A caution about CT-guided biopsies in particular: “Pleural elements can be entrapped,” Dr. Trejo Bittar said. “They look almost like pseudoinvasion.” The key is to recognize fibrous tissue underneath, he said, and the fairly benign and cytologically bland appearance (Fig. 4). “Sometimes the only useful thing is to tell the person who performed the CT-guided biopsy that there is a lot of pleura” and suggest follow-up for the possibility of pneumothorax.
Entrapped pleural fragments and mesothelial hyperplasia can be significant and appear invasive. “Any sort of mesothelial marker will be helpful to see these are actually mesothelial cells. This is not invasive carcinoma,” Dr. Trejo Bittar said.
Submucosal glands (Fig. 5) are recognized by their many characteristics—basal basement membrane, nodular arrangement of the cells, lack of atypia and invasion, and presence of serous and mucinous cells. Fig. 5 was one of Dr. Trejo Bittar’s consult cases; it had been called mucinous adenocarcinoma. “All of those characteristics should help identify that these are submucosal glands and not a mucous gland adenoma,” he said.
However, “overthinking” that something can be submucosal glands and missing a mucinous adenocarcinoma is its own problem, he said. His colleague received as benign the case in Fig. 6. The diagnostic keys to it being a mucinous adenocarcinoma are the complexity of the back-to-back glands, the clear cytologic atypia of the cells, and their diffuse appearance to signal the lack of other airway structures or nodular characteristics.
“When in doubt, immunostains will be helpful,” he said.
Dr. Trejo Bittar offers five general recommendations for lung biopsy handling:
- Collect as much tissue as possible within the constraints of patient safety to meet the need for additional downstream studies. “Keep a conversation going with your interventional pulmonologist,” he said. “Normally, CT-guided biopsies are good, but endobronchial/transbronchial biopsies can be a problem. If they are not collecting enough tissue, give them that feedback.”
- Fixation should be immediate using 10 percent pH-neutral buffered formalin.
- Consider embedding separated core/small biopsy samples for molecular testing. “Keep some for diagnostic purposes and keep others for biomarker testing to reduce the need to go back to the block,” he said.
- Consider reflex cutting of unstained slides to avoid multiple visits to the microtome and facing the block. Avoid discarding any tissue. “I tell my histotechnologist, ‘Use consecutive sections, do not face the block.’”
- Always keep molecular sterility when cutting and handling blocks and slides. “You don’t want to mix tissue.”