Faculty Bibliography

Background: Growing evidence suggests the prognostic significance of SATS in patients with early-stage lung adenocarcinoma, in particular, those with sublobar resection. However, published studies used various definitions for STAS; the diagnosis of STAS may be subject to interobserver variability that, in turn, may result in the difference in prevalence and prognostic significance of STAS across institutions.
Design(s): The study cohort consisted of stage 1 lung adenocarcinomas resected at two institutions (cohort A: n=283; cohort B: n=198) during similar time periods with similarly decent follow-up. Both institutions had applied similar grossing/processing protocols. The prevalence of STAS and its association with clinicopathologic variables, recurrence free survival (RFS), and overall survival (OS) were compared between the cohorts. The variables included type of operation, AJCC 8th stage, histologic grade, as well as the presence of lepidic, micropapillary (mPAP), or solid (SOL) patterns (5% cut-off for presence).
Result(s): The prevalence of STAS was 7% in cohort A and 39% in cohort B (p<0.0001). The tumor histologic grade (high grade: 21% in A vs. 37% in B, p=0.0001) and AJCC stage (Stage 1B: 19% in A vs. 13% in B, p=0.048) also differed between the cohorts, while no difference was seen in the other variables. STAS was associated with high grade histology, the absence of lepidic and the presence of mPAP and SOL patterns (p<0.01 for all) in both cohorts, while it was also associated with stage 1B in cohort A (p=0.016). In multivariate analysis, STAS was associated with high grade histology (p<0.0001) and marginally with the presence of mPAP (p=0.065) in cohort A, and lobectomy (p=0.016), the presence of mPAP (p<0.0001) and SOL (p=0.027) in cohort B. Regarding survival, STAS was associated with shorter RFS (p=0.030) and OS (p=0.048) in cohort B and with shorter OS (p=0.040) and marginally with shorter RFS (p=0.060) in the sublobar resection subset of cohort B by univariate analysis, while STAS had no bearing on survival in the lobectomy subset or cohort A. Of note, no difference in RFS and OS was seen as a whole between the cohorts.
Conclusion(s): The prevalence and prognostic significance of STAS differ between the two institutional cohorts. While this may be explained in part by the difference in patient populations, subjectivity to the diagnosis of STAS may potentially contribute. Additional multi-institutional studies to better define and improve reproducibility of STAS are warranted

Background: Fine needle aspiration (FNA) of salivary gland lesions is a fast, minimally invasive and cost-effective procedure that aids in early patient management decisions. Recently, the Milan System for reporting Salivary Gland cytopathology (MSRSGC) was published in order to establish diagnostic categories with implied malignancy risks and recommended clinical follow-up. Our study aims to assess the interobserver reproducibility of salivary gland cytology diagnoses using the MSRSGC.
Design(s): Salivary gland cytology slides from 101 cases with surgical pathology follow-up from 11/2016-06/2019 were blindly and independently reviewed and classified according to the MSRSGC by four cytopathologists. Unweighted and linearly weighted percent agreement and Gwet's AC1 coefficients were calculated in AgreeStat 2015.6/Windows (AgreeStat Analytics).
Result(s): Unweighted percent agreement was 0.69 (substantial agreement) and weighted percent agreement was 0.92 (almost perfect agreement). Unweighted Gwet's AC1 was 0.64 (substantial agreement), and weighted Gwet's AC1 was 0.84 (almost perfect agreement) (Table 1). 50 of 101 (49%) cases had complete agreement among all 4 observers, 77 (76%) had at least 3 observers agreeing on the same diagnosis, and 99 (98%) had at least 2 observers agreeing on the same diagnosis. Category IVA (benign neoplasm) was the most likely to show interobserver agreement: among the 51 cases in which at least 2 cytopathologists agreed on a diagnosis of category IVA, 34 (67%) showed complete agreement among all 4 cytopathologists. Two cases showed no agreement among any observers. One low-grade mucoepidermoid carcinoma had MSRSGC diagnoses ranging from I to IVB, and one secretory carcinoma had MSRSGC diagnoses ranging from III to VI. Low-grade mucoepidermoid carcinoma is reportedly the most common malignant salivary gland tumor associated with false-negative diagnoses on cytology and is often misdiagnosed as a pleomorphic adenoma, due to the presence of bland-appearing intermediate cells as well as confusion between mucin and chondromyxoid stroma (Figure 1). The case of secretory carcinoma showed scant cellularity on cytology, confounding an accurate diagnosis (Figure 2).
Conclusion(s): Interobserver reliability analyses using the MSRSGC showed substantial to almost perfect agreement among the four observers in our study. Only two cases showed no agreement. Category IVA (benign neoplasm) is the most likely to show complete agreement among all observers

The COVID-19 pandemic has presented countless new challenges for healthcare providers including the challenge of differentiating COVID-19 infection from other diseases. COVID-19 infection and acute endocarditis may present similarly, both with shortness of breath and vital sign abnormalities, yet they require very different treatments. Here, we present two cases in which life-threatening acute endocarditis was initially misdiagnosed as COVID-19 infection during the height of the pandemic in New York City. The first was a case of Klebsiella pneumoniae mitral valve endocarditis leading to papillary muscle rupture and severe mitral regurgitation, and the second a case of Streptococcus mitis aortic valve endocarditis with heart failure due to severe aortic regurgitation. These cases highlight the importance of careful clinical reasoning and demonstrate how cognitive errors may impact clinical reasoning. They also underscore the limitations of real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 testing and illustrate the ways in which difficulty interpreting results may also influence clinical reasoning. Accurate diagnosis of acute endocarditis is critical given that surgical intervention can be lifesaving in unstable patients.

