Welcome to a frigid edition of Pulmonary Pathology Reviews, a multi-institutional journal club intended to keep pace with the fast paced peer-reviewed literature relevant to those with an interest in diagnostic thoracic pathology. Today's journal club, the last of 2016, comes to you courtesy of Joe Maleszewski at Mayo Clinic Minnesota where the projected high temperature is 20 degrees Fahrenheit. What follows is Joe's OVERVIEW, highlighting what's hot and what's not in articles that appeared in print in November issues of selected journals. His OVERVIEW is followed by an ARTICLE INDEX with links to PubMed abstracts for those articles chosen for discussion and others added for notation only. Click here for Joe's article summary intended to save you the trouble of having to read all of the details. And if you want to hear the teleconference as it unfolded at 08:15 on Monday, December 19th, click here to download or stream an MP3 audiofile of the proceedings.
There were 37 articles relevant to pulmonary pathology during the month of November. As usual, the lion’s share were on various topics of neoplastic disease, while only 2 were related to non-neoplastic topics. With that said, there was a solid number of reviews this month (8), some of which were excellent reviews of non-neoplastic papers. I would certainly highlight the really excellent retrospective on the life and work of Dr. Louis “Pepper” Dehner in the field of pulmonary and pleural pathology. Four original manuscripts were chosen for more in-depth discussion.
Huynh and colleagues present a large study of PD-L1 (the companion diagnostic and the forefront of most of our minds these days) and the tumor microenvironment in lung adenocarcinomas. As we are all aware, there is a certain “all over the map” quality to data, in the literature, on the significance of PD-L1 as it pertains to outcomes. This paper adds a sizeable cohort to such. In doing so, they have provided a detailed survey of the what factors (both histologic and clinical) correlate with the inflammatory infiltrate in and around tumors as well as the reactivity of the tumor with PD-L1. Their finding of an association of PD-L1 with KRAS mutant tumors provides evidence in support of the notion that blockade of the PD-1/PD-L1 axis may be an attractive target for a subset of those individuals.
White et al published on a series of biomarkers that have previously been reported elevated in a series of IPF/UIP patients. Their blood-based tests appear to correlate well with the presence of IPF and also appear to be reasonably discriminatory in a population of ILD patients. This intriguing finding is certainly worthy of additional study as it may ultimately prove diagnostically useful, particularly in those too frail to undergo surgical biopsy.
From the world of lung transplantation, Eguiluz-Gracia and colleagues have set out to study human alveolar macrophages in effort to gain a better understanding of their life cycle. Specifically, they studied a transplant population for 2 years and found that resident graft macrophages “hang around” for some time after transplantation and are still a significant population at the 2 year mark. Peripheral blood monocytes also contribute to the resident population via migration/phenotype-switch. This raises interesting prospects for potential treatments into graft dysfunction as well as diseases of the alveolar macrophage (like alveolar proteinosis).
Lastly, Righi et al. report on another hot topic – BAP1 in malignant mesothelioma. They find that BAP1 mutations are more commonly seen in epithelioid and biphasic mesotheliomas and associated with better prognosis. Because of this finding, they advance the idea that BAP1 retention may help in the setting of atypical spindle cells when trying to decipher whether or not it is biphasic or epithelioid with reactive, atypical, mesothelial proliferation.
Aside from those articles for discussion, I would also point out two really excellent reviews. The first is by Dr. Boussiotis from Beth Israel, published in the New England Journal, on the topic of the PD-1 checkpoint. It nicely summarizes the current understanding of this important immuno-oncologic concept. The other is by Nakahira and colleagues on the concept of autophagy in pulmonary disease. As you all probably heard, this year’s Nobel in Physiology or Medicine was awarded for work on autophagy so it’s really all the rage right now, in a number of disciplines (including both pulmonary and cardiovascular pathology!)
Boussiotis, Vassiliki. Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway. N Engl J Med 2016;375:1767-78.
Bubendorf, Lukas et al. Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch (2016) 469:489-503
Casagrande, Arianna, et al. Association between Congenital Lung Malformations and Lung Tumors in Children and Adults: A Systematic Review. Journal of Thoracic Oncology. Vol 11 No. 11:1837-1845
Cottin V et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss) . Eur Respir J 2016; 48: 1429–1441
Cottin V. Lung biopsy in interstitial lung disease: balancing the risk of surgery and diagnostic uncertainty . Eur Respir J 2016; 48: 1274–1277
Eguiluz-Gracia, Ibon et al. Long-term persistence of human donor alveolar macrophages in lung transplant recipients. Thorax 2016;71:1006-101
Facchinetti, Francesco, et al. Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC. Journal of Thoracic Oncology Vol. 11 No. 11:1819-1836
Gray, Steven, et al. PD-L1 as a Companion Biomarker for Immune Checkpoint Inhibitors in NSCLC: Should RNA ISH (RISH) Be Considered? Letter to the Editor. Journal of Thoracic Oncology. Vol. 11 No. 11:143
Huynh, Tiffany et al. Programmed Cell Death Ligand 1 Expression in Resected Lung Adenocarcinomas: Association with Immune Microenvironment. Journal of Thoracic Oncology. Vol. 11 No. 11:1869-1878
Hutchinson et al. Surgical lung biopsy for the diagnosis of interstitial lung disease in England: 1997–2008. Eur Respir J 2016; 48: 1453–1461.
