Prognostic significance of adenocarcinoma in situ, minimally invasive adenocarcinoma, and nonmucinous lepidic predominant invasive adenocarcinoma of the lung in patients with stage I disease

Abstract

According to the IASLC/ATS/ERS classification, the lepidic predominant pattern consists of 3 subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and nonmucinous lepidic predominant invasive adenocarcinoma. We reviewed tumor slides from 1038 patients with stage I lung adenocarcinoma, recording the percentage of each histologic pattern and measuring the invasive tumor size. Tumors were classified according to the IASLC/ATS/ERS classification: 2 were AIS, 34 MIA, and 103 lepidic predominant invasive. Cumulative incidence of recurrence (CIR) was used to estimate the probability of recurrence. Patients with AIS and MIA experienced no recurrences. Patients with lepidic predominant invasive tumors had a lower risk for recurrence (5-y CIR, 8%) than nonlepidic predominant tumors (n=899; 19%; P=0.003). Patients with >50% lepidic pattern tumors experienced no recurrences (n=84), those with >10% to 50% lepidic pattern tumors had an intermediate risk for recurrence (n=344; 5-y CIR, 12%), and those with ≤10% lepidic pattern tumors had the highest risk (n=610; 22%; P<0.001). CIR was lower for patients with ≤2 cm tumors than for those with >2 to 3 cm tumors (for both total and invasive tumor size), with the difference more pronounced for invasive tumor size (5-y CIR, 13% vs. 21% [total size; P=0.022] and 12% vs. 27% [invasive size; P<0.001]). Most patients with lepidic predominant adenocarcinoma who experienced a recurrence had potential risk factors, including sublobar resection with close margins (≤0.5 cm; n=2), 20% to 30% micropapillary component (n=2), and lymphatic or vascular invasion (n=2). It therefore may be possible to identify lepidic predominant adenocarcinomas that carry a low or high risk for recurrence.

Figure 1. Adenocarcinoma in situ, nonmucinous type

(A) A small tumor shows a pure lepidic pattern. (B) Nonmucinous tumor cells spread along alveolar walls (lepidic pattern) without invasion.

Figure 2. Minimally invasive adenocarcinoma, nonmucinous type

(A) A small tumor shows a predominant (>90%) lepidic pattern with <5 mm stromal invasion. (B) Nonmucinous tumor cells spread along alveolar walls (lepidic pattern) without invasion. (C) Small glandular tumor cells (acinar pattern) show stromal invasion with active myofibroblastic proliferation.

Figure 3. Minimally invasive adenocarcinoma, mucinous type

(A) A small tumor shows a predominant (>90%) lepidic pattern with <5 mm stromal invasion. (B) Mucinous tumor cells spread along alveolar walls (lepidic pattern) without invasion. (C) Fused glandular tumor cells (acinar pattern) show stromal invasion with active myofibroblastic proliferation.

Figure 4. Nonmucinous lepidic predominant invasive adenocarcinoma

(A) A tumor shows a predominant (about 70%) lepidic pattern with >5 mm stromal invasion. (B) Nonmucinous tumor cells spread along alveolar walls (lepidic pattern) without invasion. (C) Tumor cells show small glandular morphology (acinar pattern).

Figure 5. Cumulative incidence of recurrence (CIR) by lepidic predominant subtypes

Patients with AIS and MIA (n=36) experienced no recurrences (5-year CIR, 0%). Patients with lepidic predominant invasive adenocarcinoma had a lower risk of recurrence (n=103, 5-year CIR, 8%) than patients with non-lepidic predominant adenocarcinoma (n=899; 5-year CIR, 19%).

Figure 6. Nonmucinous lepidic predominant invasive adenocarcinoma with micropapillary pattern and lymphatic invasion

(A) A tumor shows a predominant (about 70%) lepidic pattern with >5 mm stromal invasion. (B) Micropapillary component is identified in part of the tumor. (C) Tumor cell shows lymphatic invasion.

Figure 7. Cumulative incidence of recurrence (CIR) by percentage of lepidic pattern

Patients with >50% lepidic pattern tumors (n=84) experienced no recurrences (5-year CIR, 0%). Patients with >10%–50% lepidic pattern tumors (n=344) had a lower risk of recurrence (5-year CIR, 12%) than patients with ≤10% lepidic pattern tumors (n=610; 5-year CIR, 22%).

Figure 8. Cumulative incidence of recurrence (CIR) by total and invasive tumor size

(A) Patients with ≤2 cm total tumor size (n=564) had the lowest risk of recurrence (5-year CIR, 13%), followed by >2–3 cm (n=291; 21%) and >3–5 cm (n=183; 24%). (B) Patients with ≤2 cm invasive tumor size (n=680) had a lower risk of recurrence (5-year CIR, 12%) than those with >2–3 cm (n=220; 5-year CIR, 27%) or >3–5 cm (n=138; 5-year CIR, 26%). There were fewer tumors measuring >2–3 cm according to invasive size than to total size (220 vs 291); the CIR was worse for tumors measured according to invasive size than total size (27% vs 21%).