OBJECTIVES/OBJECTIVE:To describe the histologic features that are helpful in the diagnosis of the rare bronchiolar adenomas/ciliated muconodular papillary tumors (BAs/CMPTs) during intraoperative consultation. METHODS:Multi-institutional retrospective review of frozen sections of 18 BAs/CMPTs. RESULTS:In 14 of 18 cases, BA/CMPT was the primary reason for sublobar lung resection, and in 4 cases, BA/CMPT was an incidental finding intraoperatively for resections performed for carcinoma in other lobes. There were 11 proximal-type/classic BAs/CMPTs and 7 distal-type/nonclassic BAs/CMPTs. Only 3 (16.7%) of 18 were correctly diagnosed at the time of frozen section, all of which were proximal type/classic. The remainder were diagnosed as adenocarcinoma (n = 7); invasive mucinous adenocarcinoma (n = 1); non-small cell lung carcinoma (n = 1); cystic mucinous neoplasm, favor adenocarcinoma (either mucinous or colloid type) (n = 1); favor adenocarcinoma, cannot exclude CMPT (n = 1); atypical proliferation (n = 2); mucinous epithelial proliferation (n = 1); and mucous gland adenoma (n = 1). CONCLUSIONS:BA/CMPT can potentially be misdiagnosed as carcinoma during intraoperative consultation. On retrospective review of the frozen sections, the presence of the following may help to avoid misdiagnosis: a mixture of bland ciliated columnar cells, mucinous cells, and, most important, a basal cell layer, as well as a lack of necrosis, significant atypia, and mitoses.

Immunohistochemical (IHC) stain for PD-L1 as a biomarker for immunotherapy is recommended in non-small cell lung cancer (NSCLC). Under the FDA, the selection of patients for pembrolizumab requires companion diagnostic testing using the Dako Agilent PD-L1 IHC 22C3 pharmDx kit performed on the Dako Autostainer Link 48 platform. However, because it is not widely available, there is need for cross-platform validation. Existing studies provide incomplete protocol detail. In our study, 73 lung tumors were stained using the FDA-approved test ('gold standard'). The same blocks were stained using two different models of the Ventana DISCOVERY platform (ULTRA, n = 73 and XT, n = 70) using different parameters, and interpreted by three pathologists. The ULTRA group met College of American Pathologists (CAP) validation criteria (concordance 91.8%) while the XT group did not (concordance 67.1%). Using tumor proportion score (TPS) ≥1% and TPS ≥50% as cut-offs, the ULTRA protocol had higher sensitivity (97.8% and 91.7%) than XT (73.3% and 60.9%) and similar specificity (ULTRA 88.9% and 100%, XT 88% and 100%). Discordance between ULTRA and XT was 27%, and in all these cases ULTRA was concordant with gold standard. Interobserver reliability was substantial for ULTRA and almost perfect for XT, providing evidence that staining rather than observer variability accounts for XT's inferior performance. Cross-validation of the clinically used 22C3 anti PD-L1 antibody test with substantial interobserver agreement is possible on the commonly used the Ventana DISCOVERY ULTRA automated instrument, while the validation failed on the XT. Cautious attention to detail must be paid when choosing cross-validation parameters.

Introduction: Recent studies evaluating p16 immunohistochemistry (IHC) in cell blocks (CB) of fine needle aspirations (FNAs) in patients with oropharyngeal squamous cell carcinoma (OP-SCC) have shown good correlation between cytology and surgical pathology. Our study aimed to determine the reproducibility of p16 IHC scoring in CBs. Additionally, we evaluated whether interobserver variability would significantly affect the optimal threshold for p16 IHC positivity in CBs.
Material(s) and Method(s): 40 FNAs from 2014-2019 of head and neck squamous cell carcinoma with p16 IHC were obtained. Surgical pathology p16 IHC results were set as reference. p16 IHC stained CBs were scored independently by 5 cytopathologists and recorded as percentage of tumor cell positivity: 0%,0-1%,1-10%,10-50%,50-70%,70%. AgreeStat2015.6/Windows software was used to calculate the percent agreement (Pa) and Gwet's AC1 statistic to assess inter-rater reliability. ROC curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values (IBM SPSS version 25).
Result(s): Overall performances of the raters were similar, with areas under the curve (AUCs) ranging from 0.88-0.95 (Figure 1). >10% appeared to be the optimal threshold for p16 positivity because this was the lowest threshold to reach 100% specificity with high sensitivity (55-84%) in all 5 raters. Using the >10% as threshold, the Pa was 86% (95% CI 0.78-0.94) and Gwet's AC1 coefficient was 0.72 (95% CI 0.56-0.89).
Conclusion(s): While the goal in developing guidelines for the interpretation of p16 IHC on cytology CBs is to provide generalizable standards for all cytopathologists, interobserver variability must be taken into account. Prior studies have shown optimal cutoffs ranging from >0% (any staining) to >70%, with sensitivity and specificity values ranging from 37%-100%. While our study did not show perfect agreement, all cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold with a percent agreement of 86%. [Formula presented]
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Placental intervillous hematomas have not previously been reported to undergo any sort of change, maturation, or healing. In this article, we present the first 2 case reports of recanalization-like neovascularization within placental hematomas: a 0.15 cm focus in an intervillous fibrin thrombus and a 0.2 cm focus in a subchorionic hematoma. Increased recognition and further studies are needed to gain a better understanding of this seemingly rare phenomenon and the factors that govern the lack of typical organization in placental hematomas. This might lead to a deeper knowledge of the repair process in general and shed light on how to control it in diseases caused by excessive repair.

