Abstract
Gastrointestinal (GI) tumors are common neoplastic diseases in dogs. However, epidemiological data on canine GI tumors in Japan are limited. The present study aimed to investigate the prevalence of GI tumors in Japan and assess the association of canine breed, age, sex, and anatomical location with the development of common tumor types. A total of 1,310 canine GI tumors that were histopathologically examined between 2012 and 2024 were retrospectively analyzed. The statistical methods included a contingency table analysis, multivariable logistic regression analyses, and Mann-Whitney U tests. The most frequent GI tumor was lymphoma (58.9%), followed by adenocarcinoma (16.2%) and adenoma (15.0%). Statistical examination revealed that Shiba dogs were predisposed to T-cell lymphoma, Miniature Dachshunds to colorectal B-cell lymphoma and colorectal adenoma, Jack Russell Terriers to adenoma, acinar adenocarcinoma, papillary adenocarcinoma and tubulopapillary carcinoma, French Bulldogs to gastric signet-ring cell carcinoma and plasmacytoma, and Shih Tzus to tubulopapillary adenocarcinoma. These breed predispositions to specific tumors may be unique to the Japanese canine population. To the best of our knowledge, this is the first large-scale epidemiological investigation of canine GI tumors in Japan. The epidemiological information from the present study will serve as a useful reference for clinical veterinarians to establish the differential diagnoses of canine GI tumors.
Keywords: alimentary tumor, breed, dog, epidemiology, gastrointestinal tumor
INTRODUCTION
The gastrointestinal (GI) tract is a complex organ system composed of multiple anatomically and functionally distinct segments, ranging from the esophagus to the rectum [12, 27, 40]. This organ system consists of various tissues and develops various primary neoplasms, including epithelial, hematopoietic, and mesenchymal tumors [12, 27, 39, 45]. Among domestic animals, spontaneous GI tumors are most commonly reported in dogs, with the prevalence of canine GI tumors reported to be 1.1% [34] and 4.2% (calculated from the data presented in reference [11]). These tumors typically exhibit malignant behavior and are associated with a poor prognosis in most cases [27, 42]. In recent years, the use of ultrasonography and endoscopy in small-animal clinical practice has led to increased opportunities to diagnose GI tumors in dogs [17, 43]. Therefore, GI tumors are common neoplastic diseases in dogs, and epidemiological data are essential for clinical veterinarians.
Previous studies have reported breed predispositions to specific types of GI tumors [4, 6, 7, 13, 22, 38, 41, 49]. In Japan, several gastrointestinal tumors with breed-specific characteristics have been reported, such as T-cell lymphoma associated with chronic inflammatory enteropathy in Shiba dogs [26, 31], colorectal adenomas associated with inflammatory polyps in Miniature Dachshunds [14, 16, 37], and GI epithelial tumors associated with germline adenomatous polyposis coli (APC) mutations in Jack Russell Terriers [47, 48]. There are differences in popular dog breeds among geographic regions, which may potentially influence the epidemiological trend of GI tumors [11, 21, 44]. Therefore, it is important to compare the trends of these tumors across different regions to obtain a better understanding of the epidemiology of canine GI tumors, including breed predispositions. However, only a few epidemiological studies on canine GI tumors have been reported [30, 39], and to date, no studies have been conducted in Japan.
The aim of the present study was to investigate the prevalence of canine GI tumors in Japan and determine the breed, sex, age, and anatomical location predilections for specific GI tumors.
MATERIALS AND METHODS
Study population
Records of canine cases in which histopathological examination was performed on biopsy samples obtained between 2012 and 2024 were retrieved from a database maintained at the Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo. All tissue samples were collected and sent to the laboratory at two veterinary hospitals (the Veterinary Medical Center of The University of Tokyo and the Japan Small Animal Medical Center) for histopathological examination. Clinical data, including breed, age at the time of the diagnosis, sex, and the anatomical site of the biopsy, were reviewed. Patients with missing clinical information were excluded from the study. The canine breeds were categorized according to the Japan Kennel Club (https://www.jkc.or.jp). In this study, crossbred dogs were classified as mixed-breed. The anatomical locations of the GI tumors were categorized into the following areas: esophagus, stomach, duodenum, jejunoileum, cecum, colon, and rectum. In cases with multiple tumors of the same histological type affecting different GI regions (e.g., the stomach and colon), the anatomical location was classified as “multiple regions” and statistically analyzed as one event. In cases with multiple tumors of different histological types, each tumor was statistically analyzed as a different event [11, 21]. Multiple tissue samples from an identical GI tumor in the same animal (e.g., bowel resection following endoscopic biopsy) and recurrent tumors were analyzed as a single event, and records at the time of the first biopsy were used in the retrospective analysis.
Tumor diagnosis and classification
Histology slides were reviewed and diagnosed by two board-certified pathologists (J.K.C. and K.U.) from the Japanese College of Veterinary Pathologists, according to the World Health Organization (WHO) Classification of Tumors of Domestic Animals [12]. The presence of inflammatory polyp lesions within the same specimen has also been evaluated in colorectal epithelial tumors [16, 37]. Mucosal lymphoma was diagnosed based on a dense, monomorphic population of neoplastic lymphocytes with abnormal cell size and/or distorted architecture [20, 29]. Lymphomas were further classified into specific subtypes (T-cell or B-cell) when immunophenotype information was available. Sarcomas (excluding hemangiosarcoma and osteosarcoma) were classified based on immunohistochemistry (IHC) findings for CD117 (KIT), DOG-1, Desmin, SMA, S100, and SOX10 (Table 1, Supplementary Figs. 1 and 2). Sarcomas that were immunonegative for all markers were categorized as not otherwise specified (NOS). Secondary GI tumors were diagnosed based on the clinical history, diagnostic imaging, and histological findings of both the primary and GI lesions.
