Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Guilmette J. Clear cell. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidclearcellvariant.html. Accessed January 21st, 2025.
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
Terminology
- Papillary thyroid carcinoma, clear cell variant
Epidemiology
- Clear cell features are seen in < 2% of papillary thyroid carcinoma subtypes (Thyroid 2017;27:819)
- M = F
Sites
- Thyroid
Etiology
- May be related to thyroid stimulating hormone (TSH) overstimulation (Thyroid 2017;27:819)
Clinical features
- Neck mass
- May have obstructive symptoms
Diagnosis
- Neck ultrasound
- Fine needle aspiration
- Hemithyroidectomy versus complete thyroidectomy
Prognostic factors
- Similar to conventional / classic papillary thyroid carcinoma
- Angiolymphatic invasion, extrathyroidal extension and lymph node metastasis are associated with a worse outcome (Thyroid 2017;27:819)
- Rare case associated with anaplastic thyroid carcinoma (Int J Surg Pathol 2019;27:658)
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)
Treatment
- Similar to conventional / classic papillary thyroid carcinoma (Thyroid 2017;27:819)
- Surgical resection
- Lymph node dissection may be indicated
- Radioactive iodine may be used on case to case basis
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
Positive stains
Negative stains
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
- Follicular thyroid carcinoma with clear cell features:
- Does not have papillary thyroid carcinoma nuclear features
- Usually HBME1 negative
- Clear cell medullary carcinoma of the thyroid:
- Has C cell differentiation
- Positive for calcitonin, synaptophysin and chromogranin but negative for HBME1
- Stroma may have amyloid deposits
- Has C cell differentiation
- Intrathyroidal parathyroid tumors (Surg Pathol Clin 2019;12:1007):
- Most are composed of round, finely granular chief cells and occasionally oxyphilic / oncocytic cells
- Has PTH immunoreactivity
- Does not express TTF1 and thyroglobulin
- Metastatic clear cell renal cell carcinoma:
Board review style question #1
Which of the following papillary thyroid carcinoma (PTC) subtypes shares a similar prognosis with classic / conventional papillary thyroid carcinoma?
- Clear cell papillary thyroid carcinoma
- Columnar papillary thyroid carcinoma
- Hobnail papillary thyroid carcinoma
- Solid papillary thyroid carcinoma
- 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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Reference: Clear cell papillary thyroid carcinoma
