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Ultrastructure of a canine gastrinoma
J. COW.
PATH. 1987 VOL. 97
ULTRASTRUCTURE
OF
A CANINE
GASTRINOMA
BY
C. G. Department
of Veterinary
Pathology,
Western College Saskatchewan
ROUSSEAUX of Veterinary Medicine, S7N OWO, Canada
University
of Saskatchewan,
Saskatoon.
Gastrinoma, a tumour arising from the delta cells of the endocrine pancreas, is an uncommon finding in both man and dogs. So far only 6 cases have been reported in the dog (Jones, Nicholls and Badman, 1976; Straus, Johnson and Yalow, 1977; Happe, van der Gaag, Lamers, van Toorenburg, Renfeld and Larsson, 1980; Dragner, 198 1). This tumour has been referred to as the “ulcerogenic tumour” of the Zollinger-Ellison Syndrome (Zollinger and Ellison, 1955). In this syndrome, excess gastrin, produced by the tumour, induces hypersecretion of gastric acid causing recurrent peptic ulcers. For this reason the name gastrinoma is preferred (Ghadially, 1982). Ultrastructurally, gastrinomata and other APUD ( amine precursor uptake and decarboxylation) cells contain high or medium density intracytoplasmic secretory granules with or without a halo (Ghadially, 1982). These granules are referred to as APUD granules and are found in many neuro-ectodermal cells of neural crest origin. At present about 24 types of APUD cells have been recorded (Dobbins, 1978; Friesen, 1982). Previous reports of canine gastrinomata have noted the clinical, gross and histopathological findings associated with this tumour (Jones et al., 1976; Straus et al., 1977; Happe et al. 1980; Drazner 1981). The ultrastructure of these tumours was only vaguely described. This article reports the ultrastructural characteristics of a canine gastrinoma. An 1 l-year-old female spayed English bulldog was received for necropsy with an 18 month history of vomiting and stomach ulceration. At the onset of the vomiting, an exploratory laparotomy revealed small firm masses along the mesenteric border of the duodenum and pancreas. Excision and microscopic examination revealed a pancreatic islet-cell tumour. Because chronic melaena and haematemesis suggested peptic ulceration, a tentative diagnosis of canine gastrinoma was made. The serum gastrin concentration was raised (770 pg per ml). Cimetidine (Smith, Klein and French, Missassauga, Ontario) therapy was undertaken (Stadil and Stage, 1979) with moderate success for 12 months, after which vomiting increased in frequency and volume. Following deterioration for 6 months, the dog was destroyed and submitted for post-mortem examination. The dog was in poor body condition. It had multiple focal ulceration of the oesophagus, stomach and duodenum. The ulcers ranged from 1 to 2 cm in diameter and were largest in the stomach. The pancreas contained a 10 by 5 cm multilobular pale, bluish, soft, infiltrative OOZI-9975/87/050605
+ 03 $03.00/O
0
1987 Academic
Press Limited
606
CANINE
GASTRINOMA
mass on its caudal pole. The omentum, serosal surface of the duodenum and jejunum, mesenteric lymph nodes and mesentery contained similar masses ranging from 1 to 10 mm in diameter. Cross-section revealed areas of necrosis and minimal stroma. Microscopically, the mass was poorly demarcated from the adjacent tissues. Nests of epithelial cells arranged in acini and sheets were seen amongst numerous, well-vascularized fine connective tissue septa that radiated centripetally, dividing the mass into lobules. The tumour cells were anaplastic and pleomorphic. Cells varied from oval to cuboidal and had lightly eosinophilic and finely granular cytoplasm with indistinct cell boundaries. The nuclei were dark and condensed, with multiple nucleoli. Very few mitotic figures were seen. Ultrastructurally, some of the tumour cells contained numerous 100 to 150 nm intracytoplasmic granules of variable density. Surrounding halos were not obvious. The density of the granules ranged from light and punctate, through flocculent to dense and compact (Fig. 1). These granules were similar to those described in delta cell tumours in man and differed from other APUD granules found in pancreatic islet cell tumours originating from the alpha, beta and chromophobic cells (Ghadially, 1982). A diagnosis of canine gastrinoma syndrome was made on the basis of the clinical signs, gastrointestinal ulceration, high serum gastrin concentration and the ultrastructural features of the tumour cells i.e.. the lack of a halo and
Fig.
1. Section through a turnour cell 150 nm, with variable density.
showing Uranium
electron and
dense intracytoplasmic lead x 15 000.
granules
ranging
from
100
to
C.
G.
