What is a thyroid nodule?

The term thyroid nodule refers to an abnormal growth of thyroid cells that form a mass within the thyroid gland. About 95% of thyroid nodules are benign. About 5% of thyroid nodules contain malignant cells (thyroid cancer). In order to diagnose and treat thyroid cancer early, most thyroid nodules require careful clinical evaluation by the endocrinologist.

What are the symptoms of a thyroid nodule?

Most thyroid nodules cause no specific symptoms. Often, the nodules are diagnosed incidentally during a visit or an imaging test, such as a CT scan or ultrasound of the neck, performed for other reasons. On other occasions, however, patients themselves notice that they have a thyroid lump when they notice a swollen neck while looking in the mirror, buttoning their shirt collar, or wearing a necklace.

In some cases, thyroid nodules can produce an excessive amount of thyroid hormones and cause hyperthyroidism (benign warm nodules). However, most nodules, including malignant ones, are actually non-functional, i.e. they do not produce hormones, thus not altering the blood TSH value.

Rarely, patients may complain of pain in the neck, jaw or ear. If a thyroid nodule is large enough to compress the trachea or esophagus, it can cause difficulty in breathing (dyspnea) and / or swallowing (dysphagia). In very rare cases, the patient may have hoarseness due to the invasion of the recurrent laryngeal nerve (the nerve that controls the motility of the vocal cords) by a malignant nodule.

What is the cause of thyroid nodules?

The cause of thyroid nodules is not known. By the age of 60, about half of the population has at least one thyroid nodule that can be diagnosed through palpation by the doctor or through an imaging exam (ultrasound, CT, MRI, PET). However, over 90% of thyroid nodules are benign.

Hashimoto’s thyroiditis, which is the most common cause of hypothyroidism, is associated with an increased risk of developing thyroid nodules. Iodine deficiency, which is now very rare in Italy, is related to the development of thyroid nodules.

How is a thyroid nodule studied?

  • Thyroid ultrasound: ultrasound plays a fundamental role in diagnosing nodular thyroid disease. Ultrasound is an instrumental investigation technique based on the ability of ultrasound to cross biological tissues and generate echoes which, when properly processed, are represented as visual images on a screen. Ultrasound allows you to accurately assess the size, structure and characteristics of the thyroid nodules. Nodules that are suspicious on ultrasound will be subjected to fine needle aspiration.
  • Thyroid scan: when a hyperfunctioning nodule or goiter is suspected.
  • Ultrasound-guided thyroid needle aspiration: the technique allows the cytological diagnosis of thyroid nodules or other masses in the neck (parathyroid glands, lymph nodes, other). The material extracted by a fine needle from the lesion to be examined is deposited on slides, fixed, and subsequently examined under the microscope.

What can be the cytological results of the thyroid needle aspirate?

There are various cytological classifications of thyroid nodules. The following is the Italian classification of thyroid cytology. This classification was developed by a group of experts on behalf of the Italian Societies of Endocrinology (AIT, AME and SIE) and Pathological Anatomy and Cytology (SIAPEC-IAP).

The diagnostic categories are as follows:

TIR 1 Not diagnostic

“Nondiagnostic” reports do not allow for a cytological diagnosis. Nondiagnostic reports may be inadequate and / or unrepresentative. This percentage varies essentially in relation to technical factors. A badly streaked and / or badly fixed and / or badly stained sample is defined as unsuitable, while a sample that does not have a sufficient number of cells belonging to the lesion to make the diagnosis is defined as non-representative.

Clinical actions: TIR 1 does not allow a diagnosis and it is therefore recommended to repeat the ultrasound-guided fine needle aspiration or follow-up.

TIR 2 Not Malignant / Benign

This category includes cytology from colloid or hyperplastic nodules, from autoimmune or granulomatous thyroiditis, and from other, less frequent, non-neoplastic conditions.

Clinical actions: Clinical and ultrasound follow-up. Repeat the fine needle aspiration in case of growth or ultrasound changes of the nodule.

TIR 3 Indeterminate Cytology

The majority of these cases are represented by microfollicular pictures which correspond, on the histological level, to hyperplastic adenomatous nodules, follicular adenomas or carcinomas or follicular variants of papillary carcinoma.

Two subclasses with different risk of malignancy are distinguished:

  • TIR 3 A Indeterminate lesion with low risk of malignancy: the risk of malignancy in this category is <10%.
  • TIR 3 B Indeterminate lesion with high risk of malignancy: the risk of malignancy in this category is 15-30%.

Clinical actions: TIR 3 A: close clinical and ultrasound follow-up; repetition of a fine needle aspiration is recommended during subsequent checks. TIR 3 B: the priority option is surgical excision. Indeterminate lesions can be subjected to biomolecular genomic analysis, or to search for particular genetic mutations associated with neoplasia. Genomic characterization makes it possible to avoid a high percentage (up to 96%) of surgical interventions. The role of ablative therapies has yet to be evaluated.

TIR 4 Suspected for malignancy

It includes samples in which malignancy is strongly suspected but not certain. The majority of these cases correspond to papillary carcinoma. Other malignancies are occasionally included in this category.

Clinical actions: repetition of the needle aspiration, surgical exeresis with possible intraoperative examination or ultrasound-guided ablative therapies.

TIR 5 Malignant

Includes specimens with conclusive cytological diagnosis of malignant neoplasm (papillary, medullary, poorly differentiated, anaplastic, lymphoma, non-epithelial or metastatic tumor).

Clinical actions: Surgical resection with extension based on the cytological finding and the clinical picture. In the case of anaplastic carcinoma, lymphoma or metastatic tumor, further diagnostic procedures are necessary to define the most appropriate treatment.

In selected cases of micropapillary carcinoma <2 cm (microPTC) without lymphatic metastases (T1N0), ultrasound-guided thermal ablation can be proposed as an alternative to surgical excision of the thyroid gland.

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