Table 1.
Clinicopathological characteristics of surgically resected lung adenocarcinomas.
Table 2.
Clinical characteristics of inoperable lung adenocarcinomas.
Fig 1.
The flowchart used to assign the tumors to the four groups.
n, number of tumors; EGFR, EGFR mutation; LN, lymph node metastasis; +, positive; -, negative.
Fig 2.
Representative appearances of the major histological subtypes of lung adenocarcinoma (hematoxylin and eosin stain, ×200).
A, The lepidic subtype is characterized by the extension of neoplastic cells along the surface of the alveolar walls; B, The acinar subtype is characterized by tubular or glandular structures invading a fibrous stroma; C, The papillary subtype is characterized by the extension of neoplastic cells on the surfaces of fibrovascular cores; D, The micropapillary subtype is characterized by the formation of tufted papillary structures that lack a central fibrovascular core and float in the alveolar space; E, The solid subtype is characterized by the formation of solid nests consisting of neoplastic cells.
Table 3.
Differences in the histological elements between the EGFR(+)/LN(+) group and the other groups.
Fig 3.
Proportions of the micropapillary (mPAP) element in different stages of surgically resected lung adenocarcinomas (LADCs).
A, stage I EGFR-mutated LADCs (n = 103) versus (vs) stage II-IV EGFR-mutated LADCs (n = 39); B, stage I EGFR wild-type LADCs (n = 106) vs stage II-IV EGFR wild-type LADCs (n = 88); n, number of tumors examined mPAP element proportions are displayed as a box-and-whiskers plot with median (thick line), 25th to 75th percentile (box) and 10th to 90th percentile (whiskers) and outliers (circles). P-values were calculated using the Mann-Whitney test.
Fig 4.
Representative histological appearances of the biopsy specimens (A, EGFR-mutated lung adenocarcinoma (LADC); B, EGFR wild-type LADC).
The micropapillary element, which is composed of papillary structures lacking fibrovascular cores, floats in alveolar spaces (A, hematoxylin and eosin (HE) stain, ×200). The acinar element (and some crush artifacts) grows in collapse fibrosis (B, HE stain, ×200).
Fig 5.
Kaplan-Meier recurrence-free survival curves of the association between the proportion of micropapillary (mPAP) element and disease recurrence in patients with stage I EGFR-mutated lung adenocarcinomas.
A, tumors in which the mPAP element accounted for ≥5% of the tumor versus (vs) those in which the mPAP element accounted for <5% of the tumor (P = 0.028 in the Log-rank test); B, tumors in which the mPAP element accounted for ≥10% of the tumor vs those in which the mPAP element accounted for <10% of the tumor (P = 0.005 in the Log-rank test); C, tumors in which the mPAP element accounted for ≥20% of the tumor vs those in which the mPAP element accounted for <20% of the tumor (P = 0.102 in the Log-rank test); n, number of tumors examined; asterisk(*), statistically significant.
Fig 6.
Kaplan-Meier recurrence-free survival curves of the association between the micropapillary (mPAP) estimated volume (EV) and disease recurrence in patients with stage I EGFR-mutated lung adenocarcinomas.
A, tumors with mPAP EV of ≥5 versus (vs) those with mPAP EV of <5 (P = 0.014 in the Log-rank test); B, tumors with mPAP EV of ≥15 vs those with mPAP EV of <15 (P<0.0001 in the Log-rank test); C, tumors with mPAP EV of ≥30 vs those with mPAP EV of <30 (P = 0.032 in the Log-rank test); n, number of tumors examined; asterisk(*), statistically significant.
Table 4.
Clinicopathological characteristics and disease recurrence in patients with stage I EGFR-mutated lung adenocarcinomas (univariate analyses).
Table 5.
Multivariate analysis performed using the Cox proportional hazards model.
Table 6.
Difference in types of EGFR mutations between tumors with mPAP and without mPAP element.
Fig 7.
Hypothetical schema for histogenesis of the EGFR-mutated and the EGFR wild-type lung adenocarcinomas (LADCs).
In early stages, EGFR-mutated LADC, which may develop from terminal respiratory units (TRU) [22], exhibits lepidic patterns consisting of neoplastic cells with hobnail or spheroid morphology. In advanced stages, they progress to form papillary and micropapillary patterns (upper panel). EGFR wild-type LADC, which may develop from the central airway compartment (CAC) [22], exhibits a lepidic pattern consisting of neoplastic cells with columnar morphology, and progresses to form acinar and solid patterns (lower panel). Magnification of all photographs is ×200.