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PubMed1984

Are metaplasias in colorectal adenomas truly metaplasias?

Five thousand seven hundred seventy-eight adenomas or adenomas containing carcinoma from 3215 patients were examined by routine histologic methods for the presence of epithelial metaplasias. Three forms of epithelial metaplasia were encountered: squamous cell metaplasia (0.44%), Paneth cell metaplasia (0.20%), and melanocytic metaplasia (0.017%). In several instances multiple forms of metaplasia were encountered in the same polyp. In those cases in which the paraffin blocks were available, a Grimelius stain was performed. Grimelius-positive cells were present in 63% of the adenomas containing a metaplastic cell type. All cases with Paneth cell differentiation were immunoreactive for lysozyme; all lesions containing areas of squamous differentiation were immunoreactive for keratin except 2. The histopathologic features of these cases are discussed, and it is concluded that rather than representing a true metaplastic process, Paneth cell, squamous cell, and melanocyte differentiation represent the full range of cellular differentiation that endodermally derived tissues can exhibit, particularly when they undergo neoplastic alterations.

Adenoma↗
PubMed2004

NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression.

BACKGROUND: Mutations in NOD2, a putative intracellular receptor for bacterial peptidoglycans, are associated with a subset of Crohn's disease but the molecular mechanism linking this protein with the disease pathogenesis remains unclear. Human alpha defensins (HD-5 and HD-6) are antibiotic effector molecules predominantly expressed in Paneth cells of the ileum. Paneth cells also express NOD2. To address the hypothesis that the function of NOD2 may affect expression of Paneth cell defensins, we compared their expression levels with respect to NOD2 mutations in Crohn's disease. METHODS: Forty five Crohn's disease patients (24 with NOD2 mutations, 21 with wild-type NOD2) and 12 controls were studied. Real time reverse transcription-polymerase chain reaction was performed with mucosal mRNA for HD-5, HD-6, lysozyme, secretory phospholipase A2 (sPLA2), tumour necrosis factor alpha, interleukin 8, and human hypoxanthine phosphoribosyltransferase (housekeeping gene). Immunohistochemistry with anti-HD-5 and histological Paneth cell staining were performed in 10 patients with NOD2 mutations or wild-type genotypes. RESULTS: Ileal expression of HD-5 and HD-6, but not sPLA2 or lysozyme, were diminished in affected ileum, and the decrease was significantly more pronounced in patients with NOD2 mutations. In the colon, HD-5, HD-6, and sPLA2 were increased during inflammation in wild-type but not in NOD2 mutated patients. In both the colon and ileum, proinflammatory cytokines and lysozyme were unaffected by NOD2 status. Immunohistochemistry identified Paneth cells as the sole source of HD-5. CONCLUSION: As alpha defensins are important in the mucosal antibacterial barrier, their diminished expression may explain, in part, the bacterial induced mucosal inflammation and ileal involvement of Crohn's disease, especially in the case of NOD2 mutations.

Adolescent↗
PubMed1992

Paneth cell-like metaplasia of the prostate gland.

We report two cases of Paneth cell-like metaplasia of the prostate gland, one in poorly differentiated carcinoma and the second in benign hyperplasia. By light microscopy, the Paneth-like cells were indistinguishable from Paneth cells found in the normal small intestine and ultrastructurally showed electron-dense granules typical of Paneth cells. Immunohistochemical stains were positive for prostate-specific antigen and prostatic acid phosphatase and negative for lysozyme and alpha 1-antitrypsin. The clinical significance of Paneth cell-like metaplasia is unknown and may represent an example of the multipotential metaplastic capability of actively dividing cells.

Adenocarcinoma↗
PubMed1991

Paneth-like cells in an adenoma and adenocarcinoma in the ampulla of Vater.

A case of adenocarcinoma with significant Paneth cell differentiation arising in a villoglandular polyp at the ampulla of Vater is presented. Paneth-like cells, containing distinct fuchsinophilic granules, were a prominent component of the nonglandular invasive adenocarcinoma and were also seen in the associated adenomatous polyp. Lysozyme, trichrome, and periodic acid-Schiff digest stains, and electron microscopy confirmed that the granules were lysosomal in nature. This case confirms that cells with Paneth-like features can be a significant component in invasive neoplasms and can occur at unusual sites such as the ampulla of Vater.

