Amy Carpenter
May 2026—Preserving tissue for molecular and other biomarker studies is top of mind for many, and in a CAP25 lung cancer session last fall, an approach to doing so was presented.
“It seems that every day we wake up and there is a new, approved therapeutic in lung cancer that has a companion diagnostic tool we need to use,” said Humberto Trejo Bittar, MD, chair of the CAP/NSH Histotechnology Committee. “There is a lot of need for tissue on these small biopsies.”
He spoke at the meeting about mimickers of malignancy, the handling of lung biopsies, and recommended steps to the immunohistochemistry workup.
Carcinoid tumorlets and meningothelial-like nodules (chemodectomas) are among the mimickers of malignancy, said Dr. Trejo Bittar, associate professor, Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, and Department of Pathology, University of South Florida Morsani College of Medicine.
A tumorlet is a minute nodular proliferation of cytologically bland neuroendocrine cells, most frequently located in the wall of airways (Fig. 1). “It’s basically a carcinoid tumor that is less than 0.5 cm and will have all the histologic features and immunostain characteristics of a carcinoid tumor,” Dr. Trejo Bittar said, such as synaptophysin, TTF-1 positivity, and a low Ki-67 proliferation index. It will always occur around an airway, where the neuroendocrine cells are, and it is normally bronchiolocentric, with characteristic neuroendocrine morphology.
The tumorlet might represent an incidental finding in the background of small airway disease, scarring, or fibrosing lung disease. There can be multiple tumorlets; this should raise the possibility of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, or DIPNECH.
In contrast, meningothelial-like nodules are in the alveolated parenchyma, not near an airway (Fig. 2). They are minute proliferations of cytologically bland meningothelial-like cells (whorls and pseudoinclusions, and progesterone receptor, epithelial membrane antigen, and CD56 positive) in alveolar septae (not peribronchiolar)—an incidental finding of no clinical significance.
Bronchiolar metaplasia is a benign process that can be prominent and challenging, especially on frozen sections, Dr. Trejo Bittar said (Fig. 3). It can make nodules and look like a lesion radiologically.
The key is to recognize the bronchiolocentric, centrilobular characteristic of the process, he said, noting the need to look for cilia.
“Sometimes you will be able to see the basal cells,” he said. “You will realize this is not adenocarcinoma or any sort of malignancy.” If in doubt, a p40 immunostain will highlight the basal cells of the metaplastic bronchiolar epithelium. “There should be a discontinued layer of basal cells,” he said, “even on the things that look more distant.” Terminal bronchioles are a simplified respiratory-type epithelium. They will have almost no cilia, and p40 is helpful in being able to see the discontinued layer of p40-positive basal cells.