Equine Sinonasal Tumours Does Reporting Ofsingle Cases and Case Series Still Advance The

Clinical Commentary

Equine sinonasal tumours – does reporting ofsingle cases and case series still advance the neglected fieldof equine clinical oncology?

P.M. Dixon

Division of Veterinary Clinical Studies, The Royal Dick School of Veterinary Studies and the Roslin Institute, The University of Edinburgh, Easter Bush Veterinary Campus, Midlothian, Scotland, EH25 9RG.

Corresponding author email:

Keywords: horse; equine sinus disease;sinonasal tumours

Introduction

Whilst great advances have been made in many areas of equine veterinary science,equine oncology has not attracted significant research or clinical interest to date. Clinical oncology has long been a major discipline in human medicine and more recently has developed into sucha speciality in small animal medicine.In stark contrast,this discipline currently lags a long way behind in equine medicine (Knottenbelt 2015). More specifically, head and neck oncology has become a very advanced speciality in human medicine since the 1970s (Maran and Wilson 1993), with its progress greatly aided by the availability of advanced three-dimensional imaging such as magnetic resonance imaging and computed tomography. Head and neck cancer treatmentin humans has been enhanced by the widespread availability of,and continuing developments in radiotherapy, and, less applicable for carcinomas which are the most common malignant tumours of the sinonasal region of chemotherapy.

Primary malignant tumors of the nasal cavity and paranasal sinuses are relatively rare and account for only 3% of all head andneck cancers in humans (Grau et al. 2001; Khademi, et al.2009) but equivalent information on their prevalence in horses is unavailable. Neoplasia of the sinonasal area comprises between 2% and 19% of all equine sinonasal disorders (Knottenbelt et al.2015) but benign growths such as sinus cysts or progressive ethmoid haematomata are approximately three times more common than neoplasms at this site(Head and Dixon, 1999; Tremaine and Dixon 2001; Dixon et al. 2012).

A large variety of different tumour types can arise in multiple anatomical sites within the sino-nasal regions, with epithelial tumours (especially squamous cell carcinomas and adenocarcinomas)the most commonly recorded cell types, both in humans (Grau et al.2001; Khademiet al.2009)and in horses (Head and Dixon, 1999; Dixon and Head 1999; Knottenbelt et al.2015). In horses, the maxillary sinuses are the most commonsite for tumour development(Head and Dixon 1999), although in man, the nasal cavity can be more commonly affected by neoplasia (Grau et al.2001: Katz et al. 2002). Interestingly the (small) human frontal sinuses are rarely (<1% of cases)involved in human sinonasal neoplasia (Maranet al.1993) but a recent equine study using computed tomography showed the conchofrontal sinuses to be the most commonly involved compartments (15/15 cases) (Cissell et al. 2012). This latter study also confirmed the frequent involvement of multiple sinonasal compartments with neoplasia and, surprisingly, this 3-dimensional imaging,usually could not determine the primary site of these sinonasal neoplasms, in contrast to historical studies with radiographic imaging, where a primary site was nearly always documented (Head and Dixon 1999).

There is predisposition for certain tumour types to develop at certain anatomical locations in horses, including for squamous cell carcinoma and unspecified carcinomas to tend to develop in the maxillary sinus, whilst adenocarcinomas tend to develop in the nasal and ethmoidal areas (Head and Dixon 1999).Dixon and Head (1999) found that just 20% of 28 horses with sinonasal neoplasia had metastases to drainage lymph nodes (although another 42% of affected horses had reactive lymphadenopathy of these lymph nodes)and no distant metastases were recorded in any horse. Nevertheless, these tumours present considerable therapeutic challenges (Dixon and Head 1999; Witte and Perkins 2013) as exemplified in two of the reports(Fjordbakk et al. 2015; Federiciet al. 2015) published in this edition of Equine Veterinary Education.

Head and Dixon (1999) noted that the absence of case reports at that time contributedto the lack of advances in equine sino-nasal oncology. However, since then multiple case reports and small case series of equine sino-nasal tumours have been publishedworldwide. These case reports have been recently systematically reviewed by Knottenbelt et al. (2015), who have authored the first comprehensive textbook on equine oncology. In view of these recently published case reports/series and especially the availability of a dedicated equine oncology textbook – are case reports/series still of any real scientific merit?

