Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping Luka Brcic, MD, PhD; Gregor Vlacic, MD; Franz Quehenberger, PhD; Izidor Kern, MD  Context.—Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis. Several studies have analyzed potential prognostic markers, but histologic type remains the single most important prognostic factor. Histologic subtypes of epithelioid MPM seem to have prognostic and therapeutic implications. Interobserver agreement in histologic pattern classification should be high. Objective.—To assess interobserver and intraobserver reproducibility in histologic differentiation between the main types of MPMs, and in further subtyping of epithelioid-type mesothelioma. Design.—One representative hematoxylin-eosin–stained slide was selected from the archive for each of 200 patients with MPM. They were reviewed independently by 3 pathologists and classified according to the current World Health Organization classification of pleural tumors. After the first round of evaluations, a consensus meeting was organized where problems were addressed and represen- tative images for each histologic category were selected. Two months later, cases were reevaluated by all 3 pathologists. Results.—After the first round, overall interobserver agreement for histologic subtyping of mesothelioma was fair (j, 0.36). The agreement was increased to substantial (j, 0.63) in the second round. Improvement was found in interobserver agreement for all types of MPM and for most epithelioid subtypes. Conclusions.—Moderate to substantial agreement in histologic typing and subtyping of MPM can be achieved. However, training with additional clarification of diagnos- tic criteria, their strict application, and help from consensus-based illustrative images is needed. (Arch Pathol Lab Med. 2018;142:747–752; doi: 10.5858/ arpa.2017-0295-OA) M alignant pleural mesothelioma (MPM) is a rare tumor but is also the most common primary malignant tumor of the pleura and has a dismal prognosis. Classical cases are caused by asbestos exposure and present after a long latency period. The incidence of MPM in the United States is decreasing owing to earlier asbestos use control. 1 However, in many other developed and developing countries, it is expected to reach a peak in the next 5 to 10 years. 2 Although there are occasional reports of patients living more than 5 years after the first diagnosis, most commonly, patients are diagnosed in an advanced stage and have a median survival of up to 13 months regardless of treatment modalities. 3–5 Previous studies 6,7 have analyzed different clinical, radio- logic, and pathologic variables as prognostic factors. Histologic type is still the most important single prognostic factor. The epithelioid type of MPM is associated with significantly better survival than the sarcomatoid and biphasic types. 8,9 Even more, histologic subtyping is currently used to make treatment decisions. 10 According to the latest World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart, 11 the epithelioid type is very heterogeneous. It presents with different histologic patterns. Among these, the most common are solid, tubulopapillary, and trabecular, followed by micropapillary, adenomatoid, clear cell, transitional, deciduoid, and pleomorphic. 11 The prognostic significance of different histologic patterns of epithelioid mesotheliomas has been analyzed in a few studies, which suggest poorer survival for individuals with the pleomorphic pattern. 12–14 In contrast, the myxoid/microcystic pattern was shown to be a favorable prognostic marker. 15 Furthermore, Kadota et al 13 have reported better prognosis for individuals with meso- theliomas presenting with trabecular or tubulopapillary patterns than for those with other epithelioid mesothelioma patterns. Proper histologic subtyping of epithelioid MPM may be a potentially useful tool for prognostic stratification of patients. It is therefore essential to have uniform diagnostic criteria and terminology, as well as good interobserver reproducibility among pathologists. However, although there are few studies regarding interobserver reproducibility in the diagnosis of MPM, mainly focused on immunohistologic reproducibility, 16–18 there is only 1 Accepted for publication September 6, 2017. Published as an Early Online Release March 6, 2018. From the Institute of Pathology (Dr Brcic) and the Institute for Medical Informatics, Statistics and Documentation (Dr Quehenberg- er), Medical University of Graz, Graz, Austria; and Cytology and Pathology Laboratory, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia (Drs Vlacic and Kern). The authors have no relevant financial interest in the products or companies described in this article. Presented in part as an oral presentation at the 13th International Conference of the International Mesothelioma Interest Group (iMig 2016); May 1–4, 2016; Birmingham, United Kingdom. Corresponding author: Luka Brcic, MD, PhD, Institute of Pathol- ogy, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria (email: luka.brcic@medunigraz.at). Arch Pathol Lab Med—Vol 142, June 2018 Reproducibility of Pleural Mesothelioma Subtyping—Brcic et al 747