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

Abstract

Pulmonary sarcomatoid carcinoma is rare, with limited treatment options and poor prognosis. In contrast to other non small cell lung carcinomas, not much is known about its molecular biology. In an endemic country like India, lung cancer is often masked by tuberculosis and presents in advanced stages. We report here an unusual case of pulmonary sarcomatoid carcinoma, in a young non-smoker male, who had co-existent tuberculosis masking and delaying the diagnosis of malignancy. On molecular study, the tumor showed ALK gene rearrangement, both by immunohistochemistry and fluorescence in-situ hybridization, which has been reported only twice previously. Presence of ALK gene rearrangements in sarcomatoid carcinoma has significant therapeutic implications and potential for altering the prognosis of this fatal disease. Hence we recommend performing ALK gene rearrangement analysis in all cases of sarcomatoid lung carcinomas. The report discusses the diagnostic approach and provides insight into the molecular pathogenesis of this exceedingly rare malignancy.

Pulmonary sarcomatoid carcinoma: progress, treatment and expectations

“…For patients with EGFR -mutated tumors, the US Food and Drug Administration (FDA) has approved gefitinib, afatinib, and osimertinib for clinical therapies. 48 The benefits of successfully treating patients with mutations by using first-generation TKI drugs, including gefitinib, erlotinib, icotinib, are limited. The second- and third-generation TKIs, such as afatinib and osimertinib, respectively, 45 , 48 , 64 , 71 provide better benefits to patients with rare mutations compared with first-generation TKIs.…”

“…For the rearrangement of rare genes, such as those of the ALK1 gene, patients can take a combination of crizotinib and ceritinib. 48 There are few case reports of patients with ALK rearrangements with differing results, but most patients had invalid or partial responses; 48 however, there have been individual reports of patients with PRs. 76 New ALK –TKI drugs, such as ceritinib, are more effective in patients with crizotinib insensitivity or resistance.…”

“…57 The efficiency of EGFR TKIs varies from person to person, but the overall effectiveness in patients with PSC is not as good as those with adenocarcinoma. 3,48 Thus, EGFR receptor antagonists are not necessarily effective.…”

“…47 Similarly, another study showed that the gene mutations rates of TP53, KRAS , and MET were 70%, 30–40%, and 13–20%, respectively. 48 In the research by Lococo et al , 49 PSC cases were studied using next-generation sequencing (NGS) analysis of 26 potentially relevant genes in surgically resected tumor samples. A total of 39 PSC cases (80%) showed at least one mutation (with the highest mutation rates in TP53, KRAS, PTEN, KDR, ERBB2 and PIK3CA ), and 69% of variants were somatic mutations.…”

“…48 The benefits of successfully treating patients with mutations by using first-generation TKI drugs, including gefitinib, erlotinib, icotinib, are limited. The second- and third-generation TKIs, such as afatinib and osimertinib, respectively, 45,48,64,71 provide better benefits to patients with rare mutations compared with first-generation TKIs. Research by He et al showed that afatinib combined with crizotinib could provide partial remission in patients with PSC.…”