Pulmonary Pathology Review

April 2013 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, a monthly multi-institutional journal club in which one of several participating faculty summarizes what's hot and what's not in papers relevant to pulmonary pathology that appeared in the peer-reviewed print literature in the preceding month.  This month comes to us from the University of Michigan famous not only for its basketball but also Lindsay Schmidt, Assistant Professor of Pathology.  Check out her OVERVIEW below for a thumbnail of articles that she highlighted from March journals.  If you want the CribNotes version of the articles themselves click here to get her article summaries as a PDF file.  Lindsay's OVERVIEW is followed by an ARTICLE INDEX that includes links to PubMed abstracts (and full text versions if your institution allows it) for all included articles.  And if you want to hear how it all went down in our teleconference at 09:15 EDT on Monday, April 29th, click here.

OVERVIEW
I found 18 articles in our journals this month that I felt would be of interest to the group. As is the norm, most are neoplastic, but there are some interesting nonneoplastic articles as well, focusing on some esoteric topics that don't often get a lot of press. The three discussion articles this month all come from the neoplastic side of things.

The first article for discussion (Grogg KL et al.) comes from the Mayo group, and is a very interesting look at nodular pulmonary amyloidosis. This unusual entity is something I'm sure we all get to see from time to time, and this paper did an excellent and very thorough job of immunophenotyping a good set of these tumors.

The second paper (Doxtader EE et al.) comes from the SUNY group, and is my favorite kind of study--one based on H&E! This group looked at the biopsy site changes introduced into lung cancers through needle biopsies, and presented the interesting differential diagnosis of desmoplastic stroma. A good topic to review in light of the proposed reclassification of lung tumors.

The last article for discussion (Sholl LM et al.) is yet another look at ALK translocations. In this case, it is a comparison of FISH and immunohistochemistry that makes the case for using BOTH methods instead of one versus the other.

For notation, there are 10 additional neoplastic disease articles. Cho et al. present data on using tumor markers performed on aspirate fluid in diagnosing nonsmall cell lung carcinoma. A second ALK article this month (Conde et al) presents the rates of ALK translocation-associated lung adenocarcinomas seen at one intitution. In an article in the New England Journal,  Friboulet et al. take an interesting look at a previously described marker, ERCC1, and its implications in chemotherapeutic response. Two groups (Ishii et al. and Kadota et al.) present different immunohistochemical markers as prognostic factors in small cell lung cancer and adenocarcinoma respectively. Another prognostic paper, Liu et al. describe the prognostic factors in N1-stage II NSCLC. For the economists in the group, an Australian group (Steinfort et al.) take a look at the economic impact of method of biopsy (transbronchial versus needle) in a very hypothetical way. There are two mesothelioma articles this month: Ordonez describes the histologic, immunohistochemical, and ultrastructural findings in signet-ring cell mesothelioma, and Lee et al. describe several more IHC markers attempting to distinguish benign from malignant mesotheliomas. Lastly, William et al. publish an excellent review of lymphoproliferative neoplasms on the lung in Archives.

Five nonneoplastic articles were included for notation. Three focused on transplant patients: DeNicola et al. describe the findings in patients with anti-HLA antibodies, a topic we have discussed in this group before, and Ofek et al. describe the pathologic findings of restrictive allograft syndrome. The last, Yarmus et al., describe a newer technique being used to perform transbronchial biopsies to evaluate lung allograft rejection. Nakajima et al. present the pathologic findings of H5N1 influenza, and Furuya et al. describe the pulmonary features of Birt-Hogg-Dube syndrome and how to distinguish it from other cystic lung disease.

Happy reading!

ARTICLE INDEX
Discussion articles
Grogg KL et al. "Nodular pulmonary amyloidosis is characterized by localized immunoglobulin     deposition and is frequently associated with an indolent B-cell lymphoproliferative disorder." Am J Surg Pathol 37: 406-412.

Doxtader EE et al. "Biopsy-site changes in lung adenocarcinoma with prior core needle biopsy: a potential pitfall in the assessment of stromal invasion." Am J Surg Pathol 37: 443-446.

Sholl LM et al. "Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas." J Thoracic Oncol 8: 322-328.

Articles for notation
Neoplastic diseases
Cho A et al. "NSCLC subtype prediction using cytologic fluid specimens from needle aspiration biopsies." Am J Clin Pathol 139: 309-316.

Conde E et al. "The ALK translocation in advanced non-small-cell lung carcinomas: preapproval testing experience at a single cancer centre." Histopathology 62, 609-616.

Friboulet L et al. "ERCC1 isoform expression and DNA repair in non-small cell lung cancer." NEJM 368: 1101-1110.

Ishii J et al. "POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer." Pathol International 63: 158-168.

Kadota K et al. "Thyroid transcription factor-1 expression is an independent predictor of recurrence and correlates with the IASLC/ATS/ERS histologic classification in patients with stage I lung adenocarcinoma." Cancer 119: 931-938.

Lee AF et al. "IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations." Am J Surg Pathol 37: 421-426.

Liu CY et al. "Prognostic factors in resected pathological N1-stage II nonsmall cell lung cancer." Eur Respir J  41: 649-655.

Ordonez NG. "Mesothelioma with signet-ring cell features: report of 23 cases." Mod Pathol 26: 370-384.

Steinfort DP et al. "Radial probe EBUS versus CT-guided needle biopsy for evaluation of peripheral pulmonary lesions: an economic analysis." Eur Respir J 41: 539-547.

William J et al. "Lymphoproliferative neoplasms of the lung: a review." Arch Pathol Lab Med 137: 382-391.

Nonneoplastic diseases
DeNicola MM et al. "Pathologic findings in lung allografts with anti-HLA antibodies." J of Heart and Lung Transplantation 32:326-332.

Furuya M, Nakatani Y. "Birt-Hogg-Dube syndrome: clinicopathological features of the lung." J Clin Pathol 66: 178-186.

Nakajima N et al. "Pathological study of archival lung tissue from five fatal cases of avian H5N1 influenza in Vietnam." Mod Pathol 26: 357-369.

Ofek E et al. "Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis." Mod Pathol 26: 350-356.

Yarmus L et al. "Cyroprobe transbronchial lung biopsy in patients after lung transplantation." Chest. 143(3): 621-626.

 

March 2013 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, a multi-institutional journal club dedicated to keeping you abreast of what's hot and what's not in the fast paces world of pulmonary pathology!  Today's  comes to us courtesy of Joanne Yi at Mayo Clinic Minnesota where spring is struggling to make its presence known on a day with lows still hovering below 20 degrees fahrenheit and a forecast high just one degree warmer than freezing!  What follows is Joanne's OVERVIEW summarizing the highs and lows in peer reviewed articles that made it to print in February 2013.  Click here for her Table of Contents for a snapshot of the ground she covered this month and page numbers to help you navigate her PDF summary.  Below her OVERVIEW is an ARTICLE INDEX with links to PubMed abstracts and full text versions of the articles if your institutional license allows it.  If you want to hear how it all went down at 8:15 CDT on Monday, March 25th, click here to download an MP3 audiofile (be patient - a big file that usually takes a while but often worth the wait!).

OVERVIEW
I included 27 articles found in February journals for our review and they were definitely more on neoplastic diseases as has been the trend for a while.  A few studies on nonneoplastic diseases, however, published mainly in Blue journal raised interesting questions with some potential therapeutic implication in the future. 

