Canine colorectal proliferative lesions: A retrospective study of 217 cases

Canine colorectal proliferative lesions: A retrospective study of 217 cases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Canine colorectal proliferative lesions: A retrospective study of 217 cases Joanna Fiedorowicz, Katarzyna Paździor - Czapula, Iwona Otrocka - Domagała This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4510927/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Mar, 2025 Read the published version in BMC Veterinary Research → Version 1 posted 4 You are reading this latest preprint version Abstract Colorectal proliferative lesions are not common in dogs. However, recently we have observed an increase in the number of diagnosed cases and a lack of publications providing current epidemiological data on changes of the large intestine in dogs. The aim of this study was a retrospective analysis of 217 canine colorectal non-neoplastic and neoplastic tumours, and assessment of the frequency of occurrence of individual lesions and whether there is a risk of their occurrence depending on age, sex, or dogs breed. Histopathological diagnosis was based on routine staining (hematoxylin and eosin) and appropriate immunohistochemistry when was necessary for definitive diagnosis. Half of the cases (52.5%) were malignant tumours with male predisposition and a significant predominance of adenocarcinoma (42.9%). In the group of malignant non-epithelial lesions, lymphoma and sarcomas predominated (4.1% and 4.1%, respectively) followed by three cases of plasmacytoma. Benign neoplastic tumours constituted almost one-third of all cases (26.7%) with obvious dominance of adenoma (24.0%) and young male predisposition. Benign mesenchymal tumours were represented only by leiomyoma (2.8%). The non-neoplastic lesions were represented by a heterogeneous group of polyps (20.3%) with a slight advantage of hyperplastic type (9.7%) and less numerous inflammatory, fibroblastic, lymphoid, and hamartomatous polyps. The one case of ganglioneuromatosis in hamartomatous polyp was diagnosed. Non-neoplastic lesions were frequently diagnosed in female. We have observed for the first time that French Bulldogs are susceptible to developing colorectal proliferative lesions, including adenomas, adenocarcinomas and polyps. The results of our research provided new data expanding knowledge about the epidemiology of colorectal neoplastic and non-neoplastic proliferative lesion in dogs. We were also able to determine sex- and breed-specific risk factors associated with the occurrence of adenocarcinomas, adenomas, and non-neoplastic polyps. Our results are alarming and imply the necessity of implement routine colonoscopy in dogs in early detection of lesion and prevention of the development and progression of malignant tumours. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Over the last several decades, an increase in the frequency of diagnosed colorectal neoplasms and non-neoplastic polyps has been observed in humans (Keum and Giovannucci 2019). It has been proven that this increase is related to dietary habits, an inactive lifestyle, processed food and environmental pollution. Companion animals, especially dogs, living in the same environment as man are prone to the same civilization diseases, which is reflected in the increase in the number of tumoral colorectal diseases (Herstad et al. 2021). In addition to environmental risk factors, genetic and hereditary predispositions, as well as age, sex and breed are also under consideration in the development of intestinal proliferative lesions in dogs (van der Gaag 1988, Méric et al. 2023). Breed related development of colorectal inflammatory polyps with risk of progression to adenoma and adenocarcinoma has been shown in middle-aged Miniature Dachshunds in Japan (Uchida et al. 2016; Saito et al. 2018). In Jack Russel Terriers hereditary gastrointestinal polyposis was confirmed with gastric and colorectal distribution. While hyperplastic polyps, adenomas (tubular, tubulopapillary, papillary) and adenocarcinomas (tubular, tubulopapillary, papillary) were observed in the stomach in this breed, only papillary adenocarcinomas were observed in the colon and rectum (Yoshizaki et al. 2021). According to the current classification of tumours in domestic animals, canine intestinal neoplasms are divided into tumours of epithelial and mesenchymal origin. Epithelial tumours include adenomas, adenocarcinomas and neuroendocrine carcinomas, while mesenchymal tumours include lymphomas, plasmacytomas, mast cell tumours, non-angiogenic, non-lymphogenic intestinal mesenchymal tumours (NIMTs), gastrointestinal stromal tumours (GISTs), leiomyomas, leiomyosarcomas, intestinal neurogenic tumours, fibrosarcomas, myxosarcomas, extraskeletal osteosarcomas and angiogenic tumours. Non-neoplastic proliferative lesions in dogs most frequently develop in the rectum as hyperplastic polyps, caused by abnormal mucosal maturation, inflammatory polyps, caused by chronic inflammation, and multiple polypoid hamartomas (Munday et al. 2017). The vast majority of colorectal malignant neoplasms in dogs are adenocarcinomas, followed by lymphomas, leiomyosarcomas, haemagiosarcomas and plasmacytomas (Munday et al. 2017, Saito et al. 2020, Herstad et al. 2021, Tanaka et al. 2021). The most frequently diagnosed benign tumours in this location are adenomas (adenomatous polyps), leiomyomas and fibromas (Adamovich-Rippe et al. 2017, Saito et al. 2020, Herstad et al. 2021). Both malignant and benign neoplasms, especially of epithelial origin, may grow as single or multiple polypoid lesions of various diameters, variably involving the mucosa, and in the case of malignancies, also the submucosa and muscularis of the intestine. Therefore, on the basis of endoscopic examination, these lesions are generally referred to as colorectal polyps. Meanwhile, histopathologically, intestinal polyps are defined as non-neoplastic sessile or pedunculated exophytic growths (Uchida et al. 2016). According to the current histopathological classification, non-neoplastic colorectal polyps in humans are classified as: hyperplastic (metaplastic), hamartomatous (Peutz-Jeghers-type), juvenile, inflammatory and lymphoid (Hamilton and Aaltonen 2000, Colucci et al. 2003), and the similar classification is used in animals. In humans, the most common are hyperplastic polyps, which have a low malignant potential (Shussman and Wexner 2014). Juvenile, inflammatory, and lymphoid polyps have a low risk of neoplastic transformation, while in the case of Peutz-Jeghers-type polyps, the probability of malignant transformation is high (Chen et al. 2017, Ashktorab et al. 2020, Dong et al. 2022, Jelsig et al. 2023). In dogs, hyperplastic and inflammatory polyps are the most common. Numerous studies have shown that, as in humans, the growth of inflammatory polyps in dogs is stimulated by chronic inflammatory bowel disease, which is diagnosed with the increased frequency in animals (Ashktorab et al. 2020, Ohta et al. 2020). The aim of this retrospective study was to analyze the incidence of neoplastic and non-neoplastic colorectal proliferative lesions in dogs, depending on age, sex and breed. The results of our research will provide new data expanding knowledge about the epidemiology of colorectal neoplasms and non-neoplastic polyps in dogs and may also help to determine the possible risk factors for their development. Materials and Methods This study included 217 samples of canine colorectal proliferative lesions sent for histopathological examination during 2015–2022. All tissue samples were obtained during surgery or colonoscopy, fixed in 10% buffered formalin, processed routinely, embedded in paraffin, cut into 3 µm sections and stained with Mayer's haematoxylin and eosin (HE). When the diagnosis was not obtained on routine HE staining, additional immunohistochemistry was applied for definitive diagnosis (Table.1). Immunohistochemical examination was performed manually, and preceded by heat-induced antigen retrieval in Tris-EDTA buffer (pH 9.0) using PT-Link (Dako, Glostrup, Denmark). Primary antibodies included: CD3 (polyclonal rabbit anti-human, dilution 1:100, Dako), CD20 (monoclonal rabbit anti-human, clone SP32, dilution 1:100, Abcam, Cambridge, UK), CD79a (monoclonal mouse anti-human, clone HM57, dilution 1:100, Bio-Rad Laboratories Inc., Hercules, CA), vimentin (monoclonal mouse anti-porcine, clone V9, dilution 1:100, Dako), desmin (monoclonal mouse anti-human, clone D33, dilution 1:50, Dako), c-Kit (CD117; polyclonal rabbit anti-human, dilution 1:400, Dako), α-smooth-muscle-actin (α-SMA; monoclonal mouse anti-human, clone 1A4, dilution 1:500, Dako), neuron-specific enolase (NSE; monoclonal mouse anti-human, clone BBS/NC/Vi-H14, dilution 1:100, Dako), MUM-1 (monoclonal mouse anti-human, clone MUM1p, dilution 1:50, Dako), HLA-DR α-chain (MHC II; monoclonal mouse anti-human,, clone TAL.1B5, dilution 1:20, Dako), S-100 (polyclonal rabbit, anti-bovine, dilution 1:50, Dako), Pan Keratin (monoclonal mouse anti-human, clone AE1/AE3/PCK26, ready-to-use, Ventana, Tucson, AZ), mast cell tryptase (monoclonal mouse anti-human, clone AA1, dilution 1:200, Dako) DOG1 (monoclonal rabbit recombinant, Anti-TMEM16A, clone SP31, dilution 1:100, Abcam). Visualization system was based on the immunoperoxidase method (ImmPRESS HRP Horse Anti-Rabbit IgG Polymer Reagent – for primary rabbit antibodies, Vector, Newark, CA and ImmPRESS HRP Horse Anti-Mouse IgG Polymer Reagent for primary mouse antibodies, Vector) with 3.3-diaminobenzidine (DAB) as the substrate (ImmPACT DAB, SK-4105, Vector). The slides were counterstained with Mayer’s hematoxylin. Positive and negative control slides were processed together with the evaluated sections. Each case was evaluated and classified by three veterinary pathologists and authors (IOD, KPC, JF). Table 1 Antibody panels used in immunohistochemistry for selected tumours. Tumour Number of cases Antibodies B-cell lymphoma T-cell lymphoma Fibrosarcoma Leiomyosarcoma Gastrointestinal stromal tumor (GIST) Poorly diagnosed non-angiogenic, non - lymphogenic intestinal mesenchymal tumours (NIMTs) 6 3 4 2 2 1 CD3-, CD20+, CD79a+ CD3+, CD20-, CD79a- vimentin+, desmin-, S-100 -, c-Kit-, α-SMA- vimentin+, α-SMA+, desmin -, S-100-, c-Kit-, DOG1 - DOG1+, c-Kit +, vimentin+, α-SMA+, desmin-, S-100- vimentin+, S100+, NSE+, CD3-, CD20-, CD79a-, MHC II-, MUM1-, desmin-, c-Kit-, Pan-keratin-, α-SMA- Results Among collected cases of proliferative colorectal lesions in dogs, 120 cases were diagnosed in males (55.3%) and 97 cases in females (44.7%). The majority of proliferative lesions constituted malignant tumours (52.5%, 114/217), with the most frequent adenocarcinomas (42.9%, 93/217). Adenocarcinomas were further subtyped into papillary (72 cases, Fig. 1 ), mixed (12 cases), tubular (7 cases), mucinous (one case) and adenosquamous carcinoma (one case). Adenocarcinomas occurred with a slightly higher incidence in males (55/93) than in females (38/93) with an age ranging from 2 to 16 years (mean age: 7.9 years). The most common breeds diagnosed with adenocarcinoma were French Bulldogs (10/67), Yorkshire Terriers (7/67) and crossbreeds (7/67). Unfortunately, these data were incomplete in several cases: 7 regarding the age and 26 regarding the breed. Malignant tumours of mesenchymal origin were far less common than adenocarcinomas, and constituted 9.7% (21/217) of cases, including 9 cases of sarcomas, 9 cases of lymphomas and 3 cases of plasmacytomas. In all sarcomas and lymphomas, the final diagnosis was supported by immunohistochemistry. Sarcomas were represented by 4 cases of fibrosarcoma, 2 cases of leiomyosarcoma, 2 cases of GIST (Fig. 2 ) and one case of non-GIST, non-smooth muscle NIMT. In the group of sarcomas, sex distribution was almost equal, with an age ranging from 6 to 16 years (mean age: 10.8y.) Fibrosarcomas were confirmed in 3 females and one male, with a mean age of 10.3 years. Tumour cells showed cytoplasmic expression of vimentin and were negative to desmin, α-SMA, S-100 and c-Kit. Leiomyosarcomas were diagnosed in one female (14y.) and one male (16 y.). Tumour cells showed cytoplasmic expression of vimentin and α-SMA and were negative to desmin, S-100 and c-Kit. GISTs were confirmed in one female (9y.) and one male (10y.) Tumour cells expressed DOG1, c-Kit, α-SMA and vimentin, and were negative to desmin and S-100. Non-GIST, non-smooth muscle NIMT was diagnosed a 6-year-old male dog. Tumour cells expressed vimentin, S-100 and NSE and were negative to CD3, CD20, CD79a, MHC II, MUM1, desmin, c-Kit, cytokeratins and α-SMA. In the group of sarcomas, no association with breed was identified. Lymphomas included 6 cases of B-cell lymphoma (5 centroblastic and one centroblastic polymorphic, Fig. 3 ) and 3 cases of T-cell lymphoma (2 cases of large T-cell lymphoma and one case of lymphoblastic T-cell lymphoma). Lymphomas were diagnosed in 7 males and 2 females, with an age ranging from 3 to 12 years (mean age: 6.9y.). In B-cell lymphomas, tumour cells showed cytoplasmic expression of CD20 and CD79a and were negative to CD3. All of them were diagnosed in males with a mean age of 5.8 years. In T-cell lymphomas, tumour cells showed cytoplasmic expression of CD3 and were negative to CD20 and CD79a. This group was represented by 2 females and one male with a mean age of 9 years. In lymphomas, no breed predisposition was observed. Plasmacytomas were diagnosed in two females and one male, with an age ranging from 11 to 12 years (mean age: 11.7y.). Benign tumours constituted 26.7% (58/217) of the total cases. The most frequently diagnosed benign tumour was adenoma (52/217, Fig. 4 ), observed more often in males (32/52) than in females (20/52). The age of the affected animals ranged from 1 to 15 years (mean age: 5.5y.), and the most frequently affected breed was the French Bulldog (14/37), followed by crossbreeds (5/37) and West Highland White Terriers (4/37). Unfortunately, these data were incomplete in several cases: 5 regarding the age and 15 regarding the breed. Benign mesenchymal tumours were less numerous than adenomas and were represented by leiomyomas (6/217), observed in five females and one male, with an age ranging from 7 to 13 years a mean age of 10 years. Non-neoplastic colorectal proliferative lesions constituted 21.1% (45/217) of the total cases. In this heterogeneous group of colorectal polyps, hyperplastic polyps were the most numerous (21/217, Fig. 5 ), followed by inflammatory polyps (12/217), fibroblastic polyps (5/217), lymphoid polyps (4/217) and two hamartomatous polyps. Hyperplastic polyps were observed more often in males ( 13 ) than in females ( 7 ), with an age ranging from 2 to 14 years mean age of 6.3 years, and more often in French Bulldogs (5 cases), Yorkshire Terriers (2 cases) and crossbreeds (2 cases). Inflammatory polyps were observed more often in females ( 9 ) than in males ( 3 ), with an age ranging from 2.8 to 10 years and mean age of 7.8 years. No breed predisposition was identified. Fibroblastic polyps were diagnosed only in females, with an age ranging from 1 to 13 years and mean age of 7.5 years, without any breed predisposition. Sex distribution was equal in lymphoid polyps, with an age ranging from 3 to 14 years and mean age of 9.3 years, no breed predisposition was observed. One case of hamartomatous polyp was diagnosed in a 7-year-old female French Bulldog and the second one in a 4-year-old male Jack Russell Terrier; the latter was accompanied by ganglioneuromatosis (Fig. 6 ). The breeds most frequently affected by selected tumours and tumour-like lesions were presented in Table 2 . Detailed information, including number of cases, sex distribution and mean age were collected in Table 3 . Table 3. Frequency, sex distribution and mean age of individual lesions Discussion Neoplastic and non-neoplastic lesions of the gastrointestinal tract, especially of the large intestine, are not commonly diagnosed in dogs. Meanwhile, in humans, due to the widespread use of preventative screening tests, such as colonoscopy, these diseases can be diagnosed at an early stage and successfully treated. Hopefully, the development and improvement of diagnostic procedures in veterinary medicine, together with the increase in the longevity of dogs and the awareness of owners, will contribute to an increase in detection of colorectal lesions in dogs as well. Hence, it is very important to conduct retrospective studies assessing the frequency of occurrence and precise characteristics of colorectal proliferative neoplastic and non-neoplastic lesions in dogs, especially since the number of such studies in the available literature is limited. In this retrospective study, conducted on the large number of histologic samples, we have demonstrated that half of the proliferative colorectal lesions in dogs were diagnosed as malignant tumors, mainly of epithelial origin. Not surprisingly, adenocarcinoma was the most frequently diagnosed lesion, which is in line with the previous study (Patnaik et al. 1977). We observed that colorectal adenocarcinomas were mostly of the papillary type, in contrast to results indicating that the tubular type was the most common (Aresu et al. 2010, Saito et al. 2020). However, we diagnosed also single cases of uncommon histological types, such as mucinous adenocarcinoma and adenosquamous carcinoma. We also confirmed that males were predisposed to colorectal adenocarcinoma, which is consistent with most previous reports (Morello et al.2008; Uzal et al.2015; Spużak et al. 2017), although in one study females were more frequently affected (Frgelecová et al. 2013). The mean age of animals affected by adenocarcinoma was 7.9 years; similar finding was observed previously (Frgelecová et al. 2013; Spużak et al. 2017). Interestingly, we observed a breed predilection to colorectal adenocarcinoma in French Bulldogs and Yorkshire Terriers, which has never been observed before. In contrary, previous studies revealed that German Shepherds, Collies, Jack Russell Terriers, and Miniature Dachshunds are predisposed to this tumor (Ohmi et al.2021; Saito et al. 2022). In the present study, the second most common colorectal lesion was benign epithelial tumour - adenoma. In dogs, large intestine (and more precisely – distal rectum) is the most common site for the development of this type of lesion (Uzal et al.2017). We observed a slightly higher incidence of large intestine adenoma in males, which is consistent with another survey (Uzal et al.2017). In previous reports the mean age of affected animals was 7–8 years (Saito et al. 2020; Reineking et al. 2022). However, in our study adenomas occurred in younger dogs, with the mean age 5.5 years, and 9 cases were diagnosed in very young dogs (1–2 years old). As with colorectal adenocarcinomas, we observed a significant breed predilection in French Bulldogs for colorectal adenomas. Although the previous study suggested that Miniature Dachshunds are prone to developing colorectal adenomas (Saito et al. 2020), we did not observe any colorectal adenoma in this breed. Colorectal polyps were the third most common lesion found in the present study with a predominance of hyperplastic polyps, followed by inflammatory polyps, fibroblastic polyps, lymphoid polyps and hamartomatous polyps. Fibroblastic polyp described in humans has been recently reclassified as perineurioma, due to characteristic immunohistochemical features (van Wyk et al. 2018) and has no equivalent in veterinary medicine. Colorectal polyps were observed more commonly in females, in contrary to the previous studies, which stated than colorectal polyps were more common in males (Ohmi et al. 2012; Méric et al.2023) or sex distribution was almost equal (Seiler, 1979; Uchida et al. 2016). However, in the present study, the sex distribution varied depending on the type of polyp; thus hyperplastic polyps were more common in males, inflammatory polyps – in females, while fibroblastic polyps occurred exclusively in females. In lymphoid and hamartomatous polyps sex distribution was equal. In the present study, the mean age of dogs affected by non-neoplastic colorectal polyps was 7 years, which is in line with the previous studies (Ohmi et al.2012; Méric et al.2023). However, we observed that hyperplastic polyps occurred in younger animals (mean age 6.3 years) than other types of polyps (mean age range 7-9.3 years). Furthermore, we