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1.  Predictive factors associated with malignancy of intraductal papillary mucinous pancreatic neoplasms 
AIM: To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
METHODS: Between April 1995 and April 2010, 129 patients underwent surgical resection for IPMNs at our institute and had confirmed pathologic diagnoses. The medical records were retrospectively reviewed and immunohistochemical staining for mucin (MUC) in pancreatic tissues was performed.
RESULTS: Univariate analysis showed that the following five variables were closely associated with malignant IPMNs preoperatively: absence of extrapancreatic malignancy; symptoms; tumor size > 4 cm; main pancreatic duct (MPD) size > 7 mm; and lymph node enlargement on preoperative computed tomography (CT). Multivariate analysis revealed that the following two factors were significantly associated with malignant IPMNs preoperatively: MPD size > 7 mm [odds ratio (OR) = 2.50]; and lymph node enlargement on preoperative CT (OR = 3.57). No significant differences in the expression of MUC1, MUC2 and MUC5AC were observed between benign and malignant IPMNs.
CONCLUSION: MPD size > 7 mm and preoperative lymph node enlargement on CT are useful predictive factors associated with malignancy of IPMNs.
PMCID: PMC2980686  PMID: 21072900
Intraductal papillary mucinous neoplasms; Malignancy; Predictive factors; Pancreatic neoplasms
2.  Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules 
AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)-related HCC.
METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucose regulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.
RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman’s r = 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.
CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBV-related hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.
PMCID: PMC4305774  PMID: 15810071
Heat shock protein; Hepatocellular carcinoma; Dysplastic nodule; Hepatocarcinogenesis; Immunohisto-chemistry; Dot immunoblot analysis
5.  Extrapulmonary Lymphangioleiomyoma: Clinicopathological Analysis of 4 Cases 
Korean Journal of Pathology  2014;48(3):188-192.
Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease that predominantly affects females. Usually, LAM affects the lung; it can also affect extrapulmonary sites, such as the mediastinum, the retroperitoneum, or the lymph nodes, although these locations are rare. A localized form of LAM can manifest as extrapulmonary lesions; this form is referred to as extrapulmonary lymphangioleiomyoma (E-LAM). Due to the rare occurrence of E-LAM and its variable, atypical location, E-LAM is often difficult to diagnose. Herein, we report the clinicopathological information from four E-LAM cases, and also review previous articles investigating this disease.
Four patients with E-LAM were identified at the Samsung Medical Center (Seoul, Korea) from 1995 to 2012. All E-LAM lesions underwent surgical excision.
All patients were females within the age range of 43 to 47 years. Two patients had para-aortic retroperitoneal masses, while the other two patients had pelvic lesions; two out of the four patients also had accompanying pulmonary LAM. In addition, no patient displayed any evidence of tuberous sclerosis. Histologically, two patients exhibited nuclear atypism with cytologic degeneration.
E-LAM should be considered in the differential diagnosis of patients presenting with pelvic or para-aortic masses. We also conclude that further clinical and pathological evaluation is needed in patients with E-LAM and nuclear atypism.
PMCID: PMC4087131  PMID: 25013416
Lymphangioleiomyomatosis; Abdomen; Pelvis; Lymph nodes; Recurrence
6.  GSTT1 Copy Number Gain and ZNF Overexpression Are Predictors of Poor Response to Imatinib in Gastrointestinal Stromal Tumors 
PLoS ONE  2013;8(10):e77219.
Oncogenic mutations in gastrointestinal stromal tumors (GISTs) predict prognosis and therapeutic responses to imatinib. In wild-type GISTs, the tumor-initiating events are still unknown, and wild-type GISTs are resistant to imatinib therapy. We performed an association study between copy number alterations (CNAs) identified from array CGH and gene expression analyses results for four wild-type GISTs and an imatinib-resistant PDGFRA D842V mutant GIST, and compared the results to those obtained from 27 GISTs with KIT mutations. All wild-type GISTs had multiple CNAs, and CNAs in 1p and 22q that harbor the SDHB and GSTT1 genes, respectively, correlated well with expression levels of these genes. mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041), whereas mRNA expression levels of VEGF (P=0.025), IGF1R (P=0.026), and ZNFs (P<0.05) were significantly higher in GISTs with wild-type/PDGFRA D842V mutations than GISTs with KIT mutations. qRT-PCR validation of the GSTT1 results in this cohort and 11 additional malignant GISTs showed a significant increase in the frequency of GSTT1 CN gain and increased mRNA expression of GSTT1 in wild-type/PDGFRA D842V GISTs than KIT-mutant GISTs (P=0.033). Surprisingly, all four malignant GISTs with KIT exon 11 deletion mutations with primary resistance to imatinib had an increased GSTT1 CN and mRNA expression level of GSTT1. Increased mRNA expression of GSTT1 and ZNF could be predictors of a poor response to imatinib. Our integrative approach reveals that for patients with wild-type (or imatinib-resistant) GISTs, attempts to target VEGFRs and IGF1R may be reasonable options.
