A Case of Alpha-cell Nesidioblastosis and Hyperplasia with Multiple Glucagon-producing Endocrine Cell Tumor of the Pancreas / 대한소화기학회지

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.

Postradiation Malignant Fibrous Histiocytoma of the Colon: A Case Report

Post-radiation soft tissue sarcomas are recognized as rare complications of radiation therapy. The most common type of post-radiation soft tissue sarcoma is a malignant fibrous histiocytoma (MFH), which originates from mesenchymal cells with a predominance of histiocytes and fibroblasts. The two most common sites of occurrence for post-radiation soft tissue sarcomas are the chest wall and pelvic cavity. Post-radiation colorectal MFHs are extremely rare and all of the reported cases of post-radiation sarcomas have occurred >3 years after radiation therapy. Recently, we managed a case of colorectal MFH which developed in a 48-year-old male who had undergone a low anterior resection for rectal adenocarcinoma and had received chemoradiotherapy as adjuvant treatment. Twelve months after radiotherapy, a 4 cm mass was detected 8 cm superior to the anastomosis site on colonoscopic examination. A soft tissue sarcoma was suspected on pathologic examination of the biopsy specimen. Therefore, he underwent a Hartmann's operation and the final pathologic finding revealed MFH with a storiform pattern of tumor cells composed of pleomorphic, multinucleated giant cells. This is the first case of MFH that had a latency period <3 years (i.e., 1 year) between the time of radiotherapy and diagnosis.

Postradiation Malignant Fibrous Histiocytoma of the Colon: A Case Report

Post-radiation soft tissue sarcomas are recognized as rare complications of radiation therapy. The most common type of post-radiation soft tissue sarcoma is a malignant fibrous histiocytoma (MFH), which originates from mesenchymal cells with a predominance of histiocytes and fibroblasts. The two most common sites of occurrence for post-radiation soft tissue sarcomas are the chest wall and pelvic cavity. Post-radiation colorectal MFHs are extremely rare and all of the reported cases of post-radiation sarcomas have occurred >3 years after radiation therapy. Recently, we managed a case of colorectal MFH which developed in a 48-year-old male who had undergone a low anterior resection for rectal adenocarcinoma and had received chemoradiotherapy as adjuvant treatment. Twelve months after radiotherapy, a 4 cm mass was detected 8 cm superior to the anastomosis site on colonoscopic examination. A soft tissue sarcoma was suspected on pathologic examination of the biopsy specimen. Therefore, he underwent a Hartmann's operation and the final pathologic finding revealed MFH with a storiform pattern of tumor cells composed of pleomorphic, multinucleated giant cells. This is the first case of MFH that had a latency period <3 years (i.e., 1 year) between the time of radiotherapy and diagnosis.

Gastric Schwannoma

Schwannomas, also known as neurinomas or neurilemmomas, are generally benign, slow-growing neoplasms originating in any nerve that has a Schwann cell sheath. These neoplasms are rare among the spindle cell mesenchymal tumors of the gastrointestinal tract, but develop most commonly in the stomach representing 0.2% of all gastric tumors. We present the case of a 57-year-old female patient with a large schwannoma in the stomach that was palpable in the abdomen. She underwent subtotal gastrectomy under suspicion of gastrointestinal stromal tumor (GIST), but post-operative histopathological and immunohistochemical findings showed a fascicular arrangement of spindle cell with pallisading nuclei, and positive for S-100 protein with negative smooth muscle actin (SMA). These results confirmed schwannoma as the diagnosis.

Depressed-Type of Early Colon Cancer with Extensive Lymph Node Metastasis

Early colorectal cancer (ECC) is defined as invasive tumor limited to the colonic and rectal mucosa or submucosa, regardless of the presence or absence of lymph node metastasis. The incidence of lymph node metastasis in ECC ranges from 0 to 15.4%, and risk factors include depth of submucosal invasion, growth patterns (polypoid or non-polypoid), histologic subclassification, and lymphatic invasion. Of non-polypoid growth patterns, the depressed types of colorectal cancer have higher malignant potential than polypoid types, even for small sizes. Unfortunately, this type is also difficult to detect on colonoscopic examination. In this report, we describe a case of depressed type ECC with extensive lymph node metastasis without regional lymph node involvement.

