eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Thyroid, Follicular Carcinoma: Differential Diagnoses & Workup

Author: Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Coauthor(s): Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy; Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Contributor Information and Disclosures

Updated: Sep 25, 2009

Differential Diagnoses

Goiter
Thyroid Nodule
Goiter, Toxic Nodular
Thyroid, Anaplastic Carcinoma
Graves Disease
Thyroid, Medullary Carcinoma
Hurthle Cell Carcinoma
Thyroid, Papillary Carcinoma

Other Problems to Be Considered

Metastatic cancer
Leukemias

Workup

Laboratory Studies

  • Thyroid function: Perform complete assessment of thyroid function in any patient with thyroid lumps. Available studies are not specific for FTC.
    • Levels above the reference range of thyroxine (T4; reference range, 4.5-12.5 mcg/dL), triiodothyronine (T3; reference range, 100-200 ng/dL), and TSH (reference range, 0.2-4.7 mIU/dL) may indicate thyroid cancer.
    • Evaluate serum levels of thyroglobulin, calcium, and calcitonin.
    • Determining serum level of carcinoembryonic antigen (CEA) may be helpful; the reference value is less than 3 ng/dL. However, the implications of CEA elevation are not specific because CEA levels are elevated in several cancers, and many healthy people may have small amounts of CEA, especially pregnant women and heavy smokers.
  • TSH suppression test: Thyroid cancer is autonomous and does not require TSH for growth, whereas benign thyroid lesions do. Therefore, when exogenous thyroid hormone feeds back to the pituitary to decrease the production of TSH, thyroid nodules that continue to enlarge are likely to be malignant. However, consider that 15-20% of malignant nodules are suppressible.
    • Preoperatively, the test is useful for patients with nontoxic solitary benign nodules and for women with repeated inconclusive test results.
    • Postoperatively, the test also is useful in follow-up of FTC cases.
  • A prognostic indicator of significant value may be ras genotyping  by PCR technique, which may help in the clinical and histologic reassessment of these tumors.

Imaging Studies

  • Ultrasonography is the first imaging study that must be performed in any patient with suspected thyroid malignancy.
    • Ultrasonography is noninvasive and inexpensive, and it represents the most sensitive procedure for identifying thyroid lesions and determining the diameter of a nodule (2-3 mm).
    • Ultrasonography is also useful to localize lesions when a nodule is difficult to palpate or is located deeply.
    • Ultrasonography can determine whether a lesion is solid or cystic and can detect the presence of calcifications.
    • The rate of accuracy of ultrasonography in categorizing nodules as solid, cystic, or mixed is near 90%.
    • Ultrasonography may direct a fine-needle aspiration biopsy (FNAB).
    • Disadvantages of thyroid ultrasonography are that the test cannot distinguish benign nodules from malignant nodules, and it cannot be used to identify true cystic lesions.
    • Pulsed and power Doppler ultrasonography may provide important information about the vascular pattern and the velocimetric parameters.12 Such information can be useful preoperatively to differentiate malignant from benign thyroid lesions.
  • Prior to the introduction of FNAB, thyroid scintigraphy (or thyroid scanning) performed with technetium Tc 99m pertechnetate (99mTc) or radioactive iodine (I-131 or I-123) was the initial diagnostic procedure of choice in thyroid evaluation.
    • Thyroid scanning is not as sensitive or specific as FNAB in distinguishing benign nodules from malignant nodules.
    • The scintigraphy procedure performed with 99mTc has a high error rate because although 99mTc is trapped in the thyroid, as iodide is, it is not organified there. 99mTc has a short half-life and cannot be used to determine functionality of a thyroid nodule.
    • Radioactive iodine is trapped and organified in the thyroid and can be used to determine functionality of a thyroid nodule. Iodine-containing compounds and seafood interfere with any tests that use radioactive iodine. Scintigraphic images of the thyroid are acquired 20-40 minutes after IV administration of radionuclide. In more than 90% of cases, clearly benign nodules appear as hot because they are hyperfunctioning and have a high uptake of radionuclide and, physiologically, of iodine. Malignant nodules usually appear as cold nodules because they are not functioning.
    • Thyroid scanning is helpful and specific in localizing the tumor preoperatively and residual thyroid tissue immediately postoperatively. It also is used to follow-up for tumor recurrence or metastasis. Thyroid scanning could be useful in diagnosing thyroid tumors in patients with benign lesions (by FNAB) or solid lesions (by ultrasonography).
  • Integrated imaging, using 18F-FDG and coregistered total body PET and CT scan, seems to be effective in improving diagnostic accuracy in patients with iodine-negative differentiated thyroid carcinoma, allowing precise localization of the tumor tissue.13 In addition, image fusion by integrated PET/CT offers more information than side-by-side interpretation of single images obtained separately with CT and PET.
  • Chest radiography, CT scanning, and MRI usually are not used in the initial workup of a thyroid nodule, except in patients with clear metastatic disease at presentation. These tests are second-level diagnostic tools and are useful in preoperative patient assessment.

