eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Hurthle Cell Carcinoma: Differential Diagnoses & Workup

Author: Serhat Aytug, MD, Staff Physician, Division of Endocrinology, Diabetes and Metabolism, CrystalRun Healthcare
Coauthor(s): Lawrence E Shapiro, MD, Chief, Division of Endocrinology and Metabolism, Professor of Medicine, Department of Medicine, Winthrop University Hospital
Contributor Information and Disclosures

Updated: Nov 5, 2009

Differential Diagnoses

Goiter
Thyroid Nodule
Goiter, Diffuse Toxic
Thyroid, Anaplastic Carcinoma
Goiter, Nontoxic
Thyroid, Follicular Carcinoma
Goiter, Toxic Nodular
Thyroid, Medullary Carcinoma
Graves Disease
Thyroid, Papillary Carcinoma
Hashimoto Thyroiditis
Thyroiditis, Subacute
Thyroid Lymphoma

Other Problems to Be Considered

Hürthle cell adenoma (main differential diagnosis)
Follicular adenoma
Metastatic tumors to the thyroid
Thyroid cysts
Thyrotoxicosis

Metastatic tumors of other Hürthle cell–harboring organs, particularly metastatic renal cell carcinoma and Hürthle cell tumors, originating from the following:

  • Salivary glands
  • Pharynx
  • Larynx
  • Trachea
  • Parathyroid gland
  • Esophagus
  • Pituitary
  • Liver

Workup

Laboratory Studies

  • Thyroid function tests
    • Thyroid-stimulating hormone (TSH)
    • Thyroxine (T4)
    • Triiodothyronine (T3)
    • Free T4
  • Antiperoxidase antibodies
  • Antithyroglobulin antibodies

Imaging Studies

  • Thyroid uptake and scan: Typical finding is an area of decreased uptake, which corresponds to the tumor.
  • Thyroid ultrasound: Ultrasound usually demonstrates a solid mass, as well as characterizes the solid/cystic nature of the lesion, and is also helpful in diagnosing enlarged lymph nodes in the neck.
  • MRI of the neck: MRI will provide more detailed information about the tumor and its relation to the other neck structures.
  • CT scan of the neck: CT scan provides more detailed information about the tumor and its relation to the other neck structures. CT scan is also helpful for assessment of calcifications.
  • Octreotide scintigraphy: This study can be considered for patients with metastatic Hürthle cell carcinoma because evidence suggests that some Hürthle cell neoplasms can express somatostatin receptors.
  • Recently PET scan with 18F-FDG has been shown to be helpful in diagnosing metastatic disease in Hürthle cell carcinomas. This is particularly helpful with the tumors that have low iodine avidity. In a study by Pryma et al, 18F-FDG PET was shown to increase diagnostic accuracy over CT and radioactive iodine scan. In addition, in this study, intense 18F-FDG uptake in lesions were an indicator of poor prognosis.15

Procedures

  • Fine-needle aspiration
    • FNA can diagnose Hürthle cell neoplasm in most patients; however, the differentiation of Hürthle cell adenoma from Hürthle cell carcinoma cannot be made based on a FNA because vascular and capsular invasion cannot be assessed. Vascular and capsular invasion are the 2 main factors that differentiate carcinoma from adenoma. Elliott et al studied 139 Hürthle cell lesions with their FNA findings. In their study, of the 14 cytological features that were studied, when combined, 4 features were found statistically significant in identifying Hürthle cell neoplasms. These features were nonmacrofollicular architecture, absence of colloid, absence of inflammation, and presence of transgressing blood vessels.16
    • All patients with the cytologic diagnosis of a Hürthle cell tumor should proceed to surgery to ensure that the carcinomas are identified and managed appropriately.
  • Frozen section examination
    • Frozen section examination of the thyroid gland has variable diagnostic value based on institutional experience.
    • This procedure is limited by sampling error, variable thickness, irregularity of the capsule, freezing artifact, difficulty in distinguishing capsular entrapment from invasion, and freezing-induced distortion and collapse of the blood vessels.
    • Frozen section has no additional value in most studies; however, in one study, the diagnosis of malignant follicular or Hürthle cell carcinoma was established correctly in 78%.17
    • This study requires processing of an average of 6-15 slides per patient, which is impractical in many institutions.

Histologic Findings

Common histological malignancy criteria, such as architectural distortion, cellular atypia, or pleomorphism, are encountered in both benign and malignant follicular adenomas; these histological criteria are not helpful while evaluating a thyroid mass.

The cytologic features for Hürthle cell neoplasms are hypercellularity, with a predominance of Hürthle cells usually above 75%, few or no lymphocytes, and scanty or absent colloid. Hürthle cells are large and polygonal in shape, with indistinct cell borders. They have a large pleomorphic hyperchromatic nucleus, a prominent nucleolus, and intensely pink fine granular cytoplasm with hematoxylin-eosin staining (see Image 2).

