Thyroid gland
Thyroid cancer
Features to report

Author: Andrey Bychkov, M.D., Ph.D.

Revised: 18 January 2018, last major update December 2017

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Thyroid cancer [title] features "loattrfree full text"[sb]
Cite this page: Bychkov, A. Features to report for carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidfeatures.html. Accessed January 21st, 2018.
Definition / general
Essential features
  • Mandatory features to report (by CAP): procedure, tumor focality, tumor site, tumor size, histologic type, margins, angioinvasion, lymphatic invasion, extrathyroidal extension; number of lymph nodes examined and involved, size of the largest metastatic deposit, extranodal extension; pTNM
  • Important for cancer staging (AJCC / TNM), initial risk stratification (ATA) and treatment decision
Key features to report for Thyroid Cancer
  • Procedure
    • Lobectomy
    • Hemithyroidectomy: lobe with isthmus
    • Subtotal thyroidectomy: small portion of uninvolved thyroid gland is left to preserve endocrine function
    • Total thyroidectomy: entire gland, including posterior capsule, is removed
    • Completion thyroidectomy
  • Tumor focality
    • Unifocal
    • Multifocal
    • CAP note:
      • In multifocal cancers the protocol is applicable to the dominant excised tumor, which is defined as the most aggressive tumor - often but not necessarily the largest tumor
      • If the second tumor is clinically relevant (e.g. medullary carcinoma in case of papillary carcinoma), a second report can be generated
    • Comment:
      • Multiple foci, whether minute or large, ipsi- or contralateral, can be either independent tumors or may result from intrathyroid spread of index tumor, which is difficult to distinguish (Endocr Pathol 2012;23:101)
  • Tumor site (laterality)
    • Right lobe
    • Left lobe
    • Isthmus
    • Pyramidal lobe
  • Tumor size
    • Greatest dimension, in centimeters
    • CAP note: additional dimensions are optional
    • Comment:
      • Papillary cancers ≤ 1 cm and > 4 cm are associated with excellent and worse prognosis, respectively
      • Follicular cancer ≥ 3.5 cm has adverse prognosis
      • Average tumor size in Western practice is 2.5 cm, number of subcentimeter cancers is growing (from 20 - 30% in the USA to 80% in Korea) (J Endocrinol Invest 2017;40:683)
  • Histologic type (see topic: Thyroid gland - WHO classification - Major Updates)
    • Papillary carcinoma, specify variant
    • Follicular carcinoma, specify type
    • Poorly differentiated carcinoma
    • Anaplastic carcinoma, including just focal component
    • Medullary carcinoma
    • Comment:
      • Papillary microcarcinomas (≤ 1 cm), whether incidental / occult or nonincidental, are reported
      • Hürthle cell (oncocytic) tumors have been reintroduced as a separate entity in the new WHO classification
      • Poorly differentiated and anaplastic carcinomas are often seen with pre-existent well differentiated carcinoma
      • Minor component with high grade (insular, anaplastic) and "aggressive" histology (tall cell, solid, hobnail) can be of significance and is worth reporting as an additional feature
      • Papillary carcinoma is the most common type (up to 85 - 90% of all thyroid cancers) in daily practice, mainly represented by classic variant, follicular variant and microcarcinomas (Annu Rev Pathol 2017 Oct 30 [Epub ahead of print])
  • Margins
  • Angioinvasion (vascular invasion)
    • Present
    • Absent
    • Cannot be determined
    • CAP note: extent of invasion can be optionally reported as focal (< 4 vessels) or extensive (≥ 4 foci)
    • Comment:
      • Only extensive vascular invasion predicts adverse outcome (recurrence, distant metastasis and cancer related death) (Histopathology 2018;72:32)
      • Angioinvasion is mainly seen in encapsulated (follicular carcinoma, follicular variant of papillary carcinoma) or ex-encapsulated (poorly differentiated carcinoma) thyroid cancers
      • In nonencapsulated cancers, e.g. papillary carcinomas, it sometimes can be seen in the extraglandular component of the tumor associated with extrathyroidal extension
      • Vascular invasion is applicable to vessels of the tumor capsule or vessels beyond tumor interface
      • Areas of angioinvasion that are closely adjacent to one another are counted as separate foci (Hum Pathol 2015;46:1789)
      • Clinical significance - association with distant metastasis (bones / spine, lungs)
      • Extensive angioinvasion is a rare event, found in less than 10% of encapsulated well differentiated cancers (Hum Pathol 2015;46:1789)
  • Lymphatic invasion
    • Present
    • Absent
    • Cannot be determined
    • Comment:
      • Extremely common in papillary cancers, can be identified by peritumoral foci / seeds, psammoma bodies or (indirectly) by presence of nodal metastasis
      • Clinical significance - association with lymph node metastasis and multifocality
  • Extrathyroidal extension (ETE)
    • Present
    • Absent
    • Cannot be determined
    • Comment:
      • If present, specify extent as gross ETE (usually involving larynx / trachea, large vessels / nerves) or only microscopic / minimal ETE (perithyroid fat, strap muscles)
      • Gross ETE is identified by clinician on imaging and during surgery or by pathologist on grossing
      • Minimal ETE requires a tumor to extend beyond the contour of the gland with a desmoplastic response, invasion of strap muscles (reliable ETE) or at least perithyroidal fat (Thyroid 2016;26:512)
      • Clinical significance - association with recurrence
      • According to Amin: AJCC Cancer Staging Manual, 8th ed, 2017, minor extrathyroidal extension identified only on histologic examination is no longer a variable in determining the T category - only gross extrathyroidal extension (invasion of strap muscle, at least) has prognostic significance (CA Cancer J Clin 2017 Nov 1 [Epub ahead of print])
      • ETE is detected in 1/4 of thyroid cancers (Thyroid 2017;27:1490)
  • Additional histologic features of the tumor are optional
    • Mitotic rate in 10 consecutive HPFs at 400x in the hot spots
      • Comment: check carefully in the solid and trabecular patterned areas
    • Perineural invasion
      • Comment: search in tumors with extensive ETE
    • Grading system is not established for thyroid cancer
  • Additional pathologic findings in nonneoplastic part are optional
    • Nodular lesions: follicular adenoma, hyperplastic nodule(s)
    • Diffuse disease: thyroiditis, Graves
    • Presence of parathyroid gland
  • Results of ancillary studies are optional
    • Immunohistochemistry:
      • Tumor type specific markers, e.g. calcitonin for medullary carcinoma or beta catenin for cribriform morular papillary carcinoma
      • Markers to differentiate benign vs. malignant follicular-derived tumors (CK19, Galectin-3, HBME1)
      • Markers of high grade progression (Tg loss, Ki67 >10%, p53)
      • Mutation specific antibodies: VE1, SP174
    • Molecular testing: not common on surgical samples

    Key features to report for lymph nodes
  • Number of lymph nodes examined and involved
    • Nodal levels should be specified, e.g. levels VI-VII (central compartment) or II-V (lateral)
    • Number of nodes depends on type of neck dissection (selective, modified radical or radical)
    • CAP note:
      • Adverse prognostic influence of lymph node metastasis in patients with differentiated carcinomas is observed only in the older age group
      • Less prognostic significance in papillary than in medullary cancer
    • Comment:
  • Size of the largest metastatic deposit, in centimeters
    • Comment: micrometastases (< 2 mm and less than 5 involved nodes) likely do not increase risk of locoregional recurrence
  • Extranodal extension
    • Comment:
      • Involvement of perinodal adipose tissue is the most consistent diagnostic criteria (Thyroid 2016;26:816)
      • Reported in up to 12% of papillary thyroid carcinoma / PTC overall and 33% of nodal metastatic PTC

Diagrams / tables

Images hosted on PathOut server:

Images contributed by Andrey Bychkov, M.D., Ph.D.
Missing Image

AJCC / TNM charts

Missing Image

ATA initial stratification

Missing Image

WHO classification


Missing Image

Capsular invasion

Missing Image

Levels of the cervical lymph nodes

Microscopic (histologic) images

Images hosted on PathOut server:

Images contributed by Chan Kwon Jung, M.D., Ph.D.

Papillary thyroid carcinoma - lymphatic invasion



Images contributed by Andrey Bychkov, M.D., Ph.D.
Missing Image

Vascular invasion


Missing Image

Psammoma bodies

Missing Image

Microscopically positive margin


Missing Image


Missing Image

Extrathyroidal extension


Missing Image

Extranodal extension

Sample of case summary
    Thyroid, total thyroidectomy:
  • Papillary thyroid carcinoma of the right lobe, tall cell variant (4.7 x 2.5 x 2.5 cm)
  • Lymphatic invasion positive
  • No angioinvasion
  • Minimal extrathyroidal extension (perithyroidal fat)
  • Microscopically involved superior resection margin, all other margins negative
  • Lymph node metastasis, 2/2 nodes (perithyroid), 0.5 cm in largest diameter, no extranodal extension
  • Hashimoto thyroiditis of nonneoplastic thyroid
  • pT3a (size > 4 cm), pN1a (positive perithyroidal nodes)
Board review question #1
    Which histopathologic feature is not mandatory to report according to the CAP thyroid protocol?

  1. Extranodal extension
  2. Histologic type
  3. Lymphatic invasion
  4. Perineural invasion
  5. Tumor focality
Board review answer #1
D. Perineural invasion is an optional feature to report, because its clinical significance is not well defined.