Updated College of American Pathologists guideline recommendations include specific guidelines for validating immunohistochemistry assays performed on cytology specimens. The new recommendations may ...be the impetus needed to open the door to a wider adoption of cytology specimens into routine clinical practice for immunochemistry‐based assays that drive patient care and biomarker‐driven therapeutics.
The ability to detect clinically relevant genetic alterations by repurposing previously discarded cytology samples provides an exciting new dimension to the practice of cytopathology. Repurposing ...otherwise discarded residual fluid and supernatant fluid from fine‐needle aspiration samples allows for better use of cytology specimens.
Background
The International System for Reporting Serous Fluid Cytopathology was recently proposed as a tiered structure to provide consistent reporting terminology for serous effusions. Because of ...the variation in reporting practices for indeterminate serous effusions, namely, the atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) groups, the authors retrospectively reviewed cases in these 2 categories at their institution and determined the associated risk of malignancy (ROM).
Methods
Pleural, peritoneal, and pericardial effusions that were reported as AUS or SFM over a 1‐year period were reviewed, and their associated ROMs were calculated based on confirmation of malignancy by previous and/or subsequent fluid and/or tissue biopsy specimens from the same general location.
Results
In total, 145 AUS and 98 SFM serous effusion cases were identified. The AUS category was used when the cells in question lacked the requisite quantitative (cell number) and/or qualitative (morphologic) features for a definitive diagnosis. Immunohistochemistry (IHC) or flow cytometry (FCM) was available in 15% of cases (n = 22) with inconclusive results. The ROM based on 69 cases with available follow‐up results was 39%. In contrast, the SFM category demonstrated cells that were morphologically suspicious for malignancy but sparse, precluding IHC or FCM (n = 63; 64%) or yielding inconclusive results (n = 35; 36%). The ROM in the SFM category, based on follow‐up results of 61 cases, was 64%.
Conclusions
The ROM for SFM was significantly higher than that for AUS (P < .01), supporting separate diagnostic categories for these 2 groups.
There is considerable variation in the reporting practices for indeterminate serous effusions, namely, the categories atypia of undetermined significance and suspicious for malignancy, with limited literature on their associated risk of malignancy. The reporting practice at a single institution is examined and demonstrates that the risk of malignancy in the suspicious for malignancy category is significantly higher than that for the atypia of undetermined significance category, thus providing support for retaining these as 2 separate diagnostic categories in the tiered reporting system for serous effusions.
Biomarker testing in patients with advanced stage non–small cell lung cancer provides essential information that can be used to select the most appropriate therapy. The regular updates of guideline ...recommendations reflect the growing number of biomarkers that must be assessed, and as such signal the shift from single‐gene assays to more comprehensive genomic profiling using next‐generation sequencing modalities. Cytology and small biopsy specimens have proven to be more than adequate substrates for these types of ancillary molecular testing; however, other alternative testing substrates are beginning to emerge. These include so‐called liquid biopsies as well the supernatant fluid from cytology specimens, both of which have demonstrated promise for use in the clinical realm. This review will briefly cover the current state of non–small cell lung cancer biomarker testing in the United States, with a focus on these novel nonconventional substrates that are increasingly being incorporated into testing paradigms.
Current guideline recommendations for non–small cell lung cancer emphasize the need for broad biomarker testing to direct therapeutic decisions. Cytology specimens have been used successfully for biomarker testing, but other substrates, including liquid biopsy and supernatant fluid, are beginning to emerge.
- There has been a paradigm shift in the understanding of molecular pathogenesis of lung cancer. A number of oncogenic drivers have been identified in non-small cell lung carcinoma, such as the ...epidermal growth factor receptor ( EGFR) mutation and anaplastic lymphoma kinase ( ALK) gene rearrangement. Because of the clinical presentation at an advanced stage of disease in non-small cell lung carcinoma patients, the use of minimally invasive techniques is preferred to obtain a tumor sample for diagnosis. These techniques include image-guided biopsies and fine-needle aspirations, and frequently the cytology specimen may be the only tissue sample available for the diagnosis and molecular testing for these patients.
- To review the current literature and evaluate the role of cytology specimens in lung cancer mutation testing. We reviewed the types of specimens received in the laboratory, specimen processing, the effect of preanalytic factors on downstream molecular studies, and the commonly used molecular techniques for biomarker testing in lung cancer.
- PubMed and Google search engines were used to review the published literature on the topic.
- Mutation testing is feasible on a variety of cytologic specimen types and preparations. However, a thorough understanding of the cytology workflow for the processing of samples and appropriate background knowledge of the molecular tests are necessary for triaging, and optimum use of these specimens is necessary to guide patient management.
Context .- As our understanding of genomic alterations underlying solid tumor malignancies continues to evolve, molecular testing of tumor samples is increasingly used to guide therapeutic ...management. Next-generation sequencing (NGS) provides a novel platform for the simultaneous screening of multiple genes using small amounts of DNA. Several recent studies have described NGS mutational analysis using cytologic specimens. The cytopathologist's role in specimen assessment and triaging is critical to effectively implementing NGS in routine cytology practice. Objectives .- To review the NGS experience and a variety of preanalytic factors that affect NGS success rates of cytologic specimens at our institution. Data Sources .- To evaluate cytology specimen adequacy rates for NGS, we reviewed a 14-month period of image-guided fine-needle aspiration and core needle biopsies, used for testing. In addition, we reviewed data from our previously published studies to evaluate preanalytic factors affecting NGS success in these specimens. Conclusions .- Identifying factors that affect NGS success rates in cytology specimens is crucial for a better understanding of specimen adequacy requirements and for proper use of limited-volume tissue samples. In our practice, which uses direct smears as well as cell block sections, NGS success rates in core needle biopsy and fine-needle aspiration samples are comparable. The chance of successful testing is further increased by procuring concurrent fine-needle aspiration and core needle biopsy samples. The type of glass slides used for direct smears and the method of tissue extraction affect our DNA yield. Validating a DNA input for cytology samples that is lower than that recommended by the manufacturer has significantly increased our NGS success rate.
