Utility of different immunostains for diagnosis of metastatic breast carcinomas in both surgical and cytological specimens.

OBJECTIVE: A panel of immunostains is usually performed to confirm a metastatic carcinoma origin. GATA3 is a transcription factor and has been proven to be a useful marker for breast carcinoma. Other immunostains including mammaglobin (MGB), gross cystic disease fluid protein 15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) are also used in diagnosing metastatic breast cancer. In this study, we aimed to compare the performance of these immunostains in the work up of metastatic breast carcinoma in both surgical and cytological specimens. STUDY DESIGN: This study cohort was composed of 242 metastatic breast carcinomas (142 surgical and 100 cytological specimens) during a study period from October 2013 to December 2015. Immunostain results of GATA3, CK7, MGB, GCDFP-15, ER and PR and their correlations were examined. RESULTS: In surgical specimens, GATA3 and CK7 were highly expressed (88% and 87%), but MGB and GCDFP-15 showed much lower positivity rates (43% and 29%). In cytological specimens, GATA3, CK7 and MGB showed similar positivity rates to those in surgical specimens; but GCDFP-15, ER and PR showed significantly lower positivity rates than those in surgical specimens. All ER-positive cases were positive for GATA3 in both surgical and cytological specimens; however, GATA3 positivity showed a significantly stronger correlation with ER positivity in surgical specimens than in cytological specimens. CONCLUSIONS: GATA3 and CK7 performed better than other immunostains to detect metastatic breast carcinoma in both surgical and cytological specimens. GATA3 expression was positively correlated with ER expression, and the correlation was stronger in surgical specimens than in cytological specimens.

The reporting rates of atypical glandular cells and their HPV testing and histologic follow-up results: a comparison between ThinPrep and SurePath preparations from a single academic institution.

INTRODUCTION: The interpretation of atypical glandular cells (AGCs) remains a major challenge in gynecologic cytopathology using liquid-based cytology (LBC) (ThinPrep and SurePath). The comparison of performance of detecting glandular abnormalities using these 2 methods is lacking. We investigated the reporting rates of AGCs, human papillomavirus (HPV) testing, and histologic follow-up results in ThinPrep (TP) and SurePath (SP) samples. MATERIALS AND METHODS: In our institution, both TP and SP were utilized during the period between January 2014 and June 2017. A retrospective search was conducted to identify patients with AGCs from 58,591 LBCs (27,041 TP and 31,550 SP). Roche (Pleasanton, CA) cobas HPV testing and histologic follow-up results were collected. RESULTS: The reporting rates of AGCs for TP (0.7%) or SP (0.2%) were within the College of American Pathologists benchmark ranges, but the reporting for TP was significantly greater than that for SP (P < 0.0001). The HPV-positive rates were 26.0% and 19.4% in TP-AGCs and SP-AGCs, respectively, with no statistical significance. A total of 137 (74.9%) TP-AGCs and 54 (74%) SP-AGCs had histologic follow-up. High-grade squamous intraepithelial lesions (HSIL)/squamous cell carcinoma were identified in 8.8% (12 of 137) of TP-AGCs and 13% (7 of 54) of SP-AGCs. Adenocarcinomas including endocervical and endometrial adenocarcinomas were identified in 9.5% (13 of 137) of TP-AGCs and 13% (7 of 54) of SP-AGCs. Together, 18.2% (25 of 137) of TP-AGCs and 25.9% (14 of 54) of SP-AGCs showed either HSIL or carcinoma in histologic follow-up, but with no statistical significance. CONCLUSIONS: TP preparation detected considerably more AGCs than SP preparation. There was no statistical significant difference in HPV-positive rates or histologic follow-up outcomes between TP-detected AGCs and SP-detected AGCs.

