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Published in final edited form as:

Arch Pathol Lab Med. 2016 October ; 140(10): 1104–1110. doi:10.5858/arpa.2016-0073-OA.

DATASET FOR REPORTING OF MALIGNANT MESOTHELIOMA

OF THE PLEURA OR PERITONEUM: RECOMMENDATIONS
FROM THE INTERNATIONAL COLLABORATION ON CANCER
REPORTING (ICCR)
Andrew Churg, MD1, Richard Attanoos, MD2, Alain C Borczuk, MD3, Lucian R Chirieac,
MD4, Francoise Galateau-Sallé, MD5, Allen Gibbs, MD6, Douglas Henderson, MD7, Victor
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Roggli, MD8, Valerie Rusch, MD9, Meagan J Judge, BSc DipEd10, and John R Srigley, MD11
1Department of Pathology, University of British Columbia, and Vancouver General Hospital,
Vancouver, BC Canada
2Department of Cellular Pathology, Cardiff and Vale University Health Board, University Hospital
of Wales, Cardiff, U.K
3Department of Pathology, Weill Cornell University Medical Center, New York, New York, USA
4Departmentof Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston,
Massachusetts
5Department of Pathology, University Hospital Caen, and Department of Biopathology Cancer
Center Leon Berard, Lyon, France
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6Department of Cellular Pathology, Cardiff and Vale University Health Board, University Hospital
of Wales, Cardiff, U.K
7Department of Surgical Pathology, SA Pathology, Flinders Medical Centre, Adelaide, South
Australia
8Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
9Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York,
NY USA
10Royal College of Pathologists of Australasia, Sydney, NSW, Australia
11Program of Laboratory Medicine and Genetics, Trillium Health Partners, and Department of
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Pathology and Molecular Medicine at McMaster University, Hamilton, Ontario, Canada

Abstract
Context—The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit
organisation formed by the Royal Colleges of Pathologists of Australasia and the United
Kingdom, the College of American Pathologists, the Canadian Association of Pathologists-
Association Canadienne des Pathologists (CAP-ACP) in association with the Canadian Partnership

Address for correspondence: Dr Andrew Churg, Dept of Pathology, Vancouver General Hospital, 910 W 10th Ave, Vancouver, BC
Canada achurg@mail.ubc.ca Telephone: 604 724 8810.
 Churg et al. Page 2

Against Cancer (CPAC), and the European Society of Pathology (ESP). Its goal is to produce
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common, internationally agreed, evidence-based datasets for use throughout the world.

Objective and Design—This paper describes a dataset developed by the ICCR expert panel for
the reporting of malignant mesothelioma of both the pleura and peritoneum. The dataset is
composed of elements ‘required’ (mandatory) and ‘recommended’ (non-mandatory), which are
based on a review of the most recent evidence and supported by explanatory commentary.

Results—Eight required elements and seven recommended elements were agreed by the expert
panel to represent the essential information for the reporting of malignant mesothelioma of the
pleura and peritoneum.

Conclusions—In time, the widespread utilisation of an internationally agreed, structured

pathology dataset for mesothelioma will lead not only to improved patient management but
provide valuable data for research and international benchmarking.
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Keywords
Malignant mesothelioma; dataset; protocol; checklist; structured report; synoptic report; quality
reporting

INTRODUCTION
Evidence based structured (synoptic) pathology reports with standardized definitions for
each component have been shown to significantly enhance the completeness and quality of
data provided to clinicians.1–4 Over the last 2 decades, both the United Kingdom,5 and
United States6 and others7 have produced standardized cancer reporting protocols or
“datasets” for national use. Other minimum or comprehensive datasets have been developed
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around the world for a reporting of a variety of cancers on an individual or institutional

basis.

In 2011, the International Collaboration on Cancer Reporting (ICCR) was convened with a
view to reducing the global burden of cancer dataset development and reduplication of effort
by the different international organisations engaged in the development of standardized
cancer reporting datasets. ICCR datasets are made freely available for use by organisations
globally and it is anticipated that in time this will enable the alignment and normalization of
pathology cancer data around the world as producers of datasets adopt and incorporate the
ICCR datasets.

To date, the ICCR collaboration has successfully published five datasets on cancers of the
prostate, endometrium, lung and ovarian/fallopian tube/primary peritoneal site, and
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malignant melanoma. All of the datasets are evidence-based, have been produced by a panel
of internationally renowned experts, have been subject to international open consultation,
and are freely available for worldwide use at the following website: www.iccr-cancer.org
(accessed February 19, 2016). The process of production of each of these datasets has been
published in peer-reviewed journals.8–12

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ICCR datasets are designed to be as concise as possible so as to encourage uptake, facilitate

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future translation, limit the burden on reporting pathologists, and avoid jurisdictional pitfalls
through the exclusion of non-essential information.

