Mixed Polyps Research Articles

Serrated pathway in colorectal carcinogenesis

Serrated adenocarcinoma is a recently described subset of colorectal cancer (CRC), which account for about 10% of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC. Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed polyps. HPs are the most common serrated polyp followed by SSA and TSA. This distinct histogenesis is believed to have a major influence in prevention strategies, patient prognosis and therapeutic impact. Genetically, serrated polyps exhibited also a distinct pattern, with KRAS and BRAF having an important contribution to its development. Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype. In the present review we will address the current knowledge of serrated polyps, clinical pathological features and will update the most recent findings of its molecular pathways. The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.

Mixed serrated polyp（sessile serrated adenoma/polyp and traditional serrated adenoma）に併存して発生した盲腸SM癌の1例

Mixed serrated polyp（sessile serrated adenoma/polyp and traditional serrated adenoma）に併存して発生した盲腸SM癌の1例

Immunophenotypes and gene mutations in colorectal precancerous lesions and adenocarcinoma

To analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions. Fifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing. (1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50). Immunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.

Saving Colon

Purpose: A 47-year-old asymptomatic woman was self-referred for evaluation of diffuse colorectal polyposis. Recent colonoscopy revealed > 100 diffuse 3-7 mm polyps throughout the colon and rectum, reported as mixed hyperplastic polyps and tubular adenomas without high-grade dysplasia; colectomy was recommended by her initial gastroenterologist. Her past medical history included nephrectomy for hypernephroma at age 38, hysterectomy with bilateral oophorectomy for uterine fibroids and ovarian cysts, partial thyroidectomy for multinodular goiter, and removal of oral papillomas and soft cutaneous nodules. Physical examination revealed macrocephaly and flesh-colored cutaneous and gingival nodules. Upper endoscopy revealed multiple small raised plaques 2 mm to 10 mm in size throughout the esophagus, and multiple small sessile 3-5 mm polyps in the gastric fundus and body. Colonoscopy revealed pancolonic polyps ranging in size from 3 mm to 1 cm. Pathologic review demonstrated esophageal glycogenic acanthoses, gastric hyperplastic polyps, and colonic hamartomas. Genetic testing revealed a mutation in the phosphatase and tensin homolog (PTEN) gene, which confirmed the diagnosis of Cowden syndrome (CS). Thus, the patient was advised to undergo appropriate cancer surveillance according to National Cancer Center Network guidelines rather than total colectomy. Cowden syndrome is an autosomal dominant disorder related to germ line mutations in the PTEN gene mapped to the 10q22-23 locus, and is generally reported to be found in 80% of patients with CS. The prevalence of CS has been estimated to be between 1/200,000 and 1/250,000. Typical benign manifestations of the syndrome include trichilemmomas (83%), acral keratoses, lipomas, multinodular goiter (50-70%), macrocephaly (80%) and gastrointestinal polyposis (40%). Co-occurrence of extensive esophageal glycogenic acanthoses and colonic polyposis is rare outside of CS, and can be considered pathognomonic for this disease. Although hamartomatous polyps preponderate in CS (90%), adenomatous, inflammatory, hyperplastic, lymphoid, ganglioneuromatous, and leiomyomatous polyps can also occur throughout the entire gastrointestinal tract. The ambiguity of the prevalence and risks of colorectal polyposis in patients with CS is reflected in the lack of recommendations concerning colorectal screening or surveillance in the National Comprehensive Cancer Network (NCCN) treatment guidelines. The greatest neoplastic risks for CS patients are for breast cancer (25-50%), endometrial cancer (5-10%), and thyroid cancer (3-10%). Careful breast, thyroid, cutaneous, and genitourinary surveillance is indicated. Intervals for GI tract surveillance have not been established.

Does the incidence of unexpected malignancy in ‘benign’ rectal neoplasms undergoing trans‐anal endoscopic microsurgery vary according to lesion morphology?

