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Pushing the limits of techniques in small-sample biopsy of lung adenocarcinoma

  • Chuong D. Hoang
    Correspondence
    Address for reprints: Chuong D. Hoang, MD, Thoracic and Gastrointestinal Oncology Branch, Section of Thoracic Surgery, National Institutes of Health, National Cancer Institute, Center for Cancer Research and Clinical Center, 10 Center Dr, Rm 4-3940, Mail code 1201, Bethesda, MD 20892.
    Affiliations
    Section of Thoracic Surgery, National Institutes of Health, National Cancer Institute, Center for Cancer Research and Clinical Center, Bethesda, Md
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Open ArchivePublished:March 10, 2017DOI:https://doi.org/10.1016/j.jtcvs.2017.03.013
      Innovations in technology and novel strategies for performing small-sample biopsy of lung adenocarcinoma are needed.
      See Article page 332.
      Our recent increased understanding of lung adenocarcinoma pathobiology culminated in a new classification system summarized by the International Association for the Study of Lung Cancer.
      • Travis W.D.
      • Brambilla E.
      • Noguchi M.
      • Nicholson A.G.
      • Geisinger K.R.
      • Yatabe Y.
      • et al.
      International Association for the Study Of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma.
      Before this paradigm, adenocarcinoma represented a widely divergent clinical, radiologic, molecular, and pathologic spectrum with a variable prognosis that is poorly predicted by the older classification systems. Now, adenocarcinoma is better characterized by preinvasive, minimally invasive, and invasive histologic subtypes as described semiquantitatively in 5% tumor increments according to formalized guidelines for assigning a predominant pattern. There is consensus that histologic subtypes associate with clinical outcome, wherein for invasive adenocarcinoma the lepidic pattern has a favorable prognosis, papillary and acinar patterns have an intermediate prognosis, and micropapillary/solid patterns have the worst prognosis.
      • Hung J.J.
      • Yeh Y.C.
      • Jeng W.J.
      • Wu K.J.
      • Huang B.S.
      • Wu Y.C.
      • et al.
      Predictive value of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in tumor recurrence and patient survival.
      • Warth A.
      • Muley T.
      • Meister M.
      • Stenzinger A.
      • Thomas M.
      • Schirmacher P.
      • et al.
      The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival.
      Huang and colleagues
      • Huang K.-Y.
      • Ko P.-Z.
      • Yao C.-W.
      • Hsu C.-N.
      • Fang H.-Y.
      • Tu C.-Y.
      • et al.
      Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens.
      explore an intriguing notion to employ preoperative nonsurgical biopsy techniques to determine whether adenocarcinoma subtyping is accurate or not. They present 128 patients who had preoperative biopsy and lung surgery for invasive adenocarcinoma. They assessed the accuracy of preoperative computed tomography-guided core needle or radial probe endobronchial ultrasound biopsy results versus the pathologic specimen. However, the authors only achieved a concordance rate of 58.6% (75 out of 128) in the predominant histologic pattern among preoperative biopsy and surgical specimen. This lack of accuracy led to their main realization that the complex histologic features of lung adenocarcinoma preclude reliable assessment by small-sample biopsy techniques.
      Preoperative clinical implications of this result are multiple (assuming that frozen section analysis remains an imperfect method). Without accurate and reliable preoperative subtyping, it is more difficult to plan for a limited resection versus completion lobectomy. Because some adenocarcinoma subtypes may be associated with nodal metastases,
      • Xu L.
      • Tavora F.
      • Burke A.
      Histologic features associated with metastatic potential in invasive adenocarcinomas of the lung.
      this preoperative information could determine the need and extent of lymph node dissection. Other possible scenarios relate to those patients who cannot tolerate lung surgery. What next-best therapy is available for certain adenocarcinoma subtypes in lieu of lung resection? Finally, we can extrapolate to ask whether accurate histologic subtyping could determine which early stage patients may benefit from neoadjuvant therapy.
      It is instructive to understand the technical limitations likely responsible for the overall results of this study. As the authors indicated, computed tomography-guided core needle cannot always traverse the entire tumor diameter due to needle trajectory or intervening structures (eg, vasculature and airways). Tissue volume retrieved in the core needle is fixed, so the extent of representative sampling is limited and proportionally smaller as tumor mass increases. Multiple needle passes via different trajectories are not unlimited to allow access in all tumor regions to overcome sampling bias (secondary to inherent intratumor cellular heterogeneity
      • Travis W.D.
      • Brambilla E.
      • Noguchi M.
      • Nicholson A.G.
      • Geisinger K.R.
      • Yatabe Y.
      • et al.
      International Association for the Study Of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma.
      ). Radial probe endobronchial ultrasound biopsy relies on transbronchial biopsy using a forceps (∼ 1.5 mm), often augmented with cytologic brushings; alternatively, a 21G needle can be used.
      • Chen A.
      • Chenna P.
      • Loiselle A.
      • Massoni J.
      • Mayse M.
      • Misselhorn D.
      Radial probe endobronchial ultrasound for peripheral pulmonary lesions. A 5-year institutional experience.
      The ultrasound probe is positioned in an airway with an endobronchial tumor or in an adjacent airway (necessitating needle aspiration). Extensive sampling of tumor regions is not possible with biopsy forceps, for this would require burrowing into or through the entire tumor. These limited degree(s) of freedom for biopsy approach might be solved with future innovation in hardware and other emerging biopsy modalities.
      A valuable point is reaffirmed by this study in that histologic subtyping of adenocarcinoma influences prognosis.

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        • Geisinger K.R.
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        Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens.
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      Linked Article

      • Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens
        The Journal of Thoracic and Cardiovascular SurgeryVol. 154Issue 1
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          The prognostic significance of the new classification of lung adenocarcinoma proposed in the 2015 World Health Organization guideline has been validated. This study aimed to compare the preoperative classification of the adenocarcinoma subtype based on computed tomography–guided 18-gauge core needle biopsy (CTNB) or radial probe endobronchial ultrasound (R-EBUS) specimens, with the postoperative classification based on the resected specimens.
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