The Pathologic Workup of Lung Adenocarcinoma

Transcript:Gerald J. Berry, MD: The pathologic workup of lung adenocarcinoma, these days, gets more and more complicated, in large part because there’s a wide variety of means to gain tissue for a diagnosis. Some are done through transthoracic needle core biopsies, which are often done under CT guidance. Some are done by the interventional pulmonologists through a transbronchial biopsy or through the endoscopic ultrasound-guided or the endobronchial ultrasound-guided biopsies (EBUS). And then, in rare occasions, you still need to make the diagnosis at the time of a planned resection. So, a frozen section will be performed prior to the surgeon performing or preparing the lobectomy, or whatever the resection is going to be.

Once we obtain tissue, it’s incumbent upon the pathologist to establish a diagnosis of malignancy—confirm that it’s an epithelial tumor, that it’s a lung cancer and not a lymphoma or a metastasis. And then, once the determination of carcinoma has been established, nowadays it’s required to try and subclassify it into either adenocarcinoma or squamous cell carcinoma, and, of course, separating it out from the small cell carcinomas. And part of the reason for distinguishing adenocarcinoma from squamous carcinoma is because it will, depending on which particular type it is, determine which additional ancillary study, such as molecular studies, will be performed.

For example, in our institution, we made the decision—in conjunction with the oncology faculty as well as the multidisciplinary tumor board—that we would perform molecular testing upfront on all newly-diagnosed adenocarcinomas of the lung. So, that involves performing the ALK and ROS1 gene rearrangements and testing by FISH, or fluorescence in situ hybridization. We do the PD-L1 testing by immunohistochemistry, and we also then will send tissue for mutational testing, usually through the next generation sequencing techniques. For all new squamous cell carcinomas, we will automatically do PD-L1 testing, but not the other types, unless requested by the oncologist for very specific indications.

I think it’s then incumbent upon pathologists to attempt to distinguish adenocarcinoma from squamous cell carcinoma, and that can be in a variety of ways using immunohistochemical staining. But first and foremost, you need to look at the cells—do they show features of squamous cell or of blanch of a differentiation? And then, as I say, once that step is made, then the additional studies will ensue.

The parameters that are used in staging basically attempt to determine the degree of spread, whether it be local or distant spread. And so, that can be done either prior to a planned resection or at the time of a resection procedure. Nowadays, the interventional pulmonologist will sample the mediastinal lymph nodes—the N1 stage nodes and attempt to try and sample N2 nodes. So, that way not only can they establish the diagnosis of carcinoma, but then they can establish that is a stage 2 or a stage 3.

When we receive a resection specimen—whether it be 1 lobe or by the 2 lobes, or sometimes the entire lung—along with that will come the lymph nodes that we removed from the hilar region, as well as the peribronchial lymph nodes. But the surgeons will also sample the mediastinal nodes and the subcarinal nodes, the so-called N2 station nodes. And so, then a formal staging can take place using the guidelines of the established cancer societies. This will allow the clinicians to add whether or not there’s metastatic disease—because some of that information is not available to us—and to determine the final clinical stage of the patient. That will then, of course, determine adjuvant therapies and other considerations.

Transcript Edited for Clarity