Given the interdependence of cancer datasets with the World Health Organization (WHO)
Classification of Tumors, the ICCR has undertaken to develop datasets in synchrony with the
update of the WHO classifications. In 2015, WHO released the 4th edition of its
Classification of Tumors of the Lung, Pleura, Thymus and Heart.13 As a result the ICCR
commenced development of a series of thoracic datasets including a dataset for malignant
mesothelioma.

METHODS
Standardized cancer reporting protocols or “datasets” have been produced for national use
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for many years.5,6,7 Perforce these datasets use the same peer-reviewed evidence as the basis
of these protocols, however, each is constructed differently, uses different terminology and
similar elements may be based on different methodologies.

The adoption of a single international reporting standard avoids duplication of cancer

pathology dataset development in many different jurisdictions, which reduces the burden on
each country and improves opportunities for interoperability, international comparison and
research.

The ICCR conducted a pilot project in 2011 to standardize the initial four cancer datasets for
lung, melanoma, prostate (radical prostatectomy), and endometrial carcinoma. By using
different development processes for this initial collaboration, the ICCR has been able to
optimize the development method for all further dataset efforts, as documented in the
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Guidelines for the Development of ICCR Datasets (http://www.iccr-cancer.org/datasets/

dataset-development; accessed February 19, 2016)

For the construction of the mesothelioma dataset, a Chair was selected by the ICCR Dataset
Steering Committee and a Dataset Authoring Committee (DAC) composed of pathologists
with expertise in mesothelioma and one clinician was then empaneled. The DAC also
included an ICCR representative whose role is to provide guidance and support to the Chair
of the DAC regarding ICCR standards and committee participation and to undertake a
quality assurance role within the committee. A Project Manager was also appointed to
streamline and standardize the dataset development process, reduce individual pathologist’s
time and effort, expedite the development timeline and ensure implementation of, and
adherence to, ICCR standards.
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The dataset is composed of two types of elements: Required and Recommended.

REQUIRED elements are defined as those which are unanimously agreed by the panel to be
essential for the histological diagnosis, clinical management, staging or prognosis of
mesothelioma. RECOMMENDED elements are non-mandatory and defined as clinically
important and recommended as good practice and should ideally be included in the report,
but which are not yet validated or regularly used in patient management. Evidentiary support
at Level III-2 or above (based on prognostic factors in the National Health and Medical

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Research Council (NHMRC) levels of evidence document and defined as “Analysis of

prognostic factors amongst persons in a single arm of a randomized controlled trial”)14 is
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required to support required (mandatory) elements. Rarely, where Level III-2 evidence is not
available, an element can be categorized as required with unanimous agreement of the expert
panel. Required elements are mandatory and the sum of these is the minimum information
which should be included on the pathology report.

Commentary, i.e. explanatory text, diagrams or tables, is added where necessary to clarify
the elements: to define the way an item should be reported, to ensure clarity and conformity;
to explain why an item is included (e.g. how does the item assist with clinical management
or prognosis of the specific cancer); to cite published evidence in support of the element and
to state any exceptions or issues that may be encountered by the reporting pathologist.
Commentary is designed to provide contextual guidance to the reporting pathologist.
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As a starting point, a search for all published mesothelioma datasets was undertaken. This
scan included review of datasets from existing ICCR members and also of datasets,
protocols or checklists published in review articles or other international websites. This
information formed the foundation for a comparative review, from which elements that are
mandatory/required/core in any one or more of these datasets was extracted for
consideration by the DAC along with all responses and commentary.

A proposed dataset was developed and circulated to the DAC for their initial thoughts. This
initial feedback from the group enabled the chair to determine areas of concordance and
dissent prior to a series of web/teleconferences with the DAC to discuss the proposed
dataset.

Following agreement of the draft datasets by the DAC, the dataset was posted to the ICCR
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website for a period of 2 months for public comment. All feedback was reviewed and final
edits made.

RESULTS
Scope
The initial scope of the dataset was for resection specimens for malignant mesothelioma of
the pleura. However on consideration, this was expanded to include peritoneal as well as
pleural lesions, as peritoneal mesothelioma had more in common with pleural mesothelioma,
with respect to behaviour and treatment, than with gynaecological malignancies.

After the initial feedback from the DAC, a proposal to expand the scope to include biopsy
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specimens was discussed and agreed. A detailed review of biopsy for mesothelioma has
recently been published.15

Required Elements
The required elements are shown in Table 1

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Operative Procedure—Documentation of the operative procedure is useful, as

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correlation of the type of procedure with the material received can be important for patient
safety. In resection specimens, the type of surgical procedure is important in determining the
assessment of surgical margins.