observed a breed predilection in French Bulldogs for colorectal polyps, similarly to adenocarcinomas and adenomas, in contrast to the previous studies, revealing that predisposed breeds are Miniature Dachshunds, Jack Russel Terriers and West Highland White Terriers (Ohmi et al.2012; Yoshizaki et al.2021; Méric et al.2023). Surprisingly, both hamartomatous polyps, described in the present study, occurred in mature dogs (4 and 7 years-old), while these polyps were previously found only in puppies (Fairley et al.1990; Bemelmans et al.2012). In humans, hamartomatous polyps are usually diagnosed in children or young adolescents and they can occur spontaneously or be inherited as part of Peutz-Jeghers syndrome and juvenile polyposis syndrome (Ambe and Möslein 2020). One of the colorectal hamartomatous polyps, associated with ganglioneuromatosis, was diagnosed in a Jack Russell Terrier, which may correspond with the previous research indicating hereditary gastrointestinal polyposis in Jack Russell Terriers (Yoneji et al.2022; Yoshizaki et al.2021). The second case of colorectal hamartomatous polyp in our study was diagnosed in the French Bulldog - the breed which was the most frequently identified among all colorectal lesions. Non-epithelial malignant colorectal tumours in the present study were represented by lymphomas and sarcomas. Although T-cell lymphomas predominate among gastrointestinal tract lymphomas in dogs (Ozaki et al. 2006; Rassnick et al.2009), B-cell lymphomas occur more often in the large intestine (Van den Steen et al.2012; Desmas et al. 2017), what was also observed in the present study. Moreover, diffuse large B-cell lymphoma is the most common type of lymphoma in colon also in humans (Quayle et al. 2006). We observed a higher incidence of colorectal lymphoma in males, as opposed to reports where the sex distribution was equal in both genders (Van den Steen et al.2012; Desmas et al. 2017). The mean age od dogs with colorectal lymphomas was 6.9 years, which is consistent with one of the previous study (Van den Steen et al.2012) and is slightly higher than in another study (Desmas et al. 2017). We did not find any breed predilection to colorectal lymphoma, which is consistent with previous observation (Desmas et al. 2017). The results of our study revealed that sarcomas were far less common in the large intestine, compared to adenocarcinomas, and were represented by fibrosarcomas predominating, followed by two cases of leiomyosarcomas and GISTs. Occurrence of mesenchymal tumors in the canine gastrointestinal track was the subject of extensive study (Frost et al.2003, Bettini et al. 2003, Maas et al. 2007), especially their immunohistochemical reclassification between GISTs and leiomyosarcomas (Hayes et al.2013, Dailey et al. 2015, Del Alcazar et. al 2021). In the literature, there is limited information regarding the observation of fibrosarcoma in the canine large intestine. Interestingly, we diagnosed this type of tumour more frequently then leiomyosarcomas and GISTs. It was previously stated that GISTs developed more often in the large intestine, then in other locations of the canine gastrointestinal track (Russell et al. 2007, Frost et al.2003), however in our study, only two cases were classified as GIST. Whereas, previous statement, that canine leiomyosarcomas occurred more frequently in the stomach and small intestine (Russell et al. 2007) is consistent with the fact that we diagnosed only two cases of this lesion in the canine large intestine. We observed that sarcomas were diagnosed in older dogs, with the mean age of approximately 11 years. The previous studies revealed the similar mean age of dogs with intestinal leiomyosarcomas (Kapatkin et al. 1992; Cohen et al. 2003). However, both leiomyosarcomas included in the present study were diagnosed in dogs even older. Furthermore, the mean age of the affected dogs with GIST in our study was 9.5 years, which is slightly lower compared to the previous results which were around 11 years (Frost et al.2003; Gillespie et al.2011). All subtypes of sarcomas were observed in females and males almost equally without any notable breed predilection. Another tumour, which was diagnosed in the canine large intestine was an extramedullary plasmacytoma. Based on the current veterinary literature, plasmacytoma occasionally developed in the colorectal area of the older animals, with the mean age ranging from 9.4 to 9.7 years (Kupanoff et al.2006), though we observed an even higher mean age of 11.7 years. No gender or breed predilection for the occurrence of colorectal plasmacytoma was observed in our study. Although the most common location for leiomyoma of the gastrointestinal tract in dogs is the stomach (Frost et al.2003; Hobbs et al.2015), we observed 6 leiomyomas in the large intestine, classifying them as the second most common benign tumour, after adenomas. In the present study, leiomyoma was diagnosed with the mean age of 10 years, which is consistent with the previous report (Frost et al.2003). However, it was previously demonstrated that leiomyomas of the gastrointestinal tract occur more commonly in males (Frost et al.2003), while we observed higher incidence of this benign mesenchymal tumour in females. Among cases diagnosed with leiomyoma, no breed predisposition was observed. In summary, based on the conducted study, we have updated current knowledge regarding colorectal proliferative lesions in dogs. The vast majority of colorectal tumours in dogs were of epithelial origin, with the most common adenocarcinomas, followed by adenomas. Both adenocarcinomas and adenomas were more commonly observed in males, and adenoma was diagnosed in younger dogs, compared to adenocarcinoma. Colorectal polyps were the third most numerous group of lesions, with predominance of hyperplastic polyps, more often diagnosed in males, followed by inflammatory and fibroblastic polyps with female predisposition. Additionally, we observed for the first time the predisposition of French Bulldogs to colorectal adenocarcinomas, adenomas and colorectal hyperplastic polyps, which suggest the genetic basis of these lesions. Non-epithelial tumours occurred infrequently in the large intestine in dogs, but leiomyomas were the second most commonly observed benign tumour in this localization. Lymphomas occurred quite infrequently but were mostly of B-cell type, with the male predilection. Moreover, almost half of the cases in our study constituted adenomas and polyps, which, like in humans, can probably have a malignant potential. Therefore, the results of our research are alarming and emphasize the importance of routine diagnostics and appropriate management in the early detection of colorectal lesions and the prevention of their progression to malignant tumors. Declarations Acknowledgements : We would like to thank Cezary Zwoliński and Dominika Piech for preparing the archival samples. Authors’ contributions : Joanna Fiedorowicz collected samples, designed and performed the experiments, analysed the data, and wrote the manuscript; Katarzyna Paździor‑Czapula analysed the data and edited the manuscript; Iwona Otrocka‑Domagała super‑vised and corrected the manuscript. The authors read and approved the final manuscript. Funding Project : This work was funded by the Minister of Science under the Regional Initiative of Excellence Program. Availability of data and materials : Data used in the current research are available from the corresponding author on reasonable request. 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Ohmi, A., Tsukamoto, A., Ohno, K., Uchida, K., Nishimura, R., Fukushima, K., Takahashi, M., Nakashima, K., Fujino, Y., & Tsujimoto, H. A retrospective study of inflammatory colorectal polyps in miniature dachshunds. The Journal of veterinary medical science. 2012;74(1), 59–64. Ohta H, Tamura Y, Yokoyama N, Nagata N, Osuga T, Sasaki N, Kagawa Y, Morishita K, Takiguchi M. Gene expression of leucine-rich alpha-2 glycoprotein in the polypoid lesion of inflammatory colorectal polyps in miniature dachshunds. J Vet Med Sci. 2020 Oct 20;82(10):1445-1449. Patnaik AK, Hurvitz AI, Johnson GF. Canine gastrointestinal neoplasms. Vet Pathol. 1977;14(6):547-555. Quayle FJ, Lowney JK. Colorectal lymphoma. Clin Colon Rectal Surg. 2006;19(2):49-53. Rassnick, K. M., Moore, A. S., Collister, K. E., Northrup, N. C., Kristal, O., Chretin, J. D., & Bailey, D. B. (2009). Efficacy of combination chemotherapy for treatment of gastrointestinal lymphoma in dogs. Journal of veterinary internal medicine, 23(2), 317–322. Reineking W, Schauerte IE, Junginger J, Hewicker-Trautwein M. Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal canine intestine and in intestinal adenoma and adenocarcinoma. Vet Pathol. 2022;59(3):415-426. Russell, K. N., Mehler, S. J., Skorupski, K. A., Baez, J. L., Shofer, F. S., & Goldschmidt, M. H. (2007). Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003). Journal of the American Veterinary Medical Association, 230(9), 1329–1333. Saito T, Chambers JK, Nakashima K, et al. Histopathologic Features of Colorectal Adenoma and Adenocarcinoma Developing Within Inflammatory Polyps in Miniature Dachshunds. Veterinary Pathology. 2018;55(5):654-662. Saito T, Nibe K, Chambers JK, Uneyama M, Nakashima K, Ohno K, Tsujimoto H, Uchida K, Nakayama H. A histopathological study on spontaneous gastrointestinal epithelial tumors in dogs. J Toxicol Pathol. 2020 Apr;33(2):105-113. Seiler RJ. Colorectal polyps of the dog: a clinicopathologic study of 17 cases. J Am Vet Med Assoc. 1979;174(1):72-75. Shussman N, Wexner SD. Colorectal polyps and polyposis syndromes. Gastroenterol Rep (Oxf). 2014 Feb;2(1):1-15. Spużak J, Ciaputa R, Kubiak K, et al. Adenocarcinoma of the posterior segment of the gastrointestinal tract in dogs - clinical, endoscopic, histopathological and immunohistochemical findings. Pol J Vet Sci. 2017;20(3):539-549 . Tanaka, T., Iimori, Y., Yamazaki, H., Hidetaka, N., & Hideo, A. Contrast-enhanced computed tomography characterization of canine rectal neoplasms. Japanese Journal of Veterinary Research. 