Diagnostic Utility of p62 Expression in Intranuclear Inclusions in Thyroid Core Needle Biopsy Specimens

Core needle biopsy (CNB) has been widely used as an alternative method to ultrasound-guided fine-needle aspiration cytology for histological diagnosis of thyroid specimens. However, nuclear artifactual vacuoles (NuVas) produced during tissue processing can be very difficult and sometimes impossible to distinguish from intranuclear inclusions (NuIns). P62 is an autophagy receptor that recognizes, targets, and eliminates toxic cellular materials during autophagy. Herein, we examined the utility of p62 immunohistochemical staining to detect NuIns in thyroid core needle biopsy specimens. Thirty-five thyroid CNB slides from 32 patients and corresponding resection specimens stained with hematoxylin and eosin were reviewed by two pathologists. The immunohistochemical staining pattern of p62 was used to differentiate NuIns from NuVas. The diameter of each nucleus (A) and NuIn (B) was measured, and the number of p62-expressing NuIn-positive (p62In) cells was counted using 1/2 (B/A) and 1/3 (B/A) criteria. The criterion of 1/3 includes NuIns larger than 1/3 and smaller than 1/2 of the nuclear diameter. The criteria of 1/2 includes NuIns larger than 1/2 of the nuclear diameter. By applying the 1/2 criterion, there were no p62In cells in follicular adenoma (FA) samples. However, in papillary thyroid carcinoma (PTC) samples, 22 of 25 specimens exhibited p62In cells. The sensitivity and specificity to distinguish FA from PTC using the 1/2 criterion were 0.88 and 1.00, respectively. By applying the 1/3 criterion, there was one p62In cell hit in FA samples. However, 23 of 25 PTC specimens showed p62In cells. The sensitivity and specificity to distinguish FA from PTC using the 1/3 criterion were 1.00 and 0.90, respectively. P62 is a useful marker for distinguishing FA and PTC based on CNB specimens. We suggest the 1/2 criteria for identifying p62In cells.