Onozato et al evaluated the clinical significance of tumor island, defined as an isolated, large collection of tumor cells within alveolar space present at the periphery of the lesion.  They found that over half of the patients with tumor islands had recurrence within 5 years, even in the stage IA cohort and concluded that tumor islands are likely associated with worse prognosis after resection in early-stage lung adenocarcinoma. 

Greenland et al reported the association of large airway bronchitis with bronchiolitis obliterans syndrome (BOS) using their single center cohort of lung tranplantation patients who had surveillance endobronchial biopsies along with transbronchial biopsies as protocol between 1997-2011.  They found that the maximum inflammation score in endobronchial bx at 90 days was more accurate than A or BR scores of transbronchial biopsies in predicting development of BOS in their cohort

Shu et al examined the biologic nature of adenosquamou carcinoma by evaluation of thymidylate synthase (TS) expression that is known to be associated with resistance to pemetrexed in squamous cell carcinomas.  TS expression in adenosquamous carcinoma was comparable to that in squamous cell carcinoma, although the mutation status was more in keeping with adenocarcinomas with EGFR and KRAS mutations, even in the area with squamous morphology on microdissected tumors.  Thus, the adenosquamous carcinoma might not be a simple mixture of squamous cell carcinoma and adenocarcinoma. 

Sugano et al reported hepatocyte nuclear transcription factor 4 alpha (HNF4 expression in invasive mucinous adenocarcinomas of the lung, as expected, given its expression in mucinous tumors of other organs.  Most important and interesting aspect, though, is the fact that 4 of their 37 invasive mucinous adenocarcinoma cases were HNF4 negative and these 4 cases harbored an ALK fusion.  Therefore, they suggested that invasive mucinous adenocarcinomas of the lung may be a molecularly heterogeneous group of tumors. 

There were a few more papers on lung cancers in February.  Matsuguma et al evaluated the characteristics of subsolid pulmonary nodules for determining the optimal follow-up with CT scans, which has become a huge issue after the positive results by the National Lung Screening Trial started in 2002.  Helpful clinical characteristics were reported by Spraker et al based on SEER database.  Takahashi et al reported distinctive histopathological features of lepidic growth predominant node-negative adenocarcinomas 3 – 5 cm in size and reported lepidic predominant pattern as an independently faorable prognostic factor in these group of patients.  They did not assess the effect of the presence of unfavorable subtype of histology such as solid and micropapillary features.  Rao et al reported clinicopathologic features of 24 intrapulmonary solitary fibrous tumors, which appear pretty much comparable to extrapulmonary SFTs.  Even if it is not exactly on lung tumors, a study by Jee et al was included which could be potentially helpful in the diagnosis of pulmonary mucoepidermoid carcinoma.  They reported genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma.  Wu SG et al showed frequent EGFR mutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis, as compared to stage IV cancers that could mimic this.  Oxnard et al pointed out that lung cancers harboring EGFR exon 20 insertions behave like EFGR wild type tumors in terms of prognosis and responsiveness to EGFR inhibitors.  Napsin is not as good as TTF-1 in mucin producing adenocarcinomas as shown by Wu et al, which we noted in sarcomatoid carcinomas (Jenn Boland presented the data at USCAP this year).  There seems to be an epidemic of lung cancers in HIV patients after their life expectancy go much improved after antiviral therapy according to Winstone et al.  Finally, Toth et al. actually did a research to show that combination of histology and cytology on EBUS specimen is better than either method alone, though it seems to me pretty obvious without any study.

Among non-neoplastic papers published in February journals, a study by Miyoshi et al. seemed to me most interesting.  They showed that the integrity of alveolar epithelial cells promoted by epithelial Pten is essential in preventing acute lung injury and lung fibrosis.  Dakhlallah D et al showed an epigenetic feedback loop between miR17~92 and DNMT-1 in lung fibrosis.  There seems to be an association between aberrant DNA methylation and miRNA expression in IPF, which might prove to be useful as therapeutic target.  Beaty et al effectively showed that carefully selected patients with pretransplant malignancy could be still the candidates for lung and heart transplantations.  Kamphuis et al argued for the roles of B-cells in sarcoidosis based on their very elegant and complex methods that I could not quite follow.  There were a few reviews, commentaries and case reports that I thought could be very useful for both clinical practice or your presentations when needed.

ARTICLE INDEX
Articles for Discussion
Onozato, ML et al. Tumor Islands in Resected Early-stage Lung Adenocarcinomas are Associated With Unique Clinicopathologic and Molecular Characteristics and Worse Prognosis. Am J Surg Pathol 2013;37:287-294

Greenland, JR et al. Association of Large-Airway Lymphocytic Bronchitis With Bronchiolitis Obliterans Syndrome. Am J Respir Crit Care Med 2013;187(4): 417-423

Shu C et al. Thymidylate synthase expression and molecular alterations in adenosquamous carcinoma of the lung. Mod Path 2013;26:239-246

Sugano M et al. HNF4α as a Marker for Invasive Mucinous Adenocarcinoma of the Lung. Am J Surg Pathol 2013;37(2):211-218

Articles for notation – Neoplastic
Matsuguma H et al. Characteristics of Subsolid Pulmonary Nodules Showing Growth During Follow-up With CT Scanning. CHEST 2013;143(2):436-443

Spraker MB et al. An Analysis of Patient Characteristics and Clinical Outcomes in Primary Pulmonary Sarcoma. J Thorac Oncol 2013;8: 147-151

Takahashi Y et al. Distinctive histopathological features of lepidic growth Predominant node-negative adenocarcinomas 3 – 5 cm in size. Lung Cancer 2013;79:118-124

Rao N et al. Intrapulmonary Solitary Fibrous Tumors. Clinicopathologic And Immunohistochemical Study of 24 Cases. Am J Surg Pathol 2013;37(2):155-166

Jee KJ et al. Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma. Mod Path 2013;26: 213-222

Wu SG et al. Frequent EGFR mutations in nonsmall cell lung cancer Presenting with miliary intrapulmonary carcinomatosis. Eur Respir J 2013;41:417-424

Oxnard GR et al. Natural History and Molecular Characteristics of Lung Cancers Harboring EGFR Exon 20 Insertions. J Thor Oncol 2013;8: 179-184

Toth JW et al. Specimen Processing Techniques for Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. Ann Thorac Surg 2013;95:976-81

Iwano S et al. What causes false-negative PET findings for solid-type lung cancer? Lung Cancer 2013;79:132-136

Wu J et al. Napsin A Expression in Primary Mucin-Producing Adenocarcinomas of the Lung. Am J Clin Pathol 2013;139:160-166

Harada H et al. Methylation of Breast Cancer Susceptibility Gene 1 (BRCA 1) Predicts Recurrence in Patients With Curatively Resected Stage I Non-Small Cell Lung Cancer. Cancer 2013;119:792-8

Moua T et al. Frequency of Medastinal Lymphadenopathy in Patients With Idiopathic Pulmonary Arterial Hypertension. CHEST 2013;143(2): 344-348

Articles for notation – Non-neoplastic
Miyoshi K et al. Epithelial Pten Controls Acute Lung Injury and Fibrosis by Regulating Alveolar Epithelial Cell Integrity. Am J Respir Crit Care Med 2013;187(3):262-275