Table 1. Immunohistochemical markers used in the diagnosis of specific tumor types.
| Tumor type | Immunohistochemical markers (clone; provider) |
|---|---|
| B-cell lymphoma | CD20 (polyclonal; Thero Fisher Scientific, Waltham, MA, USA) |
| T-cell lymphoma | CD3 (polyclonal; Dako, Tokyo, Japan) |
| Gastrointestinal stromal tumor | CD117 (polyclonal; Thero Fisher Scientific) |
| DOG-1 (SP31; Thero Fisher Scientific) | |
| Leiomyosarcoma | SMA (1A4; Dako) |
| Desmin (D33; Dako) | |
| Peripheral nerve sheath tumor | S100 (polyclonal; Dako) |
| SOX10 (EPR4007-104; Abcam, Cambridge, UK) |
DOG-1, discover on GIST-1; SOX10, sex-determining region Y-box transcription factor 10.
Statistical analysis
Statistical analyses were performed using JMP Pro (ver.17.0.0; SAS Institute Japan, Tokyo, Japan) and R (ver. 4.3.2; R Foundation for Statistical Computing, Vienna, Austria). Tumor types with fewer than 20 cases were excluded from the statistical analyses owing to the limited sample size.
To assess breed and sex predispositions to GI tumors, 2 × 2 contingency tables were constructed for each tumor type by breed or sex (e.g., comparing the occurrence of lymphoma in Shiba dogs vs. non-Shiba dogs), and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated. P-values were derived using Pearson’s χ2 test. In addition, multivariable logistic regression analyses were performed to assess the association between the occurrence of canine GI tumors and the following explanatory variables: breed, sex (male or female), and age (<6, 6–11, or ≥12 years). For breed variables, breeds with fewer than 25 sample sizes were grouped under “Other breeds.” Mixed-breed dogs were used as the reference group, as they showed no statistically significant predisposition for any tumor type in the 2 × 2 contingency table analysis (Pearson’s χ2 test). Odds ratios (ORs) with 95% confidence intervals (CIs) for each explanatory variable were estimated from the regression coefficients and their standard errors. P-values were calculated using the Wald test. Statistical significance for breed and sex was defined by P-values of <0.05, in both the contingency table analysis (Pearson’s χ2 test) and the multivariable logistic regression model (Wald test). The Mann–Whitney U test was used to assess differences in age at diagnosis between groups (e.g., adenomas vs. adenocarcinomas), with P-values less than 0.05 considered statistically significant.
RESULTS
Canine population in the database, 2012–2024
Records of 12,639 canine cases that underwent tissue biopsies between 2012 and 2024 were reviewed. Among these, 3,407 involved GI tissues, with 413 samples obtained via surgical excision and 2,994 via endoscopic biopsy. The overall female-to-male ratio among the GI biopsy cases was 1:1.11, consisting of 372 intact females (10.9%), 1,240 spayed females (36.4%), 545 intact males (16.0%), and 1,250 castrated males (36.7%). The mean age of the dogs that underwent GI biopsy was 9.0 years (SD=3.2). The anatomical distribution of the sampled sites included 13 esophageal, 2,589 gastric, 2,439 duodenal, 2,211 jejunoileal, 44 ileocecal, 2,252 colonic, and 273 rectal tissue samples. The most commonly represented breeds in GI biopsy cases were Miniature Dachshunds (16.6%), Toy Poodles (13.6%), Mixed-breed dogs (8.7%), Shiba dogs (7.6%), Chihuahua (6.5%), French Bulldogs (5.5%), Jack Russell Terriers (3.9%), and Yorkshire Terriers (3.7%) (Supplementary Table 1). Each of the other breeds accounted for less than 3% of the cases.
Overview of GI tumors
The relative frequencies of GI tumor types and the distributions of age, sex, and anatomical location for each tumor type are summarized in Table 2. Additionally, breed predispositions and the distribution of age, sex, and anatomical location by breed for each tumor type are summarized in Table 3 and Supplementary Table 2. A total of 1,310 GI tumors were identified in 1,290 dogs. There was a significant male predominance among these dogs (female-to-male ratio=1:1.13) relative to other dogs that underwent GI biopsy. The mean age of dogs diagnosed with GI tumors was 9.7 years (SD=3.0).
Table 2. The relative frequencies of primary and secondary gastrointestinai tumors in the dogs and the distributions of age, sex, and anatomical location for each tumor type.
| Tumor type | No. of cases (% of cases among all gastrointestinal tumors) |
Age |
Sex |
Anatomical location |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean (SD) | Female (neutered) |
Male (neutered) |
Ratio female: male a) |
ESO | STO | DUO | JEI | CEC | COL | REC | MR | ||||
| Hematopoietic tumors | 772 (58.9) | 9.2 (3.2) | 382 (320) | 390 (266) | 1:1.02 | 0 | 39 | 104 | 131 | 4 | 26 | 24 | 444 | ||
| Lymphoma | 736 (56.2) | 9.2 (2.6) | 362 (303) | 374 (256) | 1:1.03 | 0 | 18 | 104 | 126 | 3 | 25 | 16 | 444 | ||