Due to advanced age, clinical status, or extent of disease, few mesothelioma patients are
suitable for extrapleural pneumonectomy (EPP) or radical pleurectomy/decortication (P/D)
and therefore, diagnosis is usually based upon biopsy alone. Although the volume of tissue
sampled is more restricted than for surgical resection specimens, biopsy assessment may
contribute significant observations for clinical management and prognosis, in addition to the
crucial distinction between secondary tumors affecting the serosal membranes and
mesothelioma, and between mesothelioma and benign reactive mesothelial proliferations.

The type of biopsy is important as it affects the extent to which a diagnosis may be made
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with any certainty. Accurate typing of mesothelioma16–19 has been shown to vary by
procedure - 83% for open biopsy in comparison to 74% for video-assisted thoracoscopic
surgery (VATS) biopsy, and 44% for computed tomography (CT)-guided biopsy, when
compared with the subtype assessed in a follow-up series of 83 extrapleural pneumonectomy
specimens.19

Specimen(s) Submitted—Specimen type varies according to the type of operation, and

while the nature of the specimens submitted for pathological assessment may be deduced
from the procedure, specifying the nature of specimen received provides complementary
information and confirmation that entire organ/s have been resected and submitted.

Macroscopic Tumor Site—The macroscopic site of the tumor is an important component

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for pathologic staging.

Histological Tumor Type—The major histological tumor types of malignant

mesothelioma as recognized by the WHO classification (4th edition)13 are epithelioid,
sarcomatoid and biphasic/mixed. By convention a biphasic mesothelioma is diagnosed if the
lesser component reaches 10% of the tumor examined.

There are a number of histological patterns of malignant mesothelioma which are important
to be aware of primarily because of diagnostic confusion. For epithelioid mesothelioma
these include common patterns such as solid, tubulopapillary, and trabecular, also less
common forms such as micropapillary, adenomatoid (microcystic), clear cell, transitional,
deciduoid, small cell and pleomorphic mesothelioma. It should be noted that, at present,
there is no uniformity among pathologists for the definition of many of these patterns nor
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any clear prognostic significance to most of them, and we do not recommend these names be
included as part of a diagnosis; their importance lies in recognition by the pathologist that
these are patterns seen in mesotheliomas.

For sarcomatoid mesothelioma these histological variants may comprise heterologous

(osteosarcomatous, chondrosarcomatous and rhabdomyosarcomatous) elements, and

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desmoplastic mesothelioma. Desmoplastic mesothelioma is characterized by atypical spindle

cells and dense hyalinised fibrous stroma, the latter comprising at least 50% of the tumor.20
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The conventional immunohistochemical panel of markers may require modification with

some of these patterns to prevent misdiagnosis. Some of these patterns may have prognostic
significance; however, until these prognostic patterns are clearly defined and accepted, the
current recommendation is to diagnose mesotheliomas as epithelioid, sarcomatoid/
desmoplastic, or biphasic/mixed, particularly since radical surgical approaches depend on
these general classifications.

In some cases, such as small biopsy specimens, a definitive tumor type cannot be assigned
and in this situation a value of “mesothelioma not otherwise specified (NOS)” would be
used.
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Margin Status—In extrapleural pneumonectomy specimens the bronchial resection margin

status is evaluated by intraoperative frozen section examination. In the surgical pathology
specimen, the soft tissue margin status is difficult to assess because the entire pleura
represents a margin. Usually in patients with extrapleural pneumonectomy, the surgeon is
performing a blind dissection beneath the endothoracic fascia between the pleura and chest
wall.

Extent of Invasion—Extent of invasion is part of staging for radical pleural surgical

specimens. In biopsies the presence of invasion is the most important parameter for
separating benign from malignant mesothelial proliferations.

Invasion into the endothoracic fascia is a staging parameter and should be determined only
by the surgeon or radiologist, since there are no characteristic pathological features
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appreciable by gross or microscopic examination.

The endothoracic fascia represents a connective tissue plane that lies between the parietal
pleura and the innermost intercostal muscle. Its histology is not well defined. Sections from
parietal pleura that appose the chest wall showing histologic involvement of skeletal muscle
is the best surrogate indicator that the endothoracic fascia has been breached.

Lymph Node Status—Thoracic or abdominal lymph nodes may be sampled to obtain a

diagnosis or for the staging of an already diagnosed tumor. If thoracic, they should be
identified by standard station; for abdominal lymph nodes, a suitable specimen identifier or
descriptor should be used. A lymph node station should be regarded as positive for
mesothelioma regardless of the number of malignant mesothelial cells present or the number
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of lymph nodes involved provided one node contains malignant mesothelial cells. However,
the identification of mesothelial cells in lymph nodes does not necessarily indicate
metastasis. Rarely may they represent incidental benign inclusions.21,22 The diagnosis of
metastatic mesothelioma should only be made when there is good evidence of a serosa based
tumor whether diffuse or, very rarely, localized.

Pathological Staging (Tumor-Node-Metastasis (TNM) 7th edition)—Staging by

TNM 7th edition is one of the most important prognostic factors.

