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.     

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.     

Filiform polyposis : A case report describing clinical,morphological, and immunohistochemical findings

Summary Filiform polyposis (FP) is a rare condition of uncertain pathogenesis, 28 cases of which have been published since it was first described in 1965. It is usually found in association with chronic inflammatory bowel disease, especially Crohn's disease and ulcerative colitis. The condition is characterized by the presence of numerous, densely packed, filiform polyps in the colon, which may resemble villous adenomas on endoscopy. We describe a case of FP occurring in a 33-year-old man with a 5-year history of Crohn's disease, in whom subtotal colectomy was performed because of perforation of the sigmoid colon. Microscopy revealed inflammatory pseudopolyps covered by largely normal and non-dysplastic colonic epithelium. The neuroendocrine system of the intestine in FP was investigated for the first time in this case: marked hyperplasia of endocrine cells immunoreactive for serotonin, somatostatin and enteroglucagon and of neural structures immunoreactive for substance P and vasoactive intestinal peptide was noted in the polyps and the adjacent intestinal mucosa. The patient has experienced no further complications in the 12 months since the operation. Medication administered in FP depends mainly on the nature of the underlying disease, and the amount of information published about this condition is as yet insufficient to allow any one specific type of treatment to be recommended. FP alone is not an indication for bowel resection but complications, such as massive haemorrhage or intestinal obstruction, may necessitate surgical intervention.Abbreviations ABC avidin-biotin complex - ACTH adrenocorticotropic hormone - FP filiform polyposis - H&E haematoxylin and eosin staining - PAP peroxidase-antiperoxidase - VIP vasoactive intestinal peptide     

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.     

Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.     

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.     

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.     

Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues.

BACKGROUND: Escherichia coli, listeria, and streptococcal antigens have been found in Crohn's disease tissues. Antibodies to Klebsiella pneumoniae have been found in patients with inflammatory bowel disease and ankylosing spondylitis. The presence of these bacterial antigens in Crohn's granulomas would be of aetiological interest, while their presence in ulcers alone would be more likely to indicate secondary infection. AIM: To investigate inflammatory bowel disease tissues for the presence of these bacteria. METHODS: Formalin fixed, paraffin processed sections from 53 patients (19 ulcerative colitis, 23 Crohn's disease; 11 normal tissues from cancer resections) were studied by immunohistochemistry. Control tissue consisted of normal human small bowel injected submucosally with either E coli, Listeria monocytogenes, Proteus mirabilis, or Klebsiella pneumoniae serotypes K2, 3, 17, 21, 26, 36, and 50, and colonic biopsies from a child with E coli 0114 infection. Tissues were stained by Gram-Twort, and with specific antibodies for E coli (Dako B357), L monocytogenes (Difco 2302-50), and K pneumoniae (Biogenesis 5580-5208) using an immunoperoxidase technique. RESULTS: Positive staining for E coli was observed on the luminal surface epithelium and in ulcers in 35% of Crohn's disease patients, 26% of ulcerative colitis patients, and no normal controls. Superficial staining for L monocytogenes was observed in one case of ulcerative colitis only. Staining for K pneumoniae was observed in one case of ulcerative colitis and one of Crohn's disease. No granulomas, giant cells, or germinal centres stained positively for any of the three bacterial antigens. CONCLUSIONS: These data do not support a primary role for E coli, L monocytogenes, and K pneumoniae in inflammatory bowel disease. The presence of E coli antigens in ulcers suggests secondary infection in these lesions.     