Jang, Sin Sung et al. Custom Gene Capture and Next-Generation Sequencing to Resolve Discordant ALK Status by FISH and IHC in Lung Adenocarcinoma. Journal of Thoracic Oncology Vol. 11 No. 11:1891-1900
Kao, Hua-Lin et al. Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinoma: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence iun situ hybridization methods. Lung Cancer 101 (2016) 40-47
Khanna, Swati, et al. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T-Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptibel to ADCC by the Anti-PD-L1 Antibody Avelumab. Journal of Oncology. Vol. 11 No. 11:1993-2005
Kittaneh, Muaiad. BRCA1-Associated Protein 1 Testing in Cancer. Letter to the Editor. Journal of Thoracic Oncology. Vol. 11 No. 11:e141-3145
Klinger JR. Plasma nitrite/nitrate levels: a new biomarker for pulmonary arterial hypertension? Eur Respir J 2016; 48: 1265–1267
Maher, Toby. Blood-based Diagnosis of Idiopathic Pulmonary Fibrosis. Fantasy or Reality? (Editorial). American Journal of Respiratory and Critical Care Medicine. Volume 194 Number 10. November 15.2016.
Marisa Dolled-Filhart, et al. Development of a Companion Diagnostic for Pembrolizumab in Non-Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1. Arch Pathol Lab Med-Vol 140, November 2016
Michal M et al. Histiocytosis With Raisinoid Nuclei: A Unifying Concept for Lesions Reported Under Different Names as Nodular Mesothelial/Histiocytic Hyperplasia, Mesothelial/ Monocytic Incidental Cardiac Excrescences, Intralymphatic Histiocytosis, and Others A Report of 50 Cases. Am J Surg Pathol 2016;40:1507–1516
Miller, Ross A. et al. PD-1//PD-L1, Only a Piece of the Puzzle. Arch Pathol Lab Med-Vol 140, November 2016
Nakahira, Kiichi et al. Autophagy in Pulmonary Diseases. American Journal of Respiratory and Critical Care Medicine. Volume 194 Number 10. November 15, 2016.
Neuman, Tzahi et al. A Harmonization Study for the Use of 22C3 PD-L1 Immunohistochemical Staining on Ventana's Platform. Journal of Thoracic Oncology. Vol. 11 No. 11:1863-1868
Raparia, Kirtee et al. Transbronchial Lung Cryobiopsy for Interstitial Lung Disease Diagnosis. A Perspective From Members of the Pulmonary Pathology Society. Arch Pathol Lab Med-Vol 140, November 2016
Righi, Luisella et al. BRCA1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: A Large Retrospective Study. Journal of Thoracic Oncology. Vol. 11 No. 11:2006-2017
Ritter JH et al. Pulmonary and pleural pathology: Contributions of Dr. Louis “Pepper” Dehner. Sem Diagn Pathol 33 (2016) 450–461.
Roy-Chowdhuri, Sinchita et al. Biomarker Testing in Lung Carcinoma Cytology Specimens. A Perspective From Members of the Pulmonary Pathology Society. Arch Pathol Lab Med. 2016;140:1267-1272
Ruano-Ravina, Alberto et al. Residential radon, EGFR mutations and ALK alterations in never-smoking lung cancer cases. Eur Respir J 2016; 48: 1462-1470
Shukuya, Takehito, et al. Relationship between Overall Survival and Response or Progression-Free Survival in Advanced Non-Small Cell Lung Cancer Patients Treated with Anti-PD-1/PD-L1 Antibodies. Journal of Thoracic Oncology. Vol. 11 No. 11:1927-1939
Song Zhengbo, et al. Clinicopathologic characteristics, genetic variability and therapeutic options of RET rearrangements patients in lung adenocarcinoma. Lung Cancer 101 (2016) 16-21
Takada, Kazuki, et al. Clinical Significance of PD-L1 Protein Expression in Surgically Resected Primary Lung Adenocarcinoma. Journal of Thoracic Oncology Vol. 11 No. 11:1879-1890
Thomas, Anish et al. Expression of mesothelin in thymic carcinoma and its potential therapeutic significance. Lung Cancer 101 (2016) 104-110
Thongprast, Sumitra et al. The prevalence of expression of MAGE-A3 and PRAME tumor antigens in East and South East Asian non-small cell lung cancer patients. Lung Cancer 101 (2016) 137-144
Todd, Nevins W et al. Microscopic organizing pneumonia and cellular non-specific interstitial pneumonia are widespread in macroscopically normal-appearing lung tissue in idiopathic pulmonary fibrosis. The Journal of Heart and Lung Transplantation, Vol 35, No 11, November 2016
Toki Maria I et al. EGFR-GRB2 Protein Colocalization is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma. Journal of Thoracic Oncology. Vol. 11 No. 11:1901-1911
Viola et al. Dieulafoy’s disease of the airways: a comprehensive review of a rare entity. Histopathology 2016 69(5), 883-897.
Viola P et al. Follicular dendritic cell tumour/sarcoma: a commonly misdiagnosed tumour in the thorax. Histopathology 2016, 69, 752–761.
Weissferdt A et al. Ectopic Hamartomatous Thymoma—New Insights Into a Challenging Entity A Clinicopathologic and Immunohistochemical Study of 9 Cases. Am J Surg Pathol 2016;40:1571–1576
White, Eric et al. Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias. American Journal of Respiratory and Critical Care Medicine. Volume 194 Number 10. November 15, 2016.
Williams, Andrew S. et al. ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemical and fluorescence in situ hybridization. Virchows Arch (2016) 469:533-540
Yanagawa, Naoki et al. The Clinical Impact of Solid and Micropapillary Patterns in Resected Lung Adenocarcinoma. Journal of Thoracic Oncology. Vol. 11 No. 11:1976-1983