A joint effort by three medical groups has enabled a variety of specialists to join pathologists in revising the classification of lung adenocarcinoma, and they’ve made some major changes.
A new section addresses diagnosis and classification of non–small cell lung carcinoma (NSCLC) in small biopsies and cytology, including criteria to distinguish adenocarcinoma from squamous cell carcinoma.
The new classification also recommends epidermal growth factor receptor (EGFR) mutation testing in patients with advanced lung adenocarcinoma to help predict response to tyrosine kinase inhibitors.
And it dumps the term "bronchioalveolar carcinoma" while elsewhere adding some new terms (adenocarcinoma in situ and minimally invasive adenocarcinoma) in the document published in the February issue of the Journal of Thoracic Oncology (J. Thorac. Oncol. 2011;6:244-285).
The International Association for the Study of Lung Cancer convened the multidisciplinary panel of experts to revise the previous World Health Organization classification of lung adenocarcinoma, with support and scientific oversight from the American Thoracic Society and the European Respiratory Society. Pathologists, oncologists, pulmonologists, radiologists, thoracic surgeons, and molecular biologists joined the effort.
The revisions should make it easier to stratify patients and to individualize treatment, Dr. William D. Travis, chair of the expert panel, said in an interview. The changes also could significantly influence the next revision of the TNM (tumor, node, metastases) staging system, "not only for pathologic staging but also for clinical staging," said Dr. Travis, a thoracic pathologist at Memorial Sloan-Kettering Cancer Center, New York.
The new section on small biopsies and cytology specimens is especially important because 70% of lung cancers are diagnosed in samples like these, the consensus panel’s statement said. New criteria for diagnosing adenocarcinoma vs. squamous cell carcinoma include the use of special stains in difficult cases, and emphasize the importance of preserving tissue for molecular studies.
Dr. Travis outlined three important clinical reasons to distinguish adenocarcinomas from squamous cell carcinoma, especially in advanced disease.
• Patients with advanced lung adenocarcinoma or unspecified NSCLC who test positive for EGFR mutation are more likely to respond to treatment with tyrosine kinase inhibitors than are patients without mutation.
• Patients with adenocarcinoma or unspecific NSCLC are more likely to respond to pemetrexed (Alimta) than are patients with squamous cell carcinoma.
• Bevacizumab is contraindicated in patients with squamous cell carcinoma because it can lead to life-threatening hemorrhage, he said.
The statement attempts to banish the term bronchioloalveolar carcinoma from histopathology because it is used in ways that confuse five distinct categories: adenocarcinoma in situ; minimally invasive adenocarcinoma; lepidic predominant adenocarcinoma; adenocarcinoma that is predominantly invasive with some nonmucinous lepidic component; and invasive mucinous adenocarcinoma.
"Adenocarcinoma in situ" and "minimally invasive adenocarcinoma" appear in the classification for the first time for small solitary adenocarcinomas with either pure lepidic growth or predominant lepidic growth and no more than 5 mm invasion, because these terms identify patients who have nearly a sure shot at disease-free survival after complete resection.
The statement recommends a new approach for classification of resected invasive lung adenocarcinomas using comprehensive histologic subtyping and classification according to the predominant histologic subtype. "This allows for improved stratification of patients compared to the 2004 WHO classification, and allows for identification of subtypes that have prognostic significance and that can be correlated with molecular findings," Dr. Travis said.
Introducing the concept of in situ carcinoma raised the consideration that tumor size measured according to the size of the invasive component may be a better approach than measuring total tumor size in predicting survival for patients with small solitary adenocarcinomas with a lepidic component. This concept potentially could affect both pathologic and clinical staging in the next TNM, he said.
Using CT, prognosis may be better predicted by the size of the solid component in partly solid nodules rather than by total tumor size including the ground-glass component, Dr. Travis explained. "Hopefully, this will be investigated by lung cancer groups around the world in the next 5 years, so the TNM committee can address this issue in developing the 8th edition of TNM based on validated data," he said.
One of the consensus committee members, Dr. Giorgio Scagliotti, has received honoraria from Sanofi-Aventis, Roche, Eli Lilly, and AstraZeneca. Another committee member, Dr. David Yankelevitz, is a named inventor on some patents related to the evaluation of diseases; the patents are licensed to General Electric and may produce compensation if they are commercialized. The rest of the committee reported having no financial conflicts of interest.