Cronkhite-Canada Syndrome Polyps Research Articles

Endoscopic features help to identify the histopathological patterns of colorectal polyps in Cronkhite-Canada syndrome.

Cronkhite-Canada syndrome (CCS) is a rare nonhereditary gastrointestinal hamartomatous polyposis syndrome with a high risk of colorectal cancerogenesis. It is challenging to discriminate adenomas from nonneoplastic colorectal polyps macroscopically. This study aimed to explore the endoscopic features of different histopathological patterns of colorectal polyps in CCS. Sixty-seven lesions from 23 CCS patients were prospectively biopsied or resected during the colonoscopic examinationfor histopathological analysis. The Fisher's exact test and multivariate logistical analysis were conducted to reveal the predictive endoscopic features of CCS polyps with low-grade dysplasia (LGD) and adenomas. There were seven (10.4%) adenomas, 20 (29.9%) CCS-LGD, and 40 (59.7%) nonneoplastic CCS polyps. Polyps were large (>20 mm) in none of the adenomas, 30.0% of CCS-LGD polyps, and 2.5% of nonneoplastic CCS polyps (P < 0.001). The color of the polyps was whitish for 71.4% of adenomas, 10.0% of CCS-LGD polyps, and 15.0% of nonneoplastic CCS polyps (P = 0.004). Pedunculated polyps were detected in 42.9% of adenomas, 45.0% of CCS-LGD polyps, and 5.0% of nonneoplastic CCS polyps (P < 0.001). The proportions of types IV and VI in the Kudo classification were 42.9%, 95.0%, and 35.0% in adenomatous, CCS-LGD, and nonneoplastic CCS polyps, respectively (P = 0.002). The endoscopic activity was in remission for 71.4% of adenomas, 5.0% of CCS-LGD polyps, and 10.0% of nonneoplastic CCS polyps (P < 0.001). Endoscopic features, including the size, color, sessility, Kudo's pit pattern classification of polyps, and endoscopic activity, help identify the histopathological patterns of colorectal polyps in CCS.

Endoscopic and Pathological Characteristics of Cronkhite– Canada Syndrome: A Retrospective Analysis of 76 Cases

Cronkhite-Canada syndrome (CCS) is a disease of unknown etiology characterized by the presence of multiple gastrointestinal polyps, chronic diarrhea, loss of appetite, alopecia, onychodystrophy, and cutaneous hyperpigmentation. CCS is a rare disease with an incidence rate of 1 per million. Clinicians are not aware of this disease, and the discovery of gastrointestinal polyps is often a starting point for the diagnosis of this disease. By analyzing the endoscopic and pathological characteristics of CCS, this study aims to deepen our understanding of gastrointestinal polyposis and facilitate early diagnosis of CCS.We screened databases, including the Chinese Biomedical Literature Database (CBM Web), the China Academic Journals Fulltext Database (CJFD), and PubMed for CCS cases reported from January 2010 to January 2020, and conducted a retrospective analysis of endoscopic and pathological characteristics of these cases.The endoscopic data of the 76 retrieved cases revealed that CCS is gastrointestinal polyposis with the intensive and confluent distribution. The greater the number of polyps and the higher their distribution, the brighter their color. A pathological assessment revealed that both gastric polyps and intestinal polyps are mainly juvenile hamartomatous polyps and have a high malignant transformation rate. Interstitial edema, eosinophil infiltration, and cystic dilation of glands are common features of CCS polyps, distinguishing them from other gastrointestinal polyposis syndromes.CCS is a polyp disease different from other gastrointestinal polyposis. Analysis of its endoscopic and pathological characteristics can contribute to the understanding and early diagnosis of the disease.

