BACKGROUND/AIMS: Mucin-hypersecreting bile duct tumor is rare, and has an unusual histologic characteristic of having various degrees of cellular atypia ranging from dysplasia to invasive carcinoma in the same specimen. To gain insight into the role of p16, p14 and p53 in the carcinogenic process of bile duct tumor, we analyzed the expression status of these proteins in mucin-hypersecreting bile duct tumor. METHODS: Immunohistochemical staining of p16, p14 and p53 were performed in 34 paraffin embedded tissues obtained from 22 patients of mucin-hypersecreting bile duct tumor. RESULTS: Thirty-four specimens were categorized into low-grade dysplasia (9), high-grade dysplasia (4), carcinoma in situ (CIS, 11) and invasive carcinoma (10) based on the degree of cytologic and structural atypia. p53 overexpressions were found in 6 (17.6%, 3 in CIS, 3 in invasive carcinoma) and more frequently observed in the advanced histologic stages (p<0.05). Loss of p16 staining was found only in 2 (6%) of low-grade dysplasia specimen. Loss of p14 staining was found in 21 (61.7%, 7 in low-grade dysplasia, 2 in high-grade dysplasia, 8 in CIS, and 4 in invasive carcinoma) and was frequently observed in low-grade and high-grade dysplasia compared to p53 (p<0.05). CONCLUSIONS: In mucin-hypersecreting bile duct tumor, p14 and p53 may play a role in the early and advanced stage of carcinogenesis, respectively. Further study regarding genetic and epigenetic alterations in p14 and p53 gene may be needed.
Adult ; Aged ; Bile Duct Neoplasms/*genetics/secretion ; Carcinoma/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/secretion ; English Abstract ; Female ; *Genes, p16 ; *Genes, p53 ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mucins/*secretion ; *Mutation ; Tumor Suppressor Protein p14ARF/*genetics

BACKGROUND: Lymphocytic gastritis (LG) is defined as an infiltration of more than 25 intraepithelial lymphocytes (IELs) per 100 surface epithelial cells, and the histological differential diagnosis of LG and residual mucosa associated lymphoid tissue (MALT) lymphoma can be difficult. Helicobacter pylori (H. pylori) is regarded as one of the possible causes of LG, but its clinicopathologic features of LG have not been clarified in Korea, which has a much higher prevalence of H. pylori infection than Western countries. We analyzed the clinicopathologic findings of LG in Korean patients and compared the cytologic findings of IELs of LG with those of MALT lymphoma. METHODS: Sixty six cases of LG and 59 cases of MALT lymphoma were selected and clinicopathologic features were analyzed. RESULTS: Eighteen cases (27.3%) of LG were found to be associated with H. pylori infection. The IELs in LG were found to diffusely and regularly infiltrate in the epithelium, but MALT lymphoma showed patchy IELs. IELs in LG and MALT lymphoma were CD 8+T lymphocytes and CD20+B lymphocytes, respectively. The mean nuclear size of IELs in LG was 4.37 micrometer, which was significantly smaller than those in MALT lymphoma (5.19 micrometer). CONCLUSION: LG, a rare variant of chronic gastritis is partly associated with H. pylori infection and more complex unknown causative factors. In addition to the immunophenotyping, the nuclear sizes of IELs can be helpful in the differential diagnosis of LG and residual MALT lymphoma.
Diagnosis, Differential ; Epithelial Cells ; Epithelium ; Gastritis* ; Helicobacter pylori ; Humans ; Immunophenotyping ; Korea ; Lymphocytes ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone ; Mucous Membrane ; Prevalence

BACKGROUND: Differentiation of viral hepatitis from acute cellular rejection (ACR) after liver transplantation can be difficult because of overlapping histological features. Here we investigated clinicopathologic characteristics of 311 liver allograft biopsies and searched for characteristic histopathological features that would facilitate the differential diagnosis between hepatitis B virus (HBV) infection and ACR. METHODS: A retrospective clinicopathologic examination of 311 liver allograft biopsies consisting of clinically proven ACR or HBV infection was performed. Immunohistochemical staining for HBcAg and HBsAg was done for 64 allograft biopsies showing HBV infection. RESULTS: Moderate to severe bile duct damage, diffuse centrilobular necrosis and centrilobular inflammation (p<0.000, for each) were more frequently observed in cases of ACR, whereas diffuse acidophilic bodies and spotty necrosis (p<0.000, for each) were more prevalent in cases of HBV infection. Immunopositivity for HBcAg (n=60, 93.8%) was higher than that for HBsAg (n=14, 21.9%) CONCLUSIONS: The presence of moderate to severe bile duct damage, diffuse centrilobular necrosis and centrilobular inflammation was a characteristic feature of ACR, whereas diffuse distribution of acidophilic bodies or spotty necrosis was the only characteristic feature of HBV infection. HBcAg was a more sensitive immunohistochemical marker than HBsAg for detecting HBV infection in liver allograft biopsies.
Bile Ducts ; Biopsy ; Diagnosis, Differential ; Graft Rejection ; Hepatitis ; Hepatitis B ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Inflammation ; Liver ; Liver Transplantation ; Necrosis ; Rejection (Psychology) ; Retrospective Studies ; Transplantation, Homologous