Adenocarcinoma↗
PubMed2006

Prognostic significance of paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate.

The prognostic significance of Paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate has not yet been established. We studied 36 cases of adenocarcinoma of the prostate showing Paneth cell-like neuroendocrine differentiation, including needle biopsy specimens (n = 27), radical prostatectomies (n = 8), and transurethral resection specimens (n = 1). Paneth cell-like neuroendocrine cells (NECs) were observed as either patchy isolated cells or diffusely involving glands or nests. With Gleason pattern 3, a patchy pattern of NECs was seen in 18/19 cases with only 1/19 (5.3%) case showing diffuse NECs. All the 4 Gleason pattern 4 cases had patchy NECs. Of the 21 cases with Gleason pattern 5, 18 (85.7%) had diffuse NECs with the remaining 3 exhibiting patchy NECs. Radical prostatectomy was performed in 16/36 (44.4%). Tumor was organ confined in 10/16 cases (62.5%). Extraprostatic extension (EPE) with positive surgical margins was seen in 6/16 cases (37.5%). In 4 cases, seminal vesicles were positive for cancer. Pelvic lymph nodes were free of tumor in all cases. The actuarial prostate specific antigen progression-free risk at 5 years and 7 years was 92% and 80%, respectively. Only 2 patients progressed after radical prostatectomy and they both had Gleason score 7 cancer with extraprostatic extension and seminal vesicle invasion. Of the 16 radical prostatectomy cases, 8 (50%) had a Gleason pattern 5 component either on needle biopsy or at radical prostatectomy, with nests, cords, or single cells containing Paneth cell-like neuroendocrine differentiation. Five of these 6 cases with Gleason pattern 5 and available follow-up information had no evidence of progression with mean and median follow-ups of 46 months. Radiation therapy either as monotherapy or combined with hormonal therapy was used to treat patients in 13/36 cases. Overall only 2 patients progressed, one with clinical T2 and the other T3 disease. Of the 5 cases with Gleason pattern 5 composed in part or totally by NECs treated by radiation therapy, all are without evidence of recurrence with a mean and median follow-up of 47 and 45 months, respectively. Of the remaining 5 cases with available follow-up treated with watchful waiting, hormone therapy, or cryotherapy, 4 had Gleason pattern 5 tumor with NECs. Of these 4 cases, 3 had no progression with a mean and median follow-up of 42.5 and 60.5 months, respectively. Despite the cells' bland histologic appearance, strictly applying the Gleason grading system one would have to assign a Gleason pattern 5 to these foci with no glandular differentiation. The current study demonstrates that applying the Gleason score to these foci does not accurately reflect their clinical behavior. In cases with Paneth cell-like NECs, only the conventional adenocarcinoma component should be assigned a Gleason score. In cases in which the entire tumor is composed of Paneth cell-like cells and areas of the tumor lack glandular differentiation, the tumors should not be assigned a Gleason score and a comment should be provided as to the generally favorable prognosis of this morphologic pattern of neuroendocrine differentiation.

Adenocarcinoma↗
PubMed1979

Paneth cell-rich papillary adenocarcinoma and a mucoid adenocarcinoma occurring synchronously in colon: a light and electron microscopic study.

A 71-year-old man who presented with iron deficiency anaemia and weight loss was found to have two colonic tumours: a mucoid adenocarcinoma at the splenic flexure and a papillary adenocarcinoma rich in Paneth cells in the ascending colon. The light and ultrastructural features of the neoplastic cells are described, and the significant of the presence of neoplastic Paneth cells is discussed.

Adenocarcinoma, Mucinous↗
PubMed1981

Crypt cell carcinoma of the appendix (so-called adenocarcinoid tumor).

