Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine

AIM:To clarify the correlation with phenotypic expression,clinicopathological features,genetic alteration and microsatellite-instability status in small intestinal adenocarcinoma(SIA).METHODS:The cases of 47 patients diagnosed with primary SIAs that were surgically resected at our institution in 1975-2005 were studied.We reviewed clinicopathological findings(age,gender,tumor size,gross appearance,histological morphologic type,invasion depth,lymphatic permeation,venous invasion,and lymph node metastasis),and the immunohistochemical expression of MUC5 AC,MUC6,MUC2,CD10,and mismatch-repair(MMR) proteins(MLH1 and MSH2).We analyzed KRAS and BRAF gene mutations,and the microsatellite instability(MSI) status.The immunohistochemical staining of CD10,MUC2,MUC5 AC and MUC6 was considered positive when distinct staining in > 5% of the adenocarcinoma cells was recorded.To evaluate of MMR protein expression,we used adjacent normal tissue including lymphoid follicles,inflammatory cells,and stromal cells as an internal positive control.Sections without nuclear staining in the tumor cells were considered to have lost the expression of the respective MMR protein.RESULTS:There were 29 males and 18 females patients(mean age 59.9 years,range:23-87 years).Tumors were located in the duodenum in 14 cases(30%),the jejunum in 21 cases(45%),and the ileumin 12 cases(25%).A phenotypic expression analysis revealed 20 MUC2-positive tumors(42.6%),11 MUC5AC-positive(23.4%),4 MUC6-positive(8.5%),and 7 CD10-positive(14.9%).The tumor sizes of the MUC2(+) tumors were significantly larger than those of the MUC2(-) tumors(mean,5.7 ± 1.4 cm vs 4.7 ± 2.1 cm,P < 0.05).All three tumors with adenomatous component were positive for MUC2(P < 0.05).Polypoid appearance was seen significantly more frequently in the CD10(+) group than in the CD10(-) group(P < 0.05).The tumor size was significantly larger in the CD10(+) group than in the CD10(-) group(mean,5.9 ± 1.4 cm vs 5.0 ± 2.1 cm,P < 0.05).Of 34 SIAs with successfully obtained MSI data,4 were MSI-high.Of the 4 SIAs positive for both MUC5 AC and MUC2,3 showed MSI-H(75%) and 3 were mucinous adenocarcinoma(75%).KRAS mutations were detected in 4 SIAs.SIAs had KRAS mutation expressed only MUC2,but were negative for MUC5 AC,MUC6 and CD10.CONCLUSION:These findings suggest that the phenotypic expression of SIAs is correlated with their biological behavior,genetic alteration,and MSI status.     

Crohn's disease and small intestine adenocarcinoma

INTRODUCTION: The relationship between digestive neoplasia and Crohn's disease remains debated but several cases of carcinoma have been reported in the past 10 years. EXEGESIS: We report two cases of intestinal adenocarcinoma found in young people. Patients were asymptomatic during 15 years after the diagnosis of inflammatory bowel disease and presented a sudden occlusive syndrome. Carcinoma was observed incidentally at gross examination, and histopathological study showed dysplasia adjacent to neoplasia. Despite adequate surgical resection, death occurred quickly. CONCLUSION: Crohn's carcinoma should be suspected in patients with long-standing disease, poor symptomatology, and stenosis. Intestinoscopy surveillance remains illusory because inflammatory stenosis is often present and infiltrative neoplasia is invisible. Thus, it is important to be vigilant in this clinical presentation.     

Synchronous leiomyosarcoma and adenocarcinoma of the rectum: Report of a case and review of the literature

Summary A case report of rectal leiomyosarcoma coexisting with an adenocarcinoma of the rectosigmoid is presented. We believe this to be the first reported case of this condition. Read at the Residents’ Night meeting, New York Society of Colon and Rectal Surgeons, New York, New York, March 13, 1973 (first prize essay winner).     

