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Anaplastic Thyroid Cancer

Editor: Al O. Giwa Updated: 1/1/2023 4:18:39 AM


Anaplastic thyroid carcinoma (ATC), also known as undifferentiated carcinoma, is a rare, highly aggressive malignant tumor accounting for 2% to 3% of all thyroid gland neoplasms. Anaplastic thyroid carcinoma continues to rank as one of the most deadly diseases worldwide and carries a very poor prognosis. In addition to considerable local invasion, anaplastic thyroid carcinoma often presents with metastatic spread to regional lymph nodes and distant sites.[1] Due to the aggressive nature of this type of cancer, the mortality is close to 100 percent and typically, patients already have metastatic disease by the time of diagnosis.[2] However, recent advances in understanding the genetic and molecular pathogenesis of ATC hold promise for targeted therapy for this disease.[3]


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The risk factors of ATC, according to a case-control study by Zivaljevic et al., included low education level, type B blood group, and goiter.[4]Moreover, patients with poorly-differentiated thyroid cancer with the following characteristics tend to present with more complicated and adverse clinicopathological findings; 1. older age, 2. male patient, 3. advanced locoregional disease, and 4. distant metastases.[5]


The frequency of anaplastic thyroid carcinoma is higher in areas of endemic goiter. Anaplastic thyroid carcinoma is responsible for 1.7% of all thyroid cancers in the United States. However, geographical prevalence ranges from 1.3% to 9.8%.[6][7] Patients are typically elderly (sixth to seventh decades of life); the mean age at diagnosis is 65 years, and the female-to-male ratio is 2 to 1.[3][8] According to the epidemiological data derived from the surveillance, epidemiology, and results (SEER) database, the incidence of anaplastic thyroid cancer was steady between 1973 and 2002.[3][9]


Approximately 20 percent of patients with ATC have a history of differentiated thyroid cancer.[10]  Up to 30 percent of ATC may have associated synchronous differentiated cancer. [11] The majority of the synchronous thyroid tumors are papillary cancer, but follicular types have also been reported. The transformation from differentiated to anaplastic cancer has also been described. [12]  Tp53 gene inactivation may play an important role in the progression from differentiated to undifferentiated carcinoma. Thyroid-specific rearrangements RET/PTC and PAX8/PPARγ are rarely found in poorly differentiated or undifferentiated thyroid cancer, suggesting that these genetic alterations do not predispose cells to dedifferentiation[13]


The cytogenetics are often complex and show progressive accumulation of chromosomal alterations (numerical and structural aberrations). The following gene mutation is commonly reported in ATC: p53 (most common), RAS, BRAF, β-catenin, PIK3CA, Axin, APC, and PTEN.[14][7] 


Macroscopic Findings[15]

  • Bulky mass (mean: 6 cm)
  • Homogeneous and variegated appearance
  • On cut section: light tan and fleshy with zones of necrosis and hemorrhage
  • Infiltrating, often into adjacent soft tissues and organs

Microscopic Findings

The highly variable microscopic appearances of anaplastic thyroid carcinoma are broadly categorized into three patterns, which can occur singly or in any combination:

  • Sarcomatoid
  • Giant cell
  • Epithelial
  1. The sarcomatoid form is malignant spindle cells with features commonly seen in high-grade pleomorphic sarcoma.
  2. The giant cell form is composed of highly pleomorphic malignant cells, some of which contain multiple nuclei.
  3. The epithelial form manifests squamoid or squamous cohesive tumor nests with abundant eosinophilic cytoplasm; occasional keratinization can be present.

Common to all three forms are necrosis, an elevated mitotic rate, and an infiltrative growth pattern. Vascular invasion is also often present.


Immunohistochemistry helps to distinguish anaplastic carcinoma from other undifferentiated malignancies using CD45 and other lymphoid markers along with melanocytic markers to exclude lymphoma and melanoma, respectively.

