Incidental Primary Bronchioloalveolar Carcinoma-Like Lesions in Young Patients with Pediatric Malignancies: Histopathologic and Molecular Features
M He, MF Zakowski, A Moreira, C Lau, AJ Chou, M Merchant, PR Melora, LH Wexler, MP La Quaglia, WD Travis, ML Kayton, M Ladanyi. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Primary lung adenocarcinoma is extremely rare in the pediatric age group. There have been anecdotal reports of lesions that histologically resemble usual bronchioloalveolar carcinoma (BAC) in young patients after treatment for non-pulmonary cancers. Here, we present clinical, histopathologic, and molecular data on a single-institution series of seven such cases.
Design: All cases were identified in the course of clinical care. Specimens were from open thoracotomies or thorascopic biopsies. Molecular studies for EGFR and KRAS mutations were performed in five patients with sufficient material using DNA extracted from paraffin-embedded tissues.
Results: All seven patients were nonsmokers, three male and four female. Median age at original cancer diagnosis was 14 years (range 3-23). Four had osteosarcoma (OS), one mesenchymal chondrosarcoma (MCS), one Wilms tumor and one neuroblastoma. All had received intensive chemotherapy. Median age at diagnosis of pulmonary BAC-like lesions was 15 years (range 10-24). All lesions were found incidentally either by preoperative CT (n=3) or at time of surgery. Retrospective review showed that in at least three patients the nodules were present prior to chemotherapy. Their sizes ranged from 0.1 to 0.6 cm. The histopathology ranged from AAH, to BAC, to mixed subtype with acinar or papillary features. In three patients, the BAC-like nodules were multiple and co-existed with lung metastases of the original cancer. Of five tumors tested, one was positive for the EGFR L858R mutation (patient with prior OS) and another was positive for KRAS G12V (patient with prior MCS); the remaining three were negative for common EGFR and KRAS mutations. Six patients have remained well with a median follow-up of 8 months (1-29 months).
Conclusions: Incidental BAC-like lesions in patients with pediatric cancers can show typical lung adenocarcinoma-type mutations and may not always be chemotherapy-related. Other possibilities include a selection bias effect due to enhanced radiographic scrutiny, a common predisposing germline alteration, or a common prior mutagenic exposure. The natural history and management of this entity remain to be better defined.
Monday, March 9, 2009 1:00 PM
Poster Session II # 213, Monday Afternoon