So Young Jin

The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma.

BACKGROUND/AIMS Liver biopsy for hepatocellular carcinoma (HCC) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated HCC. METHODS We investigated the diagnostic accuracy of a panel of markers (HSP70 GPC3 and GS), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (n=13), low-grade dysplastic nodules (n=21), high-grade dysplastic nodules (n=50), very well-differentiated (VWD) (n=17), well-differentiated (WD-G1) (n=40) and G2-3 (n=35) HCC. RESULTS Almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22%) but never 2 or 3. For HCC detection the overall accuracy of marker combination was 60.8% (3 markers) and 78.4% (2 markers) with 100% specificity. When restricted to VWD+WD-G1 HCC the accuracy was 57% (3 markers) and 72.9% (2 markers) with 100% specificity. CONCLUSIONS This panel proved useful to detect well-differentiated HCC in biopsy. Two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for HCC detection. The diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human models.

Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study.

Purpose As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. Materials and Methods We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. Results Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET. Conclusion The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

Multiple gastrointestinal stromal tumors: Clinicopathologic and genetic analysis of 12 patients.

Multiple gastrointestinal stromal tumors (GISTs) are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST. The aim of this study was to investigate the clinical, phenotypic, and genetic characteristics of multiple GISTs to gain insights into their underlying pathogenesis and clinical behavior. Forty-seven paraffin blocks of multiple GISTs from 12 patients were analyzed. Genomic DNA was extracted from the tumor and normal mucosa and mutations for 4 exons of KIT gene and 3 exons of PDGFRA gene were determined. Among 12 patients with multiple GISTs, 5 were sporadic, 2 were familial with germline mutations of KIT gene, and 5 were associated with type 1 neurofibromatosis. All but 1 sporadic and familial multiple GISTs showed mutations of KIT gene shared by the same mutation on each GIST mass within a patient. But in 1 sporadic case, different types of KIT mutations were observed. Two familial multiple GIST cases showed diffuse involvement of the gastrointestinal tract with diffuse hyperplasia of interstitial cell of Cajal. Multiple GISTs associated with type 1 neurofibromatosis were located in the jejunum and harbored no mutations of KIT or PDGFRA. Different types of KIT gene mutation found in our case raise a possibility that recurrence of GISTs within a gastrointestinal tract may have a chance to be a rare occurrence of multiple primary GISTs instead of true recurrence. Multiple GISTs show unique clinical, phenotypic, and genotypic characteristics that are dependent on the particular underlying mechanisms, but the overall prognosis is favorable regardless of the numbers or phenotype of GISTs.

Increased Expression of Focal Adhesion Kinase in Thyroid Cancer: Immunohistochemical Study

Focal adhesion kinase (FAK) is a tyrosine kinase that is found in cellular structures called focal adhesions. FAK appears to be a key element in signal transduction pathways involved in cell adhesion and locomotion. FAK is overexpressed in various tumors, including tumors derived from regions of the head and neck, colon, breast, prostate, and liver. In this study, we investigated immunohistochemically whether FAK expression was increased in thyroid cancers. FAK staining was not seen in any of the 20 normal thyroid tissues or the 6 nodular hyperplasia specimens. In contrast, FAK staining was observed in all of 17 papillary carcinomas, 9 follicular carcinomas, 8 medullary carcinomas, and 2 anaplastic carcinomas. Nine of 17 follicular adenomas showed FAK immunoreactivity. FAK was not expressed in normal tissue and nodular hyperplasia, but was expressed in some of the follicular adenoma, and all of the follicular, papillary, medullary and anaplastic thyroid carcinoma. This result indicates that the up-regulation of FAK may play a role in the development of thyroid carcinogenesis.

The accuracy of probe-based confocal endomicroscopy versus conventional endoscopic biopsies for the diagnosis of superficial gastric neoplasia (with videos).

