Koro Sakoda

New classification of pancreatic intraductal papillary–mucinous tumour by mucin expression: its relationship with potential for malignancy

In previous studies of the expression of MUC1 (membrane‐bound type mucin) and MUC2 (intestinal type secretory mucin) in pancreatic tumours, invasive ductal carcinoma (IDC) usually showed MUC1+ and MUC2− expression, whereas intraductal papillary–mucinous tumour (IPMT) showed MUC1− and MUC2+ expression. Recently, however, many IPMTs have been collected, a considerable number of which have shown MUC1− and MUC2− expression. In the present study, the clinicopathological features were examined of 18 IPMTs with MUC2+ and 32 IPMTs with MUC2−, and their potential for malignancy was compared. Most of the IPMTs with MUC2+ were composed of dark columnar cells, whereas most of the IPMTs with MUC2− were composed of clear columnar cells. The incidence of carcinomatous change and invasive proliferation of the carcinoma in the MUC2+ tumours was significantly higher than in the MUC2− tumours. The clinical outcome for the patients with IPMT showing the MUC2+ pattern tended to be worse than for those with IPMT showing the MUC2− pattern, although the overall outcome for the two types of IPMT was significantly better than for those with IDC. Because of the differences in mucin expression pattern, morphological appearance and potential for malignancy between the two types of IPMT, we believe that they belong to different neoplastic lineages and that it may be reasonable to classify them as different entities, although the WHO classification contains a single clinicopathological entity of IPMT forming an adenoma–carcinoma sequence. In conclusion, our classification of IPMTs by MUC2 expression pattern may be of value in the better assessment of the biological behaviour of IPMTs and their potential for malignancy. Copyright

Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: Its relationship with the biological behavior of the tumor

Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non‐invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin‐labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P < 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2− expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P < 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be correlated with tumors that demonstrate an expansive growth pattern and lower levels of invasion and metastasis.

MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreas

The expression of MUC‐1 mucin (membrane‐associated mucin) and MUG2 much (secretory mucin) were immunohistochemically examined in 46 invasive ductal carcinomas (IDC) and 16 intraductal papillary mucinous tumors (IPMT) of the pancreas. lntraductal papillary mucinous tumors usually reveal expansive growth. However, of the 16 IPMT examined in the present study, three showed an invasive growth pattern, which was similar to ‘mucinous carcinoma’, around the non‐invasive growth areas. Of 46 IDC, MUCl much detected by monoclonal antibodies, DF3 and MY.1E12, was expressed in 44 cases (96%) and in 45 cases (98%), respectively, whereas MUC‐2 mucin detected by polyclonal antibody, anti‐MRP, was not expressed in any of the cases (0%). In contrast, in the non‐invasive growth areas of the 16 IPMT, MUG1 much detected by DF3 and MY.1 E12 was expressed in four cases (25%) and in six cases (38%), respectively, whereas MUG2 mucin detected by anti‐MRP was expressed in 13 cases (81%). The invasive growth areas of the three IPMT showed positive expression of MUG‐1 mucins detected by DF3 and MY.1E12, although the non‐invasive growth areas showed negative expression of MUG1 muclns, except for their focal positive expression in one of the three cases. These findings indicate that the invasive growth areas of IPMT acquire a characteristic of MUC‐1 much expression that is usually seen In IDC.

Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: Its relationship with tumor progression and prognosis

Our previous immunohistochemical studies in the pancreas, intrahepatic bile duct, and ampulla of Vater demonstrated that an invasive carcinoma with a poor outcome showed a pattern of MUC1 (membrane‐bound mucin) positive and MUC2 (intestinal‐type secretory mucin) negative, whereas many of the non‐invasive tumors with favorable outcome showed a pattern of MUC1 negative and MUC2 positive. The aim of this study is to compare the expression profiles of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas to gain insight into the relationship between the biological nature of the carcinomas and the role of mucins. We examined the expression profiles of MUC1 of different glycoforms and MUC2 in 60 extrahepatic bile duct carcinomas using immunohistochemistry. The expression of MUC1/CORE (core peptide of MUC1), MUC1/DF3 (core peptide of MUC1 with sialyl oligosaccharides) and MUC1/MY.1E12 (sialylated MUC1) showed a significant relationship with tumor progression factors such as poor differentiation, deep invasion, lymph node metastasis, lymphatic invasion or perineural invasion. In contrast, the expression of MUC1/HMFG‐1 (fully glycosylated MUC1) did not show a significant relationship with the tumor progression factors. In the different glycoforms of MUC1 examined, the expression of MUC1/DF3 and MUC1/MY.1E12 was related with the poor outcome of the patients. In contrast, the expression of MUC2 was inversely related with the tumor progression factors and poor outcome. In the 52 patients with advanced tumors, only MUC1/DF3 high expression correlated with poor prognosis. In conclusion, MUC1/DF3 was the most useful prognosis indicator among the various glycoforms of MUC1 mucins.

Lymphoepithelial cysts of the pancreas: demonstration of lipid component using CT and MRI.

We present two cases of surgically proven lymphoepithelial cyst (LEC) of the pancreas that had a lipid component visualized by CT and MRI. Identification of this component in a pancreatic cystic lesion is a key to favor the diagnosis of LEC or splenic epidermoid cyst over other cystic lesions when the lesion is noted in an elderly patient.

Ruptured bronchial artery aneurysm associated with pleural telangiectasis and tortuous portal obstruction : report of a case

A 25-year-old woman presenting with an emergent condition of massive hemothorax due to a ruptured bronchial artery aneurysm was successfully treated by transcatheter arterial embolization. She had previously undergone portosystemic shunt splenopneumopexy for hepatic portal hypertension at 6 years of age. When undergoing right thoracotomy for the removal of a clot, a prominent telangiectasis on the pleural surface was noted. The lesion appeared to be a rare systemic vascular abnormality although this could not be confirmed.

