Abstract
Objectives
Naturally occurring tumours in domestic cats are less common than in dogs and represent the leading cause of death among older animals. The main objective of this study was to analyse a large data set of histologically diagnosed tumours to highlight the most common World Health Organization (WHO) tumour histotypes, the effect of age and sex, and the International Classification of Diseases for Oncology (ICD-O) topographical site predilections of feline breed-specific tumours.
Methods
A total of 680 feline tumours diagnosed in European Shorthair cats by three veterinary diagnostic laboratories located in central Italy from 2013 to 2019 were collected. Data on age, sex and topography of lesions were recorded. Samples were morphologically and topographically coded using the WHO and the ICD-O-3 classification system.
Results
Skin and soft tissue neoplasms comprised 55.9% of all tumours, followed by mammary gland (11%), alimentary tract (7.9%), oral cavity and tongue (7.3%), nasal cavity and middle ear (6%), lymph node (3.1%), bone (1.8%) and liver/intrahepatic bile duct (1.3%) tumours. Squamous cell carcinoma (SCC), sarcoma, lymphoma and basal cell tumours were the most diagnosed neoplasms. Malignant tumours were 82.9% of the total and the topographical sites mainly involved were skin (C44), connective/subcutaneous/other soft tissues (C49), mammary gland (C50), small intestine (C17), nasal cavity and middle ear (C30), and gum (C03).
Conclusions and relevance
This study aimed to provide an in-depth evaluation of spontaneous feline tumours in the European Shorthair cat breed. Results identify SCC as the most commonly represented skin neoplasm. It is likely that the analysed feline population, living in southern latitudes, was more subject to prolonged exposure to ultraviolet light, explaining the discrepancy with previous studies in which SCC was less represented.
Introduction
Cancer is a frequent disease in domestic cats and yet few major studies are published regarding the occurrence of tumours in the feline population in different countries, including both the USA and Europe.1–5 These studies vary with respect to data source, sample numbers, size of the assessed geographical region and availability of population data (epidemiologic denominator). Cat breeds are dispersed around the world; thus, feline medicine clinicians should be aware of the breeds more commonly encountered in their regions. As reported in a retrospective study of the Swiss Feline Cancer Registry, the European Shorthair breed is frequently encountered in continental European countries. 4
In Italy, the registration of dogs is a legal requirement; however, the national feline registry was established only in the past decade and the enrolment of domestic cats is done only voluntarily. In addition to work regarding the occurrence of spontaneous tumours in dogs, based on the data of the animal tumour registry of Genoa, and a more recent survey of canine tumours in north-west Italy, the results from a canine and feline cancer registration project conducted in northern Italy have also been published.6–8
In central Italy no reliable demographic data are yet available relating to the feline population. However, the mandatory identification by microchip introduced for colony cats will soon be extended to owned cats, allowing the collection of more data. Meanwhile, the collection of feline neoplastic cases can provide relevant information on the occurrence of tumours in this animal species for the creation of specific databases.
The purpose of our study is to describe a large data set of histologically diagnosed tumours in European Shorthair cats to highlight the most common World Health Organization (WHO) tumour histotypes, the effect of age and sex, and the International Classification of Diseases for Oncology (ICD-O) topographical site predilections of feline breed-specific tumours.
Materials and methods
Data pertaining to cancer diagnosed in European Shorthair cats living in central Italy were provided by three veterinary diagnostic laboratories from February 2013 to May 2019. Case records of 680 neoplasms diagnosed in 670 cats were collected. Information on sex (female vs male), date of birth, date of tumour removal and histopathological diagnosis were obtained. A representative portion of tissue samples was fixed in 10% neutral buffered formalin and routinely processed for histopathology. Sections 4 µm in thickness were stained with haematoxylin and eosin and observed with an Eclipse Ci-L microscope (Nikon). When deemed necessary, other histochemical stains were applied (eg, toluidine blue for suspected mast cell tumour). Tumours were classified according to the histological classification system proposed by the WHO and the anatomical locations were coded according to the ICD-O-3 system, except for mammary tumours.9,10 Moreover, as soft tissue sarcomas are a very complex and heterogeneous group of tumours with histotypes that can be difficult to differentiate based on morphology alone (eg, peripheral nerve sheath tumours, perivascular tumours, poorly differentiated sarcomas), we recorded them as sarcomas not otherwise specified (NOS).
Data were analysed using the general linear model procedure of SAS (2001).
