Grade of Stromal Invasion in Small Adenocarcinoma of the Lung

Abstract

The pathologic features of invasion such as stromal disruption and pleural/vascular involvement have been shown to be of prognostic value in adenocarcinoma. However, the relationship between the degree of invasion, histologic subtype of adenocarcinoma, and prognosis remains unclear. We retrospectively studied 380 peripheral adenocarcinomas of < or = 2.0 cm in diameter with regard to histology and clinical profiles. Their degree of invasive growth was classified into four grades as follows according to the structural deformity and its location in the adenocarcinoma lesion: Grade 0 had a pure bronchioloalveolar growth pattern and no evidence of stromal invasion. Grade 1 had stromal invasion in the area of bronchioloalveolar growth. Grade 2 had stromal invasion localized on the periphery of a fibrotic focus. Grade 3 had stromal invasion into the center of a fibrotic focus. The clinicopathological data were obtained from medical records. The distribution of the histologic grade of invasion was as follows: grade 0 in 85 tumors (22%), grade 1 in 37 (10%), grade 2 in 46 (12%), and grade 3 in 212 (56%). This histologic grade of invasion was closely related to other indicators of tumor spread. Vascular/lymphatic permeation was seen in none of grade 0, in 1 lesion each of grade 1 and grade 2, and 144 (68%) of grade 3. Lymph node metastasis was seen in 57 (27%) lesions of grade 3 but not in grades 0, 1, or 2. The 5-year disease-free survival rates were 100%, 100%, 100%, and 59.6% for tumors with grade 0, grade 1, grade 2, and grade 3 invasion, respectively. Tumors with grade 1 and grade 2 invasion, like tumors with grade 0 invasion (bronchioloalveolar carcinoma), showed an excellent prognosis. Therefore, tumors with grade 1 and grade 2 invasion could be considered "minimally invasive" or "early" adenocarcinomas.

Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors

“…These results were similar to those reported for tumors measuring r2.0 cm by Sakurai et al 11 Thus, stromal invasion grade 3 is also the important poor prognostic factor in lung pT1 adenocarcinomas. However, stromal invasion grade 3 comprised the majority of the pT1 adenocarcinoma cases (81/120 cases, 68%).…”

“…The prognostic significance of central fibrosis or scar of adenocarcinoma of the lung has been reported by several investigators. 7,11,17,[19][20][21][22] Shimosato et al 19 proposed that the central scar in carcinomas was a secondary phenomenon rather than a precursor of carcinoma, and demonstrated that the degree of collagenization in the fibrotic focus closely correlated with tumor progression and prognosis. Others indicated that the size 21 and characteristics of the central fibrosis, such as the interface pattern, 20 the presence of active fibroblast proliferation, 7 the pattern of stromal elastic frameworks, 17 and the extent of desmoplasia 22 are significant prognostic factors.…”

“…11 Briefly, stromal invasion grade 0 was defined as pure bronchioloalveolar carcinoma, which shows no evidence of stromal invasion ( Figure 1a); stromal invasion grade 1 as stromal invasion in the area of bronchioloalveolar carcinoma growth ( Figure 1b); stromal invasion grade 2 as stromal invasion localized on the periphery of a fibrotic focus ( Figure 1c); and stromal invasion grade 3 as stromal invasion into the center of a fibrotic focus (Figure 1d). Stromal invasion was confirmed by EvG staining, which demonstrated structural deformity of the stromal elastic fiber framework at the sites of invasion.…”

“…Stromal invasion was confirmed by EvG staining, which demonstrated structural deformity of the stromal elastic fiber framework at the sites of invasion. 11,17 Lung adenocarcinomas show two types of papillary structures: papillary structure and micropapillary pattern. The papillary structure is characterized by a complex papillary glandular proliferation along fibrovascular cores, 16 whereas micropapillary pattern is defined as papillary structures with tufts lacking a central fibrovascular core (Figure 2a).…”

“…Recently, Sakurai et al 11 have histopathologically graded the degree of invasion in small adenocarcinomas of r2.0 cm and explored the relationship between invasion and prognosis of patients with adenocarcinomas. Although their stromal invasion grading system closely correlated with the prognosis, their stromal invasion grade 3, representing stromal invasion into the center of a fibrotic focus, was the largest group of tumors (212/380 cases, 56%) and showed variable prognosis.…”