Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy:A case report

BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Plasma DNA methylation detection for early screening,diagnosis,and monitoring of esophageal adenocarcinoma and squamous cell carcinoma

BACKGROUND The early diagnosis rate of esophageal cancer(EC),one of the most prevalent digestive tract cancers worldwide,remains low.AIM To investigate the utility of plasma SHOX2,SEPTIN9,EPO,and RNF180 methylation in the clinical diagnosis and monitoring of EC.Plasma samples were collected from 210 patients at Hubei Cancer Hospital,and TaqMan polymerase chain reaction was employed to detect plasma SHOX2,SEPTIN9,RNF180,and EPO methylation.The area under the curve was used to estimate their diagnostic value for EC.Cox and logistic regression analyses were used to estimate the independent screening risk factors for patients with EC.RESULTS The sensitivity and specificity of combined assessment of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation for adenocarcinoma,squamous cell carcinoma(SCC),and EC detection were 66.67%and 86.27%,77.40%and 85.29%,and 76.19%and 86.27%,respectively;the area under the curve values for diagnosing adenocarcinoma,SCC,and EC were 0.737[95%confidence interval(CI):0.584–0.89],0.824(95%CI:0.775–0.891),and 0.864(95%CI:0.809–0.92),respectively.CONCLUSION According to our findings,plasma SHOX2,SEPTIN9,RNF180,and EPO methylation exhibits appreciated sensitivity for diagnosing EC.The precise measurement of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation can improve EC diagnosis and therapy efficacy monitoring.

Waist subcutaneous soft tissue metastasis of rectal mucinous adenocarcinoma: A case report

BACKGROUND Rectal mucinous adenocarcinoma(MAC)is a rare pathological type of rectal can-cer with unique pathological features and a poor prognosis.It is difficult to diag-nose and treat early because of the lack of specific manifestations in some aspects of the disease.The common metastatic organs of rectal cancer are the liver and lung;however,rectal carcinoma with metastasis to subcutaneous soft tissue is a rare finding.CASE SUMMARY In this report,the clinical data,diagnosis and treatment process,and postope-rative pathological features of a patient with left waist subcutaneous soft tissue masses were retrospectively analyzed.The patient underwent surgical treatment after admission and recovered well after surgery.The final pathological diagnosis was rectal MAC with left waist subcutaneous soft tissue metastasis.CONCLUSION Subcutaneous soft tissue metastasis of rectal MAC is rare,and it can suggest that the tumor is disseminated,and it can appear even earlier than the primary ma-lignant tumor,which is occult and leads to a missed diagnosis and misdiagnosis clinically.When a subcutaneous soft tissue mass of unknown origin appears in a patient with rectal cancer,a ma-lignant tumor should be considered.

Progress and current perspectives of diagnosis and treatment of hepatoid adenocarcinoma of the stomach

Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical symptoms closely resemble those of gastric adenocarcinoma.Because of its rarity,misdiagnosis and missed diagnoses are prevalent.Compared with gastric adenocarcinoma,HAS typically exhibits higher invasiveness and amore unfavorable prognosis.This review aimed to elaborate on the pathological features,potential mechanisms,clinical characteristics,diagnosis,and prognosis of HAS.The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.

Clinical diagnosis and management of pancreatic mucinous cystadenoma and cystadenocarcinoma:Single-center experience with 82 patients