Papillary structures and intranuclear inclusions, features that are not ordinarily associated with Hürthle cell lesions, are occasionally noted. The electron microscopic examination of Hürthle cells in tumor formation is unique, revealing a large cytoplasm that is almost completely filled with mitochondria. This examination also reveals large lysosomelike dense bodies and dilated Golgi zones confined to the apical portion of the cytoplasm. Unusual richness of chromatin is clumped against the inner nuclear membrane and nuclei that are observed as round and dense, with separation of fibrillar and granular substances.

Histopathologic differentiation of Hürthle cell carcinoma from Hürthle cell adenoma is based on vascular and capsular invasion. Capsular invasion refers to tumor cell penetration of the capsule of the neoplasm. Vascular invasion is defined by the presence of tumor penetration of blood vessels within or outside of the capsule of the Hürthle cell lesion. Capsular invasion, vascular invasion, or both diagnose Hürthle cell carcinoma.

Benign diseases (eg, Hashimoto disease, nodular goiter, toxic goiter) usually have no encapsulation. Hürthle cell changes are part of an inflammatory process.

In a study by Volante et al, the role of galectin-3 and HBME-1 (an antimesothelial monoclonal antibody that recognizes an unknown antigen on microvilli of mesothelial cells) tumor markers, as well as the peroxisome proliferator-activated receptor (PPAR) gamma protein expression, were assessed in oncocytic Hürthle cell tumors, including Hürthle cell adenomas, Hürthle cell carcinomas, and an oncocytic variant of papillary carcinoma. In these 152 Hürthle cell tumors (50 Hürthle cell adenomas, 70 Hürthle cell carcinomas, and 32 oncocytic variant of papillary carcinoma), the sensitivity of galectin-3 was 95.1%, the sensitivity of HBME-1 was 53%, and a combination of galectin-3 and HBME-1 was high at 99%. However, the specificity for both markers was 88%, lower than for nononcocytic follicular tumors.18

Interestingly, PPAR gamma protein overexpression was absent in all Hürthle cell adenomas tested and present in only 10% of Hürthle cell carcinomas, similar to other reports that confirm the low prevalence of PAX8-PPAR gamma translocations in Hürthle cell carcinomas.

Staging

Different prognostic criteria and staging systems are used in differentiating thyroid cancer and Hürthle cell cancer. No uniformly accepted staging system and prognostic classification exists for Hürthle cell carcinoma.

The tumor, node, metastases (TNM) system is the most widely used staging system (see Image 1). Most classification systems used in the evaluation of patients with Hürthle cell carcinoma consider such factors as tumor size, patient age, presence of metastases, and major capsular invasion (extensive capsular invasion in multiple sites). The other classification systems used for assessing Hürthle cell carcinoma are conducted with scoring systems, using the generally accepted prognostic factors, such as age, metastasis, extent of disease at operation, and size (AMES) and age, grade, extent, and size (AGES).

More on Hurthle Cell Carcinoma

Overview: Hurthle Cell Carcinoma
Differential Diagnoses & Workup: Hurthle Cell Carcinoma
Treatment & Medication: Hurthle Cell Carcinoma
Follow-up: Hurthle Cell Carcinoma
Multimedia: Hurthle Cell Carcinoma
References
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Further Reading

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Keywords

Hürthle cell carcinoma, Hurthle cell carcinoma, thyroid cancer, Ashkenazi cells, oncocytic tumors, oncocytoma, oxyphil tumor, follicular carcinoma oxyphilic type, differentiated thyroid cancer, Hürthle cell neoplasms, follicular carcinoma of the thyroid, follicular cell neoplasms, oncocytic cells, Hashimoto thyroiditis, Hashimoto's thyroiditis, nodular goiter, toxic goiter, thyroid gland, cancer, papillary thyroid carcinoma, PTC

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Contributor Information and Disclosures

Author

Serhat Aytug, MD, Staff Physician, Division of Endocrinology, Diabetes and Metabolism, CrystalRun Healthcare
Serhat Aytug, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, Endocrine Society, and Pituitary Society
Disclosure: Nothing to disclose.

Coauthor(s)

Lawrence E Shapiro, MD, Chief, Division of Endocrinology and Metabolism, Professor of Medicine, Department of Medicine, Winthrop University Hospital
Lawrence E Shapiro, MD is a member of the following medical societies: American Diabetes Association, American Thyroid Association, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Antoni Ribas, MD, Department of Medicine, Division of Hematology-Oncology, Assistant Professor of Medicine, University of California at Los Angeles Medical Center
Disclosure: Nothing to disclose.

Pharmacy Editor

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

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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