2021 69(3), 163–173. Tang, Y. S., Liu, L., Gao, Y., He, Q. C., Guo, H. M., & Zhao, Z. F. (2023). Minimally invasive colonoscopy treatment of inflammatory fibroid polyps in the terminal ileum. Scientific reports, 13(1), 4929 Uchida E, Chambers JK, Nakashima K, et al. Pathologic Features of Colorectal Inflammatory Polyps in Miniature Dachshunds. Veterinary Pathology. 2016;53(4):833-839. Uzal FA, Plattner BL, Hostetter JM. Neoplastic and proliferative lesions of the stomach and intestine. In: Maxie G, ed. Jubb, Kennedy & Palmer’s Pathology of Domestic Animals. 6th ed. Philadelphia, PA: Saunders Ltd; 2015:100–105p Van den Steen N, Berlato D, Polton G, et al. Rectal lymphoma in 11 dogs: a retrospective study. J Small Anim Pract. 2012;53(10):586-591. Van der Gaag I. The histological appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease. Can J Vet Res. 1988 Jan;52(1):75-82. Van Wyk AC, van Zyl H, Rigby J. Colonic perineurioma (benign fibroblastic polyp): case report and review of the literature. Diagn Pathol. 2018;13(1):16. Published 2018 Feb 20. doi:10.1186/s13000-018-0694-z Yoneji, W., Yoshizaki, K., Hirata, A., Yoneji, K., & Sakai, H. Clinical and Pathological Diagnosis of Hereditary Gastrointestinal Polyposis in Jack Russell Terriers. Veterinary sciences. 2022; 9(10), 551. Yoshizaki K, Hirata A, Nishii N, Kawabe M, Goto M, Mori T, Sakai H. Familial adenomatous polyposis in dogs: hereditary gastrointestinal polyposis in Jack Russell Terriers with germline APC mutations. Carcinogenesis. 2021 Feb 11;42(1):70-79. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Mar, 2025 Read the published version in BMC Veterinary Research → Version 1 posted Editorial decision: Revision requested 06 Jun, 2024 Editor assigned by journal 06 Jun, 2024 Submission checks completed at journal 06 Jun, 2024 First submitted to journal 31 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4510927","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":311191746,"identity":"9f1e04b1-7ca7-431a-81b9-e4f87b60fcf9","order_by":0,"name":"Joanna Fiedorowicz","email":"data:image/png;base64,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","orcid":"","institution":"University of Warmia and Mazury in Olsztyn","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Joanna","middleName":"","lastName":"Fiedorowicz","suffix":""},{"id":311191747,"identity":"e518e448-8cfb-4e35-bb83-39be28507c32","order_by":1,"name":"Katarzyna Paździor - Czapula","email":"","orcid":"","institution":"University of Warmia and Mazury in Olsztyn","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Katarzyna","middleName":"Paździor -","lastName":"Czapula","suffix":""},{"id":311191748,"identity":"f13011fe-8fee-4bf1-a1be-5cedf14d9d20","order_by":2,"name":"Iwona Otrocka - Domagała","email":"","orcid":"","institution":"University of Warmia and Mazury in Olsztyn","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Iwona","middleName":"Otrocka -","lastName":"Domagała","suffix":""}],"badges":[],"createdAt":"2024-05-31 20:08:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4510927/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4510927/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12917-025-04567-5","type":"published","date":"2025-03-05T15:57:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59050152,"identity":"59065160-5931-4e8e-8eb0-1556689958b6","added_by":"auto","created_at":"2024-06-25 19:38:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":610105,"visible":true,"origin":"","legend":"\u003cp\u003eDog, adenocarcinoma, large intestine. The tumor cells are cylindrical, polygonal with moderate to high anisocytosis and anisokaryosis and many mitoses. Loss of proper architectonic of glands with multilayer formation. Reduced stroma with congestion, infiltrated by lymphocytes and plasma cells. Hematoxylin and eosin (HE).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/adb443b4e42a008242dd8be3.png"},{"id":59050548,"identity":"d51ca49d-b58d-4355-81c3-6e23d6524d5b","added_by":"auto","created_at":"2024-06-25 19:46:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":595682,"visible":true,"origin":"","legend":"\u003cp\u003eDog, Gastrointestinal stromal tumour, large intestine. Tumour cells are spindle-shaped and densely packed with moderate to high anisocytosis and anisokaryosis, forming palisades and herringbone pattern. Hematoxylin and eosin (HE). Tumor cells show cytoplasmic expression for DOG1 (inset).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/4a48aaf37d44b0df5beb3712.png"},{"id":59050154,"identity":"64614137-3776-4069-a1a0-c3967e7cf729","added_by":"auto","created_at":"2024-06-25 19:38:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":621710,"visible":true,"origin":"","legend":"\u003cp\u003eDog, large B-cell lymphoma, large intestine. Neoplastic lymphocytes show high mitotic activity. Hematoxylin and eosin (HE). Tumor cells show cytoplasmic expression for Cd79a (inset).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/283c3f648c16586171602c66.png"},{"id":59050156,"identity":"7bb3d06e-a9f7-4a23-b34d-8d6f8d2b6183","added_by":"auto","created_at":"2024-06-25 19:38:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":649331,"visible":true,"origin":"","legend":"\u003cp\u003eDog, adenoma, large intestine. The tumor cells are oval with moderate anisocytosis and anisokaryosis, form irregular crypts, sometimes widened. Some of the glands are with double or multilayer formation. The stroma with strong congestion, infiltrated by lymphocytes, plasma cells and neutrophils. Hematoxylin and eosin (HE).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/135c51dcf9d5d0752b369122.png"},{"id":59050157,"identity":"2d5e4c26-a07c-4651-ac39-54594c17ae18","added_by":"auto","created_at":"2024-06-25 19:38:42","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":631415,"visible":true,"origin":"","legend":"\u003cp\u003eDog, hyperplastic polyp, large intestine. Uniform columnar layer of cells with minor anisocytosis and anisokaryosis, form irregular crypts, occasionally filled with mucinous secretion. The stroma is composed of collagen-rich connective tissue, withcongestion, occasionally heavily infiltrated with plasma cells, lymphocytes, variably numerous neutrophils, and eosinophils. Hematoxylin and eosin (HE)\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/3107246000c46318552a0e4e.png"},{"id":59050155,"identity":"8ebadb41-148f-46ab-9bbe-c89197c7c10c","added_by":"auto","created_at":"2024-06-25 19:38:42","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":651073,"visible":true,"origin":"","legend":"\u003cp\u003eDog, Ganglioneuromatosis in hamartomatous polyp, large intestine. Multifocal proliferation of ganglion cells, (inset) accompanied by proliferation of fibrous connective tissue. Dilated, congested blood vessels. Hematoxylin and eosin (HE).\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/494c59bccbea1c105b62f02b.png"},{"id":78181500,"identity":"df40a570-0b9f-436f-ae8c-e30329e9aaa0","added_by":"auto","created_at":"2025-03-10 17:46:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3840772,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4510927/v1/ba161b05-aaab-4f95-9189-459cbb2e7d00.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Canine colorectal proliferative lesions: A retrospective study of 217 cases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOver the last several decades, an increase in the frequency of diagnosed colorectal neoplasms and non-neoplastic polyps has been observed in humans (Keum and Giovannucci 2019). It has been proven that this increase is related to dietary habits, an inactive lifestyle, processed food and environmental pollution. Companion animals, especially dogs, living in the same environment as man are prone to the same civilization diseases, which is reflected in the increase in the number of tumoral colorectal diseases (Herstad et al. 2021). In addition to environmental risk factors, genetic and hereditary predispositions, as well as age, sex and breed are also under consideration in the development of intestinal proliferative lesions in dogs (van der Gaag 1988, M\u0026eacute;ric et al. 2023). Breed related development of colorectal inflammatory polyps with risk of progression to adenoma and adenocarcinoma has been shown in middle-aged Miniature Dachshunds in Japan (Uchida et al. 2016; Saito et al. 2018). In Jack Russel Terriers hereditary gastrointestinal polyposis was confirmed with gastric and colorectal distribution. While hyperplastic polyps, adenomas (tubular, tubulopapillary, papillary) and adenocarcinomas (tubular, tubulopapillary, papillary) were observed in the stomach in this breed, only papillary adenocarcinomas were observed in the colon and rectum (Yoshizaki et al. 2021).\u003c/p\u003e \u003cp\u003eAccording to the current classification of tumours in domestic animals, canine intestinal neoplasms are divided into tumours of epithelial and mesenchymal origin. Epithelial tumours include adenomas, adenocarcinomas and neuroendocrine carcinomas, while mesenchymal tumours include lymphomas, plasmacytomas, mast cell tumours, non-angiogenic, non-lymphogenic intestinal mesenchymal tumours (NIMTs), gastrointestinal stromal tumours (GISTs), leiomyomas, leiomyosarcomas, intestinal neurogenic tumours, fibrosarcomas, myxosarcomas, extraskeletal osteosarcomas and angiogenic tumours. Non-neoplastic proliferative lesions in dogs most frequently develop in the rectum as hyperplastic polyps, caused by abnormal mucosal maturation, inflammatory polyps, caused by chronic inflammation, and multiple polypoid hamartomas (Munday et al. 2017).