| - T cell lymphoma | 171 (13.1) | 9.9 (2.9) | 92 (88) | 79 (57) | 1:0.86 | 0 | 4 | 27 | 48 | 0 | 2 | 2 | 88 | ||
| - B cell lymphoma | 30 (2.3) | 8.0 (3.5) | 14 (13) | 16 (11) | 1:1.14 | 0 | 7 | 1 | 2 | 1 | 7 | 9 | 3 | ||
| Plasmacytoma | 26 (2.0) | 11.1 (2.7) | 14 (12) | 12 (7) | 1:0.86 | 0 | 16 | 0 | 1 | 0 | 1 | 8 | 0 | ||
| - Anaplastic plasmacytoma | 17 (1.3) | 11.0 (2.6) | 8 (6) | 9 (5) | 1:125 | 0 | 11 | 0 | 1 | 0 | 1 | 4 | 0 | ||
| - Indolent plasmacytoma | 9 (0.7) | 11.4 (2.8) | 6 (6) | 3 (2) | 1:0.5 | 0 | 5 | 0 | 0 | 0 | 0 | 4 | 0 | ||
| Histiocytic sarcoma | 7 (0.5) | 11.5 (2.3) | 5 (4) | 2 (1) | 1:0.4 | 0 | 4 | 0 | 3 | 0 | 0 | 0 | 0 | ||
| Mast cell tumor | 3 (0.2) | 9.3 (1.2) | 1 (1) | 2 (2) | 1:2 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | ||
| Epithelial tumors b) | 423 (32.3) | 10.0 (2.8) | 167 (112) | 256 (180) | 1:1.53† | 3 | 150 | 17 | 39 | 6 | 96 | 102 | 10 | ||
| Adenoma | 196 (15.0) | 9.6 (3.1) | 71 (49) | 125 (87) | 1:1.76† | 0 | 29 | 6 | 2 | 0 | 76 | 82 | 1 | ||
| - Adenoma (intestine) | 167 (12.7) | 9.5 (3.0) | 58 (41) | 109 (76) | 1:1.88† | - | - | 6 | 2 | 0 | 76 | 82 | 1 | ||
| - Tubulopapillary adenoma* | 14 (1.1) | 10.4 (3.1) | 6 (4) | 8 (5) | 1:1.3 | - | 14 | - | - | - | - | - | - | ||
| - Papillary adenoma* | 12 (0.9) | 8.8 (3.6) | 5 (2) | 7 (5) | 1:1.4 | - | 12 | - | - | - | - | - | - | ||
| - Tubular adenoma* | 3 (0.2) | 13.0 (1.7) | 2 (2) | 1 (1) | 1:0.5 | - | 3 | - | - | - | - | - | - | ||
| Adenocarcinoma | 212 (16.2) | 10.3 (2.4) | 89 (58) | 123 (87) | 1:1.38 | 3 | 112 | 8 | 36 | 5 | 20 | 20 | 8 | ||
| - Signet-ring cell carcinoma | 75 (5.7) | 9.9 (1.9) | 29 (18) | 46 (31) | 1:1.59† | - | 72 | 0 | 0 | 0 | 0 | 3 | 0 | ||
| - Acinar adenocarcinoma** | 51 (3.9) | 10.6 (2.8) | 25 (18) | 26 (22) | 1:1.04 | - | - | 6 | 15 | 3 | 14 | 11 | 2 | ||
| - Papillary adenocarcinoma | 35 (2.7) | 11.1 (2.8) | 14 (10) | 21 (13) | 1:1.5† | - | 8 | 1 | 11 | 2 | 3 | 4 | 6 | ||
| - Tubulopapillary adenocarcima* | 28 (2.1) | 9.9 (2.0) | 11 (7) | 17 (13) | 1:1.55† | - | 28 | - | - | - | - | - | - | ||
| - Mucinous adenocarcinoma | 16 (1.2) | 10.8 (1.8) | 8 (4) | 8 (6) | 1:1 | - | 1 | 1 | 9 | 0 | 2 | 3 | 0 | ||
| - Tubular adenocarcinoma* | 3 (0.2) | 10.0 (1.6) | 2 (1) | 1 (1) | 1:0.5 | - | 3 | - | - | - | - | - | - | ||
| - Adenocarcinoma (esophagus) | 3 (0.2) | 10.0 (0.8) | 0 (0) | 3 (1) | Only male | 3 | - | - | - | - | - | - | - | ||
| - Adenosquamous carcinoma | 1 (0.1) | 11.0 (−) | 0 (0) | 1 (1) | - | - | 0 | 0 | 1 | 0 | 0 | 0 | 0 | ||
| Neuroendocrine carcinoma | 8 (0.6) | 11.0 (1.7) | 4 (4) | 4 (4) | 1:1 | 0 | 3 | 3 | 0 | 1 | 0 | 0 | 1 | ||
| Undifferentiated carcinoma | 7 (0.5) | 9.6 (2.3) | 3 (1) | 4 (2) | 1:1.33 | 0 | 6 | 0 | 1 | 0 | 0 | 0 | 0 | ||
| Mesenchymal tumors | 110 (8.4) | 11.2 (2.4) | 63 (45) | 47 (34) | 1:0.75 | 5 | 37 | 5 | 24 | 13 | 14 | 11 | 1 | ||
| Gastrointestinal stromal tumor | 44 (3.4) | 10.9 (2.4) | 23 (16) | 21 (16) | 1:0.91 | 0 | 8 | 4 | 13 | 13 | 6 | 0 | 0 | ||
| Leiomyoma | 40 (3.1) | 11.8 (1.9) | 23 (17) | 17 (13) | 1:0.74 | 5 | 19 | 0 | 2 | 0 | 7 | 7 | 0 | ||
| Peripheral nerve sheath tumor | 11 (0.8) | 10.5 (2.1) | 6 (3) | 5 (2) | 1:0.83 | 0 | 8 | 0 | 0 | 0 | 0 | 3 | 0 | ||
| Sarcoma NOS | 7 (0.5) | 10.6 (3.5) | 5 (5) | 2 (1) | 1:0.4 | 0 | 1 | 0 | 6 | 0 | 0 | 0 | 0 | ||
| Leiomyosarcoma | 3 (0.2) | 11.0 (1.6) | 2 (1) | 1 (1) | 1:0.5 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | ||
| Hemangiosarcoma | 2 (0.2) | 12.0 (−) | 1 (0) | 1 (1) | 1:1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | ||
| Fibroma | 1 (0.1) | 6 (−) | 1 (1) | 0 (0) | - | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | ||
| Ganglioneuroma | 1 (0.1) | 8 (−) | 1 (1) | 0 (0) | - | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | ||
| Osteosarcoma | 1 (0.1) | 14 (−) | 1 (1) | 0 (0) | - | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | ||
| Other type of tumors | 5 (0.4) | 9.6 (1.6) | 2 (1) | 3 (1) | 1:1.5 | 0 | 0 | 1 | 1 | 0 | 1 | 2 | 0 | ||
| Mesothelioma | 2 (0.2) | 10.5 (2.5) | 1 (1) | 1 (0) | 1:1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | ||
| Secondary intestinal tumors | 3 (0.2) | 9.0 (0.8) | 1 (0) | 2 (1) | 1:2 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | ||
| All gastrointestinal tumors | 1310 | 9.7 (3.0) | 614 (478) | 696 (481) | 1:1.13 | 8 | 226 | 127 | 195 | 23 | 137 | 139 | 455 | ||
a) Tumor types with a P<0.05 (†; the contingency table analysis and the multivariable logistic regression model) were considered to have a significant male predisposition. b) Tumor types marked with * indicate gastric tumor classification, while those marked with ** indicate intestinal tumor classification. CEC, cecum; COL, colon; DUO, duodenum; ESO, esophagus; JEI, jejunoileum; MR, multiple region; REC, rectum; STO, stomach; NOS, not otherwise specified.
