Three methods are currently used the assess thyroid nodules. These are fine needle aspiration or FNA, thyroid scans, and ultrasound. Of these three, initial FNA is said to be more diagnostically useful and cost effective. Although ultrasound may be able to detect nodules that cannot be detected through palpation, it is still unable to differentiate between a malignant and benign nodule. Thyroid scans, too, can be misleading in interpreting the malignancy of thyroid nodules.
Fine needle aspiration biopsy is a technique wherein a sample of the tissue is aspirated using a fine needle to be assessed. For superficial tissue as in the thyroid, breast, or prostate, the needle is unguided but for deeper tissue, the needle must be guided radiologically.
The Normal Thyroid under the Microscope
Unlike other endocrine glands, the thyroid gland is unique in that it provides extracellular storage for its products inside cyst-like follicles. These follicles contain thyroid hormones good enough for several weeks. They are nearly spherical in shape and surrounded by a single layer of cuboidal cells. These follicles range from 0.2 to 0.9 mm in diameter and are filled with a substance referred to as colloid.
Some cytophathologists believe that there must be at least six clusters of follicular cells of 10 to 20 cells each on two slides for a thyroid biopsy to qualify as benign. A diagnosis of malignancy can be made when there are fewer cells, provided that there are other signs of malignancy present in the specimen.
Thyroid fine needle aspiration can be difficult and challenging as the amount of tissue on the slides for examination may depend on the method of aspiration. However, the evaluation of thyroid tissue should include the following:
- The presence or absence of follicles
- Cell size
- Staining characteristics of the cells
- Tissue polarity. This should be considered in cell block specimens only.
- Presence of nuclear grooves and/or nuclear clearing
- Presence of nucleoli
- Presence and type of colloid
- Monotonous population of either follicular or Hurthle cells
- Presence of lymphocytes
Almost seventy percent of cases of thyroid masses are benign lesions. Although the clinical signs in a patient may favor benign lesions, FNA it does not really mean that FNA should be excluded in the workup. These are the following clinical characteristics of benign thyroid lesions:
- A sudden onset of pain and tenderness may suggest hemorrhage into a benign adenoma or cyst, or subacute granulomatous thyroiditis, respectively. However, hemorrhage into a cancer may present with similar signs.
- Symptoms suggesting hyperthyroidism or autoimmune thyroiditis (Hashimoto’s disease).
- Family history of benign nodular disease, Hashimoto’s disease, or autoimmune thyroiditis.
- A smooth, soft, and easily movable nodule.
- A midline nodule over the hyoid bone that moves up and down with the protrusion of the tongue is most likely a thyroglossal duct cyst.
Cytological and laboratory characteristics of a benign thyroid nodule are the following:
- The presence of abundant watery colloid.
- Foamy macrophages.
- Cyst or cyst degeneration of a solid nodule.
- Hyperplastic nodule.
- Abnormal TSH levels.
- Lymphocytes and/or high thyroid peroxidase antibody levels. These may suggest Hashimoto’s disease or in rare cases, a lymphoma.
- Papillary Carcinoma
Papillary carcinoma accounts for about eighty percent of malignant lesions of the thyroid. This type of malignancy includes mixed papillary and follicular variants like the tall cell variant and the sclerosing variant. Two or more of the following cytological characteristics are suggestive of papillary carcinoma:
- nuclear inclusions, “cleared-out”, “ground glass” or “orphan annie” nuclei
- nuclear “grooves”
- overlapping nuclei
- psammoma bodies (which are rare)
- papillary projections with fibrovascular core
- “ropey” colloid
Follicular or Hurthle Cell Neoplasms
The lesions in this diagnostic category express characteristics that could be signs of malignancy but are not truly diagnostic. Factors that point to malignancy include male gender, a nodule size of more than 3 centimeters, and age greater than 40 years.
Definitive diagnosis requires histologic examination of the nodule to observe for capsular or vascular invasion. There are no genetic, histologic, or biochemical tests to date that are routinely used to differentiate between benign or malignant lesions in this category. Several studies show that thyroid peroxidase expression as measured by the monoclonal antibody MoAb 47 improves the specificity of correctly differentiating between benign and malignant neoplasms in FNA specimens. Galectin-3 has also been observed to be highly and diffusely expressed in follicular cell neoplasms but only minimally expressed in benign conditions.
Cytologic or histologic characteristics of a follicular malignancy include:
- minimal amounts of free colloid
- high density cell population of either follicular or Hurthle cells
Cytologically, these lesions may be reported as:
- “Hurthle cell neoplasm”
- “Suspicious for follicular neoplasm”
- “Follicular neoplasm/lesion”
- “Indeterminate” or “non-diagnostic”
Fifteen percent of malignancies of the thyroid are defined under this category. This type of thyroid malignancy should be suspected in patients with a family history of medullary cancer or multiple endocrine neoplasia Type 2.
Cytologic or histologic characteristics include the following:
- spindle-type cells with eccentric nuclei
- positive calcitonin stain
- presence of amyloid
- intranuclear inclusions ( which are common)
In less than one percent of patients with malignant thyroid lesions, the diagnosis is anaplastic carcinoma. This type of malignancy is more common in elderly patients with a fast growing thyroid mass. These patients may have had a slow-growing mass for many years already. It is important that anaplastic carcinoma, which has limited therapy, be differentiated from thyroid lymphoma, for which there are ready treatments.
Cytologic characteristics of anaplastic carcinoma include the following:
- extreme cellular pleomorphism
- multinucleated cells
- giant cells
This is a rare form of thyroid malignancy. A rapid growth of a neck mass in the location of the thyroid gland in an elderly patient, especially in someone with Hashimoto’s thyroiditis, is suggestive of thyroid lymphoma. Cytologic features that could further point to this diagnosis include:
- monomorphic pattern of lymphoid cells
- positive B-cell immunotyping
Although thyroid fine needle aspiration is an important technique in the assessment of thyroid lesions, a patient is always free to ask for a second opinion, especially for something as serious as thyroid carcinoma. As pointed out earlier, it is also important for the examining pathologist or cytologist to differentiate between the different malignancies. A prompt and correct diagnosis could spell the difference between a quality life, disability, or even death.