Paneth Cell Metaplasia Research Articles

Selective expression of HIP/PAP gene in IBD colonic epithelial cells (EC) is associated with paneth cell metaplasia

Background and Aims: We have established an approach to investigate IBD-associated genes using germ-free mice (Gastroenterology; 114: G43l4,1998). We demonstrated that regenerating gene (reg) I1If3and IUvwere induced in epithelial cells (EC) after bacterial reconstitution. The expression of HIPIPAP, the human homologue of reg III, was preferential in IBD EC although the number of samples was limited (Gastroenterology; 116:G34l2,1998). The aim of this study was to investigate HlPIPAP mRNA expression using a large number of samples and to characterize EC expressing this gene. Methods: HIPIPAP mRNA expression was examined by northern blotting using isolated colonic EC RNA from 17 control, 20 CD and 23 UC patients including 5 paired samples from inflamed and non-inflamed mucosae. We carried out in situ hybridization using serial tissue sections to identify the cells expressing this gene. One was routinely stained with hematoxylin eosin, and the other section with dylon, which specifically deposits to Paneth cells, to further analyze HlPIPAP expressing cells. Results: More than 60% of IBD EC (12/20 in CD, 15 /24 in UC) strongly expressed HIPIPAP mRNA but definitely none in control. When EC RNA from inflamed and non-inflamed mucosa were compared, the degree of HIPIPAP mRNA expression was predominant in cells from inflamed mucosa. In situ hybridization revealed that HIPIPAP expressing cells were completely selective and localized at the bottom of crypt in both IBD. Positive cells exhibited common features such as acidophilic granules in supranuclear space and lack of mucus, suggesting that these cells shared nature of Paneth cells. Dylon staining confirmed that HIPIPAP expressig cells were actually associated with Paneth cell metaplasia. Conclusion: HIPIPAP mRNA expression in colonic EC is strictly IBD-selective although there is no evidence that this is IBD-specific. Histochemical study clearly revealed that HIPIPAP expressing cells are associated with Paneth cell metaplasia, supporting the idea that altered gene expression in IBD EC is, at least in part, closely associated with abnormal differentiation.

Paneth cell metaplasia and collagenous colitis

Paneth cell metaplasia and collagenous colitis

Does paneth cell metaplasia occur in human small intestinal disease?

Does paneth cell metaplasia occur in human small intestinal disease?

Diversion colitis in children: an iatrogenic appendix vermiformis?

Diversion colitis (DC) is a localized, relatively benign, iatrogenic condition which occurs in almost 100% of diverted colonic segments in patients who undergo ileostomy/colostomy for various reasons. The aim of this study was to establish histological features of DC in children. Twenty-three cases of DC following colostomy for Hirschsprung's disease in young children were analysed. The distinguishing features included prominent follicular lymphoid hyperplasia (100%), chronic mucosal inflammation (100%), accompanied by a variable degree of acute inflammation (78%) and Paneth cell metaplasia (26%). Less frequent histological findings were as follows: mild goblet cell depletion (22%), foci of cryptitis (13%), crypt abscesses (13%) and mild architectural distortion (22%). A previously unrecognized feature was the presence of mucosal aggregates of eosinophils, found in 43% of cases. A striking similarity between the normal appearance of the vermiform appendix and pathological features in DC was noted and the possible relationship between the two is discussed. Histological features of DC in children are very similar to those described in adults. They should help to distinguish it from ulcerative colitis and Hirschsprung's-associated enterocolitis in order to prevent inappropriate therapy and follow-up. There are many similarities between DC and the normal appendix vermiformis.

Gallbladder Adenocarcinoma with Florid Neuroendocrine Cell Nests and Extensive Paneth Cell Metaplasia.

We report a unique case of gallbladder adenocarcinoma associated with florid neuroendocrine cell nests and extensive Paneth cell metaplasia that has not been described previously. The patient was a 79-yr-old woman with a pedunculated, polypoid mass in the gallbladder. Microscopically, the mass was composed at tumor cells showing tubular and papillary growth patterns, consistent with well-differentiated adenocarcinoma. One-third or more of the tumor cell showed Paneth cell appearance. Goblet cell-type tumors were also intermingled. In addition, neuroendocrine cell nests, that were connected to the neoplastic glands, were scattered throughout the stroma. lmmunohistochemically, the labeling index of MIB-1 in adenocarcinoma cells including Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cells forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we think that the neuroendocrine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin producing neuroendocrine cells to proliferate. We postulate that Paneth cell-type carcinoma cells may be intimately related to such substance(s) in our case.