BACKGROUND Mucinous cystic neoplasm(MCN)of the pancreas is characterized by mucinproducing columnar epithelium and dense ovarian-type stroma and at risk for malignant transformation.Early diagnosis and treatment of MCN are particularly important.AIM To investigate the clinical characteristics of and management strategies for pancreatic mucinous cystadenoma(MCA)and mucinous cystadenocarcinoma(MCC).METHODS The clinical and pathological data of 82 patients with pancreatic MCA and MCC who underwent surgical resection at our department between April 2015 and March 2019 were retrospectively analyzed.RESULTS Of the 82 patients included in this study,70 had MCA and 12 had MCC.Tumor size of MCC was larger than that of MCA(P=0.049).Age and serum levels of tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)19-9,and CA12-5 were significantly higher in MCC than in MCA patients(P=0.005,0.026,and 0.037,respectively).MCA tumor size was positively correlated with serum CA19-9 levels(r=0.389,P=0.001).Compared with MCC,MCA had a higher minimally invasive surgery rate(P=0.014).In the MCA group,the rate of major complications was 5.7%and that of clinically relevant pancreatic fistula was 8.6%;the corresponding rates in the MCC group were 16.7%and 16.7%,respectively.CONCLUSION Tumor size,age,and serum CEA,CA19-9,and CA12-5 levels may contribute to management of patients with MCN.Surgical resection is the primary treatment modality for MCC and MCA.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma:A propensity score-matched study

BACKGROUND Gallbladder mucinous adenocarcinoma(GBMAC)is a rare subtype of gallbladder adenocarcinoma(GBAC),with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis.AIM To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field.METHODS This study was conducted using data from the Surveillance,Epidemiology,and End Results database,including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017.The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts.In addition,propensity score matching(PSM)analysis was performed to balance the selection biases.Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-speci
c survival(CSS)and overall survival(OS).The Kaplan–Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients.RESULTS The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC.They included a larger proportion of patients with unmarried status,advanced American Joint Committee on Cancer(AJCC)stage,higher T stage,higher N1 stage rate and lower N0 and N2 stage rates(P<0.05).Multivariate analyses demonstrated that surgery[OS:Hazard ratio(HR)=2.27,P=0.0037;CSS:HR=2.05,P=0.0151],chemotherapy(OS:HR=6.41,P<0.001;CSS:HR=5.24,P<0.001)and advanced AJCC stage(OS:Stage IV:HR=28.99,P=0.0046;CSS:Stage III:HR=12.31,P=0.015;stage IV:HR=32.69,P=0.0015)were independent prognostic indicators for OS and CSS of GBMAC patients.Furthermore,after PSM analysis,there was no significant difference between GBMAC and matched typical GBAC patients regarding OS(P=0.82)and CSS(P=0.69).CONCLUSION The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC.However,they show similar survival prognoses.Surgery,chemotherapy,and lower AJCC stage were associated with better survival outcomes.Further research is needed in the future to verify these results.

Delayed diagnosis of ascending colon mucinous adenocarcinoma with local abscess as primary manifestation: Report of three cases

BACKGROUND Colorectal mucinous adenocarcinoma is a distinct subtype of colorectal adenocarcinoma that is not sensitive to chemotherapy and radiotherapy,and its prognosis is worse than that of nonmucinous adenocarcinoma.Early diagnosis and aggressive surgical treatment may be the key to improving the prognosis of patients.Ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess caused by non-intestinal perforation has never been reported.Moreover,since the lumen of the ascending colon is large,and early stage ascending colon cancer lacks typical clinical manifestations,the diagnosis may be delayed easily.We herein report three cases of delayed diagnosis of colorectal mucinous adenocarcinoma.CASE SUMMARY We present three patients(two females and one male)with mucinous ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess(the right area of the lumbar spine,right groin,and lower right abdomen)caused by non-intestinal perforation.At the initial clinical visit,the common causes of those abscesses,including spinal tuberculosis and urinary tract infection,were excluded.The treatment of the abscess was through an incision and drainage.However,the source of the abscess was not made clear,which led to an abscess recurrence and a delayed diagnosis of colorectal mucinous adenocarcinoma.After the patients were referred to our hospital,a definitive diagnosis of ascending colon mucinous adenocarcinoma was made with the help of tumor markers and colonoscopic findings.Because of the delayed diagnosis of the disease,two patients(case 1 and case 2)missed the chance of surgery due to disease progression and died in a short follow-up period.Only case 3 underwent radical surgery for the tumor in the right colon and partial abdominal wall resection and achieved a better prognosis.CONCLUSION Abscesses in the right area of the lumbar spine,right groin,or right lower quadrant caused by non-intestinal perforation as the primary clinical manifestation of ascending colon mucinous adenocarcinoma are extremely rare.Mucinous adenocarcinoma of the ascending colon may be one of the causes of such abscesses.Performing colonoscopy as soon as possible is of great significance in the diagnosis and treatment of the disease.

