Signet Ring Cell Features (SRCF) in Lung Adenocarcinoma: A Cytologic Feature or a Histologic Subtype?
PR Cohen, A Yoshizawa, N Motoi, GJ Riely, MG Kris, BJ Park, VW Rusch, WD Travis. Memorial Sloan Kettering Cancer Center, New York, NY; Kyoto University Hospital, Kyoto, Japan; The Cancer Institute Hospital, JFCR, Tokyo, Japan
Background: The 2004 WHO Classification recognizes SRC adenocarcinoma as an uncommon histologic variant of lung adenocarcinoma. The possibility of a molecular association was recently suggested between SRCF and EML4-ALK mutations. However, few studies have explored the pathologic spectrum and clinical significance SRCF in various adenocarcinoma subtypes.
Design: We reviewed 569 lung adenocarcinomas for the presence of signet ring cell features (SRCF) and recorded their presence in various histologic adenocarcinoma subtypes. The relationship of SRCF to clinical and pathologic features was analyzed using SPSS version 17 including crosstables with Chi-square statistics as well as survival using Kaplan Meier and Cox regression analysis.
Results: SRCF of at least 5% were found in 47 (8.3%) cases with 25F and 22M & mean age: 66 yrs (32-83). There was no significant difference in age or sex compared to non-signet ring cell cases (NSRC) cases. SRCF were found in 14/246 (5.7%) of acinar, 7/155 (4.5%) of papillary, 3/14 (21.4%) of micropapillary, 21/89 (23.6%) of solid and 2/10 (20%) of colloid predominant histologic subtypes. Only the association with SRCF and the solid subtype was significant (p<0.001). SRCF were not seen in tumors with predominant mucinous or non-mucinous BAC. SRCF was associated with a worse, 58% 5-yr disease free survival compared to 83% for NSRC cases (p<0.001). However, in multivariate analysis stratified for stage, including major histologic types and sex, only solid versus other histology and not SRCF was an independent prognostic predictor for poor survival. TTF1 was positive in 6/13 (46%).
Conclusions: In summary SRCF in lung adenocarcinoma occurs most often in association with the solid subtype but it can also be seen less often in the acinar, papillary and micropapillary patterns. The association of SRCF with poor prognosis appears to be due to its strong association with the solid subtype and it is not an independent prognostic factor. Consideration should be given to recognizing SRCF as a cytologic change that can occur in multiple histologic types, rather than a distinct adenocarcinoma subtype.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 253, Wednesday Morning