Dakhlallah D et al. Epigenetic Regulation of miR-17~92 Contributes to the Pathogenesis of Pulmonary Fibrosis. Am J Respir Crit Care Med 2013;187(4)397-405

Kamphuis LS et al. Perigranuloma Localization and Abnormal Maturation of B Cells. Am J Resp Crit Care Med 2013;187(4):406-416

Beaty CA et al. Pre-transplant malignancy: An analysis of outcomes after Thoracic organ transplantation. J Heart Lung Transplant 2013;32:202-211

Reviews, Commentaries and Case reports
Lang IM et al. Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding. Eur Respir J 2013;41:462-468

Winstone TA et al. Epidemic of Lung Cancer in Patients With HIV Infection. CHEST 2013;143(2):305-314

Weibel ER. It Takes More than Cells to Make a Good Lung. Am J Respir Crit Care Med 2013; 187(4): 342-346

Blackhall F et al. The impact of the multidisciplinary team of molecular profiling for personalized therapy in non-small cell lung cancer. Lung Cancer 2013;79:101-103

Ellison G et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol 2013;66:79-89

Geurts-Giele WRR et al. Molecular diagnostics of a single multifocal non-small cell lung cancer case using targeted next generation sequencing. Virchows Arch 2013;462:249-254

Steinestel K et al. Fatal thromboembolism to the left pulmonary artery by locally applied hemostatic matrix after surgical removal of spinal schwannoma: a case report. Human Pathology 2013;44:294-298

February 2013 Edition

Today brings the latest edition of Pulmonary Pathology Reviews, a blog intended to share assets generated by a multi-institutional journal club hosted in a monthly teleconference focusing on print literature focusing on diagnostic pulmonary pathology.  Today's journal club comes to us courtesy of Dr. Anja Roden at the Mayo Clinic in Rochester, MN.  What follows is her OVERVIEW of peer reviewed publications that appeared in print in January 2013.  Click here if you want to see her PDF summary of the articles listed in the ARTICLE INDEX below.  The ARTICLE INDEX provides links to PubMed abstracts and full text articles for those whose institutional licenses allow it.  And if you want to hear how it all went down at 8:15 CST on Monday, February 25th, click here to download an MP3 audiofile of the teleconference (be patient . . . sometimes takes a while to download).

OVERVIEW
The majority of the articles that were selected from the January editions of our journals discussed neoplastic lung diseases, a few focused on non-neoplastic processes. Many of the topics covered ongoing discussions in the pulmonary community such as: (i) Interobserver agreement in NSCLC; (ii) EGFR and KRAS mutations in NSCLC; (iii) The ALK mutation analysis in NSCLC; (iv) Prognostic significance of histologic features of lung adenocarcinoma; (v) The relationship between smoking, COPD and lung cancer; (vi) The distinction between malignant mesothelioma and reactive pleuritis; and (vii) Antibody mediated rejection in lung allografts. Other studies focused on granulomas in common variable immunodeficiency disease and how to differentiate CVID from sarcoidosis or the diagnostic accuracy of histology and cytology for Aspergillus spp. There was also an interesting report on volumetric optical frequency domain imaging of pulmonary pathology and how it correlates to histologic findings and although this imaging technique is still in its investigational stage, it might become a helpful adjunct mean to obtain better biopsies.

For discussion I have chosen four articles that I thought might be of interest for our daily practice and an article about the prognostic significance of histopathologic parameters and nuclear grade of NSCLC.

Hata et al studied EGFR mutations in SQCC amongst Japanese patients using a highly sensitive PCR method. The authors identified a relative high incidence of EGFR mutations (13.3%) in lung SQCC. EGFR mutations did not show any prognostic significance in that patient population. Furthermore, some of the cases that were included showed TTF-1 and/or napsin expression by the neoplastic cells. Moreover, CK14 and p63, markers that used for squamous differentiation in this article, have been previously shown to be expressed in some adenoCa as well. Therefore, the true incidence of EGFR mutations in SQCC and the clinical characteristic of these patients are still unclear.

A retrospective study by Lobo et al addressed whether donor-specific antibodies (DSA) are linked to cystic fibrosis (CF), antibody mediated rejection (AMR), and bronchiolitis obliterans syndrome (BOS) in lung transplant patients. The authors found that almost a third of the patients developed DSA after lung transplant with a higher proportion of CF patients, anti-HLA DQ specificity, and higher incidence of BOS. AMR developed more commonly in patients with DSA than patients without DSA. Although there was no significant difference in survival, many patients in the DSA group were thought to have died from AMR or complications associated with treatment of AMR. DAD appeared to be more common in patients with DSA.

Conklin et al studied multiple antibody and detection system combinations for IHC for ALK in an unselected patient population of NSCLC using FISH as gold standard. The authors concluded that the antibodies 5A4 by Novocastra and D5F3 by Cell Signaling with ADVANCE detection system showed the best combination of sensitivity and specificity as a screening tool for ALK rearrangement. The authors confirm that IHC might be a reliable screening tool for ALK rearrangement but it depends on antibody and detection system. In contrast to previous studies, Conklin et al did not identify a correlation between IHC score and FISH results. However, the number of ALK positive cases in this study was very low.

Predominant histologic patterns and mitotic rate were identified to have prognostic significance in resected lung adenoCa and were proposed to be used for a grading system alongside staging by van der Thuesen et al. Lepidic predominant tumors had the best prognosis while solid predominant tumors had the worst. Lepidic and papillary predominant tumors had the lowest mitotic rate while solid predominant tumors had the highest.

Bouvry D et al compared clinical, radiological and histopathologic characteristics of patients with common variable immunodeficiency disorder (CVID) to patients with pulmonary sarcoidosis and found that lung manifestations are different with poor general survival and morbidity in CVID because of infection, bronchiectasis and lymphoproliferative disorder; however, interstitial lung disease was not a critical determinant of prognosis in these patients. The quality of the granulomas in CVID was reported as ‘sarcoid-like’, however, in some patients with CVID the granulomas contained some degree of lymphoid infiltration. The distribution of the granulomas in CVID was not described.

Amongst articles for notation, under the category neoplasia, Wang W et al showed that SCLC with increased CD45+ cells within the tumor have a better survival than patients with SCLC with lower CD45+ cells. The predictive value of CD45+ cells in SCLC appears to be independent of stage and performance status. Grilley-Olson et al show that interobserver reproducibility for NSCLC using the 2004 WHO classification is poor but increases with collapsing the classification to 10 header categories of histologic diagnoses and increases further to moderate agreement when just using SQCC vs non-SQCC categories. Interobserver reproducibility increases with increased confidence of the pathologist, increased expertise of the pathologist in pulmonary pathology, longer experience of the pathologist, better differentiation of the tumor and better digital slide quality. It was proposed that agreement might further improve with ancillary staining panels for poorly differentiated Ca, improved slide quality and simplified classification.

