Welcome to the latest edition of Pulmonary Pathology Reviews, a multi-institutional journal club focused on literature relevant to those with an interest in diagnostic pulmonary pathology. Today's journal club comes to you from Kristine Konopka, pulmonary pathology fellow and soon to be Assistant Professor at the University of Michigan, and yours truly, Jeffrey Myers also at the University of Michigan. We canvassed articles from May editions of selected journals to identify a total of 13 papers, 4 of which seemed worthy of discussion (more so before we read them than after!) and another 9 included for notation. What follows is an OVERVIEW highlighting what's hot and what's not, followed by an ARTICLE INDEX with links to PubMed abstracts (full version if your institution is appropriately licensed. Click here if you want the CliffsNotes version, a PDF file compressing each article into summaries no larger than a single page. And click here if you want to download the MP3 audiofile of the teleconference as it went down at 09:15 EDT on Monday, June 29th.
As is the long time trend for this journal club, articles on lung cancer dominated this month's catch, including two focusing on the prognostic significance of overlapping histologic features: tumor spread through air spaces (STAS) and a micropapillary growth pattern. Spoiler alert . . . STAS and a micropapillary growth pattern are related! It turns out that in otherwise small, early stage adenocarcinomas STAS, described as having a micropapillary pattern in nearly two thirds of cases, predicts for recurrence in those patients who undergo less than lobectomy but had minimal impact on overall survival at 5 years. STAS had no prognostic value in patients undergoing lobectomy. In a large retrospective review of 525 resected adenocarcinomas, a little bit (≥ 1%, < 5%) of a micropapillary growth pattern mattered a little when it came to overall survival, but only tumors with 5% or more showed a statistically significantly worse disease free survival compared to patients with none (ie, < 1%).
In a comprehensive review of the multi-institutional Lung Cancer Mutation Consortium (LCMC), Lynette Sholl and associates showed consistency of results across different multiplex assays, with remarkably concordant results for a panel of small mutations in 8 genes, ALK rearrangements, and MET amplification. Detection rates were similar across all three specimen types (biopsy, cytology, surgicals) for those specimens in which sufficient material was available. Failure (QNS) rates varied, however, and were predictably highest for cytology specimens (35%) followed by biopsies (26%) and surgicals (5%). So if you want to do something good for patients, put protocols in place to limit utilization for unnecessary immunohistochemistry (or excessive routine histology for that matter) and preserve for additional testing!
Discussion articles finished up with another look at thymomas (And BTW, when did this get so hot? . . . and why?!). In a messy retrospective review collecting material from two European academic medical centers, Green and colleagues showed that in WHO type A and AB thymomas necrosis predicted for higher stage in a cohort of patients for which there were apparently no recurrences and no tumor-related deaths (although follow-up information incomplete). Is it just me, or are we spending more and more time subdividing patients into increasingly meaningless subgroups?!
Articles for notation didn’t include much that was new other than the usual list of potential biomarkers, most of dubious significance (olfactomedin 4 and receptor for hyaluronic acid-mediated motility in NSCLC, PD-L1 in thymoma, and LATS1 in mesothelioma), to add to the mind-numbing straw already weighing heavily on your back. Application of EGFR mutation-specific antibodies to distinguish adenocarcinoma from benign hyperplasia in small biopsies proved potentially useful in a subset of patients but did not seem ready for prime time to this reviewer. Yet another study showed that immunostains are pretty good but not perfect for subclassifying NSCLC on small biopsies. Abe et al reminded us that ALK FISH can yield false negative results when applied to small biopsies. Robert Homer showed that we don’t always agree with each other when it comes to staging multiple intrapulmonary cancers (I know . . . I too was SHOCKED)! The ONLY paper worthy of note in the category of non-neoplastic diseases demonstrated a previously unreported germline mutation in TINF2 in a patient with early onset UIP and a familial short telomere syndrome that included infertility in the proband and other family members.
Kadota et al. Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas. J Thorac Oncol 2015;10: 806-14.
Lee et al. Clinical Impact of Minimal Micropapillary Pattern in Invasive Lung Adenocarcinoma. Prognostic Significance and Survival Outcomes. Am J Surg Pathol 2015;39: 660-6.
Sholl et al. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma. The Lung Cancer Mutation Consortium Experience. J Thorac Oncol 2015;10: 768-77.
Green et al. Type A and AB thymomas: histological features associated with increased stage. Histopathology 2015;66: 884-91.
Articles for notation
Mimori et al. Novel use for an EGFR mutation-specific antibody in discriminating lung adenocarcinoma from reactive pneumocyte hyperplasia. Histopathology 2015;66: 816–23.
Zachara-Szczakowski et al. Accuracy of classifying poorly differentiated non–small cell lung carcinoma biopsies with commonly used lung carcinoma markers. Hum Pathol 2015;46: 776-82.
Abe et al. Heterogeneity of Anaplastic Lymphoma Kinase Gene Rearrangement in Non–Small-Cell Lung Carcinomas. J Thoracic Oncol 2015;10: 800-5.
Su et al. Low expression of olfactomedin 4 correlates with poor prognosis in smoking patients with non–small cell lung cancer. Hum Pathol 2015;46: 732-8.
Augustin et al. Receptor for hyaluronic acid-mediated motility (RHAMM, CD168) expression is prognostically important in both nodal negative and nodal positive large cell lung cancer. J Clin Pathol 2015;68: 368-73.
Homer. Pathologists’ Staging of Multiple Foci of Lung Cancer. Poor Concordance in Absence of Dramatic Histologic or Molecular Difference. Am J Clin Pathol 2015;143: 701-6.
Katsuya et al. Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer 88 (2015) 154-159.
Miyanaga et al. Hippo Pathway Gene Mutations in Malignant Mesothelioma: Revealed by RNA and Targeted Exon Sequencing. J Thoracic Oncol 2015;10: 844-51.
Alder et al. Exome Sequencing Identifies Mutant TINF2 in a Family With Pulmonary Fibrosis. Chest 2015; 147(5): 1361-8.