Programmed cell death ligand 1 expression in cytologic and surgical non-small cell lung carcinoma specimens from a single institution: Association with clinicopathologic features and molecular alterations.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression by the 22C3 pharmDx companion assay has been validated in surgical specimens to support pembrolizumab treatment decisions for patients with non-small cell lung carcinoma (NSCLC). The aims of this study were 1) to assess the adequacy of cytologic specimens for PD-L1 evaluation and 2) to explore correlations of PD-L1 expression with clinicopathologic and molecular features. METHODS: The study cohort included 100 cytology specimens (fluid [n = 28] and fine-needle aspiration [n = 72]) and 165 surgical specimens (biopsy [n = 138] and resection [n = 27]). The PD-L1 immunohistochemistry 22C3 assay and staining assessment were performed according to the manufacturer's instructions. PD-L1 expression was correlated with patients' demographics, pathologic characteristics, and molecular alterations. RESULTS: One hundred forty-two specimens (53.6%) were positive for PD-L1 expression (≥1%). No statistically significant difference in PD-L1 expression was identified between cytologic (56.0%) and surgical specimens (52.1%). Seventy-four of 190 tested cases (38.9%) had genetic alterations. PD-L1 positivity was significantly more prevalent in cases with genetic alterations than in cases without genetic alterations. Furthermore, both PD-L1 positivity and high PD-L1 expression (≥50%) had statistically significant associations with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. PD-L1 expression had no significant association with histologic phenotypes or other clinicopathologic features. CONCLUSIONS: The data indicate that cytologic specimens are comparable to surgical specimens for PD-L1 evaluation. The association of PD-L1 expression with KRAS mutations may have clinical relevance in selecting patients with NSCLC for immunotherapy.

Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules.

Background: The Afirma Gene Expression Classifier (GEC) has been used to further characterize cytologically indeterminate (cyto-I) thyroid nodules into either benign or suspicious categories. However, its relatively low positive predictive value (PPV) limited its use as a classifier for patients with suspicious results. The Afirma Gene Sequencing Classifier (GSC) was developed to improve PPV while maintaining a high negative predictive value (NPV), yet real-world assessment of its performance is lacking. Methods: We analyzed all patients who had cyto-I nodules and molecular testing with either GEC or GSC between 2011 and 2018 at a single academic medical center. Clinical information was obtained for 343 GEC-tested nodules and 164 GSC-tested nodules. Results: The GSC had a statistically significant higher benign call rate (76.2% vs. 48.1%, p < 0.001), PPV (60.0% vs. 33.3%, p = 0.01), and specificity (94.3% vs. 61.4%, p < 0.001) than the GEC. Improvement was statistically significant in both Bethesda III and Bethesda IV nodules. In particular, the benign call rate of GSC was significantly higher in nodules with Hürthle cell changes (88.8% vs. 25.7%, p < 0.01). The rate of surgical intervention in the indeterminate nodule cohort has decreased by 66.4% since switching to the GSC; 52.5% of indeterminate nodules went to surgery while using the GEC compared with 17.6% with the GSC (p < 0.001). This reduction was statistically significant in nodules with Bethesda III diagnoses, demonstrating a 70.9% decrease (GEC 51.3% vs. GSC 14.9%, p < 0.001), and in nodules with Bethesda IV cytology, a 39.2% decrease was noted (GEC 54.8% vs. GSC 33.3%, p = 0.003). Conclusions: Data from a single academic tertiary center show an improved specificity and PPV while maintaining high sensitivity and NPV for GSC compared with GEC. A statistically significant increase in benign call rates was observed in GSC compared with GEC, likely indicating fewer false positive results. After implementation of GSC, surgical interventions have been reduced by 68%.

Clinical features, onsite evaluation, and follow-up results in patients with suspicious for adenocarcinoma on EUS-guided FNA of pancreas.

BACKGROUND: Occasionally, an interpretation of suspicious for adenocarcinoma is made for endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of pancreas. In this study, we aimed to assess onsite evaluation and follow-up results for FNAs with suspicious for adenocarcinoma (FNA-SUS) in order to identify likely factors that are associated with this interpretation. DESIGN: A total of 53 pancreatic FNA-SUS cases and 149 pancreatic FNAs with an interpretation of adenocarcinoma (FNA-ADC) were included in current study. Clinical characteristics, onsite evaluation results, and follow-up results were collected and analyzed. RESULTS: Compared with FNA-ADC category, FNA-SUS category was associated with increased cystic/ill-defined lesions on imaging, increased frequency of inadequate materials (onsite evaluation), increased total smear/slide number, and increased number of cases with limited materials on permanent slides/sections. For follow-up resections, 21% of FNA-SUS cases (7 of 34) showed benign, dysplastic changes or neuroendocrine tumors and 79% (27 of 34) showed adenocarcinoma with increased frequency of well-differentiated type. In contrast, all FNA-ADC cases showed adenocarcinoma. The average age of those 7 FNA-SUS cases with non-adenocarcinoma on follow-up was significantly younger than that of 27 cases with adenocarcinoma. FNA-SUS cases with adenocarcinoma on follow-up showed even greater frequency of inadequate materials during onsite evaluation and more increased total smear slide number than FNA-ADC cases. CONCLUSION: Our data demonstrated several clinicopathologic factors that are likely associated with a suspicious cytology. In younger patients with suspicious cytology and non-mass forming lesion, surgical management should be taken with caution as a considerable percentage of patients showed only benign or low-grade dysplastic changes.