Table 3. Breed predispositions and the distribution of age, sex, and anatomical location by breed for each type of gastrointestinal tumor in dogs.
| Tumor type | Top three most affected breeds and breeds with significant predisposition | No. of cases with gastrointestinal biopsies |
No. of cases with each tumor type | Breed predisposition a) |
Age b) |
Sex ratio (female: male) |
Anatomical location |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (95% CI) c) | Mean (SD) | ESO | STO | DUO | JEI | CEC | COL | REC | MR | |||||
| T cell lymphoma (n=171) |
Shiba dog | 259 | 33 | 3.18 (2.13−4.77)† | 8.1 (3.6)‡ | 1:0.9 | 0 | 0 | 1 | 8 | 0 | 0 | 0 | 24 |
| Toy Poodle | 462 | 19 | 0.79 (0.48−1.28) | 11.4 (1.8) | 1:0.5 | 0 | 0 | 3 | 6 | 0 | 1 | 0 | 9 | |
| Mixed breed dog | 295 | 15 | 1.02 (0.59−1.75) | 10.7 (2.4) | 1:0.7 | 0 | 0 | 3 | 4 | 0 | 0 | 0 | 8 | |
| Pug | 68 | 13 | 4.76 (2.55−8.89)† | 9.4 (1.7) | 1:1.6 | 0 | 0 | 2 | 4 | 0 | 0 | 1 | 6 | |
| B cell lymphoma (n=30) |
Miniature Dachshund | 565 | 13 | 3.91 (1.89−8.10)† | 6.6 (3.6)‡ | 1:0.9 | 0 | 1 | 1 | 1 | 0 | 4 | 4 | 2 |
| Toy Poodle | 462 | 2 | 0.45 (0.11−1.91) | 9.5 (0.5) | 1:1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | |
| Mixed breed dog | 295 | 2 | 0.75 (0.18−3.17) | 8.0 (3.0) | Only male | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | |
| Chihuahua | 221 | 2 | 1.03 (0.24−4.35) | 7.5 (3.5) | Only male | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | |
| Plasmacytoma (n=26) |
French Bulldog | 186 | 5 | 4.21 (1.57−11.29)† | 10.6 (1.7) | 1:4 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Chihuahua | 221 | 3 | 1.89 (0.56−6.35) | 10.3 (4.0) | 1:0.5 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | |
| Shiba dog | 259 | 3 | 1.59 (0.47−5.34) | 12.0 (1.6) | 1:2 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | |
| Adenoma (n=196) |
Miniature Dachshund | 565 | 75 | 3.44 (2.54−4.66)† | 10.6 (2.6) | 1:1.4 | 0 | 4 | 0 | 1 | 0 | 43 | 26 | 1 |
| French Bulldog | 186 | 19 | 1.96 (1.19−3.22)† | 5.5 (2.6)‡ | 1:1.7 | 0 | 1 | 0 | 0 | 0 | 4 | 14 | 0 | |
| Jack Russel Terrier | 133 | 16 | 2.35 (1.36−4.05)† | 8.1 (2.5)‡ | 1:15 | 0 | 6 | 1 | 0 | 0 | 3 | 6 | 0 | |
| West Highland White Terrier | 25 | 4 | 3.16 (1.08−9.31)† | 10.5 (1.5) | 1:1 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | |
| Adenocarcinoma d) (n=212) |
Miniature Dachshund | 565 | 37 | 1.07 (0.74−1.54) | 11.7 (2.2) | 1:1.3 | 0 | 18 | 1 | 8 | 2 | 3 | 4 | 1 |
| French Bulldog | 186 | 22 | 2.14 (1.34−3.42)† | 9.4 (1.7)‡ | 1:2.1 | 1 | 19 | 1 | 0 | 0 | 0 | 1 | 0 | |
| Jack Russel Terrier | 133 | 22 | 3.22 (1.99−5.20)† | 9.8 (2.3) | 1:2.1 | 0 | 12 | 1 | 1 | 0 | 1 | 1 | 6 | |
| Shih Tzu | 77 | 12 | 2.94 (1.56−5.53)† | 9.4 (2.6) | 1:2 | 0 | 9 | 1 | 1 | 0 | 1 | 0 | 0 | |
| Signet-ring cell carcinoma (n=75) |
French Bulldog | 186 | 18 | 5.95 (3.42−10.33)† | 9.8 (1.5) | 1:2.6 | - | 18 | 0 | 0 | 0 | 0 | 0 | 0 |
| Miniature Dachshund | 565 | 11 | 0.86 (0.45−1.64) | 10.7 (1.7) | 1:4.5 | - | 11 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Mixed breed dog | 295 | 8 | 1.27 (0.60−2.66) | 10.0 (2.3) | 1:0.6 | - | 8 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Acinar adenocarcinoma** (n=51) |
Miniature Dachshund | 565 | 11 | 1.39 (0.71−2.73) | 13.0 (2.4) | 1:1.8 | - | - | 1 | 4 | 2 | 2 | 2 | 0 |
| Toy Poodle | 462 | 8 | 1.19 (0.56−2.55) | 10.6 (2.2) | 1:1 | - | - | 2 | 2 | 0 | 4 | 0 | 0 | |
| Jack Russel Terrier | 133 | 5 | 2.74 (1.07−7.02)† | 8.4 (1.5)‡ | 1:4 | - | - | 0 | 1 | 0 | 1 | 2 | 1 | |
| Papillary adenocarcinoma (n=35) |
Jack Russel Terrier | 133 | 9 | 8.73 (4.02−19.00)† | 10.3 (2.7) | 1:3.5 | - | 4 | 1 | 0 | 0 | 0 | 0 | 4 |
| Miniature Dachshund | 565 | 7 | 1.22 (0.53−2.79) | 12.4 (1.3) | 1:0.8 | - | 0 | 0 | 3 | 0 | 1 | 2 | 1 | |
| Toy Poodle | 462 | 3 | 0.58 (0.18−1.89) | 8.3 (2.6) | 1:0.5 | - | 0 | 0 | 1 | 1 | 1 | 0 | 0 | |
| Mixed breed dog | 295 | 3 | 0.96 (0.29−3.14) | 14.7 (1.9) | 1:2 | - | 1 | 0 | 1 | 0 | 0 | 1 | 0 | |
| Tubulopapillary adenocarcima* (n=28) |
Miniature Dachshund | 565 | 6 | 1.51 (0.61−3.79) | 11.2 (1.6) | 1:0.5 | - | 6 | - | - | - | - | - | - |
| Jack Russel Terrier | 133 | 6 | 7.69 (3.03−19.57)† | 9.5 (1.7) | 1:2 | - | 6 | - | - | - | - | - | - | |
| Shih Tzu | 77 | 6 | 14.19 (5.53−36.42)† | 9.3 (2.1) | 1:2 | - | 6 | - | - | - | - | - | - | |
| Gastrointestinal stromal tumor (n=44) |
