Immunohistochemical study of mucin expression in periampullary adenomyoma.

BACKGROUND/PURPOSE: Benign tumors and tumor-like conditions in the ampullary area are uncommon, and there are extremely rare cases of adenomyoma (AM) and adenomyomatous hyperplasia (AMH). Surgical treatment is necessary if these lesions cause biliary obstruction. In addition, the differential diagnosis of AM and AMH from carcinoma is often difficult by standard endoscopic biopsy and cytopathological analysis that may show differential findings, resulting in unnecessary surgeries sometimes being performed. METHODS: Immunohistochemical (IHC) analysis of periampullary AM and AMH was performed. RESULTS: For both types of lesions, epithelial glandular cells (EGCs) showed diffuse expression of MUC6 and focal expression of HIK1083, mainly in the inner region, and focal expression of MUC5AC, mainly at the surface. The EGCs showed no expression of MUC1 or MUC4, both of which were identified as malignant tumor markers in our previous series of mucin expression studies in pancreatobiliary tumors. The expression of CK7, which was diffusely positive in normal periampullary mucosa, was decreased in the EGCs of AM and AMH. CONCLUSIONS: A combined evaluation of IHC findings may be effective in the detection of AM and AMH, and also in distinguishing benign periampullary lesions, such as AM and AMH, from ampulla of Vater adenocarcinoma, thus avoiding excessive surgery.

Mucin expression profile in pancreatic cancer and the precursor lesions.

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary-mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.

Two families with Wilson disease in which siblings showed different phenotypes.

We investigated two families with Wilson disease in which siblings showed different clinical phenotypes and different ages at onset. In Family 1, the second and fourth male children demonstrated onset of the neurological type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In Family 2, the second male child showed neurological symptoms at 32 years of age and was diagnosed as having the hepatoneurological type of Wilson disease; then the 35-year-old first female child was found to have the hepatic type by familial screening. We performed mutation analysis of the ATP7B gene for these patients, and found that the mutation was a compound heterozygote in both families. Previous reports of siblings with Wilson disease have shown an identical clinical phenotype and similar ages at onset. In addition, hepatic-type cases generally occur at lower ages compared with the neurological type. In the present investigation, however, younger patients showed neurological symptoms earlier than their older siblings, and clinical phenotypes differed among siblings in both families. These cases appear to be rare. Individual differences in copper accumulation in hepatic cells and intolerance to copper toxicity might be the reason for this phenomenon. Furthermore, there might be a difference in the dominance of the allele expressing ATP7B protein among these cases, resulting in different clinical phenotypes, because all patients of both families were found to be compound heterozygotes.