\u003c/p\u003e \u003cp\u003eThe vast majority of colorectal malignant neoplasms in dogs are adenocarcinomas, followed by lymphomas, leiomyosarcomas, haemagiosarcomas and plasmacytomas (Munday et al. 2017, Saito et al. 2020, Herstad et al. 2021, Tanaka et al. 2021). The most frequently diagnosed benign tumours in this location are adenomas (adenomatous polyps), leiomyomas and fibromas (Adamovich-Rippe et al. 2017, Saito et al. 2020, Herstad et al. 2021). Both malignant and benign neoplasms, especially of epithelial origin, may grow as single or multiple polypoid lesions of various diameters, variably involving the mucosa, and in the case of malignancies, also the submucosa and muscularis of the intestine. Therefore, on the basis of endoscopic examination, these lesions are generally referred to as colorectal polyps. Meanwhile, histopathologically, intestinal polyps are defined as non-neoplastic sessile or pedunculated exophytic growths (Uchida et al. 2016). According to the current histopathological classification, non-neoplastic colorectal polyps in humans are classified as: hyperplastic (metaplastic), hamartomatous (Peutz-Jeghers-type), juvenile, inflammatory and lymphoid (Hamilton and Aaltonen 2000, Colucci et al. 2003), and the similar classification is used in animals. In humans, the most common are hyperplastic polyps, which have a low malignant potential (Shussman and Wexner 2014). Juvenile, inflammatory, and lymphoid polyps have a low risk of neoplastic transformation, while in the case of Peutz-Jeghers-type polyps, the probability of malignant transformation is high (Chen et al. 2017, Ashktorab et al. 2020, Dong et al. 2022, Jelsig et al. 2023). In dogs, hyperplastic and inflammatory polyps are the most common. Numerous studies have shown that, as in humans, the growth of inflammatory polyps in dogs is stimulated by chronic inflammatory bowel disease, which is diagnosed with the increased frequency in animals (Ashktorab et al. 2020, Ohta et al. 2020).\u003c/p\u003e \u003cp\u003eThe aim of this retrospective study was to analyze the incidence of neoplastic and non-neoplastic colorectal proliferative lesions in dogs, depending on age, sex and breed. The results of our research will provide new data expanding knowledge about the epidemiology of colorectal neoplasms and non-neoplastic polyps in dogs and may also help to determine the possible risk factors for their development.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis study included 217 samples of canine colorectal proliferative lesions sent for histopathological examination during 2015\u0026ndash;2022. All tissue samples were obtained during surgery or colonoscopy, fixed in 10% buffered formalin, processed routinely, embedded in paraffin, cut into 3 \u0026micro;m sections and stained with Mayer's haematoxylin and eosin (HE). When\u003c/p\u003e \u003cp\u003ethe diagnosis was not obtained on routine HE staining, additional immunohistochemistry was applied for definitive diagnosis (Table.1). Immunohistochemical examination was performed manually, and preceded by heat-induced antigen retrieval in Tris-EDTA buffer (pH 9.0) using PT-Link (Dako, Glostrup, Denmark). Primary antibodies included: CD3 (polyclonal rabbit anti-human, dilution 1:100, Dako), CD20 (monoclonal rabbit anti-human, clone SP32, dilution 1:100, Abcam, Cambridge, UK), CD79a (monoclonal mouse anti-human, clone HM57, dilution 1:100, Bio-Rad Laboratories Inc., Hercules, CA), vimentin (monoclonal mouse anti-porcine, clone V9, dilution 1:100, Dako), desmin (monoclonal mouse anti-human, clone D33, dilution 1:50, Dako), c-Kit (CD117; polyclonal rabbit anti-human, dilution 1:400, Dako), α-smooth-muscle-actin (α-SMA; monoclonal mouse anti-human, clone 1A4, dilution 1:500, Dako), neuron-specific enolase (NSE; monoclonal mouse anti-human, clone BBS/NC/Vi-H14, dilution 1:100, Dako), MUM-1 (monoclonal mouse anti-human, clone MUM1p, dilution 1:50, Dako), HLA-DR α-chain (MHC II; monoclonal mouse anti-human,, clone TAL.1B5, dilution 1:20, Dako), S-100 (polyclonal rabbit, anti-bovine, dilution 1:50, Dako), Pan Keratin (monoclonal mouse anti-human, clone AE1/AE3/PCK26, ready-to-use, Ventana, Tucson, AZ), mast cell tryptase (monoclonal mouse anti-human, clone AA1, dilution 1:200, Dako) DOG1 (monoclonal rabbit recombinant, Anti-TMEM16A, clone SP31, dilution 1:100, Abcam). Visualization system was based on the immunoperoxidase method (ImmPRESS HRP Horse Anti-Rabbit IgG Polymer Reagent \u0026ndash; for primary rabbit antibodies, Vector, Newark, CA and ImmPRESS HRP Horse Anti-Mouse IgG Polymer Reagent for primary mouse antibodies, Vector) with 3.3-diaminobenzidine (DAB) as the substrate (ImmPACT DAB, SK-4105, Vector). The slides were counterstained with Mayer\u0026rsquo;s hematoxylin. Positive and negative control slides were processed together with the evaluated sections. Each case was evaluated and classified by three veterinary pathologists and authors (IOD, KPC, JF).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntibody panels used in immunohistochemistry for selected tumours.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumour\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAntibodies\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-cell lymphoma\u003c/p\u003e \u003cp\u003eT-cell lymphoma\u003c/p\u003e \u003cp\u003eFibrosarcoma\u003c/p\u003e \u003cp\u003eLeiomyosarcoma\u003c/p\u003e \u003cp\u003eGastrointestinal stromal tumor\u0026nbsp;(GIST)\u003c/p\u003e \u003cp\u003ePoorly diagnosed non-angiogenic, non - lymphogenic intestinal mesenchymal tumours\u0026nbsp;(NIMTs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCD3-, CD20+, CD79a+\u003c/p\u003e \u003cp\u003eCD3+, CD20-, CD79a-\u003c/p\u003e \u003cp\u003evimentin+, desmin-, S-100 -, c-Kit-, α-SMA-\u003c/p\u003e \u003cp\u003evimentin+, α-SMA+, desmin -, S-100-, c-Kit-, DOG1 -\u003c/p\u003e \u003cp\u003eDOG1+, c-Kit +, vimentin+, α-SMA+, desmin-, S-100-\u003c/p\u003e \u003cp\u003evimentin+, S100+, NSE+, CD3-, CD20-, CD79a-, MHC II-, MUM1-, desmin-, c-Kit-, Pan-keratin-, α-SMA-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAmong collected cases of proliferative colorectal lesions in dogs, 120 cases were diagnosed in males (55.3%) and 97 cases in females (44.7%). The majority of proliferative lesions constituted malignant tumours (52.5%, 114/217), with the most frequent adenocarcinomas (42.9%, 93/217). Adenocarcinomas were further subtyped into papillary (72 cases, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), mixed (12 cases), tubular (7 cases), mucinous (one case) and adenosquamous carcinoma (one case). Adenocarcinomas occurred with a slightly higher incidence in males (55/93) than in females (38/93) with an age ranging from 2 to 16 years (mean age: 7.9 years). The most common breeds diagnosed with adenocarcinoma were French Bulldogs (10/67), Yorkshire Terriers (7/67) and crossbreeds (7/67). Unfortunately, these data were incomplete in several cases: 7 regarding the age and 26 regarding the breed.\u003c/p\u003e\n\u003cp\u003eMalignant tumours of mesenchymal origin were far less common than adenocarcinomas, and constituted 9.7% (21/217) of cases, including 9 cases of sarcomas, 9 cases of lymphomas and 3 cases of plasmacytomas. In all sarcomas and lymphomas, the final diagnosis was supported by immunohistochemistry. Sarcomas were represented by 4 cases of fibrosarcoma, 2 cases of leiomyosarcoma, 2 cases of GIST (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) and one case of non-GIST, non-smooth muscle NIMT. In the group of sarcomas, sex distribution was almost equal, with an age ranging from 6 to 16 years (mean age: 10.8y.) Fibrosarcomas were confirmed in 3 females and one male, with a mean age of 10.3 years. Tumour cells showed cytoplasmic expression of vimentin and were negative to desmin, \u0026alpha;-SMA, S-100 and c-Kit. Leiomyosarcomas were diagnosed in one female (14y.) and one male (16 y.). Tumour cells showed cytoplasmic expression of vimentin and \u0026alpha;-SMA and were negative to desmin, S-100 and c-Kit. GISTs were confirmed in one female (9y.) and one male (10y.) Tumour cells expressed DOG1, c-Kit, \u0026alpha;-SMA and vimentin, and were negative to desmin and S-100. Non-GIST, non-smooth muscle NIMT was diagnosed a 6-year-old male dog. Tumour cells expressed vimentin, S-100 and NSE and were negative to CD3, CD20, CD79a, MHC II, MUM1, desmin, c-Kit, cytokeratins and \u0026alpha;-SMA. In the group of sarcomas, no association with breed was identified. Lymphomas included 6 cases of B-cell lymphoma (5 centroblastic and one centroblastic polymorphic, Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) and 3 cases of T-cell lymphoma (2 cases of large T-cell lymphoma and one case of lymphoblastic T-cell lymphoma). Lymphomas were diagnosed in 7 males and 2 females, with an age ranging from 3 to 12 years (mean age: 6.9y.). In B-cell lymphomas, tumour cells showed cytoplasmic expression of CD20 and CD79a and were negative to CD3. All of them were diagnosed in males with a mean age of 5.8 years. In T-cell lymphomas, tumour cells showed cytoplasmic expression of CD3 and were negative to CD20 and CD79a. This group was represented by 2 females and one male with a mean age of 9 years. In lymphomas, no breed predisposition was observed. Plasmacytomas were diagnosed in two females and one male, with an age ranging from 11 to 12 years (mean age: 11.7y.).\u003c/p\u003e\n\u003cp\u003eBenign tumours constituted 26.7% (58/217) of the total cases. The most frequently diagnosed benign tumour was adenoma (52/217, Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e), observed more often in males (32/52) than in females (20/52). The age of the affected animals ranged from 1 to 15 years (mean age: 5.5y.), and the most frequently affected breed was the French Bulldog (14/37), followed by crossbreeds (5/37) and West Highland White Terriers (4/37). Unfortunately, these data were incomplete in several cases: 5 regarding the age and 15 regarding the breed. Benign mesenchymal tumours were less numerous than adenomas and were represented by leiomyomas (6/217), observed in five females and one male, with an age ranging from 7 to 13 years a mean age of 10 years.