Other Tests

Perform indirect or fiberoptic laryngoscopy to evaluate airway and vocal cord mobility and to have preoperative documentation of any unrelated abnormalities.

Procedures

  • Fine-needle aspiration biopsy (FNAB) is considered the best first-line diagnostic procedure for a thyroid nodule; it is a safe and minimally invasive test. It is the required procedure for the diagnostic evaluation of the classic solitary thyroid nodule.
    • Local anesthesia is administered at the puncture site, and a 21G or 23G aspiration biopsy needle is guided into the mass. The nodule is held with the fingers of the left hand while a needle is introduced through the skin into the nodule with the right hand.
    • After aspiration, the material is placed on a glass slide, fixed with alcohol-acetone, and stained according to the technique of Papanicolaou.
    • Accuracy of FNAB is better than any other test for uninodular lesions. Sensitivity of the procedure is near 80%, specificity is near 100%, and errors can be diminished using ultrasound guidance. False-negative and false-positive results occur less than 6% of the time.
    • A cytologist could experience difficulty in distinguishing some benign cellular adenomas from their malignant counterparts (ie, follicular and Hürthle cell adenomas from carcinomas).
  • Thyroid biopsy could be performed using the classic Tru-Cut or Vim-Silverman needles, but FNAB is preferable. Patients comply best with FNAB.

Histologic Findings

On gross examination, FTC appears encapsulated and solitary and is often found in necrotic and/or hemorrhagic areas (see Images 1-2).

Surgical specimen of a large goiter. Total thyroi...

Surgical specimen of a large goiter. Total thyroidectomy was performed because of the presence of a solid nodule in the right lobe (note the size of the thyroid lobe at left of the screen).

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Surgical specimen of a large goiter. Total thyroi...

Surgical specimen of a large goiter. Total thyroidectomy was performed because of the presence of a solid nodule in the right lobe (note the size of the thyroid lobe at left of the screen).



This is the same specimen shown in Image 1. The r...

This is the same specimen shown in Image 1. The right lobe of the thyroid was sectioned and reveals a large solid nodule with necrotic and hemorrhagic areas. Histologic diagnosis is follicular thyroid carcinoma.

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This is the same specimen shown in Image 1. The r...

This is the same specimen shown in Image 1. The right lobe of the thyroid was sectioned and reveals a large solid nodule with necrotic and hemorrhagic areas. Histologic diagnosis is follicular thyroid carcinoma.


Histologically, the lesion may be encapsulated and may demonstrate well-defined follicles containing colloid, making its distinction from follicular adenoma difficult. Examples of FTC are shown in Images 3-5. 

Histologic pattern of a mildly differentiated fol...

Histologic pattern of a mildly differentiated follicular thyroid carcinoma (250 X). Image courtesy of Professor Pantaleo Bufo at University of Foggia, Italy.

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Histologic pattern of a mildly differentiated fol...

Histologic pattern of a mildly differentiated follicular thyroid carcinoma (250 X). Image courtesy of Professor Pantaleo Bufo at University of Foggia, Italy.



