Angiofibroma of the nasal cavity in 13 dogs

Abstract

This case series describes a rare entity, nasal angiofibroma, in 13 dogs that were presented to the University of Wisconsin, School of Veterinary Medicine from 1988 to 2000. All dogs in this case series presented with clinical signs and radiographic changes that were strongly suggestive of a locally invasive neoplasm. However, histopathology completed on transnostral core biopsy samples revealed benign appearing vascular proliferation with secondary lymphosuppurative inflammation was established despite cytologic criteria of malignancy present in five dogs. On the basis of the outcomes in this case series, nasal angiofibroma should be considered a differential for dogs presenting with clinical signs consistent with a malignant nasal tumour.

Introduction

Nasopharyngeal angiofibroma is a rare, benign, yet locally invasive neoplasm of humans for which only a single case report in a dog exists in the veterinary literature.¹ In humans, it accounts for approximately 0.05% of head and neck tumours and is thought to be the most common benign tumour originating in the nasopharynx. It is best described in young males and is often referred to as juvenile nasal angiofibroma although there are reports of this lesion occurring in older patients, including females.² It is a histologically benign, but locally aggressive vascular nasopharyngeal tumour, characterized by a proliferation of irregular appearing blood vessels that are surrounded by a connective tissue stroma.^3,4 These tumours expand intranasally into the nasophyarynx and nasal cavity eroding bone and can invade the infratemporal fossa, orbit and middle cranial fossa. Consequently, the most frequent presenting signs in humans include nasal obstruction, chronic nasal discharge with intermittent epistaxis. Some patients present with hearing loss or diplopia from tumour extension into the cranium with resultant pressure on optic chiasm or ear canal obstruction.² Treatment options evaluated in humans include surgery, radiation therapy and chemotherapy.^5,6

This case series describes a nasal lesion in dogs with features similar to nasopharyngeal angiofibroma as described in humans. All dogs were presented with clinical signs suggestive of a locally invasive neoplasm including nasal obstruction, recurrent epistaxis and the presence of a nasal mass. Radiographically, each dog had a destructive mass lesion on either skull radiographs or computed tomography (CT) scan, which was suggestive of a locally aggressive nasal tumour. Despite the imaging characteristics of a locally invasive tumour, all lesions appeared histologically benign.

For this study, we reviewed 13 dogs diagnosed with nasal angiofibroma that were presented to the University of Wisconsin, School of Veterinary Medicine from 1988 to 2000. We documented presenting signs, signalment, radiography, cytology, histopathology, treatment and outcome in all cases. One pathologist (R. R. D.) evaluated all the histopathology samples, all skull radiographs and CT scans were evaluated by one radiologist (E. M. G.) and all cytologic evaluation was performed by one clinical pathologist (R. D. W.)

Results

The study population was composed of nine females (three intact) and four males (one intact). The age of affected animals ranged from 7 to 15 years with a median of 11 years. There were four mixed breed dogs, two Labrador retrievers and one each of a golden retriever, collie, cocker spaniel, Irish setter, springer spaniel, Shar Pei and Shih-tzu. All dogs were presented because of chronic unilateral mucopurulent nasal discharge with intermittent epistaxis. The duration of clinical signs ranged from 2 months to 2 years with a median of 7 months. Three dogs were previously treated with antibiotics, two received corticosteroids, two dogs received both corticosteroids and antibiotics and six dogs had no prior therapy. Physical exam findings in 12 of the 13 dogs were generally within normal limits, with no abnormalities related to the nasal disease. One dog had obvious facial swelling with severe mucopurulent discharge from one nares and associated eye. Complete blood cell counts and serum biochemistry profiles revealed no significant abnormalities. Complete staging, including cytological evaluation of the draining lymph nodes and thoracic radiographs, were performed on every dog. No evidence of metastatic disease was identified in any dog.

Nine dogs had skull radiographs performed, which revealed the presence of a soft tissue opacity within the nasal cavity with adjacent loss of turbinate detail. Six dogs were evaluated via skull CT scan; all dogs had a soft tissue, contrast-enhancing mass with destruction of the nasal turbinates. Five of these dogs had masses that invaded into the frontal sinus and retro-orbital space (Fig. 1A,B). Tumours in three of these dogs showed intracranial extension on CT scan.

Figure 1. CT image showing a contrast-enhancing soft tissue mass with maxillary bone lysis and turbinate destruction (A). CT image showing enhancing soft tissue mass in the rostral right olfactory lobe of the brain (arrow) in addition to the right frontal sinus and right sphenoidal sinus (B).

All 13 dogs in this case series underwent a transnostral core biopsy procedure under general anaesthesia. Excessive haemorrhage was not documented in the medical records and none of the dogs required a blood transfusion or carotid artery ligation. Ten dogs were evaluated via rhinoscopy in which all cases revealed a fleshy, well-encapsulated, highly vascular soft tissue mass. Five tumours were evaluated cytologically via tumour impressions of biopsy material and all showed some features supportive of malignancy. The cells exhibited moderate to marked anisocytosis and anisokaryosis suggesting epithelial hyperplasia or dysplasia with secondary suppurative septic inflammation (Fig. 2A,B). For the tumours evaluated cytologically, an underlying carcinoma or round cell nasal tumour could not be ruled out.