Morphologic Criteria Applicable to Biopsy Specimens for Effective Distinction of Inflammatory Bowel Disease from Other Forms of Colitis and of Crohn's Disease from Ulcerative Colitis

Background: Inflammatory bowel disease (IBD)?and Crohn's disease (CD) and ulcerative colitis (UC) in particular?could be more reliably diagnosed by using biopsy criteria incorporating the colorectal distribution of specific histologic features. The aim of this study was to elucidate criteria distinguishing IBD from other forms of colitis (non-IBD), and CD from UC on the basis of multiple colorectal biopsies. Methods: We examined multiple biopsy specimens (mean, 6.1) from 299 consecutive Japanese subjects with active colitis and performed multiple logistic regression analyses on 70 histologic features, from which 2 equations were constructed for the probabilities (PIBD and PCD) of a) IBD (versus non-IBD), and b) CD (versus UC), respectively, being present. On the basis of a receiver-operating characteristic curve, we determined four cut-off values for PIBD and constructed the criteria, consisting of the five categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. The criteria for CD versus UC were constructed in a similar manner. Their validities were evaluated using 132 Canadian subjects. Results: The statistically significant histologic features were as follows: for IBD, crypt architectural abnormalities, basal plasmacytosis with severe chronic inflammation, and distal Paneth cell metaplasia; for CD, segmental crypt architectural abnormalities and mucin depletion, mucin preservation at the active sites, and focal chronic inflammation without crypt atrophy. In the categories of probable IBD and probable non-IBD, both sensitivities and specificities exceeded 97%. Probable CD and probable UC showed high specificities of more than 97%, and their sensitivities were 94% and 89%, respectively. Kappa statistics showed these criteria to be sufficiently reproducible. Conclusions: Specific histological features together with their distribution can reliably diagnose IBD, distinguish CD from UC, and provide an estimate of the probability of the underlying disease being present.

Diverticular disease-associated chronic colitis.

A clinical syndrome of chronic colitis unique to the sigmoid colon harboring diverticular was recently reported; its histopathological appearance has not been fully elucidated. In this study, the authors analyzed the clinical and pathological features of 23 patients (age range, 38-87 years; median age, 72 years) with diverticular disease-associated chronic colitis. Nineteen presented with hematochezia; four had abdominal pain. Colonoscopic visualization of the mucosa showed patchy or confluent granularity and friability affecting the sigmoid colon encompassing diverticular ostia. Colonic mucosae proximal and distal to the sigmoid were endoscopically normal. Mucosal biopsy specimens showed features of idiopathic inflammatory bowel disease that included plasmacellular and eosinophilic expansion of the lamina propria (100%), neutrophilic cryptitis (100%) with crypt abscesses (61%), basal lymphoid aggregates (100%), distorted crypt architecture (87%), basal plasmacytosis (61%), surface epithelial sloughing (61%), focal Paneth cell metaplasia (48%), and granulomatous cryptitis (26%). Concomitant rectal biopsies obtained in five patients demonstrated histologically normal mucosa. Fourteen patients treated with high-fiber diet or antibiotics or both improved clinically, as did nine patients administered sulfasalazine or 5-aminosalicylic acid. Five patients underwent sigmoid colonic resection, three for stricture with obstruction and two for chronic blood loss anemia. Among a control population of 23 age- and gender-matched patients with diverticular disease without luminal surface mucosal abnormality, none required resection during the same follow-up period. By Fisher's exact test, a statistically significant difference in outcome for patients with and without colitis was detected (p = 0.049). In addition, three patients developed ulcerative proctosigmoiditis 6, 9, and 17 months after the onset of diverticular disease-associted colitis. The data indicate that diverticular disease-associated chronic sigmoid colitis expresses morphological features traditionally reserved for idiopathic inflammatory bowel disease. Its clinical and endoscopic profiles permit distinction from Crohn's disease and ulcerative colitis. Patients with chronic colitis in conjunction with diverticula are at increased risk for sigmoid colonic resection. Diverticular disease-associated chronic colitis may also precede the onset of conventional ulcerative proctosigmoiditis in some cases.

Clear Cell Adenocarcinoma arising from a Urethral Diverticulum

Carcinoma of the urethra is rare with only about 1,500 cases in the literature. Even more rare is carcinoma arising from a urethral diverticulum with about 100 cases reported to date. We report a case of clear cell adenocarcinoma arising from a urethral diverticulum.

