Contributed by Siddharth Bhattacharyya, MD; Simion Chiosea, MD
The patient is a man in his 70s who presented with an isolated thyroid nodule in the right mid-lower pole. He subsequently underwent fine needle aspiration, and specimens were submitted for cytology interpretation and molecular testing.
CYTOLOGY (per outside report)
"The Papanicolaou stained direct smears show small follicular cells with uniform nuclei admixed with clusters of atypical follicular cells with enlarged irregular nuclei, nuclear crowding and frequent nuclear grooves."
The cytology diagnosis was "Atypia of undetermined significance (Bethesda Category III)". ThyroSeq® was performed and showed a VHL p.I147Vfs*12 frameshift mutation resulting in premature stop-gain (33% allelic frequency). Also noted was VHL allelic imbalance/copy number alteration and very low expression of thyroid lineage markers* (TSHR, KRT7, KLK1, SLC5A5).
TSHR: encodes Thyroid stimulating hormone receptor
KRT7: encodes Cytokeratin 7
KLK1: encodes Kalikrein-1
SLC5A5: encodes Sodium/Iodine Cotransporter
DIAGNOSIS and DISCUSSION