Objective : To present an interesting case of concurrent medullary and papillary carcinoma of the thyroid gland with mixed disease in several of the lymph node metastases.
Methods : Case Report
Results : A 56-year-old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical lymph node with suspicious sonographic features. Subsequent fine needle aspiration (FNA) demonstrated papillary thyroid cancer (PTC) in the left thyroid nodule and medullary thyroid cancer (MTC) in left cervical lymph node. She underwent a total thyroidectomy with bilateral modified lateral and central neck dissections. Histopathology demonstrated multifocal PTC, largest foci in the left lobe at 1.6 cm with 3/21 lymph nodes positive for metastatic PTC. Extensive c-cell hyperplasia was identified on multiple slides. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted with 1/21 lymph nodes positive for both medullary and papillary thyroid carcinoma within the same node. Pre-operative calcitonin level was 251 pg/ml which improved to 48 pg/ml post-operatively. RET proto-oncogene mutational analysis was negative. She received 148.8 mCi of I-131 with no evidence of distant metastasis. A follow-up ultrasound 6 months later displayed an abnormal left level 4 lymph node. FNA showed features of both PTC and MTC on the cytopathology itself. Immuno-histochemical stains on the aspiration displayed PTC while a subset of the tumor cells also stained positive for calcitonin. The patient underwent repeat central and left radical neck dissection. Histopathology demonstrated 3/6 lymph nodes positive for PTC in the central neck and 2/6 lymph nodes positive for intermixed papillary and medullary carcinoma in the left neck. Calcitonin decreased further to 15 pg/ml and suppressed thyroglobulin decreased to 1.6 ng/dL. She continues to be observed with stable tumor markers.
Discussion : The origin of MTC is embryologically distinct from that of PTC. Parafollicular C cells derive from ectodermal neural crest, whereas follicular cells are of endodermal origin. The incidence, histopathology, and prognosis vary significantly. Several cases reports describe synchronous occurrence of these two carcinomas, but a mixed lesion within the same lymph tissue is rare. Most reports support the 'collision' phenomenon suggesting that two independent tumors located in the same lesion are coincidental events. Recent genetic studies evaluating RET and BRAF mutations or RET/PTC rearrangements also support distinct clonal origins in coexisting PTC/MTC.
The simultaneous occurrence of thyroid carcinomas of different cellular origin is rare and can present as either discrete tumors or a mixed lesion.
Associate Professor of Medicine
Loyola University Medical Center
Clinical Educator at Loyola University Medical Center