Colorectal mass lesions masquerading as chronic inflammatory bowel disease on mucosal biopsy

AIMS: We bring to the attention of diagnostic pathologists a further cause of mimicry of chronic inflammatory bowel disease on mucosal biopsy, namely intramural and subserosal colorectal mass lesions. METHODS AND RESULTS: In a 10-year prospective study in one centre, we describe 26 cases in which the initial colonoscopic biopsies suggested a diagnosis of chronic inflammatory bowel disease, whereas subsequent information indicated that the mucosal changes were due to underlying mass lesions, without evidence of chronic inflammatory bowel disease. These mass lesions included underlying primary adenocarcinoma, metastatic carcinoma, pneumatosis, endometriosis and complicated diverticular disease. CONCLUSIONS: In the colon and rectum, intramural and subserosal mass lesions are a significant cause of chronic inflammatory bowel disease mimicry. Possible pathogenic mechanisms include mechanical effects, lymphatic obstruction by underlying tumour, relative mucosal ischaemia and mucosal prolapse. Since the changes seen on mucosal biopsies are a secondary phenomenon, we tentatively suggest that 'secondary colitis' may be an appropriate appellation.     

Budesonide in the treatment of inflammatory bowel disease

Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, features recurrent episodes of inflammation of the GI tract. The treatment of inflammatory bowel disease is aimed at breaking the cycle of relapsing and remitting inflammation by inducing and maintaining remission. Systemically active conventional corticosteroids have long played a role in the induction of remission in both Crohn’s disease and ulcerative colitis, however, their long-term use can lead to adverse systemic effects. Budesonide, a synthetic steroid, has potent local anti-inflammatory effects and limited systemic bioavailability making it an appealing therapeutic option. Ulcerative colitis with predominantly distal disease may be treated with topical budesonide, however, novel oral controlled-release formulations have also been developed to allow for treatment of the entire colon. This article summarizes the use of budesonide in the management of inflammatory bowel disease.     

The Mongolian gerbil as a model for inflammatory bowel disease

Mongolian gerbils are used as biomedical research models for a variety of diseases and are in some cases suited better than other rodents for basic research and therapeutic studies. The aim of this study was to establish and characterize a dextran sulphate sodium (DSS)‐induced model in gerbils for the human inflammatory bowel disease (IBD) and to utilize them for a therapeutic study in vivo. Four concentrations (0.5%, 1%, 2% and 4%) of DSS were administered via drinking water for 7 days; based on these results, a concentration of 3% DSS was given for 9 days in a second approach. Fluid uptake and general clinical condition were assessed daily using a clinical score. Caecum and colon were scored histologically. Fluid uptake was affected by addition of DSS to the drinking water. First clinical symptoms were observed at day 4 of DSS treatment with a considerable increase in clinical score parameters only in gerbils receiving 2% or 4% DSS. Histologically, ulceration and inflammation were observed predominantly in the caecum of gerbils treated with at least 1% DSS; reproducible inflammation in the colon required at least 2% DSS. Using 3% DSS for 9 days, considerably more inflammation was induced in the colon, comparable with lesions usually observed in the mouse model. Using an optimized protocol, DSS treatment induces reproducibly typhlocolitis in Mongolian gerbils, rendering them as a useful model for IBD.     

Evidence for a CD14+ population of monocytes in inflammatory bowel disease mucosa--implications for pathogenesis.

Lipopolysaccharide (LPS) is abundant in the intestinal lumen. CD14 is the receptor for the LPS-LPS binding protein complex, and its presence on mononuclear phagocytes allows cell activation by pg/ml concentrations of LPS. We have shown that the recently recruited blood monocyte in inflammatory bowel disease mucosa is CD14+. This study examined the expression of CD14 on macrophages in inflamed (n = 13) and uninflamed (n = 7) intestine by immunohistochemistry, and on disaggregated lamina propria mononuclear cells (12 from inflamed, 17 from uninflamed intestine) and peripheral blood mononuclear cells (n = 26) by flow cytometry, using a panel of three MoAbs directed against CD14. Immunohistochemistry revealed that 3.7% of macrophages in uninflamed intestine were CD14+, while 25.1% of macrophages in active inflammatory bowel disease expressed CD14 (P < 0.02). Flow cytometry demonstrated that CD14 expression by macrophages from Crohn's disease and ulcerative colitis was augmented significantly (P = 0.02 and P = 0.01, respectively) compared with uninflamed intestine, with a discrete population of macrophages in inflammatory bowel disease, not present in normal intestine, which strongly expressed CD14. The characteristically high levels of CD14 on blood monocytes were unaffected by the presence of intestinal inflammation. Given the exposure of lamina propria cells to LPS present in the lumen of the terminal ileum and colon, the increased numbers of CD14+ macrophages in inflammatory bowel disease may result in greatly increased production of inflammatory mediators, thereby suggesting a mechanism for the perpetuation of mucosal inflammation.     

