of consensus among pathologists regarding MCT grading criteria, the present study demonstrates that 3 of 4 affected dogs were diagnosed with a high grade MCT, with short overall survival times ranging from 27 to 134 d. A previous study of grade 3 mucocutaneous MCTs showed a relatively short median survival time (MST) of 8 mo (17). In contrast, another study showed that patients with oral MCTs had a much longer MST of 52 mo (3). The decreased survival time seen with intranasal MCTs compared with other mucocutaneous MCTs could be associated with complicating factors such as brain or optic involvement, advanced stage of disease at presentation due to late onset of clinical signs, and complex regional anatomy preventing surgical treatment. Although the grading system for MCTs applies only to cutaneous masses, the use of these criteria may be clinically relevant for patients with nasal MCTs.

A limitation of the present study was the lack of CD117 immunohistochemical analysis of the biopsy samples. CD117 is a receptor tyrosine kinase protein involved in mast cell growth and differentiation. A C-kit staining pattern has been used for its predictive role of histological grade, tumor necrosis, and the biologic behavior in MCTs (18,19). Further studies on CD117 immunohistochemical analysis are needed to evaluate its prognostic value in predicting the biological behavior of mucocutaneous MCTs. AgNOR and Ki67 count as well as polymerase chain reaction (PCR) for C-kit mutation may also be beneficial.

Regional lymph node involvement was detected in 2 of 4 dogs in our series. In the remaining 2 patients, despite palpably normal lymph nodes, lymph node involvement cannot be excluded due to lack of further lymph node evaluation. Due to the retrospective nature of the study, staging tests were not uniformly performed. On presentation, none of the patients in this study showed signs of distant metastasis, which is a consistent feature of sinonasal neoplasms in general (9,16,20). However, all 4 dogs in the present study were euthanized due to progression of disease beyond the nasal cavity suggesting that complete staging at presentation, including a computed tomography (CT) scan and local lymph node aspiration, is warranted.

Treatment received by each patient in this series was largely dependent on clinician choice, the stage of disease at the time of diagnosis, and the owner’s decisions and financial constraints. Three of the 4 patients received a similar chemotherapeutic protocol involving alternating vinblastine and lomustine treatments, with concurrent prednisolone administration. Three of 4 patients included in the present study experienced survival times of less than 19 wk. This may be due to the selection of patients with MCT of cutaneous origin in the previous study having a less aggressive behavior (15).

Radiation therapy for the treatment of intranasal carcinomas and sarcomas has demonstrated efficacy in improving patient survival times (16). One study suggested that survival times can be further improved if patients were treated surgically after radiation, although these patients developed delayed complications including chronic rhinitis, osteomyelitis, and osteonecrosis (21). To the authors’ knowledge, there have been no studies to confirm the efficacy of radiation therapy in treating intranasal round cell tumors. Radiation therapy may be useful as adjuvant or definitive therapy for unresectable intranasal MCT disease, and the lack of treatment with radiation could account for the shorter survival times of dogs in this study (22–28).

Despite the retrospective nature and small sample size of the present study, this study was able to better characterize the biological behavior of intranasal MCTs and confirm that tumor location is an important prognostic indicator of canine MCTs. Based on the results of this report, affected patients experienced a relatively short survival time with a potential for local disease progression compared with MCTs at other sites.