Malignant transformation of pulmonary bronchiolar adenoma into mucinous adenocarcinoma:A case report

BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors,including invasive mucinous adenocarcinoma,especially based on the histopathology of intraoperative frozen sections.These tumors are now considered to be benign neoplasms,with malignant transformation reported in only a few cases.CASE SUMMARY A 57-year-old woman presented with a 17.0 mm×7.0 mm nodule in the lower lobe of the left lung.Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed.The tumor consisted of a BA area and a mucinous adenocarcinoma(MA)area.In the BA area,the tumor had a bilayered structure of luminal cells and basal cells.The basal cells were positive for CK5/6 and p40,but the MA area was negative for these biomarkers.The Ki-67 proliferation index was low(1%-2%).The patient was diagnosed with BA accompanied by MA,and had a favorable outcome.CONCLUSION The present study indicated that BA may be carcinogenic,and suggests that clinicians should be aware of its potential for malignant transformation.

Local recurrence after successful endoscopic submucosal dissection for rectal mucinous mucosal adenocarcinoma:A case report

BACKGROUND Mucinous adenocarcinoma of the colorectum is a rare histological subtype characterized by an abundant mucinous component.Mucinous tumors are frequently diagnosed at an advanced stage,which indicates an aggressive subtype.However,few case reports have been published,and little information is available concerning genetic alterations in mucinous adenocarcinoma.CASE SUMMARY A 76-year-old man underwent en bloc endoscopic submucosal dissection(ESD)for the management of a type 0-Is+IIa lesion.Histological examination revealed an intramucosal mucinous adenocarcinoma with signet-ring cell carcinoma and well-to-moderately differentiated tubular adenocarcinoma.Three years after the ESD,local recurrence was detected by an endoscopic examination,revealing a new 0-Is+IIa lesion with a phenotype similar to the previously resected lesion.Re-ESD was chosen for the management of the recurrent tumor,and the histological examination showed positive tumor infiltration at the vertical margin.Additional surgical resection was performed for the curative treatment.Genetic analysis showed pathogenic alterations in RNF43 and TP53 in the adenoma and an additional SMAD4 alteration in the carcinoma.CONCLUSION This mucinous mucosal adenocarcinoma case was suggested to have an aggressive phenotype and a careful and close follow-up are required.

Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma:A case report

BACKGROUND Lung invasive mucinous adenocarcinoma(LIMA),formerly referred to as mucinous bronchioloalveolar carcinoma,is a rare disease that usually presents as bilateral lung infiltration,is unsuitable for surgery and radiotherapy,and shows poor response to conventional chemotherapy.CASE SUMMARY We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia,but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography-guided percutaneous lung biopsy.Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d.After more than 11 months of treatment,there is no evidence of recurrence or severe adverse events.CONCLUSION Although the precise mechanism of the antitumor effects of gefitinib are not clear,our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Dissimilar survival and clinicopathological characteristics of mucinous adenocarcinoma located in pancreatic head and body/tail