Miniature Dachshund | 565 | 8 | 1.12 (0.52−2.42) | 12.8 (2.3) | 1:1 | 0 | 0 | 0 | 3 | 1 | 4 | 0 | 0 |
| Mixed breed dog | 295 | 5 | 1.36 (0.53−3.47) | 10.4 (1.2) | 1:0.7 | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 | |
| Pembroke Welsh Corgi | 76 | 4 | 4.57 (1.59−13.11) | 13.3 (0.4) | 1:1 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | |
| Chihuahua | 221 | 4 | 1.45 (0.51−4.09) | 12.0 (0.7) | 1:1 | 0 | 1 | 0 | 2 | 1 | 0 | 0 | 0 | |
| Leiomyoma (n=40) |
Mixed breed dog | 295 | 5 | 1.52 (0.59−3.9) | 10.8 (2.0) | 1:0.7 | 0 | 1 | 0 | 1 | 0 | 1 | 2 | 0 |
| Toy Poodle | 462 | 5 | 0.91 (0.35−2.33) | 10.6 (2.3) | 1:4 | 0 | 1 | 0 | 1 | 0 | 1 | 2 | 0 | |
| Chihuahua | 221 | 4 | 1.61 (0.57−4.57) | 12.0 (1.6) | Only female | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 0 | |
| Papillon | 78 | 4 | 4.94 (1.72−14.25) | 10.3 (1.3) | 1:0.3 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | |
a) Breeds with a P<0.05 (†; the contingency table analysis and the multivariable logistic regression model) were considered to have a significantly higher risk of developing the tumor type. b) Breeds with a P<0.05 (‡; Mann–Whitney U test) were considered to be significantly younger at the time of tumor diagnosis compared to other breeds. c) ORs with 95% CIs calculated using 2 × 2 contingency tables were described. d) Tumor types marked with * indicate gastric tumor classification, while those marked with ** indicate intestinal tumor classification. CI, confidence interval; OR, odds ratio; CEC, cecum; COL, colon; DUO, duodenum; ESO, esophagus; JEI, jejunoileum; MR, multiple region; REC, rectum; STO, stomach.
GI tumors were most frequently located in multiple regions (n=455 of 1,310; 34.7%), followed by the stomach (n=226; 17.3%), jejunoileum (n=195; 14.9%), rectum (n=139; 10.6%), colon (n=137; 10.5%), duodenum (n=127; 9.7%), cecum (n=23; 1.8%), and esophagus (n=8; 0.6%). Histopathologically, GI tumors included hematopoietic tumors (n=772 of 1,310; 58.9%), epithelial tumors (n=423; 32.3%), mesenchymal tumors (n=110; 8.4%), and other tumor types (n=5; 0.4%). There was an association between tumor type and anatomical location. Tumors in the stomach, colon, and rectum were predominantly epithelial (66.4%, 70.1%, and 73.4%, respectively), whereas tumors in the duodenum, jejunoileum, and multiple regions were predominantly hematopoietic (81.9%, 67.2%, and 97.6%, respectively). Tumors in the esophagus and cecum were mainly mesenchymal (62.5% and 56.5%, respectively). The three most common histopathological types of GI tumors were lymphoma (n=736 of 1,310; 58.9%), adenocarcinoma (n=212; 16.2%), and adenoma (n=196; 15.0%).
Hematopoietic tumors
Hematopoietic tumors (n=772) accounted for 58.9% of GI tumors, which included lymphoma (n=736 of 772; 95.3%), plasmacytoma (n=26; 3.4%), histiocytic sarcoma (n=7; 0.9%), and mast cell tumor (n=3; 0.4%). Histiocytic sarcomas and mast cell tumors were rare, accounting for less than 1% of cases. No significant sex predilection was observed for any of the tumor types.
Lymphoma was the most common hematopoietic tumor (n=736 of 772; 95.3%). Anatomically, these tumors were most frequently located in multiple regions (n=444 of 736; 60.3%), followed by the jejunoileum (n=126; 17.1%), and duodenum (n=104; 14.1%). Among the 444 lymphoma cases with lesions in multiple regions, small intestine segments (duodenum and jejunoileum) were involved in 308 cases (69.4%), small and large intestine segments (cecum, colon, and rectum) were involved in 86 cases (19.4%), and stomach, small intestine, and large intestine segments were involved in 28 cases (6.3%). Among the lymphomas, 575 (78.1%) were mucosal lymphomas that were predominantly diagnosed via endoscopic biopsy (Supplementary Fig. 3). Mucosal lymphomas most frequently affected multiple regions of the GI tract (n=438 of 575; 76.2%), followed by the duodenum (n=72; 12.5%), and jejunoileum (n=45; 7.8%). Non-mucosal lymphomas most frequently affected multiple regions of the GI tract (n=81 of 161; 50.3%), followed by the duodenum (n=31; 19.3%), and rectum (n=16; 9.9%). A total of 201 lymphomas were immunohistochemically classified as T-cell lymphomas (n=171) or B-cell lymphomas (n=30). The mean age of dogs with T-cell lymphoma was significantly higher than that of dogs with B-cell lymphoma (9.9 vs. 8.0 years; P=0.005).
