Thyroid gland
Other carcinoma
Anaplastic carcinoma

Author: Shuanzeng Wei, M.D., Ph.D.

Revised: 15 February 2018, last major update January 2018

Copyright: (c) 2003-2018,, Inc.

PubMed Search: Anaplastic carcinoma[TI] thyroid[TI] pathology

Related Topics: Paucicellular variant, Rhabdoid variant
Cite this page: Wei, S. Anaplastic carcinoma. website. Accessed March 24th, 2018.
Definition / general
  • Undifferentiated (high grade) carcinoma of thyroid gland
  • 2 - 5% of thyroid cancers but 40% of thyroid cancer deaths
  • Rapidly enlarging, bulky neck mass invades adjacent structures causing hoarseness, dysphagia, dyspnea
  • Most thyroid sarcoma-like tumors are probably anaplastic carcinomas; small cell types reported in past were probably lymphoma or variants of medullary or insular carcinoma (Am J Clin Pathol 1985;83:135)
Essential features
  • Highly aggressive thyroid carcinoma composed of undifferentiated follicular cells
  • Undifferentiated carcinoma, carcinosarcoma, sarcomatoid carcinoma, metaplastic carcinoma, spindle cell carcinoma, giant cell carcinoma, pleomorphic carcinoma
ICD-10 coding
  • Mean age 70 years, female to male ratio of 2:1
  • Median 1 year survival rate: 10 - 20%
  • Often presents with local and distant metastases
  • All are considered high stage (IV) tumor
  • May arise as anaplastic transformation of differentiated thyroid carcinoma (papillary, follicular or Hürthle cell carcinoma); most cases have a core of conserved mutations in well differentiated and anaplastic areas, plus increases in mutation rates in anaplastic areas (Am J Surg Pathol 2003;27:1559)
  • Unknown, may be associated with radiation and iodine deficiency
Clinical features
  • 50% have prior multinodular goiter, 20% have prior differentiated carcinoma, 20% have concurrent differentiated carcinoma
  • Rapidly enlarging, firm, ill defined neck mass
  • Hoarseness, dyspnea and dysphagia
  • 30 - 40% have distant metastases (lung, bone and brain)
  • Extrathyroidal extension in majority of cases
Radiology images

Images hosted on PathOut server:

Images contributed by Dr. Mark R. Wick:

CT scan

Case reports
  • Radiation, chemotherapy and surgery on selected patients
  • EGFR, VEGFR and ALK alteration may be used for targeted therapy
Gross description
  • Infiltrative large solid tumor with necrosis and hemorrhage
Gross images

Images hosted on PathOut server:

Images contributed by Dr. Mark R. Wick:

AFIP images:

Scant residual thyroid

Metastases to stomach with ulcerated center

Images hosted on other servers:

Encapsulated tumor with focal necrosis

Large necrotic tumor

Nodular tumor

Solid and cystic tumor

Microscopic (histologic) description
  • Three patterns (can be singly or in any combination):
    1. Sarcomatoid: malignant spindle cells resembling high grade pleomorphic sarcoma
    2. Giant cell: highly pleomorphic tumor cells with some tumor giant cells, may have cavernous blood filled sinuses resembling aneurysmal bone cyst (Am J Surg Pathol 1991;15:160)
    3. Epithelial: squamoid / squamous tumor nests with occasional focal keratinization
  • Necrosis
  • Vascular invasion with obliteration of the lumen
  • Increased mitotic figures
  • Heterologous differentiation: neoplastic bone and cartilage
  • Secondary change: acute inflammation, macrophages, osteoclast-like multinucleated giant cells
  • Paucicellular variant: few neoplastic spindle cells with significant fibrous tissue
  • Osteoclastic variant: with nonneoplastic giant cells
  • Rhabdoid variant (Am J Surg Pathol 2007;31:729)
  • Angiomatoid variant
  • Lymphoepithelioma-like variant
  • Small cell variant: extremely rare
Microscopic (histologic) images

Scroll to see all images:

Images hosted on PathOut server:

Images contributed by Dr. Shuanzeng Wei:

Anaplastic carcinoma and adjacent papillary thyroid carcinoma

Anaplastic carcinoma with necrosis and inflammation

Images contributed by Dr. Mark R. Wick:

Fibrosing variant, keratin stain

Images contributed by Dr. Stephen J. Schultenover, Vanderbilt University, Tennessee:

Spindled tumor

AE1 / AE3


AFIP images:

Squamoid differentiation with central necrosis

Elongated spindle cells

Storiform pattern resembles MFH

Hemangioperi-cytoma-like growth pattern

Focally prominent
myxoid pattern
and extensive

Diffuse infiltration
into perithyroidal
fat, resembling

Bone formation

Giant cells (AFIP):

Numerous giant cells

Bizarre nucleated tumor giant cells

Numerous osteoclast-like giant cells

Spread / metastases (AFIP):

Direct invasion of trachea

Metastasis in wall of colon

Metastases to lung

Stains (AFIP):

Keratin stains many mesenchymal-like tumor cells

Focal CEA staining

Thyroglobulin stains

Transformation from well differentiated to undifferentiated carcinoma (AFIP):

Spindled pattern with residual papillary carcinoma

carcinoma (left),
component (right)

Insular component (left), cartilaginous features (right)

Various images

Vascular invasion (AFIP):

Tumor invades wall of vein

Tumor thrombus in partially calcified artery

Intravascular tumor thrombus

Images hosted on other servers:

Large pleomorphic tumor cells

Pleomorphic and hyperchromatic cells

Partially necrotic tumor

With osteoclast-like giant cells

Arising from papillary carcinoma

Cytology description
  • High grade pleomorphic tumor cells, neoplastic giant cells, spindle cells or squamoid cells in a background of tumor diathesis and inflammation
Cytology images

Images hosted on PathOut server:

Images contributed by Shuanzeng Wei, M.D., Ph.D.

Diff-Quik and Pap stains (200x)

Diff-Quik and Pap stains (600x)

Corresponding histology shows tumor with neutrophils

Images hosted on other servers:

Bizarre tumor giant cells

Atypical cells

Giant cell type has large, bizarre cells

Spindle cell type has dyscohesive spindled cells

Positive stains
Negative stains
Electron microscopy description
Electron microscopy images

Images hosted on PathOut server:

AFIP images:

Tumor cells appear extremely primitive

Retention of microvilli

Molecular / cytogenetics description
  • TP53 mutation in 30 - 70% cases
  • BRAF V600E: 20%
  • RAS family mutation (NRAS, HRAS and KRAS)
  • Others alterations: PIK3CA, PTEN and ALK
Differential diagnosis
Board review question #1
Which of the following features are not found in anaplastic thyroid carcinoma?

  1. All are considered high stage (IV) tumor
  2. Can have squamoid / squamous differentiation

  3. Necrosis and increased mitotic figures
  4. PAX8+, thyroglobulin+, TTF1+
  5. Vascular invasion and pleomorphic nucleus
Board review answer #1
D. PAX8+, thyroglobulin+, TTF1+. 

Anaplastic thyroid carcinoma can be PAX8+ in more than 50% cases; however, this tumor is generally negative for thyroglobulin and TTF1.