Porposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I)

BACKGROUND: Cancer registries are fundamental for cancer control and multicenter collaborative research. However, there have been discrepancies among pathologists in classifying cancer and assigning the codes according to the International Classification of Disease Oncology 3 (ICD-O3). To improve the quality of cancer registries as well as to prevent the conflict with medical insurance compensation, a guideline for the coding of cancer is mandatory. METHODS AND RESULTS: Funded by the Management Center for Health Promotion, 40 members of the Gastrointestinal Pathology Study Group and the Cancer Registration Committee of the Korean Society of Pathologists participated in the 1st workshop for gastrointestinal tumor registration. The subjects of gastric epithelial tumor, intramucosal carcinoma of the colon, carcinoid tumor, gastrointestinal stromal tumor and appendiceal mucinous tumor were discussed to create a guideline. A survey to obtain consensus for the guideline proposed by the workshop was carried out by the members of the Korean Society of Pathologists and 240 members completed the questionnaire. CONCLUSION: Although there are some issues to be discussed further, such as coding of high grade dysplasia/adenoma and intramucosal carcinoma of stomach and colon, the members agreed upon most parts of the proposed guideline. Therefore, we suggest using the ICD-O3 coding guideline for gastrointestinal tumor.

Mesenchymal Hamartomas of the Liver: Comparison of Clinicopathologic Features between Cystic and Solid Forms

Mesenchymal hamartoma (MH) of the liver is an uncommon benign lesion related to ductal plate malformation. It is usually cystic and mainly composed of myxoid mesenchymal tissue with tortuous or cystic bile ducts. In order to characterize the clinicopathological features of MH, the Korean Gastrointestinal Pathology Study Group collected a total of 17 MH cases diagnosed in 7 hospitals from 1992 to 2002 and compared the clinicopathologic findings of cystic MH with those of solid variant. Among the 17 cases, 7 (41%) were solid. The solid form showed a higher serum level of alpha-fetoprotein (AFP), the smaller bile ducts, and more frequent proliferation of vessels. Serum AFP level was related to the amount of hepatocytes. Two of seven solid cases harbored a larger amount of evenly distributed hepatocytes and proliferation of small duct with focal hepatocyte-bile duct transition. These histologic findings are similar to those of mixed hamartoma. Therefore, the mixed hamartoma and the MH of both solid and cystic types could be the variants of one disease spectrum. And hepatocytes within MH might be rather a genuine tumor component than entrapped into the tumor. In conclusion, MH can show various clinicopathological features and recognition of these features will facilitate accurate diagnosis of MH.

Clinicopathologic Features of Granulomatous Mastitis

BACKGROUND: Granulomatous mastitis (GM) is a rare chronic inflammatory condition that clinically mimics a carcinoma. The diagnosis of idiopathic GM depends on the exclusion of other granulomatous inflammations. The purpose of this study is to correlate the clinicopathological features of GM with etiologies. METHODS: We reviewed the clinical records of 58 cases that were histologically diagnosed as GM. We performed special stains for microorganisms such as Ziehl-Neelsen, periodic acid Schiff and gram stains, and polymerase chain reaction (PCR) for Mycobacterium tuberculosis (TB PCR). RESULTS: The mean age of patients was 35.3 years. Most patients were parous except three. Seven patients (12.1%) were related with pregnancy or lactation. TB PCR was positive in nine patients (15.5%). Five patients (8.6%) had gram positive bacilli that were recognizable as coryneform bacteria. Culture study demonstrated Staphylococcus aureus in only one case. Infectious GM had a greater tendency to form abscesses. Fat necrosis was more likely to be present in idiopathic GM, but other histological features were similar to each other. Twenty-two cases (37.9%) showed recurrence. CONCLUSIONS: We suggest that TB PCR and gram stain are essential tests for the differential diagnosis of GM, because the histologic features considerably overlap irrespective of the various etiologies.