Mucosectomy by trans-anal endoscopic microsurgery (TEMS) allows safe and effective excision of benign rectal lesions. Preoperative endoscopic, clinical and ultrasonographic assessment aims to select benign lesions whilst avoiding inappropriate mucosectomy in lesions with malignancy. This study examines the relationship between lesion morphology and accurate benign preoperative classification of rectal lesions undergoing TEMS. Primary lesions preoperatively assessed as benign were identified from a prospective TEMS database. Operative specimen morphology was independently classified by two blinded investigators, using photographs, into flat-sessile, exophytic or mixed morphology. The accuracy of the preoperative assessment by rectal ultrasonography was compared with the results of histological examination of the excised specimen (χ(2) and Fisher's exact tests). Of 167 lesions with adequate data, the morphological classification showed 60 flat-sessile, 56 mixed morphology and 51 exophytic tumours, of which 5, 7 and 9, respectively, contained unexpected malignancy (P=0.48). Accurate preoperative assessment of a lesion as benign occurred in 89% of flat-sessile and mixed morphology (n=55 and 49, respectively) and in 70% of exophytic lesions (n=36) (P=0.01). Only the exophytic group contained patients in whom preoperative endoscopic and ultrasonographic staging could not be confidently made (uTx). Histology demonstrated six of the seven uTx cases to be benign. In this study exophytic polyps were less likely to be accurately classified as benign using preoperative ultrasonography/endoscopy when compared with flat-sessile or mixed morphology polyps.

Intramucosal Colon Cancer Developing in an Inverted Hyperplastic Polyp

Inverted hyperplastic polyps (IHPs) of the colon are unusual variant of exophytic hyperplastic polyps that are characterized by epithelial displacement or inversion of the epithelium into the submucosa.1 To date, only a few cases of IHPs associated with adenoma or adenocarcinoma have been reported.2-4 However, due to the rarity of these polyps, their malignant potential is poorly understood. A 56-year-old man was referred to Uijeongbu St. Mary's Hospital due to a positive fecal occult-blood test during a routine health check-up. The patient had a medical history of surgery for intestinal perforation and hypertension. On admission, physical examination revealed no abnormal findings and all laboratory examination were within normal range. We performed colonoscopy for further evaluation. The colonoscopy showed a subpedunculated polyp with a large dimple, 20 mm in diameter, in the sigmoid colon (Fig. 1). An endoscopic mucosal resection (EMR) using the inject and cut technique was performed and the polyp was resected en bloc. The pathology examination showed an intramucosal cancer in an IHP (Fig. 2). The intramucosal cancer consisted mainly of well-differentiated adenocarcinoma (Fig. 2). Abdominal computed tomography showed no discernible malignant lesion. Follow-up colonoscopy revealed no remarkable findings 1 year after EMR. Fig. 1 Colonoscopy shows a subpeduculated polyp with a large dimple located in the sigmoid colon. Fig. 2 Microscopic image of the resected specimen showing an inverted hyperplastic polyp associated with intramucosal cancer, as indicated by the arrowhead in the low-magnified image (H&E stain, ×100). The intramucosal cancer consisted mainly ... IHPs of the colon were initially described by Sobin5 in 1985. They represent an unusual morphological variant of hyperplastic polyps that shows epithelial displacement into the submucosa.5 IHPs of the colon are most commonly sessile lesions and are predominantly located in the left colon.1 Although the pathogenesis and natural history remain unknown, IHPs are thought to result from local trauma.1 The characteristic endoscopic features of IHPs include sessile or superficial elevated lesions with a pitted surface or central depression.6-8 Because distinctive surface pattern of IHPs is similar to that of invasive carcinoma or depressed type adenoma, IHPs are difficult to diagnose endoscopically.2,6 Observation of the pit pattern using magnifying colonoscope may be useful to precisely diagnose IHPs because it has the same surface and cellular features as ordinary hyperplastic polyps.6 The current case showed atypical endoscopic findings with large depressed portion. In addition, the histology showed the presence of well-differentiated carcinoma in the depressed portion. To date, only a small number of cases associated with adenomas or adenocarcinoma have been described. Among them, three cases with an IHP were associated with adenomas,3 and one case with invasive cancer.4 For several years, hyperplastic polyps have been considered as non-neoplastic lesions without malignant potential. However, some hyperplastic polyps show molecular features similar to those of colorectal carcinomas. Several subtypes of serrated polyps, such as sessile serrated adenoma (traditional serrated adenoma), and mixed polyp, have been proposed to be the precursors of colorectal carcinomas.9 However, due to the rarity of IHPs, their malignant potential is poorly understood. IHPs of the colon are usually asymptomatic and are often detected incidentally on endoscopy.3 In some cases, the main clinical feature of IHPs of the colon is gastrointestinal bleeding or abdominal pain.2 Usually, an endoscopic biopsy is not sufficient to make an accurate diagnosis of an IHP of the colon. The final diagnosis of an IHP of the colon depends on the pathological examinations of EMR and endoscopic polypectomy specimens.8 Treatment for IHPs continues to be debated. Since IHPs have benign cellular characteristics of exophytic hyperplastic polyps, overtreatment should be avoided. However, endoscopic treatment is necessary in cases with associated adenomatous findings, due to their malignant potential.4 In the present case, endoscopic treatment was appropriate for the large hyperplastic polyp. In conclusion, we reported a rare case of early colon cancer developing in an IHP of the sigmoid colon treated with EMR. Further studies are needed to clarify the malignant potential of IHPs.

