Small cell carcinoma of lung
A 62-year-old man presented to his general practitioner (family medicine / primary care physician) complaining of haemoptysis. Sputum analysis was negative when performed via his general practitioner. He was referred to the lung outpatient clinic and then proceeded to bronchoscopy, where bronchial brushings were performed and material sent to pathology for cytological examination. His smoking status and past history were unknown to pathology.
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Background proteinaceous fluid and benign bronchial epithelial cells with occasional small clusters of malignant epithelial cells displaying pleomorphic, hyperchromatic nuclei with granular chromatin, inconspicuous nucleoli and irregular nuclear membranes with scant cytoplasm. Nuclear molding is focally present.
Diagnosis: Positive for malignancy - features in keeping with small cell carcinoma
Whilst there wasn't an abundant amount of material in this case, there were enough groups of malignant cells displaying the characteristic features of small cell carcinoma to confidently make this diagnosis. In addition, tissue biopsy specimens taken from the patient showed similar features further confirmed the diagnosis (though this cytology case was reported on its own merits).
It is extremely important when making a definitive diagnosis of small cell carcinoma within the lung to do so appropriately, and only when you have the right amount of evidence and confidence to do so, as this may be the only tissue diagnosis the patient ever receives, and can dictate treatment pathways.
Things to remember when considering a diagnosis of small cell carcinoma in a cytology setting:
Better preserved tumor cells may look deceptively larger than you're expecting - in spite of its name, small cell carcinoma can have varying cell sizes, and some well preserved or air dried cells can look larger than you may think. That said, if all cells are very large (especially when comparing them to benign bronchial epithelial cells, or inflammatory cells), think twice before making a diagnosis of small cell carcinoma.
If cells have a moderate to abundant amount of cytoplasm, think very carefully before making a diagnosis of small cell carcinoma. Even larger 'small cell' cells shouldn't have much cytoplasm. Small cell characteristically has a scant amount of delicate cell cytoplasm exhibiting a basophilic hue.
Similarly, if cells display prominent nucleoli - think twice before making a small cell diagnosis - small cell should only have small/inconspicuous nucleoli - remember their neuroendocrine links and that they should have a similar salt and pepper chromatin pattern.
Nuclear molding needs to be just that: true molding. Nuclei need to be wrapped around each other and deforming/conforming to the shapes of their neighboring nuclei - like a big nuclear 'group hug', as I like to think of it. Cells that are simply hanging around next to each other (i.e. merely being cohesive) are not molding.
Again, this is a feature we often find as a striking red flag in histology specimens but that may be absent in a cytology preparation. If you see it, it may help, but it may not, as this feature may also be caused by over enthusiastic smearing of slides.
Apoptotic Debris, Mitotic Activity
These are also pieces of evidence you can use when making your diagnostic case, but aren't definitive in and of themselves.
- Sturgis CD, Nassar DL et.al. Cytologic Features Useful for Distinguishing Small CellFrom Non–Small Cell Carcinoma in Bronchial Brush and Wash Specimens. Am J Clin Pathol 2000;114:197-202 Full article PDF (free access)