Endoscopic features and clinical correlation analysis of 24 patients with Cronkhite-Canada syndrome

Objective: To clarify the endoscopic changes prior to corticosteroid therapy in Cronkhite-Canada syndrome (CCS) patients and to explore the correlation between endoscopic features and clinical characteristics. Methods: A total of 24 CCS patients who were hospitalized in Peking Union Medical College Hospital from January 1999 to June 2019 and underwent gastroscopy and colonoscopy before corticosteroid therapy were retrospectively enrolled. The endoscopic images were re-interpreted. The demographic characteristics, clinical manifestations, laboratory tests and histopathological data were collected and analyzed. Results: Of all 24 patients, 15 (62.5%) were male and 9(37.5%) were female, with an average age of (59±10) years and disease course of 6 (1~36) months. Based on the endoscopic findings, the percentages of stomach, colon, duodenum, rectum and terminal ileum involvement were 100%, 100%, 95.7%, 66.7% and 50.0% respectively. Gastric involvement was more severe in the lower part of the body and the antrum of the stomach, while the cardia and the fundus were spared in 5 (20.8%) cases. Colonic involvement was more severe in the right colon. No patient showed remarkable esophageal involvement. The typical appearance under endoscopy were diffuse mucosal hyperemia and edema with polyps or nodular changes. The lesions may have mulberry-like or imbricate changes in severe cases. Lymphatic dilation in the duodenum was found in 47.8% patients. Most of the polyps were pedunculated or sub-pedunculated, with occasionally seen sessile polyps in the colon. The pit patterns of the 12 resected colon polyps in 11 patients could be classified as Kudo type Ⅲ(S), Ⅲ(L), Ⅳ and Ⅴ(I), among which 2 tubular adenomas had the Kudo type Ⅲ(L). Other resected polyps were hyperplastic polyps or CCS polyps. The disease duration prior to diagnosis was positively correlated with the maximum diameter of colon polyps (r=0.625, P=0.006). Serum albumin levels in patients with whole stomach involvement were significantly lower than those in patients with cardia spared [(29±8) g/L vs (37±5) g/L, P=0.034]. Conclusions: The typical initial endoscopic finding of CCS is multiple polyps or nodular changes on the background of diffuse hyperemia and edema lining the gastric, duodenal and colonic mucosa. Lymphatic dilatation in the duodenum could also be found. Some endoscopic features are correlated to clinical characteristics.

Clinicopathologic features of Cronkhite-Canada syndrome and the significance of IgG4-positive plasma cells infiltration

Objective: To analyze the clinical and pathological features of Cronkhite-Canada syndrome (CCS), and to investigate the significance of IgG4 positive plasma cell infiltration. Methods: Clinical presentations, endoscopic appearances and morphological features of 18 patients diagnosed with CCS at Peking Union Medical College Hospital during 2000-2016 were included in the study.There were 11 male and 7 female patients. IgG4 and IgG immunohistochemical stains were performed in total of 55 biopsies from the patients (36 polyps, 10 adenoma and 9 surrounding mucosa) and a control group of 58 cases (19 colonic mucosa, 7 colonic hyperplastic polyps, 9 inflammatory bowel disease and 23 adenoma). Results: Average age of CCS was 59 years (range 47-69 years) and the male to female ratio was 11∶7. All patients had at least one ectoderm lesion. Fourteen cases had testicular abnormalities. Digestive tract symptoms were encountered in most cases. Four patients had a history of connective tissue disease. Endoscopically, multiple polyps were found to involve entire gastrointestinal tract except the esophagus. Morphologically, CCS polyps were characterized by prominent mucosal edema, mild to moderate inflammation, glands hyperplasia and cystic dilatation. Ten cases had colonic adenoma and one case had rectal adenocarcinoma. While none of the cases reached the diagnostic criteria of IgG4 disease, the positive rate of IgG4 positive plasma cells in adenoma of CCS was significantly higher than that in polyps and surrounding mucosa of CCS (60.0%∶13.9%∶0, P<0.01). The positive rate of IgG4 positive plasma cells of adenoma and polyp of CCS had an increased tendency compared to that of adenoma and polyp of control group (60.0%∶34.8%; 13.9%∶0). Conclusion: The findings in the study do not support that CCS is a variant of IgG4 disease, although IgG4 positive plasma cells may be involved in the pathogenesis of CCS, which may be explored in future investigations.

Cronkhite-Canada syndrome complicated with multiple gastric cancers and multiple colon adenomas.

