A Case of Metastatic Atypical Neuroendocrine Tumor with <i>ALK</i> Translocation and Diffuse Brain Metastases

Wang, Victoria E.; Young, Lauren; Ali, Siraj M.; Miller, Vincent A.; Urisman, Anatoly; Wolfe, John A.; Bivona, Trever G.; Damato, Bertil; Fogh, Shannon; Bergsland, Emily K.

doi:10.1634/theoncologist.2017-0054

Cited by 33 publications

(22 citation statements)

References 31 publications

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“…Among ‘druggable’ molecular targets, recent reports have demonstrated the expression of ALK, a tyrosine kinase receptor activated aberrantly in approximately 5% of NSCLC, in metastatic AC of the lung . ALK overexpression was associated with ALK rearrangement, and ALK gene alteration was detected both in tumour tissue and in circulating tumour DNA.…”

Section: Carcinoid Tumoursmentioning

confidence: 99%

“…ALK overexpression was associated with ALK rearrangement, and ALK gene alteration was detected both in tumour tissue and in circulating tumour DNA. The tumours did not respond to chemotherapy, but ALK inhibitor crizotinib reduced tumour growth successfully . Although intriguing, a word of caution has to be voiced, as these findings are based on single case reports whose diagnoses were made on biopsy specimens only; therefore, further validation is needed.…”

Section: Carcinoid Tumoursmentioning

confidence: 99%

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Molecular alterations of neuroendocrine tumours of the lung

et al. 2017

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deletions), but restriction of multiple endocrine neoplasia type 1 (MEN1) mutations to carcinoids. Highgrade carcinomas are also characterised by TP53 and RB1 gene inactivation. In this review, a critical analysis of the diagnostic and prognostic role of Ki67 labelling index and a concise discussion of the most relevant findings regarding molecular characterisation of lung neuroendocrine neoplasms are reported. In addition, we illustrate how the development of promising therapeutic strategies based on the identification of molecular targets (mTOR inhibitors in carcinoids and targeting of the Notch ligand DLL3 in SCLC) may require the assessment of predictive biomarkers, even in the group of neuroendocrine tumours of the lung.

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Section: Carcinoid Tumoursmentioning

confidence: 99%

Section: Carcinoid Tumoursmentioning

confidence: 99%

Molecular alterations of neuroendocrine tumours of the lung

et al. 2017

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“…Few cases have been reported. 10 – 19 A noteworthy phenomenon is that most of them were disseminated and high-grade lesions (3 atypical carcinoid tumors and 6 high-grade NECs). The detailed clinicopathological characters and outcome of anti-ALK targeted therapy are summarized in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

<em>ALK</em>-rearrangement neuroendocrine carcinoma of the lung: a comprehensive study of a rare case series and review of literature

Zheng¹,

Zheng²,

Jin³

et al. 2018

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Driver mutations involving tyrosine kinase receptors play crucial roles in the oncogenesis of lung adenocarcinoma. However, receptor tyrosine kinase mutations are extremely rare events in primary pulmonary neuroendocrine carcinoma (NEC), which is a molecular heterogeneous entity. In this study, we examined 4 cases of NEC with anaplastic lymphoma kinase (ALK) rearrangement between 2008 and 2018 at our hospital. We comprehensively analyzed the carcinomas’ clinicopathological features, genetic alterations, and response to ALK inhibitor. One case of atypical carcinoid tumor and 1 case of large cell NEC (LCNEC) achieved response to ALK inhibitor (crizotinib) treatment. One case of combined LCNEC with adenocarcinoma harboring KLC1-ALK (K9:A20) fusion genes was confirmed by NGS of both components, while only the LCNEC component presented RB1 mutation. Notably, tumor cells of different components exhibited different ALK-positive signal patterns by fluorescence in situ hybridization, which revealed isolated 3′ signals in the adenocarcinoma component but split signals in the LCNEC. As the largest case series study, our findings suggested that preliminary screening for ALK rearrangement should also be considered in atypical carcinoid and high-grade NEC. Patients with ALK rearrangement-positive NEC would benefit from ALK inhibitor intervention.

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confidence: 99%

“…In this issue of The Oncologist , Lai et al and Wang et al describe the presence of ALK rearrangements in two distinct malignancies and highlight the use of liquid biopsies in molecular diagnostics . Wang et al report the case of an ALK ‐rearranged atypical neuroendocrine tumor with diffuse central nervous system metastases . Of note, molecular testing could not be performed on the patient's initial diagnostic biopsy specimen due to insufficient tissue; however, genotyping of circulating free DNA (cfDNA) using a capture‐based next‐generation sequencing (NGS) platform revealed a novel SMC5‐ALK fusion.…”

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confidence: 99%