\u003c/p\u003e\n\u003cp\u003eNon-neoplastic colorectal proliferative lesions constituted 21.1% (45/217) of the total cases. In this heterogeneous group of colorectal polyps, hyperplastic polyps were the most numerous (21/217, Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e), followed by inflammatory polyps (12/217), fibroblastic polyps (5/217), lymphoid polyps (4/217) and two hamartomatous polyps. Hyperplastic polyps were observed more often in males (\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e) than in females (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e), with an age ranging from 2 to 14 years mean age of 6.3 years, and more often in French Bulldogs (5 cases), Yorkshire Terriers (2 cases) and crossbreeds (2 cases). Inflammatory polyps were observed more often in females (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e) than in males (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e), with an age ranging from 2.8 to 10 years and mean age of 7.8 years. No breed predisposition was identified. Fibroblastic polyps were diagnosed only in females, with an age ranging from 1 to 13 years and mean age of 7.5 years, without any breed predisposition. Sex distribution was equal in lymphoid polyps, with an age ranging from 3 to 14 years and mean age of 9.3 years, no breed predisposition was observed. One case of hamartomatous polyp was diagnosed in a 7-year-old female French Bulldog and the second one in a 4-year-old male Jack Russell Terrier; the latter was accompanied by ganglioneuromatosis (Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe breeds most frequently affected by selected tumours and tumour-like lesions were presented in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Detailed information, including number of cases, sex distribution and mean age were collected in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img171879512615.png\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 3. Frequency, sex distribution and mean age of individual lesions\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1718795126.png\"\u003e\u003cbr\u003e\u003c/div\u003e\n\u003c/div\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eNeoplastic and non-neoplastic lesions of the gastrointestinal tract, especially of the large intestine, are not commonly diagnosed in dogs. Meanwhile, in humans, due to the widespread use of preventative screening tests, such as colonoscopy, these diseases can be diagnosed at an early stage and successfully treated. Hopefully, the development and improvement of diagnostic procedures in veterinary medicine, together with the increase in the longevity of dogs and the awareness of owners, will contribute to an increase in detection of colorectal lesions in dogs as well. Hence, it is very important to conduct retrospective studies assessing the frequency of occurrence and precise characteristics of colorectal proliferative neoplastic and non-neoplastic lesions in dogs, especially since the number of such studies in the available literature is limited.\u003c/p\u003e \u003cp\u003eIn this retrospective study, conducted on the large number of histologic samples, we have demonstrated that half of the proliferative colorectal lesions in dogs were diagnosed as malignant tumors, mainly of epithelial origin. Not surprisingly, adenocarcinoma was the most frequently diagnosed lesion, which is in line with the previous study (Patnaik et al. 1977). We observed that colorectal adenocarcinomas were mostly of the papillary type, in contrast to results indicating that the tubular type was the most common (Aresu et al. 2010, Saito et al. 2020). However, we diagnosed also single cases of uncommon histological types, such as mucinous adenocarcinoma and adenosquamous carcinoma. We also confirmed that males were predisposed to colorectal adenocarcinoma, which is consistent with most previous reports (Morello et al.2008; Uzal et al.2015; Spużak et al. 2017), although in one study females were more frequently affected (Frgelecov\u0026aacute; et al. 2013). The mean age of animals affected by adenocarcinoma was 7.9 years; similar finding was observed previously (Frgelecov\u0026aacute; et al. 2013; Spużak et al. 2017). Interestingly, we observed a breed predilection to colorectal adenocarcinoma in French Bulldogs and Yorkshire Terriers, which has never been observed before. In contrary, previous studies revealed that German Shepherds, Collies, Jack Russell Terriers, and Miniature Dachshunds are predisposed to this tumor (Ohmi et al.2021; Saito et al. 2022).\u003c/p\u003e \u003cp\u003eIn the present study, the second most common colorectal lesion was benign epithelial tumour - adenoma. In dogs, large intestine (and more precisely \u0026ndash; distal rectum) is the most common site for the development of this type of lesion (Uzal et al.2017). We observed a slightly higher incidence of large intestine adenoma in males, which is consistent with another survey (Uzal et al.2017). In previous reports the mean age of affected animals was 7\u0026ndash;8 years (Saito et al. 2020; Reineking et al. 2022). However, in our study adenomas occurred in younger dogs, with the mean age 5.5 years, and 9 cases were diagnosed in very young dogs (1\u0026ndash;2 years old). As with colorectal adenocarcinomas, we observed a significant breed predilection in French Bulldogs for colorectal adenomas. Although the previous study suggested that Miniature Dachshunds are prone to developing colorectal adenomas (Saito et al. 2020), we did not observe any colorectal adenoma in this breed.\u003c/p\u003e \u003cp\u003eColorectal polyps were the third most common lesion found in the present study with a predominance of hyperplastic polyps, followed by inflammatory polyps, fibroblastic polyps, lymphoid polyps and hamartomatous polyps. Fibroblastic polyp described in humans has been recently reclassified as perineurioma, due to characteristic immunohistochemical features (van Wyk et al. 2018) and has no equivalent in veterinary medicine. Colorectal polyps were observed more commonly in females, in contrary to the previous studies, which stated than colorectal polyps were more common in males (Ohmi et al. 2012; M\u0026eacute;ric et al.2023) or sex distribution was almost equal (Seiler, 1979; Uchida et al. 2016). However, in the present study, the sex distribution varied depending on the type of polyp; thus hyperplastic polyps were more common in males, inflammatory polyps \u0026ndash; in females, while fibroblastic polyps occurred exclusively in females. In lymphoid and hamartomatous polyps sex distribution was equal. In the present study, the mean age of dogs affected by non-neoplastic colorectal polyps was 7 years, which is in line with the previous studies (Ohmi et al.2012; M\u0026eacute;ric et al.2023). However, we observed that hyperplastic polyps occurred in younger animals (mean age 6.3 years) than other types of polyps (mean age range 7-9.3 years). Furthermore, we observed a breed predilection in French Bulldogs for colorectal polyps, similarly to adenocarcinomas and adenomas, in contrast to the previous studies, revealing that predisposed breeds are Miniature Dachshunds, Jack Russel Terriers and West Highland White Terriers (Ohmi et al.2012; Yoshizaki et al.2021; M\u0026eacute;ric et al.2023). Surprisingly, both hamartomatous polyps, described in the present study, occurred in mature dogs (4 and 7 years-old), while these polyps were previously found only in puppies (Fairley et al.1990; Bemelmans et al.2012). In humans, hamartomatous polyps are usually diagnosed in children or young adolescents and they can occur spontaneously or be inherited as part of Peutz-Jeghers syndrome and juvenile polyposis syndrome (Ambe and M\u0026ouml;slein 2020). One of the colorectal hamartomatous polyps, associated with ganglioneuromatosis, was diagnosed in a Jack Russell Terrier, which may correspond with the previous research indicating hereditary gastrointestinal polyposis in Jack Russell Terriers (Yoneji et al.2022; Yoshizaki et al.2021). The second case of colorectal hamartomatous polyp in our study was diagnosed in the French Bulldog - the breed which was the most frequently identified among all colorectal lesions.\u003c/p\u003e \u003cp\u003eNon-epithelial malignant colorectal tumours in the present study were represented by lymphomas and sarcomas. Although T-cell lymphomas predominate among gastrointestinal tract lymphomas in dogs (Ozaki et al. 2006; Rassnick et al.2009), B-cell lymphomas occur more often in the large intestine (Van den Steen et al.2012; Desmas et al. 2017), what was also observed in the present study. Moreover, diffuse large B-cell lymphoma is the most common type of lymphoma in colon also in humans (Quayle et al. 2006). We observed a higher incidence of colorectal lymphoma in males, as opposed to reports where the sex distribution was equal in both genders (Van den Steen et al.2012; Desmas et al. 2017). The mean age od dogs with colorectal lymphomas was 6.9 years, which is consistent with one of the previous study (Van den Steen et al.2012) and is slightly higher than in another study (Desmas et al. 2017). We did not find any breed predilection to colorectal lymphoma, which is consistent with previous observation (Desmas et al. 2017).\u003c/p\u003e \u003cp\u003eThe results of our study revealed that sarcomas were far less common in the large intestine, compared to adenocarcinomas, and were represented by fibrosarcomas predominating, followed by two cases of leiomyosarcomas and GISTs. Occurrence of mesenchymal tumors in the canine gastrointestinal track was the subject of extensive study (Frost et al.2003, Bettini et al. 2003, Maas et al. 2007), especially their immunohistochemical reclassification between GISTs and leiomyosarcomas (Hayes et al.2013, Dailey et al. 2015, Del Alcazar et. al 2021). In the literature, there is limited information regarding the observation of fibrosarcoma in the canine large intestine. Interestingly, we diagnosed this type of tumour more frequently then leiomyosarcomas and GISTs. It was previously stated that GISTs developed more often in the large intestine, then in other locations of the canine gastrointestinal track (Russell et al. 2007, Frost et al.2003), however in our study, only two cases were classified as GIST. Whereas, previous statement, that canine leiomyosarcomas occurred more frequently in the stomach and small intestine (Russell et al. 2007) is consistent with the fact that we diagnosed only two cases of this lesion in the canine large intestine. We observed that sarcomas were diagnosed in older dogs, with the mean age of approximately 11 years. The previous studies revealed the similar mean age of dogs with intestinal leiomyosarcomas (Kapatkin et al. 1992; Cohen et al. 2003). However, both leiomyosarcomas included in the present study were diagnosed in dogs even older. Furthermore, the mean age of the affected dogs with GIST in our study was 9.5 years, which is slightly lower compared to the previous results which were around 11 years (Frost et al.2003; Gillespie et al.2011). All subtypes of sarcomas were observed in females and males almost equally without any notable breed predilection. Another tumour, which was diagnosed in the canine large intestine was an extramedullary plasmacytoma. Based on the current veterinary literature, plasmacytoma occasionally developed in the colorectal area of the older animals, with the mean age ranging from 9.4 to 9.7 years (Kupanoff et al.2006), though we observed an even higher mean age of 11.7 years. No gender or breed predilection for the occurrence of colorectal plasmacytoma was observed in our study.