Distinctive clinicopathological features of adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung: A retrospective study

Abstract

The aim of this study was to investigate distinguishing clinicopathological features, in addition to histological invasiveness, in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) of the lung. Materials and methods: Patients with lung adenocarcinoma who underwent surgery at our hospital between 2007 and 2014 were reviewed, focusing on computed tomography (CT) images, operative procedures and clinical outcomes, histopathology, Ki-67 immunostaining, and EGFR-mutation status. EGFR mutations were examined using a peptide nucleic acid-locked nucleic acid PCR clamp method. Group comparisons were investigated by Mann-Whitney U or Fisher's exact tests. Results: Of 629 patients with lung adenocarcinoma who underwent surgery, 91 (14%) of 103 AIS (n = 34) or MIA (n = 69) tumors were reviewed. The ratio of male to female patients with MIA compared to AIS was significantly higher (p < 0.02). Of 103 tumors, 99 (96%) were non-mucinous. By CT, 74% of AIS appeared as pure ground-glass nodules and 75% of MIAs as part-solid ground-glass nodules. Pathological tumor diameters and Ki-67 labeling index (LI) values were significantly greater for MIAs compared to AIS (p < 0.001 for both). A Ki-67 LI of ≥2.8% indicated the presence of an MIA rather than an AIS. EGFR mutations were more frequently detected in MIAs (33/69, 48%) than AIS (9/34, 26%; p = 0.055). The ratio of exon 19 deletions to exon 21 missense mutations in MIAs tended to be higher than those in AIS (p = 0.06). Patients did not experience a local recurrence or metastasis after AIS and MIAs were removed by wedge resection, segmentectomy or lobectomy. Five-year recurrence-free survival rates were 100%. Conclusion: Despite similar surgical outcomes for AIS and MIAs, we found differences in terms of gender, tumor diameters, CT findings, Ki-67 LI and a subset of EGFR mutations, highlighting the validity of classifying the two subtypes.small (≤3 cm), localized adenocarcinoma with a pure lepidic growth that lacks stromal, vascular, alveolar space, or pleural invasion. MIA is a small (≤3 cm), solitary adenocarcinoma with a predominantly lepidic growth, showing ≤5 mm invasion along its greatest dimension, and lacking lymphatic, vascular, alveolar space, or pleural invasion. Both are usually subdivided into non-mucinous and, more rarely, mucinous variants. AIS and MIA are categorized as Tis and T1mi, respectively, in the eighth TNM classification of lung cancer [2,3].

Oncologic outcomes of segmentectomy vs lobectomy in pathologic stage IA (≤2 cm) invasive lung adenocarcinoma: A population‐based study

“…Even though many studies have demonstrated that segmentectomy can be a reasonable alternative for stage I lung adenocarcinoma, especially for those ≤2 cm, most of these studies did not investigate the impact of pathological subtypes, 6‐8 which is a significant limitation because according to the IASLC/ATS/ERS classification, lung adenocarcinoma consists of heterogeneous subtypes (AAH, AIS, MIA, and IAC) with varying biological behaviors and prognoses 13,14 . The equivalent outcomes between segmentectomy and lobectomy in prior studies may be driven by the good prognosis of AAH/AIS/MIA, for which, segmentectomy is adequate 14‐16,18,28 . However, for IACs, which are more aggressive with poorer outcomes, it is still unclear whether segmentectomy is equivalent to lobectomy in terms of oncologic outcomes.…”

“…For patients with AAH/AIS/MIA, the 5‐year postsurgical survival is nearly 100% regardless of the extent of surgical resection and thus segmentectomy is a reasonable treatment 2,15‐18 . However, for early‐stage IAC, whether segmentectomy can achieve outcomes equivalent to those of lobectomy is still unknown.…”

Predicting benign, preinvasive, and invasive lung nodules on computed tomography scans using machine learning

“…When surgically resected, they have been shown to have close to a 100% 5-year survival. 15,16 However, these preinvasive lesions can only be differentiated from benign processes once surgically resected and not from needle biopsy. 14 This limitation can result in diagnostic operations for benign lesions or no treatment for possibly precancerous lesions.…”

Evaluation of dynamic image progression of minimally invasive and preinvasive lung adenocarcinomas

“…The AIS type was defined as a small (≤3 cm), localized adenocarcinoma consisting of a pure lepidic component without an invasive component. The MIA type was defined as a small (≤3 cm), solitary adenocarcinoma with a predominantly lepidic growth, and an invasive component of ≤5 mm that lacked vascular, lymph gland, alveolar, or pleural invasion (6)(7)(8)(9)(10). It has been hypothesized that morphologically, these two subtypes show a gradual malignant progression from AIS to MIA (11,12).…”