J Pathol Transl Med.  2015 Jul;49(4):300-309. 10.4132/jptm.2015.06.16.

The Utilization of Cytologic Fine-Needle Aspirates of Lung Cancer for Molecular Diagnostic Testing

• Roh MH

• KMID: 2151139
• DOI: http://doi.org/10.4132/jptm.2015.06.16

Abstract

In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve. This information is being increasingly exploited to treat advanced stage lung cancer patients with tailored, targeted therapy. During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable. Cytologic fine-needle aspirates are often utilized for this purpose and are important not only for rendering diagnoses to subtype patients' lung cancers, but also for ascertaining molecular diagnostic information for treatment purposes. Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives. In this review, strategies in utilizing fine-needle aspirates will be discussed in the context of our current understanding of the clinically actionable molecular aberrations underlying non-small cell lung cancer and the molecular assays applied to these samples in order to obtain treatment-relevant molecular diagnostic information.

Keyword

Lung neoplasms; Cytology; Biopsy, fine-needle; Molecular testing; Precision medicine

MeSH Terms

Biopsy, Fine-Needle
Carcinoma, Non-Small-Cell Lung
Diagnosis
Humans
Lung Neoplasms*
Molecular Diagnostic Techniques*
Pathology, Molecular

Figure

• 

  Fig. 1. Example of fine-needle aspiration (FNA) processing workflow. The contents of a needle pass, obtained during an FNA procedure, are expelled onto a slide to prepare smears. Typically, a pair of smears (one Diff-Quik stained and one Papanicolaou stained) is prepared per needle pass. However, additional smears can be prepared from a single needle pass by distributing the cellular material across more than two slides. The additional smears can be directly triaged for ancillary studies. For instance, an unstained smear can be sent to the Immunohistochemistry Laboratory for immunostaining (e.g., thyroid transcription factor-1 [TTF-1] immunocytochemistry). Also, a stained smear can be directly triaged to the Molecular Diagnostics Laboratory for tumor cell macro- or microdissection, nucleic acid isolation, and subsequent molecular testing (e.g., epidermal growth factor receptor [EGFR] mutation analysis).

• 

  Fig. 2. Examples of epidermal growth factor receptor (EGFR) mutations detected by the polymerase chain reaction based fragment analysis assay utilized at our institution. Our assay is a multiplex assay designed to detect the two most common mutations in EGFR: the L858R substitution (case 1) and small deletions within exon 19 (case 2).

• 

  Fig. 3. Example case of anaplastic lymphoma kinase (ALK) rearrangement fluorescence in-situ hybridization assay performed on a direct smear containing lung adenocarcinoma cells. The arrows point to the split orange and green signals that are separated by a distance of > 2 signal diameters. These nuclei would be scored as positive for the ALK rearrangement.

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