Squamous Cell Differentiation in Metastatic Papillary Thyroid Carcinoma: Metaplastic

Document Type: Case Reports


1 APHP GHU Avicenne, Bobigny, France

2 Université Paris Nord Sorbonne Cite, Bobigny, France



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.


  • Lymph node metastases  thyroid papillary thyroid carcinoma may show squamous cell differentiation.
  • The immunophenotype of this type of metaplasia is CK5/6 P63 TTF1 (thyroid transcription factor 1), thyroglobulin and, B-Raf (V-Raf murine sarcoma viral oncogene homolog B1).
  • Squamous cell differentiation in AHL: papillary thyroid carcinoma (PTC) cervical lymph node metastasis has to be  from a synchronous primary squamous cell carcinoma of a lung or other origin


Acosta AM, Pins MR. Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis. Virchows Arch 2016;468(2):239-42.   https://doi.org/10.1007/s00428-015-1875-8        PMid:26521063

Harada T, Shimaoka K, Katagiri M, Shimizu M, Hosoda Y, Ito K. Rarity of squamous cell carcinoma of the thyroid: autopsy review. World J Surg 1994;18(4):542-6.   https://doi.org/10.1007/BF00353760            PMid:7725742

Rosai J. Rosai and Ackerman's Surgical Pathology. 10ed. Philadelphia PA: Elsevier; 2011.

Bond JA, Wyllie FS, Ivan M, Dawson T, Wynford-Thomas D. A variant epithelial sub-population in normal thyroid with high proliferative capacity in vitro. Mol Cell Endocrinol. 1993;9(2):175-83.      https://doi.org/10.1016/0303-7207(93)90121-Y

Jensen K, Patel A, Larin A, Hoperia V, Saji M, Bauer A, et al. Human herpes simplex viruses in benign and malignant thyroid tumours. J Pathol. 2010;221(2):193-200. https://doi.org/10.1002/path.2701           PMid:20455254   

Benvenga S, Alesci S, Trimarchi F, Facchiano A. Homologies of the thyroid sodium-iodide symporter with bacterial and viral proteins. J Endocrinol Invest. 1999;22(7):535-40. https://doi.org/10.1007/BF03343605              PMid:10475151  

Rausch T, Benhattar J, Sutter M, Andrejevic-Blant S. Thyroid carcinoma with papillary and squamous features: report of a case with histogenetic considerations. Pathol Res Pract. 2010;206(4):263-9.       https://doi.org/10.1016/j.prp.2009.05.003      PMid:19493635

Romano RA, Ortt K, Birkaya B, Smalley K, Sinha S. An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS One. 2009;4(5):e5623.      https://doi.org/10.1371/journal.pone.0005623     PMid:19461998 PMCid:PMC2680039

Cameselle-Teijeiro J, Abdulkader I, Pérez-Becerra R, Vázquez-Boquete A, Alberte-Lista L, Ruiz-Ponte C et al. BRAF mutation in solid cell nest hyperplasia associated with papillary thyroid carcinoma. A precursor lesion? Hum Pathol. 2009;40(7):1029-35.  https://doi.org/10.1016/j.humpath.2008.11.015      PMid:19269016   

Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, et al.  BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22(29):4578-80.     https://doi.org/10.1038/sj.onc.1206706     PMid:12881714

Nowara E, Huszno J, Slomian G, Nieckula J. Skin toxicity in BRAF(V600) mutated metastatic cutaneous melanoma patients treated with vemurafenib. Postepy Dermatol Alergol. 2016;33(1):52-6.     https://doi.org/10.5114/pdia.2015.48045    PMid:26985180 PMCid:PMC4793055