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Published in: General Thoracic and Cardiovascular Surgery 5/2017

01-05-2017 | Original Article

Micropapillary histological subtype in lung adenocarcinoma of 2 cm or less: impact on recurrence and clinical predictors

Authors: Yukihiro Yoshida, Jun-ichi Nitadori, Aya Shinozaki-Ushiku, Jiro Sato, Tempei Miyaji, Takuhiro Yamaguchi, Masashi Fukayama, Jun Nakajima

Published in: General Thoracic and Cardiovascular Surgery | Issue 5/2017

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Abstract

Objective

This study examined the clinical and radiological characteristics of adenocarcinoma having the micropapillary histological subtype.

Methods

We included 233 patients who were operated from 2001 to 2012 for lung adenocarcinoma of 2 cm or less. The pathology was reviewed according to the 2015 WHO classification. We defined adenocarcinoma with a micropapillary component as adenocarcinoma in which the area of the micropapillary histological subtype exceeded 5% of the tumor. The difference in cumulative incidence of recurrence (CIR) in the presence of death as a competing risk between two groups was assessed using the methods of Gray.

Results

Twenty-one cases (9.0%) had a micropapillary component. The micropapillary component was associated with a higher frequency of lymphatic invasion (28.6 vs. 7.5% in adenocarcinoma without a micropapillary component; P = 0.008) and vascular invasion (38.1 vs. 15.1%, P = 0.014) and lymph node metastasis (31.3 vs. 5.2%, P = 0.003). The median follow-up period was 6.5 years. CIR at 5 years was 23.8% [95% confidence interval (CI), 8.3–43.7%] for adenocarcinoma with a micropapillary component, and 11.4% (95% CI, 7.4–16.2%) for adenocarcinoma without a micropapillary component (P = 0.033). Adenocarcinoma with a micropapillary component was more frequent in solid nodules (17.8%, 16/90) on high-resolution computed tomography (HRCT) than in either ground-glass nodules (1.5%, 1/67) or part-solid nodules (5.3%, 4/76) (P = 0.001). The HRCT finding was the only preoperative factor that was associated with a micropapillary component in the multivariate analysis.

