Vet. Pathol. 19:608-615 (1982)

Extracutaneous Mast-Cell Tumor in the Dog A. K. PATNAIK, E. G. MACEWEN, A. P. BLACK,and S. LUCKOW

Departments of Pathology, Oncology, and Surgery, The Animal Medical Center, New York, N.Y.

Abstract. Three neoplasms of extracutaneous mast-cell origin, arising from the nasopharynx, oral cavity, and hepatopancreatic lymph nodes respectively, were diagnosed in three dogs. The neoplasms had histologic features similar to those of cutaneous mast-cell tumors, but had limited metastasis mostly involving the regional lymph nodes. One dog had a perforating duodenal ulcer, suggesting that duodenal ulcers can occur with extracutaneous tumors as they do with some cutaneous mast-cell tumors in the dog.

Neoplasms of mast-cell origin usually affect the skin, and are among the most common cutaneous neoplasms in the dog [6, 101. In 76% of these tumors the regional lymph nodes, and less commonly other visceral organs, become involved secondarily [6]. Primary sites of canine mast-cell tumor other than the skin, including the oral cavity [3, 5 , 121 and larynx [l], have been reported rarely, and a mast-cell tumor arising from the intestines of a dog has been described recently [ 111. Focal mast-cell infiltration involving more than one lymph node in a dog has been reported, and was considered a benign accumulation of mast cells in the lymph nodes [9]. We describe three mast-cell tumors arising from three different extracutaneous sites in dogs.

Case Histories

Dog 1, a nine-year-old female mongrel, had progressive dyspnea and weight loss for four months. A mass close to the larynx on the right side was palpated. Radiography showed a retropharyngeal soft-tissue mass. Results of blood and biochemical testing were within normal limits except for a white blood cell count of 19,500 cells/pl. Examination of a biopsy specimen taken through the soft palate showed that the neoplasm was a mast-cell tumor. The dog was killed and necropsied. Dog 2, a ten-year-old male poodle with a swollen, inflamed right upper lip, had a history of chronic sneezing and weight loss, and no response to antibiotics over a period of a few weeks. Physical examination showed a 4 x 4 x 3-cm, ulcerating, mucosal mass in the upper lip, mostly to the right of the midline. The mass infiltrated the gum, anterior palate, and nasal septum. The submandibular lymph node on the 608

Mast-Cell Tumor

609

same side was moderately enlarged (2 X 2 X 2 cm). A biopsy specimen from the mass was diagnosed as medium-grade mast-cell tumor. The dog was treated with various anticancer drugs. Periods of remission of up to 25% alternated with periods of relapse over the next 6% months. Subsequently the neoplasm and the regional lymph nodes on both sides enlarged, and there was severe regional edema and profuse bleeding from the neoplasm. The dog also had anorexia and vomiting. It was killed and necropsied. Dog 3, a seven-year-old male German shepherd, was examined for heavy breathing, listlessness and vomiting of four days' duration that usually occurred after eating. On examination the dog had a high respiratory rate, slight fever (39.5' C), pain on abdominal palpation, hydroperitoneum and a palpable, midabdominal mass. The latter two abnormalities were confirmed by radiography. Abdominal exploratory surgery showed a ruptured duodenal ulcer with peritonitis, and a mass dorsal to the pylorus. Frozen and regular tissue sections from the mass were examined, and mastcell tumor was diagnosed. The dog was killed and necropsied. He had been examined regularly throughout his life, and no cutaneous tumors had ever been found.

Materials and Methods Tissue sections from all three neoplasms were fixed in 10% buffered formalin, processed routinely and stained with hematoxylin and eosin (HE), mucicarmine, and Giemsa stains.

Results Gross lesions

Dog 1 had a 6 X 4 X 4-cm, white, lobulated mass with intact mucosal surface in the right side of the nasopharynx that obstructed the passage (fig. 1) and infiltrated the surrounding tissue. The mandibular and submandibular lymph nodes on either side were moderately enlarged and firm, but no other abnormal lymph nodes were seen. The right parotid salivary gland was firm and focally mineralized. No cutaneous neoplasms were found, and no significant gross lesions were seen in the visceral organs. Dog 2 had an 8 X 6 X 6-cm, ulcerating, fungating mass that involved the upper lip and maxillary bones, and extended to the anterior palate (fig. 2). The mass partially obstructed the nasal passage but did not grow into it. The skin surface was intact. The mass, located mostly on the right of the midline, was grayish-white, firm and lobulated, and had extensive superficial necrosis. Another mass, 12 X 10 X 8 cm, involved the right mandibular lymph node. Both retropharyngeal lymph nodes were enlarged, the right to 5 x 3 X 2 cm and the left to 3 X 2 X 1 cm. The rest of the lymph nodes were of normal size. There was severe edema and hemorrhage in the mandibular and submandibular space and upper neck. The lungs were edematous. Two well-circumscribed areas, 0.5 cm in diameter, were seen in the left midventricular epicardium. The dog also had hepatic lipidosis, large adrenal glands and irregular kidneys. A search for cutaneous neoplasms was unfruitful.

