All About Papillary Thyroid Cancer

What Is Papillary Thyroid Cancer?

The epithelial cancer papillary thyroid carcinoma (PTC) exhibits follicular cell differentiation and several unique nuclear characteristics. It has the best overall prognosis and is the most common thyroid tumor. The tumor typically presents as an irregular solid mass, though it occasionally has cystic characteristics. One of its key characteristics is the capacity of papillary thyroid carcinoma to invade nearby structures, such as lymphatics. At the initial presentation, 10 % of patients may have metastatic disease. For patients under 45, the prognosis is generally favorable.

What Is the Classification of Papillary Thyroid Cancer?

The most aggressive papillary thyroid carcinoma variants are as follows:

1. The diffuse sclerosing variant (DSV).

2. Tall cell variant (TCV).

3. Columnar cell variant (CCV).

4. Solid variant (SV).

5. Hobnail variant(HV).

These variants may have lower survival rates linked to higher rates of recurrence and metastasis. Furthermore, the treatment of these patients is frequently insufficient or ineffective due to the lack of understanding of the natural history of these more aggressive variants.

What Is the Incidence of Papillary Thyroid Cancer?

About one percent of all cancers are thyroid carcinomas, which cause 0.2 % of cancer deaths. The most frequent type of malignant thyroid cancer that causes the most fatalities is papillary thyroid carcinoma. This carcinoma, which accounts for 80 to 85 % of thyroid cancers, is common in nations with iodine-rich diets.

Papillary thyroid carcinoma is rarely identified as a congenital tumor and can develop at any age. Patients are typically diagnosed with tumors between the third and fifth decades. In ratios of 2:1 to 4:1, women are affected more frequently than men. However, even teenagers and young children can develop papillary thyroid carcinoma. The incidence of papillary carcinomas and, in some cases, their morphology appears to be influenced by dietary iodine concentrations.

What Is the Etiology of Papillary Thyroid Cancer?

The etiology of papillary thyroid cancer is speculated to be low-dose radiotherapy to the head and neck for benign diseases such as lymphangiomas, hemangiomas, enlarged thymus, tonsils, and adenoids. However, thyroid cells also undergo a neoplastic transformation due to increased pituitary thyrotropin (TSH) secretion from the damaged follicular epithelium due to DNA (deoxyribonucleic acid) breakage, causing mutations and translocations.

What Are the Clinical Features of Papillary Thyroid Cancer?

• Diffuse Sclerosing Variant- Almost 6 % of all papillary thyroid cancers are diffuse sclerosing variants. This lesion frequently manifests as a diffuse thyroid gland enlargement. It differs clinically from classic papillary thyroid cancer. The diffuse sclerosing variant is most commonly diagnosed in the third decade of life, with a mean age of 30. This variant of papillary thyroid cancer is most frequently observed following exposure to high doses of radiation; additionally, 10 % of pediatric papillary thyroid cancers are diffuse sclerosing variants. They also exhibit a high frequency of cervical and pulmonary metastases at presentation and seem more aggressive than classic papillary thyroid cancer.

• Tall Cell Variant- The World Health Organization (WHO) characterized the tall cell variant as a tumor made up of cells that are two to three times as tall as they are wide and that show abundant oncocytic-like cytoplasm. Thus, tall-cell regions are found in 30 % of all papillary thyroid carcinoma tumor cells, which must be tall cells to diagnose the tall-cell variant.

How is Papillary Thyroid Cancer Diagnosed?

Diffuse Sclerosing Variant-

• Histological Features: One or both thyroid lobes are diffusely affected, and there is extensive lympho-vascular invasion, extensive squamous metaplasia, abundant psammoma bodies, patchy to dense lymphocytic infiltrates, and dense sclerosis.

• Molecular Features: The common genetic alterations are rearranged during papillary thyroid carcinoma, resulting in diffuse sclerosing variants with variable molecular profiles. Patients with advanced disease stages and poor clinical outcomes are likelier to have papillary thyroid carcinoma alterations.

Tall Cell Variant -

• Histological Features: The tall cell variant is characterized by a significant proportion of tall cells, as mentioned above, and by stretched, elongated follicles in histologic sections. This finding, also known as a "tram-track appearance," is noticed at low magnification. Although non-invasive encapsulated tall cell variants of papillary thyroid cancer make up most TCVs, one may occasionally encounter an encapsulated tumor.

• Molecular Features: Similar to papillary thyroid cancer, the BRAFV600E mutation affects tall cell variants. Its prevalence ranges from 80 % to 100 %. Cases with more than 50 % elevated cell components are more likely to have BRAF mutations. These cases also frequently have a pathogenic secondary mutation, usually in the TERT promoter gene.

What Is the Treatment for Papillary Thyroid Cancer?

• Treatment for these variants is essentially the same:

  • Total thyroidectomy.

  • Prophylactic central compartment node dissection (T3 and T4 tumors).

  • Therapeutic neck dissection if lymph nodes are involved.

• The requirement for radioactive iodine therapy after total thyroidectomy should be considered and radical approaches should be regarded to avoid a worse prognosis.

• Additionally, vigorous treatment is advised, particularly in the early stages of the illness.

• Aggressive recurrent thyroid tumors are frequently non-radioactive iodine therapy and fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive.

• Early diagnosis and close monitoring are crucial in managing these patients.

• Future therapies for these tumors might involve molecular pathway targeting. Diffuse sclerosing variant (DSV), which is more common in children and young patients, tends to be iodine-avid, and even patients with distant metastases have a good prognosis, which is one factor that must be considered.

• On the other hand, the different variants have a poor prognosis and primarily affect older patients with locally invasive or recurrent diseases.

• The biological behavior of all of the variants of papillary thyroid carcinoma becomes evident, and the aggressive ones have a poorer outcome.

• The prognosis is generally excellent and comparable to papillary thyroid carcinoma for small tumors intrathyroidal at presentation.

• Therefore, the treatment choice is based on the tumor's size at presentation rather than the histological variant of papillary thyroid carcinoma.

What Is the Prognosis for Papillary Thyroid Cancer?

Papillary thyroid carcinoma has a good prognosis and is biologically indolent.

Conclusion

The correct diagnosis of the most aggressive papillary thyroid carcinoma variants can be complex, even for experienced histopathologists. Every aggressive variant produces a worse result than traditional papillary thyroid carcinoma. In addition, the prognostic significance of the aggressive papillary thyroid carcinoma variants' morphology alone is unknown. Because of this uncertainty, skilled clinicians will decide on an individual basis how much surgical intervention and adjuvant therapy are needed based on the tumor size at the time of initial presentation. To evaluate the independent predictive value of these variants, new molecular discoveries may pave the way for future targeted therapies that could increase these persons' chances of survival.