Thyroid gland
Miscellaneous
Clear cell change

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

Revised: 22 February 2017, last major update March 2009

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: clear cell change thyroid

Cite this page: Clear cell change. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidclearcell.html. Accessed December 16th, 2017.
Definition / general
  • Nonspecific finding in benign and malignant thyroid tumors; also seen in Hashimoto 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)

Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D.

Hashimoto 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

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Signet ring follicular adenoma (AFIP)

Marked dilation of
cisternae of granular
endoplasmic reticulum (AFIP)

Differential diagnosis