NIFTP

NIFTP tumors are considered benign, pre-cancerous growths that form inside the thyroid gland.

• Because NIFTP tumors are contained entirely inside the thyroid gland, do not grow / invade into nearby structures, and do not spread outside the thyroid via the lymphatic or blood system, they are not considered cancerous.

NIFTP tumors were previously known as an Encapsulated Non-invasive Follicular Variant Papillary Thyroid Cancer and considered cancerous.

• In 2017 the World Health Organization carefully considered research studying the long-term behavior of these tumors. As a result of this, they deemed them to no longer be cancerous and changed their name to NIFTP to reflect this.

NIFTP can only be diagnosed after the tumor has been removed with surgery and must meet very strict guidelines for diagnosis.

• NIFTP cannot be diagnosed on needle biopsy (FNA) or molecular analysis.

NIFTP tumors are cured when removed completely with surgery.

Since NIFTP tumors are not cancerous, there is no risk for recurrence or spread outside the thyroid, therefore no additional surgery or Radioactive Iodine (RAI) treatment is needed.

NIFTP tumors present similar to other thyroid nodules and their work up eventually leads to an indeterminate FNA results:

• • Bethesda III – Atypia of Undetermined Significance (AUS); ~16% risk for cancer, higher risk when nuclear atypia is present.
    OR
  • Bethesda IV – Follicular Neoplasm (FN); 23% risk for cancer.
• Subsequent molecular analysis often reveals a RAS like DNA mutation.
  • Unlike other DNA alterations causing thyroid cancers, the presence of a RAS DNA mutation does not always mean the nodule is cancerous at the time of the biopsy.
  • Instead, the presence of a RAS mutation indicates the nodule will always have the potential to become cancerous and at time of the diagnosis can exist anywhere along the progression of a benign thyroid nodule to thyroid cancer:
    • Benign follicular adenoma -> pre-cancerous NIFTP -> Follicular Thyroid Cancer (FTC) or Follicular Variant of Papillary Thyroid Cancer (fvPTC).
      • Therefore, when RAS mutations are present on molecular analysis, the nodule in question has the potential to be cancerous at that time of diagnosis, or if not cancerous at that time, a high risk of developing into cancer in the future if not removed surgically.
        • Additional RNA testing with some molecular analyses can further rule out the presence of cancer at the time of biopsy.
      • Surgery (especially if the patient is younger or the nodule has been growing) or an intensified ultrasound surveillance program should be heavily considered when RAS mutations are identified.
    • If any other non-RAS like DNA alteration (such as BRAF or TERT) are also identified at the same time on molecular analysis, the tumor is highly unlikely to be benign or a precancerous NIFTP, and surgery is highly recommended.

NIFTP Tumors are an example of what the WHO describes as a benign low-risk follicular derived thyroid neoplasm – surgery is required to make the diagnosis following an indeterminate FNA result.

• These also include:
  • Follicular thyroid tumor of uncertain malignant potential (FT-UMP).
  • Well differentiated thyroid tumor of uncertain malignant potential (WD-UMP).
  • Hyalinizing Trabecular Thyroid Tumors (HTT) – these tumors can sometimes be mistaken for papillary thyroid cancer or Bethesda V – Suspicious for Malignancy (SUSP; 65% risk for cancer) on FNA.