1-year-old, male, Beagle dog.This dog was part of a 10-day oral toxicological study and was euthanized at the end of the study. There were no relevant clinical signs
An abnormal shape of the cecum was the only relevant macroscopic finding.Â
There is invagination of the tip of the cecum within its lumen.Â All parts of the cecum wall are diffusely, moderately thickened (about twice normal thickness).Â The muscularis mucosa, the submucosa, some parts of the muscular layers (particularly the longitudinal layer), and the serosa are replaced by a poorly demarcated tissue, primarily in the same location as the myenteric (Auerbachs) and the submucous (Meissners) plexuses (Fig.Â 3-1).Â This tissue is composed of irregularly-arranged wavy fascicles of nerve fibers with round and spindle cells, and some clusters of enlarged ganglion cells (Fig.Â 3-2).Â The mucosa is moderately hyperplastic, with multifocal to coalescing hemorrhages in the lamina propria, and multifocal minimal degeneration of some glands.Â Scattered in the submucosa and the proliferative neural tissue are some cells containing large pigmented brown granules (hemosiderin).
Cecum: Transmural ganglioneuromatosis, locally extensive, with intussusception.
There were no significant findings
Intestinal ganglioneuromatosis refers to a hyperplastic proliferation of ganglion cells, nerve fibers, and supporting cells of the enteric nervous system.Â In humans, intestinal ganglioneuromatosis is most often part of multiple tumor syndromes, particularly the multiple endocrine neoplasia (MEN) 2B syndrome.12 MEN-2B is inherited in an autosomal dominant fashion and is caused by a single mutation in the RET proto-oncogene.Â This heritable endocrine disorder is characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas, gastrointestinal ganglioneuromatosis, corneal nerve thickening and skeletal abnormalities.8 Gastrointestinal symptoms are common in patients with MEN-2B, and are secondary to the pseudo-obstruction caused by the ganglioneuromatosis.6 The pathogenesis of ganglioneuromatosis is not well understood, but some studies in humans indicate that it may be related to the overproduction of some nerve growth factors.Â
Immunohistochemically, some cases of ganglioneuromatosis were shown to be a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fibers.4
Some rare cases of intestinal ganglioneuromatosis or ganglioneuromas have been reported, most often in young animals: in a horse1, a steer3, a cat9, and 3 dogs.5,11,13 In all cases, there were clinical signs (e.g.Â colic, impaction, anorexia, vomiting, diarrhea, rectal prolapse) that led to surgical resection of the masses.Â Masses were located in the small intestine (3 cases), colon (1 case), colorectum (2 cases) or Vaters papilla (1 case).Â This is the first reported case of asymptomatic ganglioneuromatosis in a dog.Â
Cecum (per contributor): Ganglioneuromatosis, with intussusception, Beagle (Canis familiaris), canine.
Ganglioneuromas are composed of mature autonomic ganglion cells, satellite cells, unmyelinated and occasionally myelinated axons, Schwann cells and a fibrous stroma.Â They are generally considered benign neoplasms.Â Intestinal ganglioneuromatosis is considered a hyperplasia of similar elements; it is typically transmural.Â As noted by the contributor, both lesions are rare in animals and have not been found to be associated with MEN-like syndromes.7 Some have suggested that ganglioneuromas may actually represent hamartomas (benign, nonneoplastic, tumor-like nodules consisting of an overgrowth of mature cells that normally occur in the affected organ) rather than benign neoplasms.10
Intussusceptions are described as having three layers: (1) outer wall of the receiving segment, (2) middle returning segment of invaginated bowel, and (3) inner entering segment.Â The intussusception seen in this lesion is unusual in that it contains only two of the three layers, a feature that will occur only through the invagination of a blind pouch (in this case, the tip of the cecum).Â Cecal inversion is another term for such a lesion (Fig.Â 3-3).Â Various causes of intussusception may include linear foreign bodies, heavy parasitism, previous intestinal surgery, enteritis, and intramural lesions.Â It may also develop as a terminal, agonal or postmortem event.2
A.Â Intussusception of tubular section of bowel consisting of three layers: (1) outer wall of the receiving segment, (2) middle returning, segment of invaginated bowel, and (3) inner entering segment.Â
B.Â Intussusception of a blind pouch consisting of two layers: (1) outer wall of the receiving segment, and (2) the middle returning, segment of invaginated bowel.
We appreciate the assistance from the Departments of Gastrointestinal Pathology, Neuropathology, and Soft Tissue Pathology at the Armed Forces Institute of Pathology in consultation on this case.
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