Mucinous Cholangiocarcinoma associated with Clonorchis sinensis Infestation: A Case Report / 대한간학회지

Mucinous cholangiocarcinoma, characterized by large quantities of mucin production, is a rare subtype of peripheral cholangiocarcinoma and usually shows rapid progression and a fatal outcome. We report here a case of mucinous cholangiocarcinoma in a 69 year-old man, who was infected with Clonorchis sinensis. Histologically, the tumor was an adenocarcinoma with extensive intracellular and extracellular mucin production, up to 70% of the tumor mass and there was frequent lymphovascular invasion of the tumor cells. The liver adjacent to the mass contained eggs of Clonorchis sinensis in the bile duct lumen and showed ductal epithelial hyperplasia, mucinous metaplasia and adenomatous proliferation of intramural glands. The patient was treated with a right hepatectomy. Four months after the surgery, the tumor recurred in the soft tissue of the right flank.

Alagille Syndrome: A Case Report

Alagille syndrome is a rare autosomal dominant disorder showing complicated systemic manifestations, although the hepatic manifestations are predominant in many patients. We report a case of Alagille syndrome in a male baby who presented with a heart murmur at 2 days old and his echocardiography showed aortic stenosis. He presented with acholic stool and jaundice at 3 months old and a liver biopsy revealed paucity of the interlobular bile duct in the portal tract. This progressed to cirrhosis, for which a liver transplantation was performed at 10 months old. The explanted liver showed biliary-type cirrhosis with severe cholestasis. There was an absence of the interlobular bile ducts on microscopic examination. Bile duct paucity, associated with cholestasis, a peculiar face (prominent forehead, deep-set eyes, pointed mandible and bulbous nasal tip), and cardiac anomaly were observed, which were consistent with Alagille syndrome. He died of heart failure.

Rhabdoid Cholangiocarcinoma: A Variant of Cholangiocarcinoma with Aggressive Behavior

A rhabdoid cholangiocarcinoma is a very rare variant of sarcomatous cholangiocarcinomas. Here, we report a vimentin positive cholangiocarcinoma showing rhabdoid features in the entire tumor, with a very aggressive behavior. A 41-year-old woman was admitted to our hospital due to a huge hepatic mass. The resected liver revealed a 17x15cm sized solid mass with extensive necrosis and an infiltrative border. On microscopic examination, the entire tumor was composed of loosely cohesive round to polygonal cells, with rhabdoid features having abundant eosinophilic glassy cytoplasm and eccentrically located vesicular nuclei. Some tumor cells contained intracytoplasmic mucin vacuoles, but definite areas of glandular differentiation or spindle cell were not found. Immunohistochemical staining showed a diffuse strong positive reaction to pan-cytokeratin and vimentin, and focal positivity for the carcinoembryonic antigen. Other immunohistochemical stainings for cytokeratin 7, cytokeratin 20, S-100 protein, HMB-45, desmin, alpha-smooth muscle actin, c-kit, CD34, alpha-fetoprotein, anti-hepatocyte antigen, chromogranin and synaptophysin were all negative. After two months, the patient developed a local recurrence along the resection margin, and multiple hematogenous metastases to the lung and liver were seen on the follow-up CT scan.

Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2 in Adenocarcinomas of The Gallbladder

BACKGROUND: Matrix metalloproteinase (MMP)-2 and MMP-9 degrade type IV collagen and are antagonized by the tissue inhibitors of metalloproteinase (TIMP)-2 and TIMP-1, respectively. METHODS: We studied by immunohistochemistry the expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 72 cases of adenocarcinoma of the gallbladder. RESULTS: The MMP-2, MMP-9 and TIMP-1 expressions were significantly higher in well/moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, in adenocarcinomas that had invaded the lamina propria/proper muscle than in those that had invaded the perimuscular connective tissue or beyond the serosa, and in adenocarcinomas with fungating growth than in those with infiltrative growth. The TIMP-2 expression showed a similar pattern without statistical significance. Regarding the status of lymph node metastasis, the MMP-2 expression was significantly higher in cases without lymph node metastasis. The MMP-2 and MMP-9 expressions were significantly related to those of TIMP-2 and TIMP-1, respectively, with regard to depth of invasion, differentiation, and growth patterns of the adenocarcinomas. CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 are suggested to play important roles in the progression to early invasion of adenocarcinomas, in which the function of MMP-2 is inhibited by TIMP-2.

