Biphenotypic lung carcinoma with coexpression of TTF-1 and ΔNP63/P40 within most of the same individual cells: a further case confirming poor prognosis and a review of literature

Abstract

The WHO Classification of Tumors, Thoracic Tumors, 5th edition, has outlined the use of TTF-1 and ΔNP63/P40 to discriminate between adenocarcinoma and squamous cell carcinoma. In 2015, the first description of a rare non-small cell lung carcinoma featuring co-expression of glandular and squamous differentiation within most of the same individual tumor cells was reported on, with ultrastructural and molecular demonstration of such a biphenotypic differentiation. We herein describe an additional case of this rare tumor entity, which is confirmed to be an aggressive neoplasm despite potential targets of therapy.

Keywords: biphenotypic lung cancer; lung adenocarcinoma; lung adenosquamous carcinoma; lung cancer immunohistochemistry; lung squamous cell carcinoma.

Figure 1.

Histologic appearance and immunoreactivity of the reported case. The tumor showed a solid growth pattern with necrotic areas, moderate nuclear atypia and focal features suggestive of squamous differentiation, with no evidence of obvious keratinization (1A-B). Immunohistochemical analysis found the tumor cells to be diffusely reactive for p40 and, to a lesser extent, for TTF-1 (1C-D).

Figure 2.

Next generation sequencing results. Integrative Genomics Viewer snapshots of base change c.35G > A (p.G12D) in the exon 2 of KRAS gene, Variant Allele Frequency (VAF) 14.6% (2A) and of exon 14-skipping nucleotide substitution c.3082+2T > C in the MET gene, Variant Allele Frequency (VAF) 61.2% (2B). Integrated Genomics Viewer of MET(13)-MET(15) variant, Read Counts 82159 (2C).