PMID- 29512025 OWN - NLM STAT- MEDLINE DCOM- 20190307 LR - 20201105 IS - 1936-0568 (Electronic) IS - 1936-055X (Print) IS - 1936-055X (Linking) VI - 12 IP - 4 DP - 2018 Dec TI - Ubiquitin Immunostaining in Thyroid Neoplasms Marks True Intranuclear Cytoplasmic Pseudoinclusions and May Help Differentiate Papillary Carcinoma from NIFTP. PG - 522-528 LID - 10.1007/s12105-018-0905-7 [doi] AB - Papillary thyroid carcinoma (PTC) is defined by an invasive growth pattern and classic nuclear features: enlarged, grooved, overlapping nuclei with chromatin clearing and intranuclear cytoplasmic pseudoinclusions (INCP). True INCPs are characteristic of PTC, but may infrequently be seen in noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Nuclear abnormalities that mimic INCP ("pseudo-pseudoinclusions") are common in a variety of thyroid lesions. H&E and ubiquitin-stained whole tissue sections of classic PTC (n = 25) and NIFTP (n = 35) were evaluated. On H&E, true INCPs were present in all (100%) PTCs and absent in all NIFTPs (0%). Pseudo-pseudoinclusions were present in 13 (37%) NIFTPs. In 24 (96%) PTCs, ubiquitin was strongly expressed within INCPs. In NIFTPs, optically clear nuclei or pseudo-pseudoinclusions did not express ubiquitin (0/35). Occasionally, nuclear vacuoles in NIFTP demonstrated a marginated staining pattern, in which strong ubiquitin expression was seen at the periphery of the nucleus, but the central pale area was negative. In addition, 2 NIFTPs demonstrated intrafollicular psammomatoid calcifications which were strongly ubiquitin-positive. Psammoma bodies in PTC were ubiquitin-negative in the majority of cases. We report a previously undescribed finding: strong ubiquitin expression in true INCPs in PTC, absence of true INCPs in NIFTP, and absence of ubiquitin expression in pseudo-pseudoinclusions in NIFTP. This finding supports the difference between true INCPs (found only in PTC) and pseudo-pseudoinclusions (found in NIFTP). Using strict histologic criteria and ubiquitin immunostaining, the presence of true pseudoinclusions may exclude a diagnosis of NIFTP. Caution should be exercised when interpreting nuclear vacuoles or pseudo-pseudoinclusions. FAU - Cracolici, Vincent AU - Cracolici V AUID- ORCID: 0000-0002-6458-5517 AD - Department of Pathology, The University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA. vincent.cracolici@uchospitals.edu. FAU - Krausz, Thomas AU - Krausz T AD - Department of Pathology, The University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA. FAU - Cipriani, Nicole A AU - Cipriani NA AD - Department of Pathology, The University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA. LA - eng PT - Journal Article DEP - 20180306 PL - United States TA - Head Neck Pathol JT - Head and neck pathology JID - 101304010 RN - 0 (Biomarkers, Tumor) RN - 0 (Ubiquitin) SB - IM MH - Adenocarcinoma, Follicular/*diagnostic imaging MH - Biomarkers, Tumor/*analysis MH - Cell Nucleus/pathology MH - Diagnosis, Differential MH - Humans MH - Immunohistochemistry/methods MH - Inclusion Bodies/pathology MH - Thyroid Cancer, Papillary/*diagnosis MH - Thyroid Neoplasms/*diagnosis MH - Ubiquitin/*analysis PMC - PMC6232225 OTO - NOTNLM OT - NIFTP OT - Papillary thyroid carcinoma OT - Pseudoinclusions OT - Thyroid OT - Ubiquitin COIS- The authors declare that they have no conflict of interest. EDAT- 2018/03/08 06:00 MHDA- 2019/03/08 06:00 PMCR- 2019/03/06 CRDT- 2018/03/08 06:00 PHST- 2018/01/25 00:00 [received] PHST- 2018/02/28 00:00 [accepted] PHST- 2018/03/08 06:00 [pubmed] PHST- 2019/03/08 06:00 [medline] PHST- 2018/03/08 06:00 [entrez] PHST- 2019/03/06 00:00 [pmc-release] AID - 10.1007/s12105-018-0905-7 [pii] AID - 905 [pii] AID - 10.1007/s12105-018-0905-7 [doi] PST - ppublish SO - Head Neck Pathol. 2018 Dec;12(4):522-528. doi: 10.1007/s12105-018-0905-7. Epub 2018 Mar 6.