T-cell lymphomas were most frequently located in multiple regions (n=88 of 171; 51.5%), followed by the jejunoileum (n=48; 28.1%) and duodenum (n=27; 15.8%). Approximately half of the T-cell lymphomas (n=86; 50.3%) were mucosal lymphoma. Statistical analyses revealed that Shiba dogs and Pugs had a significantly higher risk of developing T-cell lymphoma than the rest of the canine population. Moreover, the mean age of Shiba dogs with T-cell lymphoma was significantly lower than that of other breeds with T-cell lymphoma (7.0 vs. 10.3 years; P=0.006), and 33.3% (n=11 of 33) of Shiba dogs with T-cell lymphoma were ≤5 years of age.
B-cell lymphomas were most frequently located in the rectum (n=9 of 30; 30.0%), followed by the colon (n=7; 23.3%) and stomach (n=7; 23.3%). There was no mucosal lymphoma in the B-cell lymphoma cases. Miniature Dachshunds had a significantly higher risk of developing B-cell lymphoma, particularly involving the colorectum (n=8 of 13; 61.5%). The mean age of Miniature Dachshunds with B-cell lymphoma was significantly lower than that of other breeds with B-cell lymphoma (6.6 vs. 8.5 years; P=0.03), and 46.2% (n=6 of 13) of Miniature Dachshunds with B-cell lymphoma were ≤5 years of age.
Plasmacytoma was the second most common hematopoietic tumor (n=26 of 772; 3.4%), consisting of 17 anaplastic plasmacytomas and 9 indolent plasmacytomas. These tumors were most frequently located in the stomach (n=16 of 26; 61.5%), followed by the rectum (n=8; 30.8%). French Bulldogs had a significantly higher risk of developing plasmacytoma; however, the ORs had wide 95% CIs.
Epithelial tumors
Epithelial tumors (n=423) accounted for 32.3% of GI tumors, which included adenocarcinoma (n=212 of 423; 50.1%), adenoma (n=196; 46.3%), neuroendocrine carcinoma (n=8; 1.9%), and undifferentiated carcinoma (n=7; 1.7%). The adenocarcinomas included signet-ring cell carcinomas (n=75 of 212; 35.4%), acinar adenocarcinomas (n=51; 24.1%), papillary adenocarcinomas (n=35; 16.5%), tubulopapillary adenocarcinomas (n=28; 13.2%), mucinous adenocarcinomas (n=16; 7.5%), tubular adenocarcinomas (n=3; 1.4%), unclassified adenocarcinomas of the esophagus (n=3; 1.4%), and adenosquamous carcinoma (n=1; 0.5%). The mean age of dogs with adenomas was significantly lower than that of dogs with adenocarcinomas (9.6 vs. 10.3 years; P=0.049). Epithelial tumors involving multiple regions were observed in 10 cases, including 8 adenocarcinomas (6 papillary adenocarcinomas and 2 acinar cell carcinomas), 1 neuroendocrine carcinoma, and 1 adenoma. In addition, 6 cases exhibited different types of epithelial tumors that developed independently in distinct regions of the GI tract (e.g., papillary adenocarcinoma in the stomach and adenoma in the rectum). Notably, half of these 16 cases with epithelial tumors in multiple regions or with multiple different types of epithelial tumors occurred in Jack Russell Terriers (n=8; 50%).
In adenoma, there was a significant male predominance among the adenoma cases (female-to-male ratio=1:1.76). Adenomas were most frequently found in the rectum (n=82 of 196; 41.8%) and colon (n=76; 38.8%). Miniature Dachshunds, French Bulldogs, Jack Russell Terriers, and West Highland White Terriers had a significantly higher risk of developing adenoma. For anatomical distribution by breed, adenomas were most frequently located in the colon in Miniature Dachshunds (n=43 of 75; 57.3%), whereas they were most frequently located in the rectum in French Bulldogs (n=14 of 19; 73.7%) and West Highland White Terriers (n=4 of 4; 100.0%). In Jack Russell Terriers, adenomas were most frequently located in both the stomach and rectum (n=6 of 16; 37.5%). The mean ages of French Bulldogs and Jack Russell Terriers with adenomas were significantly lower than those of other breeds with adenomas (5.5 and 8.1 years, respectively; each P<0.001). In particular, 52.6% (n=11/19) of French Bulldogs with adenomas were ≤5 years of age. In Miniature Dachshunds, more than half of colorectal adenoma cases (n=37 of 69; 53.6%) showed inflammatory polyp lesions within the same specimen (Supplementary Fig. 4).
In adenocarcinomas, no significant sex predilection was observed for any of the tumor types. Adenocarcinomas were most frequently located in the stomach (n=112 of 212; 52.8%) and jejunoileum (n=36; 17.0%). Only three adenocarcinomas (1.4%) involved the esophagus. French Bulldog, Jack Russell Terrier, Shih Tzu, and Miniature Schnauzer had a significantly higher risk of developing adenoma. The mean age of French Bulldogs with adenocarcinoma was significantly lower than that of other breeds with adenocarcinoma (9.4 vs. 10.5 years; P=0.02).
Signet-ring cell carcinoma was the most common adenocarcinoma (n=75 of 212; 35.4%). There was a significant male predominance among signet-ring cell carcinoma cases (female-to-male ratio=1:1.59). These tumors were predominantly located in the stomach (n=72 of 75; 96.0%). French Bulldogs had a significantly higher risk of developing signet-ring cell carcinoma, with all cases involving the stomach.