A Standardized Pathology Report for Colorectal Cancer

BACKGROUND AND METHODS: For standardizing the pathology report and diagnosis of colorectal cancers, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has developed a pathology reporting format for colorectal cancer in collaboration with the Korean Society of Coloproctology. RESULTS: The diagnostic parameters are divided into two parts: the standard part and the optional part. The standard part contains most of the items listed in the Japanese classification, the TNM classification by AJCC, and the WHO classification. We included detailed descriptions on each item. CONCLUSIONS: The standardized pathology report for colorectal cancers is adequate for its application to routine surgical pathology reports, and it is also helpful to decrease the discrepancies that occur during the pathologic diagnosis of colorectal cancer. Furthermore, this reporting format could encourage nationwide multi-center collaborative studies.

Risk of Adenomatous Polyps in the Proximal Colon according to Age and Gender / 대한소화기내시경학회지

BACKGROUND/AIMS: Several lines of evidences suggest that the distribution of colorectal adenomatous polyps are different according to age and gender. Therefore, the efficacy of screening sigmoidoscopy for colorectal cancer not considering age and gender necessitates reappraisal. We aimed to evaluate the distributions of colorectal adenomatous polyps according to age and gender. METHODS: Total of 1,886 patients (1,322 men, 564 women) who underwent colonoscopy at Severance hospital, Seoul, Korea between July 1995 and September 2002, were included. The proximal colon was defined as the colon proximal to the sigmoid-descending junction. The advanced polyp was defined as the adenomatous polyp with one or more of the following features: (1) 1 cm or larger in diameter, (2) villous histology, (3) high grade dysplasia or adenocarcimoma. RESULTS: The risk of adenomatous polyps in the proximal colon was higher in men than women (OR, 1.63; 95% CI, 1.33~1.99, p < 0.05), and increased with age (p < 0.05). The risk of advanced polyps in the proximal colon tended to be higher in men than women, and to increase with age, but did not reach statistical significance. Among 1,886 patients with colorectal adenomatous polyps, 587 patients (31.1%) had polyps only in the proximal colon. Among 814 patients with advanced colorectal adenomatous polyps, 217 patients (26.7%) had advanced polyps only in the proximal colon. The risks of adenomatous polyps or advanced polyps found only in the proximal colon were not different according to sex, but tended to increase with age. CONCLUSIONS: The risk of adenomatous polyps in the proximal colon was higher in men compared to women and increased with age. About one third of the patients with colorectal adenomatous polyps had polyps only in the proximal colon. Colonoscopy is a better strategy for endoscopic screening for colorectal cancer compared with sigmoidoscopy, especially, in elderly male.

Prognostic Significance of Circumferential Resection Margin following a Total Mesorectal Excision in Rectal Cancer

PURPOSE: Studies of the circumferential resection margin (CRM) in rectal cancer surgery have revealed that inadequate surgical excision correlates with a high risk of recurrence. This study was designed to evaluate the prognostic value of the CRM in rectal cancer. METHODS: All 504 patients who underwent a total mesorectal excision for rectal cancer between 1997 and 2001 were studied. The distance between the CRM and the tumor on pathology slides (HE stain, x 20 times) was measured. The CRM was stained by using the Davidson marking system(R) (Bradley Product, Inc. USA), and a micrometer was used for the measurement. We divided the patients into a negative CRM group (CRM >3 mm), an abutting CRM group (CRM 3 mm), 5.6%, 38.9%, and 5.6% in the abutting CRM group, and 8.8%, 44.1%, and 8.8% in the positive CRM group. The five-year survival rates for the negative CRM, the abutted CRM and the positive CRM groups were 73.3%, 48.4%, and 25.5% (P<0.001), respectively, and the disease-free 5-year survival rates were 63.1%, 30.6%, 24.0% (P<0.001). The CRM was shown to be an independent prognostic factor by multivariate analyses adjusted for known predictors of outcome (P<0.001). CONCLUSIONS: The prognosis for a member of the abutting or the positive CRM group was more unfavorable than it was for a member of the negative CRM group; therefore, measurement of the CRM should be reported in the pathologic report. For patients with an abutting or a positive CRM, neoadjuvant or adjuvant chemoradiotherapy should be considered for better oncologic outcomes.