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Recommended Elements
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The recommended elements are shown in Table 2.

Clinical History—Clinical information is essential to proper processing and evaluation of

pathological specimens as it can influence pre-test probability of a particular diagnosis. This
allows the pathology laboratory to accurately triage processing, including extent of
sampling. It also informs the pathologist as to decisions ultimately influencing the number
of slides to be examined (serial sections, levels) and potential ancillary studies to be
performed1, thus avoiding error.

For malignant mesothelioma, the radiologic growth pattern and history of previous cancer
are important guides to further analysis of a particular specimen. A radiologic nodular
growth pattern may prompt correlation with surgical thoracoscopic observations with regard
to nodule sampling, while a diffuse growth pattern may lead to a request for deeper or more
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extensive samples. History of prior cancer could suggest a different panel of

immunohistochemical stains to definitively rule out metastasis from a known tumor. A
cancer history can prompt a request to review prior outside material or to review an archival
in house slide record.23 Other valuable clinical information includes presence of a pleural
effusion and its characteristics (e.g. transudative, bloody, exudative); this can trigger review
of and correlation with a concurrent cytological specimen.

A history of asbestos exposure is not relevant for the diagnosis of samples in which
malignant mesothelioma is a consideration, as this history does not influence sample
processing or ultimate diagnosis.20

Neoadjuvant Therapy—A history of neoadjuvant therapy is important in the pathology

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analysis. Assessment of residual tumor, including nodal status, is critical to staging and
prognostication in the neoadjuvant setting.24,25

Tumor Size—For pleural mesotheliomas that are received as radical surgical (EPP or P/D)
specimens, attempting to measure the dimensions of individual tumor nodules is neither
simple (because the distinction between tumor and fibrotic reaction may be difficult to
assess) nor informative. Rather, measuring the maximum thickness of tumor appears to be a
more useful indicator of tumor burden and can often be compared to radiologic
measurements.6

For peritoneal mesotheliomas, the specimen is normally received in multiple parts and
dimensions of the dominant mass should be measured. Where multiple nodules are present,
the dimensions of the largest nodule should be recorded.
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Block Identification Key—The origin/designation of all tissue blocks should be recorded.

This information should be documented in the final pathology report and is particularly
important should the need for internal or external review arise. The reviewer needs to be
clear about the origin of each block in order to provide an informed specialist opinion.

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Recording the origin/designation of tissue blocks also facilitates retrieval of blocks for
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further immunohistochemical or molecular analysis, research studies or clinical trials.

Mitotic Count—In pleural malignant mesothelioma, mitotic count has not been
definitively established as an independent parameter in the diagnostic setting or as a
determinant of prognosis. However among epithelioid peritoneal malignant mesothelioma,
increased mitotic count (greater than 4 in 10 HPFa)26 was reported as a poor prognostic
indicator, and, more recently, was validated in a multi-observer study of an independent
group of patients27, establishing a lower cut-off of 5 mitoses in 50 HPF.

Ki-67 fraction may also have prognostic significance, but its use as an adjunct to mitotic
count has not been investigated.

Response to Neoadjuvant Therapy—There is no recommended or agreed system for

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tumor regression grading of mesothelioma that has been treated with neoadjuvant therapy,
however a general indication of residual viable tumor <50% and >50%, may be useful.

Coexistent Pathology—It is recommended that pathologists comment upon any

coexistent non-neoplastic findings present in the submitted materials. These include, for
extrapleural pneumonectomy specimens, such findings as emphysema, small airways
disease, respiratory bronchiolitis, asbestosis, asbestos bodies, talc granulomas and pleural
plaques.28 For diagnosing asbestosis, it is recommended that the criteria published by the
asbestosis committee of the College of American Pathologists and Pulmonary Pathology
Society be used.29 For peritoneal resection specimens, additional findings such as
endometriosis, endosalpingiosis and mesothelial inclusion cysts should be noted.
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Ancillary Studies—The three most common molecular alterations in malignant

mesothelioma are loss of neurofibromin 2 (Merlin, NF2), cyclin-dependent kinase inhibitor
2A (CDKN2A, p16), and BRCA1 associated protein-1 (BAP1). While to date NF2 loss has
not been exploited diagnostically, p16 Fluorescence in situ hybridization (FISH) and BAP1
appear to be useful markers for separating benign from malignant mesothelial
proliferations.30 Thus far both these markers have been reported as only lost in malignant
mesotheliomas when strict cut-offs are applied. One outcome of the strict cut-off is the
major problem of low sensitivity. Overall, studies reporting loss of p16 by FISH in
mesotheliomas show a sensitivity around 50%, albeit significantly higher in pleural (67%)
than peritoneal mesothelioma (25%).30

Loss of p16 by FISH in pleural mesothelioma is correlated with adverse survival.31,32

Retention of p16 by immunohistochemistry is a useful prognostic indicator in peritoneal
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epithelioid malignant mesothelioma, with a significantly prolonged survival in that group.26

The sensitivity for loss of nuclear expression of BAP1 is not well defined but probably on
the order of 50 to 70% for epithelioid mesotheliomas, and very low for sarcomatoid

aHigh Powered Field

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mesotheliomas.30 But these markers are only useful when lost; positive staining does not
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rule out a mesothelioma.