Occult carcinoma of the breast masquerading as primary adenocarcinoma of the small intestine. A case report

A fifty-year-old woman with abdominal pain, diarrhea, and weight loss ultimately required exploratory laparotomy. The entire small intestine was extensively infiltrated by poorly differentiated adenocarcinoma; mesenteric lymph nodes and surrounding omentum were involved, but no extragastrointestinal tumor was found. A presumptive diagnosis of unresectable primary carcinoma of the small bowel was made. Chemotherapy was initiated with 5-fluorouracil 300 mg/m2/day by continuous intravenous infusion. Nine months later a left breast mass with multiple ipsilateral axillary and supraclavicular lymph nodes developed; biopsy revealed a poorly differentiated adenocarcinoma morphologically identical to the tumor involving her small bowel. In spite of breast irradiation and systemic hormonal therapy, the patient deteriorated rapidly and died from progressive metastatic disease.     

Synchronous coexistence of liver metastases from cecal leiomyosarcoma and rectal adenocarcinoma: A case report

Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both intestinal leiomyosarcoma and adenocarcinoma. The patient described in this report successfully underwent resection of both primary lesions and liver metastases in combination with chemotherapy. As for the leiomyosarcoma, the primary cecal lesion was revealed more than three years after the patient's first visit. Peritoneal, lymph-node, and lung recurrences were observed afterward, and thus surgeries on those regions were performed. Pathologically, the peritoneal and lung recurrences comprised leiomyosarcoma and the lymphnode recurrence was diagnosed as adenocarcinoma. Despite newly discovered multiple lung recurrences and regional lymph-node metastases, the patient lived a normal life for 73 mo after the initial operation based on multidisciplinary therapy. He ultimately died of liver failure due to invasive lymph-node recurrence from the rectal adenocarcinoma, in addition to multiple lung recurrences from the leiomyosarcoma. Hepatic recurrence did not occur in this patient's case, which appears to be one reason for his long-term survival.     

An insight into the genetic pathway of adenocarcinoma of the small intestine

BACKGROUND: Although the adenoma to carcinoma pathway in colorectal cancer is well described, the mechanisms of carcinogenesis in the small intestine remain unclear. AIMS: The aim of this study was to investigate candidate genes in the genetic pathway of adenocarcinoma of the small intestine. SUBJECTS AND METHODS: A total of 21 non-familial, non-ampullary adenocarcinomas of the small intestine were analysed. DNA was extracted from formalin fixed paraffin wax embedded tissue using standard techniques. The replication error (RER) status was determined by amplification of BAT26. The mutation cluster region (MCR) of the adenomatous polyposis coli (APC) gene was screened using polymerase chain reaction single strand conformational polymorphism and direct sequencing. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for hMLH1, hMSH2, beta-catenin, E-cadherin, and p53. RESULTS: Fourteen male and seven female patients with a median age of 64 years (range 21-85) presented with adenocarcinoma of the duodenum (10), jejunum (7), and ileum (4). One cancer (5%) was found to be RER+, and all tumours stained positive for hMLH1 and hMSH2. No mutations were detected in the MCR of the APC gene. beta-Catenin showed increased nuclear expression with loss of membranous staining in 10 cancers (48%). Absent or decreased membrane expression of E-cadherin was found in eight cancers (38%). Strong staining of p53 was found in the nucleus of five cancers (24%). CONCLUSION: We did not detect mutations in the MCR of the APC gene, and this suggests that adenocarcinoma of the small intestine may follow a different genetic pathway to colorectal cancer. Abnormal expression of E-cadherin and beta-catenin was common and reflects an early alternative to APC in this pathway in which mutations may be found in adenocarcinoma of the small intestine.     

Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine

Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (> 20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.     

A case of adenocarcinoma developed in the small intestine with chronic strongyloidiasis

We experienced a case of intestinal strongyloidiasis complicated by jejunal carcinoma. A Japanese male in his 50s, who has a 7-year medical history of duodenal ulcers, complained of loss of appetite, nausea, vomiting and diarrhea. Computed tomography and gastroduodenal endoscopic examination revealed a stenosis of the duodenum. To remove the stenosis, gastric bypass surgery was performed. The pathological diagnosis of the resected jejunum was strongyloidiasis and well-differentiated adenocarcinoma with subserosal invasion and vascular infiltration. After administration of Ivermectin, Strongyloides stercoralis was not found in any biopsies or in the specimens of the intestine, which were resected due to cancer recurrence 2 years later. There are three possibilities for the reason of coexistence of S. stercoralis and adenocarcinoma: S. stercoralis caused the adenocarcinoma, S. stercoralis moved to the carcinoma, or just coincidence. Although it is difficult to prove a causal relationship between S. stercoralis and adenocarcinoma, this is the first report of adenocarcinoma developed in the jejunum with chronic strongyloidiasis. The number of nematode infections, including strongyloidiasis, is decreasing in Japan, although not worldwide. Therefore, it should be considered in patients with prolonged intestinal ulcers.     

