Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, −0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

BACKGROUND: Pancreatic fine-needle aspiration (FNA) is useful for diagnosing pancreatic masses. This article describes the experience of a single institution with metastases to the pancreas sampled by FNA and provides a review of the literature. METHODS: Medical records were retrospectively searched for pancreatic FNA that showed metastatic disease. Data were gathered for the tumor size, focality, and time period between the primary tumor and the metastasis. A literature search using PubMed was performed. RESULTS: Pancreatic FNA was performed 2327 times in 14 years at the authors' institution. Twenty-two cases showed metastatic disease. The average size of the metastatic lesions in their greatest dimension was 3.7 cm (range, 1.5-6.5 cm). The majority of the tumors were unifocal (16 of 22 or 73%). A rapid onsite adequacy evaluation was performed for 13 patients (4 were diagnostic of metastasis, 3 were positive for malignant cells, 6were atypical, and none were negative). There were 14 renal cell carcinomas, 2 colonic adenocarcinomas, 1 urothelial carcinoma, 1 non-small cell lung carcinoma, 1 ovarian serous carcinoma, 1 prostatic adenocarcinoma, 1 papillary thyroid carcinoma, and 1 mesenchymal chondrosarcoma. The median time between the diagnosis of the primary tumor and the initial pancreatic metastasis was 9 years (range, concurrent diagnosis to 21 years). A literature review yielded 12 case series with a variety of metastases to the pancreas diagnosed by FNA and surgical pathology specimens. CONCLUSIONS: In agreement with prior series, the most common metastasis to the pancreas was renal cell carcinoma. A variety of other primary malignancies were also documented in this study and in the literature. Also, this article reports the first case of metastatic mesenchymal chondrosarcoma to the pancreas diagnosed by FNA. Cancer (Cancer Cytopathol) 2015;123:347-55.

A nonstatistically significant increase in recurrence and death was observed among patients undergoing LA versus OA after adjusting for clinical stage. The rarity of this disease limits the ability to assess for significant differences in a single-institution series. Patients with suspected ACC should be considered for OA.

Our experience over the last 30 years confirms that FNA remains a sensitive and specific method to detect metastases to the thyroid. In any patient with a history of a malignancy, a new thyroid mass should be promptly evaluated for recurrent malignancy as early diagnosis and surgical resection resulted in a nonstatistically significant increased median survival.

Detection of ALK gene rearrangements in liquid cytology ThinPrep slides derived from patients with NSCLC can be confidently used for clinical ALK molecular testing.

NSCLC mutation analysis using NGS can be successfully performed on residual cell pellets derived from LBC samples. This approach allows the simultaneous examination of multiple mutation hotspots in a timely manner to improve patient care. Cancer Cytopathol 2017;125:178-187. © 2016 American Cancer Society.

Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP.

Purpose: Transcriptomic profiling can shed light on the biology of SCBC, nominating biomarkers and novel therapeutic targets. Experimental Design: Sixty-three SCBC patients had small cell histology confirmed and quantified by a genitourinary pathologist. Gene expression profiling was performed for 39 primary tumor samples, 1 metastatic sample, and 6 adjacent normal urothelium samples (46 total) from the same cohort. Protein levels of differentially expressed therapeutic targets, DLL3 and PDL1, and also CD56 and ASCL1, were confirmed by IHC. A SCBC PDX model was utilized to assess in vivo efficacy of DLL3-targeting antibody-drug conjugate (ADC). Results: Unsupervised hierarchical clustering of 46 samples produced 4 clusters that correlated with clinical phenotypes. Patients whose tumors had the most “normal-like” pattern of gene expression had longer OS compared to the other 3 clusters while patients with the most “metastasis-like” pattern had the shortest OS (p=0.047). Expression of DLL3, PDL1, ASCL1 and CD56 was confirmed by IHC in 68%, 30%, 52% and 81% of tissue samples, respectively. In a multivariate analysis, DLL3 protein expression on >10% and CD56 expression on >30% of tumor cells were both prognostic of shorter OS (p=0.03 each). A DLL3-targeting ADC showed durable anti-tumor efficacy in a SCBC PDX model. Conclusions: Gene expression patterns in SCBC are associated with distinct clinical phenotypes ranging from more indolent to aggressive disease. Overexpression of DLL3 mRNA and protein is common in SCBC and correlates with shorter OS. A DLL3-targeted ADC demonstrated in vivo efficacy superior to chemotherapy in a PDX model of SCBC.