A Case of Endoscopic Mucosal Resection for Esophageal Adenocarcinoma Arising from Barrett's Esophagus / 대한소화기내시경학회지

Barrett's esophagus is defined as the replacement of normal squamous epithelium of distal esophagus with metaplastic columnar epithelium. It is a well known risk factor of esophageal adenocarcinoma. If high grade dysplasia or early stage esophageal cancer develops in a patient with Barrett's esophagus, esophagectomy shoud be performed. However, operative procedures have various complications and the patients may suffer resulting in poor quality of life. Therefore, if the cancer is detected at an early stage such as superficial mucosal lesion, it is possible to resect the tumor with the use of endoscopic technique. Furthermore, endoscopic mucosal resection (EMR) also can be performed for the patients with mucosal or submucosal cancer who can not receive esophagectomy due to old age or poor general condition. We experienced a case of esophageal adenocarcinoma from Barrett's esophagus which had been successfully resected endoscopically.

A Standardized Pathology Report for Gastric Cancer

BACKGROUND AND METHODS: The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists developed a standardized pathology reporting format for gastric cancer in collaboration with the Korean Gastric Cancer Association. RESULTS: The diagnostic parameters are divided into two part: the standard part and the optional part. The standard part contains most of the items listed in the Japanese classification, the TNM classification by UICC, the WHO classification, and the Korean Gastric Cancer Association classification. Therefore, the standard part is adequate for routine surgical pathology service. We included detailed descriptions on each item. CONCLUSIONS: The authors anticipate that this standardization can improve the diagnostic accuracy and decrease the discrepancies that occur in the pathologic diagnosis of gastric cancer. Furthermore, the standard format can encourage large scale multi-institutional collaborative studies.

A Case of Pneumatosis Cystoides Intestinalis / 대한소화기내시경학회지

Pneumatosis cystoides intestinalis (PCI) is a rare condition defined as the presence of multiple gas-filled cysts in the wall of gastrointestinal tract. The etiology and pathogenesis of PCI remain uncertain. It is associated with various medicosurgical conditions, including various pulmonary and gastointestinal diseases, connective tissue diseases and endoscopic procedures. The diagnosis is confirmed by endoscopic puncture and biopsy. PCI in adults, for the most part, show a benign clinical course and better prognosis if the associated disease is well controlled. Infantile PCI is more serious condition and especially associated with necrotizing enteritis. The treatment is usually conservative, However surgical intervention is needed when complications such as intussusception, obstruction, bleeding and perforation develope. We experienced a case of PCI found during the follow-up colonoscopy in a patient taken right hemicolectomy and systemic adjuvant chemotherapy due to colon cancer.

Ovarian Cystadenofibroma in a Patient with Familial Adenomatous Polyposis / 대한소화기내시경학회지

Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the appearance of numerous polyps in the large bowel with a high potential for malignant transformation unless untreated. A variety of extracolonic manifestations were reported such as osteoma, epidermoid cyst, desmoid tumor, gastroduodenal polyps, small bowel tumor, congenital hypertrophy of the retinal pigment epithelium, hepatobiliary tumor, thyroid tumor, and tumor of the central nervous system. However, the ovarian involvement of FAP as an extracolonic manifestation was very rare and there have been only few reports. We experienced a rare case of ovarian cystadenofibroma in a patient with FAP as an extracolonic manifestation. We also found colon cancer with multiple hepatic metastasis initially manifested as intestinal obstruction in the same patient. Surgical treatment and subsequent chemotherapy for colon cancer and intraoperative radiofrequency ablation of hepatic metastasis were performed.

