Welcome to the first 2017 edition of Pulmonary Pathology Reviews, a multi-institutional journal club intended to keep you up-to-date on literature relevant to those with interest in diagnostic pulmonary pathology. This month's journal club comes courtesy of Brandon Larsen at Mayo Clinic Arizona. What follows is his OVERVIEW, highlighting the good, the bad, and the ugly in the peer reviewed literature that found print in December 2016. Below his OVERVIEW there is an ARTICLE INDEX with links to PubMed abstracts, and full text versions of those articles to which your institutional licenses provide access. Click here for a PDF version of his article summaries. And if you want to listen in to the teleconference recorded exactly as it went down at 07:15 MST on Monday, January 29, 2017, click here to download an MP3 audiofile.
In December 2016, there were 31 articles relevant to pulmonary pathology. Not surprisingly, most articles dealt with neoplastic disease, especially topics involving molecular testing and immunotherapy. However, this month also saw an important series of articles published in JTO outlining the proposed changes to TNM staging of malignant pleural mesothelioma in the 8th Edition of the AJCC Staging System for this tumor, which we will all need to become aware of. This month, we were also treated with a larger than usual number of articles on non-neoplastic lung disease, with three studies investigating mutations in fibrotic ILD, accompanied by several editorials and a review on this evolving topic. From these articles, four were chosen for further discussion.
First on the list, Davidson from Norway presents a single-authored study investigating CD24 as a novel IHC marker to differentiate high-grade serous carcinoma from benign and malignant mesothelial cells in effusions and surgical specimens. As we all know, distinguishing metastatic ovarian and breast carcinomas from mesothelial lesions in the pleura can be a challenge, as many of our classic IHC markers (e.g. WT-1, CK5/6) are relatively useless in this differential diagnostic context. In this specific scenario, CD24 may fill that gap as part of an IHC panel (along with PAX8, claudin 4, and/or BAP1), as CD24 is extensively expressed by most serous carcinomas and many breast carcinomas but is almost always absent in mesotheliomas, with only a small minority of mesotheliomas displaying minimal focal expression of this marker.
Next, Hashisako and colleagues from Japan investigate interobserver agreement among 11 pulmonary pathologists from around the world regarding the diagnosis of UIP in whole slide images of surgical lung biopsies using the 2011 ATS/ERS/JRS/ALAT consensus criteria, compared with diagnoses based on 2002 criteria. Not surprisingly, interobserver agreement was quite poor, even among subspecialized pulmonary pathologists with interest in fibrotic ILD, and was no better using the new criteria than with the old criteria. This comes as no surprise to those of us who see these cases regularly. Wouldn’t it be nice if we had better biomarkers, to more reproducibly and accurately classify these diseases into clinically meaningful groups?
Katoda and colleagues from MSKCC investigated the prognostic significance of KRAS mutations in early-stage lung adenocarcinoma, a controversial topic with mixed findings in the literature. In a large, single-institution series, these investigators nicely demonstrate the independent negative prognostic significance of KRAS mutations including overall survival and risk of recurrence, even after multivariate analysis that included important potential confounders including surgical approach, pathologic stage, and vascular invasion. This adds to the growing body of literature on the importance of specific driver mutations in the prognosis of NSCLC.
Lastly, Newton and colleagues at UT Southwestern investigated a large cohort of patients with telomere-related lung fibrosis, including patients with mutations in TERT, TERC, RTEL1, and PARN, and examined the clinical and pathologic features in these patients. Interestingly, the multidisciplinary diagnoses varied widely from IPF and chronic HP to IPAF, IPPFE, and CTD-ILD, including discordant diagnoses within 80% of families. Although cases were diagnostically heterogenous, they were universally progressive, with no significant difference between patients labeled as “IPF” versus those with a non-IPF diagnosis. We have only begun to unravel the molecular underpinnings of fibrotic lung disease, but clearly there is more to the story than the pathologic pattern or even the “multidisciplinary diagnosis”, and at some point the molecular signature of the disorder will have to be incorporated into the diagnosis and treatment plan.
Other notable articles this month include another study investigating TERT and TERC mutations in ILD that we did not have time to discuss, as well as a fascinating article reporting decreased expression of the relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF, suggesting that relaxin-based therapies may be useful in at least some patients with IPF. Along with these is an excellent review on the genetics of pulmonary fibrosis from the University of Colorado. Happy reading, everyone!
Berg K, Wright JL. The Pathology of Chronic Obstructive Pulmonary Disease: Progress in the 20th and 21st Centuries. Arch Pathol Lab Med. 2016 Dec;140(12):1423-1428.
Borie R, et al. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. Eur Respir J. 2016 Dec;48(6):1721-1731.
Davidson B. CD24 is highly useful in differentiating high-grade serous carcinoma from benign and malignant mesothelial cells. Hum Pathol. 2016 Dec;58:123-127.
Fernández-Codina A, et al. A 40-Year-Old Woman With Back Pain. Chest. 2016 Dec;150(6):e159-e165.