BAP1 immunohistochemistry in addition is useful as a screening tool for BAP1 germline

mutation syndromes, in which there are familial aggregations of mesotheliomas, melanomas
including ocular melanomas, renal cell carcinomas, and probably a variety of other
tumors.33 Interestingly, patients with BAP1 germline mutation mesotheliomas are reported
to have dramatically better survival rates.34 However, BAP1 immunohistochemistry is no
more than a screening tool in this context, since the vast majority of mesotheliomas that
show BAP1 loss only have somatic mutations, and formal genetic analysis is required to
confirm germline tumors.

Positive immunohistochemistry for EMAb, Glut1c, IMP3d and CDe 146 have all been
proposed as single markers for malignant mesothelioma when compared to benign
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proliferations.30 Since small but significant proportions of benign proliferations are positive
for each of these markers, combinations of markers have been proposed, but the correlations
are weak.35–38 Therefore in the absence of morphologic invasion (cytology, small biopsy, or
cellular atypia alone) these markers should not be relied upon as the sole determinant of
malignancy.

DISCUSSION
A series of web/conference calls were undertaken by the DAC to discuss each of the
elements in the proposed dataset for the pathological reporting of mesothelioma. Points of
consideration included the following: (1) The publication of the 4th edition of the WHO
Classification of Tumours of the Lung, Pleura, Thymus and Heart13 ; (2) Variation in local
practice, both surgical and pathological, amongst the international DAC; (3) The value of
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biopsy for the diagnosis of mesothelioma; (4) Variation in terminology in use for element
names and responses; (5) Whether localized mesothelioma should or should not be included
in the scope of the dataset. Localized malignant mesotheliomas are extremely uncommon
tumors with the microscopic appearances of diffuse malignant mesotheliomas, but are
solitary, and by definition do not show gross or microscopic evidence of diffuse pleural
spread. Roughly half of localized malignant mesotheliomas are curable by wide surgical
excision.39 It was agreed that localized malignant mesotheliomas are sufficiently different
from ordinary diffuse malignant mesotheliomas that there was little value in including these
lesions in the scope of this publication.

Each element and its value list or response e.g. “present”, “not assessable”, “not indicated”,
was discussed and agreed by the DAC. Standardized terminology with definitions for
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common terms is used to avoid any ambiguity in the assessment or meaning of the element.
The DAC was then assigned tasks for the writing of commentary for those elements
requiring further explanatory text taking into account recent and pertinent literature.

bEpithelial Membrane Antigen

cGlucose transporter −1
dHuman U3 small nucleolar ribonucleoprotein protein
eCluster of differentiation

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The goal of the ICCR is to develop a set of data elements which will form the core of any
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pathology report on the specific cancer around the world. Adoption of the ICCR datasets
will help facilitate recording of pathological data in a consistent standardized way. The
ICCR datasets need to include any element that is essential to include when reporting a
cancer and which has either supporting evidence or unanimous agreement from the DAC to
include as best practice. This dataset is therefore the core of any structured pathology report
on mesothelioma. It is not, however, the intention that the dataset be restrictive and
additional data items may be included when reporting, according to local needs. All
structured pathology reports must also include the facility for free text comments to insure
that any clarification or nuance in reporting is captured.

Acknowledgments
The authors would like to thank Avril Kwiatkowski for her considerable contributions to the development of the
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mesothelioma dataset.

Dr. Valerie Rusch’s work is funded in part by National Institutes of Health/National Cancer Institute Cancer Center
Support Grant P30 CA008748.

References
1. Cross SS, Feeley KM, Angel CA. The effect of four interventions on the informational content of
histopathology reports of resected colorectal carcinomas. J Clin Oncol. 1998; 51(6):481–482.
2. Mathers M, Shrimankar J, Scott D, Charlton F, Griffith C, Angus B. The use of a standard proforma
in breast cancer reporting. J Clin Pathol. 2001; 54(10):809–811. [PubMed: 11577136]
3. Srigley JR, McGowan T, MacLean A, et al. Standardized synoptic cancer pathology reporting: A
population-based approach. J Surg Oncol. 2009; 99(8):517–524. [PubMed: 19466743]
4. Gill AJ, Johns AL, Eckstein R, et al. Synoptic reporting improves histopathological assessment of
pancreatic resection specimens. Pathology. 2009; 41(2):161–167. [PubMed: 19320058]
Author Manuscript

