Faculty Bibliography

INTRODUCTION/BACKGROUND:There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs. METHODS:) was calculated to assess inter-rater reliability. RESULTS:= 0.79 (95% CI: 0.61-0.98). CONCLUSION/CONCLUSIONS:p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.

Introduction: SARS-CoV-2 (COVID-19) is known to cause severe respiratory infections with occasional accompanying pleural (PE), pericardial (PCE) or peritoneal effusion (PTE). The effect of COVID-19 disease on effusion cytology is not yet known. Therefore, our study aims to examine the cytomorphologic features and work-up of effusion fluid in patients in recovery from COVID-19 infection versus those with active disease.
Material(s) and Method(s): PE (n=15), PCE (n=1), PTE (n=19) samples from hospitalized patients with COVID-19 infection (6/1/2020-12/30/2020) were reviewed. EFs with metastatic carcinoma were excluded. Differential cell count (DCC), cytomorphology, and immunostains of EFs were retrospectively evaluated by a board-certified cytopathologist and compared between patients with active infection (AI, n=22, positive COVID-19 nucleic acid amplification test (NAAT) within 2 months) and recovery phase from COVID-19 (RC, n=13, negative COVID-19 NAAT for >2 months).
Result(s): Cytology diagnoses were: negative for malignancy (n=30), atypical (n=4), suspicious for malignancy (n=1). AI cases showed more atypical mesothelial cells than RC cases (Table 1, p<0.05), some with enlarged nuclei with prominent nucleoli and occasional multi-nucleation (Figure 1), and some with bizarre nuclei (Table 1, p<0.01). Immunostains were performed more often in AI than RC cases (50.0% vs 7.7%, p<0.05). DCC (available in 28 cases) showed no significant difference amongst AI and RC cases (Figure 1, p>0.05).
Conclusion(s): Our study found atypical and bizarre mesothelial cells to be present more often in effusions of cases with active COVID-19 infection than in samples from patients in recovery, though DCCs did not show significant difference. Diagnosis of malignancy may be considered in cases with such nuclear atypia, which explains increased immunostain work-up in AI cases. It is important for cytopathologists to consider the patients' COVID-19 infection status when evaluating effusion cytology cases. [Formula presented] [Formula presented] [Formula presented]
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Introduction: Preoperative diagnosis of pancreas ductal adenocarcinoma (PDAC) on endoscopic ultrasound guided fine needle aspiration (FNA) cytology is often required to determine proper therapy. Accurate cytopathology diagnosis on FNA may be challenging due to limited/suboptimal cellularity and gastrointestinal contamination with accurate diagnoses necessitating consideration of the full clinical and radiologic picture in evaluating the pancreatic lesions. In this study, we investigated predictive value of integrating cytology diagnosis, radiologic and clinical features in diagnosing pancreatic adenocarcinoma.
Material(s) and Method(s): Pancreatic FNA cases from 1/2016-12/2018 with >18 months of follow-up or histopathology diagnosis on surgical resection were retrieved (n=203). Cases were categorized as "Adenocarcinoma" or "Benign" according to the surgical resection pathology or clinical follow-up. Their documented serum CA19-9 level, and in-house radiologic reports were studied (n=177, Table 1). A multiplayer perceptron neural network (MNN) was trained and tested for the ability of using the integrated clinical and radiologic features and cytologic diagnosis to distinguish between benign and malignant cases.
Result(s): The sensitivity, specificity, and accuracy for pancreatic FNA cytology alone was 77.5%, 97.6%, and 88.4%, respectively. There were significant correlations between malignant outcome and cytology diagnosis, CA19-9 level and involvement of common bile duct (CBD), pancreatic duct (PD), superior mesenteric artery (SMA) or superior mesenteric vein (SMV) (Table 1, p<0.001). Integration of the cytology diagnosis and CA19-9 level showed 92% accuracy in predicting surgical outcome. The MNN highlighted cytopathology to be the most important factor in predicting pancreatic lesion outcomes, followed by the serum CA19-9 level and involvement of the SMA (Figure 1).
Conclusion(s): Integration of the clinical and radiologic information with cytology diagnosis can improve accuracy in evaluating pancreatic adenocarcinomas, especially in suboptimal FNA cytology specimens. [Formula presented] [Formula presented]
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Introduction: TERT promoter mutations in thyroid carcinoma suggest worse prognosis based on findings of a small number of studies. Additionally, pathologic features and clinical behavior of indeterminate thyroid nodules (ITN) with TERT promoter mutations remain less studied. Our study aims to explore the clinicopathologic features of ITN with TERT promoter mutations.
Material(s) and Method(s): A search conducted in our electronic medical record between 2015-2018 identified 18 cases with indeterminate thyroid fine-needle aspiration (FNA) cytology (Bethesda Class III, IV, and V) and a TERT mutation on molecular testing. 17 patients underwent thyroidectomy and were the subjects of this study.
Result(s): The mean age was 65 (range 38-83) with a female to male ratio of 9:8. The FNA Bethesda diagnoses were Class III in 9, IV in 8, and V in 1. Majority of patients who underwent thyroidectomy had malignant nodules (14,78%). Thyroidectomy diagnoses included classic PTC (5,29%), FVPTC (5,29%), follicular variant of papillary carcinoma (3,17%), poorly differentiated thyroid carcinoma (1, 6%), follicular adenoma (2,11%) and NIFTP (1,6%). Additional alterations were present in 11 cases, including NRAS(6), KRAS(2), and BRAF V600E (3). Of three cases with concurrent BRAF V600E mutation, two were metastatic, and one had tall cell features. Of two follicular adenoma cases, one had a concomitant NRAS mutation, and the other displayed negative results on Afirma testing. Malignant cases tended to occur in older patients, the majority exhibited follicular architecture, frequent oncocytic morphology, and higher pathologic stage (pT3 in 92%, pT2 in 8%).
Conclusion(s): Most TERT promoter mutations in ITN cytology are associated with high risk of malignancy and these malignancies are associated with unfavorable features such as advanced stage, capsular/vascular invasion, and metastatic disease. Few TERT promoter mutations have a benign outcome. Further studies on ITNs with TERT mutations are needed to determine the optimal management of these nodules.
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