Atypical X-ray manifestations of primary lung adenocarcinoma

The X-ray appearances of 722 proved cases with primary lung adenocarcinoma were reviewed. 74.5% had typical X-ray findings: peripheral pulmonary nodule (less than 4 cm). Atypical X-ray manifestations were variable. 54 cases (29.2%) had airway obstruction (obstructive pneumonitis and atelectasis), (179.2%) had hilar and/or mediastinal adenopathy as the main finding, 87 (47.0%) had pulmonary mass greater than 4 cm in diameter, 22 (11.9%) had mass with single or multiple cavities, 4 had lesions mimicked pneumonitis and 1 case had trachea and main bronchi involvement. Of the 56 poorly differentiated adenocarcinoma, 88% (49 cases) had Various X-ray findings. There were 35 cases (71.4%) had big masses (greater than 4 cm in diameter) with 5-6 cm for 19 cases and more 6 cm for 13 cases. Most of the masses with sharp margin and prompt enlargement in short period. There were 2 cases of poorly differentiated adenocarcinoma with very big mediastinal adenopathy misdiagnosed as lymphoma.     

A case of primary cancer of the small intestine]

We experienced the case that used S-1 for small intestinal cancer with peritoneal dissemination. A 51-year-old man admitted for fatigability and anemia. Small bowel series showed a stenosis lesion at the 15cm anal side from Treiz ligament, and the oral intestinal dilatasion was shown. CT showed the thickening of small intestinal wall and rectal wall. In addition, a rectal stenosis was shown by barium enema. It was diagnosed as small intestinal cancer with peritoneal dissemination, and an operation was performed. Peritoneal dissemination was recognized in the intraperitoneal whole, so jejunum partial resection was performed for primary cancer lesion. After an operation, internal use of S-1 was performed in an outpatient department. One course was assumed administration for four weeks and withdrawal for two weeks, and three courses was performed. There was not a side effect, and barium enema showed improvement of a rectal stenosis, and CT showed improvement of thickening of a rectal wall. A lesion worsened afterwards, and he died in postoperative six months.     

Clinical analysis of primary anaplastic carcinoma of the small intestine

Primary anaplastic carcinoma is a rare variant of small intestinal cancer. Most reports of primary anaplastic carcinoma of the small intestine are isolated case reports, therefore the clinicopathological features, therapeutic management, and surgical outcome of this tumor type remain unclear. This review analyzes the available clinical characteristics of primary anaplastic carcinoma of the small intestine and investigates key differences from differentiated adenocarcinoma of the small intestine. A Medline search was performed using the keywords ＇small intestine＇ and ＇anaplastic carcinoma＇ or ＇undifferentiated carcinoma＇. Additional articles were obtained from references within the papers identified by the Medline search. The literature revealed a poor prognosis for patients who underwent surgical resection for anaplastic carcinoma of the small intestine, which gave a 3-year overall survival rate of 10.8% and a median survival time of 5.0 mo. The literature suggests that anaplastic carcinoma~ is markedly more aggressive than differentiated adenocarcinoma of the small intestine. Surgical resection with the aim of complete tumor removal provides the only beneficial therapeutic option for patients with anaplastic carcinoma of the small intestine, because chemotherapy and radiation therapy have no significant effect on the rate of survival. However, despite complete tumor resection, most patients with anaplastic carcinoma of the small intestine are at great risk of disease recurrence. Multicenter clinical trials are expected to provide additional therapeutic strategies and establish the efficacy of multimodality adjuvant therapy. This report also highlights the importance of a systematic diagnostic approach for anaplastic carcinoma of the small intestine.