Histologic pattern of a rare lymph node metastasi...

Histologic pattern of a rare lymph node metastasis of follicular thyroid carcinoma (140 X). Image courtesy of Professor Pantaleo Bufo at University of Foggia, Italy.

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Histologic pattern of a rare lymph node metastasi...

Histologic pattern of a rare lymph node metastasis of follicular thyroid carcinoma (140 X). Image courtesy of Professor Pantaleo Bufo at University of Foggia, Italy.



Histologic pattern of a rare lymph node metastasi...

Histologic pattern of a rare lymph node metastasis of follicular thyroid carcinoma (250 X). Image courtesy of Professor Pantaleo Bufo at University of Foggia, Italy.

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Histologic pattern of a rare lymph node metastasi...

Histologic pattern of a rare lymph node metastasis of follicular thyroid carcinoma (250 X). Image courtesy of Professor Pantaleo Bufo at University of Foggia, Italy.


  • Histologic and cellular patterns of endocrine tumors do not allow diagnosis of carcinoma; therefore, this diagnosis is made by finding pseudocapsule and/or blood vessel invasion, not by cellular morphology.
  • High magnification of the abortive follicles may demonstrate atypia of the follicular epithelium and intervening stroma.
  • Thyrocytes are large and show an abnormal nuclear/cytoplasmic ratio with several mitoses.
  • Presence of colloid-rich follicles lined by flattened follicular cells that are occasionally accompanied by several histiocytes is maintained in a benign lesion.
  • Definitive diagnosis is often not possible with samples obtained from FNAB because accurate distinction between benign and malignant lesions cannot be made.

Because of the well-known role of the RAS-RAF-MEK-MAP kinase pathway in thyroid carcinogenesis, n-RAS expression may be evaluated to differentiate follicular and papillary cancer of the thyroid.

Staging

The accurate assessment of the proliferative grading and the extent of invasion have high prognostic value and are mandatory in every specimen.

The staging of well-differentiated thyroid cancers is related to age for the first and second stages but not related for the third and fourth stages.

  • Younger than 45 years
    • Stage I: Any T, any N, M0 (Cancer is in the thyroid only.)
    • Stage II: Any T, any N, M1 (Cancer has spread to distant organs.)
  • Older than 45 years
    • Stage I: T1, N0, M0 (Cancer is in the thyroid only and may be found in one or both lobes.)
    • Stage II: T2, N0, M0 and T3, N0, M0 (Cancer is in the thyroid only and is larger than 1.5 cm.)
    • Stage III: T4, N0, M0 and any T, N1, M0 (Cancer has spread outside the thyroid but not outside of the neck.)
    • Stage IV: Any T, any N, M1 (Cancer has spread to other parts of the body.)

More on Thyroid, Follicular Carcinoma

Overview: Thyroid, Follicular Carcinoma
Differential Diagnoses & Workup: Thyroid, Follicular Carcinoma
Treatment & Medication: Thyroid, Follicular Carcinoma
Follow-up: Thyroid, Follicular Carcinoma
Multimedia: Thyroid, Follicular Carcinoma
References
Further Reading
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Further Reading

The progress of the knowledge in molecular bases of thyroid cancers offers new therapeutic targets for FTC treatment and, in the future, prevention. A recent, interesting paper on this subject is Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis from MN Nikiforova and YE Nikiforov (Expert Review of Molecular Diagnostics, January 2008, Vol. 8, No. 1, Pages 83-95).

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Keywords

follicular thyroid carcinoma, FTC, thyroid cancer, thyroid cancer treatment, thyroid cancer medications, thyroid cancer diagnosis, thyroid cancer symptoms, thyroid cancer pictures, Hürthle cell carcinoma, Hurthle cell carcinoma, papillary carcinoma, tumor

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Contributor Information and Disclosures

Author

Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Disclosure: Nothing to disclose.

Coauthor(s)

Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy
Disclosure: Nothing to disclose.

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Medical Editor

Philip Schulman, MD, Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine
Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, and Medical Society of the State of New York
Disclosure: celgene Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; genetech/idec Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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