Kazuyoshi Nishihara

BACKGROUND: Although the biologic characteristics of papillary cystic tumors (PCT) generally indicate a good prognosis, a malignant form has been reported. METHODS: Twenty-two examples of PCT were examined to assess their malignant potential by histologic, flow cytometric, and immunohistochemical studies. RESULTS: Three had hepatic, peritoneal, and/or lymph node metastases (metastasizing tumors [MT]); the other 19 PCT had no such metastatic features (nonmetastasizing tumors [NMT]). Venous invasion was detected in all three MT and two NMT. Compared with the 19 NMT, the MT had a higher nuclear grade and more prominent necrobiotic nests characterized by aggregates of cells with pyknotic nuclei and eosinophilic cytoplasm. In the flow cytometric analysis of cellular DNA content, one MT was aneuploid, and eight NMT were diploid. Immunohistochemically, there was no difference between the MT and NMT. CONCLUSIONS: These results support the assumption that venous invasion, nuclear grade, and prominent necrobiotic nests are useful as histologic parameters to detect the malignant potential of PCT.

Twenty patients (7.4%) with adenosquamous carcinoma of the gallbladder were selected from 271 surgically resected gallbladder cancers. The 20 patients were composed of 8 men and 12 women with a mean age of 66.9 years. Histologically, all twenty tumors showed an abrupt transition between the adenocarcinoma (AC) and squamous cell carcinoma (SCC) areas, and well differentiated AC was also found in the peripheral area of the tumor. A histochemical and immunohistochemical study using alcian blue, periodic acid-Schiff, cytokeratins, involculin and tissue polypeptide antigen disclosed a different nature of the two components. DNA heterogeneity between the components was detected in 5 of 7 cases by flow cytometry. The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC areas (mean 20.55%) was larger than that of the AC areas (mean 11.40%) (P = 0.0029), which indicated that the SCC areas had a greater proliferative capacity than AC areas. These results suggest that the SCC component of adenosquamous carcinoma of the gallbladder arose by a stepwise molecular progression of the pre-existing AC. Furthermore, the prognosis of adenosquamous carcinomas of the gallbladder (mean survival: 10 months) in the advanced stage (pTNM 2-4) was less favorable than those of papillary and well differentiated AC (mean survival: 99 months and 86 months) (P < 0.0001).

BACKGROUND: In 1989, Morohoshi et al. reported an intraductal papillary neoplasm of the pancreas (IPNP), which was a morphologically distinct, but rare tumor. METHODS: Two cases with IPNP were analyzed by immunohistochemical and DNA flow cytometric methods. RESULTS: The patients included a 67-year-old man and a 71-year-old woman. Both tumors were characterized by a well-defined papillary growth in the cystically dilated main pancreatic ducts, associated with papillary and nonpapillary hyperplasia. Immunohistochemically, the tumor cells of both cases were positive for the epithelial markers (AE1/AE3 and CAM 5.2), and in one of the two cases, the tumor cells and hyperplastic cells surrounding the tumor conspicuously revealed multiple hormonal markers such as serotonin, somatostatin, glucagon, gastrin, and pancreatic polypeptide. The nuclear DNA content of the tumor cells of the first case, which showed moderate cellular atypia, was considered to be diploid, whereas that of the second case, which revealed severe atypia, was aneuploid. CONCLUSIONS: These results suggested that these tumors arose from multipotential stem cells capable of epithelial and neuroendocrine differentiation, and results of the flow cytometric study was related to the degree of cellular atypia of the tumors.