BACKGROUND Probe-based confocal laser endomicroscopy (pCLE) allows real-time in vivo histologic evaluation of GI mucosal lesions. Although pCLE has been used for various GI disorders, the significance of pCLE for gastric lesions is largely unknown. OBJECTIVE We compared the accuracy of conventional endoscopic forceps biopsy and pCLE for the diagnosis of superficial gastric neoplasia before endoscopic resection. DESIGN Prospective comparative study. SETTING Single tertiary referral center. PATIENTS This study involved 54 superficial gastric neoplasias in 46 patients. MAIN OUTCOME MEASUREMENT Accuracy of in vivo and offline pCLE diagnosis and interobserver agreement. METHODS pCLE was performed before endoscopic resection of superficial gastric neoplasias previously diagnosed by endoscopic biopsy. The overall accuracy of endoscopic, in vivo pCLE, and offline pCLE diagnosis was compared with postendoscopic resection histopathology. RESULTS Endoscopic resection was performed on 54 lesions. On final histopathology, there were 3 non-neoplastic lesions, 19 gastric dysplasias, 22 differentiated adenocarcinomas, and 10 undifferentiated adenocarcinomas. The overall agreement with the final histopathology was substantial for conventional biopsies (κ = 0.617) and excellent for in vivo pCLE (κ = 0.824) (P < .001). The overall accuracy for the diagnosis of adenocarcinoma was 91.7% for pCLE and 85.2% for conventional biopsies (P = .065). The combined accuracy of conventional endoscopic biopsies and pCLE was 98.1%. The interobserver agreement for offline pCLE diagnosis was excellent (κ = 0.931). LIMITATIONS Single-center study, small sample size. CONCLUSION Our study showed that pCLE can provide an accurate diagnosis for superficial gastric neoplasia. pCLE has the potential to compensate for the inherent limitations of a conventional endoscopic biopsy.

Current trends in the epidemiological and pathological characteristics of gastrointestinal stromal tumors in Korea, 2003-2004.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patients survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patients survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patients survival, but the mechanism still needs to be clarified through future studies.

Optical biopsies by confocal endomicroscopy prevent additive endoscopic biopsies before endoscopic submucosal dissection in gastric epithelial neoplasias: a prospective, comparative study.

BACKGROUND Confocal laser endomicroscopy (CLE) allows real-time in vivo histologic evaluation of GI lesions. To our knowledge, there is no reported prospective study comparing endoscopic and optical biopsy using CLE before endoscopic submucosal dissection (ESD) with post-ESD histopathology. OBJECTIVE We compared endoscopic and optical biopsy before ESD and thereby assessed the ability of CLE to effectively diagnose and differentiate gastric epithelial neoplasia. DESIGN Single tertiary-care center, prospective comparative study. SETTING Soonchunhyang University Hospital, between September 2009 and April 2010. PATIENTS This study involved 31 patients with 35 gastric epithelial neoplasias, previously diagnosed by endoscopic biopsy, who were scheduled for ESD. INTERVENTION Target lesions were imaged in vivo by using CLE. MAIN OUTCOME MEASUREMENTS The overall accuracy of endoscopic and CLE diagnosis was compared with post-ESD histopathology. RESULTS In histopathology after ESD, 11 of 35 lesions (31.5%) were adenomas and 24 (68.5%) were adenocarcinomas. The overall accuracy of CLE diagnosis of gastric adenomas and adenocarcinomas was significantly higher at 94.2% (95% confidence interval [CI], 81.3-98.4), versus 85.7% (95% CI, 70.6-93.7) for endoscopic biopsy (P = .031). The overall accuracy of CLE diagnosis of differentiated and undifferentiated adenocarcinomas also was higher (95.4%; 95% CI, 78.2-99.1) than that of endoscopic biopsy (84.2%; 95% CI, 62.4-94.4) but did not differ significantly (P = .146). LIMITATIONS Single tertiary-care center experience and small patient number. CONCLUSION This study demonstrates the high accuracy of diagnosis of gastric epithelial neoplasia by using CLE. The use of CLE could possibly thus reduce the number of unnecessary biopsies and mistaken diagnoses before ESD.

Appropriate indications for endoscopic submucosal dissection of early gastric cancer according to tumor size and histologic type.