A Case of Antiphospholipid Antibody Syndrome Accompanied by Valvular Heart Disease and Moya Moya Syndrome

A case of antiphospholipid antibody syndrome, accompanied by valvular heart disease and Moya moya syndrome, has never been reported. Here, we report on a case that had mitral regurgitation and Moya moya syndrome, associated with antiphospholipid antibody syndrome secondary to systemic lupus erythematosus. This patient underwent a mitral valve replacement for mitral valve regurgitation. The postoperative course was uneventful, and the pathological findings of the mitral valve showed a degenerative change, due to chronic inflammation, a proliferative fibrous change and calcification, but without thrombus formation. However, the patient returned to the hospital with a cerebral hemorrhage, which was caused by Moya moya syndrome. Surgical drainage was performed, and the patient was discharged without any complications. The patient is on anticoagulation and immunosuppression drugs, with no problems to date.

Calcitonin Producing Middle Ear Carcinoid with Amyloid Deposition: A Case Report

Carcinoid tumor of the middle ear cavity is a rare neoplasm of low malignant potential. It grows slowly and rarely metastasizes. We recently experienced a case of carcinoid tumor of the middle ear cavity occurring in a 51-year-old female who was presented with hearing loss and tinnitus of the right ear. A 1 cm sized pinkish soft mass was noted in the promontory of the middle ear. Histologically, the mass was composed of nests and cords of tumor cells with slightly pleomorphic nuclei and eosinophilic cytoplasm. The extracellular matrix was glassy pink, homogeneous and exhibited apple green birefringence under a polarized light microscope after Congo red staining. The tumor cells showed immunoreactivity for cytokeratin, chromogranin A, synaptophysin, neuron-specific enolase and calcitonin. Electron microscopic examination confirmed the presence of neurosecretory granules. The production of calcitonin and amyloid by the tumor cells suggests the possible relationship of this tumor to the thyroid C cells.

Multicentric Occurrences of Hepatocellular Carcinoma / 대한간학회지

No abstract availalbe.

Teratoid Hepatoblastoma: Multidirectional Differentiation of Stem Cell of the Liver

Hepatoblastoma is the most common malignant hepatic neoplasm of childhood, showing a wide spectrum of epithelial and mesenchymal components. Teratoid hepatoblastoma, which reveals multiple lines of tissue differentiation such as mucinous epithelium, melanin pigment, endocrine differentiation, glial and mesenchymal components, has rarely been observed. We report a case of teratoid hepatoblastoma in a 22-month-old girl. She had been diagnosed with hepatoblastoma through percutaneous needle biopsy of the liver and treated with 10 chemotherapy cycles of epirubicin, VP-16 and cisplatin and with hepatic artery embolization. After 10 months, an extended left lobectomy was performed. Grossly, a multinodular, partly well-demarcated, solid mass (7 x 5 cm) with dense fibrosis and focal cystic change occupied almost the entire specimen. There was extensive necrosis due to preoperative treatment. Microscopically, the tumor showed multiple lines of differentiation, which was composed of embryonal, fetal hepatocytes and mesenchymal elements with numerous foci of osteoid. There were also other components showing endodermal, neural, melanocytic and endocrine differentiation. These teratoid components were considered relatively resistant to preoperative chemotherapy, in contrast to extensive necrosis of both embryonal and fetal hepatocytes. These teratoid features of hepatoblastoma are considered to be a multidirectional differentiation of the small epithelial cells or stem cells of the tumor.

Intestinal Type of Cholangiocarcinoma Associated with Hepatolithiasis / 대한간학회지

No abstract available

A case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma in the liver / 대한내과학회지

Mucoepidermoid carcinoma is a common malignant tumor of the salivary glands, but rare in other sites. Only 10 cases of mucoepidermoid carcinoma of liver have been reported, and there was 1 case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma. The definite diagnosis and pathogenesis are still controversial. However, hepatocellular carcinoma is the second most common cancer in Korea. Its etiology is better known compared to mucoepidermoid carcinoma. We report a rare case of double primary cancer of mucoepidermoid carcinoma and hepatocellular carcinoma in liver.

Angiomyolipoma / 대한간학회지

No abstract available

Biliary Papillomatosis / 대한간학회지

No abstract availalbe.

