Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Abstract

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1,057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC.Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as diseasefree survival (DFS) and overall survival (OS).Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4-113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death.Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs.

Clinicopathological features of cytokeratin 5‐positive pulmonary adenocarcinoma

“…If cribriform, signet‐ring solid and discohesive patterns were observed they were recorded separately from acinar or solid patterns. The cribriform was defined according to a previous report 15 . A signet‐ring solid pattern was defined as a type of solid pattern with abundant cytoplasmic mucin and eccentric nuclei in individual cells.…”

“…In the TMA cohort, the relationship between CK5 expression and gene alterations was investigated; 231, 230, 233, 149, 336 and 336 patients were analysed for EGFR , KRAS , BRAF and HER2 mutations and ALK and ROS1 rearrangements, respectively. The data of gene alterations were used from our previous studies 12,14,15,19–21 …”

“…The cribriform was defined according to a previous report. 15 A signetring solid pattern was defined as a type of solid pattern with abundant cytoplasmic mucin and eccentric nuclei in individual cells. A discohesive pattern was defined as an invasive growth pattern comprising single trabeculae or small nests of tumour cells together with a desmoplastic reaction, 16 which was presented as a complex glandular pattern in the 2021 WHO criteria.…”

To explore the prognostic value of spread through air spaces and develop a nomogram combined with spread through air spaces in lung squamous cell carcinoma

“…For preoperative prediction, ground glass opacity (37), solid component (38,39) predominant pattern (38,(47)(48)(49) and solid-predominant pattern (47,48) are common in STAS. Nakajima et al (50) found that cribriform pattern was also related to STAS. At the genetic level (47), epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), Kirsten rat sarcoma viral oncogene (KRAS), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are the 5 most common changes in STAS-positive lung adenocarcinoma.…”

Deep learning for histopathological subtyping and grading of lung adenocarcinoma

“…For instance, the poor prognosis when micropapillary and solid subtypes are present in a tumour is welldocumented, even as non-predominant subtypes [21][22][23][24][25][26]. It has been demonstrated that cribriform arrangements of tumour glands or complex glandular patterns, described within the acinar subtype of LADC, exhibit aggressive behaviour with poor prognosis [27,28]. Semiquantitative reporting of these subtypes is recommended in 5% increments to include even a small amount of prognostically significant subtypes [29].…”