  TTF1 and {\Delta}Np63/p40 have been used to differentiate ADC and SQC in
hypofractionated NSCLC because of their sensitivity and specificity. There are
few cases where TTF1 and {\Delta}Np63/p40 are expressed together in the same
tumour cells, and little is known about the clinicopathological features,
treatment and prognosis of such cases. We investigated the electron microscopic
features, immunohistochemical expression and molecular variation of a case of
TTF1/p40 co-expressing NSCLC and reviewed and summarised the relevant
literature. Our patient was a 58-year-old male with a CT showing a left-sided
lung occupancy. As in all other cases reported in the literature, the tumour
showed a solid growth pattern with polygonal cells, eosinophilic cytoplasm and
clearly visible nuclear fission. Immunohistochemistry showed positive for
TTF-1, p40, CK5/6, CK7, P63 and p53, and negative for NapsinA and ALK. Electron
microscopy showed tumour cells characterised by bidirectional differentiation
of adenocytes and squamous cells, consistent with previous reports.
Second-generation sequencing suggested co-mutation of STK11/LKB1 and NF1 genes
in this case. Mutations in STK11/LKB1 and NF1 genes have been found in ADC and
SQC and are often associated with drug resistance and poor prognosis, but
STK11/NF1 co-mutation has not been reported and more cases are needed to reveal
the association. p40/TTF1 co-expression in NSCLC may be an under-recognised
variant of NSCLC The origin may be a double positive stem cell-like basal cell
located in the distal airway, with rapid clinical progression and poor
prognosis.