Accumulation of immunoglobulin-containing cells in the gut mucosa and presence of faecal immunoglobulin in severe combined immunodeficient (scid) mice with T cell-induced inflammatory bowel disease (IBD)

Scid mice transplanted either with a gut wall graft or with low numbers of purified CD4⁺ T cells from immunocompetent syngeneic donor mice show clinical signs of IBD 3–4 months post-transplantation. The disease is mediated by mucosa-infiltrating CD4⁺ TCRαβ⁺ T cells. The pathology of 52 individual colon segments obtained from 20 gut wall- or CD4⁺ T cell-transplanted diseased scid mice was evaluated by histology and the numbers of infiltrating immunoglobulin-containing cells were determined. In particular, cells positive for IgM, IgA and non-inflammatory immunoglobulin isotypes such as IgG1 and IgG2b were found to accumulate in colon segments displaying the most severe histopathology, including inflammatory cellular infiltration, epithelial hyperplasia and ulcerative lesions. Compared with colon segments of normal C.B-17 mice, the lesional scid colon shows increased levels of cells positive for the IgG classes. Faecal extracts of the CD4⁺ T cell-transplanted scid mice revealed the presence of all six murine immunoglobulin isotypes. Disease progression was accompanied by an increased level of excreted IgM and IgG3 and decreased levels of IgA. It is concluded that locally secreted immunoglobulins may play an immunomodulating role in the pathological changes observed in the present model of T cell-induced inflammatory bowel disease.     

Reliability of rectal biopsy in distinguishing between chronic inflammatory bowel disease and acute self-limiting colitis

Aims : In order to assess the validity of previously proposed criteria for the differentiation of chronic inflammatory bowel disease (CIBD) from acute self-limiting colitis (ASLC) all rectal biopsies were reported by a single histopathologist with a long-term gastrointestinal interest over a 4.5-year period. Methods and results : The presence or absence of distorted crypt architecture, increased lymphocytes and plasma cells, villous mucosal architecture, granulomata, basal lymphoid aggregates, basal giant cells and Paneth cell metaplasia was noted for each biopsy. The definite presence of any of the above features, with the exception of intramucosal granulomata, was regarded as indicative of CIBD. Eighteen months later all available case notes were examined and the presenting clinical symptoms and working clinical diagnosis extracted. The final diagnosis, histopathological diagnosis and the presence or absence of any of the above histopathological features were correlated and the positive predictive value of each histopathological feature was calculated. A correct diagnosis of either CIBD or ASLC was made in 80 of 84 and 29 of 31 cases, respectively. Conclusions : Villous mucosal architecture and Paneth cell metaplasia were found to be specific features of CIBD. Distorted crypt architecture, basal lymphoid aggregates and plasma cell infiltration of the lamina propria were also useful features but strict definition of these features is required and discussed. Intramucosal epithelioid granulomas were identified in eight cases of CIBD and four cases of ASLC. In association with ruptured crypts intramucosal granulomas are not specific features of Crohn's colitis.     

