Intramucosal fat is uncommon in large bowel polyps but raises three differential diagnoses.

AIMS: This case series intends to expand currently limited knowledge regarding the existence and diagnostic significance of intramucosal fat in colorectal polyps. METHODS: Clinicopathological features of nine such polyps were reported following histopathological review, including S100 and EMA immunohistochemistry. RESULTS AND CONCLUSIONS: Such review subdivided seven polyps into three groups: (1) mucosal perineurioma/serrated polyps with fat among the perineurial stroma (three cases); (2) submucosal lipomas with adipose tissue extending into the overlying mucosa (two cases) and (3) polyps with intramucosal adipose tissue only, that is, the newly described but less-recognised entity known as intramucosal lipoma (two cases). The two remaining polyps of this series did not include submucosa but, from assessing their muscularis mucosae, were favoured to represent intramucosal lipomas. The first two phenomena are formally described for the first time by this case series. The last of these three diagnoses should prompt investigations for Cowden syndrome, but intramucosal lipomas are more often sporadic/non-syndromic.

Rectal gastrointestinal stromal tumor as an incidental finding in a patient with rectal polyps.

A patient who was diagnosed as rectal polyps in the local hospital went to our hospital for surgical treatment. Abdominal CT demonstrated a large irregular extra-luminal tumor of at least 5 cm cross-section on the ventral side of the lower rectal wall. Intraoperatively, a large irregular extra-luminal tumor (about 5×4.5×4 cm) was found. Anterior resection with end colostomy and rectal stump (Hartmann's procedure) was performed. Postoperative histological examination showed simultaneous development of rectal GIST and polyps.

Elastofibromatous change of the intestine: report of four lesions from three patients with review of the literature.

Elastofibromatous change, also referred to as elastofibromatous polyp or elastofibroma, has been extremely rarely described in the gastrointestinal tract. This lesion is characterized histopathologically by an excessive accumulation of elastic fibers occasionally with a fibrous component involving the submucosa and/or muscularis mucosae of the gastrointestinal tract. Herein, we report four additional lesions of the intestine and review the clinicopathological features of this rare lesion. Three patients (76-, 72-, and 52-year-old males) were detected with polypoid lesions in the jejunum, transverse and sigmoid colons, and sigmoid colon, respectively. All four lesions showed fundamentally the same histopathological and immunohistochemical features. The polypoid lesions were covered by non-neoplastic epithelium, and degenerated and truncated elastic fibers occasionally with a fibrous component had accumulated in the submucosa and/or muscularis mucosae. The characteristic feature was the elastofibromatous change centered around collections of elastotic submucosal vessels. Desmin-positive degenerative ruptured smooth muscle fibers were scattered within the elastic fibers in the submucosa. Our analyses of the clinicopathological features of the previously reported 32 cases of elastofibromatous change of the gastrointestinal tract as well as the present cases demonstrated that this type of lesion is most commonly found in the colon or rectum (29 cases), males, and middle-aged to elderly persons. Although the pathogenesis remains unclear, the convincing hypothesis that this lesion represents elastic degeneration of submucosal vessels by previous persistent vascular injury has been proposed. The collections of degenerative elastotic vascular walls may have an important role in the development of this lesion.

Duodenal mucosal damage is associated with proliferative activity of Brunner's gland hamartoma: a case report.