610

Patnaik et al.

Fig. 1: Nasopharyngeal mass obstructing the passage (dog 1). Fig. 2 Mass involving maxilla, mucosal surface of upper lip, and nasal passage (dog 2).

Dog 3 had a 10 X 7 x 5-cm, well-circumscribed, grayish, multilobed mass with central necrosis in the area of the hepatopancreatic lymph nodes, close to the pancreas (fig. 3). The duodenal ulcer, approximately 3 cm in diameter and located 6 cm from the pylorus, had been sutured during surgery and was not physically related to the mass. The remainder of the intestines were edematous, and contained material mixed with blood, but no masses were seen. There was severe hemorrhage in the esophageal and gastric mucosa. No cutaneous lesions were found, and the lymph nodes, both peripheral and visceral (except the hepatopancreatic lymph nodes), were normal. Histology

The neoplasm in dog 1 was characterized by groups of round to spindle-shaped cells with indistinct, faintly eosinophilic, granular cytoplasm. There was minimal

Mast-Cell Tumor

611

Fig. 3: Well-encapsulated mass close to the pancreas (dog 3).

cellular and nuclear pleomorphism (fig. 4). The nuclei were hyperchromatic and vesiculated. There were scattered eosinophils, and no mitotic cells were seen. In some areas of the neoplasm, thick bands of connective tissue trapped groups or single rows of neoplastic cells. The connective tissue consisted mostly of collagen tissue with areas of hyalinization and necrosis. At the periphery of the tumor, neoplastic cells infiltrated the skeletal muscles, replacing the fibers. Most of the mandibular lymph node tissue was replaced with neoplastic cells with the same pattern as in the primary tumor, and only remnants of the lymphoid follicles remained. Tissue sections of the salivary glands showed areas of edema, necrosis, and mineralization. Neoplastic cells were not seen in other visceral organs, including the bone marrow. The neoplasm in dog 2 had the same histologic pattern as the primary tumor in dog 1, except that in dog 2 the neoplastic cells were mostly round, had hyperchromatic, condensed nuclei, and had more obvious cellular and nuclear pleomorphism. Eosinophils and mitotic figures were more common than in dog 1. Metastasis was seen in the lymph nodes, myocardium, and pituitary gland (fig. 5 , 6 ) . Neoplastic cells were not seen in other visceral organs nor in the bone marrow. In addition to the tumor, dog 2 had diffuse, focal, myocardial degeneration and necrosis, intramural coronary arteriosclerosis, and fibrinoid necrosis of arterioles of the heart, lungs, kidney, and brain. There was severe adrenocortical necrosis and atrophy. The glomerular capillaries were thick and granular and some were hyalinized. The neoplasm in dog 3 had a thick, fibrous capsule and was characterized by groups of mostly round cells with indistinct, slightly eosinophilic, granular cytoplasm separated by thin, fibrous stroma (fig. 7). The nuclei of the neoplastic cells were

6 12

Patnaik et al.

Fig. 4 Nasopharynx with neoplasm consisting of round cells with ample, pale, granular cytoplasm (dog 1). Inset: Dark intracytoplasmic granules. Giemsa. Fig. 5 Myocardium with cellular infiltrates (dog 2). Inset: Higher magnification. Pleomorphic cells with ample, granular cytoplasm in some cells.

Mast-Cell Tumor

613

Fig. 6 Pituitary gland with area of cellular infiltration (dog 2). Fig. 7: Hepatopancreatic lymph node replaced with neoplasm; remnants of a lymph follicle (dog 3).

6 14

Patnaik et al.

hyperchromatic and condensed, with little mitotic activity or pleomorphism. A few giant cells were seen. The neoplastic cells infiltrated and replaced the adjoining pancreatic tissue. There were scattered eosinophils and areas of increased amounts of connective tissue in the neoplasm. Large groups of neoplastic cells were seen in the mesenteric lymph nodes, mostly in the medullary sinuses. Neoplastic cells were not seen in any other visceral organs nor in the bone marrow. The lesion in the duodenum was characterized by an ulcer extending to the serosa, with hemorrhage, necrosis, and growth of granulation tissue. The blood vessels in the area showed degeneration, fibrinoid necrosis, and thrombosis. There was severe, acute necrotizing peritonitis. Other lesions were congested liver, spleen, and kidneys, diffuse focal myocardial degeneration and necrosis, and parathyroid hyperplasia. Slides stained with Giemsa stain showed metachromatic intracytoplasmic granules in both the primary and metastatic sites in all three neoplasms (fig. 4, inset).