Identification of tumor suppressor loci on the long arm of chromosome 5 in primary small cell lung cancers / 결핵

BACKGROUND: Recent cytogenetic studies indicated that loss of the long arm of chromosome 5 is a frequent event in small cell lung cancer (SCLC), suggesting the presence of a tumor suppressor gene is its place. To map the precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 15 primary SCLCs. METHODS: The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Nineteen polymorphic microsatellite markers located in the long arm of chromosome 5 were used in the microsatellite analysis. RESULTS: We found that ten (66.7%) of 15 tumors exhibited LOH in at least one of tested microsatellite markers. Two (13%) of 10 tumors exhibiting LOH lost a larger area in chromosome 5q. LOH was observed in five common deleted regions at 5q. Among those areas, LOH between 5q34-qter and 5q35.2-35.3 was most frequent (75%). LOH was also observed in more than 50% of the tumors at four at other regions, between 5q14-15 and 5q23-31, 5q31.1, 5q31.3-33.3, and 5q34-35. Three of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 2.5% (7 of 285) of the loci tested. CONCLUSION: Our data demonstrated that at least five tumor-suppressor loci exist in the long arm of chromosome 5 and that they may play an important role in small cell lung cancer tumorigenesis.

Analysis of Tumor Angiogenesis in Invasive Cervical Cancer / 대한산부인과학회잡지

OBJECTIVE: Tumor angiogenesis is believed to conelate with tumor growth, progression and metastasis. Studies of angiogenesis in breast, prostate and melanoma have shown that angiogenesis, the induction of new capillaries and venules, is associated with tumor metastases and recurrences. The purpose of this study was to investigate the angiogenesis as a prognostic factor in invasive cervical cancer. METHODS: Forty-three formalin fixed embedded blocks of invasive cervical cancers were examined using immunohistochemical staining with a monoclonal antibody against factor VIII-related antigen. RESULTS: The miaovessel counts were 53.50+/-20,07 in patients with lymph node metastasis, and 45.97+/-28.12 in those without such metastasis. There was a trend for the microvessel count to increase with lymph node metastasis. However, thae was no significant difference in microvessel counts regarding node status. There was no significant difference between microvessel counts in patients with stage I(47.90+/-25.89) and those with stage Il(45.50+/-29.27), The microvessel counts in squamous cell carcinoma(46.54+/-27.79) were not significantly different from those in adenocarcinoma(47,50+/-27.05), The microvessel count in patients with tumor size >-4 cm(53.00+/-21.17) was not significantly higher than in those with tumar size <4 cm(46.20+/-27.94). CONCLUSION: There was no significant correlation between microvessel counts and clinical stage of disease, pathological type, tumor size or lymph node metastasis in patients with invasive cervical cancer. There was a trend for the microvessel count to increase with lymph node etastasis.

Histological Grading and Staging of Chronic Hepatitis Standardized Guideline Proposed by the Korean Study Group for the Pathology of Digestive Diseases

The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice. Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.

Relationship between Proliferative Activity and Expression of HBcAg and p53 Protein in Hepatocellular Carcinoma and Surrounding Nontumorous Liver

In an attempt to discover the factors contributing to the increased proliferative activity in hepatocytes and subsequent development of HCC, the proliferative activity of hepatocytes was compared with the size of regenerative nodules and HBcAg expression status in the surrounding nontumorous liver of 45 surgically resected hepatocellular carcinomas, including 34 HBV related ones. In the tumor, the difference in proliferative activity and the histological grade was analyzed in terms of p53 gene alteration. The proliferative activity was assessed by immunohistochemical methods using Ki-67 monoclonal antibody. HBcAg expression in the surrounding nontumorous liver correlated with both the inflammatory and proliferative activity of hepatocytes (p0.05). p53 overexpression was not evident in surrounding nontumorous liver including cirrhosis. In conclusion, the above results are in line with the view that hepatic carcinogenesis is a mutistep, progressive process. In the initial stage, chronic cellular injury incurred by immumologic reaction against HBcAg seems to play a pivotal role in increased cellular regeneration. However, once transformation of hepatocytes occur the major contributor to tumor growth seems to be alteration in p53 tumor suppresor gene.

Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor

Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.

Analysis of p53 Protein Overexpression in Invasive Cervical Cancer / 대한산부인과학회잡지

The p53 gene is a tumor suppressor gene and mutations in this gene play an import-ant role in the development of many human malignancies. The purpose of this study was to investigate the overexpression of p53 protein as a prognostic factor in invasive cervical cancer. Forty-three formalin fixed, paraffin wax embedded blocks of invasive cervical can-cers were examined using immunohistochemical staining with a monoclonal antibody against p53. The result were as follows : 1. Immunostaining for p53 consistent with overexpression was seen in 23.8%(5 of 21) of stage I cancers and in 13.7%(4 of 22) of stage II cancers. 2. Immunostaining for p53 consistent with overexpression was seen in 21.6%(8 of 37) of squamous cell carciomas and in 0%(0 of 6) of adenocarcinomas. 3. The incidence of p53 overexpression was 25.0%(1 of 4) in cases with lymph node metastasis, compared with 17.9%(7 of 39) in cases without lymph node metastasis. 4.. The incidence of p53 overexpression was 20.0%(8 of 40) in cases with less than 4 cm, compared with 0%(0 of 3) in cases with equal to or larger than 4cm. In conclusion, p53 overexpression was not associated with stage, histologic type, and tumor size. However, there were trend for p53 overexpression to increase in patients with lymph node metastasis.

Esophagus, Stomach & Intestine; Adenocarcinoma Arising from Barrett's Esophagus: A case report / 대한소화기내시경학회지

Barrett's esophagus is a metaplastic process in which the squamous epithelium of the lowet esophagus is replaced by columnar epithelium. Most cases are believed to be related to prolonged gastroesophageal reflux. Detection of Barretts esophagus is important in that it results in adenocarcinoma in about 10% of patients. We report a case of adenocarcinoma arising from Barrett's esophagus in a 56 year-old man, diagnosed incidentally at a physical check-up. Grossly, the esophagogastric junction was irregular and there were two small ulcers in the lower esophagus. Microscopically, ihe squamous epithelium of the lower hagus was replaced by specialized intesinal mucosa with a small focus of adenocarcinona confined to the submucosa in one area. Many separate dysplastic foci were also present in the nearby esophageal mucosa.

Clonality of Large Regenerative Nodule Accompanied by Hepatocellular Carcinoma

In order to clarify the preneoplastic nature of large regenerative nodules without dysplastic change, we analysed the clonality of hepatocellular carcinomas (HCCs) and large nodules, diameter > or =0.5 cm, of cirrhotic liver by X-linked human androgen receptor (HUMARA) gene assay, using the principle of random X chromosome methylation and inactivation in female. Ten cases of HCC and 5 cases of large nodules without dysplasia from 9 female patients were selected. All the tumors, large nodules and paired normal control cells were selectively microdissected from deparaffinized hematoxylin and eosin stained slides. Genomic DNA was isolated and digested with HhaI. Polymerase chain reaction(PCR) amplication of the HUMARA locus was performed using 32P-a-dCTP containing PCR mixtures. The PCR amplified products were separated by gel electrophoresis and analysed by autoradiography. Nine HCCs from 8 patients were monoclonal and 1 case was polyclonal and the remaining 1 case was not polymorphic at the HUMARA locus. The HCC case which showed polyclonality contained many inflammatory cells. All the large nodules were polyclonal by HUMARA assay. These results suggest that all or most of the cells composing the large regenerative nodules without dysplasia are polyclonal. This assay may be informative for the differentiation between regenerative and preneoplastic nodules in cirrhotic liver and the size of nodule may be not important in hepatocarcinogenesis.