Rapid tumour-like growth of giant filiform polyposis in a patient without a history of chronic bowel inflammation

Long-term inflammation of the colonic mucosa during chronic inflammatory bowel disease with alternating periods of ulceration and healing may lead to the formation of finger-like projections, so-called filiform polyps. In rare cases, several filiform polyps form large tumour masses, termed giant filiform polyposis. We present a case of giant obstructing filiform polyposis in a patient without previous evidence of chronic bowel inflammation. The resected ascending colon from a 37-year-old woman was evaluated macroscopically and microscopically, and the presence of gene polymorphisms was studied by means of multiplex capillary electrophoresis single-strand conformation polymorphism assay, DNA sequencing, TaqMan analysis, and restriction enzyme cleavage. The giant filiform polyposis was restricted to a 15 cm segment of the ascending colon, and the remaining colonic mucosa was entirely without inflammatory changes. During the post-operative follow-up period, the patient developed symptoms and signs of distal bowel inflammation. Gene polymorphism studies were inconclusive as to Crohn's disease. In conclusion, we present an unusual pathological entity of giant filiform polyposis, which developed relatively rapidly in a colon without any history or macroscopic changes suggestive of chronic inflammatory bowel disease. Although the patient subsequently developed symptoms in keeping with Crohn's disease, studies of genetic polymorphism were unable to confirm this notion, and colorectal tissue has not been sampled postoperatively for histological evaluation.     

Filiform polyposis: A benign entity? Case report and literature review

Filiform polyposis (FP) is a distinctive and unusual form of benign non syndromic polyposis that is occasionally encountered in the colon of patients with inflammatory bowel disease (IBD) history. FP is characterized by one to hundreds, slender, arborizing, vermiform projections in the colon lined by normal or inflammatory colonic mucosa. Only rare cases without history or evidence of IBD have been reported. In those cases, the sigmoid colon was the most common location and none of them showed dysplasia or malignancy neither at first evaluation nor during follow-up. In this report, we present the first case of FP associated with six adenomas developed on filiform polyps and invasive adenocarcinoma in the right colon of a 54 year-old man without a past medical history of IBD.     

Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis

A case of giant inflammatory polyposis associated with a localized inflammatory bowel disease of the descending colon in a 49-year-old man is presented. Lower abdominal distension rapidly appeared without any previous history of gastrointestinal disease. Two months later, he underwent a left hemicolectomy. Postoperative recovery was complete and he remains in good health more than 2 years later. The resected colon showed a giant and bizarre polyposis measuring up to 12 cm in length and 2 cm in height and covering the entire circumference of the colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregularly shaped ulcers, which sometimes extended into muscularis propria. Although longitudinal ulcers or scars, stricture, and a cobble-stone appearance were not observed, transmural inflammation and deep fissures were found in the interpolypoid area. From these findings, this case seems to be more similar to Crohn's disease than other inflammatory bowel diseases.     

Diffuse filiform polyposis with unique histology mimicking familial adenomatous polyposis in a patient without inflammatory bowel disease

Filiform polyposis is an uncommon entity that is most often encountered in the colon of patients with a history of inflammatory bowel disease (IBD). Filiform polyposis is characterized by a large number of "wormlike" polyps lined by histologically normal colonic mucosa. These polyps can mimic adenomatous polyps. Only rare cases without a history or evidence of IBD have been reported. Neuromuscular and vascular hamartoma of the small bowel is a rare, focal disorder characterized by disorganized smooth muscle fascicles throughout the submucosa accompanied by fibrosis, nerve fibers, ganglion cells, and vessels. To our knowledge, there is only one report of this lesion in the large bowel (cecum), where it presented as a mass. Here we report the case of a 50-year-old man with no known history or symptoms of IBD presenting with filiform polyposis involving the entire colon, clinically mimicking familial adenomatous polyposis, and showing histologic features similar to neuromuscular and vascular hamartoma of the small bowel.     

Malignant lymphoma, immunoblastic with plasmacytic differentiation, complicating Crohn''s disease

A case of malignant lymphoma (immunoblastic with plasmacytic differentiation) of the colon complicating Crohn's disease is reported. The rarity of this complication in inflammatory granulomatous disease of the intestine is stressed. The possible relationship between intestinal lymphoma and Crohn's disease is discussed.     