Hambly N, Kolb M. Pathways to Precision Medicine in Idiopathic Pulmonary
Fibrosis. Time to Relax? Am J Respir Crit Care Med. 2016 Dec 1;194(11):1315-1317
Hashisako M, et al. Interobserver Agreement of Usual Interstitial Pneumonia Diagnosis Correlated With Patient Outcome. Arch Pathol Lab Med. 2016 Dec;140(12):1375-1382.
He P, et al. Diagnosis of lung adenocarcinoma in situ and minimally invasive adenocarcinoma from intraoperative frozen sections: an analysis of 136 cases. J Clin Pathol. 2016 Dec;69(12):1076-1080.
Hofman P, Popper HH. Pathologists and liquid biopsies: to be or not to be? Virchows Arch. 2016 Dec;469(6):601-609.
Ibrahim M, et al. ALK Immunohistochemistry in NSCLC: Discordant Staining Can Impact Patient Treatment Regimen. J Thorac Oncol. 2016 Dec;11(12):2241-2247.
Ilie M, et al. PD-L1 expression in basaloid squamous cell lung carcinoma: Relationship to PD-1(+) and CD8(+) tumor-infiltrating T cells and outcome. Mod Pathol. 2016 Dec;29(12):1552-1564.
Kadota K, et al. KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma. Am J Surg Pathol. 2016 Dec;40(12):1579-1590.
Kim S, et al. PD-L1 expression is associated with epithelial-to-mesenchymal transition in
adenocarcinoma of the lung. Hum Pathol. 2016 Dec;58:7-14.
Kim Y, et al. Overexpression of β-Catenin and Cyclin D1 is Associated with Poor Overall Survival in Patients with Stage IA-IIA Squamous Cell Lung Cancer Irrespective of Adjuvant Chemotherapy. J Thorac Oncol. 2016 Dec;11(12):2193-2201.
Langer CJ, et al. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment. J Thorac Oncol. 2016 Dec;11(12):2066-2081.
Liu L, et al. Ciliated Muconodular Papillary Tumors of the Lung Can Occur in Western Patients and Show Mutations in BRAF and AKT1. Am J Surg Pathol. 2016 Dec;40(12):1631-1636.
Mansuet-Lupo A, et al. Intratumoral Immune Cell Densities Are Associated with Lung
Adenocarcinoma Gene Alterations. Am J Respir Crit Care Med. 2016 Dec 1;194(11):1403-1412.
Masai K, et al. Clinicopathological, Immunohistochemical, and Genetic Features of Primary Lung Adenocarcinoma Occurring in the Setting of Usual Interstitial Pneumonia Pattern. J Thorac Oncol. 2016 Dec;11(12):2141-2149.
Mathai SK, et al. Pulmonary fibrosis in the era of stratified medicine. Thorax. 2016;71:1154-1160.
Merck SJ, Armanios M. Shall we call them "telomere-mediated"? Renaming the
idiopathic after the cause is found. Eur Respir J. 2016 Dec;48(6):1556-1558.
Newton CA, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016 Dec;48(6):1710-1720.
Nowak AK, et al. The IASLC Mesothelioma Staging Project: Proposals for Revisions of
the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2089-2099.
Pass H,et al. The IASLC Mesothelioma Staging Project: Improving Staging of a
Rare Disease Through International Participation. J Thorac Oncol. 2016 Dec;11(12):2082-2088.
Rice D, et al. The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2100-2111.
Rusch VW, et al. The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma. J Thorac Oncol. 2016 Dec;11(12):2112-2119.
Shi R, et al. An Anaplastic Lymphoma Kinase Immunohistochemistry-Negative but Fluorescence In Situ Hybridization-Positive Lung Adenocarcinoma Is Resistant to Crizotinib. J Thorac Oncol. 2016 Dec;11(12):2248-2252.
Tan J, et al. Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies. Am J Respir Crit Care Med. 2016 Dec 1;194(11):1392-1402.
Tay CK, et al. Primary angiomatoid fibrous histiocytoma of the lung with mediastinal lymph node metastasis. Hum Pathol. 2016 Dec;58:134-137.
Torres A, et al. Laboratory diagnosis of pneumonia in the molecular age. Eur Respir J. 2016 Dec;48(6):1764-1778.
Weissferdt A, et al. Pleuromediastinal Epithelial-Myoepithelial Carcinomas: A Clinicopathologic and Immunohistochemical Study of Two Cases. Am J Clin Pathol. 2016 Dec;146(6):736-740.
Wu HH, et al. Utilization of Cell-Transfer Technique for Molecular Testing on Hematoxylin-Eosin-Stained Sections: A Viable Option for Small Biopsies That Lack Tumor Tissues in Paraffin Block. Arch Pathol Lab Med. 2016 Dec;140(12):1383-1389.
Zhou F, Moreira AL. Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations. Arch Pathol Lab Med. 2016 Dec;140(12):1331-1337