Elsevier

Human Pathology

Volume 45, Issue 2, February 2014, Pages 213-220
Human Pathology

Original contribution
Cribriform and fused glands are patterns of high-grade pulmonary adenocarcinoma

https://doi.org/10.1016/j.humpath.2013.10.011Get rights and content

Summary

The 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification of pulmonary adenocarcinoma recognizes the prognostic significance of different histologic patterns but does not address the issue of tumor grade. We previously developed an objective and prognostic grading system for pulmonary adenocarcinomas that is based on associating patterns with their metastatic potential. The best prognostic stratification was achieved by summing the grades of the 2 most predominant patterns (histologic score). Here, we extend this work by evaluating the prognostic importance of variant patterns of adenocarcinoma, which are not recognized by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Pathologic specimens from 249 resected stage I adenocarcinomas were reviewed. The proportions of standard and nonstandard patterns (cribriform and fused glands) were recorded for each case. The associations between the presence of standard and nonstandard patterns, tumor histologic score, and disease-free survival were evaluated. Cribriform and fused gland patterns were observed in 15% and 29% of tumors, respectively. These nonstandard patterns each composed 10% to 100% of the entire tumors but were the predominant pattern in only 5% and 7% of tumors, respectively. The presence of complex glandular patterns was associated with solid pattern (P < .001) and high histologic score (P < .0001). Disease-free survival for tumors with predominant complex glandular patterns was similar to that for high-grade tumors (P = .932) and was significantly worse than that for low- and intermediate-grade tumors (P = .0025). Complex glandular patterns have a significant prognostic value and should be considered patterns of high-grade adenocarcinoma.

Introduction

Pulmonary adenocarcinomas are histologically heterogenous because they are typically composed of an intermixture of multiple growth patterns. When the current World Health Organization (WHO) classification of lung cancer [1] is applied, approximately 90% of adenocarcinomas are classified as “mixed subtype” [2]. The new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) classification of lung adenocarcinoma [3] recommends that these tumors be classified by their predominant pattern, which can be associated with prognosis [4], [5], [6], [7].

We previously proposed an objective grading system for pulmonary adenocarcinoma that associates the presence of multiple patterns of growth with prognosis [8]. In this grading system, each pattern of adenocarcinoma is assigned a grade associated with its metastatic or recurrence potential (grade 1, lepidic; grade 2, acinar and papillary; and grade 3, solid and micropapillary), with the grades corresponding to low, intermediate, and high metastatic potential. We found, in a highly homogeneous population of stage I tumors, that the sum of the grades of the 2 most predominant patterns was a better predictor of prognosis than the grade of the predominant pattern alone or any other combination [8]. In this objective grading system, well-differentiated tumors (histologic score 3) are composed of lepidic pattern (as the predominant or secondary pattern) and either acinar or papillary pattern and are associated with low rates of recurrence. By contrast, poorly differentiated tumors (histologic score 5 and 6) are composed of solid or micropapillary pattern in combination with either acinar or papillary pattern and are associated with higher rates of recurrence. Moderately differentiated tumors (histologic score 4) are composed of pure acinar, papillary, or a combination of acinar and papillary as the predominant and second predominant patterns. The moderately differentiated category also includes rare tumors that have a predominant lepidic pattern (grade 1) in association with solid or micropapillary patterns (grade 3; therefore 1 + 3 = histologic score 4). In the original publication, complex glandular patterns (defined as cribriform and fused glands) were not evaluated objectively—rather, only the classical patterns of pulmonary adenocarcinoma, as described by the current WHO classification of lung cancer, were evaluated [1].

In tumors arising from organs other than the lung for which an objective grading system exists, complex glandular patterns (such as cribriform and fused glands) are recognized as patterns of high grade [9], [10], [11]. In this study, we investigated the association between complex glandular patterns, the WHO and IASLC/ATS/ERS types of adenocarcinoma, grade, and prognosis.

Section snippets

Patients

Approval for this study was obtained from the Memorial Sloan-Kettering Cancer Center institutional review board. All clinical information on patients was collected according to Health Insurance Portability and Accountability Act regulations. In total, 249 patients who had undergone surgical resection of stage I pulmonary adenocarcinomas between 1995 and 2010 were retrospectively identified from a database prospectively maintained by the Thoracic Service of the Department of Surgery of Memorial

Patient and tumor characteristics

The patient population consisted of 91 men and 158 women (average age, 68 ± 9 years) who underwent R0 resection of previously untreated pathologic stage I pulmonary adenocarcinomas at Memorial Sloan-Kettering Cancer Center, without adjuvant chemotherapy or radiotherapy. In total, 74% of the patients were current smokers, 10% were former smokers, and 16% were never smokers. The average tumor size at the time of resection was 2.2 ± 0.9 cm.

Histologic distribution

Among the 249 cases, the distribution of the 5 standard

Discussion

Lung adenocarcinomas are histologically heterogeneous. The current IASLC/ATS/ERS classification of lung adenocarcinoma recognizes only lepidic, acinar, papillary, solid, and micropapillary patterns as defined tumor types [3]. However, variants or nonstandard patterns can occur and have the potential to create confusion for classification and grading, as well as for reproducibility studies of the new classification [14]. In this study, we have demonstrated that nonstandard patterns like

Acknowledgments

The authors thank Joe Dycoco for his help with the maintenance and management of the surgical database for information concerning patient follow-up. We also thank Drs Kim Geisinger and William Travis for their critical comments and review of the article and David B. Sewell for editorial help.

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    Disclosure: The authors declare no conflicts of interest.

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