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

Abstract

Recently, the stromal invasion grading system was proposed for small adenocarcinomas of r2.0 cm. The system is based on the presence or absence of a fibrotic focus, and the extent of invasion into the fibrotic focus. Although stromal invasion grading system closely correlated with the prognosis, stromal invasion grade 3, representing stromal invasion into the center of a fibrotic focus, was the largest group of tumors and showed variable prognosis. In this study, we investigated whether stromal invasion grading system could be applied to and validated in pT1 adenocarcinomas as the TNM classification is the most universally used system. Furthermore, we investigated whether stromal invasion grade 3 cases could be subclassified according to the presence and absence of micropapillary pattern. The study included 120 cases of pT1 lung adenocarcinomas, of which 81 (68%) cases were stromal invasion grade 3. Micropapillary pattern was positive in 80% of grade 3 cases. For stromal invasion grade 3 cases, the 5-year survival rate of patients with micropapillary patternpositive carcinomas was 63%, which was significantly worse than 94% of those with micropapillary patternnegative carcinomas (P ¼ 0.0196). The latter was very close to that for patients with stromal invasion grade 0-2 (95%). Moreover, small cluster invasion was observed at sites of stromal invasion significantly more often in micropapillary pattern-positive cases than negative cases. Thus, the stromal invasion grading system is reproducible and correlates with prognosis even in pT1 lung adenocarcinomas. Moreover, among patients with stromal invasion grade 3 carcinomas, favorable prognosis is noted in micropapillary pattern-negative cases. The micropapillary pattern subclassification provides an advantage to the stromal invasion grading system and reconfirms the importance of micropapillary pattern as a prognostic marker. Our study is the first to point to the possible association of micropapillary pattern-positive carcinomas and small cluster invasion.

Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases

“…28,29 The adverse prognosis associated with the micropapillary pattern, confirms observations in multiple previous studies and supports the addition of this new subtype to the classification. 10,11,[30][31][32][33] However, varied criteria for the diagnosis have been used with percentage of the micropapillary component including as little as 6% of the total tumor and none of these studies have utilized comprehensive histological subtyping to define this subgroup according to the predominant subtype showing comparison with survival of the other histological subtypes as we have done. 10,11,[30][31][32][33] Our finding that colloid adenocarcinomas also fit into this poor prognostic group was somewhat surprising as these tumors are often regarded as well-differentiated tumors, but this is the largest series of these tumors reported where survival analysis compared outcome with other adenocarcinoma histological types.…”

Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma

“…The significance of these other patterns includes poorer prognosis in micropapillary [22][23][24][25][26][27] cancer with a higher rate of node metastasis, and emerging observations of poorer prognosis in solid type adenocarcinoma. 17,28 In addition, certain histological subtypes have been associated with specific molecular alterations, such as KRAS mutation in mucinous adenocarcinoma, 29 EML4-ALK translocation in cribriform mucinous and signet ring type adenocarcinoma, 30,31 and b-catenin mutations in fetal type adenocarcinoma.…”

Invasive micropapillary variant of the gallbladder adenocarcinoma and its aggressive potential for lymph node metastasis

“…Patient prognosis for IMPV has not been clarified extensively. However, it is well known that lymph node metastasis is one of the most important prognostic factors in gallbladder cancer (5,23,30), and several prior studies of the other organs have shown a strong association between IMPV histology and shortened patient survival (11,20,21). We speculate that the patient prognosis of carcinomas with IMPV is poorer than a conventional carcinoma of the gallbladder.…”