Squamous Cell Differentiation in Metastatic Papillary Thyroid Carcinoma: Metaplastic Reversion or Progression?

Squamous cell differentiation (SCD) may occur in papillary thyroid carcinoma (PTC) only at metastatic sites. We have studied cytokeratin CK5/6 and P63 along with TTF1 (thyroid transcription factor 1) and B-Raf (V-Raf murine sarcoma viral oncogene homolog B1) immunohistochemical expression in neck lymph node metastases of thyroid PTC showing SCD. The patient (21-years) presented with a neck mass. The check-up revealed bilateral thyroid nodules. Total thyroidectomy and neck lymph node dissection were performed. The diagnosis was that of bilateral PTC with lymph node metastases (pT1N1Mx). The metastases were peculiar by the presence of cystic change and of SCD. The thyroid PTC expressed P63 focally and, TTF1 and B-Raf diffusely. Cytokeratin 5/6 was expressed only in the lymph node metastases, in the metastatic cyst lining and in the SCD foci. The P63+ cells outnumbered those CK5/6+. TTF1 expression was faint in SCD. Metastatic, both classical PTC- and SCD-epithelia expressed B-Raf. The expression patterns of CK5/6, P63, TTF1 suggest a luminal/central-to-abluminal/peripheral direction for SCD development from PTC-epithelia in lymph node metastases. Whether this metaplasia type may reflect a regression to a less aggressive morphotype or a progression-switch to squamous cell carcinoma-type differentiation in a composite tumor remains matter of debate.