A series of 16 carcinoid tumors of the appendix, including four examples of so-called adenocarcinoid tumors, has been studied immunohistochemically for the presence of lysozyme, secretory component (SC) and IgA, within tumor cells. Stains for mucin, Paneth cells, and APUD cells were also performed. Of the conventional carcinoid tumors, eight showed focal tubule formation with production of PAS-positive material. In contrast to conventional carcinoids, including those showing tubule formation, adenocarcinoids contained few APUD cells and showed positive staining of tumor cells for lysozyme, SC, and IgA. Paneth cells, staining positively for lysozyme, were present in two cases and mucin-containing Paneth cells were observed. A parallel study of normal small intestinal mucosa demonstrated a population of lysozyme containing goblet cells within the crypts. It is suggested that so-called adenocarcinoid tumors are not derived from APUD cells but from lysozyme-producing cells of the type normally present in small intestinal crypts.

Adenocarcinoma↗
PubMed1989

Qualitative assessment and morphometry in the study of the ileal reservoir after restorative proctocolectomy.

Little is known about the long-term effects on the reservoir mucosa in patients with ulcerative colitis and familial polyposis coli who undergo proctocolectomy with subsequent construction of ileal reservoir/pouch and ileoanal anastomosis. In these patients, questions regarding adaptation towards a more colon-like mucosa and/or development of (pre)malignant changes are of particular importance. With the aim of designing a method for reliable evaluation of the mucosa in the ileal pouch, biopsies from 10 patients were studied by semiquantitative assessment and morphometry. The findings were compared with those obtained from normal jejunum, ileum, and colon. The following parameters were found to be important: Villous surface density, quantity of goblet cells, number of mitoses, and the presence/absence of predominantly sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The villous surface density was determined by a cycloid test system applied to vertical sections. Semiquantitative assessment was a sufficiently precise method for the evaluation of the quantity of goblet cells. The counting of sulphated mucin+ goblet cells was not reproducible, instead a simple statement about the presence or absence of these cells was judged to be adequate. The number of mitoses and of Paneth cells were counted directly. During the first year of function the ileal pouch showed signs of adaptation towards a colon-like mucosa: Reduction of villous surface density, increased mitotic activity, and appearance of sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The amount of goblet cells was generally not increased, rather reduced in some patients.

Adult↗
PubMed1985

Assessment of the symmetry of stem-cell mitoses.

A model of Paneth-cell renewal in the small intestinal epithelium is used to estimate the probability that epithelial stem-cell mitoses are symmetric in the sense that they produce two cells of the same type. I found that counts of the number of Paneth cells per crypt (Paneth cells are terminally differentiated cells derived from small intestinal epithelial stem cells) support a model in which most, if not all, stem-cell mitoses are symmetric.

Animals↗
PubMed1988

Ultrastructural immunolocalization of lysozyme in paneth-like cells in undifferentiated (gastric)-type carcinoma of the stomach.

Five cases of gastric carcinoma of undifferentiated (gastric) type containing Paneth-like cells were studied by immunoelectron microscopy for lysozyme using two methods. The Paneth-like cells in these carcinomas had lost their cellular polarity and possessed electron-dense granules. These granules varied in size (0.5-3 micron in diameter), electron density and shape. Post-embedding method revealed immunolocalization of lysozyme in these granules in all cases, similar to that in normal Paneth cells. Pre-embedding method showed immunoreactivity diffusely or focally located in the cytoplasm, but this approach was unable to reveal immunoreactivity in the granules, a feature also common to normal cells. Our study therefore confirmed that Paneth-like carcinoma cells and normal Paneth cells had the same features, and indicated that undifferentiated-type gastric carcinoma could possess specially differentiated cells, providing further support that such carcinoma could express multipotentiality. The difference in the results obtained by the two immunoelectron microscopy methods was discussed.

Carcinoma↗
PubMed2004

Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice.