Síndrome de poliposis hiperplásica: diversidad fenotípica y asociación a cáncer colorrectal

Background and objetiveHyperplastic polyposis syndrome (HPS) is an uncommon disorder characterized by hyperplastic polyps (HP) occasionally associated with serrated adenomas (SA) or mixed polyps (MP) and defined by clinical criteria (OMS/Cleveland). HPS is heterogeneous regarding the number and size of polyps, and it is associated with colorectal cáncer (CRC) and a family history. Its genetic basis is unknow. We describe individuals with HPS criteria from a series of families assessed in our Unit of Genetic Advice for colonic polyposis. Our objective is to identify the clinical characteristics of this syndrome. Patients and methodsRetrospective study of 197 families with colonic polyposis (1998-2011), identifying patients with HPS criteria. To know the number of polyps, we took into account polypectomies and/or the histologic study of surgical samples. Polyps were classified into adenomas, serrated lesiones (HP and SA) and MP. Genetic studies revealed: microsatellite instability (MSI), MUTYH gene variants (p.Tyr165Cys, p.Gly382Asp and p.Glu396GlyfsX43) and APC gene. ResultsEighteen individuals, with a median age of 51.1 years, had criteria of HPS (11M/7F). Number of HP varied between 14 and 100 coexisting with classical adenomas, SA and MP in 14 individuals (77.8%). Localization of polyps: ascending and descending colon in 13 individuals (72.2%) and only descending colon in 5 (27.8%). A CRC was detected in 10/18 (55.6%) patients, and 3 of them had a double CRC, a family history in 3 patients (16.7%) and a history of HPS in one. IMS was not detected in 8 CRC nor in 3 adenomas studied; we detected 2/13 heterozygous mutations in the MUTYH gene (p.Gly382Asp) and one variant with an unknown biological significance in the APC gene (p.Ser926Pro). ConclusionsThe phenotypic variability of HPS difficults its identification, hence it is important to adhere to the clinical criteria established for its classification as well as to establish screening guidelines for CRC on the basis of its high incidence.

P-0206 Early-Onset Colorectal Cancer: The Comparative Molecular Classification Suggests The Existence of Two new Different Groups Within Colorectal Cancer

