Primary lung adenocarcinomas in children and adolescents treated for pediatric malignancies.
BACKGROUND
Primary lung adenocarcinoma is extremely rare in the pediatric age group. There have been anecdotal reports of lesions that are histologically indistinguishable from adult-type pulmonary adenocarcinoma in young patients after treatment for nonpulmonary cancers. Herein, we present clinical, histopathologic, and molecular data on eight such cases.


METHODS
Histopathologic evaluation of the tumors was performed according to the World Health Organization classification. Molecular studies for EGFR and KRAS mutations were performed on six patients with sufficient material.


RESULTS
All eight patients were never smokers, four males and four females. Median age at nonpulmonary cancer diagnosis was 14 years (range, 3-23 years). Pulmonary adenocarcinomas were diagnosed at a median age of 15 years (range, 10-24 years); tumors were 0.1 to 2.0 cm in size and in some cases coexisted with metastases from the original cancer. Retrospective review showed that in at least three patients, the nodules were radiographically present before chemotherapy. Of six patients whose tumors were tested for common EGFR and KRAS mutations, two were positive for the former and one for the latter. At a median follow-up of 11 months (range, 2-29 months), six patients remained well without lung nodules and two had additional small, peripheral lung nodules that have not been biopsied.


CONCLUSIONS
Pulmonary lesions found in young patients with pediatric cancers can be histologically indistinguishable from lung adenocarcinoma seen in adults, may display typical adenocarcinoma-associated mutations of EGFR and KRAS, and may precede the administration of cytotoxic chemotherapy.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Mark L
ML
Kayton
Mai
M
He
Maureen F
MF
Zakowski
Andre L
AL
Moreira
Christopher
C
Lau
Alexander J
AJ
Chou
Melinda
M
Merchant
Pamela R
PR
Merola
Leonard H
LH
Wexler
Michael P
MP
La Quaglia
William D
WD
Travis
Marc
M
Ladanyi
D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D001859:Bone Neoplasms / Q000150:complications / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics / Q000469:parasitology; D009447:Neuroblastoma / Q000150:complications / Q000628:therapy*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012509:Sarcoma / Q000150:complications / Q000628:therapy*; D015996:Survival Rate; D009396:Wilms Tumor / Q000150:complications / Q000628:therapy*; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins