Histologic and Cytomorphologic Features of ALK-Rearranged Lung Adenocarcinomas.
Michiya Nishino, Veronica E Klepeis, Kristin Bergethon, Eugene J Mark, A John Iafrate, Mari Mino-Kenudson. Massachusetts General Hospital, Boston
Background: Chromosomal rearrangements leading to constitutive activation of anaplastic large cell lymphoma kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy. Our previous study with a limited number of ALK-rearranged (ALK+) tumors has shown their association with a solid histology with numerous signet ring cells; however, experience of others appears to be different. Thus, we evaluated the histologic and cytomorphologic characteristics of ALK+ lung adenocarcinomas from a large cohort of patients.
Design: We examined biopsy, resection, and cytology specimens from 119 patients with lung adenocarcinomas that were positive for an ALK rearrangement by fluorescence in situ hybridization. Histologic subtypes and distinctive cytomorphologic features were assessed in each case and were compared with 117 ALK rearrangement-negative (ALK-) lung adenocarcinomas. In mixed-subtype tumors, the predominant histologic subtype was used in the analysis.
Results: The 119 ALK+ lung adenocarcinoma specimens consisted of 60 resections or excisional biopsies of primary or metastatic tumor, 49 core or transbronchial biopsies, and 10 cell blocks. The most common predominant histologic subtype was solid pattern (58%), followed by micropapillary (17%), acinar (14%), papillary (7%), and bronchioloalveolar (3%). In one specimen, the tumor was predominantly infiltrative with single cells and cords. Tumors with a predominantly solid subtype were more frequent in ALK+ cases compared to ALK- cases (58% vs. 31%, P < 0.0001). In 35% of the ALK+ tumors, signet ring cells comprised 10% or more of the tumor cells, and a solid histology with numerous signet ring cells was seen in 24% (vs. 3% of ALK- tumors, P < 0.0001). Large hepatoid cells with abundant eosinophilic cytoplasm and prominent nucleoli were observed in 26% of the ALK+ cases but were rarely seen in the ALK- tumors.
Conclusions: The evaluation of a large cohort of ALK+ lung adenocarcinomas confirmed a solid subtype with numerous signet ring cells as their characteristic histology and cytomorphology. Identification of this particular pattern as well as cells with hepatoid features may be useful in predicting the subset of lung adenocarcinomas harboring ALK rearrangements.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 262, Tuesday Afternoon