Conventional transbronchial needle aspiration is promising for identifying EGFR mutations in lung adenocarcinoma

Abstract

Background: Conventional transbronchial needle aspiration (TBNA) is advantageous for the one-step diagnosis and staging of lung adenocarcinoma under topical anesthesia and conscious sedation. We examined its efficacy for identifying EGFR mutations.

Methods: Forty-seven patients with proven or suspected lung adenocarcinoma indicated for hilar-mediastinal lymph node (LN) staging between June 2011 and December 2017 were enrolled. The cellblock was prepared using the plasma-thrombin method. TaqMan PCR was used to detect mutations. Considering cost effectiveness, only the sample with the highest tumor cell fraction in the same patient was chosen for analysis.

Results: TBNA provided positive results of malignancy in 27 patients. Seventeen patients (63.0%) had cellblocks eligible for mutation testing. Bronchial biopsy (n = 6), neck LN fine needle aspiration (n = 1), and brushing (n = 1), provided higher tumor cell fractions for analysis in eight patients. TBNA was the exclusive method used in nine patients (19.1%). For patients with an inadequate TBNA cellblock, bronchial biopsy (n = 5), neck LN fine needle aspiration (n = 3), computed tomography-guided transthoracic needle biopsy (n = 1), and brushing (n = 1) were used for analysis. Modification to specimen processing to prevent exhaustion by cytology after June 2016 improved the adequacy of cellblock samples (9/10, 90% vs. 8/17, 47.1%; P = 0.042).

Conclusions: These findings suggest the promising role of conventional TBNA and highlight the challenges of doing more with less in an era of precision medicine.

Keywords: Adenocarcinoma; bronchoscopy; epidermal growth factor receptor; lung cancer; transbronchial needle aspiration.

Figure 1

The plasma‐thrombin method (ThinPrep) for cellblock preparation.

Figure 2

A 37‐year‐old female patient with right upper lobe lung adenocarcinoma. Analysis of a cellblock obtained via conventional transbronchial needle aspiration of the right paratracheal #4R lymph node (a) was negative for EGFR mutation (b‐d) (hematoxylin and eosin, original × 100).

Figure 3

Conventional transbronchial needle aspiration using different needles and specimen processing methods for EGFR mutation testing in lung adenocarcinoma. The cellblock obtained using a 21 G NA‐2C‐1 needle (Olympus Optical, Tokyo, Japan) from the same patient in Figure 2. (a) The cellblocks obtained using a 21 G needle from the right paratracheal #4R LN with all needle pass rinses processed for the cellblock (except the first for onsite examination) in (b) a 45‐year‐old male patient and a (c) 71‐year‐old male patient with lung adenocarcinoma demonstrated exon 19 deletion and exon 21 L858R mutation, respectively. (d) The cellblock obtained using a 19 G eXcelon needle (Boston Scientific, Boston, MA) from the right paratracheal #4R LN in a 72‐year‐old patient with left upper lobe lung adenocarcinoma revealed a negative EGFR mutation result (hematoxylin and eosin, original × 100).

Figure 4

(a,b) Analysis of a cellblock obtained via brushing revealed an exon 19 deletion in a 63‐year‐old male patient with left lower lobe lung adenocarcinoma whose transbronchial needle aspiration cellblock was positive for malignancy but inadequate for analysis (hematoxylin and eosin, original × 100 and 400). (c,d) Analysis of a cellblock obtained via brushing revealed an exon 21 L858R mutation in a 71‐year‐old male patient with right upper lobe lung adenocarcinoma (hematoxylin and eosin, original × 100 and 400).

Figure 5

A 65‐year‐old female patient with right lower lobe lung adenocarcinoma. A cellblock obtained via conventional transbronchial needle aspiration of the right main bronchus #4R lymph node (a) showed strong positive nuclear staining of TTF‐1 (b) (Leica, clone SPT24) and a negative EGFR mutation result; subsequent testing for ALK (c) (Roche, clone D5F3) and PD‐L1 (d) (Roche, clone SP263) showed no cytoplasmic staining in cancer cells (original × 200).

Figure 6

(a) A 46‐year‐old female breast cancer patient was diagnosed with mediastinal recurrence by conventional transbronchial needle aspiration of the right main bronchus #4R lymph node. The cellblock illustrated triple negative for (b) ER, (c) PR, (d) HER2/neu, contrast with ER 3+, PR 2+ and no overexpression of HER2/neu in the primary tumor (original × 400).