Calcitonin Non-Secreting Mixed Medullary-Papillary Thyroid Carcinoma: Report of a Rare Entity and Therapeutic Implications

Abstract

Background: Medullary thyroid carcinoma (MTC) is a relatively rare and aggressive form of thyroid malignancy arising from parafollicular cells. The biochemical hallmark of MTC is elevated serum calcitonin (CTN), which aids initial diagnosis and disease surveillance. An atypical form of calcitonin non-secreting MTC has been previously described, with just over 50 cases published in the literature. This case report of a true mixed medullary-papillary thyroid carcinoma with a non-secretory medullary component is exceptionally rare. Clinical Case: A 67-year-old male presented with new-onset hoarseness and was found to have a 4 cm thyroid nodule replacing the right lobe with associated ipsilateral cord paralysis and ipsilateral cervical lymphadenopathy. The patient had no family history of endocrinopathies. A diagnosis of MTC was rendered at core-needle biopsy, based on the characteristic morphological findings and positive immunohistochemistry (IHC) for calcitonin (CTN) and CEA. Cervico-thoracic CT demonstrated tracheal and esophageal involvement by the tumor. The serum CEA was 8.7 pg/ml [0-5]; however, serum CTN was undetectable < 2 pg/ml [2-8.2]. The patient subsequently underwent a total thyroidectomy with bilateral central neck dissection and right lateral neck dissection. Excision of the tumor necessitated the dissection of involved esophageal muscle from mucosa and removal of four tracheal rings with part of the cricoid. The surgical specimen demonstrated a single 3.6 cm tumor in the right thyroid lobe composed of medullary and papillary intermixed neoplastic cells (mixed MTC-PTC) with predominant medullary component and gross extrathyroidal extension. Positive IHC for calcitonin, CEA, and thyroglobulin confirmed the diagnosis. Out of ninety resected lymph nodes in total, five nodes were involved with medullary carcinoma (with extranodal extension), and three had papillary carcinoma micrometastases. Postoperatively, the patient underwent adjuvant external beam radiation to the surgical bed. At four-month follow-up, CEA levels were 1.4 pg/ml [0-5], TSH 0.04 µIU/ml [0.35-4.9] and thyroglobulin (Tg) with Tg Ab levels were undetectable. The patient continues close surveillance. Conclusion: Calcitonin non-secreting MTC management is challenging due to the lack of a reliable biomarker that aids initial diagnosis, surveillance, and prognostic stratification. Whether a rare form of non-secretory MTC represents a more aggressive variant is yet to be determined. The prognosis of patients with mixed MTC-PTC tumors appears to be driven by the medullary component that prioritizes the optimal surgical approach and further management.