For certain case reports/series documenting unrecorded or poorly documented histological types of equine sinonasal tumours or those that havean accurate diagnosis and good follow-up informationif treated, the answer is a resounding yes! The four informative papers on equine sino-nasal tumours contained in this edition of Equine Veterinary Education certainly fulfil these criteria.

Four case reports

In the unique case series Maxillary odontogenic myxoma in young horses: 6 cases (2003–2011),Fjordbakk et al. (2015) describe 6 young horses that presented with maxillary swellings and other signs of sinus diseasethat were all caused by myxomas involving maxillary cheek teeth. Such odontogenic myxomas have been well described in younger humans but have not been reported in horses. In addition to the presence of infiltrative sinus tumours, all affected cheek teeth showed extensive changes includingmalformation or displacement, sometimes involving unerupted teeth or dental precursors. The authors pertinently note that these latter features may be diagnostically helpful in recognising future casesof this disorder if detected on imaging. Because of the rapid growth, and the extent of these odontogenic myxomas when diagnosed, effective treatment was not considered possible (as is often the situation withsinonasal tumours - as later discussed) and all cases were euthanased.The diagnosis of 6 cases of such a rare tumour over a short period in a single clinic, raises obvious questions of common genetic or environmental factors in the aetiopathogenesis of these tumours, that hopefully will be addressed in future studies.

The case report Peripheral nerve sheath tumour of the equine maxillary sinus by Federiciet al. (2015) describes a previously unrecorded tumour of the equine maxillary sinus, i.e. a peripheral nerve sheath tumour, that also developed in a young horse. This case originally presented with evidence of dental sinusitis on two separate occasions, with a total of three maxillary cheek teeth having apical infection. It appears possible to this commentator that such an unusually high number of apically infected cheek teeth (especially in Triadan positions 10 and 11) could in fact be related to the peripheral nerve sheath tumour; if the tumourdeveloped in the infraorbital nerve (which lies directly on the apices of young maxillary cheek teeth) it could have damaged their alveolar blood supply, leading to their death and subsequent infection.Regardless of the aetiopathogenesis of the cheek teeth infections, the prognosis for complete treatment of the maxillary sinus tumour in this young horse was poor, and it was euthanased. This case report has excellent three-dimensional images of the affected head, including CT and MRI along with comparative transverse post-mortem anatomical sections of the affected area. Consequently, it is a valuable addition to the literature on the unusual histological nature of this tumour and also from clinical and imaging educational viewpoints.

The case report Suture exostosis with concurrent nasal septum chondrosarcoma in a horse by Bonilla et al. (2015)describes a 15-year-old Hanoverian mare that presented with a 10-day history of maxillary and frontal area swellings and intermittent epistaxis. Computed tomography of the skull confirmed periostitis of multiple facial bone sutures, including of the nasofrontal, nasolacrimal,zygomaticomaxillary and lacrimomaxillary sutures, in addition to thickening of the nasal septum that contained hypo-attenuated regions. Histology of anasal septumbiopsy showed a chondrosarcoma, a tumour not previously reported at this site in horses. As the owner declined surgical treatment, the horse was treated with rest and anti-inflammatory agents. The facial swelling and epiphora had improved at 7 months later, but the longer term outlook for this case must still be guarded. This article has excellent CT images of the nasal septal tumour and the facial suture exostoses, and interestingly,it documents the specific sites of suturitis around the lacrimal bone, information that is usually lacking in such cases (Dixon 2014). Histological images of theperplexing disorder of facial bone suture periostitis are also presented. The authors aptlysuggest that the suture line exostoses may have developed due to an alteration of the biomechanics of the skull sutures causedby the nasal septal tumour.

The case reportby Lechartier et al. (2015) describes a gingival tumour that later spread to the nasal cavity. This case is also of interest because equine sinonasal squamous cell carcinomas can alsooriginate in the oral cavity (Head and Dixon 1999; Knottenbelt et al. 2015), although in some cases, it is impossible to determine whether they originated in the upper respiratory or alimentary tracts (Dixon and Head 1999). The tumour in this case was initially histologically classified as an aggressive fibrosarcoma, a tumour type that usually recursin horses unless completely excised. However, the non-recurrence of the tumour in this case, despite incomplete surgical resection, and histological re-evaluation of the resected tumour allowed a diagnosis of ossifying fibroma to be later made.

