Cancer Res Treat.  2021 Apr;53(2):601-606. 10.4143/crt.2020.952.

A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation

• Zhao S
• Liu W
• Li S
• Shi T
• Chen Q
• Li Q
• Sun L
• Ren D
• Song Z
• Huang C
• Xu S

• KMID: 2514941
• DOI: http://doi.org/10.4143/crt.2020.952

Abstract

A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK, and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post-crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

Keyword

rearrangement; Crizotinib; Adenocarcinoma of lung; Inflammatory myofibroblastic tumor; Ventana; Alectinib

Figure

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  Fig. 1 Computed tomography (CT), positron emission tomography (PET)-CT, and bronchoscope findings. (A) PET-CT image prior the treatments. (B) Endobronchial inflammatory myofibroblastic tumor was shown by CT and bronchoscopic examination prior and post the endobronchial cryotherapy. (C) Enhanced chest CT images of left lung adenocarcinoma during the first-line crizotinib treatment and second-line alectinib treatment.

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  Fig. 2 H&E and immunohistochemical staining of lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). (A) Positive expression of thyroid transcription factor 1 (TTF-1), napsin A, epithelial membrane antigen (EMA), cytokeratin (CK) 7, and anaplastic lymphoma kinase (ALK) Ventana in lung adenocarcinoma. (B) Positive expression of vimentin, smooth muscle actin (SMA), calponin, and ALK Ventana, as well as negative expression of CK for IMT.

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  Fig. 3 Identification of anaplastic lymphoma kinase (ALK) fusion by next-generation sequencing. (A) Sequencing read of LOC101927285-ALK fusion is shown by the Integrative Genomics Viewer. (B) Schematic structure of the genomic DNA sequence shows fusion points for the LOC101927285-ALK fusion. (C) Sequencing read of TMP3-ALK fusion is shown by the Integrative Genomics Viewer. (D) Schematic structure of the genomic DNA sequence shows fusion points for the TMP3-ALK fusion. (E) The chimeric reads of RNA-based next generation sequencing showed EML4-ALK rearrangement.

Reference

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