Pathological Analysis of 62 Liver Biopsy Cases with Hepatocellular Cholestasis: Drug and Toxin Induced Liver Injury

BACKGROUND: Hepatocellular cholestasis denotes the alteration of bile secretion by hepatocytes. The causes, degree of hepatocyte injury and concomitant bile duct loss are considered to influence the clinical course. METHODS: The causes and pathological features of hepatocellular cholestasis were analyzed in 62 cases of liver biopsies; and the causes of primary biliary cirrhosis, primary sclerosing cholangitis, and biliary obstruction were not included. RESULTS: The mean age of the patients was 42.2 years, and the ratio of male to female was 1.8:1. Fifty-eight cases (94%) showed cholestatic hepatitis, and 4 cases (6%) showed pure cholestasis without hepatitis activity. The majority of the cases (52 cases, 84%), including 19 cases of herbal medicine, was related to drugs. Loss of bile duct was found in 12 cases (19%), which were all cases of chronic cholestasis. All of them had drug histories, including 9 cases of herbal medicine. Clinical follow-up was performed in 9 out of the 12 cases with bile duct loss, and all of them showed elevated total bilirubin and/or alkaline phosphatase levels for more than 6 months. CONCLUSION: Drugs are the major cause of hepatocellular cholestatic hepatitis/cholestasis; and information about drugs, including herbal medicines, should be considered for proper evaluation of liver biopsy with hepatocellular cholestasis. Bile duct loss should be evaluated in the cases of chronic hepatocellular cholestasis, especially in drug induced cases.

Sclerosing Hepatic Carcinoma / 대한간학회지

No abstract availalbe.

Expression Pattern of DNA Mismatch Repair Genes in Tumors of Microsatellite Mutator Phenotype

Microsatellite mutator phenotype (MMP) tumors were reported in a subset of gastrointestinal carcinomas. The molecular pathogenesis of MMP tumors shows defects in the DNA mismatch repair genes, and also many germline and somatic mutations were reported in the MMP tumors. However, the detection of genetic defects in the MMP tumors is very difficult, mainly because many genes are included in the DNA mismatch repair genes. This study was undertaken to determine the best strategy for detecting defects in the DNA mismatch repair genes in gastrointestinal carcinomas. One of the effective ways for detecting defects in DNA mismatch repair genes is to screen the MMP tumors and evaluate the products of DNA mismatch repair genes by performing the multiplex RT-PCR method. We have screened the MMP tumors by using 5 microsatellite markers in the 12 cancer cell lines, 120 colon carcinomas and 99 gastric carcinomas and found 6 MMP cell lines, 10 MMP colon cancers, and 9 MMP gastric carcinomas. In addition, we evaluated 6 DNA mismatch repair gene products (hMSH2, hMSH3, hMSH6, hMLH1, hPMS1 and hPMS2) by multiplex RT-PCR analysis and found decreased expression of the DNA mismatch repair genes in 5 (hMSH6 in DLD-1 and HCT-15; hMSH2 in LoVo; hMLH1 and hMSH3 in HCT-116; hMLH1 in SNU-638) out of 6 MMP cell lines. We also found a decreased expression of hMLH1 in 3 out of 10 MMP colon carcinomas, and in 6 out of 9 MMP gastric carcinomas. Our results indicate that the expression analysis of the DNA mismatch repair genes by multiplex RT-PCR method can reduce the number of genes subjected to mutational analysis and is convenient for screening the responsible DNA mismatch repair genes.

Sarcomatoid Hepatocellular Carcinoma / 대한간학회지

No abstract availalbe.

Non-cirrhotic Portal Hypertension in Idiopathic Myelofibrosis: A case report

We report a case of non-cirrhotic portal hypertension in a 73 year-old woman, who had 19-year history of idiopathic myelofibrosis. There were esophageal varix, splenomegaly, and ascites. The biopsied liver showed irregular sinusoidal/ perisinusoidal fibrosis and occasional central-to-central fibrous connection. In areas with extensive fibrosis, coarse collagen fibers filled the sinusoidal spaces and compressed hepatocytes. However, nodular regeneration was absent. Double immunohistochemical stain for smooth muscle actin and proliferation cell nuclear antigen (PCNA) revealed diffusely activated stellate cells, some of which showed nuclear PCNA staining. There was also extramedullary hematopoiesis with bizarre megakaryocytes. The portal vein and its branches were patent. Idiopathic myelofibrosis is a rare cause of non-cirrhotic portal hypertension: the portal hypertension was considered to be the result of sinusoidal/perisinusoidal fibrosis in this case.