Pathology of Sporadic and Hereditary Medullary Thyroid Carcinoma

Abstract

Although cases of “malignant goitre with amyloid stroma” had already been described by the turn of this century in the German literature (Burk 1901; Jaquet 1906; Stoffel 1910), it is only 30 years since medullary carcinoma of the thyroid (MTC) was first clearly separated from the other types of thyroid carcinoma (Hazard et al. 1959). During the following decade, the classical histological features of MTC were described (Williams et al. 1966), the thyroid C-cell as the cell of origin delineated (Williams 1966), and the link with calcitonin (CT) production demonstrated (Cunliffe et al. 1968; Milhaud et al. 1968). It was, in addition, realized that a proportion of cases of MTC were genetically determined, occurring in association with phaeochromocytoma, or with phaeochromocytoma and multiple mucosal neuromas (Williams 1965; Schimke et al. 1968; Williams and Pollock 1966). Afterwards, the terms multiple endocrine neoplasia (MEN) 2 and MEN 3 were introduced by Steiner et al. (1968) and Khairi et al. (1975), respectively, to distinguish these combinations of tumours from Wermer’s syndrome (parathyroid, pituitary, and endocrine pancreatic tumours), which was given the name MEN 1 as it was described first. MEN 2 has been subsequently subdivided into MEN 2A (which includes MTC, phaeochromocytoma, and hyperparathyroidism) and MEN 2B (which refers to the neuromata syndrome including MTC, phaeochromocytoma, mucosal neuromata, gastrointestinal ganglioneuromatosis and marfanoid habitus) (Chong et al. 1975), and the term MEN 2B is now more commonly used than MEN 3 to designate the neuromata syndrome. The genetic defects leading to the development of familial MTC inherited in the setting of the MEN 2 syndromes are described in detail in R.F. Gagel et al., this volume. The aetiology and concrete pathogenesis of sporadic (non-hereditary) MTC has, in contrast, not yet been elucidated. It is, however, generally accepted that exogenous factors such as hypercalcaemia, hypervitaminoses D and A and irradiation known to be associated with higher incidence of MTC in various mammals are not carcinogenic to human C-cells (Saad et al. 1984a).

Supported by the Deutsche Forschungsgemeinschaft, the Hamburger Krebsgesellschaft and the Hamburger Stiftung zur Förderung der Krebsbekämpfung.

The skilful technical assistance of Mr. Jochen Koppelmeyer in preparing the micrographs is gratefully acknowledged.