Insulinoma of the pancreas with insular-ductular differentiation in its liver metastasis - indication of a common stem-cell origin of the exocrine and endocrine components

We describe an insulinoma of the pancreas in a 56-year-old patient, which s howed insular-ductular differentiation in its liver metastasis. Although th e primary tumor was uniformly endocrine in nature with insulin production. the metastasis contained two distinct cell types in organoid arrangement. O ne cell type was insulin-positive and was arranged in islet-like structures ; the other was insulin-negative but distinctly pan-cytokeratin and cytoker atin 7 positive and arranged in ducts. In the primary tumor and the metasta sis. the tumor cells were surrounded by a desmoplastic stroma. As to the hi stogenesis of the tumor and its metastasis. we discuss the following possib ilities: (1) the tumor cells might derive from a common stem cell that matu res into two phenotypically different cell lines. resembling the situation in embryogenesis and (2) one tumor cell type originates from the other by t ransdifferentiation (metaplasia). We conclude that the parallel occurrence of endocrine and ductal differentiation supports the concept that, under ce rtain conditions, islet cells and ductular cells may also originate from is lets and that mixed endocrine/exocrine pancreatic tumors do not necessarily arise from totipotent duct cells but might also have a primary endocrine c ell origin. endocrine tumors arise within islets but rather originate from pluripotential stem cells or committed endocrine precursor cells of ducts [ 1]. Only rarely have neoplasms with extensive exocrine and endocrine differenti ation been observed [12, 13, 19, 26, 30]. Controversial issues are the exis tence of hybrid cells with both exocrine and endocrine characteristics [2, 5, 17] and the observations of Pour et al. [22] that probably all pancreati c tumors (exocrine and endocrine) arise from Langerhan's islets. In the pre sent report, a classical insulinoma of the pancreas is described which, in its liver metastasis. exhibited an endocrine insular and an exocrine ductul ar component. To the best of our knowledge, this situation has not been rep orted previously.