Imaging findings of mantle cell lymphoma involving gastrointestinal tract

Clinical manifestations and imaging findings of mantle cell lymphoma involving gastrointestinal tract were evaluated. The subjects were 7 cases of mantle cell lymphoma involving the gastrointestinal tract. All cases were pathologically confirmed in our hospital during the period from April 1994 to July 2000. Five patients were male and 2 were female, and their age ranged from 49 to 63 years (average 57.4). The objectives were: 1) characteristics and distribution of multiple polyposis, 2) presence, location and enhancement pattern of bowel wall thickening or mass formation, 3) presence of splenomegaly, 4) presence and location of abdominal lymph node enlargement, 5) involved extra-abdominal organs, 6) combined cancer and location, and 7) other findings. All mantle cell lymphomas occurred in elderly persons, over 40 years, and most showed multiple polyposis (6/7), bowel wall thickening or mass formation (6/7), lymph node enlargements (6/7) and extra- abdominal involvement (5/7). All cases of polyposis involved the small bowel and colon, and the size of the polyps ranged from 0.1-4.0cm. Four of 6 patients showed combined sessile and polypoid polyps, while the other 2 showed only sessile polyps. Most of or some of the polyps in 3 patients showed small central ulcerations. Most of the patients (5/6) showed an uncountable number of polyps. Polyposis was predominant in the rectum, ascending colon, rather than other sections in the colon, and the ileum were almost always involved by polyposis. Bowel wall thickening or mass formation developed exclusively in the ascending colon, rectum or ileum. Extra- abdominal involvement developed either simultaneously or nonconcurrently with gastrointestinal involvement. Some of patients showed splenomegaly (3/7), appendiceal enlargement (2/7), and intussusception (1/7), and some had associated adenocarcinomas (3/7).     

Acid sphingomyelinase inhibition suppresses lipopolysaccharide-mediated release of inflammatory cytokines from macrophages and protects against disease pathology in dextran sulphate sodium-induced colitis in mice

Lipopolysaccharide (LPS) and inflammatory cytokines cause activation of sphingomyelinases (SMases) and subsequent hydrolysis of sphingomyelin (SM) to produce a lipid messenger ceramide. The design of SMase inhibitors may offer new therapies for the treatment of LPS- and cytokine-related inflammatory bowel disease. We synthesized a series of difluoromethylene analogues of SM (SMAs). We report here the effects of the most potent SMase inhibitor, SMA-7, on the LPS-mediated release of tumour necrosis factor-alpha, interleukin-1beta and interleukin-6 from THP-1 macrophages and the pathology of dextran sulphate sodium (DSS)-induced colitis in mice. SMA-7 suppressed the LPS-induced cytokine release and nuclear factor-kappaB activation. LPS stimulation caused a four-fold increase in acid SMase activation, but little increase in neutral SMase activity. The presence of 10 microm SMA-7 caused acid SMase to remain at the control levels and reduced the formation of ceramide. HT-29 cells had significantly decreased cell viability when incubated with media from LPS-stimulated THP-1 macrophages. However, incubating the colon cells in media from both SMA-7 and LPS-treated macrophages caused little decrease in viability, suggesting that ceramide has a role in the LPS-stimulated signalling that releases cytotoxic factors against colon cells. Oral administration of SMA-7 to mice with 2% DSS in the drinking water, for 10 or 21 consecutive days, reduced significantly the cytokine levels in the colon and the severity of colonic injury. These findings suggest a central role for acid SMase/ceramide signalling in the pathology of DSS-induced colitis in mice, indicating a possible preventive or therapeutic role for SMase inhibitor in inflammatory bowel disease.     

