Faculty Bibliography

BACKGROUND:Hurthle cell lesions often pose diagnostic challenges, despite their common occurrence on thyroid fine-needle aspiration cytology (FNAC). The associated molecular alterations are also not well understood. Therefore, our study aimed to delineate the molecular profile of Hürthle cell lesions classified as Bethesda Categories III or IV (atypia of undetermined significance (AUS) or suspicious for follicular neoplasm (SFN)) on FNAC and to correlate this molecular profile with surgical resection findings. METHODS:This study consisted of 188 Hürthle cell lesions with indeterminate cytology and ThyroSeq® v2/v3 molecular testing results. Surgical follow-up was available for 33 cases. RESULTS:The majority of indeterminate Hürthle cell lesions had negative ThyroSeq® results (61%) and were benign on available surgical follow-up. The most prevalent mutations involved the RAS gene (21%), which were associated with benign lesions, non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and malignancy. The remaining mutations involved less than 18% of the cases, including PAX8/PPARG (3.7%), TSHR (3.7%), EIF1AX (2.7%), MET (2.1%), PTEN (1.6%), clonal copy number alteration (1.6%), TERT (1.1%), and 0.5% each of GNAS, PIK3CA, and TP53 mutations. On follow-up, 45% were benign, 24% were NIFTP, and 30% were malignant. The malignant cases had different molecular alterations. CONCLUSION/CONCLUSIONS:No single molecular alteration defines cytologically indeterminate Hürthle cell lesions; the majority of cases have low-risk or no molecular alterations and are benign on follow-up. These findings suggest that molecular testing may be useful, but is not definitive, in determining which cases may be managed conservatively; additional studies are needed to fully determine the negative predictive value in ruling out malignancy.

Objectives/UNASSIGNED:To evaluate whether non-small cell lung carcinoma (NSCLC) cytology specimens are reliable for programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) testing. Methods/UNASSIGNED:Fifty-two cell blocks (CBs) with corresponding surgical pathology PD-L1 IHC testing were stained with a Dako PD-L1 pharmDX antibody (clone-22C3). Tumor cellularity was recorded as <100 or ≥100 cells. PD-L1 IHC was scored by percentage of tumor cells staining (<1%, ≥1%-49%, ≥50%) and compared between matched cases. Results/UNASSIGNED:Substantial agreement (κ = 0.63; 95% CI, 0.53-0.73) was reached between matched CB and surgical cases in CBs with ≥100 tumor cells compared to CBs with <100 tumor cells (slight agreement, κ = 0.19; 95% CI, 0.04-0.35). Overall, there was 67% agreement among paired cases (35/52 cases, κ = 0.51; 95% CI, 0.42-0.60). Conclusions/UNASSIGNED:CBs can be utilized for PD-L1 IHC testing, as illustrated by the 67% agreement between CB and surgical cases in our study. Disagreement is attributable to intratumoral heterogeneity and CB cellularity.

Cells with their nucleus pushed to the periphery in a crescent-like fashion by intracytoplasmic vacuole(s) are referred to as signet ring cells when the vacuole(s) contain mucin and signet ring-like cells when they are empty or contain a material other than mucin. Signet ring cells are commonly associated with adenocarcinomas. These cells are uncommon in the endometrium and have been found to be associated with both malignant and benign processes. We report the first case of signet ring-like cells within endometrial glands with Arias-Stella reaction.