Natural Disease. Feline Intestinal Adenocarcinoma

Transcription

1 Natural Disease Vet. Pathol. 13: 1-10 (1976) Feline Intestinal Adenocarcinoma A Clinicopathologic Study of 22 Cases A. K. PATNAIK, S.-K. LIU and G. F. JOHNSON Departments of Pathology and Medicine, The Animal Medical Center, New York, N.Y. Abstract. Twenty-two cases of intestinal adenocarcinoma were diagnosed in an 11- year survey of 3 I45 feline necropsies. Histologically, tumors were grouped into four classes: (I) carcinoma with solid groups of cells, (2) adenocarcinoma with solid and acinar cells, (3) papillary adenocarcinoma, and (4) mucinous adenocarcinoma. Tumors were commonest in the ileum. Connective tissue, as well as epithelial metaplasia, were associated more often in this group of intestinal adenocarcinomas than seen before. Hypertrophy and hyperplasia of muscular layers of the unaffected sections of intestines were seen in most of the small bowel and in half of the large bowel carcinomas in this series. Intestinal adenocarcinoma occurs more rarely in the cat than in man and the dog. Adenocarcinomas of all segments of the intestine have been seen in cats, but the ileum is the commonest site (8.25%) [8]. In contrast, the commonest sites in man and the dog are the colon and duodenum [8]. Sixtyeight cases of intestinal adenocarcinoma in the cat, excluding duodenal adenocarcinoma, have been reported [8]. The reported incidence of intestinal adenocarcinoma among all feline neoplasms varied from 0.4 to 2.9% [4-6, , whereas the incidence among neoplasms of the alimentary tract varies only from 6.6 to 13.0% [2,4]. Sex and breed predispositions were not reported in any previous studies, but the reported ages of the animals ranged from 4 to 14 years. Materials and Methods A review of feline neoplasms recorded in the necropsy files of 3145 cats at the Animal Medical Center pathology department showed that 22 cases of adenocarcinoma of various intestinal segments had been diagnosed during an I I-year period. The clinical history,

2 2 PATNAIK/LIU/JOHNSON complete autopsy records, and all available slides were studied. All tissues were processed using standard techniques and were stained with hematoxylin and eosin. In required cases, special staining procedures for rnucin and connective tissue elements were done. Results A total of 289 nonhematopoietic neoplasms were diagnosed in 264 cats. There were 83 neoplasms of the digestive system, of which 22 were intestinal adenocarcinomas. Eighteen of the adenocarcinomas were in the small bowel, and four in the large bowel. The frequency of all intestinal adenocarcinoma was 8.3"" among the cats with neoplasms and 0.7", among the 3145 cats necropsied during this period. Intestinal adenocarcinomas also composed the single largest group (26.5",,) of neoplasms of the digestive system. The ages of affected cats varied from 5 to 17 years, with a mean of 11.3 years. The frequency of adenocarcinoma in Siamese cats was nearly three times that in domestic short-haired cats, which was the only other breed found to have intestinal adenocarcinomas (table I). The frequency of adenocarcinoma in males (0.9"") was more than twice that in females (0.400), although all malignant nonhematopoietic neoplasms were more frequent in females (table 11). The common clinical signs associated with the adenocarcinomas were depression, anorexia, and loss of weight over periods from 5 days to 6 months. Vomiting was also a common clinical sign, especially with small bowel adenocarcinomas. Swollen, fluid-filled abdomens and palpable masses (in six cats) occurred in most cats. Partial intestinal obstruction could be seen in radiographs in most cats after administration of barium. One cat with rectal carcinoma suffered from wasting, anorexia, ascites, constipation, and straining to defecate. Eighteen of the 22 adenocarcinomas occurred in the small bowel and four in the large bowel. The ileum was the commonest site, accounting for half of the tumors (table 111). The distribution of the four carcinomas of the large bowel was as follows: one in the cecum and colon, two in the colon alone, and one in the rectum. In more than half the cases, fluid was seen in the abdominal cavity at surgery or at necropsy. Distinct peritoneal neoplastic implants were seen in eight (36.49,) cats. In all cases of small bowel adenocarcinoma, the intestinal lesions consisted of annular constrictions affecting 1- to 6-cm lengths of the intestine,