PMCID: PMC3790698  PMID: 24124608
7.  Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples 
Korean Journal of Pathology  2013;47(4):348-354.
Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical.
BRAF mutations were tested by dual-priming oligonucleotide-polymerase chain reaction (DPO-PCR), direct sequencing and subsequently retested with a real-time PCR assay, cobas 4800 V600 mutation test. In total, 64 tumors including 34 malignant melanomas and 16 papillary thyroid carcinomas were analyzed. DNA was extracted from formalin-fixed paraffin embedded tissue samples and the results of cobas test were directly compared with those of DPO-PCR and direct sequencing.
BRAF mutations were found in 23 of 64 (35.9%) tumors. There was 9.4% discordance among 3 methods. Out of 6 discordant cases, 4 cases were melanomas; 3 cases were BRAF V600E detected only by cobas test, but were not detected by DPO-PCR and direct sequencing. One melanoma patient with BRAF mutation detected only by cobas test has been on vemurafenib treatment for 6 months and showed a dramatic response to vemurafenib. DPO-PCR failed to detect V600K mutation in one case identified by both direct sequencing and cobas test.
In direct comparison of the currently available DPO-PCR, direct sequencing and real-time cobas test for BRAF mutation, real-time PCR assay is the most sensitive method.
PMCID: PMC3759634  PMID: 24009630
BRAF mutation; Melanoma; Real-time polymerase chain reaction; Sanger sequencing; Dual-priming oligonucleotide-PCR
8.  Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis 
Korean Journal of Pathology  2013;47(3):245-251.
The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.
We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.
The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.
Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.
PMCID: PMC3701820  PMID: 23837017
Colorectal neoplasms; Pathology, surgical; Multicenter study; Incidence; Diagnosis
9.  DPC4 Expression in the Small Intestinal Adenocarcinomas 
Korean Journal of Pathology  2012;46(5):415-422.
Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis.
We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology.
Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival.
The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.
PMCID: PMC3490110  PMID: 23136567
Smad4/DPC4; Adenocarcinoma; Intestine, small; Immunohistochemistry
10.  Neuroendocrine tumor in gastric adenoma: a diagnostic pitfall mimicking invasive adenocarcinoma 
Diagnostic Pathology  2012;7:102.
Neuroendocrine tumor (NET) in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients’ clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3487888  PMID: 22894753
Neuroendocrine tumor; Adenoma; Microcarcinoid; Diagnosis
11.  Role of transduodenal ampullectomy for tumors of the ampulla of Vater 
Tumors arising from the ampulla of Vater can be benign or malignant. Recently, endoscopic papillectomy has been employed in the management of benign ampulla of Vater tumors; however, surgical resection is the treatment of choice. The aim of this study was to define indications and suggest a role for transduodenal ampullectomy in the management of ampulla of Vater tumors.
We retrospectively reviewed the medical records of 54 patients treated for ampulla of Vater tumors between January 1999 and December 2008.
Twenty-two endoscopic papillectomies and 21 transduodenal ampullectomies were performed. Four patients underwent transduodenal ampullectomy after endoscopic papillectomy due to a recurrent or remnant tumor. Recurrence or a remnant tumor was found in one patient after transduodenal ampullectomy compared to six patients after endoscopic papillectomy. Immediate intraoperative conversion from transduodenal ampullectomy to pancreaticoduodenectomy was performed in five patients based on intraoperative frozen biopsy analysis.
Transduodenal ampullectomy should be performed to treat ampulla of Vater tumors that are unsuitable for endoscopic papillectomy. Transduodenal ampullectomy can serve as an intermediate treatment option between endoscopic papillectomy and pancreaticoduodenectomy in the management of ampulla of Vater tumors.
