Lung Cancer of Unknown Primary Site with EGFR Mutation as Indicated by Frozen Bone Specimen

Case Report

Austin J Pulm Respir Med 2015; 2(3): 1030.

Lung Cancer of Unknown Primary Site with EGFR Mutation as Indicated by Frozen Bone Specimen

Boku S¹*, Takase N¹, Onoe T¹, Shibata Y¹, Matsumoto K¹, Satouchi M², Sakuma T³, Sudo T4 and Negoro S¹

¹Department of Medical Oncology, Hyogo Cancer Center, Japan

²Department of Thoracic Oncology, Hyogo Cancer Center, Japan

³Department of Diagnostic Pathology, Hyogo Cancer Center, Japan

4Section of Translational Research, Hyogo Cancer Center, Japan

*Corresponding author: Shogen Boku, Department of Medical Oncology, Hyogo Cancer Center, 13-70 Kitaojicho, Akashi-City, Hyogo 673-8558, Japan

Received: September 25, 2015; Accepted: November 02, 2015; Published: November 03, 2015

Abstract

We reported a case of lung cancer of unknown primary site harboring EGFR mutation revealed in frozen bone specimens. Tumor cells obtained from bone metastasis are associated with a higher rate of molecular testing failure. We submitted the preserved frozen bone specimens and detected EGFR exon 19 deletions. She has achieved long-term disease-free survival from gefitinib. This result shows the importance of gene analysis of frozen bone specimens in CUP with bone metastases.

Keywords: Lung cancer; EGFR mutation; Bone metastasis; Gefitinib

Case Report

A 75 year-old Japanese women was referred to our hospital complaining of left-sided chest pain. Her performance status (ECOG) was 1. She was a never smoker. On physical examination, there was no palpable mass on her trunk or extremities. Blood examination showed significant elevation of Carcinoembryonic Antigen (CEA) to 209.5 ng/ml. Chest-X rays and Computed Tomography (CT) did not detect the primary lesion in her lung or pleura. Positron Emission Tomography and Computed Tomography (PET-CT) detected abnormal FDG uptake of left 5th and 6th rib and subaortic (Botallo’s) lymph nodes (standardized uptake value-max 5.0, Figure 1A). We performed open biopsy of her left 5th rib in order to ascertain malignancy. We performed decalcification, and some of the samples were H&E (hematoxyline-eosin)-stained. We fixed the rest of the specimens in liquid nitrogen and kept them at -70oC in a deep freezer to be used in any future genetic testing. The HE staining showed the tumor cells to be adenocarcinoma. Immunohistochemical testing showed that the tumor cells to be positive for Thyroid Transcription Factor-1 (TTF-1), Napsin A, and CAM5 2 (Figure 2). Our opinion was that this bony malignancy derived from lung. To examine the gene mutations, we submitted the preserved frozen specimens to the laboratory cooperation (LSI Medience Corporation) and requested processing with protease. EGFR exon 19 deletions were detected by PNA-LNA PCR clamp. We started the patient on gefitinib and bonemodifying agent (zoledolnic acid) in Feb 2013. Skin rash associated with gefitinib was observed on her legs. It was tolerable without dose reduction or discontinuation. Serum levels of CEA normalized four months after she received gefitinib. The PET-CT at the 24th month did not detect the signs of recurrence or progression in terms of either bone metastasis or mediastinal lymph nodes (Figure 1B).