Thyroid Cancer

Frequently, for differentiated tumors, the diagnosis is accidental: following radiological examinations performed for other problems or controls. 
In patients undergoing neck irradiation, with familiarity for thyroid neoplasia, with the presence of rapidly growing thyroid nodules, or fixed and hard thyroid nodules, or in case of appearance of suspicious lymph nodes in the neck, it is recommended to perform an in-depth ultrasound in order to discriminate nodules in which it is necessary to perform a needle aspiration from those not suspicious.
Only in particular cases, when ultrasound suggests extracapsular extension or mediastinal involvement, the radiological diagnosis can be integrated with CT (computerized axial tomography) of the neck or MRI (magnetic resonance imaging) with contrast mediu.
For bone marrow cancer the situation is different:
In 1 case out of 2, there is the involvement of neck lymph nodes that can be the first sign of disease, and in 1/5 of cases, there are also metastases to liver, lung and bone.  
Serum calcitonin assay is one of the screening tests for medullary thyroid cancer, as is CEA (carcinoembryonic antigen), which should be assayed along with calcitonin.
Ultrasonography associated with needle aspiration in case of suspicion is the diagnostic test of reference followed by second level investigations such as CT and MRI with the same value of differentiated tumor.
In contrast, PET with radiolabeled glucose (FDG) is usually not very sensitive, whereas PET with gallium 68 might be more indicative.
In addition, all patients with medullary thyroid cancer should be screened for the RET gene mutation, which indicates a familial transmission and therefore an increased risk of developing medullary thyroid cancer. In fact, if mutation is present, relatives of the patient should also be examined.
Anaplastic thyroid cancer is the most aggressive: in 80% of cases it presents as a locally advanced disease with involvement of the lymph nodes of the neck, and 50% already have metastases to the lung, bone or brain to the moment of examination carried out as for differentiated tumors, with the addition of PET with FDG to better characterize the metastatic disease. In addition, a thorough laryngoscopic or panendoscopic examination allows assessment of the respiratory space and involvement of the neck structures responsible for breathing and feeding.

The decision for differentiated cancers is made first based on risk levels:

Low risk:

• No metastases
• No residual tumor
• Non-invasive and non-aggressive tumor

Medium risk:

• presence of tissue invasion around the thyroid gland
• involvement of neck lymph nodes
• uptake of iodine by tissues outside the thyroid after the first radiometabolic treatment.

High risk:

• Invasive tumor
• Tumor not completely eliminated by surgery
• Presence of metastases
• High or rapidly increasing thyroglobulin values

If the tumor is still small (<4cm) and localized (negative lymph nodes), it is removed by surgery that may involve the total removal (total thyroidectomy) or partial removal (hemithyroidectomy) of the thyroid gland (LOW RISK). In case of risk factors, such as extracapsularity or lymph node involvement, removal should be total (HIGH RISK), associated with removal of neck lymph nodes (lymphadenectomy).
Adjuvant therapy (after surgery) with radioiodine (radiometabolic therapy) is considered in differentiated thyroid tumors (papillary and follicular) in the presence of:

• Tumor > 1 cm or aggressive type
• Tumor > 4 cm
• Extrathyroidal extension
• Lymph node localizations (pN+); in aggressive histologic forms 

In case of tumors <1cm with microscopic extrathyroidal extension, and in case of tumors with less than 5 central compartment lymph node metastases <2 mm, instead, radiometabolic therapy can be avoided (MEDIUM RISK). 
In any case, the initiation of hormonal therapy with recombinant TSH at doses that maintain TSH at the lower limit of the normal range is always recommended to reduce the risk of relapse. 
If, after surgery and radiometabolic therapy, there is a relapse of the disease (recurrence) or evidence of persistence, the possibility of a new surgery should be evaluated and, if not, a radiotherapy treatment with external beams can be scheduled, even if in slow-growing diseases, very localized and small (<3cm) in low-risk patients it is possible to proceed initially with a strict control and intervene only later. 
If, on the other hand, the disease is at an advanced stage, involving other organs (metastatic), the goal can no longer be recovery but the chronicity of the disease by means of: radiometabolic therapy after performing scintigraphy to verify sensitivity to iodine. 
In case of iodine resistant diseases progressing after radiometabolic therapy, the initiation of biological therapies with tyrosine kinase inhibitors (TKI), e.g. Sorafenib and Lenvatinib, is indicated.
In case of progression to biological therapy, in patients who maintain good general conditions, it is expected to start chemotherapy generally with adriamycin 60 mg/m2 every 3 weeks up to a maximum of 459mg/m2 totally to avoid side effects on the heart. Subsequently, treatment with taxol or taxotere could be evaluated, even if the data in favor of these drugs are still insufficient.
For bone marrow tumors, subject to poor results of medical, radiometabolic and radiotherapy therapies, surgery is the only truly effective therapy, and includes both thyroid (total thyroidectomy) removal and possibly removal of neck lymph nodes. Hormone replacement therapy with levothyroxine should be initiated 4-6 weeks after total thyroidectomy.
In addition, for these types of tumor, in case of recurrence, surgery is the main choice, but, if it is not feasible, the choice will be external beam radiotherapy, the same as for such risk factors as: disease that with the involvement tissues outside the thyroid, disease extended to the mediastinum, and residual disease after surgery. At the same time, radiotherapy should be considered for disease extensively involving lymph nodes and in the presence of extracapsularity (disease extending from lymph nodes to surrounding tissues).
In the case of metastatic disease, biological therapy with drugs that block the growth of blood vessels (antiangiogenetics) supported by local symptomatic treatments or targeted to treat single metastases is the main choice.
The drugs available to us today are 2 tyrosine kinase inhibitors: Vandetanib and Cabozantinib. Subsequently, chemotherapy with adriamycin associated or not with cisplatin or dacarbazine associated or not with 5-fluorouracil is the treatment of choice.
For anaplastic tumor, the first choice treatment is surgery (total thyroidectomy) with removal of neck lymph nodes (lymphadenectomy) possibly preceded by external beam radiotherapy or chemotherapy concomitant with radiotherapy, where possible, to reduce the tumor mass or followed by the same (within 3 weeks after surgery) to increase local and lymph node disease control (locoregional).
On the other hand, chemotherapy combined with radiotherapy is the best choice for the treatment of inoperable tumors.
The chemotherapeutic drugs most frequently used for the treatment of metastatic disease are taxanes (taxol/taxotere), platinants (cisplatin/carboplatin) and adriamycin, alone or even more effectively in combination.