Although Thoracic SMARCA4-deficient undifferentiated tumour (SD-UT) is a recognized entity in the 5th edition of the WHO classification of thoracic tumors, this alteration occurs in garden-variety lung cancer as well (and in many other tumors too!)
In fact, it is likely SD-UT exists on a continuum with SMARCA4-deficient lung cancer.
I recently came across an interesting case that demonstrated this phenomenon. The same patient presented with two synchronous lung lesions, one peripheral and one central, with different morphologies and immunoprofiles.
However, both lesions showed loss of SMARCA4 by immunohistochemistry:
In further support of clonal relatedness, both lesions were positive for the same TP53 frameshift variant. Therefore, the central lesion is best described as a dedifferentiated metastasis of the peripheral lesion, with loss of SMARCA4 occurring before dedifferentiation and metastasis.
As testing for SMARCA4 becomes more and more used in clinical practice, these sorts of cases are becoming commonplace, adding additional anecdotal evidence that a large amount of SD-UTs are in fact very undifferentiated non-small cell lung cancers. One hopes that therapeutic improvements and targeted therapies will follow accordingly!
Acknowledgments
Many thanks to Dr. Pierre-Olivier Fiset for sharing this case.