Primary lung adenocarcinoma with morule-like components: a unique histologic hallmark of aggressive behavior and EGFR mutation.

Background: Lung adenocarcinoma with morule-like components is an unusual variant of lung adenocarcinoma, comprising uniform, tightly packed spindle-shaped cells, which fill the lumen of the glandular structures of the carcinoma. The aim of the study was to outline the clinicopathologic features of this variant.

Patients And Methods: We examined a series of 904 surgically resected adenocarcinomas. We defined morule-like components as small buds of spindle-cell proliferation in the tumor lumen of the glandular structures of the carcinoma and calculated their proportion of total tumor mass. Targeted genotyping was performed for KRAS, EGFR, HER2, and BRAF. ALK rearrangements were analyzed immunohistochemically. Immunopositive cases were confirmed using RT-PCR and/or FISH.

Results: We detected 17 cases of adenocarcinoma with morule-like components. This variant, representing only 1.9% was associated with unfavorable outcomes and a mutation in the EGFR. Histologic examination revealed adenocarcinoma with morule-like components accounting for 5-50% of tumors. Among the morule-like components, 10 (58.8%) of the 17 samples showed intracytoplasmic lumina formation containing eosinophilic mucinous material. The presence of micropapillary components in adenocarcinoma with morule-like components suggests that morule-like components could be merely excessive growth of the micropapillary pattern. However, our results indicated no statistical differences in the MIB-1 indices of the morule-like components and the adjacent tumor components or the micropapillary components. The univariate and multivariate analyses revealed a correlation between the presence of a morule-like components and an unfavorable outcome.

Conclusions: Our study clearly indicated that adenocarcinoma with morule-like components is distinct unfavorable prognostic and predictor for EGFR mutation.