Histogenesis of medullary carcinoma of the thyroid

Abstract

SYNOPSIS Thirty-one dog thyroid tumours and 28 spontaneous rat thyroid tumours were studied histologically and the findings compared with those of a study of 67 cases of medullary carcinoma of the human thyroid.Five of the dog tumours and 24 of the rat tumours were considered to belong to the same group of tumours as medullary carcinoma, a group characterized by solid sheets or lobules of uniform cells with granular cytoplasm and without papillary or follicular differentiation. In the rat tumours it was shown that the cell of origin was the parafollicular cell and not the thyroid follicle epithelial cell.It is suggested that medullary carcinoma is also derived from a parafollicular cell and that this origin would resolve the discrepancy between the relatively good prognosis and the apparently undifferentiated structure of this tumour. It is also concluded that the whole spectrum of clinical and pathological features of medullary carcinoma makes more sense if it is considered as a parafollicular cell tumour.Medullary carcinoma of the thyroid is a distinct and clearly defined entity, and the histological features of 67 examples are discussed in the previous paper (Williams, Brown, and Doniach, 1966). The survival of patients with this tumour is often prolonged although paradoxically the vast majority of cases show no evidence of differentiation towards a thyroid epithelial pattern. This paradox is based on the assumption that medullary carcinoma of the thyroid is derived from the thyroid follicular epithelial cells; if this were not so then the absence of papillary or follicular structures would not necessarily imply a lack of differentiation. A second type of thyroid epithelial cell, the 'light' or parafollicular cell, is well described in many animals and the concept that medullary carcinoma of the thyroid is a parafollicular cell tumour seemed plausible.

The Oncogenic Activity of RET Point Mutants for Follicular Thyroid Cells May Account for the Occurrence of Papillary Thyroid Carcinoma in Patients Affected by Familial Medullary Thyroid Carcinoma

“…Stimulation of MAPK is a hallmark of RET activation. 1 Thus, as a read-out of RET signaling, we measured MAPK phosphorylation levels by blotting with phospho-specific antibodies. Expression of the different RET oncogenes in PC Cl 3 cells was accompanied by constitutive phosphorylation of MAPK; however, MAPK activation levels were approximately fourfold higher in RET/PTC than in RET point mutants expressing cell clones ( Figure 4C).…”

“…We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/ PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. We show that the various RET point mutants, but not wild-type RET, scored constitutive kinase activity and exerted mito- Medullary thyroid carcinoma (MTC) is a malignant tumor arising from neural crest-derived calcitonin-secreting C cells of the thyroid, 1 whereas papillary thyroid carcinoma (PTC) derives from endoderm-derived follicular cells. 2 MTC often occurs in the context of autosomal dominant multiple endocrine neoplasia type 2 syndromes (MEN2), whereas PTC is sporadic in most of the cases.…”

Nodular Amyloidosis in the Trachea of a Dog

“…This neoplasm was studied by WILLIAMS [6] who stated that in rats it definitely arose from the parafollicular cell; he suggested tlie same origin i n man and dog. None of this group of five neoplasms in dogs in his series produced…”

Prognostic factors in medullary carcinoma of the thyroid

“…Since its identification as a distinct form of thyroid cancer (Hazard et al 1959) and the demonstration that it arises from the parafollicular cells (Williams 1966), subsequently shown to belong to the APUD (amine precursor uptake and decarboxylation) system (Pearse 1968), medullary thyroid carcinoma (MTC) continues to attract interest with respect to its endocrinology.…”