Wu D et al confirms that p16 FISH but not p16 promoter methylation is useful to distinguish between sarcomatoid mesotheliomas and fibrous pleuritis. Furthermore, both, p16 deletion and p16 promoter methylation were proposed as prognostic markers for malignant mesothelioma. Mogi A et al studied GLUT-1, MCT1 and MCT4 in malignant mesotheliomas and found that the combination of GLUT-1 and MCT-1/MCT-4 immunostaining might increase our capacity to distinguish malignant mesotheliomas from reactive mesothelial hyperplasia. The authors also found that mesothelioma cells preferentially utilize glycolysis for their energy supply and that suppressing glucose uptake inhibits glycolysis and cell proliferation. Bayram M et al show in a study on a population that was born in close proximity to naturally occurring asbestos (NOA) in an area in Turkey that malignant mesothelioma and pleural plaques were related to the proximity of the birthplace to NOA and that women appeared to be at higher risk then men.

Powell HA et al in a case control study of 12,062 lung cancer and 47,980 controls showed that women appear to be more susceptible to cigarette smoke than men to develop lung Ca and that women who have ever smoked moderately or heavily have a higher risk of lung cancer than men. However, those differences could not be explained by lung volume and the reason for these differences in susceptibility are only speculated. The same population is used by the same author (Powell HA et al) to identify whether COPD might represent an increased risk for lung cancer beyond the common smoking problem. However, the authors concluded that the association between COPD and lung Ca is largely due to confounding by smoking and ascertainment bias and COPD is not an independent risk factor for lung Ca.

Kim YT et al studied completely resected NSCLC and demonstrated that although EGFR mutations are predictive marker for EGFR-TKI treatment in patients with recurrence, these mutations have no independent prognostic value for NSCLC or adenoCa. Kaboyashi S et al studied compound EGFR mutations which are EGFR TKI–sensitizing mutation (e.g., G719X, exon 19 deletions, L858R or L861Q) that coexist with an uncommon mutation involving other residues of the tyrosine kinase domain of EGFR. The incidence of compound EGFR mutations appears low (14% of EGFR mutated NSCLC) but most of the tumors harboring a compound mutation responded to EGFR-TKI treatment. In a study of the prognostic value of EGFR and KRAS mutations in stage IV lung adenoCa, Johnson ML et al showed that patients with EGFR mutations lived longer and that KRAS mutation was an independent factor associated with shorter survival.

Yoshizawa A et al studied the proposed IASLC/ATS/ERS classification of lung adenoCa in a Japanese cohort. The authors found that pathological stage, size of invasion and tumor grade by the IASLC/ATS/ERS classification (low/intermediate – AIS/MIA, lepidic, acinar, papillary, IMA; high – solid, micropapillary, colloid) are associated with disease free survival (DFS) and pathological stage and IASLC/ATS/ERS classification are associated with overall survival (OS) in this patient cohort. They further confirmed that AIS/MIA (including 3 mucinous) have 100% 5-year DFS and OS. Patients with EGFR mutations had longer OS. 

Hokka D et al studied Psf3 which is involved in a complex that regulates DNA replication. Psf3 also might be required for cell proliferation, particularly immature cells such as stem cells and progenitor cells. The authors showed that Psf3 expression was associated with TNM stage, invasion of pulmonary vein and lymphatic invasion and that increased expression of Psf3 was related to poor patient prognosis. Xu X et al investigated the association between eIF3 polymorphism and the response to platinum-based chemotherapy in lung Ca and found that the A allele of rs3740556 of eIF3a might be predictive of better platinum response and appears to be associated with a favorable survival for NSCLC and SCLC. eIFs play a role in the initiation and regulation of  translation. Dong X et al studied BIRC6 in NSCLC. BIRC6 is part of the inhibitors of apoptosis proteins (IAP) that bind to and inhibit proapoptotic factors thereby suppressing drug- and radiation induced apoptosis. The results indicate that elevated BIRC6 expression might be a poor prognostic factor for patients with NSCLC and that BIRC6 protein is involved in the malignant progression of NSCLC. The authors further show that down-regulation of BIRC6 leads to sensitization of NSCLC cells to cisplatin. The significance of Sema 7a in IPF and in a mouse model of pulmonary fibrosis was studied by Reilkoff RA et al. Their data suggest that strategies targeting Sema 7a and/or aberrant Treg responses might be beneficial in IPF.

Thomas A et al investigated 5 cases of thymic epithelial neoplasm (TEN) with cardiac involvement. The authors concluded that patients with paracardial TEN should be closely monitored radiologically for cardiac involvement because development of symptoms may occur late and early recognition of intracardiac involvement might facilitate complete surgical resection. Although immediate surgical resection is indicated if hemodynamic compromise is imminent from obstructed cardiac outflow by an intracardiac lesion, long-term palliation with surgery for myocardial involvement seems poor. Induction chemotherapy may be an option in patients with no impending compromise and limited cardiac involvement. Furthermore, this report describes that the histology of the cardiac mass can differ from the original TEN. Ganeshan B et al found that CT texture (e.g., coarseness, regularity) analysis might be a potential prognostic biomarker for patients with NSCLC given the correlation between tumor texture and hypoxia.

The original articles for notation in the non-neoplastic category included the ISHLT summary statement concerning the pathology of pulmonary antibody-mediated rejection – an update from the 2012 Pathology Council of the ISHLT, authored by Berry G et al. Shah AA et al identified a diagnostic accuracy rate of surgical/cytology specimens for Aspergillus spp.of 78% when culture was used as gold standard. However, the recovery rate of Aspergillus spp. from cultures is not 100%. Hariri LP et al performed volumetric optical frequency domain imaging (OFDI) through (a) bronchoscopic airway-centered imaging and (b) parenchymal imaging. OFDI is a non-invasive imaging modality that generates high resolution cross-sectional images of tissue microstructure (2- and 3-dimensional) and a penetration depth of 2-3mm. Its resolution is <10µm - comparable to 4x microscopy. This technique might be useful to improve biopsy sampling of lung tissue in that bronchoscopic OFDI could identify optimal bx site increasing the diagnostic yield in central airway tumors (SQCC, neuroendocrine tumors – not tested yet). It also appears to be useful in identifying optimal bx site in peripheral disease.

Weissferdt & Moran reviewed staging of primary mediastinal tumors focusing on thymomas and thymic carcinomas and giving a short review of staging of mediastinal germ cell tumors. Jakobsen J et al reviewed the recent literature in regards to Ki-67 labelling index in NSCLC concluding that there does not appear to be a consensus of the prognostic value of Ki-67. Ordóñez NG published a great review on IHC to distinguish epithelioid mesothelioma from metastatic carcinoma. Popper HH provided historical aspects, morphologic findings and recent developments of interstitial lung diseases and combined literature findings with own experience.

Several interesting case reports were published including Derweduwen AM on lymphangioleiomyomatosis with extrapulmonary involvement; Kluka EM on extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with amyloid deposition presenting as cystic and nodular lung disease; Prat L on cutaneous lymphangitis carcinomatosa, a rare disease that can mimick infectious skin disease; Chai GT on Erdheim-Chester Disease, and Kurata A on intracaval and intracardiac extension of invasive thymoma complicated by superior and inferior vena cava syndrome. Hirota T described a case of a lung transplant in which morphologic features consistent with pleuroparenchymal fibroelastosis were identified and raised the question whether PPFE might be a manifestation of chronic lung rejection. 


Enjoy the reading!

ARTICLE INDEX
Articles for discussion
Hata A et al. How Sensitive Are Epidermal Growth Factor Receptor– Tyrosine Kinase Inhibitors for Squamous Cell Carcinoma of the Lung Harboring EGFR Gene–Sensitive Mutations? J Thorac Oncol. 2013;8: 89–95.