5. RCP (Royal College of Pathologists). [Accessed 19th Feb 2016] Cancer datasets and tissue
pathways. 2015. www.rcpath.org/profession/publications/cancer-datasets.html
6. CAP (College of American Pathologists). [Accessed 19th Feb 2016] Cancer protocol templates.
www.cap.org/web/home/resources/cancer-reporting-tools/cancer-protocol-templates?_adf.ctrl-
state=10jd5draq2_17&_afrLoop=78742816534289#!%40%40%3F_afrLoop
%3D78742816534289%26_adf.ctrl-state%3D4596lsm96_4
7. RCPA (Royal College of Pathologists of Australasia). [Accessed 19th Feb 2016] Cancer Protocols.
www.rcpa.edu.au/Library/Practising-Pathology/Structured-Pathology-Reporting-of-Cancer/Cancer-
Protocols
8. Scolyer RA, Judge MJ, Evans A, et al. Data Set for Pathology Reporting of Cutaneous Invasive
Melanoma: Recommendations From the International Collaboration on Cancer Reporting (ICCR).
Am J Surg Pathol. 2013; 37(12):1797–1814. [PubMed: 24061524]
9. McCluggage WG, Colgan T, Duggan, et al. Data Set for Reporting of Endometrial Carcinomas:
Recommendations From the International Collaboration on Cancer Reporting (ICCR) Between
United Kingdom, United States, Canada, and Australasia. International Journal of Gynecological
Author Manuscript

Pathology. 2012; 32(1):45–65.

10. Jones KD, Churg A, Henderson DW, et al. Data Set for Reporting of Lung Carcinomas:
Recommendations From International Collaboration on Cancer Reporting. Arch Pathol Lab Med.
2013; 137(8):1054–1062. [PubMed: 23899061]
11. McCluggage WG, Judge MJ, Clarke BA, et al. Dataset for reporting of ovary, fallopian tube and
primary peritoneal carcinoma: Recommendations from the International Collaboration on Cancer
Reporting (ICCR). Mod Path. 2015; 28(8):1101–1122. [PubMed: 26089092]

Arch Pathol Lab Med. Author manuscript; available in PMC 2017 January 26.
 Churg et al. Page 11

12. Kench J, Delahunt B, Griffiths DF, et al. Dataset for reporting of prostate carcinoma in radical
prostatectomy specimens: recommendations from the International Collaboration on Cancer
Author Manuscript

Reporting. Histopathology. 2013; 62(2):203–218. [PubMed: 23240714]

13. Travis, WD., Brambilla, E., Burke, AP., Marx, A., Nicholson, AG. WHO Classification of Tumours
of the Lung, Pleura, Thymus and Heart. 4. Lyon, France: IARC Press; 2015.
14. Merlin T, Weston A, Tooher R. Extending an evidence hierarchy to include topics other than
treatment: revising the Australian ‘levels of evidence’. BMC Med Res Methodol. 2009; 9:34.
[PubMed: 19519887]
15. van Zandwijk N, Clarke C, Henderson D, et al. Guidelines for the diagnosis and treatment of
malignant pleural mesothelioma. J Thorac Dis. 2013; 5(6):E254–307. [PubMed: 24416529]
16. Bueno R, Reblando J, Glickman J, Jaklitsch MT, Lukanich JM, Sugarbaker DJ. Pleural biopsy: a
reliable method for determining the diagnosis but not subtype in mesothelioma. Ann Thorac Surg.
2004; 78(5):1774–1776. [PubMed: 15511473]
17. Greillier L, Cavailles A, Fraticelli A, et al. Accuracy of pleural biopsy using thoracoscopy for the
diagnosis of histologic subtype in patients with malignant pleural mesothelioma. Cancer. 2007;
110(10):2248–2252. [PubMed: 17886249]
Author Manuscript

18. Attanoos RL, Gibbs AR. The comparative accuracy of different pleural biopsy techniques in the
diagnosis of malignant mesothelioma. Histopathology. 2008; 53(3):340–344. [PubMed: 18647189]
19. Kao SC, Yan TD, Lee K, et al. Accuracy of diagnostic biopsy for the histological subtype of
malignant pleural mesothelioma. J Thorac Oncol. 2011; 6(3):602–605. [PubMed: 21266919]
20. Husain AN, Colby T, Ordonez N, et al. Guidelines for pathologic diagnosis of malignant
mesothelioma: 2012 update of the consensus statement from the International Mesothelioma
Interest Group. Arch Pathol Lab Med. 2013; 137(5):647–667. [PubMed: 22929121]
21. Parkash V, Vidwans M, Carter D. Benign mesothelial cells in mediastinal lymph nodes. Am J Surg
Pathol. 1999; 23(10):1264–1269. [PubMed: 10524528]
22. Goyal M, Kodandapani S, Sharanabasappa SN, Palanki SD. Mesothelial cell inclusions mimicking
adenocarcinoma in cervical lymph nodes in association with chylous effusion. Indian J Med
Paediatr Oncol. 2010; 31(2):62–64. [PubMed: 21209767]
23. Wick MR. Medicolegal liability in surgical pathology: a consideration of underlying causes and
selected pertinent concepts. Semin Diagn Pathol. 2007; 24(2):89–97. [PubMed: 17633350]
Author Manuscript

