Thyroid & parathyroid

Papillary thyroid carcinoma

Main variants

Papillary thyroid carcinoma - classic

Deputy Editor-in-Chief: Nat Pernick, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Bin Xu, M.D., Ph.D.

Topic Completed: 7 April 2020

Minor changes: 28 May 2021

Copyright: 2020,, Inc.

PubMed Search: Classic papillary thyroid carcinoma[TIAB]

Bin Xu, M.D., Ph.D.
Page views in 2020: 5,318
Page views in 2021 to date: 11,701
Cite this page: Xu B. Papillary thyroid carcinoma - classic. website. Accessed December 6th, 2021.
Definition / general
  • Classic variant of papillary thyroid carcinoma is characterized by two cardinal features:
    • The presence of true papillae defined as papillae with a central vascular core
    • Nuclear features in the overlying epithelial cells defined by nuclear enlargement, nuclear membrane irregularity and a distinct chromatin pattern
Essential features
  • Defined by two cardinal features: true papillae with a fibrovascular core and nuclear features of papillary carcinoma
  • One of the most common types of papillary carcinoma
  • Tendency to spread to regional lymph nodes
  • High frequency of BRAF V600E mutation
  • Papillary carcinoma, conventional type (variant)
  • Papillary carcinoma, usual type (variant)
ICD coding
    • ICD-O: 8260/3 - papillary adenocarcinoma, NOS
    • ICD-10: C73 - malignant neoplasm of thyroid gland
  • One of the most common variants of papillary thyroid carcinoma (J Clin Endocrinol Metab 2014;99:E276)
    • Previously was most common type of papillary thyroid carcinoma but now papillary microcarcinoma and papillary thyroid carcinoma, follicular variant are more common
  • Female predominance; F:M ratio = ~3:1
  • Median age of diagnosis in 50s
  • Ionizing radiation is the best established risk factor, including:
    • Iatrogenic (e.g., radiation for head and neck cancer)
    • Post Chernobyl nuclear accident (Endocr Pathol 2006;17:307)
    • Post atom bomb
  • Can be familial in 4.5% of cases (Surgery 2009;145:100)
Clinical features
  • Painless palpable thyroid mass
  • Typically, the diagnosis is first rendered on ultrasound guided pre-operative fine needle aspiration cytology
  • Surgical pathology report of a resected specimen provides further information about the subtyping (i.e., variant) and microstaging
Radiology description
  • Diagnostic thyroid ultrasound with survey of cervical lymph nodes is the recommended imaging modality for patients with thyroid nodule(s) (Thyroid 2016;26:1)
  • The following ultrasound findings are associated with thyroid carcinoma, in particular papillary thyroid carcinoma (Thyroid 2016;26:1):
    • Hypoechogenicity compared with surrounding thyroid or strap muscles
    • Irregular border
    • Microcalcification
    • Tall shape (i.e., a nodule that is taller than wide measured on a transverse view)
Radiology images

Images hosted on other servers:

ATA nodule sonographic patterns

Prognostic factors
  • AJCC pathologic staging and the American Thyroid Association (ATA) initial risk stratification provide prognostic information (Amin: AJCC Cancer Staging Manual, 8th Edition, 2018, Thyroid 2016;26:1)
  • Pathologic parameters included in the risk stratification for a classic variant of papillary thyroid carcinoma are:
    • ATA intermediate risk: microscopic invasion into perithyroidal soft tissue, lymphovascular invasion and > 5 pathologically positive lymph nodes with all involved lymph nodes < 3 cm in size
    • ATA high risk: gross extrathyroidal extension, incomplete resection, distant metastasis and pathologic nodal metastasis ≥ 3 cm in greatest dimension
Case reports
  • Commonly treated with surgical resection (e.g., total thyroidectomy, subtotal thyroidectomy, hemithyroidectomy or lobectomy)
  • Post operative radioactive iodine treatment may be considered if the tumor exhibits aggressive features (ATA intermediate or high risk) (Thyroid 2016;26:1)
Gross description
  • Solid or cystic mass with papillary projections
Gross images

Contributed by Bin Xu, M.D., Ph.D.

Thyroid mass

Frozen section description
  • Frozen section of papillary thyroid carcinoma is strongly discouraged as frozen artifacts distort the nuclear features necessary for diagnosis
  • The standard care is to perform pre-operative fine needle aspiration to establish the diagnosis and to determine the most appropriate surgical procedure
Microscopic (histologic) description
  • Characterized by two cardinal features:
    • The presence of true papillae defined as finger-like projection with a fibrovascular core
    • The lining cells show nuclear features of papillary carcinoma, defined as 1) nuclear enlargement, 2) nuclear membrane irregularity and 3) chromatin clearing
  • Lack diagnostic features of other aggressive variants (e.g., tall cell variant, columnar variant and hobnail variant)
  • Other histologic findings that may be present include:
    • Psammoma bodies: laminated microcalcification, common in classic variant
    • Prominent cystic degeneration / cystic change
    • Ossification or dystrophic calcification
Microscopic (histologic) images

Contributed by Bin Xu, M.D., Ph.D.

Papillary projections

Nuclear features

Psammoma body

Cystic change with BRAF V600E

Osseous metaplasia

Cytology description
  • Cytology sample shows nuclear features of papillary thyroid carcinoma: oval nuclei, nuclear overlapping, nuclear membrane irregularity, powdery chromatin, chromatin margination, nuclear grooves and nuclear pseudoinclusions
  • In classic variant, large papillary projections may be seen in cytology samples
Cytology images

Contributed by Bin Xu, M.D., Ph.D.

Papanicolaou stain

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Thyroid, left lobe and isthmus, left hemithyroidectomy:
    • Papillary carcinoma, classic type, 2.3 cm (see synoptic report)
Differential diagnosis
  • Papillary foci of Graves disease or other papillary hyperplasia
    • May have abundant papillary infoldings and the cytoplasm may be tall or columnar
    • However, the nuclei are small and round and lack nuclear clearing
  • Medullary thyroid carcinoma, papillary variant
    • May occasionally contain true papillary architecture (so called papillary variant)
    • Lesional cells show nuclear features of neuroendocrine tumors with “salt and pepper” nuclei
    • Positive for calcitonin, synaptophysin and chromogranin
Board review style question #1

A thyroid tumor is resected, as shown above. What is the most common molecular alteration of this tumor?

  1. BRAF V600E mutation
  2. HRAS Q61R mutation
  3. NRAS Q61R mutation
  4. RET-PTC rearrangement
Board review style answer #1
A. BRAF V600E mutation. This is papillary thyroid carcinoma, classic type.

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Reference: Classic papillary thyroid carcinoma
Board review style question #2
Which of the following histologic findings is a feature of classic type of papillary thyroid carcinoma?

  1. Composed entirely of follicles
  2. Nuclei of the lesional cells are small and round without nuclear membrane irregularity
  3. Contains well formed papillae with a fibrovascular core
  4. Lesional cells have a cell height at least 2 - 3 times of the cell width
Board review style answer #2
C. Contains well formed papillae with a fibrovascular core

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Reference: Classic papillary thyroid carcinoma
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