Lobo LG et al. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant 2013;32:70–77.

Conklin CMJ et al. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J Thorac Oncol. 2013;8:45-51.

Von der Thuesen JH et al. Prognostic Significance of Predominant Histologic Pattern and Nuclear Grade in Resected Adenocarcinoma of the Lung Potential Parameters for a Grading System. J Thorac Oncol. 2013;8:37-44.

Bouvry D et al. Granulomatosis-associated common variable immunodeficiency disorder: a case–control study versus sarcoidosis. Eur Respir J 2013; 41: 115–122.

Articles for notation – Neoplastic
Wang W et al. Histologic assessment of tumor-associated CD45+ cell numbers is an independent predictor of prognosis in small cell lung cancer. Chest 2013; 143(1):146-51.

Grilley-Olson JE et al. Validation of  Interobserver Agreement in Lung Cancer Assessment: Hematoxylin-Eosin Diagnostic Reproducibility for Non–Small Cell Lung Cancer. The 2004 World Health Organization Classification and Therapeutically Relevant Subsets.  Arch Pathol Lab Med. 2013;137:32–40.

Wu D et al. Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis. AJCP 2013; 139:39-46.

Mogi A et al. Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma. Virchow Archives. 2013. 462:83-93.

Bayram M et al. High Risk of Malignant Mesothelioma and Pleural Plaques in Subjects Born Close to Ophiolites. CHEST 2013; 143(1):164–171.

Powell HA et al. The association between smoking quantity and lung cancer in men and women. Chest 2013; 143(1):123-9.

Powell HA et al. Chronic Obstructive Pulmonary Disease and Risk of Lung Cancer. The Importance of Smoking and Timing of Diagnosis. J Thorac Oncol. 2013; 8: 6–11.

Kim YT et al. The Presence of Mutations in Epidermal Growth Factor Receptor Gene Is Not a Prognostic Factor for Long-Term Outcome after Surgical Resection of Non–Small-Cell Lung Cancer. J Thorac Oncol.  2013. 8:171-8.

Kobayashi, S et al. Compound EGFR Mutations and Response to EGFR Tyrosine Kinase Inhibitors. J Thorac Oncol. 2013;8:118–122.

Johnson ML et al. Association of KRAS and EGFR Mutations With Survival in Patients With Advanced Lung Adenocarcinomas. Cancer 2013;119:356-62.

Yoshizawa A et al. Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations. Analysis of 440 Japanese Patients. JTO. 2013;8: 52–61.

Hokka D et al. Psf3 is a prognostic biomarker in lung adenocarcinoma. Lung Cancer 79 (2013): 77–82.

Xu X et al. The A/G allele of eIF3a rs3740556 predicts platinum-based chemotherapy resistance in lung cancer patients. Lung Cancer 79 (2013) 65–72.

Dong X et al. Elevated Expression of BIRC6 Protein in Non–Small-Cell  Lung Cancers is Associated with Cancer Recurrence and Chemoresistance. J Thorac Oncol. 2013;8: 161–170.

Reilkoff RA et al. Semaphorin 7a1 Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-b1–induced Pulmonary Fibrosis. Am J Respir Crit Care Med Vol 187, Iss. 2, pp 180–188, Jan 15, 2013.

Thomas a et al. Characterization and Management of Cardiac Involvement of Thymic Epithelial Tumors. J Thorac Oncol. 2013;8: 246–249.

Ganeshan B et al. Non-small cell lung cancer: Histopathologic Correlates for Texture Parameters at CT. Radiology 266(1):326-36.

Non-Neoplastic
Berry G et al: ISHLT summary statement. Pathology of pulmonary antibody-mediated rejection: 2012 update from the Pathology Council of the ISHLT. JHLT 2013 (32):14-21.

Shah AA et al: Diagnostic accuracy of histopathologic and cytopathologic examination of Aspergillus species. AJCP 2013;139:55-61.

Hariri LP et al. Volumetric optical frequency domain imaging of pulmonary pathology with precise correlation to histopathology. Chest 2013; 143(1):64-74.

Current Topics/Review Articles:
Weissferdt A, Moran CA. Staging of primary mediastinal tumors. Adv Anat Pathol 20(1):1-9.

Jakobsen J et al. Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung Cancer. 2013 79:1-7.

Ordóñez, NG Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update. Human Pathology (2013) 44, 1–19.

Popper HH e al. Interstitial lung diseases—can pathologists arrive at an etiology-based diagnosis? A critical update.  Virchows Archives. 2013; 462:1-26.

Case reports
Derweduwen AM et al. Extrapulmonary lymphangioleiomyomatosis: a wolf in sheep’s clothing. Thorax 2013;68:111–113.

Kluka EM, Enlarging Lung Nodules and Cysts in a 53-Year-Old Woman With Primary Sjögren Syndrome. CHEST 2013; 143(1):258–261.

Prat L et al. Cutaneous lymphangitis carcinomatosa in a patient with lung adenocarcinoma: Case report and literature review. Lung Cancer 2013. 79:91-3.

Chai GT et al. Diffuse Reticulonodular Shadows A Rare Manifestation of a Rare Disease. CHEST 2013; 143(1):252–257.

Kurata A et al. Intracaval and intracardiac extension of invasive thymoma complicated by superior and inferior vena cava syndrome. Pathology International 2013; 63: 56–62.

Hirota T et al. Pleuroparenchymal fibroelastosis as a manifestation of chronic lung rejection? Letter to the editor. Eur Respir J. 2013;41:243-5.

January 2013 Edition

HAPPY NEW YEAR!  Tom Colby rings in the first Pulmonary Pathology Reviews of 2013 from sunny Scottsdale, Arizona with a review of the best (and the worst) of peer reviewed publications that appeared in print in December 2012.  He focuses on a broad range of papers, at least some of which are almost certain to be of interest.  If not, you may have stumbled into the wrong blog!  His OVERVIEW follows and provides a roadmap for what's hot and what's not.  Click here if you want to bypass having to read each article in detail and instead download Tom's thumbnail summaries for each article.  Click here if you want to download an MP3 audiofile (be patient, it may take a while) to hear how the international, multi-institutional teleconference went down on Monday morning, January 14th.  And as always, feel free to comment if you want to join the conversation!

OVERVIEW
There were actually quite a few articles of interest found in the journals reviewed for December of 2012. 

Articles for Discussion
I chose articles for discussion primarily because they have some practical application or are timely.  The article by Takamura, et al compares chronic HP with IPF and there were a number of interesting findings, some of which appeared to have clinical significance, but it remains to be seen how good these will be in prospective biopsy evaluation.  Key features in chronic HP that they mention include centrilobular fibrosis, bridging fibrosis, and the presence of fibroblast foci in central regions as opposed to peripheral regions, with the latter being more in IPF.  Not surprisingly bronchiolitis and granulomas were features of chronic HP.  Chronic HP also had isolated giant cells and none of these were noted in IPF.  I have often considered these nonspecific but perhaps I should take more note of them.

Walts and Marchevsky did a root cause analysis of frozen section errors in the frozen section diagnosis of adenocarcinoma.  This is timely because we are being asked more frequently to distinguish between the low grade variance of adenocarcinoma (AIS and MIA) and more conventional invasive adenocarcinoma.  I got a little lost in the details of the root cause analysis but there are number of recommendations that I think we all can use.