Common thyroid-lineage markers such as TTF1 and thyroglobulin are usually absent, whereas PAX, also a thyroid-lineage marker, is retained in approximately half of all cases. Positive cytokeratin expression supports the epithelial nature of anaplastic thyroid carcinoma, but negative immunostaining for cytokeratin does not exclude the diagnosis.[16]

History and Physical

The most common clinical presentation of anaplastic thyroid carcinoma are:

  • Rapidly growing, painful, firm, low anterior neck mass usually fixed to the underlying structures
  • Compressive symptoms include:
    • Hoarseness, dysphagia, dyspnea, and cough
  • Regional nodal metastases and vocal cord paralysis present in 40% and 30%, respectively.[17][18][19]



The most common ultrasonographic findings of anaplastic thyroid carcinoma include[20]:

  • Solid masses
  • Marked hypoechogenicity
  • Irregular margin
  • Internal calcification
  • Wider than tall shape
  • Cervical lymph node involvement

Fine Needle Aspiration (FNA)[20]

A fine-needle biopsy is a useful diagnostic modality. However, the diagnosis of anaplastic carcinoma must be established by surgical biopsy or during surgery.

Cytologic findings of anaplastic thyroid carcinoma include:

  1. Biphasic population: tumor and uninvolved thyroid
  2. Highly cellular with single cells and focal clusters composed of remarkable atypical cells
  3. Mitotic figures are prominent
  4. Background necrosis and inflammatory cells may be present

Intraoperative Frozen Section and Pathology Consultation

Intraoperative consultation provides a rapid diagnosis to determine the ongoing operative extent and approach. 

Computed Tomography Scan

Anaplastic thyroid carcinomas usually present as large isodense or slightly hyperdense masses relative to skeletal muscle. Calcification and necrosis are present and often are extensive.[21] A computed tomography scan is useful in defining the local extent of anaplastic thyroid carcinoma and detecting lymph node metastases.

Magnetic Resonance Imaging

Magnetic resonance imaging can be useful to best assess tumor extension, particularly in the esophagus musculature, trachea, and carotid vessel.[22]

F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET)

Staging assessment with F-fluorodeoxyglucose positron emission tomography (FDG-PET) fused coincident computerized tomography scan (FDG-PET/CT) is uniquely valuable in anaplastic thyroid carcinoma due to its enhanced expression of glucose transporter (GLUT-1), resulting in increased glucose uptake.[23]

Treatment / Management

The recommended treatment for anaplastic thyroid carcinoma is based on surgery when feasible and chemoradiation either concurrently or sequentially.[3] Most cases of anaplastic thyroid carcinoma are unresectable at presentation because of the invasion of cervical structures. Surgery should aim to secure the patient’s airway.


Debulking surgery is the most common procedure in anaplastic thyroid carcinoma. It consists of removing any gross tumor that is potentially threatening the airway with the aim of preserving the larynx. However, a tracheostomy may be necessary in cases of airway compromise. While complete excision is often impossible due to the local extension of the disease, the quality of resection is a significant prognostic factor for survival.[24][15](A1)

Radiation Therapy and Chemotherapy

External-beam irradiation is effective in improving local control. For patients with locally advanced unresectable disease, definitive radiation therapy and chemotherapy are the recommendations.[25][15] Adjuvant radiation therapy should be performed in all cases, including completely resected small-size incidental anaplastic thyroid carcinoma and anaplastic thyroid carcinoma with a differentiated component.[26](A1)

Anaplastic thyroid carcinoma is usually not responsive to I131 therapy. Radioiodine is only a recommendation upon identification of a differentiated iodine-positive component.[15] New insights into biological behavior and the genetic and molecular pathogenesis of anaplastic thyroid carcinoma might offer novel targeted therapies.[27](A1)

Differential Diagnosis

Histological differential diagnosis:

  • Metastatic disease to the thyroid, including metastatic clear-cell renal carcinoma
  • Primary thyroid lymphoma
  • Primary thyroid sarcoma
  • Poorly differentiated thyroid carcinoma
  • Squamous cell thyroid carcinoma
  • Medullary carcinoma[28]

Medical Oncology

Management of anaplastic thyroid cancer includes expedited staging and tissue sampling with biopsy or fine-needle aspiration to detect next-generation molecular sequencing.[29] 


Thyroid carcinomas staging is according to the 8th edition of the American joint committee on cancer (AJCC) classification. According to the International Union Against Cancer (UICC)—TNM staging and AJCC system, all anaplastic thyroid carcinomas are considered stage IV.[3] Stage IVA and IVB patients have intrathyroidal tumors (IVA) and extrathyroidal tumors (IVB) and no distant metastatic disease, whereas stage IVC patients have distant metastasis.