Acinar and papillary adenocarcinomas were the third and fourth most common adenocarcinomas, respectively (n=51 of 212; 24.1%; n=35 of 212; 16.5%, respectively). There was a significant male predominance among the papillary adenocarcinoma cases (female-to-male ratio=1:1.5). Both tumor types were most frequently located in the jejunoileum (n=15 of 51; 29.4%; n=11 of 35, 31.4%, respectively). Jack Russell Terriers had a significantly higher risk of developing both acinar and papillary adenocarcinomas. The mean age of Jack Russell Terriers with acinar adenocarcinoma was significantly lower than that of other breeds with acinar adenocarcinoma (5.5 and 8.1 years, respectively; P=0.035).
Tubulopapillary adenocarcinoma was the fifth most common adenocarcinoma (n=28 of 212; 13.2%). There was a significant male predominance among the tubulopapillary adenocarcinoma cases (female-to-male ratio=1:1.55). Jack Russell Terriers and Shih Tzus had a significantly higher risk of developing tubulopapillary adenocarcinoma.
Other less common types of adenocarcinomas included mucinous adenocarcinomas (n=16 of 212; 7.5%), tubular adenocarcinomas (n=3; 1.4%), unclassified adenocarcinomas of the esophagus (n=3; 1.4%), and adenosquamous carcinoma (n=1; 0.5%). No significant sex predilection was observed for any of these tumor types. Mucinous adenocarcinomas were most frequently located in the jejunoileum (n=9 of 16; 56.3%).
Other less common types of epithelial tumors included neuroendocrine carcinomas (n=8; 1.9%) and undifferentiated carcinomas (n=7; 1.7%). No significant sex predilection was observed for any of these tumor types. Neuroendocrine carcinomas were most frequently located in the stomach and duodenum (each n=3 of 8; 37.5%), whereas undifferentiated carcinomas were primarily located in the stomach (n=6 of 7; 85.7%).
Mesenchymal tumors
Mesenchymal tumors (n=110) accounted for 8.4% of GI tumors, which included gastrointestinal stromal tumor (GIST) (n=44 of 110; 40.0%), leiomyoma (n=40; 36.4%), peripheral nerve sheath tumor (n=11; 10%), sarcoma NOS (n=7; 6.4%), leiomyosarcoma (n=3; 2.7%), hemangiosarcoma (n=2; 1.8%), and fibroma (n=1; 0.9%), ganglioneuroma (n=1; 0.9%), and osteosarcoma (n=1; 0.9%). No significant sex predilection was observed for any of the tumor types.
GISTs were the most common mesenchymal tumors (n=44 of 110; 40.0%). These tumors were most frequently located in the cecum and jejunoileum (each n=13 of 44; 29.5%), followed by the stomach (n=8; 18.2%). Pembroke Welsh Corgis exhibited a high odds ratio for GIST, although the difference was not statistically significant.
Leiomyomas were the second most common mesenchymal tumors (n=40 of 110; 36.4%). These tumors were most frequently located in the stomach (n=19 of 40; 47.5%). No specific breed predisposition has been identified for leiomyoma.
Other less common types of mesenchymal tumors included peripheral nerve sheath tumors (n=11 of 110; 10.0%), sarcoma not otherwise specified (NOS; n=7; 6.4%), leiomyosarcoma (n=3; 2.7%), hemangiosarcoma (n=2; 1.8%), and fibroma, ganglioneuroma, and osteosarcoma (each n=1; 0.9%). Peripheral nerve sheath tumors were most frequently located in the stomach (n=8 of 11; 72.7%). One case of ganglioneuromatosis involved the jejunoileum, colon, and rectum.
Other types of tumors
Mesothelioma (n=2) was a rare tumor located in the jejunoileum (n=1) and colon (n=1). There were three cases of secondary GI tumors. Of these, two involved invasive lesions of perianal gland tumors in the rectum, and the other involved an invasive lesion of pancreatic acinar cell carcinoma in the duodenum.
DISCUSSION
The present study describes the epidemiological trends of canine GI tumors based on an analysis of 1,310 GI tumor cases submitted to our laboratory between 2012 and 2024. Most dogs that underwent GI biopsy were small- or medium-sized breeds, which is largely consistent with the trend observed in the canine population in Japan [2, 15]. The reported prevalence of canine GI tumors varies according to the region and study period. The prevalence of canine GI tumors was 1.1% in the USA (1962–1975) [34] and 4.2% (calculated from the data presented in reference [12]) in Switzerland (1955–2008). In the present study, the prevalence was 10.4% (1,310/12,639 cases), which was higher than that previously reported. As this study population consisted of referral cases from secondary hospitals, there is a potential selection bias. Despite this bias, to the best of our knowledge, this is the first large-scale investigation of canine GI tumors in Japan.
The WHO classification of tumors in domestic animals serves as an important reference for both pathological diagnosis and epidemiological research on canine GI tumors [7, 27, 30, 34, 35, 39, 45]. Lymphoma is one of the most common types of GI tumors [11, 19, 27, 30, 49]. In the present study, the relative frequency of lymphoma was 56.3%, which is higher than that reported in previous studies [11, 30]. Most of these lymphomas were considered primary GI tract tumors, based on the results of blood tests and imaging examinations performed before the biopsy. Histologically, the majority were mucosal lymphomas predominantly diagnosed using endoscopic biopsy samples. Because mucosal lymphoma does not typically form a distinct mass and may appear unremarkable on imaging, endoscopic examination is considered a useful modality for its detection in affected dogs [8, 25, 49]. In the present study, endoscopic GI biopsy was performed to determine the cause of chronic and refractory GI symptoms. Therefore, the high relative frequency of lymphomas observed in the present study may be attributed to the increased detection of mucosal lymphoma by endoscopic examination, which is likely to be used more often than in the previous studies. In the participating secondary referral hospitals, a large number of biopsy samples were collected per endoscopic procedure, and high-quality histopathological specimens were obtained by mounting the biopsy samples on filter paper [28]. In addition, ileal biopsies—which were not routinely performed in earlier years—have recently been conducted more proactively. These factors may have contributed to improved diagnostic accuracy for GI lymphoma. The prevalence of gastrointestinal tumors was 4.8% when excluding the 736 lymphoma cases, which is comparable to the prevalence in previous studies [12]. This suggests that the high overall prevalence of GI tumors in the present study may be attributed to increased diagnosis of mucosal lymphoma by endoscopic biopsy.