ABSTRACT Introduction Early-onset colorectal cancer (CRC) is an indicator of a hereditary component, but recently this is changing. The aim of our study was to compare the CRC molecular classification from the three main carcinogenetic pathways for two different populations, young and elderly, in order to identify any particular group in the early-onset population. Methods We analyzed a total of 119 CRC-patients from 2002 to 2008. Forty-five were early-onset CRC, and 74 older than 69. We analyzed the microsatellite instability (MSI) and CpG Islands Methylator Phenotype (CIMP) in both populations, classifying them into 4 main subtypes: MSI with CIMP-high (group A), MSI with CIMP low-0 (group B); Microsatellite Stability (MSS) with CIMP-high (group C), and MSS with CIMP low-0 (group D). We analyzed the clinic-pathological and familial differences between every group within each population and also each group between both populations. Only statistically significant differences are shown. Results Within early-onset CRC we observed that in group A, 100% of CRC were located in right colon versus group D, in which 90% of CRC were in left colon and rectum. In majority of groups tumours were mucinous, except in group D (89% were not). A 100% and 40% of CRC in group A and B were Lynch syndrome cases, whereas none within the other groups. The majority of early-onset CRC associated polyps. In group C, 100% were mixed polyps whereas in group D and A, 72% and 50% were adenomatous polyps, respectively. Familial cancer history in young CRC was frequent but different depending on the subtype. In group A and B 100% and 80% of the patients fulfilled Amsterdam II criteria; in group C and D, 57% and 52% had only familial aggregation for Lynch syndrome-related and unrelated cancers. Within elderly CRC population we observed that in group A and B, 67% and 100% of tumours were located in the right colon whereas in group C and D, 75% and 59% were in the left colon and rectum, respectively. Mlh1 expression were absent in 83% and 50% of cases in group A and B. Taking into account the comparison of each correlative group between both populations, no significant differences were found for groups A and B. For group C, 57% of early-onset CRC were right colon tumours compared with 75% of the elderly CRC (rectum). 100% of polyps within early-onset CRC were mixed vs 62.5% of adenomatous in the elderly. 43% of early-onset CRC had familial aggregation while all of the elderly were sporadic. For group D, 52% of young CRC were located in the left colon compared with 41% of right in the elderly. 46% of early-onset CRC showed familial aggregation whereas 83.6% of sporadic in the elderly. 51.6% and 32.3% of early-onset CRC had familial history for Lynch syndrome-related and unrelated cancers, respectively, compared with 32.3% and 10% of the elderly. Conclusion We identified two differential groups within early-onset CRC, with MSS, depending on the CIMP subtype, showing group C mainly anatomo-clinical differences, and group D familiar differences.

P-0235 Comparative Analysis of CpG Island Methylator Phenotype Between Different Groups of Colorectal Cancer According to the age of Onset

ABSTRACT Introduction Colorectal Cancer (CRC) should no longer be considered one disease but rather a family of diseases, which is caused by genetic/epigenetic substrate. It is known that there are three main different carcinogenetic pathways for CRC. Extensive gene promoter methylation in CRC has been termed “CpG island methylator phenotype” (CIMP). This carcinogenetic pathway, also known as the “Methylator” phenotype, is the most recently identified and has a distinct clinical, pathologic, and molecular profile. The aim of our study was to characterize the clinical, pathological and familial features of CIMP-positive colorectal carcinomas within two different groups of onset, and consecutively identify possible differential features between both groups: early-onset and elderly CRC. Methods The methylation status of the promoter regions of the CIMP panel genes was carried out: CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1. CIMP-high was defined as the presence of ≥6/8 methylated promoters, CIMP-low as 1/8 to 5/8 methylated promoters and CIMP-0 as total absence (0/8) of methylated promoters. Statistical analyses were performed. We characterized the clinical, pathological and familial features of each group within each category of age, and compared each CIMP category between both groups of age. Only statistical significance differences are showed. Results Within early-onset CRC, 20% showed CIMP-High, 29% CIMP-low and 51% CIMP-0. Main differential features from CIMP-High tumours were: a higher proportion of tumours located at the right colon (67%), higher rate of low-grade of differentiation and mucinous tumours (29% and 57%, respectively), and a larger proportion of mixed polyps (adenomatous and hyperplastic) during follow-up (83%). Within elderly CRC, 24% showed CIMP-High, 26% CIMP-low, and 50% CIMP-0. Main features featuring CIMP-High tumours were: More female (67%), more tumours located at rectum (50%) and right colon (33%), more Microsatellite Instability (MSI) tumours (33%), with an absent of expression of Mlh1 (56%), and a higher proportion of BRAF mutations (28%). We compared each group of CIMP between both population groups (early-onset and elderly CRC). Comparing CIMP-High groups, early-onset against elderly, the first one showed more mucinous tumours (57%); more hiperplastic polyps (83% vs 29%); and more important familial component. For CIMP-low groups, early-onset showed more left-colon tumours (54% vs 16%); less proportion than within the elderly group of Multiple primary neoplasm and Synchronous or metachronous CRC; and finally there is a more important proportion of familial component. Finally, for CIMP-0 groups, early-onset CRC showed differential features: less right-colon tumours (9% vs 40%), they were earlier diagnosed, and with a higher familial component. Conclusion CIMP-High early-onset CRC showed different clinicopathological and familial features, compared with CIMP-High within elderly CRC. Methylation MLH1 and BRAF mutations are predominant in elderly CRC (sporadic cases with MSI). Whilst, some features of CIMP-High early onset overlap with Lynch syndrome characteristics. When we compared both populations, there are enough differences to suggest a different molecular basis in the development of the different groups of CIMP within early-onset CRC, compared with elderly CRC. This work was funded by the Spanish Fondo de Investigaciones Sanitarias (grant number FIS-PI10/0683).

