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2014, Volume 30, Number 2, Page(s) 105-110
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DOI: 10.5146/tjpath.2014.01231 |
Interobserver Agreement Among Histological Patterns and Diagnosis in Lung Adenocarcinomas |
Halide Nur ÜRER1, Rengin AHISKALI2, Naciye ARDA1, Sebnem BATUR3, Leyla CÝNEL4, Gerhard DEKAN5, Neslihan FENER1, Pýnar FIRAT6, Silvana GELEFF5, Büge ÖZ3, Yasemin ÖZLÜK6, Kürþat YILDIZ7, Emine Dilek YILMAZBAYHAN6, Handan ZEREN8, Atilla UYSAL9 |
1Departments of Pathology, Yedikule Chest Diseases and Chest Surgery Education and Research Hospital, ISTANBUL, TURKEY
2Department of Pathology, Marmara University, Faculty of Medicine, ISTANBUL, TURKEY
3Istanbul University, Cerrahpaþa Medicine Faculty, ISTANBUL, TURKEY
4Ministry of Health Istanbul Medeniyet University, ISTANBUL, TURKEY
5Medical University of Vienna, VIENNA, AUSTRIA
6Istanbul University, Istanbul Medicine Faculty, ISTANBUL, TURKEY
7Kocaeli University, Faculty of Medicine, ISTANBUL, TURKEY
8Acibadem University, Faculty of Medicine, ISTANBUL, TURKEY
9Departments of Chest Diseases, Yedikule Chest Diseases and Chest Surgery Education and Research Hospital, ISTANBUL, TURKEY |
Keywords: Adenocarcinoma, Lung neoplasms, Interobserver variations |
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Objective: The aim of this study was to investigate the interobserver
agreement in determination of the dominant histological pattern and
the final diagnosis in lung adenocarcinomas.
Material and Method: A total of 12 patients with a diagnosis of
primary lung adenocarcinoma were included in the study. Twelve
pathologists from eight study centers were asked first to determine
the dominant histological pattern in these cases and then to decide
whether the final diagnosis was in situ, minimally invasive or invasive
adenocarcinoma.
Results: The kappa value for the agreement in determining the
dominant pattern among the pathologists was 0.36 (p<0.001), with
the values for the lepidic, acinar, papillary, solid, micropapillary
patterns and mucinous character of adenocarcinoma being 0.34, 0.28,
0.30, 0.80, 0.16 and 0.38 respectively (p<0.001, p<0.001, p<0.001,
p<0.001, p<0.001, p<0.001). None of the cases was diagnosed as
in situ adenocarcinoma. On the other hand, the kappa value for
the agreement in differentiating minimally invasive from invasive
adenocarcinoma among reviewers was 0.17 (p<0.001).
Conclusion: The agreement among pathologists in determining the
subtype of lung adenocarcinomas that depends on the identification
of the dominant pattern was at intermediate level. In addition, the
agreement in deciding whether the case is minimally invasive or
invasive, was at low level. The criteria defining the histological
patterns should be clarified and described in more detail. Educational
activities and larger multicenter studies might be helpful in improving
the agreement and standardization. |
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Lung adenocarcinomas (ACs) are different from other
organ ACs due to the presence of heterogeneous tumors
with morphological diversity 1. The coexistence of more
than one histological pattern (mixed-type) is observed in
80-90% of tumors, and determining the dominant pattern
in the tumor is important in terms of disease prognosis 2,3,4. According to the 2011 consensus report of the
International Association for the Study of Lung Cancer,
American Thoracic Society and the European Respiratory
Society (IASL C/ATS /ERS), identifying the dominant
pattern as well as other histological patterns in AC along
with defining the terms “in situ AC” and “minimally
invasive AC” were important prognostic and predictive
factors (Table I) 5. Moreover, the various studies have
highlighted the prognostic importance of the new AC
classification system 6,7.
In this study, we aimed to investigate the interobserver
agreement in terms of the dominant histological AC pattern
and final diagnosis of AC. |
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Abstract
Introduction
Methods
Results
Disscussion
References
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A total of 12 patients with a diagnosis of primary lung
AC who underwent a complete surgical resection were
randomly selected from the archives of the pathology
department of Yedikule Chest Diseases and Chest Surgery
Education and Research Hospital. In all cases, the tumors
were located outside of the bronchi in the peripheral
parenchyma. The largest tumor diameter was 3 centimeters,
with a median of 1.9 centimeters (range 1-2.5). For the
most widespread representation of tumors in each case, sets
consisting of three glass slides originating from one or two
paraffin blocks were prepared and stained with H&E, PAS,
and Elastica Van Gieson.
The study included a total of 12 pathologists from eight
institutions who specialized in lung pathology. The samples
were evaluated under light microscopy according to the
histologic criteria specified in the 2011 IASL C/ATS /
ERS international multidisciplinary classification of lung
adenocarcinoma consensus5. The reviewers were asked to
determine the dominant AC pattern, presence of mucinous
character and final diagnosis in each case. Adenocarcinoma
patterns were lepidic, acinar, papillary, solid, micropapillary
as described in the IASL C/ATS /ERS report. They were also
asked to decide whether the case is a minimally invasive
adenocarcinoma (MIAC) or an invasive adenocarcinoma
(IAC) according to the morphology and the diameter of the
invasive focus.