BACKGROUND Endoscopic submucosal dissection (ESD) is increasingly being performed for early gastric cancers (EGCs) that are larger than 2 cm and those that are not intestinal-type (IT) cancers by Laurens classification. The technical feasibility of ESD for these EGCs has not been fully evaluated. OBJECTIVE To identify appropriate expanded indications for ESD of EGC. DESIGN AND SETTING A retrospective analysis of prospectively collected data was performed on consecutive patients who underwent ESD at a single tertiary center. PATIENTS AND METHODS In total, 487 EGCs in 461 patients treated by ESD were classified by size and histologic type: IT EGCs 2 cm or less (257 lesions in 235 patients), IT EGCs larger than 2 cm (172 lesions in 168 patients), and non-IT EGCs (58 lesions in 58 patients). MAIN OUTCOME MEASUREMENTS Curative resections were assessed among the 3 groups, and logistic regression analysis was used to analyze factors related to curative resection. RESULTS The rates of curative resection significantly decreased from IT EGCs 2 cm or less (88.7%) to IT EGCs larger than 2 cm (73.3%) to non-IT EGCs (37.9%). Tumor size (>3 cm), ulceration, histologic type (non-IT), and piecemeal resection were independently unfavorable factors in curative resection. LIMITATIONS Small sample size and short-term duration of follow-up study. CONCLUSIONS ESD with curative intent is technically most feasible for nonulcerative and IT EGCs smaller than 3 cm.

Nonspecific Interstitial Pneumonia/Fibrosis: Clinical Manifestations, Histologic and Radiologic Features

Objectives Customarily used classification of IPF did not satisfy a sizable group of patients with IPF that in the past had been lumped with UIP and now currently has begun to be recognized as nonspecific interstitial pneumonia/fibrosis (NIP). There are few reports about the clinical features of NIP. Methods The pathologic slides of 66 patients having open lung biopsy (OLB) for the differential diagnosis of interstitial lung diseases (ILD) from 1984 to 1995 were reviewed. Seven cases were confirmed as NIP. The clinical record, pulmonay function tests (PFT), chest PA and HRCT were reviewed and analysed retrospectively. Results Six patients with NIP were female. The median age was 56 years. Mean duration of symptoms was 4 months. Five patients had systemic flu-like symptoms. the most common respiratory symptom was gradual dyspnea Two patients revealed a mild degree of anemia Four cases had leukocytois of more than 10,000/mm3. ESR and CRP O.K. elevated in all measured cases. Anti-nuclear antibody (ANA) was positive in three of six patients and ds-DNA antibody was positive in one of six patients Restrictive pattern of PFT was predominant. Diffusion capacity of carbonmonoxide (DLCO) decreased markedly. In bronchoalveolar lavage (BAL), total cell counts elevated about three times of normal value. On differntial counts of BAL cells, lymphocytes, neutrophils and eosinophils were higher than those of normal controls. The prominent finding of chest radiology was bilaterally patchy opacifications in parenchyme of lower lung zones. On HRCT, bilaterally patchy areas of ground-glass attenuation and/or areas of alveolar consolidation were commonly shown. The number of pathologic type was one case of group I, four cases of group II and two cases of group III. The average period from diagnosis to the last follow-up was 24.8 months. Five patients were clinically recovered to the previously well-being state. Conclusion Patients with NIP had different clinical features from UIP, AIP and DIP. They also had characteristic findings of radiology and their prognosis seems to be better than UIP.

Pancreatic Resection Guided by Preoperative Intraductal Ultrasonography for Intraductal Papillary Mucinous Neoplasm

OBJECTIVES:Successful treatment requires reliable preoperative assessment of the highly variable extension of intraductal papillary mucinous neoplasms (IPMNs). We aimed to determine the role of intraductal ultrasonography (IDUS) in predicting the extension of IPMN, and in selecting the method of pancreatic resection and the long-term outcome after surgery.METHODS:Randomized prospective study. Forty consecutive patients who underwent IPMN resection were included in the study. Patients were randomly assigned to an IDUS group or control group, in which IDUS was not performed.RESULTS:Preoperative assessment by IDUS had an 85% (17 of 20) diagnostic accuracy for tumor extension of IPMN compared with 50% (10 of 20) in cases assessed by other imaging methods without IDUS (P=0.018). In 9 of 15 patients with invasive carcinoma, the tumor was located in the pancreatic head, and 11 had a main duct-type tumor. Recurrent disease was identified in 5 of 15 (33%) patients with invasive IPMN at a mean follow-up of 50 months; of them, 1 underwent preoperative IDUS and 4 were assessed by other imaging methods. None of the 25 patients with noninvasive IPMN had recurrent disease at follow-up. The overall cumulative 3-year survival rate was 79%.CONCLUSIONS:Preoperative IDUS was useful in determining the type of surgery and the extent of resection, especially in main-duct IPMN.