A Case of Mixed Hyperplastic-adenomatous Rectal Polyp with Composition of Invasive Adenocarcinoma

Departments of Internal Medicine and Pathology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 Epithelial colon polyps are largely divided into hyperplastic and adenomatous polyps. Adenomatous polyps are premalignant lesions, whereas hyperplastic polyps are regarded as benign lesions. However, this histological classification has been blurred, as cases of malignant changes in hyperplastic polyposis, mixed hyperplastic adenomatous polyps (MHAPs), and serrated adenomas in the colon have been reported. Rare cases of MHAP have been reported, and are mainly found at the proximal colon with a relatively large size. MHAPs seem to be an intermediate stage of the hyperplastic polyp-adenoma sequence or a collision tumor. Here, we report on a case of a single polyp in the rectum diagnosed with a MHAP combined with an invasive adenocarcinoma. (Intest Res 2012;10:295-299) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Externalization of Saw-Tooth Architecture in Small Serrated Polyps Implies the Presence of Methylation of IGFBP7

Serrated polyps have been considered to be precursors of colorectal cancer with microsatellite instability. However, the biological and/or morphological changes which occur during the course of serrated polyp to cancer remain to be elucidated. Twenty-eight colorectal serrated polyps including five mixed polyps (MP) from 20 patients were observed by chromoendoscopy with magnification, and subsequently resected endoscopically. The presence of mutations in two genes (K-ras and BRAF) and the methylation status of six genes (MLH1-A, MLH1-C, ESR1, P16, SOCS1, and IGFBP7) were examined. The 28 polyps included 32 histological serrated lesions (22 sessile serrated adenomas [SSA], six hyperplastic polyps [HP], and four traditional serrated adenoma [TSA]-like lesions). BRAF mutation was frequently observed in SSAs (19/22), while K-ras mutation was dominant in HPs (5/6). The externalization of saw-tooth architecture in serrated polyps was endoscopically observed more frequently in those with high levels of IGFBP7 methylation (P=0.03). Moreover, the endoscopic finding was observed in five of six small serrated lesions (<10mm) which contained both BRAF mutation and high levels of IGFBP7 methylation. TSA-like lesions in small MPs demonstrated the endoscopic finding with no or little MLH1 methylation, while the counterparts in the mixed polyps had high levels of MLH1 methylation with relatively low levels of IGFBP7 methylation. Our data suggests two distinct pathways may be involved in the early stages of the serrated pathway: one where MLH1 is primarily methylated, and a second where methylated IGFBP7 is associated with an externalization of saw-tooth architecture.

