Cytology Sample Transforming into DNA

Second Life for Cytology Samples: How Repurposing Old Specimens is Revolutionizing Molecular Testing

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Mira Elwood in Health & Wellness August 2025 • 4 min read.

"Unlock Hidden Insights: Discover how molecular cytopathology transforms residual samples into valuable diagnostic tools, enhancing precision medicine and patient care."


The field of cytopathology is undergoing a major transformation, driven by the increasing use of molecular techniques in routine clinical practice. From traditional methods like HPV testing and urine analysis to cutting-edge nucleic acid and protein-based assays, molecular cytopathology is playing an increasingly important role in medical decision-making. This evolution, however, presents a significant challenge: the need to extract more information from limited tissue samples obtained through minimally invasive procedures like fine-needle aspiration (FNA).

Fortunately, the versatility of cytology specimen preparations offers a solution. Cytopathologists are pioneering innovative methods to derive genomic insights from even the smallest samples, including the often-overlooked residual cytologic substrates. For years, residual liquid-based cytology (LBC) preparations from gynecological samples have been used for high-risk HPV detection. LBC media not only preserves cellular morphology for accurate diagnosis but also safeguards nucleic acids for downstream DNA and RNA analysis.

This practice is now expanding to non-gynecological FNA samples, with promising results. Studies have demonstrated the feasibility of extracting nucleic acids from residual LBC solutions of thyroid FNA specimens for mutation analysis. These analyses employ sophisticated techniques like high-resolution melting polymerase chain reaction (PCR), pyrosequencing, and next-generation sequencing (NGS) to identify critical genetic alterations.

Repurposing Residual Samples: A Step-by-Step Guide

Cytology Sample Transforming into DNA

One notable study detailed the use of residual PreservCyt specimens from FNA samples and body fluids to extract DNA for multigene NGS analysis. Another study explored the use of residual CytoLyt from endobronchial ultrasound-guided transbronchial needle aspirates for NGS evaluation. These methods showcase the potential of extracting valuable genetic information from what was previously considered waste material.

Moreover, research indicates that post-centrifuged supernatant fluid from FNA samples, when combined with residual PreservCyt, yields sufficient DNA for mutational analysis via NGS. This is particularly significant because supernatant fluid from FNA needle rinses has long been recognized as a source of DNA suitable for assays like microsatellite fragment analysis and hotspot-based mutational analysis.

Key benefits of repurposing residual cytology samples:
  • Maximizes the use of limited tissue.
  • Reduces the need for additional biopsies.
  • Provides comprehensive genomic information.
  • Improves diagnostic accuracy.
A recent study by our group demonstrated that supernatant fluid samples from FNA needle rinses can provide adequate DNA for NGS and droplet digital PCR, delivering clinically relevant genomic information for various solid tumors, including lung carcinoma, melanoma, and colorectal adenocarcinoma. Another study has demonstrated the feasibility of using supernatant DNA fluid from patients with lung cancer for tumor genotyping by mutational analysis. Given that this centrifuged FNA supernatant fluid routinely is discarded after cell pelleting, the implications of providing critical molecular testing from these samples are significant.

The Future of Cytopathology

In an era where resources are precious, and the demand for comprehensive genomic information is ever-increasing, cytopathologists must embrace innovative approaches. Repurposing discarded cytology samples offers a path forward, allowing for better utilization of available resources and improved patient care. As with any clinical diagnostic assay, it is crucial to optimize preanalytic aspects of specimen processing and validate tests before implementation. However, the ability to detect clinically relevant genetic alterations from previously discarded samples introduces a new dimension to cytopathology, enhancing its role in precision medicine.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1002/cncy.22076, Alternate LINK

Title: Molecular Testing Of Residual Cytology Samples: Rethink, Reclaim, Repurpose

Subject: Cancer Research

Journal: Cancer Cytopathology

Publisher: Wiley

Authors: Sinchita Roy‐Chowdhuri

Published: 2018-10-14

Everything You Need To Know

1

How has molecular cytopathology changed the way cytology samples are analyzed?

Molecular cytopathology has transformed the examination of cytology samples by enabling the analysis of nucleic acids and proteins. This method uses advanced molecular techniques, expanding the capabilities of traditional cytology from just morphological assessment to detailed molecular profiling, thus improving diagnostic accuracy and personalized treatment strategies.

2

Why are residual liquid-based cytology (LBC) preparations so important in molecular testing?

Residual liquid-based cytology (LBC) preparations are crucial because they preserve both cellular morphology and nucleic acids, allowing for both accurate cytological diagnosis and subsequent DNA or RNA analysis. This is particularly significant in gynecological samples for high-risk HPV detection and is now being applied to non-gynecological fine-needle aspiration (FNA) samples for comprehensive genetic analysis.

3

What are the key advantages of repurposing residual cytology samples for molecular testing?

Repurposing residual cytology samples minimizes the need for additional invasive biopsies, provides comprehensive genomic information from limited tissue, and enhances diagnostic accuracy, facilitating personalized medicine. For instance, utilizing post-centrifuged supernatant fluid combined with residual PreservCyt from FNA samples yields sufficient DNA for mutational analysis via Next-Generation Sequencing (NGS).

4

What specific techniques are used to extract and analyze genetic material from residual cytology samples?

Several techniques are employed, including high-resolution melting polymerase chain reaction (PCR), pyrosequencing, and next-generation sequencing (NGS). For instance, NGS is used to detect genetic alterations in DNA extracted from residual PreservCyt specimens and post-centrifuged supernatant fluid from FNA samples. These sophisticated methods allow for the detection of critical mutations that guide treatment decisions.

5

What impact does analyzing supernatant fluid samples from FNA needle rinses have on cancer diagnosis and treatment?

By using methods like droplet digital PCR and next-generation sequencing on supernatant fluid samples from FNA needle rinses, clinically relevant genomic information can be obtained for various solid tumors, including lung carcinoma, melanoma, and colorectal adenocarcinoma. Furthermore, the application of these techniques to what was once considered waste material significantly enhances the role of cytopathology in precision medicine, optimizing resource utilization and improving patient outcomes without requiring additional invasive procedures.

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