\u003c/p\u003e \u003cp\u003eAlthough the most common location for leiomyoma of the gastrointestinal tract in dogs is the stomach (Frost et al.2003; Hobbs et al.2015), we observed 6 leiomyomas in the large intestine, classifying them as the second most common benign tumour, after adenomas. In the present study, leiomyoma was diagnosed with the mean age of 10 years, which is consistent with the previous report (Frost et al.2003). However, it was previously demonstrated that leiomyomas of the gastrointestinal tract occur more commonly in males (Frost et al.2003), while we observed higher incidence of this benign mesenchymal tumour in females. Among cases diagnosed with leiomyoma, no breed predisposition was observed.\u003c/p\u003e \u003cp\u003eIn summary, based on the conducted study, we have updated current knowledge regarding colorectal proliferative lesions in dogs. The vast majority of colorectal tumours in dogs were of epithelial origin, with the most common adenocarcinomas, followed by adenomas. Both adenocarcinomas and adenomas were more commonly observed in males, and adenoma was diagnosed in younger dogs, compared to adenocarcinoma. Colorectal polyps were the third most numerous group of lesions, with predominance of hyperplastic polyps, more often diagnosed in males, followed by inflammatory and fibroblastic polyps with female predisposition. Additionally, we observed for the first time the predisposition of French Bulldogs to colorectal adenocarcinomas, adenomas and colorectal hyperplastic polyps, which suggest the genetic basis of these lesions. Non-epithelial tumours occurred infrequently in the large intestine in dogs, but leiomyomas were the second most commonly observed benign tumour in this localization. Lymphomas occurred quite infrequently but were mostly of B-cell type, with the male predilection. Moreover, almost half of the cases in our study constituted adenomas and polyps, which, like in humans, can probably have a malignant potential. Therefore, the results of our research are alarming and emphasize the importance of routine diagnostics and appropriate management in the early detection of colorectal lesions and the prevention of their progression to malignant tumors.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: We would like to thank Cezary Zwoliński and Dominika Piech for preparing the archival samples.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e:\u0026nbsp;Joanna Fiedorowicz collected samples, designed and performed the experiments, analysed the data, and wrote the manuscript; Katarzyna Paździor‑Czapula analysed the data and edited the manuscript; Iwona Otrocka‑Domagała super‑vised and corrected the manuscript. The authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Project\u003c/strong\u003e: This work was funded by the Minister of Science under the Regional Initiative of Excellence Program.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e: Data used in the current research are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e: Ethics approval is not applicable under the Act of 15 January 2015 on the protection of animals used for scientific or educational purposes \u0026ndash; Journal of Laws of the Republic of Poland (Journal of Laws 2015 item 266) and Local Ethics Committee for Animal Experiments. \u0026nbsp;\u003cbr\u003eEthical review and approval were waived for this study, as this study used only archival diagnostic specimens collected in the Department of Pathological Anatomy, University of Warmia and Mazury.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAdamovich-Rippe KN, Mayhew PD, Marks SL, Selmic LE, Culp WT, Youello AM, Runge JJ, Holt DE, Kass PH, Peauroi JR. Colonoscopic and histologic features of rectal masses in dogs: 82 cases (1995-2012). J Am Vet Med Assoc. 2017 Feb 15;250(4):424-430.\u003c/li\u003e\n\u003cli\u003eAmbe, P.C., M\u0026ouml;slein, G. (2020). Management of Hamartomatous Polyps. In: Guillem, J., Friedman, G. (eds) Management of Hereditary Colorectal Cancer. Springer, Cham.\u003c/li\u003e\n\u003cli\u003eAresu, L., Pregel, P., Zanetti, R., Caliari, D., Biolatti, B., \u0026amp; Castagnaro, M. (2010). E-cadherin and \u0026beta;-catenin expression in canine colorectal adenocarcinoma. Research in veterinary science, 89(3), 409\u0026ndash;414.\u003c/li\u003e\n\u003cli\u003eBemelmans I, K\u0026uuml;ry S, Albaric O, Hordeaux, J., Bertrand, L., Nguyen, F., \u0026amp; Abadie, J. Colorectal Hamartomatous Polyposis and Ganglioneuromatosis in a Dog. Veterinary Pathology. 2011;48(5):1012-1015. \u003c/li\u003e\n\u003cli\u003eBettini, G., Morini, M., \u0026amp; Marcato, P. S. (2003). Gastrointestinal spindle cell tumours of the dog: histological and immunohistochemical study. Journal of comparative pathology, 129(4), 283\u0026ndash;293.\u003c/li\u003e\n\u003cli\u003eChen H-Y, Jin X-W, Li B-R, et al. Cancer risk in patients with Peutz\u0026ndash;Jeghers syndrome: A retrospective cohort study of 336 cases. Tumor Biology. 2017;39(6). \u003c/li\u003e\n\u003cli\u003eCohen M, Post GS, Wright JC. Gastrointestinal leiomyosarcoma in 14 dogs. J Vet Intern Med. 2003;17(1):107-110.\u003c/li\u003e\n\u003cli\u003eColucci PM, Yale SH, Rall CJ. Colorectal polyps. Clin Med Res. 2003 Jul;1(3):261-2. \u003c/li\u003e\n\u003cli\u003eDailey DD, Ehrhart EJ, Duval DL, Bass T, Powers BE. DOG1 is a sensitive and specific immunohistochemical marker for diagnosis of canine gastrointestinal stromal tumors. Journal of Veterinary Diagnostic Investigation. 2015;27(3):268-277.\u003c/li\u003e\n\u003cli\u003eDel Alcazar, C. M., Mahoney, J. A., Dittrich, K., Stefanovski, D., \u0026amp; Church, M. E. (2021). Outcome, prognostic factors and histological characterization of canine gastrointestinal sarcomas. Veterinary and comparative oncology, 19(3), 578\u0026ndash;586.\u003c/li\u003e\n\u003cli\u003eDesmas I, Burton JH, Post G, et al. Clinical presentation, treatment and outcome in 31 dogs with presumed primary colorectal lymphoma (2001-2013). Vet Comp Oncol. 2017;15(2):504-517.\u003c/li\u003e\n\u003cli\u003eDong J, Ma TS, Xu YH, et al. Characteristics and potential malignancy of colorectal juvenile polyps in adults: a single-center retrospective study in China. BMC Gastroenterol. 2022;22(1):75. Published 2022 Feb 21. \u003c/li\u003e\n\u003cli\u003eFairley RA, McEntee MF. Colorectal ganglioneuromatosis in a young female dog (Lhasa Apso). Vet Pathol. 1990;27(3):206-207. \u003c/li\u003e\n\u003cli\u003eFrgelecov\u0026aacute;, L., \u0026Scaron;korič, M., Fictum, P., \u0026amp; Husn\u0026iacute;k, R.Canine gastrointestinal tract tumours: a restrospective study of 74 cases. Acta Veterinaria Brno. 2013;82(4), 387\u0026ndash;392. \u003c/li\u003e\n\u003cli\u003eFrost D, Lasota J, Miettinen M. Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases. Vet Pathol. 2003;40(1):42-54.\u003c/li\u003e\n\u003cli\u003eGillespie V, Baer K, Farrelly J, Craft D, Luong R. Canine Gastrointestinal Stromal Tumors: Immunohistochemical Expression of CD34 and Examination of Prognostic Indicators Including Proliferation Markers Ki67 and AgNOR. Veterinary Pathology. 2011;48(1):283-291.\u003c/li\u003e\n\u003cli\u003eHamilton SR, Aaltonen LA, eds. World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of the Digestive System. Lyon: IARC; 2000.\u003c/li\u003e\n\u003cli\u003eHayes S, Yuzbasiyan-Gurkan V, Gregory-Bryson E, Kiupel M. Classification of Canine Nonangiogenic, Nonlymphogenic, Gastrointestinal Sarcomas Based on Microscopic, Immunohistochemical, and Molecular Characteristics. Veterinary Pathology. 2013;50(5):779-788.\u003c/li\u003e\n\u003cli\u003eHerstad KMV, Gunnes G, R\u0026oslash;rtveit R, Kolbj\u0026oslash;rnsen \u0026Oslash;, Tran L, Skancke E. Immunohistochemical expression of \u0026beta;-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas. BMC Vet Res. 2021 Mar 12;17(1):119\u003c/li\u003e\n\u003cli\u003eHobbs, J., Sutherland-Smith, J., Penninck, D., Jennings, S., Barber, L., \u0026amp; Barton, B. Ultrasonographic features of canine gastrointestinal stromal tumors compared to other gastrointestinal spindle cell tumors. Veterinary radiology \u0026amp; ultrasound: the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association. 2015;56(4), 432\u0026ndash;438.\u003cu\u003e \u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eJelsig AM, Wullum L., Kuhlmann TP, Ousager LB, Burisch J., Karstensen JG. Cancer risk and mortality in patients with solitary juvenile polyps\u0026mdash;a nationwide cohort study with matched controls. United European Gastroenterol J. 2023; 11(8): 745\u0026ndash;749.\u003c/li\u003e\n\u003cli\u003eKapatkin AS, Mullen HS, Matthiesen DT, Patnaik AK. Leiomyosarcoma in dogs: 44 cases (1983-1988). J Am Vet Med Assoc. 1992;201(7):1077-1079.\u003c/li\u003e\n\u003cli\u003eKeum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16(12):713-732.\u003c/li\u003e\n\u003cli\u003eKupanoff PA, Popovitch CA, Goldschmidt MH. Colorectal plasmacytomas: a retrospective study of nine dogs. J Am Anim Hosp Assoc. 2006;42(1):37-43.\u003c/li\u003e\n\u003cli\u003eMaas, C. P., ter Haar, G., van der Gaag, I., \u0026amp; Kirpensteijn, J. (2007). Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs: clinical, histologic, and immunohistochemical evaluation. Veterinary surgery : VS, 36(4), 302\u0026ndash;313.\u003c/li\u003e\n\u003cli\u003eM\u0026eacute;ric T, Issard J, Maufras T, Hugonnard M, Senecat O, Lecoindre A, Leal RO, Bertolani C, Toulza O, Lecoindre P, Brisebard E, Ledevin M, Larcher T, Drut A, Darnis E, Hernandez J. Recurrence and survival in dogs with excised colorectal polyps: A retrospective study of 58 cases. J Vet Intern Med. 2023 Nov-Dec;37(6):2375-2384.