Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (≤20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours)

Aims:  A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (≤20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)-type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation. However, BAC-type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma. Methods and results:  One hundred and twenty-two cases of small lung adenocarcinomas (≤20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP. Of the 122 cases, 67 (55%) were MPP-positive and 55 (45%) were MPP-negative. Lymph node metastasis and pleural invasion were significantly more frequent in the MPP-positive group: 74% and 66% in the positive group versus 26% and 34% in the negative group, respectively. The 5-year survival of the MPP-positive group was 54%, whereas that of the MPP-negative group was 81% (P = 0.024). The 5-year survival rates of BAC (Noguchi's type A and B) (n =14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n = 85) and invasive adenocarcinoma (Noguchi's type D and F) (n = 23) were 100%, 68% and 36%, respectively. In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5-year survival of the MPP-positive group (n = 51) was 54%, significantly lower than that of the MPP-negative group (n = 23) of 100% (P = 0.02). Conclusions:  MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (≤20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).