A Poorly Differentiated Malignant Neoplasm Lacking Lung Markers Harbors an EML4-ALK Rearrangement and Responds to Crizotinib

Abstract

Suspected metastatic site lesions that are poorly differentiated present a diagnostic challenge when morphologic and immunohistochemical profiling cannot establish the primary tumor site. Here we present a patient diagnosed with both a malignant neoplasm in the lung and a right upper extremity (RUE) neoplasm of unclear histogenetic origin. Immunohistochemical staining performed on the latter specimen was inconclusive in determining the site of origin. Although the lung biopsy sample was insufficient for molecular testing, hybrid capture-based comprehensive genomic profiling (FoundationOne) identified an EML4-ALK rearrangement in the RUE lesion. Crizotinib treatment resulted in a major response in both the RUE and the lung lesions. This report illustrates the utility of comprehensive genomic profiling employed at the initial presentation of an unknown primary malignant neoplasm, which resulted in the front-line use of targeted therapy and a significant and sustained antitumor response.

Keywords: ALK; Crizotinib; Poorly differentiated lung neoplasm; Unknown primary tumor site.

Fig. 1

a Photomicrograph. Low power (40×) and high power (×200; inset) of the biopsy specimen from the right upper extremity. b EML4-ALK fusion. EML4 (in blue; exons 1–6), which includes the coiled-coil domain (CC), is fused to ALK (in red; exons 20–29), which includes the kinase domain. c–f Imaging studies before and after crizotinib treatment. c Pretreatment CT scan of the chest shows a right hilar mass measuring 6.5 × 7 cm. d Posttreatment CT scan was taken 1 month after beginning crizotinib treatment. e Pretreatment PET scan shows the RUE mass and multiple lung masses. f Posttreatment PET scan was taken 2 months after beginning crizotinib treatment.