Results
This retrospective study consisted of 680 spontaneous feline neoplasms, including multiple records for the same subject in the case of multiple tumours of either different or identical histotypes. Multiple tumours with different histotypes were diagnosed in seven cats, while the same neoplasm showed multiple localisations in three cats. More specifically, different histotypes were mainly observed in neutered females aged 7–15 years: a basal cell carcinoma and a lipoma in a 7-year-old queen, a squamous cell carcinoma (SCC) and a basal cell carcinoma (BCC) in a 9-year-old queen, an SCC and a sarcoma NOS in a 9-year-old queen; and a mammary fibroadenoma and a mammary simple carcinoma in a 15-year-old queen. In addition, an intact female, aged 13 years, had a mammary carcinoma and a cutaneous sarcoma. Among the male cats, one cat (11 years of age) had an SCC and a ceruminous gland adenoma, and a second cat (13 years old) a lipoma and a cutaneous sarcoma. Tumours of the same histotype in multiple sites were encountered in two neutered females (8 years old) and were diagnosed as a bilateral SCC of the ears and a bilateral carcinoma NOS of the ears. Additionally, a single intact female (10 years old) presented two mammary masses, both diagnosed as simple carcinoma.
Skin and soft tissues were the most affected anatomical sites, being involved in 55.7% of all tumour cases. The other most common tumour sites were mammary glands (11%), the intestinal tract (8%), the oral cavity and tongue (7.9%), the nasal cavity and middle ear (6%), and lymph nodes (3.1%) (Figure 1).
Benign and malignant tumour distribution in European Shorthair cats according to topographical site (International Classification of Diseases for Oncology-3)
The mean age of cats with benign tumours was 9.8 ± 3.8 years, while for malignant tumours it was 9.5 ± 3.3 years.
Skin tumours accounted for 35.1% of the analysed samples. Of these, 68.2% were malignant. The most frequently diagnosed benign tumours were trichoblastoma (15.8%) and apocrine gland adenoma (5.4%), while SCC (28.8%), mast cell tumour (18.8%) and apocrine gland adenocarcinoma (10.8%) represented the most common malignancies. With respect to sex, female cats accounted for 62.3% of all skin tumours. The skin of lips (C44.0), eyelids (C44.1), external ears (C44.2), scalp and neck (C44.4), trunk (C44.5), upper limb and shoulder (C44.6), and lower limb and hip (C44.7) were the anatomical sites involved in both groups.
Soft tissue tumours represented 20.6% of all neoplasms and 90.7% were malignant. Benign tumours were lipoma (7.1%) and fibroma (2.1%), while malignant histotypes were sarcomas NOS (56.4%), fibrosarcoma (25%) and haemangiosarcoma (8.6%). Regarding fibrosarcoma, both feline injection site and non-injection site sarcomas were identified. As observed for skin neoplasms, female cats showed the highest percentage of tumours (53.6%). Regarding benign tumours, the most affected anatomical sites were the connective/subcutaneous/other soft tissues of the head, face and neck (C49.0), lower limb and hip (C49.2), and thorax (C49.3). Regarding malignant tumours, the head, face and neck (C49.0), upper limb and shoulder (C49.1), lower limb and hip (C49.2), abdomen (C49.4), and trunk (C49.6) were the most affected sites.
Mammary gland tumours represented 11% of all neoplasms in both males and females, and 97.3% were malignant. In females the mean age was 10.8 ± 3.8 years, while the only male with a simple mammary carcinoma was a 20-year-old cat. Malignant tumours accounted for 97.3% of tumours and were all of a simple carcinoma histotype. Topography of mammary tumours according to the ICD-O-3 system definitions was not possible because the topographical codes used for humans are not appropriate for cats or dogs owing to anatomical differences.Tumours of the alimentary tract (from the oesophagus to the rectum) accounted for 7.9% of all tumours. Of these, 96.3% were malignant and the mean ± SD age of cats was 10 ± 4.2 years. The most commonly represented tumours were lymphoma (55.5%), followed by adenocarcinoma (22.2%) and sarcoma (9.2%). Female cats showed the highest percentage of tumours (51.8%). Regarding the topographical code of malignant tumours, oesophagus (C15), stomach (C16) and small intestine (C17) were the most affected sites.
Tumours of the oral cavity and tongue represented 7.3% of all tumours and 78% were malignant. SCC (46%) and odontogenic fibroma (20%) were the most common tumours of the oral cavity and tongue diagnosed in this study. Female and male cats showed the same frequency of tumours (50%). The upper gum (C03.0) was the main anatomical site implicated.
Nasal cavity and middle ear tumours represented 6% of all neoplasms and 85.4% were malignant. The most common malignant histotypes were ceruminous gland adenocarcinoma (43.9%) and lymphoma (36.6%). Females and males showed a comparable tumour frequency (50%). The nasal cavity (C30.0) and the middle ear (C30.1) were equally involved.
Tumours of the lymph nodes accounted for 3.1% of the analysed samples. Lymphoma (90.5%) was the most frequently diagnosed neoplasm, followed by thyroid carcinoma metastatic to the regional lymph nodes (9.5%). In these last cases primary tumours were not sent for histopathology. Males were the most represented sex (61.9%). In most of the cases the site of the affected lymph nodes was not specified. The intra-abdominal lymph nodes (C77.2) were involved in 36.8% of cases.
Bone tumours accounted for 1.8% of all feline tumours and all were malignant. Osteosarcoma (50%) and sarcoma NOS (33.3%) were most commonly diagnosed. Male and female cats showed the same frequency (50%). Long (C40.0) and short bones (C41.0) were equally involved.
Hepatic and intrahepatic bile duct tumours represented 1.3% of all neoplasms, all were malignant and 66.7% of cases involved males. The most common tumours were hepatocellular carcinoma (44.4%) and myelolipoma (22.2%). Tumour of the bile ducts comprised SCC (11.1%) and cholangiocellular carcinoma (11.1%). The most common were primary hepatic tumours (C22.0), followed by bile duct (C22.1) tumours.
Other (miscellaneous) tumours accounted for 5.4% of the analysed samples. Of these, 83.8% were malignant; 44.7% were adenocarcinoma/carcinoma, 31.6% sarcoma and 21% lymphoma. The most common sites were bladder (C67), eyes (C69), lung (C34) and spleen (C42). Females showed a tumour frequency of 54%.
Data were also used to assign an age–sex distribution, as summarised in Table 1.
Proportion of tumours by sites (International Classification of Diseases for Oncology-3) and age–sex distribution
WHO = World Health Organization; F = female; M = male; NOS = not otherwise specified; NA = not applicable
Adenocarcinoma/carcinomas (excluding SCC), lymphoma, mast cell tumour, sarcoma and SCC were the most frequent histotypes diagnosed in this study. A representation of differences regarding age of onset of the most frequent histotypes related to sex is presented in Figure 2. Carcinomas, sarcomas and SCC showed no differences. For both lymphomas and mastocytomas, age of onset in males was lower than in females (P = 0.0214 and P = 0.0256, respectively).
Differences in age (years) of onset of the most frequent histotypes according to sex. F = female; M = male
Discussion
This study aims to provide information on the occurrence of feline spontaneous tumours, and a more in-depth estimation of such neoplasms in the European Shorthair cat breed. As reported in the scientific literature, skin and soft tissue and mammary tumours were the most frequently diagnosed.1,2,4,7
Among the skin neoplasms the most commonly seen benign tumours were trichoblastoma and apocrine gland adenoma, generally included in the basal cell tumour group. This is comparable to the data reported in previous studies.1,5,11,12 SCC was the main tumour histotype diagnosed in this study, while it was only the second most common in an earlier UK-based study, and the third most common in American, Swiss and South African studies, as well as in the most recent UK-based study, the last reporting only skin-related tumours.1,2,4,5,13 Moreover, in our study this tumour type was also the most common feline cancer observed in the oral cavity (46%), usually affecting older cats, and with 54.5% of cases originating from gingival mucosa. According to the recent literature, 10% of all tumours diagnosed in cats are oral tumours and SCC is the most common; gingiva, the sublingual area and tongue were reported as the most commonly affected sites.14,15
Comparing our data with data available in the literature, the percentage of mast cell tumours that we detected appeared to be higher than reported in the Swiss study and the most recent UK-based study, but more similar to the study conducted in the USA.1,2,4 The mean age of occurrence was significantly higher in females compared with males (P = 0.0256).
Soft tissue sarcomas, a general term that refers to a group of tumours of mesenchymal origin (eg, connective tissue, fat, blood vessels, lymph vessels, etc.), were the primary soft tissue tumours observed in this study. Focusing on the main represented histotypes, sarcoma NOS, fibrosarcoma and haemangiosarcoma appeared in our cases. These data are similar to those of the Swiss study and the most recent UK-based study.1,2
Lymphoma occurred most frequently with the involvement of the gastrointestinal tract (intestine and stomach), lymph nodes and nasal cavity/middle ear (4.7%, 2.8% and 2.6%, respectively, of all neoplasms). As for mast cell tumours, the mean age of occurrence was significantly higher in females compared with males (P = 0.0214).
