A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases

Oncologist. 2017 Jul;22(7):768-773. doi: 10.1634/theoncologist.2017-0054. Epub 2017 May 15.

Abstract

A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies. In this article, we present a case of a 52-year-old never-smoking male who presented with widely metastatic atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping using DNA harvested from a bone metastasis was unsuccessful due to limited material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical significance of the mutation in this particular cancer type and therapeutic strategies are discussed.

Key points: To our knowledge, this index case represents the first reported ALK translocation identified in an atypical carcinoid tumor.Liquid biopsy such as circulating tumor DNA is a feasible alternative platform for identifying sensitizing genomic alterations.Second-generation ALK inhibitors represent a new paradigm for treating ALK-positive patients with brain metastases.

Publication types

  • Case Reports

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Humans
  • Liquid Biopsy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neuroendocrine Tumors / diagnostic imaging
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / pathology*
  • Neuroendocrine Tumors / therapy*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Translocation, Genetic*

Substances

  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases