Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, known to have an increased risk of benign and malignant tumours. Medullary thyroid carcinomas (MTC) are rare tumours arising from the parafollicular cells and have been associated with multiple endocrine neoplasia type 2 (MEN2). The association of NF1 and MTC is rare, and are seldomly associated with other endocrine tumours.
A 23-year-old female with a history of chronic necrotising pancreatitis and background of NF1 was found to have an incidental large mediastinal mass (28x47x30mm), confirmed to be of neuroendocrine origin on biopsy. Further investigations with FDG and DOTATATE PET scans demonstrated a bulky thyroid with increased uptake in bilateral cervical chains. She was subclinically hyperthyroid with serum calcitonin 40,206pg/mL [0-10], CEA 19.0ug/L [<3] and normal metanephrines. The remainder of the pituitary panel was normal. A thyroid ultrasound noted a large left inferior pole solid, hypoechoic lesion 20x40x24mm in size with irregular margins and internal punctate echogenic foci of calcification (TIRADS 5). Subsequent biopsies of a left lobe nodule and bilateral cervical chain nodes confirmed metastatic medullary thyroid carcinoma. Calcitonin level on needle rinse at all biopsied sites was >80,000ng/L.
Multidisciplinary team reviews were suggestive of a contiguous thyroid and mediastinal mass likely MTC with significant retrosternal extension and lymph node metastasis. She underwent surgical resection of both masses with histopathology and gene sequencing pending. Adjuvant therapy will be considered dependent on her post-operative course.
This is a rare case of a MTC in a patient with NF1, with only a handful reported in literature to date. NF1 has been linked with thyroid carcinomas such as thyroid C-cell hyperplasia and papillary thyroid carcinoma. We await further results to determine whether there are direct links between the NF1 gene and MTC in our patient, or if co-existing culprit oncogene mutations are present.