October 2021 – Endocrine

A 54-year-old man underwent a right lobectomy for a right thyroid nodule. At time of surgery the thyroid was very firm, nodular, and adherent to the trachea. On gross examination, within the lower pole, there was a 2.2 cm, well-circumscribed, nonencapsulated, firm and white mass. 

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Which of the following is the most likely diagnosis?  

  • Fibrous variant of chronic lymphocytic thyroiditis
  • Squamous cell carcinoma
  • Sclerosing mucoepidermoid carcinoma with eosinophilia
  • Hodgkin's lymphoma

The correct answer is ...

Sclerosing mucoepidermoid carcinoma with eosinophilia.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare thyroid neoplasm and a described entity in the World Health Organization Classification of Tumours of Endocrine Organs. (1) SMECE occurs most often in women (female-to-male ratio of 7:1) and has been documented in a wide age range (32-89 years). (1,2) Patients usually present with a slow growing, painless thyroid mass. Unlike the association between conventional salivary gland mucoepidermoid carcinoma and the CRTC1-MAML2 fusion transcript, no consistent molecular alteration has been identified in SMECE. (3) 

Microscopically SMECE is characterized by a dense hyalinized fibrotic stroma, a mixed inflammatory infiltrate with abundant eosinophils, and a neoplastic cellular infiltrate with squamous and glandular differentiation. The neoplastic cells form thin strands and variable sized nest. By immunhistochemically staining the tumor cells are strongly reactive to antibodies against p63 and show variable reactivity to antibodies against TTF-1. (4,5) Special stain mucicarmine highlights the scattered mucocytes. 

SMECE invariably occurs in a background of chronic lymphocytic thyroiditis, therefore, a main differential is the fibrosing variant of chronic lymphocytic thyroiditis with squamous metaplasia. The squamous nests in lymphocytic thyroiditis should be relatively bland and not have malignant features, such as vascular or perineural invasion. Additional distinguishing features include fibrosis confined to the thyroid and lack of the following mucocytes, mucin pools, and abundant eosinophils. Primary thyroid squamous cell carcinoma (SCC) is a rare occurrence and is more likely to represent metastasis. Differentiating SCC from SMECE may be challenging, especially if the glandular component is not prominent. However, SCC tends to show more pronounced atypia, lacks mucin pools, and is less commonly associated with a prominent fibrohyalinized stroma with abundant eosinophils. Approximately one-third of SMECE cases will metastasize to lymph nodes (6) and can easily be mistaken for nodular sclerosing Hodgkin’s lymphoma. However, cohesive groups of cells and lack of Reed-Sternberg cells will help make the correct diagnosis.


  1. Lloyd, Ricardo V., et al. WHO Classification of Tumours of Endocrine Organs. International Agency for Research on Cancer, 2017.
  2. Chi-Yun, Lai., et al. “Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review” International Journal of Clinical & Experimental Pathology, vol. 8, no. 5, 2015, pp. 5947-5951
  3. Shah, Akeesha A., et al. “Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: a clinicopathologic and molecular analysis of a distinct entity.” Modern Pathology, vol 30, no. 3, 2017, pp. 329–339.
  4. Hunt, J., et al. “p63 expression in sclerosing mucoepidermoid carcinomas with eosinophilia arising in the thyroid.” Modern Pathology, vol 7, no. 5, 2004, pp. 526-529.
  5. Albores-Saavedra, J., et al. “Clear cells and thyroid transcription factor I reactivity in sclerosing mucoepidermoid carcinoma of the thyroid gland.” Annals of Diagnostic Pathology, vol 7, no. 6, 2003, pp. 348-353. 
  6. Shehadeh, N., et al. “Sclerosing mucodepidermoid carcinoma with eosinophilia of the thyroid: a case report and review of the literature.” American Journal of Otolaryngology, vol 25, no. 1, 2004, pp. 48-53. 

Lacey Schrader, M.D.

Fellow, Surgical Pathology
Mayo Clinic

Michael Rivera, M.D.

Consultant, Anatomic Pathology
Mayo Clinic

Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.