Morphology alone should be sufficient for diagnosis in up to 70 percent of cases, Dr. Trejo Bittar noted, and a stepwise approach to the IHC workup has proved to be helpful. First decide: Is it malignant? Carcinoma? Lung cancer? Are there neuroendocrine features? Can it be called small cell carcinoma? Is it squamous cell carcinoma or adenocarcinoma?
“If you follow this kind of thought process, you will be able to order the least amount of immunostains,” he said.
Use a minimum amount of IHC and avoid the systematic use of panels. Protect material for the anticipated need of molecular testing.
Other recommendations:
- Be familiar with all the specimens available. “Often I get frustrated,” Dr. Trejo Bittar said, “thinking, ‘I need to save the tissue.’ And then there is this cell block full of tumor cells that was also procured in the case. So communicating with your cytopathologist could save you a lot of headaches.”
- Start with TTF-1 and p40. TTF-1 (at least focal) and p40 (positive in majority of the tumor cells often, but at least 50 percent) positivity are recommended for the diagnosis of adenocarcinoma and squamous cell carcinoma, respectively.
- To confirm neuroendocrine morphology, use neuroendocrine markers (synaptophysin, INSM1, chromogranin, CD56).
- The only role for Ki-67 IHC is to help establish a diagnosis of high-grade neuroendocrine carcinoma.
- There is no useful marker to differentiate pulmonary mucinous adenocarcinoma from metastatic mimics, Dr. Trejo Bittar said. “It is better to leave it to the clinicians to decide where the tumor comes from.”
- There is no specific IHC panel for the differential diagnosis of primary versus metastatic lung tumors. Morphologic and molecular comparison is crucial.
The absolute number of tumor cells or the proportion of tumor cells to all cells in the sample is used to determine sample adequacy for molecular and other ancillary testing. Assess adequacy on an H&E slide done immediately after the unstained slides.
“Always estimate the percentage of tumor cells that are present on each block, not whether it is sufficient,” Dr. Trejo Bittar said, “because each laboratory has different validations.” He recommends, for example, reporting “block A has 20 percent and block A2 has 50 percent” and so on.
An adequacy statement should be in all reports.
“Ultimately, give the patient the benefit of the doubt. If you think you do not have enough tumor cells for NGS or you’re on the fence, or maybe this is just enough, still send it. Molecular techniques have improved a lot,” he said, “and now we do a lot with way less tissue.”
Amy Carpenter is CAP TODAY senior editor.