Undifferentiated (Anaplastic) Carcinoma

Undifferentiated (Anaplastic) Carcinoma

Lester D. R. Thompson, MD

There is a pleomorphic epithelial proliferation immediately adjacent to a papillary carcinoma image. This is a typical appearance for an undifferentiated carcinoma of the thyroid.

Osteoclastic-type giant cells are seen. The nuclei are relatively bland, aggregated within the cell. These cells are CD68-positive histiocytes. The malignant part is between these cells.



  • Anaplastic carcinoma

  • Spindle and giant cell carcinoma

  • Sarcomatoid carcinoma

  • Pleomorphic carcinoma

  • Dedifferentiated carcinoma

  • Metaplastic carcinoma

  • Carcinosarcoma


  • Highly aggressive malignant thyroid neoplasm composed of undifferentiated cells that exhibit immunohistochemical or ultrastructural epithelial differentiation


Environmental Exposure

  • Radiation

    • ˜ 10% of patients report radiation exposure

  • Iodine deficiency (for at least 20 years)

Thyroid Disease

  • Preexisting benign or malignant thyroid disease in nearly all cases

    • Longstanding goiter (nodules)

      • Often decades

      • Constant stimulation improves odds of transformation

  • Transformation (dedifferentiation) of preexisting differentiated carcinoma

    • Papillary, follicular, or poorly differentiated carcinoma

      • Identified in up to 80% of undifferentiated carcinoma (UC)

      • Papillary carcinoma is most common (80%)


  • Thyroid follicular epithelial cell origin

    • Difficult to show origin in many cases



  • Incidence

    • Represents ˜ 2% of all thyroid gland malignancies

    • Approximately 1-2/1,000,000 population annually

    • Higher in endemic goiter regions (iodine deficiency), Europe, and low socioeconomic status

  • Age

    • Elderly

    • Vast majority are > 65 years at diagnosis

  • Gender

    • Female > Male (1.5:1)


  • Most are single (60%) lobe tumors

  • Multifocal (40%) or bilateral (25%)


  • Rapidly expanding neck mass

    • Exceedingly fast tumor doubling: 1-2 weeks

    • Fixed and hard mass

  • Usually long history of thyroid disease

  • Hoarseness, dysphagia, vocal cord paralysis, cervical pain, and dyspnea are common

    • Invades into soft tissues (muscle, fat and nerves), esophagus, trachea

  • Lymphadenopathy common

  • Hyperthyroidism is uncommon; results from rapid destruction of follicles with hormone release

Laboratory Tests

  • Leukocytosis can be seen (secretion of macrophage colony-stimulating factor)


  • Options, risks, complications

    • Multimodality therapy required

    • Targeted therapy (such as gelfitinib, an EGFR inhibitor and bevacizumab, an antibody against VEGF-R) shows promise

  • Surgical approaches

    • Value of surgery is yielding diagnostic material and palliation

      • Debulking, as resectability is unlikely

    • May be valuable in limited disease cases

  • Adjuvant therapy

    • Combination chemotherapy (doxorubicin, cisplatin)

    • Response is poor at best

  • Radiation

    • Radiation (external beam, 3 dimensional conformal therapy, intensity modulated radiotherapy)

      • Hyperfractionation or accelerated dosing regimens improves efficacy

      • Rapid doubling rate requires accelerated dosing

      • Chemosensitization (doxorubicin) may help

      • Careful monitoring to minimize toxicity


  • Rapidly progressive local disease

  • Many patients have lymph node disease at presentation

    • Up to 50% cervical adenopathy

  • Metastases to distant sites common

    • Up to 50% at presentation

      • Lungs (50%), bones (15%), brain (10%)

  • Grave overall prognosis

    • > 95% die from disease

    • Median survival: 3 months

    • Accounts for > 50% of all thyroid cancer deaths

  • Better prognosis in cases where anaplastic carcinoma is confined to encapsulated tumor or minor component of another tumor

  • Worse prognosis if patients > 60 years, male, have tumors > 5 cm, or have extensive local disease


General Features

  • Computed tomography shows extent of disease

  • Infiltrative (carotid and internal jugular), heterogeneous mass with irregular borders, and necrosis

  • Calcifications may be seen


General Features

  • Fleshy to firm mass, typically completely replacing thyroid parenchyma

  • Infiltrative with irregular borders

    • Extrathyroidal extension: Soft tissue, larynx, trachea, esophagus, lymph nodes

  • Pale, white-tan, brown

  • Commonly variegated, with areas of necrosis and hemorrhage

Sections To Be Submitted

  • Adequate sampling required to find preexisting or coexisting carcinoma


  • Range: 1-20 cm

  • Mean: 6 cm


Histologic Features

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Undifferentiated (Anaplastic) Carcinoma
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