With advancments in technology for minimally invasive sampling techniques, pathology laboratories are receiving increasing numbers of small biopsy and cytology specimens for multiple ancillary ...studies to help in the diagnosis and management of pulmonary diseases. A recently published evidence‐based guideline from the College of American Pathologists (CAP), in collaboration with 8 other professional medical societies, provides recommendations to clinicians for the collection of adequate material for diagnostic and ancillary testing as well as optimal handling in an attempt to prioritize ancillary testing. The primary goal of developing this CAP guideline is to assist pathologists and their clinical colleagues to better collect and handle small thoracic pathology specimens to help guide therapeutic decisions.
Genomic profiling of tumor from malignant effusions have conventionally been performed on tumor cells derived from cytologic preparations such as cell block preparations, direct smears, cytospin ...preparations and liquid based cytologic preparations. The study by Yang et al. exemplifies the rapid progress of molecular cytopathology as cytopathologists increasingly delve into novel sources for genomic testing in an attempt to provide the theranostic information necessary for patient care.
Objectives
The practice of cytopathology has evolved over the past decade with a growing need for doing more with less tissue. Changes in clinical practice guidelines and evolving needs in tissue ...acquisition for diagnosis and treatment have affected various areas of cytopathology in different ways. In this study, we evaluated the changing trends in cytopathological practice at our institution over the past decade.
Methods
We performed a retrospective review of our institutional database for cytopathology cases from calendar years 2009 (n = 28038) and 2019 (n = 31386) to evaluate the changing trends in practice.
Results
The overall number of exfoliative cases decreased 10% over the past decade, primarily due to a 64% decrease in gynaecological Pap testing. However, the volume of serous body cavity and cerebrospinal fluids increased 125% and 44%, respectively. The overall volume of fine needle aspiration (FNA) cases increased 38% from 2009 to 2019. The number of FNA cases increased across most body sites, driven primarily by a 180% increase in endobronchial ultrasound‐guided transbronchial needle aspiration cases. In contrast, breast FNA volume decreased 43%. Ancillary studies increased substantially over the past decade, including immunostains (476%) and molecular testing (250%).
Conclusions
The trends in our cytopathological practice showed an increased volume of cases, especially in non‐gynaecological specimens. As expected, the number of FNA cases used for immunostains and molecular testing increased substantially, indicating an upward trend in ancillary studies in cytopathological practice.
The trends in our cytopathological practice showed an increased volume of cases, especially in non‐gynaecological specimens. The number of FNA cases used for immunostains and molecular testing increased substantially, indicating an upward trend in ancillary studies in cytopathological practice.
ABSTRACT
Background and objective
Analysis of programmed death ligand‐1 (PD‐L1) in tumour samples is necessary to identify candidates for anti‐PD‐L1/PD‐L1 therapy. Because PD‐L1 is evaluated by ...immunohistochemistry (IHC), an adequate amount of tumour tissue is a prerequisite for PD‐L1 testing. To examine whether pleural fluid might be an alternative to biopsy/resection specimens for IHC evaluation of PD‐L1 in patients with non‐small cell lung carcinoma (NSCLC), we compared PD‐L1 by IHC between histological specimens and matched pleural fluid.
Methods
A retrospective cohort study of patients with NSCLC who underwent core biopsy of a lung mass/surgical resection with PD‐L1 IHC and had a pleural fluid cell block (CB) available for PD‐L1 staining was conducted. PD‐L1 was categorized as negative (PD‐L1 in <1% of tumour cells), moderately positive (PD‐L1 in ≥1% to <50%), strongly positive (PD‐L1 ≥ 50) or inadequate for PD‐L1 testing (<100 tumour cells in the CB). Weighted Cohen's kappa was calculated to evaluate the agreement between PD‐L1 on biopsy/resection specimen and pleural fluid for variables with more than two categories.
Results
Of the 115 patients included in this study, 82 (71.3%) had at least 100 tumour cells and were included in the analysis. Of these, 80 (97.6%) had adenocarcinoma. For PD‐L1 of histological specimens versus pleural fluid categorized as negative, moderately positive or strongly positive, the weighted kappa statistic was 0.76 (95% CI: 0.64–0.88), and the concordance was 0.78 (95% CI: 0.68–0.86).
Conclusion
Correlation and concordance are high between PD‐L1 in histological specimens and matched pleural fluid. Evaluation of PD‐L1 in pleural fluid should be considered in patients unable to undergo histological biopsies.
Programmed death ligand‐1 (PD‐L1) expression in pleural fluid is reliable with fairly good correlation and concordance with PD‐L1 expression in surgical biopsy/resection specimens and should be considered in patients who are unable to undergo histological biopsies.
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