Treatment of sinonasal neoplasia

Whilethe outcome for all horses with maxillary sinus neoplasia,including the 6 cases of odontogenic myxoma byFjordbakk et al. (2015) and the case with a nerve sheath tumour (Federiciet al.2015) was disappointing,with all 7 horse being euthanased, this is perhaps not surprising.Sinus tumours developin air filled cavities and even in humans, are usually at an advanced stage before recognisable symptomsdevelop as a result of local infiltration of the tumour;usually nasal discharge due to secondary sinonasal infection or facial remodelling. Even when symptoms occur in humans, these patients arefrequently initially diagnosed as having an infectious or allergic sinonasal disorder, thus delaying the instigation of appropriate tumour therapy (Maran et al. 1993; Khademi et al. 2009). Likewise in horses, cases of sinonasal neoplasia are usually initially diagnosed as having a sinus infection and in a recent study, 75% of equine sinonasal tumour cases received antibiotic therapy prior to referral and clinical signs of sinus diseasewere present for a median of 70 daysbefore referral(Dixon et al.2011), with the tumours obviously being present for an unknown duration prior to that. Therefore, although early diagnosis of sinonasal neoplasia is important if they are to be effectively treated (Witte and Perkins 2011), because of the unique anatomical site that these tumour develop in, early diagnosisis usually impossible. In horses, the less common, benign fibro-osseous sinonasal tumours that are well defined, allow complete surgical excision and can be effectively treated even when longstanding (Dixon and Head 1999).

Most people under 45 years of age with head and neck tumours have a worse prognosisthan older patients as there may be an immunological dysfunction that allowed these tumour to develop (Maran et al. 2003). The fact that all 7 maxillary sinus tumours reported by Fjordbakk et al. (2015) and Federiciet al. (2015) were all in young horses may have meant that theprognosis was worse, even if treatment had been attempted. Other features that make therapy of manysinus neoplasmsdifficult in horses, include the absence of recognisable surgical boundaries between thesinonasaltumour and the normal sinonasal mucosa; the many and variable recesses within, and the vascular nature of the sinonasal region, and finally, the presence of multiple, immediately adjacent vital structures such as the calvarium, cranial nerves, orbit, and dental alveoli,that make radical resection of suspected tumourwith suitable surgical margins difficult or impossible. The limitations of surgical treatment are well recognised in humans, where many maxillary sinus neoplasms are treated by radiotherapy with or without surgical resection (Katz et al. 2002).Radiotherapyeither by teletherapy (from external radiation sources) or brachytherapy (from radiation sources implanted in the tumour) are available in a few equine centres, with the latter having the advantage for horsesof avoiding of multiple general anaesthetics, but the disadvantage of limited radius of therapy and practical and safety considerations with administering this therapy. With the increasing availability of equine teletherapy (including currently one clinic in UK and six clinics in USA), hopefully results from larger case series will be made available, allowing more informed treatment decisions on radiotherapy to be made in the future. However radiation therapy is not without risk, including causing bilateral irradiation of the optic nerves risking blindness(Katz et al. 2002;Khademi et al. 2009).

Intralesional chemotherapy with agents such as cisplatin combined with surgical debulking is an alternative treatment (Theon et al. 1997;Witte and Perkins, 2011), but evidence of efficacy of this multimodal therapy is currently lacking and such therapy in the ethmoid region risks causing barin damage (Maischberger et al. 2014) . Case reports on the response of equine sinonasal tumours to such multimodal therapy would be further welcome additions to the body of knowledge on equine oncology. It must be remembered that not all cases of equine sinonasal neoplasia are treatable. Because of the site and nature of some of these tumours in humans, even when resources can be almost limitless, Maran et al. (1993) note thatsome patients are untreatable and some that are potentially treatable are better off not treated. In retrospect, the management of the above 7 cases of maxillary neoplasia was appropriate using current standards.

Conclusion

Although single case reports and small case series represent the weakest level of scientific evidence (Eddy 1990), the current shortage of information relating to the uncommon tumours affecting the equine head, mean that valuable information can be gleaned from these four publications published in this edition of Equine Veterinary Education.

Conflict of Interest

The author declares no conflict of interest.

Acknowledgements

My thanks to Richard Reardon and Bruce McGorum for reviewing this manuscript.

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