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.

<p>Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma</p>

“…The first clues about the genetic landscape of PSC became available only in the most recent years. [81][82][83][84][85][86] The raise and rapid expansion of the new sequencing techniques, together with the collection of relatively large series of PSC samples available for the analysis have represented major turning points in getting clues into the genetic assets of these tumors.…”

“…Together with alterations in TP53, KRAS mutations are also quite frequent in PSCs with a reported occurrence that range between 15% and 39% depending on series. [81][82][83][84][85] Mutations in 12 codon are the most frequent even if mutation in codon 61 has also been reported. KRAS mutations have been found significantly associated with pure sarcomatoid or with PSC with an adenocarcinoma component.…”

Alk1 gene rearranged pulmonary sarcomatoid carcinoma masquerading as tuberculosis in a young male

“…(13). Since then, only handful of reports of ALK rearrangements were reported in PSC and the effects of targeted therapies against this mutation have been shown to be varied, but mostly with ineffective or partial responses (13)(14)(15)(16)).…”

Apatinib-based targeted therapy against pulmonary sarcomatoid carcinoma: a case report and literature review

“…Clinical detection of sarcomatoid carcinoma is a rare event [ 1 – 3 ]. In this study, we reported a case of sarcomatoid carcinoma occurring in the lung.…”

“…Sarcomatoid carcinoma is a rare form of cancer characterized by a combination of epithelial and sarcoma or sarcoma-like components [ 1 ]. Sarcomatoid carcinoma has been detected at multiple anatomic sites such as the prostate [ 2 ], lung [ 3 ], gallbladder [ 4 ], jejunum [ 5 ], and pelvic cavity [ 6 ]. Pulmonary sarcomatoid carcinoma accounts for 0.1–0.4% of all pulmonary cancers [ 7 ].…”