PMCID: PMC3219850  PMID: 22111080
Ampulla of vater; Transduodenal ampullectomy; Ampullary neoplasm; Endoscopic papillectomy
12.  Pancreatic serous cystadenocarcinoma with invasive growth into the colon and spleen 
Serous cystic neoplasms of the pancreas are almost always benign lesions. However, there are some case reports of malignant serous neoplasms of the pancreas. It is very difficult to distinguish malignant and benign tumors. Indeed, only clinicopathologic findings of locoregional invasion and metastasis represent a malignancy. We report a serous cystadenocarcinoma of the pancreas that was initially considered to be colon cancer. Post-operatively, the tumor was confirmed to be a malignant serous cystic tumor of the pancreas. One year later, the patient remains disease-free.
PMCID: PMC3204548  PMID: 22066125
Pancreas; Cystadenocarcinoma; Colon; Spleen
13.  Graft-versus-host disease after kidney transplantation 
Journal of the Korean Surgical Society  2011;80(Suppl 1):S36-S39.
Graft-versus-host disease (GVHD) is a rare complication after kidney transplantation. We describe a 62-year-old female with end-stage renal disease due to hypertension. She received a kidney with 4 mismatched human leukocyte antigen (HLA) out of 6 HLA - A, B, DR from a deceased donor. After the procedure, the patient showed watery diarrhea on postoperative day (POD) 45. An endoscopic biopsy of the colon revealed some apoptotic cells consistent with GVHD. Thrombocytopenia was gradually developed on POD 54. She received steroid pulse therapy, and thrombocytopenia did not progress. However, pneumonia, renal failure, and cardiac failure occurred. She died due to multiple organ failure. We must consider GVHD in renal transplant recipients without homozygous or identical HLA, who had only watery diarrhea without other typical GVHD symptoms such as skin rash and fever, although GVHD is rare in renal transplant recipients.
PMCID: PMC3205370  PMID: 22066080
Graft-versus-host disease; Human leukocyte antigen; Kidney donation; Kidney transplantation
14.  A Rare Case with Primary Undifferentiated Carcinoma of Pericardium 
A primary pericardial tumor is very rare. A 77-year-old woman was admitted to our hospital with chief complaint of exertional dyspnea due to large amount of pericardial effusion. She was finally diagnosed as pericardial undifferentiated carcinoma without definite histopathologial, immunochemistry feature. Despite palliative radiation therapy, the patient died of multiple organ failure. The prognosis of primary pericardial undifferentiated carcinoma is known to be very poor, especially in old people.
PMCID: PMC2955333  PMID: 20967159
Primary pericardial tumor; Pericardial effusion; Echocardiography; Undifferentiated carcinoma
15.  Cystic Lesions of the Gastrointestinal Tract: Multimodality Imaging with Pathologic Correlations 
Korean Journal of Radiology  2010;11(4):457-468.
The cystic lesions of the gastrointestinal (GI) tract demonstrate the various pathologic findings. Some lesions may present a diagnostic challenge because of non-specific imaging features; however, other lesions are easily diagnosed using characteristic radiologic features and anatomic locations. Cystic masses from the GI tract can be divided into several categories: congenital lesions, neoplastic lesions (cystic neoplasms, cystic degeneration of solid neoplasms), and other miscellaneous lesions. In this pictorial review, we describe the pathologic findings of various cystic lesions of the GI tract as well as the radiologic features of GI cystic lesions from several imaging modalities including a barium study, transabdominal ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging.
PMCID: PMC2893317  PMID: 20592930
Cystic lesions; Gastrointestinal tract; Barium study; Ultrasound (US); Computed tomography (CT); Magnetic resonance (MR)
16.  Intraductal Tubular Carcinoma of the Pancreas: a Case Report with the Imaging Findings 
Korean Journal of Radiology  2008;9(5):473-476.
We describe here a case of intraductal tubular carcinoma of the main pancreatic duct. Gadolinium-enhanced pancreas magnetic resonance (MR) imaging showed an enhancing mass that was confined in the dilated main pancreatic duct of the pancreatic body, along with dilatation of the upstream main pancreatic duct and chronic pancreatitis that was due to obstruction. MR cholangiopancreatography and an endoscopic retrograde pancreatogram showed a filling defect that was due to an intraductal mass of the pancreatic body, along with dilatation of the upstream main pancreatic duct and no dilatation of the downstream main pancreatic duct. The pathological findings demonstrated an intraductal nodular appearance without papillary projection or mucin hypersecretion.