BACKGROUND: Brunner's gland hamartoma is a rare tumor, predominantly found in the fifth to sixth decades of life. Generally, it is a single pedunculated polyp, rarely larger than 5 cm. Asymptomatic cases are found incidentally, but cases with a large polyp tend to have gastrointestinal bleeding and/or obstructive symptoms. Polyp size increases in a time-dependent manner, however, the growth mechanism is unknown. We report a Japanese male case in his mid-twenties with an over 6 cm sized polyp. CASE PRESENTATION: A 26-year-old man presented black stools and anemia. Endoscopic examination revealed a large pedunculated polyp at gastroduodenal junction. The polyp, subsequently resected by distal gastrectomy, was lobulated with random surface erosions and sized 6.4 × 3 cm. Histological examination revealed that the polyp arose from duodenal mucosa and was composed of hyperplastic Brunner's glands in lobules separated by fibromuscular septa, associated with lymphocytic infiltrate and lymphoid follicles. No evidence of malignancy was found. Thus, the lesion was diagnosed as Brunner's gland hamartoma. Further immunohistochemical studies indicated that gastric foveolar metaplasia is associated with surface epithelium covering upper two thirds of the polyp, showing immunohistochemical positivity for mucin 5 AC (MUC5AC). Below the metaplastic surface epithelium, Brunner's glands had high proliferative activity (MIB-1 labeling index: 7.9%). The similar staining pattern was observed at surface erosive sites (MIB-1 labeling index in Brunner's glands: 9%). On the other hand, surface epithelium in the lower side of the polyp still preserved intestinal nature, containing CDX2-positive nuclei and MUC2-positive goblet cells. Brunner's glands below the surface epithelium with intestinal characteristics showed low proliferative activity (MIB-1 labeling index: 0.77%). CONCLUSION: Proliferative activity of Brunner's glands was high at the sites with surface erosion and also below the epithelium showing gastric foveolar metaplasia. As gastric foveolar metaplasia occurs along with a mucosal repair process in the duodenum, mucosal damages underlay the hamartomatous proliferation of Brunner's glands and eventually resulted in a formation of large polypoid mass in this case.

Malignant paraganglioma of the rectum: the first case report and a review of the literature.

Paragangliomas typically develop in the extra-adrenal sites along the sympathetic and/or the parasympathetic chain. Occasionally, the tumors may arise in some exotic sites, including the head and neck region and the urogenital tract. Paraganglioma presenting as a primary rectal neoplasm has not been well described in the literature. Here, we report the first case of malignant paraganglioma arising in the rectum of a 37-year-old male. He presented to the clinic because of hematochezia with tenesmus. The anorectal digital examination and colonoscopic examination revealed a polypoid mass of the rectum, measuring approximately 4 cm in diameter. The overall morphology and immunophenotype were consistent with a typical paraganglioma. However, the tumor exhibited features suggestive of malignant potential, including local extension into adjacent adipose tissue, nuclear pleomorphism, confluent tumor necrosis, vascular invasion and metastases to regional lymph nodes. In conclusion, we present the first case of rectal malignant paraganglioma. Due to the unexpected occurrence in this region, malignant paraganglioma may be misdiagnosed as other tumors with overlapping features; in particular, a neuroendocrine tumor of epithelial origin. Because of the differences in treatment, separating paraganglioma from its mimics is imperative. Combination of morphology with judicious immunohistochemical study is helpful in obtaining the correct diagnosis.

Muco-submucosal elongated polyps of the gastrointestinal tract: a case series and a review of the literature.

We present three cases of gastrointestinal muco-submucosal elongated polyps, two located in the duodenum and one in the descending colon. All three cases had a characteristic, "worm-like" endoscopic appearance and were lined by unremarkable mucosa. The vascular component was located in the submucosa and was composed of a mixture of variably dilated blood vessels (capillaries and veins) and lymphatics. The duodenal polyps displayed lipomatous metaplasia of the submucosal stroma. The dual vascular phenotype of the vascular component was confirmed by immunohistochemistry with D2-40 and CD31.

Primary perivascular epithelioid cell tumor in the rectum: a case report and review of the literature.

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions.

Composite intestinal adenoma-microcarcinoid clues to diagnosing an under-recognised mimic of invasive adenocarcinoma.

AIMS: Microcarcinoids refer to microscopic nests of monotonous cells with endocrine and squamoid features. Their peculiar morphology can appear infiltrative with a desmoplastic-like background, raising concerns for an infiltrating adenocarcinoma. To further characterise microcarcinoids, we undertook a prospective clinicopathological study. METHODS: 11 specimens originating from five men and six women (average age=58.9 years) were prospectively collected from December 2004 to December 2011. RESULTS: Microcarcinoids were most commonly identified in high-risk adenomas (size ≥10 mm (n=10), villous components (n=8) and/or high-grade dysplasia (n=4)). All polyps had mucosal prolapse and four displayed background fibrosis reminiscent of desmoplasia. The microcarcinoid component was most often multifocal (n=7) within the individual polyp and extended over an average length of 3.9 mm. The individual microcarcinoid cells were cuboidal with abundant eosinophilic cytoplasm. All cases had monotonous nuclei which lacked pleomorphism, hyperchromasia and mitotic activity. All available microcarcinoids were ß-catenin and synaptophysin reactive and non-reactive for chromogranin and p53 with a negligible Ki-67 proliferation index (<2%). In addition, the microcarcinoids were variably reactive for p63 and/or CK 5/6, thereby demonstrating focal squamoid features. Two of the study cases were submitted with a concern for invasive carcinoma. Clinical information was available in 10 patients with up to 24 months of follow-up: all patients are alive and well and no subsequent malignancy has been reported. CONCLUSIONS: Awareness of this unique morphology is important to avoid overdiagnosing microcarcinoids as invasive adenocarcinoma. Moreover, this immunohistochemical panel can be helpful in discriminating microcarcinoids from its malignant mimic in challenging cases.