Eradication of Gastric Polyposis after Withdrawal of PPI Therapy

Purpose: Long term proton pump inhibitor (PPI) use is associated with up to four fold increase risk of Fundic Gland Polyps (FGP); the risk of malignant transformation is negligible. These polyps develop because of parietal cell hyperplasia resulting from acid suppression and consist of microcysts composed of chief and parietal cells. Clinically FGP are usually silent. We report a case of massive gastric polyposis associated with iron deficiency anemia that resolved with cessation of PPI therapy. A 54 years old female with reflux symptoms and esophagitis, documented by endoscopy, was treated with PPI (lansoprazole 30 mg twice daily) for over 10 years. She presented two years ago with iron deficiency anemia. Outside endoscopy showed diffuse proximal gastric polyposis. Biopsies demonstrated FGP. Colonoscopy was negative except for 8 mm mixed hyperplastic adenomatous polyp. Because of increasing size of the gastric polyps and anemia she was referred for further management. On referral, Hemoglobin and Hematocrit were 11.0 and 32, respectively, associated with iron deficiency anemia (ferritin level of 6) treated with intravenous iron therapy. Family history was negative for Familial Adenomatous Polyps. Her father died of lung cancer; her mother has had bilateral mastectomy for breast cancer. Her mother's siblings had a history of colon, breast, prostate and lung cancer. She has 2 children alive and well. Repeat upper Endoscopy showed massive polyposis of the proximal stomach; too numerous to count (see Figure 1). There was no duodenal, specifically, peri-ampullary lesions. Several of the larger polyps were removed. Histology showed fundic gland polyps with dilated foveolae. No Helicobacter pylori organisms were seen. It was recommended for the patient to discontinue PPI therapy. Reflux symptoms were treated with sucralfate. Follow up endoscopy 24 months later showed resolution of gastric polyposis; Iron deficiency anemia has resolved Hemoglobin and Hematocrit were 14 and 42. She has not required any iron therapy since. To our knowledge, this is the first documented case of eradication of massive gastric polyposis associated with iron deficiency anemia that resolved with cessation of PPI therapy. FGP attributable to PPI therapy can presents with iron deficiency anemia.Figure 1: No Caption available.

Clinicopathological and Molecular Features of Colorectal Serrated Neoplasias With Different Mucosal Crypt Patterns

Endoscopic examination shows that serrated neoplasias (SNs), such as serrated adenomas and sessile serrated adenomas, exhibit different mucosal crypt patterns. However, it remains unclear whether advanced serrated polyps with different mucosal crypt patterns have different clinicopathological or molecular features. We classified the mucosal crypt patterns of 86 SNs into three types (hyperplastic, adenomatous, and mixed pattern) and evaluated their clinicopathological and molecular features. We found significant differences in the proliferative activity status between SNs with mixed/adenomatous patterns and those with the hyperplastic patterns. SNs with the hyperplastic pattern were frequently located in the proximal colon and had a macroscopically superficial appearance, whereas SNs with the adenomatous pattern were often located in the distal colon and had a protruding appearance. Furthermore, a significant difference was observed in the frequency of the CpG island methylator phenotype (CIMP), involving the methylation of two or more CIMP-related genes (MINT1, MINT2, MINT31, p16, and MLH1), between SNs with the hyperplastic pattern and those with the mixed/adenomatous patterns (18/32 (56%) vs. 8/28 (29%) or 7/26 (27%); P=0.0309 or P=0.0249, respectively). Moreover, the prevalence of KRAS mutations was significantly higher in SNs with the adenomatous pattern than in those with the hyperplastic pattern (7/26 (27%) vs. 1/32 (3%); P=0.0173). In comparison with other patterns, the mixed pattern was detected more frequently in mixed serrated polyps (MSPs), which contain separate histological components. Some MSPs exhibited concordant molecular alterations among the different histological components. The clinicopathological and molecular features of SNs correlated strongly with their mucosal crypt patterns, which were observed using chromoendoscopy.

Serrated polyps of the colon

Until recently, colonic polyps were traditionally classified as either hyperplastic or adenomatous, and only the latter were believed to have the potential to progress to carcinoma. However, it is now appreciated that a subset of serrated polyps also appear to have malignant potential. Serrated polyps are a heterogeneous group of colon polyps that include hyperplastic polyps, sessile serrated adenomas (SSAs), traditional serrated adenomas, and mixed polyps. Insights into these polyps were derived, in part, from studies of patients with the hyperplastic polyposis syndrome. SSAs show a predilection for the right colon, have a distinct histology, and their molecular genetic profile has recently been linked to a pathway for colon tumorigenesis that is characterized by microsatellite instability. Based upon available evidence, it is recommended that patients with serrated adenomas undergo colonoscopic follow-up at the same frequency as for conventional adenomas. It is important that physicians are aware of serrated polyps, particularly serrated adenomas and their relationship to colon cancer, and their proper clinical management.

