Single thyroid tumour showing multiple differentiated morphological patterns and intramorphological molecular genetic heterogeneity

Aims: A 49-year-old man presented with a single thyroid tumour that showed a combination of conventional papillary carcinoma, follicular variant of papillary carcinoma, clear cell papillary carcinoma, columnar cell carcinoma and poorly differentiated carcinoma. As all of the morphologies have been associated with papillary carcinoma in the literature, we wished to determine if they contained identical or different molecular abnormalities. Methods: Targeted next generation sequencing (NGS) of each morphological component and metastases was performed. Results: NGS revealed a BRAF p.K601E mutation in both the clear cell papillary carcinoma and poorly differentiated carcinoma and a KRAS p.G12R mutation in the papillary carcinoma, follicular variant. Two different areas of columnar cell variant were tested, with one showing a KRAS p.G12D mutation but no mutation in the other area. A KRAS p.G12R mutation was seen in the metastatic clear cell variant. Two different lymph nodes had metastatic columnar cell carcinoma, one negative for mutations but the other with a compound KRAS p.G12R and KRAS p.G12V mutation on different alleles. No mutations including BRAF and KRAS were seen in the conventional papillary carcinoma. Conclusions: Although all of the morphological patterns in this tumour have been reported as having aetiological or other association with one another, there was only partial concordance with their molecular signatures. There was significant molecular discordance, however, even with identical morphologies.