Home >> ALL ISSUES >> 2017 Issues >> AMP case report: Primary pulmonary adenocarcinoma with an unusual molecular profile of the EGFR gene at initial presentation, October 2017

AMP case report: Primary pulmonary adenocarcinoma with an unusual molecular profile of the EGFR gene at initial presentation, October 2017

image_pdfCreate PDF

Hasan Khatib, MD; Cheryl Bissaillon; Kim Lebel; Giovanna Crisi, MD, PhD; Franklin Moore, MD, PhD

AMP-CT-Logo_2014October 2017—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from the University of Massachusetts Medical School-Baystate, Springfield. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung carcinoma, consisting of adenocarcinoma and squamous cell carcinoma, makes up about 80 percent of lung cancers and occurs most commonly in smokers. In the past decade, much progress has been made in the molecular profiling of lung cancer. This research has led to the development of several effective targeted therapies, especially against certain EGFR mutations and rearrangements of the ALK and ROS genes in adenocarcinomas. Among adenocarcinomas arising in smokers, KRAS mutations are most commonly detected, occurring in up to 45 percent of cases. Unfortunately, the development of targeted therapies against KRAS mutations has thus far been hampered by toxicity, though additional clinical trials are ongoing. In adenocarcinomas, mutations affecting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) gene are detected in 10 to 60 percent of patients, depending on gender, ethnicity, and smoking status. Mutations in the EGFR gene are generally mutually exclusive with KRAS mutations. Deletions in exon 19 and the L858R point mutation in exon 21 are the most common EGFR mutations, accounting for up to 90 percent overall.

Fig. 1. Moderately differentiated adenocarcinoma, acinar predominant with peripheral lepidic growth.

Fig. 1. Moderately differentiated adenocarcinoma, acinar predominant with peripheral lepidic growth.

Currently, there are several FDA-approved first-generation tyrosine kinase inhibitors (TKI, e.g. gefitinib and erlotinib) that target these two sensitizing mutations when present. Other EGFR mutations such as G719X, S768I, L861Q, and exon 20 insertions are less commonly detected, accounting for most of the remaining 10 percent of EGFR mutations. Some, but not all, of these less common mutations confer variable sensitivity to first-generation TKIs. An additional mutation of EGFR, T790M, is detected primarily in tumors with a previous sensitizing mutation after treatment with TKIs. The T790M mutation is detected in more than half of all cases in which acquired resistance to TKIs develops post-treatment but in only a few percent of untreated tumors. A third-generation TKI, osimertinib, is FDA approved as targeted therapy against the T790M mutation in the EGFR gene.

Here, we present a case of a newly diagnosed pulmonary adenocarcinoma with an unusual molecular profile.

Case. A 69-year-old Caucasian man presented to the emergency department at our institution with worsening shortness of breath. His past medical history is significant for severe chronic obstructive pulmonary disease with a remote 50-pack-per-year smoking history and a past myocardial infarction. Notably, his father and brother died of lung cancer. His laboratory results were non-contributory. A CT scan of the chest showed multiple bilateral pulmonary spiculated nodules ranging in size from a few millimeters to more than 3 cm. A PET scan demonstrated increased metabolic activity of several of the nodules worrisome for neoplasia. Tissue sampling was recommended. The patient then underwent a right upper lobectomy and mediastinal lymphadenectomy.

CAP TODAY
X