Ileal Vanek's tumor mimicking cecal carcinoma.

Inflammatory fibroid polyps or Vanek's tumors are rare benign pseudotumoral lesions with morphological characteristics similar to those of submucosal mesenchymal tumors. They have been described in the gastrointestinal tract, most frequently in the gastric antrum. We present a case of ileal Vanek's tumor associated with a raised carcinoembryonic antigen level and with radiological and endoscopic features mimicking cecal carcinoma.

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.

BACKGROUND: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. AIMS: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. METHODS: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. RESULTS: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. CONCLUSION: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

Sessile serrated adenomas of the large bowel. Clinicopathologic and immunohistochemical study including comparison with common hyperplastic polyps and adenomas.

Sessile serrated adenoma (SSA) is a newly characterized type of the large bowel adenoma. It arises in hyperplastic polyp (HP) and represents a precursor lesion of colorectal carcinoma with microsatellite instability. SSAs differ from common HPs by abnormal proliferation of the crypt epithelium and by nuclear atypia. We examined 15 SSAs from 15 patients. The age range was 25-80 years (average 60 years). Six patients were females and 9 were males. For comparison, we examined 10 conventional tubular adenomas and 10 common HPs with vesicular cells. The sites of SSAs were as follows: 8 in rectum, 4 in rectosigmoid colon, 1 in transverse colon, 1 next to mucinous carcinoma of ascending colon, 1 in anastomosis after resection of the transverse colon adenocarcinoma. The diameter of the lesions ranged from 5 to 12 mm. Histologically, SSAs showed asymmetrical proliferation of the epithelium, irregular shape of the crypts with their branching and some crypt dilatations especially in the basal parts of the crypts. Cellular atypia (dysplasia) was usually low. In 5 cases the nuclei were focally stratified and localized in the lower part of the cells. High-grade dysplasia was found only in SSA adjacent to mucinous adenocarcinoma. Immunohistochemically, SSAs showed secretion of gastrointestinal mucin expressing MUC2 and MUC5A. Both MUC2 and MUC5A were also positive in mucinous carcinoma. In previous studies these expressions were considered specific for serrated type of carcinogenesis. However, our study found positivity of MUC2 and MUC5A also in conventional adenomas. Expression of p53 in SSAs was minimal. SSAs have malignant potential comparable with conventional adenomas and for this reason they must be distinguished from HPs.

Adenoma with gastric differentiation (so-called pyloric gland adenoma) in a heterotopic gastric corpus mucosa in the rectum.

In a 46-year-old man, a pedunculated rectal polyp measuring 3.0x3.0x2.0 cm was diagnosed histologically as a pyloric gland-type adenoma arising in heterotopic gastric corpus mucosa. The luminal site was covered by glands of the gastric foveolar type, displaying focal marked proliferation interpreted as low-grade intraepithelial neoplasia. A bidirectional gastric differentiation was found: most lower glandular structures showed positivity for the deep gastric mucin core protein Muc 6 and superficial positivity for gastric foveolar epithelium mucin core protein Muc 5AC. Pyloric gland adenoma has so far been described in one larger series only and a few case reports of the stomach, gallbladder, pancreatic duct and within heterotopic gastric corpus mucosa of the duodenal bulb. The present case report is the first case of a pyloric gland-type adenoma within a gastric corpus heterotopia of the rectal mucosa.

Inflammatory fibroid polyp: an immunohistochemical study.