Neither direct nor developmental exposure to bisphenol A alters the severity of experimental inflammatory colitis in mice

Abstract

Bisphenol A (BPA) is a high production volume endocrine disrupting chemical that is widely used in many consumer products and prevalent in human biological fluids. Recent studies suggest that BPA is active even at low levels, raising concern about its potential harm to human health. Given that the main route of exposure to BPA is oral, via the consumption of BPA-tainted foods and beverages, intestinal tissues could be particularly vulnerable to BPA-induced changes. A novel examination is reported here of whether oral exposure to BPA affects inflammatory bowel disease (IBD), an immune-mediated disease of the colon, using a mouse model of inflammatory colitis. In addition to direct exposure, the possible contribution of maternal BPA exposure to disease later in life is explored. It was found that daily oral exposure to BPA at the US Environmental Protection Agency described oral reference dose (50?µg/kg/day), either via direct oral route or through maternal sources (i.e. developmental exposure), did not significantly alter disease outcomes of body weight, survival, or colonic pathology. These observations suggest that oral BPA exposure, at this dose and for this exposure duration, has minimal influence on aspects of the inflammatory response that regulate immune mediated diseases of the gastrointestinal tract.     

Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease.

Previous studies have demonstrated the presence of much more marked macrophage heterogeneity in colonic mucosa affected by the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn's disease) than in normal mucosa. This study examines the morphology, distribution and phenotypic expression of mucosal macrophage-like cells in biopsies from patients with idiopathic inflammatory bowel disease in comparison with disease control samples from patients with colonic infection or ischaemia. Approximately 80% of macrophage-like cells in histologically normal mucosa co-express the antigens recognized by the monoclonal antibodies RFD1 (an interdigitating cell marker) and RFD7 (a marker for mature tissue macrophages). In idiopathic inflammatory bowel disease, the normal colonic macrophage population is partly replaced by cells staining positively with RFD7 alone, and, to a lesser extent, with RFD1+ dendritic cells. Sections from patients with infections and ischaemia exhibited epithelial HLA-DR positivity and infiltration of the lamina propria by a more heterogeneous population of macrophages than that seen in histologically normal mucosa. However, the displacement of the normal colonic macrophage phenotype by RFD7+ tissue macrophages occurred to a significantly greater extent in idiopathic inflammatory bowel disease than in disease control mucosa. A pathognomonic feature of the ulcerative colitis and Crohn's colitis sections was the clustering of RFD9+ epithelioid cells at the bases of disrupted crypts and adjacent to areas of mucosal damage. It is concluded that a degree of macrophage heterogeneity and macrophage infiltration can occur as a non-specific response to colonic mucosal damage. The distinctive feature of idiopathic inflammatory bowel disease mucosa is the almost complete replacement of the normal colonic mucosal macrophage population by tissue macrophages and epithelioid cells, and this phenomenon may be important in promoting the development of a chronic inflammatory state.     

Genetic dissection of inflammatory bowel disease: unravelling etiology and improving diagnostics

Over the past 10 years, remarkable advances in the mapping and identification of genes involved in susceptibility to inflammatory bowel disease have been witnessed. Most notable among these advances has been the discovery of variants in the CARD15, DLG5, SLC22A4 and SLC22A5 genes, which are associated with increased risk of inflammatory bowel disease or specifically Crohn’s disease. These discoveries have provided critical new insights into the molecular pathophysiology of inflammatory bowel disease and the pathways wherein genetic and environmental factors such as enteric bacterial flora may interact to trigger immune dysregulation and intestinal inflammation. This review will outline the discovery of these inflammatory bowel disease-related genes, describe future prospects for further inflammatory bowel disease gene identification, and consider the impact of a genetic understanding of inflammatory bowel disease on future clinical practice.     

Primary localized extranodal hodgkin disease of the transverse colon

Extranodal Hodgkin disease presenting as a primary localized neoplasm is uncommon, with rare case reports describing primary sites other than lymph nodes. The gastrointestinal tract is the most frequent site of involvement by extranodal Hodgkin disease, typically involving the stomach or small bowel. To date, we have been able to find only one fully documented case of Hodgkin disease of the sigmoid colon confirmed by immunohistochemical studies. We report a case of extranodal Hodgkin disease involving the transverse colon, presenting as inflammatory bowel disease and documented by light microscopic, immunohistochemical, cytogenetic, and molecular studies.