Discussion Lack of cutaneous lesions, presence of distinct masses at the described sites (i.e., nasopharynx, oral cavity, and hepatopancreatic lymph nodes), and results of histologic examination established extracutaneous sites of origin for the three mast-cell neoplasms reported here. The oral cavity is a common site for the extracutaneous mast-cell neoplasms described in the dog [3, 5, 121; mast-cell tumor has not been reported in the nasopharynx or visceral lymph nodes. In dog 3, in which the hepatopancreatic lymph nodes were concluded to be the primary site, primary mast-cell and neuroendocrine neoplasms arising from the stomach, intestines, pancreas, and liver with metastasis to these lymph nodes were all part of the differential diagnosis. Specifically, a Zollinger-Ellison-like syndrome that has been described in the dog was considered seriously [4, 141. Careful gross and microscopic examination of the stomach, intestines, and liver, however, showed no neoplastic process. Although neoplastic cells had infiltrated the adjoining pancreatic tissue, there were no masses in the pancreas. Histologically, the tumor did not have the peritheliomatous arrangement typical of neuroendocrine neoplasms, but instead had features similar to those of mast-cell tumors previously described at other sites [2, 6, 8, 101. The neoplastic cells contained intracytoplasmic, metachromatic granules that stained with Giemsa stain, and the dog had no clinical signs suggestive of neuroendocrine tumor except for the duodenal ulcer [4, 141. Focal, non-neoplastic accumulationsof mast cells in the visceral lymph nodes have been described in a dog [9]. We believe that in our dog, a similar accumulation in the hepatopancreatic lymph nodes became malignant. Gastroduodenal ulcers associated with cutaneous mast-cell tumors have been described in the dog and cat, and the pathogenesis of these lesions is not clearly understood [7, 13, 151. In a study of 20 dogs with gastroduodenal ulcers associated with cutaneous mast-cell neoplasms, vascular alterations and thromboses were seen frequently, and it was thought that the vascular changes, in addition to hyperacidity and hypermotility, may have contributed to the ulcerative process [7]. Lesions in our

Mast-Cell Tumor

615

dog 3 suggest that extracutaneous mast-cell tumors also may lead to gastroduodenal ulceration, producing similar vascular changes.

References 1 BEAUMONT, P.R.; O’BRIEN,J.B.; ALLEN,H.L.; TUCKERS, J.A.: Mast cell sarcoma of the

larynx in a dog: A case report. J Small Anim Pract 2 0 19-25, 1979 2 BOSTOCK, D.E.: The prognosis following surgical removal of mastocytomas in dogs. J Small Anim Pract 14:27-40, 1973 3 GORLIN,R.J.; CLARK,J.J.; CHAUDHURY, A.P.: Oral pathology of domestic animals. Oral Pathol11:500-535, 1958 4 HAPPE,R.P.; VAN DER GAAG,I.; LAMERS, C.B.H.W.; VAN TOORENBURG, J.; REHFELD, J.F.; LARSSON, L.I.: Zollinger-Ellison syndrome in three dogs. Vet Pathol 17:177-186, 1980 5 HERMAN, L.H.; SLAUGHTER, L.J.; MARTIN,D.P.: Malignant mastocytoma in a dog. J Am Vet Med Assoc 151322-1324, 1967 6 HOTTENDORF, G.H.; NIELSON,S.W.: Pathologic report of 29 necropsies on dogs with mastocytoma. Pathol Vet 5 102-121, 1968 7 HOWARD, E.B.; SAWA,T.E.; NIELSON,S.W.; KENYON, A.J.: Mastocytoma and gastroduodenal ulceration. Pathol Vet 6 146-158, 1969 8 JONES,R.A.; DAWSON, I.M.P.: Morphology and staining patterns of endocrine cell tumors in the gut, pancreas and bronchus, and their possible significance. Histopathology 1: 137-150, 1977 9 LUND,J.E.; PARK,J.F.: Focal mastocytosis in lymph nodes from a Beagle dog. Vet Pathol 156467, 1978 10 NIELSON, S.W.; COLE,C.R.: Canine mastocytoma-A report of one hundred cases. Am J Vet Res 19417-432, 1958 11 PATNAIK, A.K.; TWEDT,D.C.; MARETTA, S.M.: Intestinal mast cell tumor in a dog. J Small Anim Pract 21:207-212, 1980 12. RISER,W.H.: Treatment of tumors in the dog. Comparison of surgery and physiotherapy. In: Proceedings, 91st Annu Meeting, Am Vet Med Assoc, pp. 279-285, 1954 13 SEAWRIGHT, A.A.; GRONO,L.R.: Malignant mast cell tumor in a cat with perforating duodenal ulcer. J Pathol Bacteriol87: 107, 1964 14 STRAUS, E.; JOHNSON, G.F.; YALOW,R.S.: Cznine Zollinger-Ellison syndrome. Gastroenterology 72380-381, 1977 15 ZONTINE, W.J.; MEIERHENRY, E.F.; HICKS,R.F.: Perforated duodenal ulcer associated with rnastocytoma in a dog. A case report. J Am Vet Radio1 SOC18: 162-163, 1978

Request reprints from A.K. Patnaik, DVM, Department of Pathology, The Animal Medical Center, 510 East 62nd Street, New York, NY 10021 (USA).