BACKGROUND Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics,which have a significant impact on prognosis.However,no study has reported the differences between pancreatic mucinous adenocarcinoma(PMAC)in the head vs the body/tail of the pancreas.AIM To investigate the differences in survival and clinicopathological characteristics between PMAC in the head and body/tail of pancreas.METHODS A total of 2058 PMAC patients from the Surveillance,Epidemiology,and End Results database diagnosed between 1992 and 2017 were retrospectively reviewed.We divided the patients who met the inclusion criteria into pancreatic head group(PHG)and pancreatic body/tail group(PBTG).The relationship between two groups and risk of invasive factors was identified using logistic regression analysis.Kaplan-Meier analysis and Cox regression analysis were conducted to compare the overall survival(OS)and cancer-specific survival(CSS)of two patient groups.RESULTS In total,271 PMAC patients were included in the study.The 1-year,3-year,and 5-year OS rates of these patients were 51.6%,23.5%,and 13.6%,respectively.The 1-year,3-year,and 5-year CSS rates were 53.2%,26.2%,and 17.4%,respectively.The median OS of PHG patients was longer than that of PBTG patients(18 vs 7.5 mo,P<0.001).Compared to PHG patients,PBTG patients had a greater risk of metastases[odds ratio(OR)=2.747,95%confidence interval(CI):1.628-4.636,P<0.001]and higher staging(OR=3.204,95%CI:1.895-5.415,P<0.001).Survival analysis revealed that age<65 years,male sex,low grade(G1-G2),low stage,systemic therapy,and PMAC located at the pancreatic head led to longer OS and CSS(all P<0.05).The location of PMAC was an independent prognostic factor for CSS[hazard ratio(HR)=0.7,95%CI:0.52-0.94,P=0.017].Further analysis demonstrated that OS and CSS of PHG were significantly better than PBTG in advanced stage(stage III-IV).CONCLUSION Compared to the pancreatic body/tail,PMAC located in the pancreatic head has better survival and favorable clinicopathological characteristics.

Value of Texture Analysis of Intravoxel Incoherent Motion Parameters in Differential Diagnosis of Pancreatic Neuroendocrine Tumor and Pancreatic Adenocarcinoma

Objective To evaluate the value of texture features derived from intravoxel incoherent motion(IVIM) parameters for differentiating pancreatic neuroendocrine tumor(pNET) from pancreatic adenocarcinoma(PAC).Methods Eighteen patients with pNET and 32 patients with PAC were retrospectively enrolled in this study. All patients underwent diffusion-weighted imaging with 10 b values used(from 0 to 800 s/mm2). Based on IVIM model, perfusion-related parameters including perfusion fraction(f), fast component of diffusion(Dfast) and true diffusion parameter slow component of diffusion(Dslow) were calculated on a voxel-by-voxel basis and reorganized into gray-encoded parametric maps. The mean value of each IVIM parameter and texture features [Angular Second Moment(ASM), Inverse Difference Moment(IDM), Correlation, Contrast and Entropy] values of IVIM parameters were measured. Independent sample t-test or Mann-Whitney U test were performed for the betweengroup comparison of quantitative data. Regression model was established by using binary logistic regression analysis, and receiver operating characteristic(ROC) curve was plotted to evaluate the diagnostic efficiency.Results The mean f value of the pNET group were significantly higher than that of the PAC group(27.0% vs. 19.0%, P = 0.001), while the mean values of Dfast and Dslow showed no significant differences between the two groups. All texture features(ASM, IDM, Correlation, Contrast and Entropy) of each IVIM parameter showed significant differences between the pNET and PAC groups(P = 0.000-0.043). Binary logistic regression analysis showed that texture ASM of Dfast and texture Correlation of Dslow were considered as the specific imaging variables for the differential diagnosis of pNET and PAC. ROC analysis revealed that multiple texture features presented better diagnostic performance than IVIM parameters(AUC 0.849-0.899 vs. 0.526-0.776), and texture ASM of Dfast combined with Correlation of Dslow in the model of logistic regression had largest area under ROC curve for distinguishing pNET from PAC(AUC 0.934, cutoff 0.378, sensitivity 0.889, specificity 0.854). Conclusion Texture analysis of IVIM parameters could be an effective and noninvasive tool to differentiate pNET from PAC.