A Significant Number of Sessile Serrated Adenomas Might Not Be Accurately Diagnosed in Daily Practice

The diagnosis of hyperplastic polyps (HPs) may involve a conglomeration of subgroups of serrated polyps. The diagnosis of HPs may therefore be revisited if this is sessile serrated adenoma (SSA). The aim of this study was to determine clinically and endoscopically relevant information associated with reclassification to SSA. After reviewing the data from 1,372 patients who underwent colonoscopic polypectomy, 49 HPs larger than 10 mm were analyzed in this study. Two gastrointestinal pathologists reclassified each of the original 49 HPs as conventional HPs, SSAs, and others. Among the 49 initially diagnosed HPs, 18.4% were reclassified into SSAs or mixed polyps. Overall architectural features were useful for the diagnosis of SSA, but cytological features were less useful. The patient and polyp characteristics did not differ between HPs with and without reclassification of the initial pathological diagnosis. A significant number of SSAs might not be accurately diagnosed in daily clinical practice without any predilection for size, shape, and location. Therefore, when large HPs are diagnosed in clinical practice, it is necessary for physicians to have greater awareness of the diagnosis of SSA and to individualize subsequent surveillance.

Benign Serrated Colorectal Fibroblastic Polyps/Intramucosal Perineuriomas Are True Mixed Epithelial-stromal Polyps (Hybrid Hyperplastic Polyp/Mucosal Perineurioma) With Frequent BRAF Mutations

Colorectal fibroblastic polyp and intramucosal perineurioma are 2 synonyms for a recently described benign mucosal lesion with a predilection for the rectosigmoid colon. These lesions are characterized by aggregates of bland spindled cells separating and distorting mucosal crypts. The latter frequently showed a serrated architecture. The pathogenesis of fibroblastic polyp/intramucosal perineurioma and the nature of serrated crypts observed in them are poorly understood. We analyzed the clinicopathological features of 29 fibroblastic polyps and investigated them for the first time for mutations known to be involved in serrated colorectal epithelial polyps (BRAF, KRAS, and PIK3CA). Patients were 23 women and 6 men with a mean age of 64 years (range: 47 to 84 y). All lesions represented asymptomatic solitary polyps (mean size 3.5 mm) localized predominantly in the rectosigmoid colon (81%). Hyperplastic polyps, classical adenoma, and sessile serrated adenoma/lesion coexisted in 12 (44%), 12 (44%), and 5 (17%) patients, respectively. All lesions showed irregular aggregates of bland spindled cells separating and distorting mucosal crypts. Serrated (hyperplastic) crypts were observed on the top or contiguous with the lesion in all cases. Immunohistochemistry revealed expression of at least one perineurial cell marker (epithelial membrane antigen, claudin-1, and glucose transporter-1) in 26 out of 27 lesions (96%), but expression of CD34 was less common (8 of 27; 30%). Immunostaining for hMLH1 showed a normal nuclear expression. Molecular analysis in 22 cases showed V600E BRAF mutation in 14 cases (63%) and KRAS mutation in 1 (4%). The remainder were wild-type for all 3 genes. Our results indicate that serrated fibroblastic polyps/intramucosal perineuriomas represent a unique type of mixed epithelial-stromal polyps (hybrid hyperplastic polyp/mucosal perineurioma). The perineurial stromal component might be derived from modified pericryptic fibroblasts as a consequence of a yet poorly understood epithelial-stromal interaction.

Polipose hiperplásica: relato de caso

A polipose hiperplásica é uma condição rara, caracterizada pela presença de pólipos hiperplásicos múltiplos no cólon. Relata-se o caso de um paciente de 29 anos que apresentou polipose hiperplásica associada a pólipos mistos.