A total of 97.3% of mammary gland tumours were malignant and affected older females. Our results are in line with previously published studies.16–18 Interestingly, one malignant tumour occurred in a 20-year-old neutered male cat. Published research data suggest that this type of tumour is extremely rare in males (with reported cases aged 3.5–19 years) and represents approximately 1–5% of diagnosed mammary carcinomas in the feline species. 19 It has to be considered that to follow the comparative approach adopted in the present retrospective study and allow its application to all the tumours recorded, it is necessary to create a specific ICD-O topographic subdivision to compare data recorded in both humans and animals.
The global percentage of neoplasms affecting the alimentary tract is comparable to that reported in the Swiss study, albeit the percentage of malignant tumours is lower in the Swiss study. These tumours preferentially involved the small intestine and the most common malignant tumours were lymphoma and adenocarcinoma, whereas the Swiss study indicated adenocarcinomas as being the most common neoplastic category; however, these data are influenced by the fact that neoplasms of the liver and pancreas are grouped with alimentary tract tumours. 1
In previous studies, the neoplasms of the oral cavity were grouped with those of the pharynx; for instance, in the Swiss study neoplasms at these sites accounted for 5.3% of cases. 1 In our study, tumours were topographically coded using the ICD-O-3 system. Tumours of the oral cavity and tongue and those of the nasal cavity and middle ear constitute 7.3% and 6%, respectively, of all diagnosed cancers. So even when excluding tumours of the nasal cavity from the count (considered as a part of the respiratory system in previous studies), our study reports a slightly higher occurrence of oral and pharyngeal neoplasms, with SCC the most frequent cancer of the oral cavity and tongue, and ceruminous gland adenocarcinoma as the most frequent tumour of the ear.4,6–8
Conclusions
A large collection of tumours diagnosed in European Shorthair cats living in central Italy was reported. Our study identified SCC as the most commonly represented feline skin neoplasm. Given the number of cases collected in this preliminary retrospective survey, we can only advance a hypothesis regarding this higher percentage. We can speculate that the southern latitude distribution of the analysed population results in more subjects experiencing prolonged exposure to ultraviolet (UV) light, explaining the discrepancy with previous Italian and European studies in which SCC was less commonly represented.
Global Solar Atlas 2019 data (https://globalsolaratlas.info/map) report a global increase in UV radiation, more evident in the Mediterranean area than in continental Europe, thus providing a possible explanation for the increase in cutaneous tumours in both animals, as presented in this retrospective study, and humans. 20
The scientific literature indicates that cutaneous SCCs could also be associated with a Felis catus papillomavirus (PV)-2 infection, acting as a primary cause, or as a cofactor potentiating the effect of other carcinogens such as UV light. Among the cases collected in our study, there were only two types of lesions that could be associated with PV infection: cutaneous SCC and BCC. Immunohistochemistry or PCR investigations were not carried out to classify these carcinomas as PV-positive or PV-negative lesions.21–23 However, this evaluation could be conducted as a desirable additional step in future retrospective or prospective studies.
Further endeavour is required to increase the accuracy of feline epidemiological studies by, for example, extending the population size by including owned cats identified by microchip. Also to initiate a feline cancer registry in Italy through an effective collaboration between public and private diagnostic laboratories for the collection of cases with complete patient and history data.
Finally, a feline cancer registration is not common worldwide and it would be desirable to promote comparable studies based on international and standardised classifications (WHO, ICD-O).
Footnotes
Acknowledgements
We would like to thank all the veterinary practitioners for giving us the opportunity to start collecting cancer cases and contributing to the health observatory as an adjunct to the One Health concept.
Conflict of interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
This research was performed as part of a research project supported by the Marche region (PAM072019).
Ethical approval
This work involved the use of non-experimental animals only (including owned or unowned animals and data from prospective or retrospective studies). Established internationally recognised high standards (‘best practice’) of individual veterinary clinical patient care were followed. Ethical approval from a committee was therefore not necessarily required.
Informed consent
Informed consent (either verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (either experimental or non-experimental animals) for the procedure(s) undertaken (either prospective or retrospective studies). No animals or humans are identifiable within this publication, and therefore additional informed consent for publication was not required.