Background:We experienced a case in which Cronkhite-Canada Syndrome presented with complications of multiple gastric cancers and multiple colon adenomas.Case Report:Our case is a 64-year-old male who visited a nearby hospital with diarrhea and weight loss. The patient was anemic and hypoproteinemic, with multiple polyps in the stomach, duodenum, and large intestine. He also presented with alopecia, onychatrophia, cutaneous pigmentation, and dysgeusia, and was diagnosed with Cronkhite-Canada Syndrome. Follow-up examinations found multiple gastric cancers and colon adenomas. We performed a total gastrectomy and a polypectomy of the large intestine lesions, revealing 4 well-differentiated adenocarcinomas in the resected stomach, and tubular adenomas in the large intestine lesions. Intraoperative findings included scattered melanoid pigmentation on the mesentery and the small intestinal wall. Tumor cells were positive for p53 and Ki67 and partially positive for MUC5AC and MUC2. Cronkhite-Canada Syndrome polyps are generally classified as juvenile type polyps, and these polyps rarely become cancerous. However, of the 383 cases of Cronkhite-Canada Syndrome reported in Japan, complications of gastric cancer were found in 39 cases (10.2%), and only 8 cases with multiple gastric cancer were reported in Japan. including the cases we have personally experienced. There were only two English literatures on Cronkhite-Canada Syndrome complicated with gastric cancer. So it is necessary to notify this information of Cronkhite-Canada Syndrome to the world.Conclusions:Close gastrointestinal examination and strict follow-up are believed to be essential for Cronkhite-Canada Syndrome patients.

ENDOSCOPICALLY TREATED CRONKHITE-CANADA SYNDROME ASSOCIATED WITH MINUTE INTRAMUCOSAL GASTRIC CANCER: AN ANALYSIS OF MOLECULAR PATHOLOGY

There have been no reports of Cronkhite-Canada syndrome (CCS) associated gastric cancer resected with endoscopy because it is very difficult to identify small cancers that are candidates for endoscopic resection. We report a case of CCS with gastric cancer treated with endoscopic submucosal dissection, and we evaluate the molecular pathological analysis of malignant transformation in patients with CCS. A 74-year-old man had an advanced rectal cancer and gastrointestinal polyposis after presenting with hypoproteinemia, partial hair loss and atrophic nails as well as hyperpigmentation on the hands. He was diagnosed as having CCS. On upper endoscopy, a 7 mm discolored polyp with an irregular microvascular pattern revealed by magnified narrow-band imaging (NBI) was identified in gastric diffuse CCS polyposis. This lesion was treated with endoscopic submucosal dissection and diagnosed as a flat, elevated-type, mucosal well-differentiated tubular adenocarcinoma without lymphatic or venous infiltration, and with tumor-free margins. Microsatellite instability was detected in both the cancer and the surrounding CCS polyps. Mucin-histochemical analysis of the cancer area showed the complete intestinal type, and thus may have differentiated the CCS polyps from that of the common gastric hyperplastic polyps. This case illustrates that a clue to detecting small cancers may be to look for the discolored lesion among reddish CCS polyposis and thereafter to observe the irregular vascular pattern with NBI endoscopy. From the viewpoint of genetic alterations, patients with CCS polyps are considered to be at high risk for developing gastric cancer, and therefore careful follow-up examinations are necessary for the early detection of malignancies.

Clinicopathologic Features and Treatment Outcomes in Cronkhite–Canada Syndrome: Support for Autoimmunity