Heart transplantation was first performed in 1967. It is now regarded as a well-established treatment modality for end-stage cardiac diseases. Once the transplantation is performed, endomyocardial biopsy(EMB) is the examination of choice in monitoring the transplanted heart. We analyzed the pathological findings of follow-up EMB of 6 heart transplant patients. All patients have been suffered from severe heart failure. Four patients were adult male and two were adult females. All the hearts, except for one, displayed characteristic features of dilated cardiomyopathy. The remaining heart was diagnosed as having giant cell myocarditis. Post-transplantion EMBs were performed according to the protocol and standard cardiac biopsy grading of ISHT (1990). The standards were applied for grading of cellular rejection. In five patients, there were one or two episodes of biopsy proven acute rejection, grade II or IIIA without any clinical symptoms of rejection. Immediate "pulse therapy" was performed and follow-up biopsies were done. All episodes of rejection were cleared in subsequent biopsies. All patients are doing well without evidence of cardiac problem. The postoperative monitoring of acute rejection is critical since clinical signs of rejection are usually absent. At present, EMB is regarded as the most reliable method for diagnosis and grading of acute rejection and is an efficient guide to the monitoring of the cardiac recipients. Our experience of post-transplantation EMB corresponds with previously published reports.
Adult ; Male ; Female ; Humans ; Biopsy

BACKGROUND: Idiopathic duct centric pancreatitis (IDCP) is a subtype of autoimmune pancreatitis (AIP) that is histologically characterized by granulocytic epithelial lesion and scarce IgG4-positive cells. This subtype of AIP has not been documented in Asian countries. METHODS: We reviewed 38 histologically confirmed AIP cases and classified them into lymphoplasmacytic sclerosing pancreatitis (LPSP) and IDCP. Then, clinicopathological characteristics were compared between LPSP and IDCP. RESULTS: Fourteen cases (36.8%) were IDCP. IDCP affected younger patients more than LPSP. IDCP was associated with ulcerative colitis in 35.7% of cases, whereas LPSP was associated with IgG4-related sclerosing diseases such as cholangitis, retroperitoneal fibrosis or sialadenitis in 41.7% of cases. IDCP was microscopically characterized by neutrophilic ductoacinitis with occasional granulocytic epithelial lesions, whereas LPSP was characterized by storiform inflammatory cell-rich fibrosis and obliterative phlebitis. IgG4-positive cells were not detected in any IDCP case but more than 20 IgG4-positive cells per high-power-field were invariably detected in LPSP cases. All patients with IDCP responded dramatically to steroids without recurrence, whereas 33.3% of patients with LPSP developed recurrences. CONCLUSIONS: IDCP is clinicopathologically distinct from LPSP and can be diagnosed when neutrophilic ductoacinitis or granulocytic epithelial lesions are observed in a pancreatic biopsy under the appropriate clinical setting.
Asian Continental Ancestry Group ; Biopsy ; Biopsy, Needle ; Cholangitis ; Colitis, Ulcerative ; Fibrosis ; Humans ; Neutrophils ; Pancreatitis ; Phlebitis ; Recurrence ; Retroperitoneal Fibrosis ; Sialadenitis ; Steroids

