Large nest micropapillary pattern of lung adenocarcinoma has poorer prognosis than typical floret pattern: analysis of 1,062 resected tumors

BACKGROUND: A micropapillary pattern (MP-p) is related to poor prognosis in patients with lung adenocarcinoma (L-ADC). In 2015, the WHO defined the MP-p as “papillary tufts forming florets that lack fibrovascular cores and may appear detached from alveolar walls”; however, the sizes of tumor clusters in air space were not mentioned in this classification. METHODS: We evaluated the MP-p dividing the cluster sizes in the air space by reviewing 1,062 cases of resected L-ADCs. We classified MP-p into two types according to cluster size as follows: typical floret MP-p, tumors with small-to-medium-sized clusters (1–20 tumor cells); and large nest MP-p, tumors with large-sized clusters (>20 tumor cells, large nest). We then recorded the frequency of each type and investigated the association between the MP-p type and clinicopathological factors. RESULTS: Twenty-nine percent of L-ADCs (n=308) were MP-p-positive. Typical floret MP-p and large nest MP-p were observed in 244 tumors (22.9%) and 64 tumors (6.0%), respectively. Only 7 additional micropapillary ADCs were detected when we reclassified ADCs in addition to large nest MP-p. Tumors with large nest MP-p showed the highest frequency of node metastasis and worse prognosis compared to those with typical floret MP-p and absent (P<0.001). In multivariate analysis, patients with L-ADC with typical floret MP-p and large nest MP-p showed a higher recurrence rate [hazard ratio (HR): 1.762 (type 1 vs. absent), HR: 2.450 (type 2 vs. absent)]. CONCLUSIONS: Large nest MP-p should be included in the original MP-p and recorded separately.