BACKGROUND AND AIMS: Gastric intestinal metaplasia, which is mainly induced by Helicobacter pylori infection, is thought to be a precancerous lesion of gastric adenocarcinoma. Intestinal metaplastic mucosa expresses intestine specific homeobox genes, Cdx1 and Cdx2, in the human gastric mucosa. We and others have reported that ectopic expression of Cdx2 in the gastric epithelium generates intestinal metaplasia in the transgenic mouse model. METHODS: To clarify the differences in the roles of Cdx1 and Cdx2 in intestinal metaplasia, we generated transgenic mice expressing Cdx1 in the gastric mucosa and compared Cdx1 induced gastric mucosal morphological changes with Cdx2 induced intestinal metaplasia. RESULTS: The gastric mucosa in Cdx1 transgenic mice was completely replaced by intestinal metaplastic mucosa, consisting of all four intestinal epithelial cell types: absorptive enterocytes, goblet, enteroendocrine, and Paneth cells. Paneth cells, which were not recognised in Cdx2 transgenic mice, were in the upper portion of the intestinal metaplastic mucosa. Pseudopyloric gland metaplasia, which was induced in Cdx2 transgenic mice, was not recognised in Cdx1 transgenic mice. Proliferating cell nuclear antigen (PCNA) positive cells were diffusely scattered in Cdx1 induced intestinal metaplastic mucosa while PCNA positive cells in Cdx2 induced intestinal metaplastic mucosa were in the base of the metaplastic mucosa. Intestinal metaplastic mucosa of Cdx1 transgenic mouse stomach was significantly thicker than that of wild-type or Cdx2 transgenic mouse stomach. CONCLUSIONS: We have confirmed that Cdx1 induced gastric intestinal metaplasia but that it differed from Cdx2 induced intestinal metaplasia in differentiation, structure, and proliferation.

Animals↗
PubMed2006

[A case report of early gastric cancer with Paneth-like tumor cells].

A 55-year-old man was given a diagnosis of grade 0IIc type gastric cancer of the midgastric posterior wall following endoscopy of the upper digestive tract, and subsequently underwent distal gastrectomy. Tumor cells resembling Paneth cells were occasionally observed in differentiated adenocarcinoma that had invaded the submucosal layer, the tumor was CD10-positive, and showed differentiation to complete intestinal metaplasia. In addition, p53-positive cells were also occasionally observed. Although complete intestinal metaplasia is associated with a low incidence of malignant transformation, this case was considered to be different from complete intestinal metaplasia, on which a mutation of the gene of p53 is involved in the early period of carcinogenesis.

Adenocarcinoma↗
PubMed2003

Responses of inbred mouse strains to infection with intestinal nematodes.

Comparisons were made of the immune and inflammatory responses of four strains of inbred mice to infection with the intestinal nematodes Trichinella spiralis and Nippostrongylus brasiliensis to determine whether genetically determined 'high responsiveness' to infection, seen most clearly in intestinal responses, is independent of the parasite concerned and necessarily correlated with protection. The time course of infection was followed by counting adult worms at intervals after infection. Mucosal mast cells and Paneth cell numbers were determined as indices of the intestinal inflammatory response. Levels of IgG2a and IgG1 antibodies and of the cytokines IFN-gamma and IL-5 released from in vitro-stimulated mesenteric node lymphocytes were measured to assess type 1 and type 2 responses. NIH and CBA mice were the most resistant to T. spiralis and N. brasiliensis respectively, resistance in each case being correlated with the most intense intestinal inflammatory responses. C57BL/10 (B10) and B10.BR were the least resistant to T. spiralis, but were as resistant as CBA to N. brasiliensis, despite their intestinal inflammatory responses to both parasites being much lower than the other two strains. Mice infected with T. spiralis made the expected switch from a type 1 (IFN-gamma) to a type 2 (IL-5) response between days 2 and 8, and there were no significant differences in levels of these cytokines between the strains. In contrast, when infected with N. brasiliensis, CBA showed an IFN-gamma response at day 4, all strains switching to IL-5 by day 8 and NIH mice releasing the greatest amount of IL-5. The results indicate that the "high responder" phenotype to intestinal nematode infection is in part determined by host characteristics, but is also determined by the parasite concerned--seen most clearly by the differences between NIH and CBA when infected with T. spiralis and N. brasiliensis. The fact that "low responder" B10 background mice were more resistant to N. brasiliensis than "high responder" NIH implies that each parasite elicits a particular pattern of protective host responses, rather than parasites being differentially susceptible to the same response profile.

Animals↗
PubMed2001

Requirement of Math1 for secretory cell lineage commitment in the mouse intestine.