BACKGROUND: Surgical resection is the treatment of choice of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. However, the benefit of clearing resection margin is still controversial. METHODS: We reviewed 281 surgically resected cases of IPMN. The recurrences were compared according to the histologic grade (benign or borderline IPMN, malignant noninvasive IPMN, invasive carcinoma) and size (pancreatic intraepithelial neoplasia, PanIN, less than 0.5 cm in the long axis; and IPMN, greater than or equal to 0.5 cm) of the residual lesions at the resection margin. RESULTS: Sixty cases (21.4%) were invasive carcinoma, and 221 (78.6%) noninvasive cases included 87 (31.0%) benign, 107 (38.1%) borderline and 11 (3.9%) malignant noninvasive IPMN cases. In noninvasive IPMN, increased recurrence in patients with five or more years of follow-up was only related to the involvement of resection margin by severe dysplasia. The recurrence of invasive carcinoma was high (27.3%) even when the resection margin was clear, and was not related to the grade or size of residual tumors at the resection margin. CONCLUSIONS: Invasiveness is a strong risk factor for recurrence in IPMN regardless of the status of the resection margin. However, in noninvasive IPMN, histologic grading of residual lesions at the resection margin predicts local recurrence.
Carcinoma, Intraductal, Noninfiltrating ; Follow-Up Studies ; Humans ; Mucins ; Neoplasm, Residual ; Pancreas ; Recurrence ; Risk Factors

Primary mucinous cystic neoplasms of the retroperitoneum in women are rare and show histologic features similar to their ovarian or pancreatic counterparts. We present three cases of primary retroperitoneal mucinous neoplasms of variable malignant potentials including a cystadenocarcinoma in a 50-year-old woman, a cystic neoplasm of borderline malignancy in a 31-year-old woman, and a cystadenoma in a 67-year-old woman. All cases showed histologic features similar to mucinous tumors of the ovary. Immunohistochemical study demonstrated positivity for calretinin in case 3. The histogenesis of these neoplasms can be assumed most likely to be mucinous metaplasia of the mesothelium or undetected heterotopic pancreatic tissue. Appropriate management is thought to be the same as for analogous ovarian neoplasms.
Adult ; Aged ; Calbindin 2 ; Cystadenocarcinoma ; Cystadenoma ; Epithelium ; Female ; Humans ; Metaplasia ; Middle Aged ; Mucins* ; Ovarian Neoplasms ; Ovary

BACKGROUND: The resurgence of tuberculosis and the widespread emergence of multidrug-resistant M. tuberculosis have emphasized the importance of rapid and accurate diagnostic procedures. Recently, the oligonucleotide chip has proven to be a useful tool in the rapid diagnosis of infectious diseases. The purpose of this study was to rapidly and accurately detect specific mutations in the rpoB, katG and rpsL genes associated with rifampin, isoniazid and streptomycin resistance in M. tuberculosis, respectively, using a single oligonucleotide chip. METHOD: For detection of drug-resistance, 7 wild-type and 13 mutant-type probes for rifampin, 2 wild-type and 3 mutant-type probes for isoniazid, and 2 wild-type and 2 mutant-type probes for streptomycin were designed and spotted onto glass slides. Fifty-five cultured samples of M. tuberculosis were amplified by PCR, and then underwent hybridization and scanning. Direct sequencing was done to verify the results from the oligonucleotide chip and to analyze the types of mutations. RESULT: Thirty-five cases out of 40 rifampin-resistant strains(~88%) had mutations in the rpoB gene. One case had a new mutation(D516F, GAC R TTC) and another known mutation together. Twenty cases out of 42 isoniazid-resistant strains(~50%) had mutations in the katG gene, while 7 cases out of 9 streptomycin-resistant strains(~78%) had mutations in the rpsL gene. From these results, the oligonucleotide chip was confirmed to be able to detect the most frequent mutations from the genes associated with rifampin, isoniazid and streptomycin resistance. The results proved that the drug-resistance detection probes were specific. When the results from the oligonucleotide chip and DNA sequencing were compared, the types of mutations were exactly matched. CONCLUSION: The diagnostic oligonucleotide chip with mutation specific probes for drug resistance is a very reliable and useful tool for the rapid and accurate diagnosis of drug resistance against rifampin, isoniazid and streptomycin in M. tuberculosis infections.
Communicable Diseases ; Diagnosis ; Drug Resistance ; Drug Resistance, Multiple ; Glass ; Isoniazid ; Mycobacterium tuberculosis* ; Mycobacterium* ; Polymerase Chain Reaction ; Rifampin ; Sequence Analysis, DNA ; Streptomycin ; Tuberculosis

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. METHODS: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. RESULTS: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. CONCLUSIONS: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.
Biomarkers ; Classification ; Humans ; Immunohistochemistry ; Keratin-19* ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreas ; Prognosis ; Survival Rate ; World Health Organization

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.
Carcinogenesis* ; Classification ; Disease-Free Survival ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreas ; Pancreatic Neoplasms ; Progesterone* ; Prognosis ; Receptors, Progesterone* ; Survival Rate ; Telomere ; World Health Organization