Cronkhite-Canada syndrome (CCS) is a noninherited condition, associated with high morbidity, and characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. All features may respond to immunosuppressive therapy, but little is known about the etiology. An autoimmune origin has been suggested but not proved. From a retrospectively selected cohort, we evaluated clinicopathologic features, including immunostaining for IgG4 (an antibody associated with autoimmunity), and therapeutic outcomes in a cohort of CCS patients to provide further insights into this disease. Cases included 14 consecutive CCS patients seen at the Mayo Clinic on whom tissue and follow-up were available. All histology was reviewed by an expert gastrointestinal pathologist. Immunostaining for IgG4 was performed on 42 polyps from CCS cases and on control tissues, including 46 histologically similar hamartomas [from juvenile polyposis syndrome (JPS)] and 20 normal mucosae (six stomach, three small bowel, and 11 colon). Clinical features and treatment outcomes were descriptive. All CCS cases had both upper and lower gastrointestinal polyps; most had typical dermatologic features of alopecia, hyperpigmentation, and onychodystrophy; and most had evidence of protein-losing enteropathy. Ten patients (71%) had adenomatous polyps and 2 (14%) had colorectal cancer. IgG4 immunostaining was positive (>5 cells/HPF) in 52% of CCS polyps compared to 12% of JPS polyps (P = 0.001); IgG4 staining was negative in all other control tissues. Of 11 CCS patients treated with oral corticosteroids, 91% achieved remission. Relapse was common with steroid tapering. Five patients who initially responded to corticosteroids were maintained in remission on azathioprine (2 mg/kg/day) with no relapse after a median of 4.5 years. Immunostaining for the autoimmune-related IgG4 antibody is significantly increased in CCS polyps compared to disease and normal control tissues. Furthermore, immunosuppression by corticosteroids or long-term azathioprine may eradicate or lessen manifestations of CCS. These histologic findings and treatment responses are consistent with an autoimmune mechanism underlying CCS.

Cecal Intussusception in an Adult with Cronkhite-Canada Syndrome Relieved by Colonoscopy

Cronkhite-Canada syndrome (CCS) is a rare, noninherited gastrointestinal polyposis syndrome associated with characteristic ectodermal abnormalities. Here, we report a case of Cronkhite-Canada syndrome with cecal intussusception relieved by colonoscopy. A 52-year-old man who was diagnosed as CCS pathologically two years previously presented abdominal pain and sub fever-up. Physical examination revealed the palpable mass sized approximate 10 cm in diameter in the upper abdominal site, in addition to the symptoms of alopecia, absent fingernails and toenails. However, abdominal wall rigidity and rebound tenderness were never expressed. Abdominal plain CT showed concentric circles from the ascending to the middle of the transverse colon, and a tumor in the lumen at the middle of the transverse colon. Colonoscopic reduction was performed first because we diagnosed it as intussusception due to CCS polyps without peritoneal irritation, and his symptoms were improved dramatically after careful reduction. Therefore, he was able to undergo the laparoscopic ascending colectomy as scheduled.

Cronkhite-Canada syndrome complicated with huge intramucosal gastric cancer

Cronkhite-Canada syndrome (CCS) is a rare nonhereditary disorder with gastrointestinal polyposis and associated ectodermal changes. This report documents a 59-year-old Japanese man with CCS who underwent a total gastrectomy for gastric tumors. The resected specimen showed a huge gastric adenocarcinoma with numerous polyps throughout the stomach. The cancer was pathologically limited to within the mucosa and its histological structure resembled that of hyperplasia in CCS polyps, which led us to suppose that the carcinoma had arisen from hyperplastic CCS polyps. These results urged us to study the phenotypic expression of mucins, which revealed MUC2(-) and MUC5AC(+) and supported the diagnosis of the tumor as a gastric-type well-differentiate adenocarcinoma. A literature search revealed that 32 gastric carcinomas which developed in patients with CCS were mostly limited to within the submucosa in spite of their huge sizes, and such cancer development in CCS polyposis is therefore not considered to be unusual.

Complete Remission in Cronkhite-Canada Syndrome

A case of Cronkhite-Canada syndrome, where there was complete remission confirmed by radiology, endoscopy, and histology, is reported. On presentation, there was generalized gastrointestinal polyposis, hypoalbuminemia, skin pigmentation, onycho-dystrophy, and alopecia. Enteral nutrition alone was administered for 10 wk, with resolution of the ectodermal features and disappearance of the polyps within 4 mo of commencement of the treatment. This report of complete remission supports the generally accepted nonneoplastic and essentially inflammatory nature of the polyps in Cronkhite-Canada syndrome. Consideration needs to be given to nutritional deficiency as a cause of the syndrome.