A low power image demonstrates a replacement of the lamina propria by stromal cells. Architectural distortion is minimal.
A proliferation of spindled cells have expanded the lamina propria.
Collections of mature ganglion cells are evident in the lower left hand corner. The proliferation of spindled cells are seen surrounding the colonic glands. If one were to perform IHC, the spindled cell population would be S-100 reactive, and the ganglion cells would be synaptophysin reactive.
A higher power image of ganglion cells and associated stroma (spindled cells in a fibrillary matrix) streaming between colonic glands.
Ganglioneuromas, whether solitary/sporadic or as part of ganglioneuromatosis polyposis, demonstrate a fairly well-demarcated of proliferation of spindled cells under normal epithelium. Ganglion cells are not evident at this power. In diffuse ganglioneuromatosis (not seen here), there would be a permeative and poorly demarcated proliferation of spindled cells that may involve the entire bowel wall and cause significant architectural distortion. One may also find expansion and hyperplasia of the enteric plexuses.
Ganglioneuromas of the intestinal tract into can be categorized into three groups: polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis.
Polypoid ganglioneuromas consists of small sessile or pedunculated polyps which are usually solitary or few in number. Nerve ganglion cells and spindled stromal cells are found in nests in the mucosa and submucosa, usually without significant disarray in the architecture of the glands. These solitary polyps are not associated with a hereditary syndrome; they are asymptomatic and usually found incidentally.
In ganglioneuromatous polyposis, typically greater than 20 sessile or pedunculated mucosal and/or submucosal lesions are present. Microscopically, the polyps may be indistinguishable from polypoid ganglioneuromas. Some authorities mention an association with familial adenomatous polyposis (FAP)1 , however, this has not been well-documented in the literature. Co-existing cutaneous or mucosal lipomas have been occasionally reported in patients, and Chan (2006) theorized that ganglioneuromatous polyposis may be a manifestation of a rare yet-to-be named syndrome.2
Diffuse ganglioneuromatosis is a disseminated, nodular proliferation of neural elements that involves the enteric plexuses and is intra- or transmural in extent. These are sizable poorly demarcated lesions (1–17 cm), which may distort the surrounding architecture. Diffuse ganglioneuromatosis may exist as an isolated finding, or it is often observed as a component of MEN IIb or NF1. In fact, diffuse ganglioneuromatosis is present in virtually all MEN IIb patients and generally precede the development of endocrine lesions.2
Note that intestinal ganglioneuromatosis is a hereditary polyposis syndrome, which can be broadly divided into adenomatous (epithelial neoplasms with malignant potential) or hamartomatous (benign malformations of mature tissues native to that region, in this case, the GI tract). Ganglioneuromatosis falls under the latter category, and other examples of hamartomatous polyposis syndromes include Cowden syndrome, juvenile polyposis syndrome and Peutz-Jeghers syndrome. Although genetic mutations have been identified for many of the polyposis syndromes (ie. APC gene in familial adenomatous polyposis, SMAD4 gene in juvenile polyposis syndrome), none have yet been identified in ganglioneuromatosis. Authorities speculate the pathogenesis may involve a combination of several tumor suppressor gene mutations.1
Can occur anywhere in the GI tract, but most common in the left colon and rectum. Presents endoscopically as solitary (or very few) polyps sporadic cases and numerous (20 or more) polyps in ganglioneuromatous polyposis. In contrast, diffuse ganglioneuromatosis, which arises in the muscularis propria and presents as a poorly demarcated whitish mural thickening +/- stricture, can involve up to 17 cm of colon wall.2
Excellent. Although some hamartomatous polyposis syndromes (Peutz-Jeghers syndrome and juvenile polyposis sydnrome) carry an increased risk for intestinal cancer, no such connection has been established for ganglioneuromatosis. Patients with diffuse ganglioneuromatosis and MEN IIb or NF1 may have co-morbidities associated with these hereditary syndromes such as endocrine abnormalities and other neoplasms.
1 Iacobuzio-Donahue CA, Montgomery EA. Gastrointestinal and Liver Pathology: Foundations in Diagnostic Pathology. Philadelphia, PA: Elsevier; 2005: 214-7.
2 Chan OTM, Haghighi P. Hamartomatous Polyps of the Colon. Ganglioneuromatous, Stromal and Lipomatous. Arch Pathol Lab Med. 2006;130:1561-1566.