Thyroid & parathyroid

Papillary thyroid carcinoma

Other subtypes

Clear cell

Editorial Board Member: Marc Pusztaszeri, M.D.

Last staff update: 17 May 2023 (update in progress)

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PubMed Search: Clear cell papillary thyroid carcinoma

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Cite this page: Guilmette J. Clear cell. website. Accessed June 2nd, 2023.
Definition / general
  • Unusual morphologic subtype of papillary thyroid carcinoma (PTC) with retained papillary nuclear features and clear cytoplasm
  • Clear cell features are likely due to the mitochondrial expansion, abundant glycogen, lipid or thyroglobulin in the tumor cells (Am J Surg Pathol 1985;9:705)
Essential features
  • Rare papillary thyroid carcinoma subtype which comprises < 2% of all papillary thyroid carcinomas (Thyroid 2017;27:819)
  • Not associated with a worse prognosis
  • Needs to be distinguished from clear cell metastatic tumors to the thyroid
  • Papillary thyroid carcinoma, clear cell variant
  • Clear cell features are seen in < 2% of papillary thyroid carcinoma subtypes (Thyroid 2017;27:819)
  • M = F
  • Thyroid
Clinical features
  • Neck mass
  • May have obstructive symptoms
  • Neck ultrasound
  • Fine needle aspiration
  • Hemithyroidectomy versus complete thyroidectomy
Prognostic factors
Case reports
  • 49 year old woman with euthyroid status after total thyroidectomy due to functioning lung metastases from a clear cell variant of papillary thyroid carcinoma (Thyroid 2012;22:1084)
  • 64 year old woman diagnosed with clear cell variant of papillary thyroid carcinoma (J Med Cases 2019;10:113)
  • 79 year old woman with clear cell variant of papillary thyroid carcinoma with associated anaplastic thyroid carcinoma (Int J Surg Pathol 2019;27:658)
Gross description
  • Solitary or multifocal masses with average size of 1.9 cm (range: 0.2 - 5.5 cm) (Thyroid 2017;27:819)
  • Solid in consistency
  • Ranges from pale to white in color
  • Contour may be well defined to infiltrative
Microscopic (histologic) description
  • Architecture may be follicular, solid or papillary
  • Tumor cell cytoplasm may be entirely clear to somewhat granular
  • Nuclear size and shape range from largely round to irregular
  • Classic nuclear features of papillary thyroid carcinoma: enlarged overlapped nuclei, chromatin clearing, irregular contours, grooves and intranuclear cytoplasmic pseudoinclusions are frequently observed throughout the tumor
  • Tumor proportion with clear cell features may vary and can be only focal
  • Psammoma bodies may be seen
  • Necrosis, increased mitotic activity and cytological pleomorphism are worrisome features of dedifferentiation (Int J Surg Pathol 2019;27:658)
Microscopic (histologic) images

Contributed by Julie Guilmette, M.D.

Predominantly follicular architecture

Clear cell features

Nuclear characteristics

HBME1 stain

Cytology description
  • Cells show cytoplasmic clearing (Clin Nucl Med 2015;40:885)
  • Range from watery clear to granular in appearance
  • Cells are cuboidal to columnar in shape
  • Typical nuclear features of papillary thyroid carcinoma are present but may only be focal
Electron microscopy description
  • Reveals dilated empty mitochondria, which can explain the clear cell feature
  • Characteristic findings of conventional papillary thyroid carcinoma were observed as well (Am J Surg Pathol 1980;4:501)
    • Microvilli
    • Infolded nuclei
    • Nuclear bodies
Molecular / cytogenetics description
  • Few described molecular alterations (Thyroid 2017;27:819):
    • RAS mutation
    • PAX8::PPARy translocation
    • EML4::ALK translocation
    • TFG::MET translocation
Sample pathology report
  • Thyroid, total thyroidectomy:
    • Papillary thyroid carcinoma, clear cell subtype, 1.5 cm, isthmus (see synoptic report)
    • Negative for lymphatic invasion and extrathyroidal extension; resection margin negative
Differential diagnosis
Board review style question #1

Which of the following papillary thyroid carcinoma (PTC) subtypes shares a similar prognosis with classic / conventional papillary thyroid carcinoma?

  1. Clear cell papillary thyroid carcinoma
  2. Columnar papillary thyroid carcinoma
  3. Hobnail papillary thyroid carcinoma
  4. Solid papillary thyroid carcinoma
  5. Tall cell papillary thyroid carcinoma
Board review style answer #1
A. Clear cell papillary thyroid carcinoma

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Reference: Clear cell papillary thyroid carcinoma
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