A case is presented in which a preoperatively diagnosed hydatid cyst was found to be a mature cystic teratoma on pathological examination. Diagnostic dilemmas surrounding each disease are discussed.

OBJECTIVES/OBJECTIVE:Recent investigations have shown strong correlations between cytology and surgical non-small cell lung carcinoma (NSCLC) specimens in programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) evaluations. Our study aims to evaluate the reproducibility of PD-L1 IHC scoring in NSCLC cytology cell blocks (CBs) and to assess the impact of CB cellularity, method of sample collection, and observer subspecialty on scoring agreement. METHODS:PD-L1 IHC was performed on 54 NSCLC cytology CBs and was scored independently by seven cytopathologists (three of seven with expertise in pulmonary pathology). Three-tier scoring of negative (<1%), low positive (1%-49%), and high positive (≥50%) and interrater agreement were assessed. RESULTS:Total and majority agreement among cytopathologists was achieved in 48% and 98% of cases, respectively, with κ = 0.608 (substantial agreement; 95% confidence interval, 0.50-0.72). Cytopathologists with pulmonary pathology expertise agreed in 67% of cases (κ = 0.633, substantial agreement), whereas the remaining cytopathologists agreed in 56% of cases (κ = 0.62, substantial agreement). CB cellularity (P = .36) and sample collection type (P = .59) had no statistically significant difference between raters. CONCLUSIONS:There is substantial agreement in PD-L1 IHC scoring in cytology CB specimens among cytopathologists. Additional expertise in pulmonary pathology, sample collection type, and CB cellularity have no statistically significant impact on interobserver agreement.

Background: Little is known about Warthin-like variant of papillary thyroid carcinoma (WL-PTC). Its clinicopathologic features are thought to be similar to the classic variant of papillary thyroid carcinoma (PTC). Our aim was to evaluate clinical histories, laboratory findings, cytologic (FNA) and histopathologic features to better understand and characterize WL-PTC.
Design(s): We performed a retrospective review of PTC resection cases from 2013-2019 in our pathology database. Cases with a predominant WL-PTC pattern were chosen for further review. Corresponding clinical histories, laboratory results, and FNA cases were assessed.
Result(s): Of 3,731 thyroid surgical resection cases, 1,671 were diagnosed with PTC. 25/1,671 were reported to have Warthin-like features, but only 15/25 cases displayed Warthin-like features in >50% of tumor cells and were included in our study (Table 1). 80% were white, 6.7% Asian/Pacific Islander and 13.3% did not report race. 3/15 FNA cases were Bethesda III due to few follicular cells with nuclear atypia in a background of lymphocytes, making it difficult to distinguish atypia from PTC (Figs 1a-d). On resection, all cases had concomitant Hashimoto thyroiditis (HT). All cases tested for BRAF V600E immunohistochemistry were positive (4/4). All 5/15 cases with lymph node metastases had coexisting classic or tall cell features, though not all cases with classic or tall cell features metastasized. 46.7% required post-operative radioactive iodine therapy. To date, the median survival is 100% (range 1 to 6 years). (Table presented)
Conclusion(s): Of all PTC resections at our institution 0.9% were WL-PTC. WL-PTC cases had a prominent lymphocytic infiltrate within papillary fronds and oncocytic cytoplasm (Fig 2a). The unique histologic features of WL-PTC add unique challenges to its diagnosis. Due to its strong association with HT, WL-PTC, particularly microcarcinomas, may be overlooked as endocrine atypia (Fig 2c). As WL-PTC possesses oncocytic features, it can resemble tall cell variant PTC which has a poorer prognosis (Fig 2b). Moreover, minor co-existing tall cell components can actually occur in some WL-PTCs. Foci with tall cell features should be distinguished from WL-PTC by lack of lymphocytic infiltrate within long papillae, and taller than wide cells with distinct cell borders. Like the classic variant, WL-PTC has a favorable prognosis. Metastasis seems to be associated with the presence of classic or tall cell features. More studies are needed to further elucidate this association