Sustentacular cells in sporadic paraganglioma-like medullary thyroid carcinoma: report of a case with diagnostic and histogenetic considerations

Sustentacular cells (SCs) are glial supporting cells of the fetal, adult normal, and neoplastic extra and adrenal human chromaffin cell lineage. SCs have also been identified in some cases of medullary thyroid carcinoma (MTC), raising both diagnostic and histogenetic problems. We report a rare case of a sporadic paraganglioma-like variant of MTC showing numerous S-100 protein and glial fibrillar acid protein (GFAP) positive SCs encircling neoplastic cells in a nesting (Zellballen) pattern similar to that observed in paragangliomas or pheochromocytomas. Although stromal amyloid deposits were only focally detected, diagnosis was immunohistochemically confirmed by immunoreactivity of the neoplastic cells for cytokeratin, CEA, calcitonin, chromogranin A, neuron-specific-enolase, and synapthopysin. As for the histogenesis of SCs, if we assume that MTC is a neural crest-derived tumor, it is likely that these cells reflect the ability of the common precursor cell to differentiate towards a sustentacular-type glial cell lineage in addition to the typical neuroendocrine one. This viewpoint is supported by the evidence that rare cases of MTC may contain neoplastic or supporting cells showing a multidirectional differentiation (usually neuroendocrine and melanocytic) that recapitulates the different cell lineages arising from the developing neural crests.