24. Van Schil PE, Opitz I, Weder W, et al. Multimodal management of malignant pleural
mesothelioma: where are we today? Eur Respir J. 2014; 44(3):754–764. [PubMed: 24525443]
25. de Perrot M, Feld R, Cho BC, et al. Trimodality therapy with induction chemotherapy followed by
extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural
mesothelioma. J Clin Oncol. 2009; 27(9):1413–1418. [PubMed: 19224855]
26. Borczuk AC, Taub RN, Hesdorffer M, et al. P16 loss and mitotic activity predict poor survival in
patients with peritoneal malignant mesothelioma. Clin Cancer Res. 2005; 11(9):3303–3308.
[PubMed: 15867227]
27. Krasinskas AM, Borczuk AC, Hartman DJ, et al. Prognostic Significance of Morphologic Subtypes
and Mitotic Index of Epithelioid Malignant Peritoneal Mesothelioma. Arch Pathol Lab Med. Epub
ahead of print.
28. Mark EJ. The second diagnosis: the role of the pathologist in identifying pneumoconioses in lungs
excised for tumor. Hum Pathol. 1981; 12(7):585–587. [PubMed: 7275097]
29. Roggli VL, Gibbs AR, Attanoos R, et al. Pathology of asbestosis - An update of the diagnostic
criteria: Report of the asbestosis committee of the College of American Pathologists and
Author Manuscript

Pulmonary Pathology Society. Arch Pathol Lab Med. 2010; 134(3):462–480. [PubMed: 20196674]
30. Churg A, Sheffield BS, Galateau-Salle F. New Markers for Separating Benign From Malignant
Mesothelial Proliferations: Are We There Yet? Arch Pathol Lab Med. Epub ahead of print.
31. Dacic S, Kothmaier H, Land S, et al. Prognostic significance of p16/CDKN2A loss in pleural
malignant mesotheliomas. Virchows Arch. 2008; 453(6):627–635. [PubMed: 18958493]
32. Lopez-Rios F, Chuai S, Flores R, et al. Global gene expression profiling of pleural mesotheliomas:
overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical
evaluation of microarray-based prognostic prediction. Cancer Res. 2006; 66(6):2970–2979.
[PubMed: 16540645]

Arch Pathol Lab Med. Author manuscript; available in PMC 2017 January 26.
 Churg et al. Page 12

33. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer.
2013; 13(3):153–159. [PubMed: 23550303]
Author Manuscript

34. Baumann F, Flores E, Napolitano A, et al. Mesothelioma patients with germline BAP1 mutations
have 7-fold improved long-term survival. Carcinogenesis. 2015; 36(1):76–81. [PubMed:
25380601]
35. Minato H, Kurose N, Fukushima M, et al. Comparative immunohistochemical analysis of IMP3,
GLUT1, EMA, CD146, and desmin for distinguishing malignant mesothelioma from reactive
mesothelial cells. Am J Clin Pathol. 2014; 141(1):85–93. [PubMed: 24343741]
36. Lagana SM, Taub RN, Borczuk AC. Utility of glucose transporter 1 in the distinction of benign and
malignant thoracic and abdominal mesothelial lesions. Arch Pathol Lab Med. 2012; 136(7):804–
809. [PubMed: 22742553]
37. Monaco SE, Shuai Y, Bansal M, Krasinskas AM, Dacic S. The diagnostic utility of p16 FISH and
GLUT-1 immunohistochemical analysis in mesothelial proliferations. Am J Clin Pathol. 2011;
135(4):619–627. [PubMed: 21411785]
38. Lee AF, Gown AM, Churg A. IMP3 and GLUT-1 immunohistochemistry for distinguishing benign
from malignant mesothelial proliferations. Am J Surg Pathol. 2013; 37(3):421–426. [PubMed:
Author Manuscript

23108021]
39. Allen TC, Cagle PT, Churg AM, et al. Localized malignant mesothelioma. Am J Surg Pathol.
2005; 29(7):866–873. [PubMed: 15958850]
Author Manuscript
Author Manuscript

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 Churg et al. Page 13

Table 1

Required Data Items for Pathological Reporting of Mesothelioma

Author Manuscript

DATA ELEMENT AGREED PERMITTED RESPONSE

Operative procedure • Not provided
OR
• Core biopsy
• Open biopsy
• VATS biopsy
• Decortication
• Radical pleurectomy
• Extrapleural pneumonectomy
• Debulking
• Other (specify)
Author Manuscript

