Noninvasive Encapsulated Papillary RAS-Like Thyroid Tumor (NEPRAS)

Abstract

Abstract Introduction: The diagnosis of thyroid tumors arising from follicular cells that are encapsulated/well delimited and noninvasive is a challenge. When unequivocal nuclear alterations are present, the final diagnosis can range from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and classical/encapsulated papillary thyroid cancer (PTC), including aggressive subtypes, to poorly differentiated carcinoma. As proposed recently, the presence of papillae in the absence of exuberant nuclear alterations (nuclear score 2), given that the other criteria for NIFTP are met, may not be sufficient for the diagnosis of PTC. This condition is called “noninvasive encapsulated papillary RAS-like thyroid tumor” (NEPRAS), whose nature would be borderline and not malignant. Revising our cases of tumors > 1 cm that were diagnosed previously as PTC and that were encapsulated/well delimited and noninvasive, we found three cases of NEPRAS. We now revised our cases of tumors > 1 cm diagnosed previously as well-differentiated tumor of uncertain malignant potential (WDT-UMP) because the nuclear alterations were not considered to be sufficient for the diagnosis of PTC on that occasion. Case: In a 29-year-old euthyroid male patient with a single thyroid nodule whose fine-needle aspiration had revealed indeterminate cytology, a single tumor measuring 3.2 cm was reclassified from WDT-UMP to NEPRAS. For this diagnosis, the tumor met the following criteria: encapsulation or clear demarcation, no vascular or capsular invasion, presence of papillae, < 30% solid/trabecular/insular growth pattern, no tumor necrosis or high mitotic activity, and nuclear score 2. The BRAFV600E mutation was absent. The patient continues to show no signs of recurrence 7 years after lobectomy. Conclusion: Despite the presence of papillae, some tumors may be reclassified from malignant (encapsulated PTC) to borderline (NEPRAS). This proposal would result in a change of management, with the same implications as those seen for the change from noninvasive encapsulated follicular variant of PTC to NIFTP.