Top 10 Clear Cell Head and Neck Lesions to Contemplate

Head Neck Pathol. 2023 Mar;17(1):33-52. doi: 10.1007/s12105-022-01518-6. Epub 2023 Mar 16.


Background: Optically clear cytoplasm may occur in neoplastic and non-neoplastic conditions, either as a characteristic feature of a disease entity or as a morphologic rarity, potentially creating diagnostic dilemmas in various organ systems. In the head and neck, clear cell change can occur in lesions of salivary, odontogenic, thyroid, parathyroid, or sinonasal/skull base origin, as well as in metastases to these regions.

Methods: This review elaborates the top ten clear cell lesions in the head and neck, emphasizing their distinguishing histologic, immunohistochemical, and molecular attributes, and presents a rational approach to arriving at an accurate classification.

Results: Cytoplasmic pallor or clearing may be caused by accumulations of glycogen, lipid, mucin, mucopolysaccharides, water, foreign material, hydropic organelles, or immature zymogen granules. Overlapping morphologic features may present a diagnostic challenge to the surgical pathologist. Similarity in immunohistochemical profiles, often due to common cell type, as well as rare non-neoplastic mimics, furthers the diagnostic conundrum.

Conclusions: The top ten lesions reviewed in this article are as follows: (1) clear cell carcinoma (salivary and odontogenic), (2) mucoepidermoid carcinoma, (3) myoepithelial and epithelial-myoepithelial carcinoma, (4) oncocytic salivary gland lesions, (5) squamous cell carcinoma, (6) parathyroid water clear cell adenoma, (7) metastatic renal cell carcinoma (especially in comparison to clear cell thyroid neoplasms), (8) sinonasal renal cell-like adenocarcinoma, (9) chordoma, and (10) rhinoscleroma.

Keywords: Clear cell; Head and neck; Odontogenic; Salivary; Sinonasal; Skull base; Thyroid.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma, Clear Cell* / pathology
  • Carcinoma, Renal Cell*
  • Carcinoma, Squamous Cell*
  • Epithelial Cells / pathology
  • Humans
  • Kidney Neoplasms*
  • Salivary Gland Neoplasms* / diagnosis
  • Salivary Gland Neoplasms* / pathology