Figure 2. Cytological evaluation of biopsy material impression smears showed some features supportive of malignancy. The cells exhibited moderate to marked anisocytosis and anisokaryosis suggesting epithelial hyperplasia or dysplasia with secondary suppurative septic inflammation.

All biopsy samples were submitted for routine histopathology. In each case, a diagnosis of vascular proliferation with secondary lymphosuppurative inflammation was made. The distinguishing histopathologic features for all dogs were as follows: a well-demarcated papilliferous mass with intact epithelium lining expansile, moderately cellular, proliferative fibrocollagenous stroma, admixed with regionally dependent, variably sized, shaped and sometimes inconspicuous vascular profiles. No mass-associated turbinate bone was identified. Spindle cell proliferation and vessel formation vastly outstripped inflammation as the principle players in the pathology. The morphologic hallmark of the inflammatory characteristics would include oedema, mild neutrophilic infiltrate (never necrotizing) and minimal lymphocytic infiltrate. No significant features of malignancy such as cellular atypia, anisocytosis or anisokaryosis were observed; rather samples appeared to be formed by a monotonous cell population effacing the normal tissues of the area. However, the lesions were aggressively destructive like a neoplastic lesion (Fig. 3A,B).

Figure 3. Photomicrograph of tissue sections showing a papillary growth pattern with intact epithelium lining an expansile fibrocollagenous stroma composed of well-differentiated spindle to stellate cells and random, variable sized and variably conspicuous vessels (A). There is evidence of exaggerated, scattered and variable vascular proliferation H&E bar = 200 mm (B). Note the mucosal epithelium and subepithelial mesenchyme showing marked vascular proliferation with associated oedema and fibrosis (arrows) H&E bar = 80 mm.

Six dogs in this series had a dorsal rhinotomy de-bulking procedure for tissue cytoreduction purposes. Of these dogs only two had a pre-operative CT scan delineating the nasal mass. For both dogs the CT scan revealed tumour extension with resulting lysis of the frontal sinus and one dog had evidence of tumour in the retro-orbital space. The remaining four dogs had evidence of a soft tissue opacity consistent with a nasal tumour that appeared localized to the rostral nasopharynx noted on skull radiographs. One dog with mass extension into the frontal sinus died postoperatively because of significant blood loss. Three dogs died from unrelated causes within 4 years after the surgery with no clinical evidence of recurrence, none of these dogs had a postmortem examination. One dog who had a pre-operative CT scan and had evidence of disease extending into the frontal sinus and retro-orbital space presented 2 years postsurgery with nasal obstruction, mucopurulent nasal discharge, facial swelling and exophthalmia of the previously affected nasal passage. The owners declined a second CT scan or second biopsy and the dog was subsequently euthanized 3 months later because of disease progression. One dog was still alive 9 months after surgery.

Seven dogs did not have surgery. Five of the seven dogs died or were euthanized as a result of this disease but in none of these cases was a necropsy performed. One dog was euthanized at the time of diagnosis and one died of an unknown cause 7 days after the biopsy procedure (no postmortem was obtained). One dog was euthanized 1 year after the initial diagnosis because of the development of neurologic disease. One dog was still alive 2 years after presentation despite evidence of intracranial extension of the tumour. In this case, corticosteroid administration was used to alleviate the clinical manifestations of the disease. This dog was euthanized because of progressive ataxia and other neurologic deficits that were not well defined in the medical record. Two dogs were lost to follow-up after diagnosis. One dog received radiation therapy to a total of 42 Gray (given over 12 days). This dog subsequently developed aspiration pneumonia and was euthanized 7 days after the end of therapy. An evaluation of the effectiveness of radiation therapy was not possible, although the dog did have an improvement in clinical signs during the course of therapy. Interestingly, a necropsy was obtained on this dog, which revealed a ruptured splenic mass that was a histologically benign haemangioma (reviewed by R. R. D.).

Discussion

This article is the first to describe a case series of a nasal angioproliferative tumour in dogs. This tumour is a histologically benign though locally aggressive vascular tumour that should be considered as a differential diagnosis for any dog with a destructive nasal tumour. All dogs in this study were presented with clinical signs similar to those with other malignant nasal tumours including nasal obstruction, recurrent epistaxis and the presence of a nasal mass. Histopathological evaluation confirmed a morphologically benign tumour consisting of random, variably sized, vascular profiles in an expansile fibrocollagenous stroma; however, radiographically each dog had a destructive mass-like lesion on either skull radiographs or CT scan.

