Thyroid gland
Miscellaneous
Clear cell change

Author: Shahidul Islam, M.D., Ph.D. (see Authors page)

Revised: 26 October 2016, last major update March 2009

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Clear cell change [title]

Cite this page: Clear cell change. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidclearcell.html. Accessed December 5th, 2016.
Definition / General
  • Nonspecific finding in benign and malignant thyroid tumors; also seen in Hashimoto's thyroiditis and dyshormonogenetic goiter

  • Follicular adenoma and carcinoma: due to empty vacuoles associated with dilated endoplasmic reticulum and Golgi (Ultrastruct Pathol 2001;25:361, Am J Surg Pathol 1988;12:240) or intracellular lipid and mucin (Acta Cytol 2002;46:757)
  • Follicular carcinoma with McCune-Albright syndrome: due to uncontrolled fatty acid synthesis (Mod Pathol 1999;12:969)
  • Lipid-rich cell adenoma: due to neutral fat
  • Medullary carcinoma: may be thyroglobulin negative (Hum Pathol 1985;16:844)
  • Papillary carcinoma: due to glycogen
  • Signet ring or lipoblast type tumors: vacuoles may contain thyroglobulin (Am J Surg Pathol 1985;9:705)
  • Undifferentiated carcinoma: due to glycogen
Case Reports
Gross Images

Images hosted on PathOut server:

Nodular hyperplasia with
clear cell change (AFIP)

Micro Images

Images hosted on PathOut server:

Courtesy of Andrey Bychkov, M.D., Ph.D.

Hashimoto's thyroiditis with clear cells

Nodular hyperplasia



Papillary carcinoma

Clear cell change

Clear cell change
(follicular variant)



Follicular neoplasms

Follicular carcinoma

Follicular neoplasm with clear cell change

Signet ring follicular adenoma



Oncocytic neoplasms

Sharp demarcation between clear and oncocytic cells

Gradual transition from oncocytic to clear cells

Both patterns exist in same cell



Renal cell carcinoma metastases

Clear cell type

Signet ring follicular
adenoma is thyroglobulin+

Cytology Description
  • Follicular carcinoma:
    • Clearing due to intracellular lipid and mucin
    • Cohesive sheets of round/oval cells with abundant pale staining cytoplasm, tumor cells often cluster around branching capillaries, also frequent fat cells with discrete cell borders, cytoplasm distended by fat globules and eccentric nuclei (Acta Cytol 2002;46:757)
Positive Stains
Electron Microscopy Images

Images hosted on PathOut server:

Signet ring follicular adenoma (AFIP)

Marked dilation of
cisternae of granular
endoplasmic reticulum (AFIP)

Differential Diagnosis