BACKGROUND: Inflammatory fibroid polyp is a localized lesion, which arises in the submucosa of the gastrointestinal tract, most often in the stomach. Although it is generally believed to represent a reactive, nonneoplastic condition, its histogenesis remains controversial. AIM: To study inflammatory fibroid polyp by immunohistochemistry in an attempt to further clarify their histogenesis. MATERIAL AND METHODS: Nine cases were studied by immunohistochemistry using a panel of antibodies against smooth-muscle actin, vimentin, S-100 protein, factor VIII- R.Ag and macrophage (HAM-56). RESULTS: There was a strong diffuse positive staining pattern in the spindle cells with vimentin antibody. A patchy staining for smooth-muscle actin was observed in these cells. Immunophenotyping revealed a heterogeneous reaction with HAM-56. In edematous areas, HAM-56-positive cells show voluminous cytoplasm and reniform nuclei. In cell-rich areas, the HAM-56-positive cells had fusiform cytoplasm. Stains for S-100 and factor VIII RAg were negative in the proliferating elements. CONCLUSIONS: The present immunohistochemical study refutes the suggested neural or vascular nature of the lesion. The strong positivity for vimentin in all cases suggests a major component of spindle cells best recognizable as fibroblasts. These results would favor the existence of a span of morphological and immunohistochemical patterns possibly indicating evolutive phases of an inflammatory reaction.

Nuclear beta catenin as a potential prognostic and diagnostic marker in patients with colorectal cancer from Hong Kong.

AIMS: To study the expression of nuclear beta catenin in patients with colorectal cancer, colorectal adenoma, and colorectal polyps to elucidate its role in carcinogenesis, and its potential for prognosis and diagnosis. METHODS: The expression of nuclear beta catenin was studied by immunohistochemistry using paraffin wax embedded specimens. Sixty specimens each of colorectal carcinoma, colorectal adenoma, colorectal polyp, and normal colorectal specimens were analysed. The potential for prognosis was assessed by correlating nuclear beta catenin expression in 60 and 75 patients with colorectal cancer with lymph node metastasis and survival, respectively. The diagnostic capacity was explored by comparing nuclear beta catenin expression in 60 patients with colorectal cancer with other cytokeratin 20 (CK20) positive adenocarcinomas, namely: 30 colonic mucinous adenocarcinomas, 30 gastric adenocarcinomas, 27 pancreatic adenocarcinomas, and 12 ovarian mucinous adenocarcinomas. RESULTS: Nuclear beta catenin expression was highly associated with progression of colorectal tissue from normal epithelial tissue, polyps, adenomas, to carcinomas (r = 0.875; p < 0.0001). Nineteen patients with colorectal adenoma who subsequently developed colorectal carcinoma had higher nuclear beta catenin expression than those with colorectal adenomas alone (p < 0.0001). Moreover, those patients with colorectal cancer and high nuclear beta catenin expression had a higher incidence of lymph node metastasis (chi(2) = 16.99; p < 0.005) and shorter overall survival (p < 0.0001). Finally, nuclear beta catenin expression in colorectal adenocarcinomas was significantly higher than in other CK20 positive adenocarcinomas. CONCLUSIONS: Nuclear beta catenin expression is a potential prognostic factor in patients with colorectal cancer, and together with CK20, it could be used to identify colorectal carcinoma in the Hong Kong population.

Vanek's tumor (inflammatory fibroid polyp). Report of 18 cases and comparison with three cases of original Vanek's series.

Eighteen cases of Vanek's tumors are presented. The patients included nine men and nine women between the ages of 45 and 93 years (mean, 66.2 years). Nine cases were clinically diagnosed as polyps of the gastric antrum, five cases as polyps of the stomach (not otherwise specified), one polyp was located in the ileum and the three remaining polyps in the small intestine (not otherwise specified). The thirteen polyps with available size information measured from 0.4 to 5 cm in the greatest diameter (mean, 2.2 cm). Immunohistochemically, the affections were positive for vimentin (18/18) and CD34 (15/18). All the cases negative for CD34 also lacked concentric onion skin-like formations of the spindle cells around glands and vessels. The different immunophenotype and absence of concentric formations could be explained by the existence of two different lesions commonly designated as Vanek's tumor (inflammatory fibroid polyp) or by the hypothesis of various evolutional stages. In the differential diagnosis, it is important to distinguish namely eosinophilic gastroenteritis, gastrointestinal stromal tumor, inflammatory pseudotumor, hemangioendothelioma, and hemangiopericytoma. In contrast to gastrointestinal stromal tumors, genetically no substitution, deletion, or insertion occurred in c-kit exon 11 in all analyzed samples. Likewise, no deletion or insertion in part of c-kit exon 9 was observed.

Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation.

A 70-year-old woman underwent right hemicolectomy and six carcinomas were recognized in the resected colon. These carcinomas were considered to be of a cell lineage common to serrated adenoma (SA) and hyperplastic (metaplastic) polyp (H/MP), because of the occurrence of multiple SAs and H/MPs around the carcinomas, as well as the co-existence of SA and H/MP areas within the carcinomas. These carcinomas had the following common histological and immunohistochemical features: a serrated structure resembling SA; a lace-like structure; infiltrative growth within the muscularis propria, with dedifferentiation at the invasive front; and immunohistochemical expression of pS2 and human gastric mucin. Based on these features, a new subtype of carcinoma is proposed, with a cell lineage common to SA and H/MP. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.

'Serrated' adenoma of the colorectum, with reference to its gastric differentiation and its malignant potential.

Serrated adenoma of the colorectum was a newly proposed entity in 1990, characterized by epithelial neoplasia combining the architectural features of a hyperplastic (metaplastic) polyp with the cytological features of an adenoma. Its histogenesis and natural history still remain unclear. Forty-six serrated adenomas were obtained from 46 patients. The clinicopathological features were summarized. Paraffin-embedded blocks from 34 serrated adenomas were available for immunohistochemical studies using pS2, human gastric mucin, and p53 protein. Eighteen hyperplastic (metaplastic) polyps, 16 tubular adenomas, and 12 early-stage adenocarcinomas were randomly selected as control groups for immunohistochemical analysis. The patients' ages ranged from 32 to 86 (average 61.4) years. Males were more frequently affected than females. Serrated adenomas were predominantly present in the left-side of the colon and in the rectum (72 per cent). Their sizes ranged from 3 to 26 mm (average 9. 2mm). Six lesions (13 per cent) contained foci of high-grade dysplasia. These adenomas were significantly larger (12.7 mm) than those containing no high-grade dysplasia (8.6mm). pS2 and human gastric mucin were expressed significantly more frequently in both hyperplastic (metaplastic) polyps and serrated adenomas than in tubular adenomas or adenocarcinomas. p53-positive cells were present in 18 of the 29 pure serrated adenomas (62 per cent) and in one of the five areas of low-grade dysplasia in serrated adenomas with high-grade dysplasia (20 per cent), most of which revealed a sporadic distribution. Only five of the 29 serated adenomas with no high-grade dysplasia (17 per cent) were regarded as demonstrating p53 overexpression. On the other hand, three of the five areas of high-grade dysplasia in serrated adenomas (60 per cent) revealed diffuse positivity (3+) for p53 protein. The serrated adenoma, which possibly shows gastric differentiation, is considered to be an independent histological entity among the various phenotypes of colorectal adenomas. Serrated adenoma would seem to be a precursor of carcinoma, its potential for malignant transformation being similar to that of the traditional tubular adenoma. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.

Fibroid polyps of intestinal tract are inflammatory-reactive proliferations of CD34-positive perivascular cells.

AIMS: Our aim was to determine the histogenesis of fibroid polyps (FP). These polyps are rare inflammatory-reactive, tumour-like lesions of unknown aetiology, arising in the submucosa or mucosa of the gastrointestinal tract. They are mainly due to a proliferation of characteristic spindle cells. METHODS AND RESULTS: Nine FP were investigated by light microscopy and immunohistochemistry with endothelial markers (Factor VIII, CD34, CD31), a neuronal marker (S100), muscular markers (desmin, alpha-smooth muscle actin) and histiocytic markers (PGMI, KP1, MAC387) using the highly sensitive avidin-biotin-peroxidase technique. We demonstrate, for the first time, a consistent positivity of the characteristic spindle cells of FP for CD34. The proposed endothelial, histiocytic or neuronal origin of FP could be completely ruled out. CONCLUSIONS: Because of the consistent positivity of the spindle cells of FP for CD34 we suggest an origin of these lesions from primitive perivascular or vascular cells. This origin and a probable relationship to gastrointestinal stromal tumours (GIST) is discussed.