To determine the interobserver agreement among dominant
patterns (lepidic, acinar, papillary, solid, micropapillary
and mucinous), and between IAC and MIAC the results
were evaluated using Fleiss kappa statistics (StataCorp.
2011, Stata Statistical Software: Release 12, College Station,
TX, USA, StataCorp LP). The meaning of kappa values
representing agreement among observers is presented in
Table II8.
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Abstract
Introduction
Methods
Results
Disscussion
References
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A total of 144 diagnoses were made in 12 cases by 12
reviewers. Of the 144 diagnoses, 117 were IAC and 27 were
MIAC (Figure 1). In only three cases, over 80% agreement
were obtained with two different histologic patterns. In
three cases, over 70% agreement were obtained with the
three different histologic patterns. The other six cases
(50%) showed <70% agreement with ≥3 histologic patterns
(Figure 2A-D, 3). The agreement for the dominant patterns
among reviewers was intermediate level (kappa=0.36;
p<0.001), and the kappa values for the histological lepidic,
acinar, papillary, solid, micropapillary patterns and
mucinous character were 0.34, 0.28, 0.30, 0.80, 0.16, and
0.38, respectively (p< 0.001) (Table III).
Click Here to Zoom |
Figure 2: A) Lepidic pattern (H&E; x40), B) Acinar pattern (H&E; x200), C) Papillary pattern (H&E; x100), D) Lepidic and acinar
pattern (H&E; x100). |
The agreement in establishing stromal invasion was 100%
and none of the cases were diagnosed as in situ AC.
However, the agreement for the IAC and MIAC among
reviewers was low level (kappa=0.17; p<0.001). |
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Abstract
Introduction
Methods
Results
Disscussion
References
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In the lung tumors classification of World Health
Organisation (WHO), ACs with heterogeneous histology
has been put together under the category of “mixedtype” 1. Recent regulations in the lung adenocarcinoma
classification have led to some changes in terms of
histopathological approach and diagnosis, all of which
affect disease prognosis 5. Thus, the diagnosis of “mixed
adenocarcinoma” was replaced with “dominant pattern
adenocarcinoma”, and the concepts of “minimally invasive”
and “in situ” were included in the differential diagnosis
for tumors with a diameter of 3 cm or less. Invasion is described as tumor cells infiltrating the myofibroblastic
stroma or presence of any histological pattern other than
lepidic. Furthermore, “invasive mucinous adenocarcinoma”
was defined as a variant that includes most of the former
mucinous-type bronchioloalveolar adenocarcinomas 5.
Various studies exist that have discussed relatively high
reproducibility of histological subtyping of lung ACs9,10. However, there are also some other studies suggesting
that the level of agreement is low for determining subtypes
because of differentiation and the complex heterogeneous
framework11,12. The main reason for this lies in
the interlaced lepidic, acinar, and papillary patterns in
the absence of desmoplasia. In addition, differentiating
micropapillary and lepidic patterns from papillary may
also be problematic; the classification requires that lepidic
growth in the alveolar space filled with papillary structures
should be considered as papillary AC in the absence of
myofibroblastic stroma5,13. These studies suggest that
the differential diagnosis of the patterns (especially lepidic, acinar and papillary) is still open to discussion. On the
other hand, the solid pattern, which consists of lined-up
tumor cells without a definite frame and space, shows the
highest rate of agreement14. In the present study, weak
and intermediate agreement was detected in patterns
other than the solid subtype; our results were similar to
other studies. Noguchi and Warth reported that education
programs performed with the assistance of experienced
pathologists have increased the agreement. However, the
fact that their results did not reach perfect levels indicates
that further studies are needed involving larger series with
non-randomized cases14,15.
Our study showed that the level of agreement in
differentiating IAC form MIAC is low. Not only detecting
the cells invading the stroma individually but also presence
of any pattern other than lepidic defines invasion5. As
explained above, when there is no desmoplasia due to
the difficulty in differentiating patterns, measuring the
magnitude of invasive focus under this complex frame is
technically challenging16.
The main limitation of our study was the low number of
cases. In addition, the selected cases were indeed difficult
to subtype. In studies performed on tumors with typical
morphology, high levels of agreement were reported when
compared with the agreement rates in problematic cases9. Furthermore, the study was of a single-step design and
had no reference pathologist.
When determining the subtype of lung ACs in this
study, we observed an intermediate level of agreement in
identifying different patterns and a weak level of agreement
in the diagnosis of MIAC. Our findings indicate that
further studies are necessary and the classification criteria
should be described in more detail to clarify some possible
miscategorizations that currently exist. Educational
activities and larger multicenter studies might be helpful
for standardization. |
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Abstract
Introduction
Methods
Results
Discussion
References
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Abstract
Introduction
Methods
Results
Discussion
References
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