Anaplastic thyroid carcinoma is poorly responsive to any multimodality therapy.[15]  The most recent Surveillance, Epidemiology, and End Results database analysis (1986-2015) reported median survival of 4 months and a 6-month OS of 35%[2].  Survival beyond 2 years is 12%.[30]

Prognostic Factors

The favorable prognostic indicators of anaplastic thyroid carcinoma are[31][32][33][34]:

  • Younger age (less than or equal to 60 years old)
  • An absence of cervical or distant metastases
  • Small tumors (less than or equal to 5 to 7 cm)
  • Unilateral tumors
  • An absence of local invasion of the surrounding tissue or nodal involvement
  • An incidental finding of anaplastic thyroid carcinoma within a thyroidectomy specimen


Local invasion of the surrounding structures occurs in almost 70% of patients as observed in large series: muscles (65%), trachea (46%), esophagus (44%), laryngeal nerve (27%), and larynx (13%). Lymph node metastases are a feature in almost 40% of patients.[35]

The progression of anaplastic thyroid carcinoma is rapid, and most patients die from local airway obstruction or complications of pulmonary metastases within one year.[15] Metastases occur in up to 75% of patients. They most frequently involve the lungs (80%), the brain (5 to 13%), and bones (6 to 15%).

Pearls and Other Issues

To avoid the development of anaplastic carcinoma, longstanding goiters, as well as benign nodules, should be followed carefully and considered for resection if they grow or do not respond to medical therapy. Moreover, total thyroidectomy for malignant disease can prevent the development of anaplastic carcinoma.

Enhancing Healthcare Team Outcomes

Due to the aggressive nature of the disease, prompt diagnosis is critical in determining appropriate treatment options. Management of anaplastic thyroid carcinoma is complex and needs an interprofessional team approach involving a team that consists of an ENT surgeon, a surgical oncologist, a radiation oncologist, a pathologist, an endocrinologist, a radiologist, and a nuclear medicine specialist. The pharmacist reviews prescribed medications to provide patient education and monitors compliance. Oncology pharmacists assist in planning chemotherapy and provide feedback to the team. Specialty trained otolaryngology and oncology nurses help coordinate care, educate patients and their families, schedule follow up, and inform the team of status changes. Palliative care and hospice nurses and doctors are commonly involved in improving end-of-life care. [Level 5]



Simões-Pereira J,Capitão R,Limbert E,Leite V, Anaplastic Thyroid Cancer: Clinical Picture of the Last Two Decades at a Single Oncology Referral Centre and Novel Therapeutic Options. Cancers. 2019 Aug 15     [PubMed PMID: 31443283]


Maniakas A,Dadu R,Busaidy NL,Wang JR,Ferrarotto R,Lu C,Williams MD,Gunn GB,Hofmann MC,Cote G,Sperling J,Gross ND,Sturgis EM,Goepfert RP,Lai SY,Cabanillas ME,Zafereo M, Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019. JAMA oncology. 2020 Sep 1;     [PubMed PMID: 32761153]


Nagaiah G,Hossain A,Mooney CJ,Parmentier J,Remick SC, Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment. Journal of oncology. 2011;     [PubMed PMID: 21772843]


Zivaljevic V,Slijepcevic N,Paunovic I,Diklic A,Kalezic N,Marinkovic J,Zivic R,Vekic B,Sipetic S, Risk factors for anaplastic thyroid cancer. International journal of endocrinology. 2014     [PubMed PMID: 24949009]


Ibrahimpasic T,Ghossein R,Shah JP,Ganly I, Poorly Differentiated Carcinoma of the Thyroid Gland: Current Status and Future Prospects. Thyroid : official journal of the American Thyroid Association. 2019 Mar     [PubMed PMID: 30747050]


O'Neill JP,Shaha AR, Anaplastic thyroid cancer. Oral oncology. 2013 Jul;     [PubMed PMID: 23583302]