Notably, a similar disease exists in humans and is referred to as juvenile nasopharyngeal angiofibroma.² It most commonly occurs in male adolescents although there are scattered reports of older patients, including females, in the human literature.^2–4 In humans, the masses appear to originate from the posterolateral wall of the nasal cavity in proximity to the superior aspect of the sphenopalatine foramen.^2,4 Like the dog lesion, it is a histologically benign mass composed of vascular tissue and fibrous stroma with coarse or fine collagen fibres and is locally aggressive with evidence of bone erosion which, in humans, typically occurs in the maxillary sinus or through the hard palate.^2,4,7 The behaviour and presentation of this tumour in humans is virtually identical to what we encountered for the 13 dogs described in this case series. Classically, human patients will present with signs consistent with a functional obstruction within the nasal cavity with unilateral episodic epistaxis and mucopurulent discharge as was seen in these 13 dogs.

The high incidence of this tumour in male adolescents is unusual and is suggestive of a hormonal influence on tumour development. However, studies evaluating an abnormality of the pituitary-sex hormone axis in these patients have revealed no association.^6,8,9 Also the previous work evaluating androgen receptor expression, in particular estrogen receptor (ER) expression, have had variable results.^9–11 However, a recent study utilizing immunohistochemical studies utilizing antibodies specific to ER-β revealed strong expression of ER-β and low expression of ER-α in all cases evaluated.^10,11 Results from this work suggest there may be a role for estrogen antagonists as a form of therapy for this tumour in humans.

Unlike in humans, our study population composed mostly of females (four total/three intact) than males (four total/one intact). However, it is notable that there are a high percentage of intact females (33%) in this population of dogs, which suggests there may be a role of estrogen exposure in the development of this tumour in dogs. Immunohistochemical analysis was not completed on any of the dogs evaluated in this case series but should be considered to characterize in greater detail this lesion with respect to the expression of estrogen (α and β) receptors.

This unusual tumour was first described as a disease entity as a case report in 1968 in which a Great Dane presented with a history of right-sided epiphora and pain when opening it's mouth. In this case, skull radiographs revealed a soft tissue opacity with adjacent loss of bone within the frontal sinus. A surgery was performed in which a large mass extending into the maxillary sinus was removed. The author of this case report noted that the associated bone was soft, moveable and partially eroded. Shortly after surgery, the dog was euthanized because of worsening neurologic signs.¹

While there are other forms of benign vascular proliferation described in the veterinary literature, such as angiomatosis, hamartoma and haemangioma, the histologic appearance of nasal angiofibroma differs from these entities in which the most profound areas of vasoproliferation are not uniform but scattered and variable within the overall mass lesion.^12–16 Also the vessels are typically thin profiles consisting only of endothelium with a minimal often-discontinuous smooth muscle layer, which lack elastic fibres. Additionally, this lesion is more of oedema, fibrosis and exaggerated reactive vascular proliferation than that observed in angiomatosis, hamartoma or benign haemangioma.

It is intriguing that in this case series, five of the masses that were evaluated cytologically exhibited criteria for malignancy despite confirmation of a benign abundance of vascular tissue histologically. It is likely a secondary inflammatory component to the tumour that triggered a hyperplastic response of associated tissues, which induced changes such as increased cytoplasmic basophilia, prominent nucleoli and mitotic figures. Importantly, this finding supports the need to submit a tissue sample for histologic evaluation to establish a definitive diagnosis rather than relying on cytologic evaluation alone.

In humans, surgical resection is the most commonly employed treatment.^4,7 Previous studies have shown that up to 92% of patients treated with surgery alone were disease-free at 1-year follow-up.⁴ Radiation therapy has also been utilized in conjunction with surgery or as a primary form of therapy for inoperable tumours with cure rates as high as 80%.^5,17 Indeed, based on the 6 of 13 dogs treated with a dorsal rhinotomy, it appears that surgery may be considered the treatment of choice for this uncommon tumour. While this procedure is generally well tolerated, it is important to note that one dog died postoperatively because of significant blood loss. Similarly, blood loss is one of the most common complications encountered in humans with the need for repeat blood transfusions after surgery, although this has been significantly reduced with pre-operative angiographic embolization.^2,4

Radiation therapy may also be considered as a form of therapy for dogs based on efficacy in humans with juvenile nasopharyngeal angiofibroma.^5,17 In particular, veterinary patients may benefit with adjuvant or neoadjuvant radiation therapy as our patients are often presented with advanced disease that may not be amenable to complete surgical resection.

Examples of spontaneous regression of this tumour, while rare, have been described in the human literature.^18,19 Notably, there were two dogs in this study in which no surgery or other treatment was pursued, with both dogs alive 2 years after presentation. It is not clear whether this represents spontaneous regression in these two dogs as no follow-up imaging was performed, but it is intriguing given the few reports in humans.

In summary, this is the first retrospective case series describing an unusual tumour that has a similar presentation and biologic behaviour as nasopharyngeal angiofibroma in humans. Unfortunately because of the small number of cases and the variable treatments used, it is not possible to comment on response to treatment(s), outcome or prognostic indicators. Nevertheless based on this case series, nasal angiofibroma should be considered a differential for dogs presenting with clinical signs consistent with a malignant nasal tumour.