Thunnissen and colleagues in the IASLC adenocarcinoma group have put together a reproducibility study of histologic subtyping of adenocarcinoma and determination of whether or not invasion is present.  The results are at all surprising from this exhaustive and complex analysis.  In short, the study confirmed what most of know.  Most histologic subtypes of adenocarcinoma are readily recognizable with good inter-observer agreement with the worst being for the micropapillary pattern; in regards to invasion easy cases are easy and hard cases are hard with a very poor kappa statistic for inter-observer agreement. 

Articles for Notation
I include Joanne Yi’s review article on IgG4 disease in the lung from Seminars in Diagnostic Pathology even though it did not occur in December.  It does not appear to have been picked up in prior journal clubs.  This is a very useful article with all you want to know about IgG4 disease in the lung.  There is a large study from Heidelberg by Warth, et al, looking at immunomarkers for subtyping non-small cell lung cancer.  The findings are not new but they are very well illustrated with nice grafts and percentages and this may be a useful article for summarizing and talks.

A large series from Japan by Woo, et al, looked at stage 1 adenocarcinomas and the findings tended to confirm the 2011 adenocarcinoma classification.

Among the non-neoplastic diseases there is a review of pulmonary hypertension and right ventricular failure that has some nice graphs.  There is a series by Lee, et al, on the CT findings and familial interstitial pneumonias.  It turns out that a radiologic UIP pattern is not uncommon in the setting of familial pulmonary fibrosis but most cases do not conform to typical UIP or NSIP patterns.

ARTICLE INDEX
Discussion Articles
Takemura T, et al. Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia. Histopathology. 2012 Dec; 61(6):1026-35.

Walts AE, Marchevsky AM. Root cause analysis of problems in the frozen section diagnosis of in situ, minimally invasive and invasive adenocarcinoma of the lung. Arch Pathol Lab Med. 2012 Dec; 136(12):1515-21.

Thunnissen E, et al.  Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma, an international interobserver study.  Mod Pathol. 2012;25:1574-83.

Articles for Notation
I.  NEOPLASTIC LUNG DISEASE
Warth A, et al.  Large-scale comparative analyses of immunomarkers for diagnostic subtyping of non-small cell lung cancer biopsies.  Histopathology 2012;61:1017-1025.

Wulf M-A, et al.  Silver-enhanced in situ hybridization (SISH) for determination of EGFR copy number alterations in non-small cell lung cancer.  Am J Surg Pathol  2012;36:1801-1808.

Thunnissen E, et al.  Correlation of immunohistochemical staining for p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non-small cell lung cancer.  Virchows Archives 2012;461:629-638.

Matsukuma S, et al.  Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: case report with review of the literature.  Pathology International 2012;62:817-822.

Woo T, et al.  Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases.  Pathology International 2012;62:785-791.

Schmidt LA, et al.  Napsin-A is differentially expressed in sclerosing hemangiomas of the lung.  Arch Pathol Lab Med 2012;136:1580-1584

Nelson DR.  Intravascular lymphoma as a cause of respiratory failure.  J Thorac Oncol 2012;7:e34-e35

Heist RS, et al.  FGFR1 amplification in squamous cell carcinoma of the lung.  J Thorac Oncol 2012;7:1775-1780

Cardarella S, et al.  The introduction of systematic genomic testing for patients with non-small-cell lung cancer.  J Thorac Oncol  2012;7:1767-1774.

Zupa A, et al.  A pilot characterization of human lung NSCLC by protein pathway activation mapping.  J Thorac Oncol  2012;7:1755-1766

Lawson K, et al.  Successful treatment of progressive diffuse PEComatosis.  Eur Respir J  2012;40:1578-1580.

McCormack FX, et al.  Lymphangioleiomyomatosis: calling it what it is: a low-grade, destructive, metastasizing neoplasm.  Am J Respir Crit Care Med  2012;186:1210-1212.

King L, et al.  Primary intrathoracic dermatofibrosarcoma protuberans.  Am J Surg Pathol  2012;36:1897-1902.

II.  THE HOUSTON LUNG SYMPOSIUM, Part II (Arch Pathol Lab Med 2012;136:1476-1535).
Some of the articles from this symposium are included in other sections of this journal club.  Those that are not included include:
•    Evolving frontlines in the diagnosis and treatment of pulmonary diseases (Cagle)
•    Worldwide overview of the current status of lung cancer diagnosis and treatment (Bunn)
•    Lung cancer genotype-based therapy and predictive biomarkers: present and future (Cagle and Allen)
•    In vivo optical coherence tomography: the role of the pathologist (Hariri)
•    Differential diagnosis of lung carcinoma with coherent anti-Stokes Raman scattering imaging (Gao)
•    Screening for lung cancer: who should be screened? (Jett)
•    Guiding the pulmonologist’s hand: what they need to know about lung pathology and what is lost in translation (Kradin)

III.  NON-NEOPLASTIC LUNG DISEASE
Voelkel NF, et al.  Pathobiology of pulmonary arterial hypertension and right ventricular failure.  Eur Respir J  2012;40:1555-1565

Lara AR, et al.  Increased lymphatic vessel length is associated with the fibroblast reticulum and disease severity in usual interstitial pneumonia and non-specific interstitial pneumonia.  Chest  2012;142:1569-1576.

Yi ES, et al.  Pathologic manifestations of immunoglobulin(Ig)G4 related lung disease.  Semin Diagn Pathol 2012;29:219-225.

Lee HY, et al.  High resolution CT scan findings in familial interstitial pneumonia do not conform to those of idiopathic interstitial pneumonia.  Chest 2012;142:1577-1583.

Belchis DA, et al.  A unique, histologic lesion in a subset of patients with spontaneous pneumothorax.  Arch Pathol Med 2012;136:1522-1527.

December 2012 Edition

Welcome to the December 2012 Edition of Pulmonary Pathology Reviews, your one stop when it comes to keeping pace with the fast-paced, always exciting, and frequently controversial world of pulmonary pathology!  Today's review comes to you courtesy of Dr. Andras Khoor at sunny Mayo Clinic Florida.  What follows is his high level OVERVIEW of what's good and what's not, followed by an ARTICLE INDEX with links to PubMed abstracts (and full text if your institutional license allows it).  Click here if you want to read his thumbnail reviews in PDF format; click here if you want to hear the teleconference as it unfolded on Monday, December 17, 2012 at 09:15 EST.

OVERVIEW
Reviewing the November issues of our favorite 22 journals, I found 18 pulmonary pathology related articles, some of them quite interesting.  The first Discussion article was written by Dr. Kevin Leslie (Mayo Clinic Arizona) et al.  They studied 30 cases of familial idiopathic interstitial pneumonia.  In contrary to prevailing wisdom, diagnostic features of usual interstitial pneumonia (UIP) were seen in less than 50% of samples and findings unexpected in UIP were prevalent. 

The study by Nishino et al. has confirmed the previous notion that signet ring cells show a significant association with ALK rearrangements. 

Kudo et al. investigated visceral pleural invasion in non-small cell lung cancer and recommend modification in the TNM classification of the Union of International Cancer Control staging system.

Brcic et al studied expression of Sox2 in squamous cell carcinomas of the lung.