Unveiling the clinicopathological enigma of crawling-type gastric adenocarcinoma

In this editorial we comment on the article by Xu et al.Gastric adenocarcinoma(GA)is a malignancy which arises from the gastric mucosa and encompasses heterogenous tumors with varying characteristics.There are two main classifications:Lauren’s and the World Health Organization distinguishing the diverse types of GA depending on clinical,genetic,morphological and epidemiological features.“Crawling-type”adenocarcinoma(CRA)is a subtype characterized by irregularly fused glands with low-grade cellular atypia.Moreover,CRA represents differentiated tumor cells resembling intestinal metaplasia which results in misdiagnosis.The diagnosis is of utmost importance,as well as the subclassification and thorough pathological assessment.With regard to the symptoms of GA,these depend on the stage of the disease.Diagnostic methods play a crucial role in assessing the extent of the tumor and the stage of the disease.Nevertheless,early detection of CRA remains challenging due to its histological features.In summary,CRA is a distinct type of GA with particular clinicopathological and histological characteristics.Despite its significance,it not distinguished as a subtype,resulting in diagnostic challenges.Diagnosis is based on careful observation and thorough biopsy analysis,indicating the importance of comprehensive pathological assessment.

Limited, local, extracolonic spread of mucinous appendiceal adenocarcinoma after perforation with formation of a malignant appendix-to-sigmoid fistula: Case report and literature review

A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic resonance imaging demonstrated a dilated appendix forming a fistula to the sigmoid colon. Open laparotomy revealed a bulky abdominal tumor involving appendix, cecum, and sigmoid, and extending up to adjacent viscera, without ascites or peritoneal implants. The abdominal mass was removed en bloc, including resection of sigmoid colon, cecum(with preservation of ileocecal valve), appendix, right vas deferens, testicular vessels, and minimal amounts of anterior abdominal wall; and shaving off of small parts of the walls of the urinary bladder and small bowel. Gross and microscopic pathologic examination revealed an appendix-to-sigmoid malignant fistula secondary to perforation of mucinous adenocarcinoma of the appendix with minimal local spread(stage T4). However, the surgical margins were clear, all 13 resected lymph nodes were cancer-free, and pseudomyxoma peritonei or peritoneal implants were not present. The patient did well during 1 year of follow-up with no clinical or radiologic evidence of local recurrence, metastases, or pseudomyxoma peritonei despite presenting with extensive stage T4 cancer that was debulked without administering chemotherapy, and despite presenting with malignant appendiceal perforation. This case illustrates the non-aggressive biologic behavior of this low-grade malignancy. The fistula may have prevented free spillage of cancerous cells and consequent distant metastases by containing the appendiceal contents largely within the colon.

Role of endoscopic ultrasound in diagnosis and therapy of pancreatic adenocarcinoma

Since its advent more than 20 years ago, endoscopic ultrasound （EUS） has undergone evolution from an experimental to a diagnostic instrument and is now established as a therapeutic tool for endoscopists. Endoscopic ultrasound cannot accurately distinguish benign from malignant changes in the primary lesion or lymph node on imaging alone. With the introduction of the curved linear array echoendoscope in the 2990s, the indications for EUS have expanded. The curved linear array echoendoscope enables the visualization of a needle as it exits from the biopsy channel in the same plane of ultrasound imaging in real time. This allows the endoscopist to perform a whole range of interventional applications ranging from fine needle aspiration （FNA） of lesions surrounding the gastrointestinal tract to celiac plexus block and drainage of pancreatic pseudocyst. This article reviews the current role of EUS and EUS-FNA in diagnosis, staging and interventional application of solid pancreatic cancer.