Analysis of the results of 1221 colonoscopies in the hospitals of Burkina Faso, 1994-1997

The authors report the results of 1221 colonoscopies. It appears from their analysis that whereas functional diseases of the colon remain predominant and topical, organic diseases appear to be increasing in frequency (polyps, polyposis, rectocolic cancer, parasitical colitis, diverticulis). Inflammatory bowel diseases are also beginning to be seen. The reported cases of Crohn's disease and ulcerative colitis are, so far as they know, the first in their country.     

Human gut mucosal mast cells: ultrastructural observations and anatomic variation in mast cell-nerve associations in vivo.

One hundred and seventeen coded intestinal biopsy specimens were examined by electron microscopy. All surgical biopsies were obtained from uninvolved sites of patients with two inflammatory bowel diseases (ulcerative colitis or Crohn's disease) and from patients with preneoplastic and neoplastic diseases (adenocarcinoma, rectal polyp, familial polyposis). Biopsy sites included normal ileum, colon, and rectum as well as conventional ileostomies and continent pouches constructed from the ileum. The data reported here describe the ultrastructural anatomy of human gastrointestinal tract mucosal mast cells in vivo and their anatomic associations with enteric nerves.     

Lipomatosis coli,a mimicker of familial polyposis

Multiple intestinal lipomas (lipomatous polyposis) are quite rare, and they can be quite challenging to diagnose because this condition may be clinically confused with familial adenomatous polyposis with a suggestive family history. Herein, we present a case of lipomatous polyposis that was presented with abdominal pain and, in colonoscopy, had more than 100 polyps. The patient was admitted for surgery with diagnosis of familial polyposis. Resected colon specimen had multiple polyps ranging from 0.1 to 1.5 cm. Microscopically, the polyps were composed of mature adipose tissue with normal overlying mucosa. There were also increased fat cells in the submucosa of the colon adjacent to the polyps. Lipomatous polyposis rarely occurs and can be confused with familial polyposis. Polypectomy is a simple and cost-effective procedure to help in diagnosis and prevent a major surgery.     

Diffuse giant inflammatory polyposis: a challenging clinicopathologic diagnosis

Giant inflammatory polyposis of the colon is an uncommon manifestation of inflammatory bowel disease. We report a unique case of localized diffuse giant inflammatory polyposis in a 58-year-old white man, which was characterized by recurrence following initial surgical resection. The patient presented with symptoms of abdominal pain and passing blood per rectum. Colonoscopic examination revealed a near-obstructing, "fungating" mass in the sigmoid colon, which clinically was thought to represent colon carcinoma. Histology of several colon biopsies revealed marked acute inflammation with microabscess formation of the polyps and the adjacent mucosa. There was no evidence of dysplasia or malignancy. Because malignancy was strongly suspected and to relieve the obstructive symptoms, the patient underwent a segmental colectomy. The histologic features of the resected mass showed giant polyps with acute inflammation diagnostic of giant inflammatory polyposis. Again, there was no evidence of malignancy. Seven months later, following an uneventful initial postoperative recovery, the patient developed a recurrence of the mass with obstructive symptoms and required further surgical resection. The gross and histologic features of the lesion were similar to the previous findings. This case highlights the varied presenting symptoms and deceptive gross colonoscopic and radiologic features of localized diffuse giant inflammatory polyposis. Finally, the presence of inflammation at the resection margins appears to predict recurrence or persistence of the disease.     

Chemokines in the Inflammatory Bowel Diseases

Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by proinflammatory cytokines and chemokines. In inflammatory bowel disease, intestinal inflammation is not downregulated, in part due to defective or absent inhibitory processes. Studies to date have demonstrated that IL-8, MCP-1, and ENA-78 are highly expressed in the intestinal mucosa in areas of active Crohn's disease and ulcerative colitis. Neutrophils and macrophages in the inflamed intestine synthesize and secrete large amounts of chemokines in patients with inflammatory bowel disease. Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine–chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease.     