MUC1 mucin expression in follicular dendritic cells and lymphoepithelial lesions of gastric mucosa‐associated lymphoid tissue lymphoma

Membrane‐associated mucin MUC1 is expressed in various adenocarcinoma cells and active T lymphocytes. We tried to find out whether MUC1 is expressed in gastric mucosa‐associated lymphoid tissue (MALT) lymphoma lesion. MUC1 was not expressed in infiltrating T lymphocytes; however, MUC1 was found on the cell surface of follicular dendritic cells (FDC) of germinal centers and in the epithelial cytoplasm of lymphoepithelial lesion (LEL) of the lymphoma, which were immunohistochemically detected by monoclonal antibodies DF3 and MY.1E12. MUC1 was also expressed in the FDC of control cases (gastrectomy specimen containing reactive lymphoid follicles, n = 10, MUC1/DF3, 100%; MUC1/MY.1E12, 40%), and FDC in MALT lymphomas (n = 59) showed lower MUC1 expression rates (MUC1/DF3, 32%; MUC1/MY.1E12, 0%) than the control (P < 0.001). Lymphoepithelial lesion in the low‐grade MALT lymphomas (n = 23) showed a higher MUC1/DF3 expression rate (30%) than those in the high‐grade MALT lymphomas (n = 36; 6%; P < 0.05). T lymphocytes in the surface mucosa were more frequent in MALT lymphoma (91.4 ± 80.6/unit area) than those in the control (20.0 ± 23.6) (P < 0.001). S100‐positive dendritic   cells around LEL were more frequent in the low‐grade  (19.0 ± 9.4/unit area) than  in  the high‐grade (11.7 ± 9.7) (P < 0.005). This study demonstrated MUC1 mucin expression on FDC for the first time. Mucosa‐associated lymphoid tissue lymphoma, especially low‐grade, shows immunologically active state, where FDC MUC1 expression may be suppressed by some factors released from lymphoma cells. Further study to elucidate the pathogenetic role of MUC1 in MALT lymphoma is necessary.

Immunohistochemical studies of mucin antigens in pancreas and intrahepatic bile-duct tumors

Our previous studies of pancreatic and intrahepatic bile-duct tumors revealed that MUC2 mucin (“secretory mucin”, detected by a polyclonal antibody, anti-MRP) was highly expressed in intraductal papillary-mucinous tumors of the pancreas (IPMTs) and bile duct cystadenocarcinomas of the liver (BDCs) with expansive growth pattern and favorable prognosis, whereas it was rarely or not expressed in invasive ductal carcinomas of the pancreas (IDCs) and cholangiocarcinomas of the liver (CCs) with invasive growth pattern and poor prognosis. In contrast, MUC1 mucin (“membrane-bound mucin” detected by the monoclonal antibody, DF3) was rarely or not expressed in IPMTs and BDCs, but was always expressed in IDCs and CCs (Cancer 71:2191–2199, 1993;Int J Cancer 55:82–91, 1993). The results of these studies suggest that the difference in the expression of MUC1 and MUC2 mucins is a useful indicator of malignant potential in neoplasms of the pancreas and intrahepatic bile duct. This article is a review of our previous studies described above. In addition, we present longer-term follow-up data for the cases reported in our previous studies as well as demonstrating pathological prognostic factors, such as lymph node status, lymphatic infiltration, and perineural invasion. We also examined several additional cases of IPMTs and analyzed the same prognostic factors. We could confirmed the findings of our previous studies, and found that most IPMTs and BDCs with a MUC1(−) and MUC2(+) expression pattern showed less aggressive pathological factors than most IDCs and CCS with a MUC1(+) and MUC2(−) expression pattern.

Two Successfully Treated Cases with Ruptured Duodenal Varices.

十二指腸静脈瘤出血の2例を報告した.症例1は50歳の男性で, 主訴は下血.肝外門脈閉塞症手術の既往歴をもっていた.上部消化管X線造影・内視鏡検査によって十二指腸球部前壁に屈曲蛇行する隆起が認められ, 血管造影にて同部位に蛇行・拡張した血管が認められ, 血行郭清術を行った.症例2は69歳の女性で, 主訴は下血.肝硬変を有していた.内視鏡検査によって十二指腸下行脚に蛇行する隆起と同部位からの出血が認められた.内視鏡的硬化療法を行ったが, 再出血を起こしたため開腹下に血管結紮術を行った.2例とも術後経過は順調で再出血も認められていない.十二指腸静脈瘤は門脈圧亢進症の1病態としてまれにみられる.消化管出血を認めた場合には十二指腸まで十分に検索し, 十二指腸静脈瘤が出血源であることが判明したらなるべく早期に血管結紮術または血行郭清術を行うのが望ましいと考えられた.

External biliary decompression: a clinical study.

減黄術 (percutaneous transhepatic biliary decompression 54例, 胆道外瘻造設術11例) を施行した悪性腫瘍による閉塞性黄疸65例について種々の検討を行ったが, とくに減黄術後早期死亡 (24±14日以内) が17例 (26.1%) と高率であったことから, 予後不良因子について検討し以下の結果を得た.(1) 減黄術による種々の合併症が減黄術後早期死亡群では23.5%～35.3%と高率であり, これらの合併症が成績に大きく影響した.(2) 減黄前の病態や臨床検査成績から, 血清総ビリルビン値が25mg/dl以上, BUN/creatinine比が11以下の2因子の他に体重減少 (>10%), 胆管炎 (38℃ 以上の発熱, WBC>10,000), 腹水, 消化管出血およびStage IVの進行癌などの因子が成績を不良にしたと考えられた.