Lung Carcinomas in Young Patients: A Clinicopathologic and Immunohistochemical Assessment of 140 Cases.
Randall L Woodford, Alykhan S Nagji, David R Jones, Edward B Stelow. University of Virginia, Charlottesville
Background: Although lung carcinomas demonstrate significant genetic diversity, underlying molecular abnormalities such as activating mutations of EGFR and the EML4-ALK fusion gene have been identified in some tumors. Recent studies have suggested that carcinomas harboring these abnormalities demonstrate distinct clinicopathologic features. Additionally, immunohistochemistry (IHC) with EGFR mutation-specific antibodies and ALK can accurately identify the abnormalities in lieu of molecular analysis. Given the increased incidence of lung cancer with age, these studies have predominantly evaluated tumors from older individuals. This study used histologic examination and IHC to evaluate the clinicopathologic features of lung carcinomas in patients 50 and younger.
Design: 140 lung carcinomas in patients 50 and younger were identified. Patient age, sex, and tobacco history were recorded. Each tumor was classified according to WHO guidelines. Tumor grade, size, stage, and large vessel invasion were evaluated in addition to lymph node status and other lung pathology. IHC for TTF1, p63, ALK, the E746-A750 EGFR deletion, and the L858R EGFR point mutation was performed.
Results: The 140 cases exhibited the following characteristics: age (range 31-50; mean 46; median 47), sex (75 female, 65 male), and tobacco history (111 smokers, 7 nonsmokers, 22 unknown). Histologic types were 90 adenocarcinomas (58 mixed, 16 acinar, 12 solid, 3 non-mucinous BAC, 1 mucinous BAC), 27 squamous, 17 large cell undifferentiated, 4 large cell neuroendocrine, 1 adenosquamous, and 1 sarcomatoid. Immunoreactivity with EGFR mutation-specific antibodies was seen in 10 adenocarcinomas, all of which demonstrated acinar and/or non-mucinous BAC morphology; focal solid growth was seen in only 1 case. The EGFR positive cases had an average smoking history of 29 pack years, while the negative cases had an average smoking history of 36 pack years. Immunoreactivity for ALK was identified in 1 tumor, which was from a non-smoker and demonstrated predominantly acinar histology with a minor solid component.
Conclusions: Lung carcinomas in young patients are typically adenocarcinomas. Within this group, the rate of EGFR mutations and the EML4-ALK fusion gene appears similar to that seen in studies consisting predominantly of older patients. This somewhat surprising finding is likely related to the high rate of tobacco use within our study. Similar to other studies, EGFR and ALK positive cases did not overlap, only rarely had a solid component, and were associated with a less extensive smoking history.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 268, Tuesday Afternoon