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

Abstract

Background/Aim: Core needle biopsy (CNB) has been widely used as an alternative method to ultrasoundguided 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. Patients and Methods: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. Results: 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. Conclusion: P62 is a useful marker for distinguishing FA and PTC based on CNB specimens. We suggest the 1/2 criteria for identifying p62In cells.Ultrasound-guided fine-needle aspiration cytology (FNAC) is a common and useful method for diagnosing thyroid nodules (1). If FNAC fails or is inconclusive, patients should receive repeated FNAC or diagnostic surgery (2,3). Ultrasound-guided thyroid core needle biopsy (CNB) is widely used to diagnose lesions with inconclusive or atypia of undetermined significance FNAC results (3-6). CNB has the benefit of allowing for immunohistochemical staining (IHC) and observation of the features of stromal invasion. However, artifactual nuclear vacuoles (NuVas), intranuclear artifacts derived from the production of hematoxylin and eosin (HE)-stained slides, can be very difficult and sometimes impossible to distinguish from intranuclear inclusions (NuIns). NuIns are important pathological features for the diagnosis of papillary thyroid carcinoma (PTC). In PTC, NuIns have more sharply delineated rims than NuVas, whereas NuVas are more irregular in shape and only lightly stained withHE (2). Schwertheim et al. (7) used IHC of several autophagy-associated proteins, including p62, to detect NuIns in PTC. Theyproved that NuIns are entirely 1...