Specimen(s) submitted • Not provided

OR
Pleura/Thoracic:
• Diaphragm
• Lung
– Right
♦ Wedge
♦ Lobe
♦ Entire Lung
– Left
♦ Wedge
♦ Lobe
Author Manuscript

♦ Entire Lung
• Mediastinal fat
• Pericardium
• Parietal pleura
• Contralateral pleura
• Visceral pleura
• Endothoracic fascia
• Chest wall
• Rib
• Spine
• Port Site
Peritoneum:
Author Manuscript

• Peritoneum
• Omentum
• Right ovary
• Left ovary
• Right fallopian tube

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 Churg et al. Page 14

DATA ELEMENT AGREED PERMITTED RESPONSE

• Left fallopian tube
Author Manuscript

• Uterus
• Other intra-abdominal organs (Specify)
Other submitted specimens:
• Lymph nodes (Specify site(s))
• Other (Specify)

Macroscopic tumour site • Indeterminate

OR
Pleura/Thoracic:
• Diaphragm
• Lung
– Right
– Left
Author Manuscript

• Mediastinal fat
• Pericardium
• Parietal pleura
• Contralateral pleura
• Visceral pleura
• Endothoracic fascia
• Chest wall
• Rib
• Spine
• Port site
Peritoneum:
• Peritoneum
Author Manuscript

• Omentum
• Right ovary
• Left ovary
• Right fallopian tube
• Left fallopian tube
• Uterus
• Other intra-abdominal organs (Specify)
Other:
• Lymph Node/(s)
• Other site (Specify)

Histological tumour type • Epithelioid (Epithelial)

• Sarcomatoid (Sarcomatous)
Author Manuscript

• Biphasic (Mixed epithelial and sarcomatous)

• Malignant mesothelioma, NOS

Margin status * • Cannot be assessed

• Not applicable

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 Churg et al. Page 15

DATA ELEMENT AGREED PERMITTED RESPONSE

• Not involved
Author Manuscript

• Involved (Specify margin/s, if possible)

*Applicable to extrapleural pneumonectomy specimens only

Extent of invasion • Cannot be assessed

OR
• No evidence of primary tumour
• Parietal pleura without involvement of the ipsilateral visceral pleura
• Parietal pleura with focal involvement of the ipsilateral visceral pleura
• Endothoracic fascia (as determined by surgeon/radiologist)
• Mediastinal fat
• Localised focus of tumour invading the soft tissue of the chest wall
• Diffuse or multiple foci invading soft tissue of chest wall
• Through the pericardium or diaphragm
Author Manuscript

• Into but not through the pericardium or diaphragm

• Rib(s)
• Peritoneum through the diaphragm
• Great vessels/oesophagus/trachea or other mediastinal organ
• Extension into contralateral pleura
• Spine
• Myocardium
• Confluent visceral and parietal pleural tumour (including fissure)
• Mediastinal organ(s) (specify)
• Other (specify)

Lymph node status • Cannot be assessed

OR
Author Manuscript

• No nodes submitted or found

OR
• Lymph node station/location or specimen identification (list each and for each record:)
– Involved
– Not involved

Pathological staging (TNM 7th edition) pT (y and r prefix and (m) suffix if applicable)
pN
Author Manuscript

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 Churg et al. Page 16

Table 2

Recommended Data Items for Pathological Reporting of Mesothelioma

Author Manuscript

DATA ELEMENT AGREED PERMITTED RESPONSE

Clinical history • Not provided
OR
• Radiological appearance (specify)
• History of previous cancer (specify)
• Other (specify)

Neoadjuvant therapy • Information not provide

• Not administered
• Administered (specify)

TUMOUR SIZE - PLEURAL SPECIMENS

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Maximum thickness of any mass • Indeterminate

OR
• Numeric (mm)

Dimensions of dominant mass • Indeterminate

OR
• Length x width x depth (mm)

TUMOUR SIZE - PERITONEAL SPECIMENS

Dimensions of dominant mass • Indeterminate

OR
• Length x width x depth (mm)
Author Manuscript

OR Dimensions of largest nodule • Indeterminate

OR
• Length x width x depth (mm)

Block identification key Text

Mitotic count* Numeric per mm2
* Applicable to peritoneal specimens only

Response to neoadjuvant therapy • Not applicable

• Cannot be determined
• Greater than 50% residual tumour
• Less than 50% residual tumour
• No residual tumour found
Author Manuscript

Coexistent pathology • None identified

OR
specify

Ancillary studies • Not performed

• Performed

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 Churg et al. Page 17

DATA ELEMENT AGREED PERMITTED RESPONSE

– Immunohistochemistry (list stains)
Author Manuscript

– Other (specify)
Author Manuscript
Author Manuscript
Author Manuscript

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