3 Feline Intestinal Adenocarcinoma 3 Table I. Breed distribution of 22 cats with intestinal adenocarcinoma Breed Number of intestinal Number of cats Number of feline adenocarcinomas with neoplasms (264) necropsies (3145) Domestic shorthair 14 Siamese 8 Others Table 11. Sex distribution of 22 cats with intestinal adenocarcinoma Sex Number of intestinal Number of cats Number of feline adenocarcinomas with neoplasms (264) necropsies (3145) Male Female Not recorded Location Table III. Segmental distribution of intestinal adenocarcinoma Small intestine Duodenum 2 Jejunum 1 Multiple (jejunum and duodenum) 1 Ileum 9 Site not described 5 Large intestine Cecum and colon 1 Colon 2 Rectum 1 Number of tumors resulting in various degrees of stenosis. Although the intestinal walls were thicker than normal, various lengths of poststenotic dilatation of the lumen were seen. The degree of dilatation varied in different cases (fig. 1). Gross mucosal ulceration was commoner in large bowel carcinomas than in the small bowel carcinomas, but was seen in 1 I of the 22 cats, especially at the junction of the dilatation. In most cases of small bowel carcinoma, the wall of the entire anterior part of the intestines was grossly thickened and the

4 4 PATNAIK/LIU/JOHNSON Fig. 1. Adenocarcinoma in the ileum of a cat. showing annular constriction (A), poststenotic dilatation (B), and hypertrophied muscular wall (C). intestinal loops less pliable than usual. Often the mesentery or the omentum, or both, adhered to the neoplastic section of the intestines. In the cases of colonic or cecal adenocarcinomas, the stenosis was less obvious, although the bowel wall was thickened at and anterior to the tumor site. In the case of the rectal adenocarcinoma, there was constriction preceded by ulcerated polypoid intraluminal growths. The rectal wall was grey and thickened and contained serosal implants. Intraluminal growths were not seen in any of the other cases of adenocarcinoma. The 18 tumors were considered highly malignant. Gradual anaplastic changes from normal to malignant tissue were present in almost all of them, and they had infiltrated the submucosa, muscular layer, and serosa. In 15, they extended into the mesentery, resulting in diffuse peritoneal carcinomatosis. Ulceration at the primary site, severe desmoplastic reaction, muscular hypertrophy, infiltration of neoplastic cells, and luminal stenosis were characteristic features. Anaplastic changes were seen around the lumen and close to the constriction. Adenocarcinomas were classified into four groups according to histologic characteristics. Adenocarcinoinas with solid groups of cells (carcinoid). Two neoplasms, both in the ileum, were characterized by solid group cells in the lamina (fig. 2). They had also infiltrated the layers of the intestines, either in

5 Feline Intestinal Adenocarcinoma 5 Fig. 2. Adenocarcinoma with solid groups of cells showing infiltrating polygonal and round epithelial cells with vesiculated nuclei and prominent nucleoli. HE. small compact groups or in single file. There was marked muscular hypertrophy and a mild desmoplastic reaction. There were very few acinar structures, and individual cells were polygonal to round with large vesiculated nuclei and prominent nucleoli. Ample granular and eosinophilic cytoplasm was seen in the tumor cells, especially in the infiltrating cells. Both tumors had metastasized to the mesentery, omentum, and the regional lymph nodes. Adenocarcinomas with solid and acinar cells. Half (nine) of the small bowel adenocarcinomas belonged to this group. In six cats, the tumors were in the ileum, whereas in one the tumor was in the duodenum. The exact site of the tumors in two cats was not recorded. Tumors in this group were characterized by undifferentiated cells that formed small acini or solid groups of cells in the lamina, submucosa, and muscularis. Desmoplastic reactions were severe, resulting in complete replacement of the muscular layers and mesentery. Areas of hyalinization in this group of tumors were commoner than in the other three groups and, in one case, resulted in osteoid metaplasia around the acinar cells of the adenocarcinoma. The acinar cells were mainly columnar, rarely cuboid. The solid groups were mainly round or polygonal. The individual cells were large with ample pale cytoplasm and vesiculated nuclei

6 6 PATNAIK/LIU/JOHNSON with prominent nucleoli. Mucin production and papillary formations were not characteristic of this group of tumors. Diffuse peritoneal carcinomatosis was seen in seven of the nine cats. Metastasis was seen in the regional lymph nodes in three cats, in the lungs in two, and in the spleen in one. Papillary adenocarcinoma. There were three cats in this group. One had multiple tumors in the duodenum and jejunum, one had a tumor in the ileum, and the third a duodenal tumor. All these tumors were characterized by a high proportion of well-differentiated columnar cells that formed large acini containing secretions and cellular debris. The acini often formed papillary structures (fig. 3). These histologic structures were maintained as malignant cells infiltrated the intestinal wall, mesentery, and other organs. The neoplasm in the duodenum showed areas of squamous metaplasia with transition from columnar to squamous cells in some acini (fig. 4). There was peritoneal carcinomatosis with a connective tissue reaction in all the cases. Metastases to the regional lymph nodes, kidney, and spleen were seen in this group. These neoplasms were histologically similar to the adenocarcinomas of the large bowel. Mucinous adenocarcinoma. Four of the 18 small bowel tumors, three of the ileum and one of the jejunum, were characterized by small acini and solid groups of cells that produced mucin and infiltrated the intestinal wall and the mesentery (fig. 5). Large areas of mucin that had replaced the normal structures were seen in both the muscular layers of the intestine and in the metastases. These areas contained few cellular elements. The cells forming the acini were mostly cuboidal or columnar, but many signet ring cells were also seen. In addition, the adenocarcinoma in the jejunum contained large cystic structures lined with columnar cells and condensed secreted material, some of which showed osteochondroid metaplasia, seen primarily in the serosa. Peritoneal carcinomatosis had occurred in three of the four cases, and metastasis to the lymph node and the spleen had occurred in one. Although the primary intestinal lesions involved a very small segment of the small intestines, infiltration of the intestinal wall occurred in all cases. The metastasis to other organs was as follows: regional lymph nodes, eight; spleen, three; lungs, two; and kidney, one. In 14 of the 18 cases of small bowel adenocarcinomas, distinct hypertrophy and hyperplasia of the muscular layers, not directly involved with tumor and mostly anterior to it, were seen. The inner circular layer was more severely affected than the longitudinal layer. Some were more than four to five times their normal thickness. Segments of fibrosis were seen in the submucosa in some cases, although the mucosa remained essentially normal in

7 Feline Intestinal Adenocarcinoma 7 Fig. 3. Papillary adenocarcinoma showing intraluminal papillary projections. HE. Fig. 4. Papillary adenocarcinoma showing squamous metaplasia. HE. Fig. 5. Mucinous adenocarcinoma showing infiltrating signet ring cells and mucinous spaces. HE.

8 8 PATNAIK/LIU/JOHNSON all. Significant connective tissue reactions were not seen in those areas, in contrast to neoplastic areas. In contrast to the small bowel neoplasms, the four adenocarcinomas of the large bowel, including the rectal tumor, were histologically similar and were much like the group of papillary adenocarcinomas of the small bowel. They formed large acinar structures with multiple intraluminal papillary projections. Cellular debris was seen in the acini of these tumors, and mucin was seen in two cases. These large acinar structures infiltrated the muscularis and the mesentery. The cells were well differentiated, primarily of the columnar type, with ample eosinophilic cytoplasm and large hyperchromic nuclei. The connective tissue reaction was less marked. In three of these cases, infiltration of the pelvic (rectal) and peritoneal cavities occurred. Only one tumor, originating from the cecum and colon, had metastasized to the lungs. Discussion Although all domestic animals, including the cat, share the same environment as man, they have fewer adenocarcinomas of the intestines [8]. Adenocarcinomas of the rectum and colon are among the most frequent neoplasms in man, and duodenal neoplasms compose 45 O,, of the small bowel carcinomas in man [7]. Although intestinal carcinomas are rare in the dog, the rectum and colon are the commonest sites [l, 81. In contrast, the commonest site of intestinal tumors in the cat is the small bowel, especially the ileum [2-4]. In this series of 22 bowel adenocarcinomas, half of the 18 that involved the small bowel originated in the ileum. There was only one rectal adenocarcinoma. The age incidence in cats in our series agreed with previous reports [2,8], but a higher incidence in the males and in the Siamese cats was noted for the first time (table I). Racial predisposition of some human bowel carcinomas has been reported [7], and rectal carcinomas in man are twice as frequent in males as in females [7]. Among the reported cases of rectal carcinomas in dogs, males were more frequently affected than females [8]. Boxers have the highest incidence of any breed in many types of cancer, including neoplasms of the gastrointestinal tract [2]. All the neoplasms in this group were considered malignant. In 18, there were various degrees of peritoneal involvement, indicating that these cases had been diagnosed late. The papillary adenocarcinomas were the most histologically differentiated tumors, and therefore considered likely to be the