607
ROUSSEAUX
crystalline core. This is an uncommon diagnosis in described here are consistent with previous reports Ultrastructurally, canine gastrinoma or delta-cell differentiated from other types of islet-cell tumours by intracytoplasmic APUD granules (Ghadially, 1982).
dogs, but the findings (Happe et al., 1980). islet tumour can be the morphology of the The alpha islet-cell
tumour contains dense core granules, with a halo around the core, whereas the beta pancreatic islet-cell contains similar sized granules with a crystalline core and the chromophobic C cell lacks granules. Because the ultrastructural findings of the different islet-cell tumours are so routine ultrastructural examination of endocrine pancreatic distinctive, tumours is useful. This may provide a definite diagnosis and aid in reaching a prognosis at the time when an initial biopsy is taken. ACKNOWLEDGMENT
I gratefully acknowledge the assistance and guidance and C. Dick of the Department of Anatomy, University
given by Dr F. N. Ghadially of Saskatchewan.
REFERENCES
Dobbins, W. 0. (1978). Diagnostic pathology of the intestine and colon. In Diagnostic Electron Microscopy, vol. 1, B. F. Trump and R. T. Jones, Eds, John Wiley and Sons, New York, pp. 253-339. Dragner, F. H. (1981). Canine gastrinoma: a condition anaolagous to the Zollinger-Ellison syndrome in man. California Veterinarian, 35, 6-11. Friesen, S. R. (1982). Tumours of the endocrine pancreas. The New England Journal of Medicine, 306, 580-590. Ghadially, F. N. (1982). Ultrastructural Pathology of the Cell and Matrix, Butterworths, Toronto, pp. 288-294. Happe, R. P., van der Gaag, I., Lamers, C. B. H. W., van Toorenburg, J., Renfeld, J. F. and Larsson, L. I. (1980). Zollinger Ellison syndrome in three dogs. Veterinary Pathology, 17, 177-186. Jones, B. R., Nicholls, T. R. and Badman, R. (1976). Peptic ulceration in a dog associated with an islet cell carcinoma of the pancreas and an elevated plasma gastrin level. Journal of Small Animal Practice, 17, 593-598. Stadil, F. and Stage, J. G. (1979). The Zollinger-Ellison Syndrome. Clinics in Endocrinology and Metabolism, 8, 433-446. Straus, E., Johnson, G. F. and Yalow, R. S. (1977). Canine Zollinger-Ellison syndrome. Gastroenterology, 72, 380-38 1. Zollinger, R. M. and Ellison, E. H. (1985). P rlmary . peptic ulceration of the jejunum associated with islet cell tumours of the pancreas. Annals of Surgery, 142, 709-728. [Receioed for publication,
June 3rd, 19861
PATH. 1987 VOL. 97
ULTRASTRUCTURE
OF
A CANINE
GASTRINOMA
BY
C. G. Department
of Veterinary
Pathology,
Western College Saskatchewan
ROUSSEAUX of Veterinary Medicine, S7N OWO, Canada
University
of Saskatchewan,
Saskatoon.
Gastrinoma, a tumour arising from the delta cells of the endocrine pancreas, is an uncommon finding in both man and dogs. So far only 6 cases have been reported in the dog (Jones, Nicholls and Badman, 1976; Straus, Johnson and Yalow, 1977; Happe, van der Gaag, Lamers, van Toorenburg, Renfeld and Larsson, 1980; Dragner, 198 1). This tumour has been referred to as the “ulcerogenic tumour” of the Zollinger-Ellison Syndrome (Zollinger and Ellison, 1955). In this syndrome, excess gastrin, produced by the tumour, induces hypersecretion of gastric acid causing recurrent peptic ulcers. For this reason the name gastrinoma is preferred (Ghadially, 1982). Ultrastructurally, gastrinomata and other APUD ( amine precursor uptake and decarboxylation) cells contain high or medium density intracytoplasmic secretory granules with or without a halo (Ghadially, 1982). These granules are referred to as APUD granules and are found in many neuro-ectodermal cells of neural crest origin. At present about 24 types of APUD cells have been recorded (Dobbins, 1978; Friesen, 1982). Previous reports of canine gastrinomata have noted the clinical, gross and histopathological findings associated with this tumour (Jones et al., 1976; Straus et al., 1977; Happe et al. 1980; Drazner 1981). The ultrastructure of these tumours was only vaguely described. This article reports the ultrastructural characteristics of a canine gastrinoma. An 1 l-year-old female spayed English bulldog was received for necropsy with an 18 month history of vomiting and stomach ulceration. At the onset of the vomiting, an exploratory laparotomy revealed small firm masses along the mesenteric border of the duodenum and pancreas. Excision and microscopic examination revealed a pancreatic islet-cell tumour. Because chronic melaena and haematemesis suggested peptic ulceration, a tentative diagnosis of canine gastrinoma was made. The serum gastrin concentration was raised (770 pg per ml). Cimetidine (Smith, Klein and French, Missassauga, Ontario) therapy was undertaken (Stadil and Stage, 1979) with moderate success for 12 months, after which vomiting increased in frequency and volume. Following deterioration for 6 months, the dog was destroyed and submitted for post-mortem examination. The dog was in poor body condition. It had multiple focal ulceration of the oesophagus, stomach and duodenum. The ulcers ranged from 1 to 2 cm in diameter and were largest in the stomach. The pancreas contained a 10 by 5 cm multilobular pale, bluish, soft, infiltrative OOZI-9975/87/050605