Carcinoid tumour complicating inflammatory bowel disease: A study of two cases with review of the literature

Two cases of carcinoid tumour complicating inflammatory bowel disease (IBD) are presented. Both tumours were located in the appendiceal tip. The first case occurred in a man with Crohn's disease (CD), and the second one in a woman suffering from ulcerative colitis (UC). Histochemical and immunohistochemical studies were not allowed on case 1 because the tumour was not still present on serial sections of the appendix. On case 2, tumour cells were not reactive with Grimelius and Masson-Fontana stainings, but were strongly stained with anti-keratin and anti-chromogranin monoclonal antibodies (MAb), and faintly expressed neuron specific enolase (NSE), and Leu-7. Both cases occurred in inflammatory or damaged mucosa which exhibited Paneth cell metaplasia and hyperplasia and areas indefinite for dysplasia. Along with these lesions, hyperplasia of enteroendocrine cells was pointed out in the neighbouring appendiceal and colonic mucosa by means of anti-chromogranin MAb. These data suggest that the association of carcinoid tumour with IBD, albeit rare, is not coincidental and is the result of hyperplastic and dysplastic troubles that may involve enteroendocrine cells as well as such other derivatives of digestive stem cells as columnar cells, goblet cells and Paneth cells.

A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Clinical findings and early diagnosis.

In 105 patients with a first attack of colitis, clinical, microbiologic, laboratory, and histologic features were studied prospectively with the aim of differentiating inflammatory bowel disease (IBD) from infectious colitis as early as possible. Of the patients who proved to have IBD the mode of onset of diarrhoeal symptoms was insidious in 56% and non-insidious in 44%, whereas in 81% of those who proved to have infectious colitis the onset was acute. Most patients with infectious colitis presented within 1 week, had early fever, and did not show histologic features characteristic of IBD. Most IBD patients with a more acute onset had clinical warning signs of IBD such as slight previous bowel symptoms, a late presentation time (> 1 week), and absence of early fever or had histologic features characteristic of IBD. These features were basal plasmacytosis, crypt distortion, more than two vertical crypt branches, villous mucosa, mucosal atrophy, epithelioid granuloma, and Paneth cell metaplasia. Moreover, 61% of the IBD patients with a non-insidious onset fell ill in connection with travelling abroad, gastrointestinal infection, or treatment with antibiotics. Knowledge of the above clinical and histologic factors will facilitate differentiation of IBD from infectious-type colitis.

The morphologic features of diversion colitis: Studies of a pediatric population with no other disease of the intestinal mucosa

Studies of diversion colitis have not shown a consistent pattern of histopathologic features, and many descriptions are difficult to interpret because of the presence of underlying intestinal mucosal disease. To define the histologic changes in patients free of other mucosal inflammatory disease, we studied the resected segments of bypassed colorectum from 37 patients with Hirschsprung's disease treated by a two-stage procedure, using rectal biopsy specimens taken for initial diagnosis and trimmings from proximal to the stoma as controls. Biopsy specimens from a further 14 patients of similar age but without colorectal mucosal disease were used as additional controls. The histology of the bypassed segment was abnormal in all patients. Twenty-six had diversion colitis characterized by diffuse follicular lymphoid hyperplasia; lamina propria expansion by plasma cells, lymphocytes, and some neutrophils; cryptitis; reactive epithelium; and mucin depletion. Crypt abscesses, aphthous ulcers, mild architectural distortion, and Paneth cell metaplasia were noted in more severe cases. The remaining 11 patients had mild follicular lymphoid hyperplasia and an increase in lymphoplasmacytic infiltrates, with absence of neutrophils, epithelial injury, and other changes seen in diversion colitis, a pattern we term “diversion reaction.” Diversion colitis is common in children with a bypassed colorectum. It can be distinguished histologically from other mucosal diseases in most cases. We hypothesize that diversion reaction may be an inevitable consequence of colonocyte nutrient deficiency and that diversion colitis may be superimposed by a second insult, such as a low-grade pathogen.

Lysozyme gene expression in inflammatory bowel disease

Riboprobe in situ hybridization (rISH) demonstrates active lysozyme synthesis in ulcerative colitis and Crohn's disease. Maximal labeling was seen in Paneth cells, macrophages, and granulomas. Diffuse infiltration of the mucosa by lysozyme-rich polymorphs characterizes ulcerative colitis but obscures reactivity in other cell lineages in immunohistochemical studies; lysozyme mRNA is not detected in polymorphs, rISH giving a clearer picture than immunohistochemical studies of the active synthesis of lysozyme within the gut in inflammatory bowel disease. In ulcerative colitis, strong signals localized to Paneth cell metaplasia were found in 11 of 20 cases and to a lesser degree in non-Paneth cell lineages in regenerative mucosa in 13 of 20 cases. In Crohn's disease, abundant labeling was seen in tuberculoid granulomas (5 of 20) and over macrophage aggregates in the lamina propria in another 7, characteristic patterns not encountered in ulcerative colitis. Low levels of lysozyme messenger RNA were found in the ulceration-associated cell lineage (“pseudopyloric metaplasia”). These results support the view that neutrophils are largely responsible for elevated fecal lysozyme levels in ulcerative colitis and macrophages for elevated serum lysozyme levels in Crohn's disease.

