Malignant Thyroid Nodules


Dr Roberto Novizio

Malignant thyroid nodules can be classified as: 

- Differentiated: originating from a tumor degeneration of thyroid cells (thyrocytes responsible for follicular thyroid cancer and papillary thyroid cancer; parafollicular cells responsible for medullary thyroid carcinomas);

- Undifferentiated: Anaplastic thyroid cancer, resulting from the dedifferentiation of a differentiated tumor of the thyroid. Unlike differentiated tumors, anaplastic carcinomas lose the ability to collect iodine (and therefore intuitively they cannot be treated with radiotherapy with radioactive iodine).

- Non-Epithelial cells (rare): Linfoma; Sarcoma; Metastasis (frequently from kidney, lung and mammary gland)


About 75-80% of thyroid malignancy is Papillary thyroid cancer (PTC). It can be diagnosed on cytology obtained by fine needle aspiration, where It has characteristic nuclear and cytoplasmic changes. 

thyroid cancer
thyroid cancer
Malignant thyroid nodules can be classified as:

Papillary thyroid cancer has a peak of incidence in the third and fourth decade of life. Ofter it presents itself as multifocal, with very low tendency to give blood metastasis (to lungs, liver, bones and central nervous system), which however increases in untreated patients or elderly. 

PTC has a local invasiveness through the glandular and lymphatic capsule, therefore it presents very early metastasis to lymph nodes. Fortunately, it is good to remembered that it has an extremely slow growth, and even if there is any lymph node metastasis, the prognosis is very good when well treated. 

Surgery and radioiodine are very effective treatments: 95% of patients survive after 10 years from diagnosis.

One type of papillary carcinoma does not capture iodine and is poorly differentiated: Insular Thyroid Cancer. It is recognizable by histological examination, and it does not follow the classic course of PTC. The prognosis is usually poor. 


About 10-15% of thyroid malignancies are Follicular Thyroid Cancers. Differently from follicular thyroid adenoma, the follicular thyroid carcinoma invades the follicular capsule and the vessels, with very low tendency to give lymph node metastases but high tendency to give hematogenous metastases towards lung, bone and Central Nervous System. They have a worse prognosis than PTC. 

Follicular thyroid cancer is not multifocal, and it has a relatively slow growth. Treatments involve surgery and radioiodine: 75% of patients survive after 20 years from diagnosis.

These carcinomas include Hurtle cell cancer, which is a slightly more aggressive variant.


About 5% of thyroid malignancies are Medullary Thyroid Cancers: it occurs sporadically in 75% of cases, or in family forms (15% of cases) where it tends to be multifocal. 

This type of thyroid cancer does not originate from thyrocytes (cells that from thyroid follicle) but from parafollicular cells (or C cells), whose job is to produce calcitonin, an hormone involved in Calcium homeostasis.

They are involved in two characteristic endocrine tumor genetic syndromes: multiple endocrine neoplasia 2 or MEN2. In this syndrome, medullary thyroid cancer coexists with pheochromocytoma: that's why as a doctor diagnoses Medullary cancer he has also to look for pheochromocytoma before suggest surgical removal of the thyroid (when possible).

It has a very high tendency to early lymph node diffusion and for this reason it has surgical indication of lymphadenectomy (lymph nodes surgical removal) even if there is no evidence of pathological lymph nodes.

One of the peculiar markers of these tumor types is the increase in calcitonin levels which strongly addresses the diagnosis. However confirmation by cytological examination is mandatory. 

Survival is 75% at 10 years and therapy this time does not involve radioiodine, since C cells do not pick up iodine.


Anaplastic thyroid carcinoma is characterized by a very high subversion of cell morphology. It is very rare, but more frequent in elderly patients (because in older patients cancer has the time to dedifferentiate from a differentiated form, often from a follicular cancer). 

It has a very high tendency to infiltrate adjacent structures such as trachea, esophagus, vessels blood, skin. It is a very aggressive tumors that are often detected when inoperable or when it has already given distant metastases. 

Palliative therapies such as feeding tubes (in case of esophageal infiltration), tracheal prostheses to keep the lumen patent and any chemotherapy, radiotherapy and surgery to reduce mass are usually used in these patients.

It is very invasive locally, lymphatically and hematogenously and has an average survival time from the diagnosis of 6 months.