Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution.

Ten cases of the rare solid and cystic pancreatic tumors are presented. All except one occurred in young women (mean age, 25 +/- 9.2 years). The large neoplasms were evenly distributed across the pancreas; in one case, metastasis occurred; all other cases were free from disease after complete resection. Histologic hallmarks of solid and cystic neoplasms were papillary growth, large intracytoplasmic granules, and immunoreactivity with alpha 1-antitrypsin, alpha 1-antichymotrypsin, phospholipase A2, and neuroendocrine markers (neuron-specific enolase [NSE], synaptophysin). This suggests both endocrine as well as exocrine differentiation.

Two cases of somatostatinomas of the major and minor papilla are reported. The tumors were characterized by solid trabecular and tubular arrangements of tumor cells and in one case by the presence of microvilli and psammoma bodies. The tumor cells contain many amine precursor uptake and dicarboxylation (APUD)-granules with a diameter of 300 to 500 nm and low electron density. Immunoperoxidase stain showed intense staining only for somatostatin and low density of neuron-specific enolase. Those tumors either resulted from pluripotent endocrine cells or from D-cells of the mucosa or glands of the papilla.

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Phospholipase A2, injected as a bolus into the jugular vein of adult male Wistar rats was investigated with respect to its action upon lung morphology and blood- plasma- histamine. In comparison with the injection of saline, phospholipase A2 causes hyperemia of the lungs, sequestration of granulocytes and intraalveolar pulmonary edema; the histamine level is increased to the sixfold. Pretreatment of the animals with indomethacin diminishes the toxic effect of phospholipase A2 upon the lungs and the histamine level.