Ocular metastasis of lung adenocarcinoma with ELM4-ALK translocation: A case report with a review of the literature

Abstract

Choroidal metastasis is the most common intraocular neoplasm and is associated with significant morbidity. In a small percentage of patients, ocular manifestation may be the initial presentation of a systemic malignancy and can be diagnostically difficult to distinguish from ocular primary malignancies. Herein, we present a case of a never-smoker whose ocular pathology was integral to the diagnosis and management of a lung adenocarcinoma harboring a rare oncogene. Through this case, we have explored important diagnostic and therapeutic considerations of pulmonary metastases to the choroid.

Keywords: Adenocarcinoma; Choroidal metastasis; Crizotinib; EML4-ALK translocation; Non-small cell lung carcinoma; Targeted therapy.

Figure 1

(A) Left fundus of a choroidal metastasis showed a large dome-shaped amelanotic tumor with retinal pigment epithelium clumping. (B) Left lower lobe lesion was revealed by lateral chest X-ray. (C–E) Using serial MRI studies, it was noted that combined radiotherapy and chemotherapy were initially effective at reducing tumor size (arrows) (C, pre-treatment; D, post-treatment). However, over the subsequent 1.5 years, tumor size slowly enlarged (E, arrow) causing significant ocular pain. (F) Cross sections of the enucleated left globe revealed an amelanotic tumor mass (CA) in the posterior aspect of the globe measuring 20 mm in base and 9 mm in height. (G) The tumor cells invaded through the lamina cribrosa (arrow) to the margin of the surgical transection (hematoxylin-eosin, ×25).

Figure 2

(A–E) The ocular tumor formed gland-like structure (A, hematoxylin-eosin, ×100) with numerous signet ring cells with a vacuolated cytoplasm and a displaced crescent shaped nucleus (B, arrows, hematoxylin-eosin, ×400) and stained strongly positive for mucus production (C, arrows, periodic acid-Schiff, ×400; D, arrows, colloidal iron, ×400; E, arrow, mucicarmine, ×400). (F) Transmission electron microscopy of the ocular specimen identified tumor cells with the cytoplasm filled with a predominantly radiolucent vacuolated fibrillo-granular material with displacement of the nucleus into a crescent cap (arrow) in a signet ring configuration (original magnification × 2500). (G and H) Reassessment of the lung nodule FNAB (G, hematoxylin-eosin, ×400) and mediastinal lymph node (H, hematoxylin-eosin, ×400) demonstrated similar signet ring cells (arrows).

Figure 3

(A–C) Immunohistochemical staining for ALK gene rearrangement using anti-ALK antibody (5A4) showed extensive positivity in all three biopsy specimens (A, lung nodule FNAB, ×100; B, mediastinal lymph node, ×100; C, choroidal metastasis, ×100). (D) FISH analysis of the choroidal metastatic lesion is positive for ALK translocation as indicated by the separation of the red and green fluorescent marks. In the absence of gene translocation, the red and green fluorophores overlap (arrows).