Thyroid gland
Other carcinoma
Anaplastic carcinoma


Topic Completed: 1 January 2018

Revised: 13 September 2019

Copyright: 2003-2019, PathologyOutlines.com, Inc.

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

Shuanzeng Wei, M.D., Ph.D.
Page views in 2018: 11,857
Page views in 2019 to date: 11,015
Cite this page: Wei S. Anaplastic carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidUndiff.html. Accessed October 19th, 2019.
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)
  • Paucicellular variant: uncommon; resembles Riedel's thyroiditis; may be due to extensive infarction
  • Rhabdoid variant: very rare; aggressive, often metastasizes; to date, always rapidly fatal
Essential features
  • Highly aggressive thyroid carcinoma composed of undifferentiated follicular cells
Terminology
  • Undifferentiated carcinoma, carcinosarcoma, sarcomatoid carcinoma, metaplastic carcinoma, spindle cell carcinoma, giant cell carcinoma, pleomorphic carcinoma
ICD coding
Epidemiology
  • Mean age 70 years, female to male ratio of 2:1
  • Median 1 year survival rate: 10 - 20%
  • Rhabdoid variant: usually women, mean 56 years, range 42 - 67 years
Sites
  • Often presents with local and distant metastases
  • All are considered high stage (IV) tumor
Pathophysiology
  • 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)
Etiology
  • 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

Contributed by Dr. Mark R. Wick

CT scan

Case reports
Treatment
  • 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
  • Paucicellular variant: hard fibrotic mass
Gross 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
  • Variants:
    • Angiomatoid
    • Lymphoepithelioma-like
    • Osteoclastic: with nonneoplastic giant cells
    • Paucicellular: infiltrative, composed of acellular or necrotic fibrous tissue with hypocellular foci of mildly atypical spindle cells obliterating large blood vessels, mixed with collagen and small lymphocytes (Am J Clin Pathol 1996;105:388)
    • Rhabdoid: highly cellular, solid infiltrative growth with extracapsular invasion; tumor cells are large and pleomorphic with abundant cytoplasm, eosinophilic inclusions, eccentric nuclei with distinct nucleoli (Am J Surg Pathol 2007;31:729)
    • Small cell: extremely rare
Microscopic (histologic) images

Contributed by Dr. Shuanzeng Wei

Anaplastic carcinoma and adjacent papillary thyroid carcinoma

Anaplastic carcinoma with necrosis and inflammation




Contributed by Dr. Stephen J. Schultenover

Spindled tumor


AE1 / AE3

CK903




Spread / metastases (AFIP):

Direct invasion of trachea

Metastasis in wall of colon


Stains (AFIP):

Keratin stains many mesenchymal-like tumor cells

Focal CEA staining

Thyroglobulin stains



Images hosted on other servers:

Rhabdoid variant: various images

Cytology, gross, H&E

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

Contributed by Ayana Suzuki, Cytotechnologist, Japan

Pleomorphism



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
  • No junctional complexes or obvious epithelial elements in osteoclast-like giant cells (Am J Surg Pathol 1978;2:401)
  • Rhabdoid variant: whorled cytoplasmic filaments
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
  • Rhabdoid variant: RET-PTC3 gene rearrangement
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.
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