In treatment of non-small cell carcinoma differentiating adeno from squamous cell carcinoma is essential.When morphological diagnosis is difficult IHC is done and sometimes we get adeno and squamous cell marker co-expression by same group of cells.
As you already stated adeno-& squamous- lung carcinoma histologic markers may co-exist and rarely there are NSCLC of mixed histologic types.
In these cases, I think one has to treat with a "broad-spectrum" regimen addressed to both adenocarcinomas as well as squamous cell carcinomas, and such regimen is Paclitaxel/Carboplatin. Avastin might at first sight seem contraindicated because of the squamous carcinoma component, but to my view if the disease is of peripheral and not central location, one could administer Avastin with the Pac/Carbo regimen.
For diagnostic purposes the question is if you are dealing with a biopsy specimen or a resection specimen.
In a biopsy specimen if on the HE-staining you do not see clear signs of adenocarcinoma and you excluded small cell carcinoma than the first level of diagnosis is NSCC (non-small cell carcinoma), NOS. If you performed immunohistochemical stains then the question is which of the markers is homogeneously positiv in all your cancer cells. In your case if TTF-1 would be positiv in all/most of the cancer cells and p40/p63 would be more focal than TTF-1 then the final diagnosis according to the WHO 2015 classification would be "NSCC, favour adenocarcinoma".
For a squamous carcinoma you would expect a homogeneously strong p63 and p40 staining.
We know that p63 and p40 can be focally expressed in adenocarcinomas. Citing from the WHO book, page 18: "However, recent data suggest that p63 is less specific than was previously thought, since p63 expression can also occur in up to a third of adenocarcinomas. Virtually all tumors that lack squamous cell morphology and show coexpression of p63 and TTF1 are preferably classified as adenocarcinomas".
At our institution for a case with "NSCC, favour adenocarcinoma" we would perform EGFR-mutation and ALK-translocation analysis.
Hi to all,
I would strongly agree to Lorand L Kis- we would go for deep sequencing which is by far more informative than any ,,superficial'' staining method.
Kind regards,
Wolfgang
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