Finally, Gruver et al. came up with an immunohistochemical panel that could help separate urothelial carcinoma and squamous cell carcinoma of the lung. 

From among the remaining articles, a review of ROS1 by Chin at al. seems to be the most important.  ROS1 has recently emerged as a potential target for crizotinib in non-small cell lung cancer and we all should know about it.

ARTICLE  INDEX
Articles for Discussion
Leslie KO et al. Familial Idiopathic Interstitial Pneumonia: Histopathology and Survival in 30 Patients. Arch Pathol Lab Med. 2012;136:1366–1376.

Nishino M et al. Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas. Modern Pathology (2012) 25, 1462–1472.

Kudo Y et al. Impact of visceral pleural invasion on the survival of patients with non-small cell lung cancer. Lung Cancer 78 (2012) 153– 160.

Brcic L et al. Morphologic and Clinicopathologic Features of Lung Squamous Cell Carcinomas Expressing Sox2. Am J Clin Pathol 2012;138:712-718.

Gruver AM et al. Selective Immunohistochemical Markers to Distinguish Between Metastatic High-Grade Urothelial Carcinoma and Primary Poorly Differentiated Invasive Squamous Cell Carcinoma of the Lung. Arch Pathol Lab Med. 2012;136:1339–1346.

Articles for Notation

Non-neoplastic
Zhang Y et al. Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis. Eur Respir J 2012; 40: 1191–1200.

Neoplastic
Ordonez NG. Deciduoid mesothelioma: report of 21cases with review of the literature. Modern Pathology (2012) 25, 1481–1495.

Kato T et al. EGFR mutations and human papillomavirus in lung cancer. Lung Cancer 78 (2012) 144– 147.

Schildhaus H-U et al. Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Modern Pathology (2012) 25, 1473–1480.

Mukhopadhyay S and Katzenstein A-LA. Comparison of Monoclonal Napsin A, Polyclonal Napsin A, and TTF-1 for Determining Lung Origin in Metastatic Adenocarcinomas. Am J Clin Pathol 2012;138:703-711.

Finn RS et al. Postmortem Findings of Malignant Pleural Mesothelioma: A Two-Center Study of 318 Patients. CHEST 2012; 142(5):1267–1273.
     
Case Reports
Boyd C et al. Pulmonary-type adenocarcinoma and signet ring mucinous adenocarcinoma arising in an ovarian dermoid cyst: report of a unique case. Human Pathology (2012) 43, 2088–2092.

Christopher-Stine L et al. Case 37-2012: A 21-Year-Old Man with Fevers, Arthralgias, and Pulmonary Infiltrates. N Engl J Med 2012;367:2134-46.

Khozin S et al. Hepatoid Carcinoma of the Lung with Anaplastic Lymphoma Kinase Gene Rearrangement. Journal of Thoracic Oncology • Volume 7, Number 11, 2012, e29-31.

Kinoshita T et al. The recurrence of malignant pleural mesothelioma 14 years after extrapleural pneumonectomy: Possible histological transformation. Pathology International 2012;62:754–757.

Review Articles
Mani H and Zander DS. Immunohistochemistry. Applications to the Evaluation of Lung and Pleural Neoplasms: Part 1. CHEST 2012; 142(5):1316–1323.

Mani H and Zander DS. Immunohistochemistry. Applications to the Evaluation of Lung and Pleural Neoplasms: Part 2. CHEST 2012; 142(5):1324–1333.

Chin LP et al. Targeting ROS1 with Anaplastic Lymphoma Kinase Inhibitors: A Promising Therapeutic Strategy for a Newly Defined Molecular Subset of Non–Small Cell Lung Cancer. J Thorac Oncol. 2012;7:1625–1630.

November 2012 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, a monthly journal club intended to keep you up to date when it comes to peer reviewed literature of interest to diagnostic pulmonary pathologists.  Today's journal club comes to you from Joe Maleszewski at the Mayo Clinic Minnesota (reporting 16 degrees Fahrenheit at 7:25 this morning) with help from pulmonary pathology fellow, Sindy Chang.  Click here for a PDF file of Joe's article summaries, thumbnails that point out the highs and lows of this month's hot topics.  You might want to first check out his OVERVIEW highlighting what's hot and what's not.  Following Joe's OVERVIEW is an ARTICLE INDEX with links to PubMed abstracts and full text articles if your institutional license allows.  And if you want to hear how it all went down in the course of a multi-institutional teleconference launched at 08:15 CST on Monday, November 26, 2012 click here to download an MP3 audiofile (tends to be a large file, so be patient - may take a while).

OVERVIEW
This month’s collection of pulmonary pathology-related journals ample, containing a very good mix of both neoplastic and non-neoplastic topics. The raw number of articles was helped by the fact that the October edition of Archives of Pathology & Laboratory Medicine contained a special section from the Houston Lung Symposium, resulting in a number of very high quality review articles. In all, nineteen original articles (12 neoplastic, 7 non-neoplastic), eleven review articles, and five case reports were gleaned from the usual journals.

Arguably, the article with the probable highest impact was published in The New England Journal of Medicine, by Pass et al, on the topic of fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. I found this article interesting for a number of reasons. First of all, they present compelling data that shows that plasma fibulin-3 can distinguish healthy persons with exposure to asbestos from patients with mesothelioma. In support of their data, they also present (in supplemental – online only – format) immunoperoxidase data that appears to suggest that malignant transformation of mesothelium can be detected using antibodies directed against fibulin-3.

A number of groups focused efforts on the molecular pathways of lung cancer, including: Yanangawa et al looking at the prognostic role of PTEN, Vincenten et al looking at the role of TTF-1 as a surrogate marker for treatment selection during EGFR-mutation analysis, and Planchard et al looking at p38 signaling and ERCC1 expression in lung cancer from never or light smokers. Other groups remain focused on elucidating the EGFR and KRAS mutations and further refining the diagnostic algorithms that should be used in practice.

Additionally, there were several very solid studies examining the role of staging in prognosis as well as a very nice article on the prognostic impact of malignant pleural effusions in patients with metastatic NSCLC by Morgensztern and colleagues.

Studies focused on non-neoplastic disease were equally intriguing, and included very interesting work by Yu et al focused on the molecular pathways involved in regulating fibroblastic proliferation in a murine model as well as a study (by Cipriani and colleagues) focused on the pathologic quantification of connective tissue disease-associated UIP vs. idiopathic UIP, though this latter study didn’t appear to yield a great deal of unexpected findings.

Our own Drs. Boland, Tazelaar, Colby, Leslie and Yi published a very nice series on a rare phenomenon, diffuse pulmonary lymphatic disease presenting as interstitial lung disease in adults. The non-neoplastic category was rounded-out by two articles related to infectious disease, one involving Chickenpox-related pulmonary granluomas and the other involving the mechanisms behind pulmonary hemorrhage in the setting of leptospirosis (a must-read before going spelunking or caving in Hawaii!).

The plethora of review articles (coming primarily from The Archives) covered a range of neoplastic and non-neoplastic topics. The included a number of nice reviews from some of the esteemed members of this journal club (Colby, Larsen, Myers, Tazelaar, and Leslie). Personally, I found the review by Cagle and Myers regarding the changing role of the surgical pathologist in the diagnosis/treatment of lung cancer to be of particular interest in this ever expanding molecular-era we find ourselves in.

