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.

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.

Intraductal oncocytic papillary neoplasm(IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm(IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas(DAs) and IPMNs(SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as with antibodies to mucins and differentiation markers(MUC1/MUC2/MUC5AC/MUC6/CDX2/HepPar-1) was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors. Expression of mesothelin and claudin-4 were dissimilar between these tumor types: a higher proportion of IOPNs labeled with mesothelin[21/24(87.5%) of IOPNs, 6/22(27%) of IPMNs, p<0.001], while the reverse was true for claudin-4[2/23(9%) of IOPNs, 9/22(41%) of IPMNs, p=0.01]. The results of immunolabeling for SMAD4/β-catenin/p53 were similar in both: None of the cases showed SMAD4 loss in the intraductal components and only 1/21(5%) of IOPNs and 2/22(9%) of IPMNs revealed abnormal β-catenin expression(p=0.49). Nuclear p53 accumulation was seen mostly in architecturally complex/high grade dysplasia areas in both. Immunolabeling for MUC proteins showed that almost all lesions expressed MUC5AC. 12/24(50%) of IOPNs and 6/22(27%) of IPMNs(p=0.11) labeled for MUC1, whereas 7/24(29%) of IOPNs and 10/22(45%) of IPMNs labeled for MUC2(p=0.25). MUC6 was expressed in 8/9(89%) of IOPNs(strong) and 6/21(29%) of IPMNs(weak)(p=0.002). 14/23(61%) of IOPNs and 4/22(18%) of IPMNs labeled for HepPar-1(p=0.003). These results show that IOPNs have distinct immunoprofile and provide support for the proposition that IOPN is a distinct entity developing through a mechanism different from other pancreatic ductal neoplasms.

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. Cancer 2002;94:62–77. © 2002 American Cancer Society.

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.

Forty-two women attending a colposcopy clinic for evaluation of abnormal cervical cytology and 13 normal controls were studied for the presence of lymphocyte proliferation (LP) cell-mediated immune (CMI) responses and serological reactivity to E7 peptides of human papillomavirus type 16 (HPV-16). HPV was typed by Southern blot hybridization of exfoliated cervicovaginal cell DNA. Positive LP responses (stimulation index /> 5-0) to one or more E7 peptides were observed in 28.6% (12 of 42) of patients and 23.1% (three of 13) of controls. Of patients infected with HPV-16, -31 or -33, 63"6 % (seven of 11) showed a positive LP response compared with 14.3 % (two of 14) of women infected with other HPV types (P = 0.02), 17'6 % (three of 17) negative for HPV (P = 0.02) and 23"1% (three of 13) of controls (HPV status unknown) (P = 0"05). Cterminal peptide 109 (amino acids 72 to 97) elicited positive LP responses in 45.4 % (five of 11) of patients infected with HPV -16, -31 or -33 compared with 7"1% (one of 14) patients infected with other HPVs (P = 0.04), 5"9 % (one of 17) of women negative for HPV (P = 0"02) and 7"7% (one of 13) of controls (P = 0.05). HPV-16 group-specific LP responses of borderline significance were also observed against E7 peptides 103,105 and 108 (17-37, 37-54 and 62-80) (P = 0.07). ELISA reactivity (IgG) to E7 peptide 109 (72-97) was present in 7"7 % (one of 13) of controls, 35.3 % (six of 17) of HPVnegative patients, 42.9 % (six of 14) of patients infected with other HPVs, and only 9.1% (one of 11) of patients infected with HPV-16, -31 or -33. CMI responses to C-terminal HPV-16 E7 peptide 109 (72-97) were thus significantly related to ongoing cervical infection with HPV-16 and closely related types, whereas serological reactivity to E7 peptides was not HPV type-specific.

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Sarcoma associated with osteonecrosis or bone infarction is a rare but well-documented pathological event. In this report, a 69-year-old man with sickle cell trait presented with malignant fibrous histiocytoma (MFH) in his distal tibia. The resected tumor was found in association with a large medullary infarct that extended 10 cm proximal from the tumor site. Bone infarcts can be caused by a number of processes including corticosteroid overuse, alcoholism, dysbarism, and hemoglobinopathies such as sickle cell disease. Patients with sickle cell anemia often develop osteonecrosis, but osteonecrosis has also been reported in people with sickle cell trait, albeit much more rarely. Our patient is only the third reported case of infarct-related bone sarcoma in a patient with sickle cell trait. Bone infarction may be a rare though serious consequence of sickle cell trait.