T-cell lymphomas commonly involved the jejunoileum, duodenum, and multiple regions, whereas B-cell lymphomas commonly involved the colon, rectum, and stomach, consistent with previous findings [4, 6, 7, 9, 19, 27]. Previous studies in the USA have reported breed predispositions to GI lymphoma in Boxers, Labrador Retrievers, Shar Peis, Golden Retrievers, and Rottweilers [4, 6, 49]. In Japan, previous studies have reported that Shiba dogs may be predisposed to T-cell lymphoma associated with chronic inflammatory enteropathy [26, 31, 32] and that Miniature Dachshunds may be predisposed to colorectal B-cell lymphoma at a young age [19, 33]. The present study confirmed that Shiba dogs and Pugs have a higher risk of developing T-cell lymphoma than other dog breeds. Shiba dogs are often affected at younger ages. In addition, the present study confirmed that Miniature Dachshunds have a higher risk of developing B-cell lymphoma, particularly in the colorectum, and are often affected at a young age. The high prevalence of GI lymphomas in these breeds may be unique to the Japanese canine population.
Plasmacytomas were primarily located in the stomach and rectum, which is consistent with previous findings [12, 18, 23]. The results of the present study suggest that French Bulldogs have a higher risk of developing plasmacytoma, but the ORs had wide 95% CIs. This may be due to the small sample size; further studies with larger populations are needed to confirm the potential breed predisposition.
Epithelial tumors are among the most common types of GI tumors in dogs [11, 30]. In this study, the prevalence of gastrointestinal epithelial tumors was 3.3% (n=423 of 12639), which was comparable to the prevalence reported in a previous study (3.4%; estimated from the data presented in reference [11]). A significant male predominance was observed. Additionally, dogs with adenomas were significantly younger than those with adenocarcinomas. Adenomas are predominantly located in the colorectum, whereas adenocarcinomas are most frequently located in the stomach. These findings are consistent with those of previous reports [1, 12, 37]. The underlying biological mechanisms of this male predominance remain unclear and further studies focusing on sex hormones and genetic factors are required.
Several previous studies have reported breed predispositions to GI epithelial tumors, including German Shepherds and Collies to intestinal adenocarcinomas [41], French Bulldogs and West Highland White Terriers to colorectal adenomas [7, 27], and Tervuren Belgian Shepherds, Bouvier des Flandres, Groenendaels, Collies, Standard Poodles, and Norwegian Elkhounds to gastric adenocarcinomas [13, 22, 38]. In contrast, the present study found breed predispositions to epithelial tumor types, primarily in small- and medium-sized breeds. This discrepancy may reflect differences in breed popularity across countries.
Jack Russell Terriers bred in Japan are known to develop hereditary gastrointestinal polyposis associated with germline APC mutations, presenting as single (predominantly gastric) or multiple GI epithelial tumors [46,47,48]. In the present study, Jack Russell Terriers had a higher risk of developing adenoma, acinar adenocarcinoma, papillary adenocarcinoma, and tubulopapillary carcinoma. These tumors often affect the stomach or multiple GI sites. In addition, this breed often develops adenomas and acinar adenocarcinomas at a younger age. Therefore, the high prevalence of epithelial tumors in Jack Russell Terriers may be associated with hereditary gastrointestinal polyposis.
Among the other breeds, Miniature Dachshunds, French Bulldogs, and West Highland White Terriers had a higher risk of developing adenoma, most commonly in the colorectum. French Bulldogs often develop colorectal adenomas at a young age, which is consistent with previous reports [7]. In Miniature Dachshunds, more than half of colorectal adenoma cases exhibited inflammatory polyp lesions within the same specimen. In Japan, colorectal epithelial tumors associated with inflammatory colorectal polyps have been reported in this breed [37]. These findings suggest that adenoma pathogenesis in Miniature Dachshunds may be associated with inflammatory colorectal polyps. In addition, French Bulldogs had a higher risk of developing signet-ring cell carcinoma, and Shih Tzus had a higher risk of developing tubulopapillary adenocarcinoma. To our knowledge, these predispositions have not been reported in other countries and may be unique to the canine population in Japan.
Mesenchymal tumors were relatively uncommon in the GI tract, except in the cecum and esophagus, consistent with previous reports [12, 27, 36]. In the present study, GISTs were the most common mesenchymal tumors, in contrast to earlier studies that reported leiomyosarcoma as the most common [27, 34, 39, 45]. GISTs frequently harbor c-kit mutations and respond to tyrosine kinase inhibitors. [3, 5, 10, 36]. Therefore, distinguishing GISTs from other mesenchymal tumors is of clinical importance. Previous studies have shown that many tumors initially diagnosed as leiomyosarcomas using H&E slides were later reclassified as GISTs following IHC evaluation using KIT and DOG-1 [24, 36]. In the present study, sarcomas (excluding hemangiosarcoma and osteosarcoma) were classified based on IHC findings, which may explain the discrepancy with earlier reports and highlight the importance of IHC for the accurate classification of GI mesenchymal tumors.
The present study revealed breed predispositions for specific GI tumor types, which may be unique to the Japanese canine population. These findings are useful for the diagnosis and treatment of canine GI tumors. This study also revealed that some breeds tended to develop specific GI tumors at a younger age. However, differences in average lifespan among breeds were not adopted in the statistical analyses, and this limitation should be considered when interpreting breed-specific age distributions [15]. Although there was a potential selection bias and statistical limitation in the study population, this is the first epidemiological investigation of canine GI tumors in Japan. Further genetic studies are necessary to elucidate the mechanisms underlying breed-specific predispositions to GI tumors.
CONFLICT OF INTEREST
The authors declare no potential conflicts of interest for the research, authorship, and/or publication of this manuscript.
Supplementary
Acknowledgments
The authors thank the Data Science Commons at the Mathematical and Informatics Center, The University of Tokyo, for their valuable comments on the statistical analysis in this study.
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