Level 1 (high-level) evidence


Smallridge RC,Copland JA, Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clinical oncology (Royal College of Radiologists (Great Britain)). 2010 Aug;     [PubMed PMID: 20418080]


Wang HM,Huang YW,Huang JS,Wang CH,Kok VC,Hung CM,Chen HM,Tzen CY, Anaplastic carcinoma of the thyroid arising more often from follicular carcinoma than papillary carcinoma. Annals of surgical oncology. 2007 Oct;     [PubMed PMID: 17638058]


Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006 May 10:295(18):2164-7     [PubMed PMID: 16684987]

Level 2 (mid-level) evidence


Venkatesh YS,Ordonez NG,Schultz PN,Hickey RC,Goepfert H,Samaan NA, Anaplastic carcinoma of the thyroid. A clinicopathologic study of 121 cases. Cancer. 1990 Jul 15;     [PubMed PMID: 1695118]

Level 2 (mid-level) evidence


Carcangiu ML,Steeper T,Zampi G,Rosai J, Anaplastic thyroid carcinoma. A study of 70 cases. American journal of clinical pathology. 1985 Feb     [PubMed PMID: 2578727]

Level 3 (low-level) evidence


Ambelil M,Sultana S,Roy S,Gonzalez MM, Anaplastic Transformation in Mandibular Metastases of Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Review of the Literature. Annals of clinical and laboratory science. 2016 Sep     [PubMed PMID: 27650625]

Level 3 (low-level) evidence


Soares P,Lima J,Preto A,Castro P,Vinagre J,Celestino R,Couto JP,Prazeres H,Eloy C,Máximo V,Sobrinho-Simões M, Genetic alterations in poorly differentiated and undifferentiated thyroid carcinomas. Current genomics. 2011 Dec;     [PubMed PMID: 22654560]


Smallridge RC,Marlow LA,Copland JA, Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocrine-related cancer. 2009 Mar     [PubMed PMID: 18987168]

Level 3 (low-level) evidence


Sun XS,Sun SR,Guevara N,Fakhry N,Marcy PY,Lassalle S,Peyrottes I,Bensadoun RJ,Lacout A,Santini J,Cals L,Bosset JF,Garden AS,Thariat J, Chemoradiation in anaplastic thyroid carcinomas. Critical reviews in oncology/hematology. 2013 Jun;     [PubMed PMID: 23218594]

Level 1 (high-level) evidence


Walczyk A,Kopczyński J,Gąsior-Perczak D,Pałyga I,Kowalik A,Chrapek M,Hejnold M,Góźdź S,Kowalska A, Histopathology and immunohistochemistry as prognostic factors for poorly differentiated thyroid cancer in a series of Polish patients. PloS one. 2020     [PubMed PMID: 32092093]


Hadar T,Mor C,Shvero J,Levy R,Segal K, Anaplastic carcinoma of the thyroid. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 1993 Dec;     [PubMed PMID: 8270035]

Level 2 (mid-level) evidence


Nel CJ,van Heerden JA,Goellner JR,Gharib H,McConahey WM,Taylor WF,Grant CS, Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases. Mayo Clinic proceedings. 1985 Jan;     [PubMed PMID: 3965822]

Level 3 (low-level) evidence


Ain KB, Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid : official journal of the American Thyroid Association. 1998 Aug;     [PubMed PMID: 9737368]


Suh HJ,Moon HJ,Kwak JY,Choi JS,Kim EK, Anaplastic thyroid cancer: ultrasonographic findings and the role of ultrasonography-guided fine needle aspiration biopsy. Yonsei medical journal. 2013 Nov;     [PubMed PMID: 24142644]


Takashima S,Morimoto S,Ikezoe J,Takai S,Kobayashi T,Koyama H,Nishiyama K,Kozuka T, CT evaluation of anaplastic thyroid carcinoma. AJR. American journal of roentgenology. 1990 May;     [PubMed PMID: 2108546]

Level 2 (mid-level) evidence


Ng TSC,Gunda V,Li R,Prytyskach M,Iwamoto Y,Kohler RH,Parangi S,Weissleder R,Miller MA, Detecting Immune Response to Therapies Targeting PDL1 and BRAF by Using Ferumoxytol MRI and Macrin in Anaplastic Thyroid Cancer. Radiology. 2021 Jan     [PubMed PMID: 33107799]


