Elsevier

Lung Cancer

Volume 82, Issue 1, October 2013, Pages 69-75
Lung Cancer

Adequacy of CT-guided biopsies with histomolecular subtyping of pulmonary adenocarcinomas: Influence of ATS/ERS/IASLC guidelines

https://doi.org/10.1016/j.lungcan.2013.07.010Get rights and content

Abstract

Introduction

As metastatic pulmonary adenocarcinomas are routinely investigated for EGFR, KRAS, and ALK mutations/rearrangement, adequacy of CT-guided trans-thoracic needle biopsies (TTNB) needs to be evaluated in respect with the 2011 ATS/ERS/IASLC guidelines.

Methods

Two series of consecutive TTNB with 18-gauge needles performed before and after the publication of the ATS/ERS/IASLC guidelines, were retrospectively compared regarding their adequacy for histological sub-typing and EGFR/KRAS mutations and ALK rearrangement testing; the first series included 43 TTNB collected from January 2010 to February 2011, and the second one 48 TTNB collected from March 2011 to December 2012.

Results

28 women and 63 men were included; the 2 groups were comparable in age, in mean size of lesions (32.5 mm), and distance of the lesion from the pleura. By comparing the first to the second series, the number of biopsies increased from 1.6 to 1.85, their mean length increased from 10.9 to 12.5 mm, and the mean number of stainings (TTF1, P63, CK5-6, mucins) per biopsy decreased from 2.6 to 1. Mean tumor cell percentage was 42%, mean total DNA extracted increased from 2.7 to 3.8 μg. In the first series, 85% of TTNB allowed EGFR exons 19 and 21 and KRAS mutations pyrosequencing and 72% additional EGFR exons 18 and 20 mutation analyses, versus 98% and 92% in the second.

Conclusions

With respect to ATS/ERS/IASLC guidelines, radiologists, biologists and pathologists have improved their practice; accordingly, CT-guided TTNB enable a precise histological sub-typing and provide sufficient DNA amount for genetic analyses.

Introduction

Lung cancer is the leading cause of cancer deaths worldwide, with 1.2 million of people diagnosed every year and 1.1 million deaths. Its prognosis remains dramatically poor, as nearly 75% of NSCLC patients have unresectable advanced disease at the time of diagnosis. Therefore, radiotherapy and chemotherapy with conventional cytotoxic agents were the only therapeutic approaches, until the discovery of “driver” oncogenic mutations in a subset of lung tumors [1], [2], [3]. This led to the subsequent development of corresponding targeted therapies. Rebiopsy is now recommended in the clinical setting of acquired resistance to EGFR or ALK Tyrosine Kinase Inhibitors, and trans-thoracic needle biopsies (TTNB) is included in the strategy of molecular profiling during patient clinical evolution [4].

Adenocarcinomas are the most frequent lung tumors, accounting for nearly 50% of the cases, and their histological recognition is mandatory as some adenocarcinomas harbour activating mutations or translocations of growth promoting oncogenes, responsible for a permanent tyrosine kinase activation targeted by specific inhibitors. Accordingly, the recent IASCLC/ATS/ERS classification of adenocarcinomas [5], provides histological guidelines for the identification on surgical specimens of the predominant architectural patterns [6], [7]; in addition, it provides histo and immunohistochemical algorithms for the diagnosis of adenocarcinomas on small specimens, which are often the only material available for NSCLC patients at advanced stages.

Computed tomography (CT)-guided TTNB is an established technique for the diagnosis of malignant lung neoplasms of peripheral location [8]. Core needle biopsy represents a very informative material for histological diagnosis, including immunohistochemical and histochemical analyses [9], [10]. In addition, with the incorporation of molecular profiling into personalized clinical care, mutation analyses must be feasible from this material. Few studies have been conducted to assess the sufficiency of core needle biopsy for molecular profiling. The purpose of this study was to retrospectively evaluate the adequacy of core needle biopsy specimens for histological and immunohistochemical diagnosis as well as mutation analyses (KRAS, EGFR, ALK mutations/rearrangement) in patients with primary adenocarcinomas of the lung.

Section snippets

Patients

From January 2010 to December 2012, 250 core needle biopsies of thoracic nodules or masses have been performed in our institution. Prior to each procedure, the risks and benefits of TTNB were discussed, and signed informed consent was obtained from each patient. Among them, we included 91 patients with the diagnosis of pulmonary adenocarcinomas. Forty-three TTNB were collected from January 2010 to February 2011 before the ATS/ERS/IASLC guidelines publication, and 48 from March 2011 and to

Patients (Table 1)

Sixty-three males and 28 females were enrolled in the present study. Overall, 73 patients were former or current smokers, and 18 were non-smokers. The mean size of the biopsied lesions was 32.6 mm (SD, 20.5 mm; ranging from 9 mm to 120 mm) on CT. Eighty-six patients (95%) had a nodule or a mass while 5 patients (5%) presented with chronic pulmonary consolidations. 85 (93%) lesions were within the lung parenchyma; 4 (4%) were located within the mediastinum; one was a lytic lesion of the 5th rib; one

Discussion

Image-guided core needle biopsy has become an accepted minimally invasive technique for histopathologic diagnosis of lung lesions [14]. Percutaneous tissue sampling of a pulmonary lesion is performed when a histological diagnosis is required and when it cannot be established by bronchoscopic techniques. TTNB can be used as a less invasive alternative to thoracoscopy and mediastinoscopy. It has an accuracy varying from 80 to 95% for the confirmation of pulmonary malignancy [14]. The negative

Conflict of interest statement

G.R.F. received payment for lectures from Roche, Lilly, Boehringer, Astra Zeneca; B.B. declared non conflict of interest; F.deF. received payment for lectures from Roche, Astra Zeneca; E.R. declared non conflict of interest; A.McF. declared consultancy fees for Pfizer; L.M.M. declared non conflict of interest; D.M.S. received money for board membership from Roche, Lilly, Boehringer, Pfizer, received money for consultancy for Roche; declared lectures for Amgen, Lilly, Astra Zeneca, Boehringer;

Acknowledgment

Molecular analyses were supported by INCA (Institut National Du Cancer).

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