Conclusions

The micropapillary component in adenocarcinoma should be regarded as indicative of a high-grade malignancy and was associated with the HRCT finding.
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Literature
1.
go back to reference Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, editors. WHO classification of tumours of the lung, pleura, thymus and heart, 4th ed. Lyon: International Agency for Research on Cancer; 2015. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, editors. WHO classification of tumours of the lung, pleura, thymus and heart, 4th ed. Lyon: International Agency for Research on Cancer; 2015.
2.
go back to reference Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244–85.CrossRefPubMedPubMedCentral Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244–85.CrossRefPubMedPubMedCentral
3.
go back to reference Mansuet-Lupo A, Bobbio A, Blons H, Becht E, Ouakrim H, Didelot A, et al. The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort. Chest. 2014;146:633–43.CrossRefPubMed Mansuet-Lupo A, Bobbio A, Blons H, Becht E, Ouakrim H, Didelot A, et al. The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort. Chest. 2014;146:633–43.CrossRefPubMed
4.
go back to reference Hung JJ, Jeng WJ, Chou TY, Hsu WH, Wu KJ, Huang BS, et al. Predictive value of the international association for the study of lung cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in tumor recurrence and patient survival. J Clin Oncol. 2014;32:2357–64.CrossRefPubMed Hung JJ, Jeng WJ, Chou TY, Hsu WH, Wu KJ, Huang BS, et al. Predictive value of the international association for the study of lung cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma in tumor recurrence and patient survival. J Clin Oncol. 2014;32:2357–64.CrossRefPubMed
5.
go back to reference Tsubokawa N, Mimae T, Sasada S, Yoshiya T, Mimura T, Murakami S, et al. Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma. Eur J Cardiothorac Surg. 2016;49:293–9.CrossRefPubMed Tsubokawa N, Mimae T, Sasada S, Yoshiya T, Mimura T, Murakami S, et al. Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma. Eur J Cardiothorac Surg. 2016;49:293–9.CrossRefPubMed
6.
go back to reference Chao L, Yi-Sheng H, Yu C, Li-Xu Y, Xin-Lan L, Dong-Lan L, et al. Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients. Lung Cancer. 2014;86:164–9.CrossRefPubMed Chao L, Yi-Sheng H, Yu C, Li-Xu Y, Xin-Lan L, Dong-Lan L, et al. Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients. Lung Cancer. 2014;86:164–9.CrossRefPubMed
7.
go back to reference Zhang Y, Wang R, Cai D, Li Y, Pan Y, Hu H, et al. A comprehensive investigation of molecular features and prognosis of lung adenocarcinoma with micropapillary component. J Thorac Oncol. 2014;9:1772–8.CrossRefPubMed Zhang Y, Wang R, Cai D, Li Y, Pan Y, Hu H, et al. A comprehensive investigation of molecular features and prognosis of lung adenocarcinoma with micropapillary component. J Thorac Oncol. 2014;9:1772–8.CrossRefPubMed
8.
go back to reference Nitadori J, Bograd AJ, Kadota K, Sima CS, Rizk NP, Morales EA, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2 cm or smaller. J Natl Cancer Inst. 2013;105:1212–20.CrossRefPubMedPubMedCentral Nitadori J, Bograd AJ, Kadota K, Sima CS, Rizk NP, Morales EA, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2 cm or smaller. J Natl Cancer Inst. 2013;105:1212–20.CrossRefPubMedPubMedCentral
9.
go back to reference Sobin LH, Gospodarowicz MK, Wittekind C. International Union Against Cancer (UICC). TNM Classification of Malignant Tumours. 7th ed. Oxford: Wiley; 2009. Sobin LH, Gospodarowicz MK, Wittekind C. International Union Against Cancer (UICC). TNM Classification of Malignant Tumours. 7th ed. Oxford: Wiley; 2009.
10.
go back to reference Abramoff MD, Magelhaes PJ, Ram SJ. Image Processing with Image J. Biophotonics Int. 2004;11:36–42. Abramoff MD, Magelhaes PJ, Ram SJ. Image Processing with Image J. Biophotonics Int. 2004;11:36–42.
11.
go back to reference Suzuki K, Asamura H, Kusumoto M, Kondo H, Tsuchiya R. “Early” peripheral lung cancer: prognostic significance of ground glass opacity on thin-section computed tomographic scan. Ann Thorac Surg. 2002;74:1635–9.CrossRefPubMed Suzuki K, Asamura H, Kusumoto M, Kondo H, Tsuchiya R. “Early” peripheral lung cancer: prognostic significance of ground glass opacity on thin-section computed tomographic scan. Ann Thorac Surg. 2002;74:1635–9.CrossRefPubMed
12.
go back to reference Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004;350:1713–21.CrossRefPubMed Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004;350:1713–21.CrossRefPubMed
13.
go back to reference Pisters KM, Evans WK, Azzoli CG, Kris MG, Smith CA, Desch CE, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non small-cell lung cancer guideline. J Clin Oncol. 2007;25:5506–18.CrossRefPubMed Pisters KM, Evans WK, Azzoli CG, Kris MG, Smith CA, Desch CE, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non small-cell lung cancer guideline. J Clin Oncol. 2007;25:5506–18.CrossRefPubMed
14.
go back to reference Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, et al. Non-small cell lung cancer. J Natl Compr Canc Netw. 2010;8:740–801.PubMed Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, et al. Non-small cell lung cancer. J Natl Compr Canc Netw. 2010;8:740–801.PubMed
15.
go back to reference Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e369S–e399S.CrossRefPubMed Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e369S–e399S.CrossRefPubMed
16.
go back to reference Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.CrossRefPubMed Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.CrossRefPubMed
17.
go back to reference Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16:1141–54.CrossRef Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16:1141–54.CrossRef
18.
go back to reference Scrucca L, Santucci A, Aversa F. Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant. 2007;40:381–7.CrossRefPubMed Scrucca L, Santucci A, Aversa F. Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant. 2007;40:381–7.CrossRefPubMed
19.
go back to reference Lee G, Lee HY, Jeong JY, Han J, Cha MJ, Lee KS, et al. Clinical impact of minimal micropapillary pattern in invasive lung adenocarcinoma: prognostic significance and survival outcomes. Am J Surg Pathol. 2015;39:660–6.CrossRefPubMed Lee G, Lee HY, Jeong JY, Han J, Cha MJ, Lee KS, et al. Clinical impact of minimal micropapillary pattern in invasive lung adenocarcinoma: prognostic significance and survival outcomes. Am J Surg Pathol. 2015;39:660–6.CrossRefPubMed
20.
go back to reference Trejo Bittar HE, Incharoen P, Althouse AD, Dacic S. Accuracy of the IASLC/ATS/ERS histological subtyping of stage I lung adenocarcinoma on intraoperative frozen sections. Mod Pathol. 2015;28:1058–63.CrossRefPubMed Trejo Bittar HE, Incharoen P, Althouse AD, Dacic S. Accuracy of the IASLC/ATS/ERS histological subtyping of stage I lung adenocarcinoma on intraoperative frozen sections. Mod Pathol. 2015;28:1058–63.CrossRefPubMed
21.
go back to reference Yeh YC, Nitadori J, Kadota K, Yoshizawa A, Rekhtman N, Moreira AL, et al. Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ≤3 cm: accuracy and interobserver agreement. Histopathology. 2015;66:922–38.CrossRefPubMedPubMedCentral Yeh YC, Nitadori J, Kadota K, Yoshizawa A, Rekhtman N, Moreira AL, et al. Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ≤3 cm: accuracy and interobserver agreement. Histopathology. 2015;66:922–38.CrossRefPubMedPubMedCentral
22.
go back to reference Cha MJ, Lee HY, Lee KS, Jeong JY, Han J, Shim YM, et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg. 2014;147:921–8.CrossRefPubMed Cha MJ, Lee HY, Lee KS, Jeong JY, Han J, Shim YM, et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg. 2014;147:921–8.CrossRefPubMed
Metadata
Title
Micropapillary histological subtype in lung adenocarcinoma of 2 cm or less: impact on recurrence and clinical predictors
Authors
Yukihiro Yoshida
Jun-ichi Nitadori
Aya Shinozaki-Ushiku
Jiro Sato
Tempei Miyaji
Takuhiro Yamaguchi
Masashi Fukayama
Jun Nakajima
Publication date
01-05-2017
Publisher
Springer Japan
Published in
General Thoracic and Cardiovascular Surgery / Issue 5/2017
Print ISSN: 1863-6705
Electronic ISSN: 1863-6713
DOI
https://doi.org/10.1007/s11748-017-0747-3

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