Loh TL,Zulkiflee AB, Anaplastic thyroid carcinoma mimicking thyroid abscess. AME case reports. 2018;     [PubMed PMID: 30264016]

Level 3 (low-level) evidence


Haigh PI,Ituarte PH,Wu HS,Treseler PA,Posner MD,Quivey JM,Duh QY,Clark OH, Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer. 2001 Jun 15;     [PubMed PMID: 11413523]


Tennvall J,Lundell G,Wahlberg P,Bergenfelz A,Grimelius L,Akerman M,Hjelm Skog AL,Wallin G, Anaplastic thyroid carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery. British journal of cancer. 2002 Jun 17;     [PubMed PMID: 12085174]


Pierie JP,Muzikansky A,Gaz RD,Faquin WC,Ott MJ, The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma. Annals of surgical oncology. 2002 Jan-Feb;     [PubMed PMID: 11833496]

Level 2 (mid-level) evidence


Eckhardt S,Hoffmann S,Damanakis AI,Di Fazio P,Pfestroff A,Luster M,Wunderlich A,Bartsch DK, Individualized multimodal treatment strategy for anaplastic thyroid carcinoma-Case report of long-term remission and review of literature. International journal of surgery case reports. 2016;     [PubMed PMID: 27379749]

Level 3 (low-level) evidence


Silver JA,Roy CF,Lai JK,Caglar D,Kost K, Metastatic Clear Renal-Cell Carcinoma Mimicking Anaplastic Thyroid Cancer: A Case Report. Ear, nose, & throat journal. 2021 Dec 13     [PubMed PMID: 34903079]

Level 3 (low-level) evidence


Bible KC,Kebebew E,Brierley J,Brito JP,Cabanillas ME,Clark TJ Jr,Di Cristofano A,Foote R,Giordano T,Kasperbauer J,Newbold K,Nikiforov YE,Randolph G,Rosenthal MS,Sawka AM,Shah M,Shaha A,Smallridge R,Wong-Clark CK, 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid : official journal of the American Thyroid Association. 2021 Mar;     [PubMed PMID: 33728999]


Tennvall J,Lundell G,Hallquist A,Wahlberg P,Wallin G,Tibblin S, Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish Anaplastic Thyroid Cancer Group. Cancer. 1994 Aug 15;     [PubMed PMID: 8055459]


Besic N,Hocevar M,Zgajnar J,Pogacnik A,Grazio-Frkovic S,Auersperg M, Prognostic factors in anaplastic carcinoma of the thyroid-a multivariate survival analysis of 188 patients. Langenbeck's archives of surgery. 2005 Jun;     [PubMed PMID: 15599758]

Level 2 (mid-level) evidence


Sugitani I,Miyauchi A,Sugino K,Okamoto T,Yoshida A,Suzuki S, Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World journal of surgery. 2012 Jun;     [PubMed PMID: 22311136]

Level 2 (mid-level) evidence


Yau T,Lo CY,Epstein RJ,Lam AK,Wan KY,Lang BH, Treatment outcomes in anaplastic thyroid carcinoma: survival improvement in young patients with localized disease treated by combination of surgery and radiotherapy. Annals of surgical oncology. 2008 Sep;     [PubMed PMID: 18581185]


Kim TY,Kim KW,Jung TS,Kim JM,Kim SW,Chung KW,Kim EY,Gong G,Oh YL,Cho SY,Yi KH,Kim WB,Park DJ,Chung JH,Cho BY,Shong YK, Prognostic factors for Korean patients with anaplastic thyroid carcinoma. Head     [PubMed PMID: 17274052]

Level 2 (mid-level) evidence


Polistena A,Monacelli M,Lucchini R,Triola R,Conti C,Avenia S,Rondelli F,Bugiantella W,Barillaro I,Sanguinetti A,Avenia N, The role of surgery in the treatment of thyroid anaplastic carcinoma in the elderly. International journal of surgery (London, England). 2014;     [PubMed PMID: 25167852]

Level 2 (mid-level) evidence