The Presence of Large Serrated Polyps Increases Risk for Colorectal Cancer

There is evidence that serrated polyps (serrated adenomas and hyperplastic polyps) have different malignant potential than traditional adenomas. We used a colonoscopy database to determine the association between the presence of serrated colorectal polyps and colorectal neoplasia. We performed a multicenter observational study of 10,199 subjects who underwent first-time colonoscopies. Data collected on study subjects included age and sex and the location, size, and histology of polyps or tumors found at colonoscopy. Serrated polyps were defined as those diagnosed by the pathologists in the participating hospitals as a serrated lesion (a lesion given the term of "classical hyperplastic polyp," "traditional serrated adenoma," "sessile serrated adenoma," or "mixed serrated polyp"). Large serrated polyps (LSPs) were defined as those ≥ 10 mm. There were 1573 patients (15.4%) with advanced neoplasia, 708 patients (6.9%) with colorectal cancer (CRC), and 140 patients (1.4%) with LSPs in our cohort. Multivariate analysis associated the presence of LSPs with advanced neoplasia (odds ratio [OR], 4.01; 95% confidence interval [CI], 2.83-5.69) and CRC (OR, 3.34; 95% CI, 2.16-5.03). The presence of LSPs was the greatest risk factor for CRC, particularly for proximal CRC (OR, 4.79; 95% CI, 2.54-8.42). Proximal and protruded LSPs were the highest risk factors for proximal CRC (OR, 5.36; 95% CI, 2.40-10.8 and OR, 9.00; 95% CI, 2.75-19.2, respectively). The presence of LSPs is a risk factor for CRC, particularly CRC of the proximal colon.

Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)—proposal for diagnostic criteria

Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas-because of their cytological atypia-were recognized as the precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression mainly because hyperplastic polyps are missing cytological atypia. Meanwhile, it is recognized that the lesions, formerly classified as hyperplastic, represent a heterogeneous group of polyps with characteristic serrated morphology some of which exhibit a significant risk of neoplastic progression. These serrated lesions show characteristic epigenetic alterations not commonly seen in colorectal adenomas and progress to colorectal carcinoma via the so-called serrated pathway (CpG-island-methylation-phenotype pathway). This group of polyps is comprised not only of hyperplastic polyps, but also of sessile serrated adenomas, traditional serrated adenomas and mixed polyps, showing serrated and "classical" adenomatous features. Diagnostic criteria and nomenclature for these lesions are not uniform and, therefore, somewhat confusing. In a consensus conference of the Working Group of Gastroenterological Pathology of the German Society of Pathology, standardization of nomenclature and diagnostic criteria as well as recommendations for clinical management of these serrated polyps were formulated and are presented herein.

Frequent Gastrointestinal Polyps and Colorectal Adenocarcinomas in a Prospective Series of PTEN Mutation Carriers

Germline phosphatase and tensin homolog (PTEN) mutations cause Cowden syndrome (CS), associated with breast and thyroid cancers. Case reports found 35%-85% of CS patients had gastrointestinal (GI) hamartomas. The association of benign and malignant GI neoplasias with CS remains debatable. Our goal is to describe the GI phenotype in a prospective series of PTEN mutation carriers. Patients who met relaxed International Cowden Consortium criteria (N = 2548) or with 5 or more GI polyps, 1 or more of which was hyperplastic or hamartomatous (N = 397), were prospectively recruited. Germline PTEN mutation/deletion analysis was performed. Of the 2945 patients, 127 (123 of 2548 and 4 of 397, respectively) patients having clear pathogenic PTEN mutations were eligible for this study. Esophagogastroduodenoscopy, colonoscopy, and pathology reports were reviewed. The Fisher 2-tailed exact test, unpaired t tests, and age- and sex-adjusted standardized incidence ratio were calculated. Of 127 PTEN mutation carriers, 69 underwent 1 or more endoscopies with 64 (93%) having polyps. Of the 64, half had hyperplastic polyps. There were one to innumerable polyps in the colorectum, ileum, duodenum, stomach, and/or esophagus, with 24 subjects having both upper and lower GI polyps. Nine (13%) subjects had colorectal cancer, all younger than the age of 50. The adjusted standardized incidence ratio was 224.1 (95% confidence interval, 109.3-411.3; P < .0001). PTEN-associated CS should be considered a mixed polyp syndrome, with hyperplastic polyps most prevalent, with a risk of early onset colorectal cancer. Routine colonoscopy should be considered in PTEN-associated CS, especially in the context of hyperplastic and/or adenomatous polyps.