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.


TERMINOLOGY


Synonyms



  • Anaplastic carcinoma


  • Spindle and giant cell carcinoma


  • Sarcomatoid carcinoma


  • Pleomorphic carcinoma


  • Dedifferentiated carcinoma


  • Metaplastic carcinoma


  • Carcinosarcoma


Definitions



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


ETIOLOGY/PATHOGENESIS


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%)


Pathogenesis



  • Thyroid follicular epithelial cell origin



    • Difficult to show origin in many cases


CLINICAL ISSUES


Epidemiology



  • 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)


Site



  • Most are single (60%) lobe tumors


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


Presentation



  • 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)



Treatment



  • 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


Prognosis



  • 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


IMAGE FINDINGS


General Features



  • Computed tomography shows extent of disease


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


  • Calcifications may be seen


MACROSCOPIC FEATURES


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


Size



  • Range: 1-20 cm


  • Mean: 6 cm


MICROSCOPIC PATHOLOGY


Histologic Features

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