Mucinous adenocarcinoma:A unique clinicopathological subtype in colorectal cancer

Mucinous adenocarcinoma(MAC)is a unique clinicopathological subtype of colorectal cancer,which is characterized by extracellular mucinous components that comprise at least 50%of the tumor tissue.The clinical characteristics,molecular features,response to chemo-/radiotherapy,and prognosis of MAC are different from that of non-MAC(NMAC).MAC is more common in the proximal colon,with larger volume,higher T-stage,a higher proportion of positive lymph nodes,poorer tumor differentiation,and a higher proportion of peritoneal implants compared to NMAC.Although biopsy is the main diagnostic method for MAC,magnetic resonance imaging is superior in accuracy,especially for rectal carcinoma.The aberrant expression of mucins,including MUC1,MUC2 and MUC5AC,is a notable feature of MAC,which may be related to tumor invasion,metastasis,inhibition of apoptosis,and chemo-/radiotherapy resistance.The genetic origin of MAC is mainly related to BRAF mutation,microsatellite instability,and the CpG island methylator phenotype pathway.In addition,the poor prognosis of rectal MAC has been confirmed by various studies,and that of colonic MAC is still controversial.In this review,we summarize the epidemiology,clinicopathological characteristics,molecular features,methods of diagnosis,and treatments of MAC in order to provide references for further fundamental and clinical research.

Primary Mucinous Adenocarcinoma of the Thymus: A Case Report and Literature Review

THYMIC carcinoma is a rare malignant tumor, but the most common malignant tumor of the ante-rior mediastinum. According to the latest World Health Organization （WHO） classification, primary thymic carcinoma has a variety of histological types, mainly including squamous cell, basaloid, mucoepidermoid,lymphoepithelioma-like, sarcomatoid, clear cell and neuro-endocrine carcinomas, and papillary adenocarcinoma.1-4 Thymic mucinous adenocarcinoma was discovered in re-cent years, and only 10 cases were reported. In this paper, we described a case of thymic mucinous adenocarcinoma, the histopathological findings and immunohistochemical results.

SIGNET-RING MUCINOUS ADENOCARCINOMA OF THE PANCREAS

An 88-year-old man presented symptoms and signs of ascending cholangitis and died 20 days after the onset of illness. Postmortem examination revealed a mucinous tumor arising from the head of the pancreas, encasing the common bile duct and invading the liver with multiple hepatic metastasis. The tumor showed a unique and uniform histological apperarance, consisting of signet-ring neoplastic cells floating in mucin pools. The rapid clinical course and widespread hepatic metastasis of this patient suggest that this pure, signet-ring variant of mucinous adenocarcinoma of the pancreas might have a poorer prognosis.

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.

Comparison between colorectal low- and high-grade mucinous adenocarcinoma with MUC1 and MUC5AC

AIM:To explore useful prognostic factors for mucinous adenocarcinoma(MAC) in the colon and rectum.METHODS:MAC was divided into low-and high-grade types based on the degree of structural differentiation;low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma,and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma.Immunohistochemically,the expression of 2 types of MUC1(MUC1/DF and MUC1/CORE),MUC2,2 types of MUC5AC(MUC5AC/CHL2 and HGM),MUC6,CDX2,and CD10 was examined in 16 cases of MAC consisting of 6 low-and 10 high-grade types.RESULTS:MUC1/DF3 was expressed in 3 of 6 low-grade MAC(50) and 10 of 10 high-grade MAC(100).MUC1/CORE was expressed in 1 of 6 lowgrade MAC(16.7) and 7 of 10 high-grade MAC(70).MUC2 was expressed in all MAC regardless of the grade.MUC5AC was expressed in 6 of 6 low-grade MAC(100) and 4 of 10 high-grade MAC(40).HGM was expressed in 5 of 6 low-grade MAC(83.3) and 6 of 10 high-grade MAC(60).Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade.CDX2 was expressed in 5 of 6 low-grade MAC(83.3) and 7 of 10 high-grade MAC(70).Taken together,MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade,and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade.CONCLUSION:It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.