The mouse small intestinal epithelium consists of four principal cell types deriving from one multipotent stem cell: enterocytes, goblet, enteroendocrine, and Paneth cells. Previous studies showed that Math1, a basic helix-loop-helix (bHLH) transcription factor, is expressed in the gut. We find that loss of Math1 leads to depletion of goblet, enteroendocrine, and Paneth cells without affecting enterocytes. Colocalization of Math1 with Ki-67 in some proliferating cells suggests that secretory cells (goblet, enteroendocrine, and Paneth cells) arise from a common progenitor that expresses Math1, whereas absorptive cells (enterocytes) arise from a progenitor that is Math1-independent. The continuous rapid renewal of these cells makes the intestinal epithelium a model system for the study of stem cell regeneration and lineage commitment.

Alleles↗
PubMedDate not supplied

Intestinal type cholangiocarcinoma of intrahepatic large bile duct associated with hepatolithiasis--a new histologic subtype for further investigation.

Intestinal metaplasia is regarded as a possible predisposing factor of cancer, particularly of the intestinal type adenocarcinoma. The clinicopathologic features of intestinal type adenocarcinoma have been well documented in the stomach, and intestinal metaplasia and intestinal type adenocarcinoma has also been reported in the gallbladder. However, regarding the intrahepatic bile ducts, the clinicopathologic features are not yet clear and there have been no reports in English literature on intestinal type intrahepatic cholangiocarcinoma. We report a case of intestinal type cholangiocarcinoma associated with hepatolithiasis in the large intrahepatic bile duct. The tumor showed mainly intraductal papillary growth primarily composed of absorptive columnar cells. Particularly, Paneth cell metaplasia of carcinoma cells was widespread, and goblet cells and neuroendocrine cells were also observed in the carcinoma tissue, to a varied degree. It showed an intraluminal spread along the dilated intrahepatic ducts with minimal ductal stromal invasion. In the vicinity of the tumor, intestinal metaplasia was also identified in the adjacent hyperplastic and dysplastic bile duct epithelium. Some bile ducts contained stones and the mural glands of the bile ducts showed hyperplastic change secondary to stones. This case is considered to provide the evidence supporting the concept of the metaplasia-dysplasia-carcinoma sequence via intestinal metaplasia in the stone-containing intrahepatic bile ducts.

Aged↗
PubMed1986

Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study.

The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.

Adult↗
PubMed2005

Colonic adenocarcinoma with numerous paneth and endocrine cells.

Numerous granular eosinophilic cells corresponding to Paneth cells were unexpectedly revealed in a moderately differentiated adenocarcinoma of the hepatic flexure of the colon in a 76-year-old man. These cells were clearly seen in routine slides and their nature was confirmed by Masson's trichrome stain, by immunohistochemical reaction for lysozyme, and by electron microscopy. The tumor contained also cells intermediate between Paneth and goblet cells (with both supranuclear granules and mucous globules), observed in Masson's trichrome stain and in electron microscope. Additionally, immunohistochemical reaction for chromogranin A was performed and irregularly scattered neoplastic endocrine cells were visualized in the tumor. The light microscopic and ultrastructural features of this rare neoplasm are described together with detailed clinical data. The incidence and significance of the Paneth cell and endocrine differentiation in colorectal carcinomas are discussed with the review of the literature.

Adenocarcinoma↗
PubMed1995

[A case report of prostate cancer with Paneth cell-like change].

We report one case of Paneth cell-like change of prostate cancer. An 81-year-old male reported to our hospital with the chief complaint of urinary retention. The serum concentration of prostate specific antigen, 168 ng/ml, was high, and digital examination was performed. Because we suspected prostate cancer, needle biopsy of the prostate was performed. Histological examination revealed moderately-poorly differentiated adenocarcinoma. Computed tomography revealed no invasion to the prostatic wall and no metastasis to the lymph node. 99mTc-HMDP revealed no bone metastasis. We chose intravenous hormonotherapy (fosfestrol 500 mg/day, 20 days), but urinary retention did not improve. Therefore, we performed transurethral prostatectomy to improve the symptoms. Histological examination of the removed specimen revealed moderately differentiated adenocarcinoma with Paneth cell-like change. Immunochemical and histochemical stains were positive for Grimelius, serotonin and prostatic acid phosphatase and negative for periodic acid-Schiff reaction, lysozyme, neuron specific enolase, prostate specific antigen, alpha-1-antitrypsin and IgA.

Adenocarcinoma↗