Differential expression of vasoactive intestinal peptide receptor 1 expression in inflammatory bowel disease

There is conflicting evidence regarding the significance of vasoactive intestinal peptide (VIP) in inflammatory bowel disease (IBD). Involvement of the VIP receptor in IBD has not been reported. We examined the expression and localization of the VIP receptor in IBD. We determined the location of VIP receptor 1 (VIPR1) immunohistologically in surgically resected intestinal samples from 10 controls, 15 patients with ulcerative colitis, and 10 patients with Crohn's disease. A fluorescein-linked immunohistological study was performed using anti-VIPR1 antibody, with double-staining with antibodies to CD3, CD19, and CD68. Correlations with interleukin (IL)-4 and TNF-alpha expression were also investigated. Results showed that the number of VIPR1-positive cells was significantly increased in the inflammatory mucosa. VIPR1 was expressed in CD3-, CD19-, and CD68-positive cells. The proportion of VIPR1-positive cells among CD3-positive cells was significantly higher in the lamina propria of patients with ulcerative colitis than in those with Crohn's disease and the controls. The proportion of VIPR1-positive cells among CD68-positive cells was significantly higher in patients with ulcerative colitis and Crohn's disease than in the controls. A correlation between the numbers of VIPR1- and IL-4-positive cells was found in patients with ulcerative colitis, and between the numbers of VIPR1- and TNF-alpha-positive cells in patients with Crohn's disease. In conclusion, VIPR1 was widely expressed in infiltrating inflammatory cells, especially CD3- and CD68-positive cells in ulcerative colitis mucosa and CD68-positive cells in Crohn's disease mucosa. The differential expression of VIPR1 in ulcerative colitis and Crohn's disease mucosa suggests that the VIP system plays different roles in the pathogenesis of IBD.     

Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2

Proteinase-activated receptor (PAR)-2, a G-protein-coupled receptor for trypsin and mast cell tryptase, is highly expressed in the intestine. Luminal trypsin and tryptase are elevated in the colon of inflammatory bowel disease patients. We hypothesized that luminal proteinases activate PAR-2 and induce colonic inflammation. Mice received intracolonically PAR-2 agonists (trypsin, tryptase, and a selective PAR-2-activating peptide) or control drugs (boiled enzymes, inactive peptide) and inflammatory parameters were followed at various times after this treatment. Colonic administration of PAR-2 agonists up-regulated PAR-2 expression and induced an inflammatory reaction characterized by granulocyte infiltration, increased wall thickness, tissue damage, and elevated T-helper cell type 1 cytokine. The inflammation was maximal between 4 and 6 hours and was resolved 48 hours after the intracolonic administration. PAR-2 activation also increased paracellular permeability of the colon and induced bacterial trans-location into peritoneal organs. These proinflammatory and pathophysiological changes observed in wild-type mice were not detected in PAR-2-deficient mice. Luminal proteinases activate PAR-2 in the mouse colon to induce inflammation and disrupt the integrity of the intestinal barrier. Because trypsin and tryptase are found at high levels in the colon lumen of patients with Crohn's disease or ulcerative colitis, our data may bear directly on the pathophysiology of human inflammatory bowel diseases.     

The -295T-to-C promoter polymorphism of the IL-16 gene is associated with Crohn's disease

Recently, a T-to-C polymorphism at position -295 in the promoter region of the human interleukin-16 (IL-16) gene was reported. The expression of IL-16 is increased in inflammatory bowel disease, in particular in Crohn's disease. However, data concerning the IL-16 promoter polymorphism in inflammatory bowel disease are lacking. Thus, the current study aimed at the assessment of this polymorphism in Crohn's disease and ulcerative colitis. One hundred three patients with Crohn's disease, 100 patients with ulcerative colitis, and 120 healthy unrelated controls were genotyped for the promoter polymorphism. Furthermore, patients with Crohn's disease were stratified according to disease localization and the respective clinical phenotype (fistulizing, fibrostenotic, or inflammatory). The frequencies of the T allele (P < 0.01) and the TT genotype (P < 0.01) were significantly increased in patients with Crohn's disease compared to the controls, regardless of the disease phenotype or the site of intestinal involvement. An association with ulcerative colitis was not observed. Herein a new association between a promoter polymorphism of the IL-16 gene and Crohn's disease was observed and correlates with the previously described increased mucosal expression of IL-16 in inflammatory bowel disease.     