+ 03 $03.00/O
0
1987 Academic
Press Limited
606
CANINE
GASTRINOMA
mass on its caudal pole. The omentum, serosal surface of the duodenum and jejunum, mesenteric lymph nodes and mesentery contained similar masses ranging from 1 to 10 mm in diameter. Cross-section revealed areas of necrosis and minimal stroma. Microscopically, the mass was poorly demarcated from the adjacent tissues. Nests of epithelial cells arranged in acini and sheets were seen amongst numerous, well-vascularized fine connective tissue septa that radiated centripetally, dividing the mass into lobules. The tumour cells were anaplastic and pleomorphic. Cells varied from oval to cuboidal and had lightly eosinophilic and finely granular cytoplasm with indistinct cell boundaries. The nuclei were dark and condensed, with multiple nucleoli. Very few mitotic figures were seen. Ultrastructurally, some of the tumour cells contained numerous 100 to 150 nm intracytoplasmic granules of variable density. Surrounding halos were not obvious. The density of the granules ranged from light and punctate, through flocculent to dense and compact (Fig. 1). These granules were similar to those described in delta cell tumours in man and differed from other APUD granules found in pancreatic islet cell tumours originating from the alpha, beta and chromophobic cells (Ghadially, 1982). A diagnosis of canine gastrinoma syndrome was made on the basis of the clinical signs, gastrointestinal ulceration, high serum gastrin concentration and the ultrastructural features of the tumour cells i.e.. the lack of a halo and
Fig.
1. Section through a turnour cell 150 nm, with variable density.
showing Uranium
electron and
dense intracytoplasmic lead x 15 000.
granules
ranging
from
100
to
C.
G.
607
ROUSSEAUX
crystalline core. This is an uncommon diagnosis in described here are consistent with previous reports Ultrastructurally, canine gastrinoma or delta-cell differentiated from other types of islet-cell tumours by intracytoplasmic APUD granules (Ghadially, 1982).
dogs, but the findings (Happe et al., 1980). islet tumour can be the morphology of the The alpha islet-cell
tumour contains dense core granules, with a halo around the core, whereas the beta pancreatic islet-cell contains similar sized granules with a crystalline core and the chromophobic C cell lacks granules. Because the ultrastructural findings of the different islet-cell tumours are so routine ultrastructural examination of endocrine pancreatic distinctive, tumours is useful. This may provide a definite diagnosis and aid in reaching a prognosis at the time when an initial biopsy is taken. ACKNOWLEDGMENT
I gratefully acknowledge the assistance and guidance and C. Dick of the Department of Anatomy, University
given by Dr F. N. Ghadially of Saskatchewan.
REFERENCES
Dobbins, W. 0. (1978). Diagnostic pathology of the intestine and colon. In Diagnostic Electron Microscopy, vol. 1, B. F. Trump and R. T. Jones, Eds, John Wiley and Sons, New York, pp. 253-339. Dragner, F. H. (1981). Canine gastrinoma: a condition anaolagous to the Zollinger-Ellison syndrome in man. California Veterinarian, 35, 6-11. Friesen, S. R. (1982). Tumours of the endocrine pancreas. The New England Journal of Medicine, 306, 580-590. Ghadially, F. N. (1982). Ultrastructural Pathology of the Cell and Matrix, Butterworths, Toronto, pp. 288-294. Happe, R. P., van der Gaag, I., Lamers, C. B. H. W., van Toorenburg, J., Renfeld, J. F. and Larsson, L. I. (1980). Zollinger Ellison syndrome in three dogs. Veterinary Pathology, 17, 177-186. Jones, B. R., Nicholls, T. R. and Badman, R. (1976). Peptic ulceration in a dog associated with an islet cell carcinoma of the pancreas and an elevated plasma gastrin level. Journal of Small Animal Practice, 17, 593-598. Stadil, F. and Stage, J. G. (1979). The Zollinger-Ellison Syndrome. Clinics in Endocrinology and Metabolism, 8, 433-446. Straus, E., Johnson, G. F. and Yalow, R. S. (1977). Canine Zollinger-Ellison syndrome. Gastroenterology, 72, 380-38 1. Zollinger, R. M. and Ellison, E. H. (1985). P rlmary . peptic ulceration of the jejunum associated with islet cell tumours of the pancreas. Annals of Surgery, 142, 709-728. [Receioed for publication,
June 3rd, 19861