PMCID: PMC2627216  PMID: 18838860
Intraductal tubular tumor; Intraductal tubular carcinoma; Computed tomography (CT); Magnetic resonance (MR); Pancreas
17.  Adenosquamous Carcinoma of Extrahepatic Bile Duct: Clinicopathologic Study of 12 Cases 
Adenosquamous carcinoma is a rare histologic subtype of extrahepatic bile duct (EBD) carcinoma and limited information is available on its clinicopathologic characteristics. Twelve cases of adenosquamous carcinoma were collected from 3 institutions and their clinicopathologic characteristics were examined and compared with those of 176 EBD adenocarcinomas. The adenocarcinoma component was more often seen at the surface of the tumor (7 of 12 cases, 58%), while the squamous carcinoma component was slightly more frequent at the advanced edge (7 of 12 cases, 58%). Immunohistochemistry, available in 10 cases, revealed that S100A2 was positive in the squamous carcinoma component in all 10 cases (100%), while it was present in the adenocarcinoma component in only 2 of 10 cases (20%, chi-square test, p=0.001). S100A4 expression did not show any difference between the two components. Patients with adenosquamous carcinomas had worse survival (median survival, 11 months) than those with adenocarcinoma (median survival, 32 months; log-rank test, p=0.003). Patients with predominant squamous cell carcinoma component at the leading edge had worse survival than those without it. In conclusion, patients with adenosquamous carcinoma demonstrated worse survival than those with pure adenocarcinoma. S100A2 immunohistochemical staining may be helpful in detecting the squamous component.
PMCID: PMC2480552  PMID: 18784802
Adenosquamous carcinoma; extrahepatic bile duct; cholangiocarcinoma; S100A2; prognosis
18.  Isolated Biliary Granulocytic Sarcoma Followed by Acute Myelogeneous Leukemia with Multilineage Dysplasia: A Case Report and Literature Review 
Journal of Korean Medical Science  2006;21(3):550-554.
Granulocytic sarcoma is a rare extramedullary tumor composed of myeloid progenitor cells. Primary involvement of the biliary tract without evidence of leukemia is exceedingly rare. Here, we report an isolated biliary granulocytic sarcoma in a 30-yr-old man who presented with jaundice, fever, and chill without any evidence of leukemia. However, five months after the diagnosis, he developed acute myelogenous leukemia with multilineage dysplasia and chromosomal abnormality. A rare possibility of biliary granulocytic sarcoma should be considered as a differential diagnosis in patients with obstructive jaundice. A histologic evaluation by aggressive diagnostic intervention is important and may improve prognosis.
PMCID: PMC2729966  PMID: 16778404
Sarcoma, Granulocytic; Leukemia; Jaundice, Obstructive; Bile Ducts
19.  A case of colonic lymphoid tissue invasion by Gymnophalloides seoi in a Korean man 
A 65-year old Korean man, living in Mokpo-city, Jeollanam-do, Republic of Korea, visited a local clinic complaining of right upper quadrant pain and indigestion. At colonoscopy, he was diagnosed as having a carcinoma of the ascending colon, and thus, a palliative right hemicolectomy was performed. Subsequently, an adult fluke of Gymnophalloides seoi was incidentally found in a surgical pathology specimen of the lymph node around the colon. The worm was found to have invaded gut lymphoid tissue, with characteristic morphologies of a large oral sucker, a small ventral sucker, and a ventral pit surrounded by strong muscle fibers. This is the first reported case of mucosal tissue invasion by G. seoi in the human intestinal tract.
PMCID: PMC2532654  PMID: 16514288
Gymnophalloides seoi; tissue parasitism; colon; gut lymphoid tissue; case report; man
20.  Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in colorectal carcinomas. 
The alteration of the mucin profile have been known to play a role in colorectal carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in colorectalcarcinomas. Overexpression of p53 is frequently noted in colorectal carcinomas with deep invasion or lymph node metastasis. However, there have been few reports about the association between MUC1, MUC2, and p53 expression with respect to the metastatic potential. This study was aimed to investigate the relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive, 39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression. Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were associated with a higher frequency of lymph node metastasis (p<0.05). The right colon showed a higher MUC1 positivity and frequent lymph node metastasis than the left colon (p<0.05). These results suggest that the coexpression of MUC 1 with p53 or MUC2 are involved in regional lymph node metastasis in colorectal carcinomas. The high expression of MUC1 in the right colon cancer was revealed to relate with lymph node metastasis.
PMCID: PMC3054826  PMID: 11850585
21.  Bronchus-Associated Lymphoid Tissue (BALT) Lymphoma of the Lung Showing Mosaic Pattern of Inhomogeneous Attenuation on Thin-section CT: A Case Report 
Korean Journal of Radiology  2000;1(3):159-161.
The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjögren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities
PMCID: PMC2718185  PMID: 11752947
Lung, diseases; Lung neoplasms, CT; Lymphoma, CT

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