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A 60–year-old Asian female had a 4-cm lung mass biopsied by core needle biopsy.

She never smoked and has no history of cancer or comorbidities.

What testing do you ask for to confirm the suspicion of lung cancer?

What other histology findings are important if lung cancer is confirmed?

Learning Objectives

  1. What is the new World Health Organization (WHO) classification of lung cancer?

  2. What are the markers distinguishing squamous from non-squamous lung cancer?

  3. What terminology has replaced the former bronchoalveolar carcinoma?

  4. What are scar carcinomas?

  5. What are poor prognostic histologies in non-squamous lung cancer?

Historically, the basis of all classifications of lung tumors was based on the sections routinely stained with hematoxylin-eosin (H&E) demonstrating the histomorphologic features of tumor cells: cell size and tumor architecture, cellular differentiation along the known types of histology, and the stage at which arrest of differentiation occurs. The biologic behavior was extensively studied, and clinical outcome was correlated with types and even subtypes of tumors based on some peculiar histomorphologic differences. The introduction of ultrastructural, immunohistochemical markers and lately molecular markers has supplemented but not supplanted the morphologic diagnosis.

To understand how tumors would behave is to understand how they develop and progress from one stage to another based on a multistep progression model that has been studied over decades. Pathologists have observed this process in other organ systems and concluded it is valid in the case of lung tumors.


Lung tumors have been grouped under different major groups with subgroups assigned under those in a branched tree model that not only reserved the broad characteristics but also recognized additional distinctive features. As our understanding of the histogenesis and due to the heterogeneity of tumors, which could create overlapping features and hence confusion, the classification of lung cancer has evolved over the years. The standard classification is the one adopted by WHO, which is meant to be applied worldwide, taking into consideration the variability of practices and differences in the availability of resources in different parts in the world. The last iteration is the one from 2015, and it introduced some transformational improvements based on the revolutionary changes with the advent of targeted therapy and immunotherapy.1 It not only has altered the classification of resection specimens but also has made recommendations applicable for the diagnosis of small biopsies and cytology specimens.

Lung cancer can be broadly divided into epithelial tumors and mesenchymal tumors. The former includes 4 major groups: adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma (Table 6-1). Historically, the most important distinction was between small cell carcinoma and non–small cell carcinoma for lack of therapeutic benefit for distinguishing squamous cell carcinoma from adenocarcinoma. A diagnosis of non–small cell carcinoma (not otherwise specified) was frequently used, especially on small biopsies and cytology specimens. Large cell ...

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