9 Feline Intestinal Adenocarcinoma 9 least malignant but had the highest frequency of metastasis. Thus, the histologic grading [8] may not be a very useful method of classification for these tumors. Histologic classification is still useful to determine the location of the neoplasms in most cases. The mixed solid and acinar carcinomas affected all segments of the small bowel. Only three out of the 18 small bowel carcinomas, but all the large bowel neoplasms, were classified as papillary adenocarcinomas. All the mucinous adenocarcinomas occurred in the small bowel, and in three of these occurred in the ileum. The histologic characteristics of the two solid adenocarcinomas in the ileum were similar to those of the carcinoids of man [7]. The clinical signs seen in man did not occur in these cases in the cat. Metaplasia associated with these adenocarcinomas was more frequent than previously described. Two cases of osteoid or osteochondroid metaplasia in the associated tissues were seen. In a third case, squamous metaplasia of the neoplastic acinar cells was seen. Osteoid metaplasia has been described in only one tumor [3]. Hypertrophy and hyperplasia of the muscular layers of the small bowel occurred in the non-affected intestinal segments in 14 of the small bowel, and two of the large bowel adenocarcinomas. This was considered to be a compensatory reaction caused by obstruction of the normal flow of contractile movements resulting from infiltrating neoplastic cells, reactive connective tissue replacing muscular cells, or damaged nerve plexuses at the primary site of the neoplasm. Ackno wledgenient Support of the Bodman Foundation is gratefully acknowledged. References I BRODEY, R. S. and COHEN, D. : An epizootiologic and clinicopathologic study of diseases of gastrointestinal neoplasms in the dog. Scient. Proc. IOlst Annu. Meet. Am. Vet. Med. Ass., pp (1964). 2 BRODEY, R.S.: Alimentary tract neoplasms in the cat. A clinicopathologic survey of 46 cases. Am. J. vet. Res. 27: (1966). 3 COTCHIN, E.: Further examples of spontaneous neoplasms in the cat. Br. Vet. J. 112: (1956). 4 COTCHIN, E.: Neoplasia in the cat. Vet. Rec. 69: (1957). 5 DORN, C.R.; TAYLOR, D.O.; FRYE, F.L., et al.: Survey of animal neoplasms in Alameda and Contra Costa Counties, California. I. Methodology and description of cases. J. natn. Cancer Inst. 40: (1968).

10 10 PATNAIK/LIL/JOHNSON 6 ENGLE, G.C. and BRODEY, R.S.: A retrospective study of 395 feline neoplasms. J. Am. Anim. Hosp. Ass. 5: (1962). 7 EVANS, R. W. : Histological appearance of tumors; 2nd ed., pp (Livingstone, London 1966). 8 LINGEMANN, C.H. and GARKER, F. M.: Comparative study of intestinal adenocarcinomas of animals and man. J. natn. Cancer Inst. 48: (1972). 9 MULLIGAN, R.M.: Spontaneous cat tumors. Cancer Res. 11: 271 (1951). 10 NEILSON, S. W. : Neoplastic diseases; In CATCOTT Feline medicine and surgery, pp (American Veterinary Publications, Inc., Santa Barbara, Calif. 1964). I1 SCHMIDT, R.E. and LANGHAM, R.F.: A survey of feline neoplasms. J. Am. vet. med. ASS. 151: (1967). I2 SMITH, H.A. and JONES, T.C.: Veterinary pathology; 3rd ed. (Lea & Febiger, Philadelphia 1966). 13 TAYLOR, P. F. and KAFER, J. C.: Adenocarcinoma of the intestines of dog and cat. Aust. vet. J. 30: (1954). 14 WHITEHEAD, J.E.: Neoplasia in the cat. Vet. Med.lSmall Anim. Clin. 62: (1967). Dr. A.K. PATNAIK, Department of Pathology, The Animal Medical Center, 510 East 62nd St., New York, NY (USA)