Endoscopic ultrasound-guided fine-needle aspiration diagnosis of secondary tumors involving pancreas: an institution's experience.

INTRODUCTION: Metastases that present as pancreatic masses are rare. Understanding and recognizing this uncommon occurrence during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) will help in making an accurate diagnosis and planning for clinical management. In this study, we reviewed our experience in diagnosing pancreatic secondary tumors. MATERIALS AND METHODS: A pathology archive database search was performed for EUS-FNAs of the pancreas with a diagnosis of metastatic tumor at our institution. The corresponding clinical presentations, imaging studies, cytological diagnoses, ancillary studies, and surgical follow-up were collected. RESULTS: A total of 30 cases were identified with 18 male and 12 female patients. Twenty-eight patients (93.3%) had a prior history of malignancy, with a latency ranging from 0 to 36 years. The secondary tumors included carcinoma (18 of 30), neuroendocrine tumor (5 of 30), melanoma (4 of 30), and sarcoma (3 of 30). The most common metastatic tumor was clear cell renal cell carcinoma (37%, 11 of 30). Correct diagnoses were rendered in 28 cases (93.3%). The remaining 2 cases failed to be accurately diagnosed: one pleomorphic carcinoma (reported as pleomorphic sarcoma) and one liposarcoma (reported as poorly differentiated malignant neoplasm). Both cases did not have immunohistochemistry performed because of a lack of diagnostic materials in cell blocks. CONCLUSIONS: Our data demonstrated that metastatic clear cell renal cell carcinoma was the most common secondary tumor involving the pancreas. Secondary tumors involving the pancreas can be accurately diagnosed by EUS-FNA. Knowing the prior history of malignancy, recognizing uncommon cytomorphologic features, and performing ancillary studies are keys to improve diagnostic accuracy.

Impact of touch imprint cytology on imaging-guided core needle biopsies: An experience from a large academic medical center laboratory.

BACKGROUND: Imaging-guided core needle biopsy is a minimally invasive and effective tissue sampling method. Touch imprint cytology (TIC) can provide immediate on-site preliminary interpretation and adequacy of core needle biopsy. We investigated on-site TICs' impact on minimizing the number of core needle biopsy passes required for diagnosis. METHODS: Five hundred and sixty imaging-guided CNBs with TICs including 393 malignant lesions, 136 benign lesions, 29 nondiagnostic specimens, and 2 atypical lesions were reviewed for adequacy, preliminary interpretation, final histological diagnosis, and the number of core needle biopsy passes. RESULTS: The adequacy rate determined by on-site TICs was 76%, with 50% for benign lesions, and 88% for malignant lesions. The correlation rate between TICs' preliminary interpretation and histological diagnosis was 91%, with 100% for benign lesions and 89% for malignant lesions. In malignant lesions, the adequacy rate was lowest in cases with sarcomas (58%), followed by hepatocellular carcinoma and renal cell carcinoma. When all cases are stratified by locations, the adequacy rate determined by on-site TICs was lowest in lesions from soft tissue (45%), followed by pelvic mass or kidney. The average number of cores was 4.1 per case in adequate specimens, significantly lower than that in specimens without TICs. In contrast, the average number of cores was 7.1 per case in inadequate specimens, significantly greater than that in specimens without TICs. CONCLUSIONS: On-site TICs showed its usefulness in reducing the number of cores required for adequate diagnostic materials. In the meantime, TICs accurately provided preliminary interpretations, especially in adequate malignant carcinoma cases.