Intramucosal ganglion cells are common in diverticular disease

AIMS: Ganglion cells were thought not to occur within the mucosa of the normal colon and found only in the setting of inflammatory bowel disease and neuronal intestinal dysplasia. The aim of this study was to firmly establish the incidence of intramucosal ganglion cells in diverticular disease, normal mucosa and in a spectrum of gastrointestinal diseases. METHODS: We retrospectively reviewed 50 resection specimens from cases of symptomatic diverticular disease and biopsies and/or resection specimens for several neoplastic and non-neoplastic gastrointestinal diseases (50 normal and 120 cases for a variety of gastrointestinal diseases). Normal cases were constituted by biopsies with no clinical history of large bowel disease and no pathology detected microscopically. RESULTS: All 50 cases of diverticular disease contained intramucosal ganglion cells, located within the muscularis mucosae (49/50 cases) as well as within the lamina propria in nine cases. Intramucosal ganglion cells occurred throughout the colorectum within the muscularis mucosae or lamina propria in normal mucosa in 11 cases and in a further 26 colorectal specimens with Crohn's disease (11/20), ulcerative colitis (11/20), adenocarcinoma (1/20), tubular adenoma (2/20), and mucosal prolapse (1/20). None of the 20 hyperplastic polyps contained intramucosal ganglion cells. CONCLUSIONS: We have firmly established the existence of the intramucosal ganglion cells in normal and diseased colorectum, especially in the mucosa of cases of diverticular disease (100% of cases), Crohn's disease and ulcerative colitis. These three conditions are linked by motility abnormalities which may underlie the reason for the presence of intramucosal ganglion cells.     

Primary malignant lymphoma of the large intestine complicating chronic inflammatory bowel disease

Ten cases of malignant lymphoma of the colon and rectum complicating chronic inflammatory bowel disease are presented. Seven patients had chronic ulcerative colitis with a history varying from 6 to 20 years. There was extensive colitis in six of these patients and left-sided colitis in one. All seven lymphomas showed the pathological and immunohistological features of primary B-cell tumours of the gastrointestinal tract with a predominance of high-grade tumours. Three patients had Crohn's disease of the large intestine complicated by malignant lymphoma of the sigmoid colon or rectum. The history of Crohn's disease varied from 30 months to 20 years and in each case there was fissuring and fistulae. There was extensive anal involvement in two cases. Histologically the three lymphomas were heterogeneous: one was of 'granulomatous' T-cell type and the other two were markedly polymorphic and of equivocal phenotype. They were also characterized by numerous multinucleate tumour giant cells. Primary colorectal malignant lymphoma should be regarded as a rare, but significant, complication of ulcerative colitis. Immunosuppression may be an additional factor in the genesis of intestinal lymphoma in Crohn's disease. The prognosis appears to be dependent on factors already known to be of prognostic significance in primary gut lymphomas: a predominance of high-grade tumours suggests that the outlook is generally worse than that for idiopathic primary large intestinal lymphoma.     

Two cases of pericarditis associated with inflammatory bowel disease

Extraintestinal manifestations are common complications of inflammatory bowel disease (IBD) whereas the association of cardiac disease with IBD is rarely reported. Cardiac manifestations may be diagnosed before, concomitantly or after the diagnosis of the specific type of inflammatory bowel disease. Pericarditis and myocarditis are potentially serious complications. This extraintestinal manifestation developed in one patient concomitantly with onset of intestinal disease. One patient had ulcerative colitis (UC), while other had Crohn's disease (CD). Indomethacin was effective in one and the other patient required prednisone in addition. Chest symptoms in patients with inflammatory bowel disease should be evaluated to exclude myopericardial disease.     

Increased neuropeptide Y-immunoreactive innervation of aganglionic bowel in Hirschsprung's disease

Summary The pathophysiology of Hirschsprung's disease has not been fully elucidated but is known to have a neurogenic basis. In recent years, new neural proteins and peptides have been discovered and our aim in this study was to use immunocytochemistry to investigate their involvement in the neuronal abnormalities associated with this condition. Large bowel samples from 9 children undergoing surgery for Hirschsprung's disease were compared with those taken from 8 children with other gastrointestinal diseases but no aganglionosis. Immunocytochemistry was carried out using antibodies to a wide range of neuron specific proteins and peptides. Examination of sections immunostained for the general neuronal markers, protein gene product 9.5, neuron specific enolase and neurofilament triplet proteins, allowed rapid identification of aganglionic segments. Nerves containing vasoactive intestinal polypeptide/peptide histidine methionine (VIP/PHM), galanin, substance P, somatostatin, met-enkephalin or calcitonin gene-related peptide (CGRP) showed a marked reduction in all layers of the aganglionic bowel. However, scattered VIP/PHM immunoreactive fibres were also found in the hypertrophied nerve bundles. In contrast with these reduced peptide-containing nerves, fibres displaying NPY immunoreactivity showed a marked increase in all aganglionic segments, particularly in the circular muscle where few are found normally. Our findings shed further light on the neurobiology of aganglionic bowel and suggest that immunostaining of neural proteins and the peptide NPY can aid rapid histopathological diagnosis of congenital aganglionosis.     

CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice

Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, increase the risk of colorectal cancer in humans. It has been recently shown in humans and animal models that intestinal microbiota and host immunity are integral in the progression of large bowel diseases. Lymphocytes are widely believed to prevent bacterially induced inflammation in the bowel, and lymphocytes are also critical in protecting against primary tumors of intestinal epithelia in mice. Taken together, this raises the possibility that lymphocytes may inhibit colon carcinogenesis by reducing bacterially driven inflammation. To examine the role of bacteria, lymphocytes, and inflammatory bowel disease in the development of colon cancer, 129/SvEv Rag-2-deficient and congenic wild-type mice were orally inoculated with a widespread enteric mouse bacterial pathogen, Helicobacter hepaticus, or sham-dosed with media only. H. hepaticus-infected Rag2-/-, but not sham-dosed Rag2-/- mice, rapidly developed colitis and large bowel carcinoma. This demonstrated a link between microbially driven inflammation and cancer in the lower bowel and suggested that innate immune dysregulation may have an important role in inflammatory bowel disease and progression to cancer. H. hepaticus-infected wild-type mice did not develop inflammation or carcinoma showing that lymphocytes were required to prevent bacterially induced cancer at this site. Adoptive transfer with CD4+ CD45RBlo CD25+ regulatory T cells into Rag-deficient hosts significantly inhibited H. hepaticus-induced inflammation and development of cancer. These results suggested that the ability of CD4+ T cells to protect against intestinal cancer was correlated with their ability to reduce bacterially induced inflammatory bowel disease. Further, regulatory T cells may act directly on the innate immune system to reduce or prevent disease. These roles for T cells in protection against colon carcinoma may have implications for new modes of prevention and treatment of cancer in humans.     

Defensin deficiency, intestinal microbes, and the clinical phenotypes of Crohn's disease

Crohn's disease is a chronic, inflammatory disease of the intestinal mucosa. Although intestinal bacteria are implicated in disease pathogenesis, the etiology is still unclear. The main location of disease is the small intestine (ileum) and the colon. Ileal disease has been linked to a mutation in the NOD2 gene. Defensins are antimicrobial peptides and in the ileum, are mainly expressed in Paneth cells, epithelial cells that also express NOD2. In the colon, defensins are expressed by enterocytes or metaplastic Paneth cells. Crohn's disease patients with ileal involvement, compared with controls or Crohn's patients without ileal involvement, have diminished expression of ileal Paneth cell defensins. This decrease is even more pronounced in Crohn's patients displaying a NOD2 mutation. In contrast, Crohn's disease of the colon is characterized by an impaired induction of beta-defensins in enterocytes. The colonic expression of the constitutive beta-defensin 1 is also decreased in the inflamed colonic mucosa, but this decrease is less specific to Crohn's disease, as it can also be found in ulcerative colitis patients. In conclusion, the regional localizations of Crohn's disease, ileal or colonic disease, can be linked to different defensin profiles. Crohn's disease of the ileum is associated with diminished defensin expression in Paneth cells. Crohn's disease of the colon is associated with diminished beta-defensin expression in enterocytes. Thus, it can be speculated that decreased defensin levels lead to a weakened intestinal barrier function to intestinal microbes and might be crucial in the pathophysiology of Crohn's disease.     

Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients.

Increased levels of rheumatoid factors (RF) have been observed in the serum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9.7 ng/ml IgA RF, 11.6 ng/ml IgM RF and 64.6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21.4 ng/ml IgA RF, 21.4 ng/ml IgM RF, and 108.15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198.3 ng/ml of IgA anti-Fc(IgG) from involved versus 50.0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF (7.1 ng/ml IgA RF, 6.2 ng/ml IgM RF, and 42.3 ng/ml IgA anti-Fc(IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened state of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF.