Clinical Significance and Next-Generation Sequencing of Chinese Pulmonary Sarcomatoid Carcinoma

Abstract

Pulmonary Sarcomatoid Carcinoma (PSC) constitutes a heterogeneous group of non-small-cell lung carcinomas (NSCLCs) with a poor prognosis. In this study, a group of 7 patients with PSC was studied. Microscope analysis of all 7 cases revealed a pleomorphic carcinoma subtype. Moreover, 5 cases (71.4%) were composed entirely of malignant sarcomatoid-like elements, and 2 cases (28.6%) were composed of malignant sarcomatoid-like elements and at least 10% adenocarcinoma-like elements. Immunohistochemically, the PSC components of all 7 cases were positive for vimentin and cytokeratins, including cytokeratin (CK) and cytokeratin 7 (CK7). Next-Generation Sequencing (NGS) was performed, and a total of 136 putative somatic variants and one gene fusion were identified, of which 16 variants were considered hot spot mutations, including the genes EGFR, EML4-ALK, MET, BRAF, PIK3CA, and TP53. Of these hot spot mutations, one sample expressing an EML4-ALK fusion was further confirmed by Ventana IHC, and one sample containing an EGFR exon 19 deletion was also confirmed. The NGS results imply that TP53 mutations occur often in PSCs and that EML4-ALK fusion events and EGFR exon deletions also occur in these rare tumors. Molecular targeted therapy may be a useful treatment strategy for these rare lung tumors.

Figure 1

Pathological characteristics demonstrated by H&E staining. Cases 1, 2, 3, 4, and 7 were composed entirely of malignant sarcomatoid cells (spindle cells and malignant cells) and showed poorly differentiated bizarre giant cells that were distributed evenly among abundant spindle-shaped cells. In cases 5 and 6, we observed an adenoid structure among the malignant sarcomatoid components.

Figure 2

Immunohistochemical characteristics of our study. All 7 cases were reactive to vimentin and cytokeratin immunostaining, showing diffuse staining in the cytoplasm. Cases 1–6 was positive for CK7 staining, whereas case 7 was negative for CK7 staining.

Figure 3

(A) Mutation types according to the type of nucleotide substitution and the variant consequence. (B) Somatic mutation events detected in PSC.

Figure 4

Immunohistochemical and H&E staining for EML4-ALK gene fusions. Case 4 harbored an EML4-ALK gene fusion that was discovered by NGS. Immunohistochemical staining with monoclonal rabbit antibody (Ventana D5F3, ROCHE, CH) confirmed the presence of an EML4-ALK fusion.