Sui Zee

BACKGROUND: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are intraductal tumors with variable amounts of papilla formation, mucin production, and cytoarchitectural atypia. Associated invasive carcinomas, reported to occur in up to 30% of patients, often are mucinous and clinically indolent. METHODS: The clinical and pathologic features of 28 IPMNs resected at Memorial Sloan-Kettering Cancer Center between 1983 and 1997 were reviewed. RESULTS: There were 16 females and 12 males with a mean age of 68 years (range, 44-79 years) and a mean tumor size of 4.5 cm (range, 1.5-11.0 cm). The head of the gland was the predominant tumor site (89%). Abdominal pain, weight loss, and acholic stool were the most common symptoms at presentation. According to histology, two types of papillae were identified: intestinal (22 patients) and pancreatobiliary (6 patients). In the intraductal component, cytologic atypia was minimal (i.e., intraductal papillary-mucinous [IPM] adenoma) in 2 patients and moderate (IPM borderline tumor) in 5 patients, and severe atypia (IPM carcinoma in situ) was seen at least focally in 21 patients. In addition, invasive carcinoma was identified in 15 patients (53%), 4 of whom had only microscopic foci. Invasive carcinoma was of the mucinous type (colloid) in six patients and of the tubular type (conventional ductal adenocarcinoma) in nine patients. At a median follow-up of 35 months, four patients died of disease; two of these patients had only borderline atypia with no identified in situ or invasive carcinoma in the sections submitted. Eighteen patients had no evidence of disease, 1 patient was alive with recurrent disease, and 5 patients died of other causes. The actuarial 5-year disease free survival rate was 78%. Of the 14 patients with invasive carcinoma, 5 of 6 patients with colloid type tumors were free of tumor at a mean of 55 months. Of the patients with tubular type invasive carcinoma, two patients died of their disease (at 4 years and 7 years), three patients died of other causes, and four patients were alive (three were free of disease, and one experienced disease recurrence) at an average follow-up of 7.5 years. CONCLUSIONS: Two distinct patterns of intraductal papillae are seen in patients with IPMNs: intestinal and pancreatobiliary. Both in situ and invasive carcinoma may be encountered more commonly than previously recognized. Tubular type invasive carcinomas occur as well as mucinous type (colloid) carcinomas. Although the neoplasms are less aggressive as a group than conventional pancreatic ductal adenocarcinoma, patients with IPMNs may pursue a deadly course, even in the absence of identifiable invasive carcinoma. Conversely, patients with tubular type invasive carcinoma arising in the background of IPMN may follow a more favorable course than patients with conventional ductal adenocarcinoma without IPMN, emphasizing the importance of recognizing the IPMN component in patients with pancreatic adenocarcinoma.

PURPOSE: In some organs (eg, the lung), endocrine tumors are classified on the basis of mitotic rate and necrosis. The purpose of this study was to evaluate prognostic factors in pancreatic endocrine neoplasms recently treated at a single institution. PATIENTS AND METHODS: In 136 patients undergoing surgery from 1979 to 1998, the influence on disease-free survival (DFS) and disease-specific survival (DSS) of tumor size, mitotic rate, vascular invasion, necrosis, metastases, and nuclear grade was determined. Cases were further grouped according to an existing proposed classification system and then regrouped on the basis of mitotic rate (< 2 mitoses per 50 high-power fields v higher) and necrosis (present or absent) into low- and intermediate-grade groups. RESULTS: Correlations with DFS and DSS in univariate analysis included < or = 2 mitoses per 50 high-power fields (P =.001, P =.002), vascular invasion (P =.02, P =.04), size < or = 2 cm (P =.01, P =.05), metastases (P =.0002, P =.07), necrosis (P =.002, P =.16), and nuclear grade (P =.04, P =.33), respectively. By multivariate analysis, for DFS, tumor necrosis and presence of metastases retained significance (P =.01, P =.04, respectively). For DSS, only mitotic rate was a prognostic factor (P =.02). Among the 18 macroadenomas, eight borderline tumors, and 48 low-grade carcinomas, there was no significant difference in DSS between any groups (P =.3). However, in evaluating our newly proposed groups, the differences in DFS and DSS between low- and intermediate-grade groups were highly significant (P =.0007, P =.006, respectively). CONCLUSION: Pancreatic endocrine neoplasms exhibit a spectrum of biologic behavior, and the proposed benign (macroadenoma) and borderline groups contain potentially aggressive tumors. An alternative system based on mitotic rate and necrosis correlates strongly with survival without specifically designating any group as benign.

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.

We tested the hypothesis that the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) could distinguish among carcinomas arising from different primary sites. A total of 384 cases of carcinomas primary to various organs, as well as 16 cases of malignant mesothelioma, were evaluated using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase technique. The subset of tumors strongly expressing both CK 7 and CK 20 included virtually all bladder transitional cell carcinomas and the majority of pancreatic adenocarcinomas; the tumors negative for both CK 7 and CK 20 were largely restricted to hepatocellular, prostate, and renal cell carcinomas in addition to squamous cell and neuroendocrine carcinomas of lung. The CK 7-/CK 20+ immunophenotype, however, was highly characteristic of adenocarcinomas of colorectal origin, whereas CK 7+/CK 20- immunophenotype was typically seen in the vast majority of carcinomas arising from other sites, including ovary, endometrium, breast, and lung, as well as malignant mesothelioma. Gastric carcinomas were the most heterogeneous subgroup with respect to CK 7/CK 20 immunophenotype. In the subset of mucinous tumors, striking immunophenotypic differences were noted among those primary to the breast (CK 7+/CK 20-), gastrointestinal tract (CK 7-/CK 20+), and ovary (CK 7+/CK 20+). In all cases investigated, this CK immunophenotype was invariant in metastatic vs. primary tumors. It is concluded that, in the appropriate clinical setting, the CK 7/CK 20 immunophenotype of carcinomas is a valuable diagnostic marker in the determination of primary site of origin.

BACKGROUND: Peripheral intrahepatic cholangiocarcinoma (PIC) is an intrahepatic primary liver neoplasm which is clinicopathologically distinct from hepatocellular carcinoma and major duct cholangiocarcinoma. The clinical outcome after resection of these rare tumours is not well documented. METHODS: Review of the hepatic database and tumour registry at Memorial Sloan-Kettering Cancer Center identified 32 cases of PIC resected for cure over a 23-year period. Intrahepatic cholangiocarcinomas with major bile duct involvement were excluded from this analysis. Demographics, pathological features, biochemical markers, operative results and survival were analysed. RESULTS: The majority of patients presented with abdominal pain (n=19). Only two patients had pathological evidence of hepatic cirrhosis. Serum marker levels included 7-fetoprotein (AFP; median 3.7 (range 0-225) ng/ml) and carcinoembryonic antigen (CEA; median 1-6 (range 0-30) ng/ ml). Type of hepatic resection included: wedge (n=2), lobectomy (n=14) and extended lobectomy (n=16). There was one postoperative death. Median follow-up time was 27 months. Median survival was 59 months with an actuarial 5-year survival of 42 per cent. Vascular invasion and intrahepatic satellite lesions were predictors of worse survival (P < 0.05). CONCLUSION: PIC is a rare hepatic primary tumour, which usually presents in non-cirrhotic livers with a normal serum AFP and CEA level. In selected patients, complete surgical resection can be performed safely and is associated with long-term survival.