The Prognostic and Biological Significance of Cellular Heterogeneity in Medullary Thyroid Carcinoma: A Study of Calcitonin, L-Dopa Decarboxylase, and Histaminase

Scott M. Lippman, Geoffrey Mendelsohn, Donald L. Trump, Samuel A. Wells, Stephen B. Baylin

Research output: Contribution to journalArticle


We evaluated the cellular distribution of calcitonin (CT), L-dopa decarboxylase (DDC), and histaminase [diamine oxidase (DAO)] in 33 patients with medullary thyroid carcinoma (MTC). CT immunostaining was uniform (>90% of the cells) and intense (4+) in lesions from 7 patients with C-cell hyperplasia and 6 with microscopic MTC: conversely, patchy CT staining (<40% of the cells) and diminished intensity (1+) were found in metastases from 8 patients who died of virulent disease. In 17 patients who underwent thyroidectomy for macroscopic cervical MTC with no evident distant metastases, CT staining was intense (3−4+) and homogeneous (>90%) in 11 subjects who were well 0.5-16 yr postoperatively. Six patients with similar clinical presentations had heterogeneous staining for CT in primary tumor (< 40% of the cells; 1−2+ intensity); 5 died of disseminated MTC 0.5-5 yr postoperatively (P < 0.001). Biochemical studies of distant metastases revealed an inverse relationship between the distribution of CT and that of both DDC (r = −0.71; P < 0.01) and DAO (r = −0.81; P < 0.001). We conclude that cellular heterogeneity in MTC tissue is associated with a distinct biochemical pattern, and its presence, whether in a primary or metastatic lesion, indicates a virulent neoplasm associated with a grave prognosis.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - Feb 1982


ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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