Paneth cell-like change of the prostate gland. A histological, immunohistochemical, and electron microscopic study.

Paneth cell-like change (PCLC) of the prostatic glandular epithelium was focally observed in one case of normal glandular epithelium, two cases of glandular and stromal hyperplasia, one case of prostatic intraepithelial neoplasia, and four cases of prostatic adenocarcinoma. The distinctive cells were characterized by bright, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained material. The cytoplasmic granules in the benign prostatic epithelium were periodate-Schiff's procedure (PAS)-positive and diastase resistant and immunohistochemically negative for lysozyme, neuron-specific enolase, chromogranin, and serotonin. The eosinophilic granules in the prostatic intraepithelial neoplasia and adenocarcinoma cases were immunohistochemically positive for chromogranin, serotonin, and neuron-specific enolase, and negative for lysozyme. By electron microscopy the eosinophilic granules represented exocrine-like or lysosomal-like vesicles in the benign epithelium and neuro-endocrine granules in the malignant epithelium. The lesion represents a prostatic epithelial PCLC rather than a Paneth cell metaplasia. PCLC is the common histological manifestation of two different phenomena: (a) a PAS-positive and diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic epithelium, and (b) endocrine differentiation with neuroendocrine granules in dysplastic and malignant prostatic epithelia. The importance of recognizing PCLC lies in its differentiation from other possible prostatic cytoplasmic inclusions.

‘Metaplastic lesions’ in intrahepatic bile ducts in hepatolithiasis: A histochemical and immunohistochemical study

Pathology of the intrahepatic bile ducts bearing calculi was examined with an emphasis on metaplasia in 22 cases of hepatolithiasis and in seven cases of normal livers. Normal livers contained few glandular elements within the bile duct walls and no metaplastic lesions or endocrine cells. In hepatolithiasis, a number of mucous glands resembling pyloric glands (pseudopyloric gland metaplasia) were seen within duct walls in all cases. The epithelial cells of the glands were positive for class III mucin with paradoxical concanavalin A staining which is known to be specific for pyloric glands. These cells were also positive for neutral, sialo- and sulfomucin to a variable extent. Intestinal metaplasia, including goblet cell and Paneth cell metaplasia, was found within duct walls and in covering epithelia in five (23%) cases. Endocrine cells, including argyrophil, argentaffin and gut hormone-containing cells were present in these metaplastic lesions in 13 (59%) cases. The occurrence of endocrine cells was closely associated with intestinal metaplasia, although there were a few endocrine cells in metaplastic pseudopyloric glands. These findings suggest that metaplastic lesions similar to the well-known metaplastic lesions in the gallbladder occur in the intrahepatic bile duct walls in hepatolithiasis. The appearance of metaplastic lesions and endocrine cells may be causally related to chronic inflammatory processes associated with hepatolithiasis.

Unusual urethral diverticulum lined by colonic epithelium with Paneth cell metaplasia

Diverticulum of the female urethra has an incidence of 1.4% to 4.7%. It is generally agreed that the majority of these are acquired lesions. There is, however, evidence that some are of congenital origin. Documented cases of diverticula with colon-type tissue are rare. A case of urethral diverticulum with colonic epithelium and features of Paneth cell metaplasia is presented. Causes, symptoms, diagnostic methods, and treatment are discussed.

Persistence of enterocolitis following diversion of faecal stream in Hirschsprung's disease

Mucosal defence mechanisms of the excluded bowel were studied in 12 patients with Hirschsprung's disease. The entire resected segment of colon obtained following Swenson's operation was cut at 0.5-cm intervals and serially examined by routine haematoxylin and eosin staining, immunocytochemistry, and mucin histochemistry. Seven patients who had clinical evidence of enterocolitis prior to defunctioning colostomy showed histological and immunological evidence of enterocolitis (crypt abscesses, ulceration, leucocyte aggregation, Paneth cell metaplasia, and marked immunocyte responses) in the excluded bowel even several months after diversion of the faecal stream. Mucin histochemistry showed marked depletion of neutral mucins and sulphomucins in the excluded bowel with inflammatory changes and reversal of the sialo- to sulphomucin ratio. These results indicate that patients with enterocolitis complicating Hirschsprung's disease have persistent inflammatory changes in the excluded large bowel after diversion of the faecal stream by colostomy. Environmental factors such as bacterial stimulation and proliferation probably cause inhibition of cell renewal, resulting in abnormalities of mucin fractions. Changes in mucin composition, which is an important mechanical and chemical factor of the mucosal defence mechanism, may lead to altered susceptibility to bacterial degradation and hence may be important in the pathogenesis of enterocolitis.