\u003c/li\u003e\n\u003cli\u003eMorello E, Martano M, Squassino C, et al. Transanal pull-through rectal amputation for treatment of colorectal carcinoma in 11 dogs. Vet Surg. 2008;37(5):420-426.\u003c/li\u003e\n\u003cli\u003eMunday J.S., L\u0026ouml;hr C.V., Kiupel M.: Tumors of the Alimentary Tract. In Meuten D.J.: Tumors in Domestic Animals. 5th ed. Ames, Iowa: John Wiley \u0026amp; Sons, Inc.; 2017. p.579.\u003c/li\u003e\n\u003cli\u003eMunday JS, L\u0026ouml;hr CV, Kiupel M. Tumors of the alimentary tract. In: Tumors in domestic animals, 5th Edit., Meuten DJ, eds John Wiley \u0026amp; Sons Inc., 2017; p. 588-592\u003c/li\u003e\n\u003cli\u003eOhmi, A., Ohno, K., Chambers, J. K., Uchida, K., Nakagawa, T., Tomiyasu, H., \u0026amp; Tsujimoto, H. Clinical and histopathological features and prognosis of gastrointestinal adenocarcinomas in Jack Russell Terriers. The Journal of veterinary medical science. 2020;83(2), 167\u0026ndash;173. \u003c/li\u003e\n\u003cli\u003eOhmi, A., Tsukamoto, A., Ohno, K., Uchida, K., Nishimura, R., Fukushima, K., Takahashi, M., Nakashima, K., Fujino, Y., \u0026amp; Tsujimoto, H. A retrospective study of inflammatory colorectal polyps in miniature dachshunds. The Journal of veterinary medical science. 2012;74(1), 59\u0026ndash;64.\u003c/li\u003e\n\u003cli\u003eOhta H, Tamura Y, Yokoyama N, Nagata N, Osuga T, Sasaki N, Kagawa Y, Morishita K, Takiguchi M. Gene expression of leucine-rich alpha-2 glycoprotein in the polypoid lesion of inflammatory colorectal polyps in miniature dachshunds. J Vet Med Sci. 2020 Oct 20;82(10):1445-1449.\u003c/li\u003e\n\u003cli\u003ePatnaik AK, Hurvitz AI, Johnson GF. Canine gastrointestinal neoplasms. Vet Pathol. 1977;14(6):547-555.\u003c/li\u003e\n\u003cli\u003eQuayle FJ, Lowney JK. Colorectal lymphoma. Clin Colon Rectal Surg. 2006;19(2):49-53.\u003c/li\u003e\n\u003cli\u003eRassnick, K. M., Moore, A. S., Collister, K. E., Northrup, N. C., Kristal, O., Chretin, J. D., \u0026amp; Bailey, D. B. (2009). Efficacy of combination chemotherapy for treatment of gastrointestinal lymphoma in dogs. Journal of veterinary internal medicine, 23(2), 317\u0026ndash;322.\u003c/li\u003e\n\u003cli\u003eReineking W, Schauerte IE, Junginger J, Hewicker-Trautwein M. Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal canine intestine and in intestinal adenoma and adenocarcinoma. Vet Pathol. 2022;59(3):415-426.\u003c/li\u003e\n\u003cli\u003eRussell, K. N., Mehler, S. J., Skorupski, K. A., Baez, J. L., Shofer, F. S., \u0026amp; Goldschmidt, M. H. (2007). Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003). Journal of the American Veterinary Medical Association, 230(9), 1329\u0026ndash;1333.\u003c/li\u003e\n\u003cli\u003eSaito T, Chambers JK, Nakashima K, et al. Histopathologic Features of Colorectal Adenoma and Adenocarcinoma Developing Within Inflammatory Polyps in Miniature Dachshunds. Veterinary Pathology. 2018;55(5):654-662.\u003c/li\u003e\n\u003cli\u003eSaito T, Nibe K, Chambers JK, Uneyama M, Nakashima K, Ohno K, Tsujimoto H, Uchida K, Nakayama H. A histopathological study on spontaneous gastrointestinal epithelial tumors in dogs. J Toxicol Pathol. 2020 Apr;33(2):105-113.\u003c/li\u003e\n\u003cli\u003eSeiler RJ. Colorectal polyps of the dog: a clinicopathologic study of 17 cases. J Am Vet Med Assoc. 1979;174(1):72-75.\u003c/li\u003e\n\u003cli\u003eShussman N, Wexner SD. Colorectal polyps and polyposis syndromes. Gastroenterol Rep (Oxf). 2014 Feb;2(1):1-15.\u003c/li\u003e\n\u003cli\u003eSpużak J, Ciaputa R, Kubiak K, et al. Adenocarcinoma of the posterior segment of the gastrointestinal tract in dogs - clinical, endoscopic, histopathological and immunohistochemical findings. Pol J Vet Sci. 2017;20(3):539-549\u003cu\u003e.\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eTanaka, T., Iimori, Y., Yamazaki, H., Hidetaka, N., \u0026amp; Hideo, A. Contrast-enhanced computed tomography characterization of canine rectal neoplasms. Japanese Journal of Veterinary Research. 2021 69(3), 163\u0026ndash;173.\u003c/li\u003e\n\u003cli\u003eTang, Y. S., Liu, L., Gao, Y., He, Q. C., Guo, H. M., \u0026amp; Zhao, Z. F. (2023). Minimally invasive colonoscopy treatment of inflammatory fibroid polyps in the terminal ileum. Scientific reports, 13(1), 4929\u003c/li\u003e\n\u003cli\u003eUchida E, Chambers JK, Nakashima K, et al. Pathologic Features of Colorectal Inflammatory Polyps in Miniature Dachshunds. Veterinary Pathology. 2016;53(4):833-839.\u003c/li\u003e\n\u003cli\u003eUzal FA, Plattner BL, Hostetter JM. Neoplastic and proliferative lesions of the stomach and intestine. In: Maxie G, ed. Jubb, Kennedy \u0026amp; Palmer\u0026rsquo;s Pathology of Domestic Animals. 6th ed. Philadelphia, PA: Saunders Ltd; 2015:100\u0026ndash;105p\u003c/li\u003e\n\u003cli\u003eVan den Steen N, Berlato D, Polton G, et al. Rectal lymphoma in 11 dogs: a retrospective study. J Small Anim Pract. 2012;53(10):586-591.\u003cu\u003e \u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eVan der Gaag I. The histological appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease. Can J Vet Res. 1988 Jan;52(1):75-82.\u003c/li\u003e\n\u003cli\u003eVan Wyk AC, van Zyl H, Rigby J. Colonic perineurioma (benign fibroblastic polyp): case report and review of the literature. Diagn Pathol. 2018;13(1):16. Published 2018 Feb 20. doi:10.1186/s13000-018-0694-z\u003c/li\u003e\n\u003cli\u003eYoneji, W., Yoshizaki, K., Hirata, A., Yoneji, K., \u0026amp; Sakai, H. Clinical and Pathological Diagnosis of Hereditary Gastrointestinal Polyposis in Jack Russell Terriers. Veterinary sciences. 2022; 9(10), 551. \u003c/li\u003e\n\u003cli\u003eYoshizaki K, Hirata A, Nishii N, Kawabe M, Goto M, Mori T, Sakai H. Familial adenomatous polyposis in dogs: hereditary gastrointestinal polyposis in Jack Russell Terriers with germline APC mutations. Carcinogenesis. 2021 Feb 11;42(1):70-79.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-veterinary-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [BMC Veterinary Research](http://bmcvetres.biomedcentral.com/)","snPcode":"12917","submissionUrl":"https://submission.nature.com/new-submission/12917/3?","title":"BMC Veterinary Research","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4510927/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4510927/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eColorectal proliferative lesions are not common in dogs. However, recently we have observed an increase in the number of diagnosed cases and a lack of publications providing current epidemiological data on changes of the large intestine in dogs. The aim of this study was a retrospective analysis of 217 canine colorectal non-neoplastic and neoplastic tumours, and assessment of the frequency of occurrence of individual lesions and whether there is a risk of their occurrence depending on age, sex, or dogs breed. Histopathological diagnosis was based on routine staining (hematoxylin and eosin) and appropriate immunohistochemistry when was necessary for definitive diagnosis. Half of the cases (52.5%) were malignant tumours with male predisposition and a significant predominance of adenocarcinoma (42.9%). In the group of malignant non-epithelial lesions, lymphoma and sarcomas predominated (4.1% and 4.1%, respectively) followed by three cases of plasmacytoma. Benign neoplastic tumours constituted almost one-third of all cases (26.7%) with obvious dominance of adenoma (24.0%) and young male predisposition. Benign mesenchymal tumours were represented only by leiomyoma (2.8%).\u003c/p\u003e \u003cp\u003eThe non-neoplastic lesions were represented by a heterogeneous group of polyps (20.3%) with a slight advantage of hyperplastic type (9.7%) and less numerous inflammatory, fibroblastic, lymphoid, and hamartomatous polyps. The one case of ganglioneuromatosis in hamartomatous polyp was diagnosed. Non-neoplastic lesions were frequently diagnosed in female. We have observed for the first time that French Bulldogs are susceptible to developing colorectal proliferative lesions, including adenomas, adenocarcinomas and polyps.\u003c/p\u003e \u003cp\u003eThe results of our research provided new data expanding knowledge about the epidemiology of colorectal neoplastic and non-neoplastic proliferative lesion in dogs. We were also able to determine sex- and breed-specific risk factors associated with the occurrence of adenocarcinomas, adenomas, and non-neoplastic polyps. Our results are alarming and imply the necessity of implement routine colonoscopy in dogs in early detection of lesion and prevention of the development and progression of malignant tumours.\u003c/p\u003e","manuscriptTitle":"Canine colorectal proliferative lesions: A retrospective study of 217 cases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-25 19:38:37","doi":"10.21203/rs.3.rs-4510927/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-06T06:42:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-06T04:59:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-06T04:58:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Veterinary Research","date":"2024-05-31T20:01:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-veterinary-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [BMC Veterinary Research](http://bmcvetres.biomedcentral.com/)","snPcode":"12917","submissionUrl":"https://submission.nature.com/new-submission/12917/3?","title":"BMC Veterinary Research","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f48db27-3a62-44ce-9b8a-6956a03d53a3","owner":[],"postedDate":"June 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-10T17:09:57+00:00","versionOfRecord":{"articleIdentity":"rs-4510927","link":"https://doi.org/10.1186/s12917-025-04567-5","journal":{"identity":"bmc-veterinary-research","isVorOnly":false,"title":"BMC Veterinary Research"},"publishedOn":"2025-03-05 15:57:24","publishedOnDateReadable":"March 5th, 2025"},"versionCreatedAt":"2024-06-25 19:38:37","video":"","vorDoi":"10.1186/s12917-025-04567-5","vorDoiUrl":"https://doi.org/10.1186/s12917-025-04567-5","workflowStages":[]},"version":"v1","identity":"rs-4510927","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4510927","identity":"rs-4510927","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}