Incorporating cytologic adequacy assessment into precision oncology workflow using telepathology: An institutional experience

Abstract

BACKGROUND:Tumor sample quality and quantity determine the success of somatic mutation analysis. Thus, a rapid on-site evaluation (ROSE) tumor cytology adequacy assessment was incorporated into the workflow of precision oncology at Weill Cornell Medicine in New York City. Optimal samples were obtained from 68 patients with metastatic cancer. METHODS:Cytopathologists performed ROSE on fine-needle aspirate samples via telepathology, and subsequently core-needle biopsies were obtained. In a retrospective manner, the concordance between adequacy assessment and the success rate of the procedure was evaluated to obtain sufficient tumor tissue for next-generation sequencing (NGS). RESULTS:Out of the 68 procedures, 43 were documented as adequate and 25 were documented as inadequate. The diagnostic yield of adequate procedures was 100%. Adequacy evaluation predicted the success rate of molecular profiling in 40 of 43 procedures (93%; 95% CI, 80.9-98.5 procedures). The success rate of molecular testing was significantly higher in the adequate group: 93% compared with 32% in the inadequate group (P < .0005). Seven procedures that failed to provide quality material for mutational analysis and pathological diagnosis were evaluated as inadequate. Cell block provided sufficient DNA for NGS in 6 cases. In 2 cases, a core biopsy could not be performed; hence, the fineneedle aspirate material confirmed the diagnosis and was used for NGS testing. CONCLUSION: These results support the incorporation of ROSE into the workflow of precision oncology to obtain high-quality tissue samples from metastatic lesions. In addition, NGS testing of concurrent cytology specimens with adequate cellularity can be a surrogate for NGS testing of biopsy specimens.

Digital pathology world tour

“…Despite advances in the application of WSI for general surgical pathology (histopathology), areas such as cytopathology that have lagged behind are slowly gaining traction. 29 – 31 Nevertheless, further research and validation studies demonstrating the diagnostic validity of DP in routine cytology practice is still required. 32 There are several reasons why WSI usage in cytopathology has been slower than its use in histopathology.…”

Consistency and reproducibility of large panel next-generation sequencing: Multi-laboratory assessment of somatic mutation detection on reference materials with mismatch repair and proofreading deficiency

“…Clinical FFPE specimen are not reproducible and replaceable, and the mutational profile is heterogenous [26] . Moreover, the quality and quantity of DNA extracted from them are crucial for performing genomic profiling, which generally depend on pre-analytical factors such as fixation time, within block position, and DNA extraction methods [27] , [28] . Noting this, the pre-analytical workflow has been widely evaluated by previous multicenter studies using FFPE cell line samples that could closely mimic the real FFPE samples [29] , [30] , [31] , [32] .…”

Molecular testing of cytology specimens: Issues in specimen adequacy and clinical utility

“…First, most review the impact of specimen type (cell block, smear, cytospin, and liquid based specimens) on success of NGS testing as well as impact of DNA yield and tumor fraction rather than the impact of NGS results on selection of therapy. [19][20][21][22][23] Second, most of the reports in the literature have summarized findings from large cancer centers or research institutes using "in house" NGS testing rather than results from medium or small sized institutions sending specimens to one of the large national laboratories furnishing NGS testing. Our study addresses both of these issues.…”