Calcitonin-secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis

Abstract

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

Keywords: calcitonin; ectopic; lung; neuroendocrine neoplasm; paraneoplastic; systematic review.

Figure 1

Flow diagram demonstrating the breakdown of the screening process.

Figure 2

CT scan with transverse plane view of the 4 × 4.5 cm right upper lobe lung lesion.

Figure 3

¹⁸FDG-PET coronal CT displaying two avid lesions, in the right upper lobe and left gluteal region.

Figure 4

(A) Haematoxylin & eosin staining of the left gluteal lesion composed of sheets of cells with abundant eosinophilic cytoplasm and eccentric nuclei with stippled chromatin, some with nuclear pseudo-inclusions. Twenty-five mitotic figures/2 mm slides. (B) Positive immunoperoxidase staining, ×100 magnification, A: Synaptrophysin, B: Calcitonin, C: PAX8, D: TTF1. (C) Negative immunoperoxidase staining, ×100 magnification, A: thyroglobulin, B: chromogranin.

Figure 5

Thyroid USS demonstrating a 2.6 cm left confluence of spongiform thyroid nodules, with hypoechoic halos (U2). No cervical lymphadenopathy.

Figure 6

⁶⁸Ga-DOTATATE PET/CT scan with arrows pointing to the upper lobe primary, pleural and nodal disease.