Once a broad tumor class is established, more specific differentiation markers can be pursued (e.g., lineage-restricted transcription factors for adenocarcinoma; p40 for squamous cell carcinoma; chromogranin A and synaptophysin or INSM1 for neuroendocrine neoplasms).
Although P40 staining for the sarcomatous component was positive along with squamous carcinoma, E-cadherin expression disappeared while vimentin was expressed.
Negativity or focal occurrence of p40 made SQC diagnosis unlikely on molecular grounds, but suggested ADC confirming validity of the axiom "no p40, no squamous."
Spatial proximity between bronchus and ALK-rearranged tumors and frequent solid histologic subtype with p63 expression may cause diagnostic difficulties to differentiate squamous cell carcinoma in the small biopsy, whereas p40 was rarely expressed in ALK-rearranged adenocarcinoma.
Diagnostic combinations were p40-/TTF1+ or TTF1- for AD (where p40was negative, apart from 5/30 AD showing at the best 1-2% tumor cells with low intensity); p40+/TTF1- (p40 strong and by far higher than 50%) for SQC; and p40+/TTF1+ or p40+/TTF1- (p40 strong and less than 50%) for ADSQC.