Micropapillary histology: a frequent morphology of mutation-associated lung adenocarcinoma?

Non–small cell lung carcinoma is a histologically diverse group of tumors that until recently has been treated homogeneously. As a result, pathologists recognized major classes of squamous, adenocarcinoma, and large cell carcinoma, with subclasses and variants to ensure accurate diagnosis, to identify rare subtypes, to assist pathologist communication, and to create uniformity in research despite the fact that these classes did not generally influence clinical decision-making. This has changed radically in the last few years. Chemotherapeutic regimens may be tailored based on histolog-ic subtype, and targeted therapies are contraindicated in certain histologic subtypes. Molecular classification has led to insights into tumor pathogenesis, prognostication, and therapeutics. While the molecular age in lung cancer diagnostics and targeted therapeutics is driving the movement towards per-sonalized medicine, it needs to be emphasized that pathologists have been providing personalized information all along. In fact, if we divide the patient-specific information into 4 categories—histologic classification, pathologic staging, prognostic markers of survival, and predictive markers of therapeutic response—pathologists can better understand the interplay of existing practice and novel findings in their current and future practice. In this issue of the American Journal of Clinical Pathology, Achcar and colleagues 1 provide an example of how morphologic classification and molecular classification provide complementary data that serve different components of personalized patient-specific information. In fact, this work demonstrates the issues that exist once these distinct data sets are merged, and shows us the challenges that face the surgical pathologists, thoracic pathologists, and molecular pathologists of the future. Micropapillary adenocarcinoma of the lung is a his-tologic subgroup that is considered to be an aggressive adenocarcinoma with greater likelihood of presentation at an advanced stage. It was not defined in the 1999 and 2004 World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC) classification, 2 and as a result the specific criteria for inclusion in this group remain elusive. In their work, Achcar et al 1 use an established definition of Silver and Askin 3 for papillary carcinoma, but this may not have been the case in other studies of micropapillary adenocarcinoma. The importance of a precise definition in the lung is underscored by the fact that this may not be the same pattern that bears that name in primary tumors of other organs. Therefore histologic classification requires a pulmonary definition for this entity in the next IASLC classification that is reproducible and generalizes for all pathologists who apply …