Hopefully, you’ll get a chance to peruse the articles for this past month. There’s lots to learn for both the general surgical pathologist as well as the pulmonary aficionado.

ARTICLE INDEX
Articles for Discussion
Pass HI et al. Fibulin-3 as a Blood and Effusion Biomarker for Pleural Mesothelioma. N Engl J Med. 2012 Oct 11;367(15):1417-27.

Yanagawa N et al. Loss of phosphatase and tensin homolog protein expression is an independent poor prognostic marker in lung adenocarcinoma. J Thorac Oncol. 2012 Oct;7(10):1513-21.

Vincenten J et al. Negative NKX2-1 (TTF-1) as temporary surrogate marker for treatment selection during EGFR-mutation analysis in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10):1522-7.

Cipriani N et al. Pathologic quantification of connective tissue disease-associated versus idiopathic usual interstitial pneumonia. Arch Pathol Lab Med. 2012 Oct;136(10):1253-8.


Articles for Notation
Neoplastic
Mohammad T et al. Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice. Am J Surg Pathol. 2012 Oct;36(10):1503-8.

De Costa Souza P et al. Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma. Histopathology. 2012 May 15.

Planchard D et al. p38 mitogen-activated protein kinase signaling, ERCC1 expression, and viability of lung cancer cells from never or light smoker patients. Cancer. 2012 Oct 15;118(20):5015-25.

Morgensztern D et al. Prognostic impact of malignant pleural effusion at presentation in patients with metastatic non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10):1485-9.

Morgensztern D et al. Prognostic significance of tumor size in patients with stage III non-small-cell lung cancer: a surveillance, epidemiology, and end results (SEER) survey from 1998 to 2003. J Thorac Oncol. 2012 Oct;7(10):1479-84.

Cadranel J et al. Impact of systematic EGFR and KRAS mutation evaluation on progression-free survival and overall survival in patients with advanced non-small-cell lung cancer treated by erlotinib in a French prospective cohort (ERMETIC project--part 2). J Thorac Oncol. 2012 Oct;7(10):1490-502.

Fibla JJ et al. Re-Evaluation of the Prognostic Value of Visceral Pleura Invasion in Stage IB Non-Small Cell Lung Cancer Using the Prospective Multicenter ACOSOG Z0030 Trial Data Set. Lung Cancer 2012 Oct;78:259-262.

Kawahara A et al. A Diagnostic Algorithm Using EGFR Mutation-Specific Antibodies for Rapid Response EGFR-TKI Treatment in patients with Non-Small Cell Lung Cancer. Lung Cancer 2012. Oct;78:39-44.

Inoue M et al. An Accurate and Rapid Detection of Lymph Node Metastasis in Non-Small Cell Lung Cancer Patients Based on One-Step Nucleic Acid Amplification Assay. Lung Cancer 2012. Oct;78:212-218.

Non-neoplastic
Rossi G et al. Chickenpox-related pulmonary granulomas in immunocompetent adults: clinicopathologic and molecular features of an underrated occurrence. Am J Surg Pathol. 2012 Oct;36(10):1497-502.

Boland JM et al. Diffuse pulmonary lymphatic disease presenting as interstitial lung disease in adulthood: report of 3 cases. Am J Surg Pathol. 2012 Oct;36(10):1548-54.

Kottmann RM et al. Lactic Acid Is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation via pH-Dependent Activation of Transforming Growth Factor-β. Am J Respir Crit Care Med. 2012 Oct 15;186(8):740-51.

Yu G et al. Matrix metalloproteinase-19 is a key regulator of lung fibrosis in mice and humans. Am J Respir Crit Care Med. 2012 Oct 15;186(8):752-62.

Del Carlo Bernardi F et al. Immune receptors and adhesion molecules in human pulmonary leptospirosis. Hum Pathol. 2012 Oct;43(10):1601-10.

Review Articles
MacConaill LE. Advancing personalized cancer medicine in lung cancer. Arch Pathol Lab Med. 2012 Oct;136(10):1210-6.

Borczuk AC. Neoplastic and nonneoplastic benign mass lesions of the lung. Arch Pathol Lab Med. 2012 Oct;136(10):1227-33.

Dacic S. Dilemmas in lung cancer staging. Arch Pathol Lab Med. 2012 Oct;136(10):1194-7.

Dromparis P et al. F2-isoprostanes: an emerging pulmonary arterial hypertension biomarker and potential link to the metabolic theory of pulmonary arterial hypertension? Chest. 2012 Oct 1;142(4):816-20.

Larsen BT et al. Update for pathologists on idiopathic interstitial pneumonias. Arch Pathol Lab Med. 2012 Oct;136(10):1234-41.

Churg A et al. The separation of benign and malignant mesothelial proliferations. Arch Pathol Lab Med. 2012 Oct;136(10):1217-26.

Lindeman N. Molecular diagnostics of lung cancers at the Brigham and Women's Hospital and Dana-Farber Cancer Institute: technology in rapid evolution. Arch Pathol Lab Med. 2012 Oct;136(10):1198-200.

Oxnard GR. Strategies for overcoming acquired resistance to epidermal growth factor receptor: targeted therapies in lung cancer. Arch Pathol Lab Med. 2012 Oct;136(10):1205-9.

Cagle PT et al. Precision medicine for lung cancer: role of the surgical pathologist. Arch Pathol Lab Med. 2012 Oct;136(10):1186-9.

Schneider F et al. Pleuropulmonary pathology in patients with rheumatic disease. Arch Pathol Lab Med. 2012 Oct;136(10):1242-52.

Bang YJ. Treatment of ALK-positive non-small cell lung cancer. Arch Pathol Lab Med. 2012 Oct;136(10):1201-4.

Case Reports / Letters to the Editor
Gautschi O et al. A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J Thorac Oncol. 2012 Oct;7(10):e23-4.

Mattsson JS et al. Consistent mutation status within histologically heterogeneous lung cancer lesions. Histopathology. 2012 Mar 28.

Weiner J et al. Diffuse talc granulomatosis in a patient with Crohn's disease. Am J Respir Crit Care Med. 2012 Oct 1;186(7).

Ackerman A et al. EGFR delE709_T710insD: a rare but potentially EGFR inhibitor responsive mutation in non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10).

Lewin-Smith M et al. Detection of silicone in lung tissue. Arch Pathol Lab Med. 2012 Oct;136(10):1179-80; author reply 1180.

October 2012 Edition

Welcome to a delayed edition of Pulmonary Pathology Reviews, intended as a journal club focused on keeping those interested in diagnostic pulmonary pathology up-to-date on the latest developments in a fast moving world!  October's journal club came to us courtesy of Henry Tazelaar at Mayo Clinic Arizona on Monday, October 29th.  What follows is his OVERVIEW followed by a list of articles and links to PubMed abstracts (and full text versions if your institutional license allows it).  Click here if you want Henry's summary of each article in PDF format.  Click here if you want to hear the actual teleconference as it unfolded at 06:15 MST very early on a Monday morning in October that predated the switch away from daylight savings time for most (but not all) of the country!

OVERVIEW
There was no shortage of pulmonary pathology related articles this month.  There are several worth noting particularly because the entities they describe are new.  The first is by Wenzel et al, with Sam Yousem as the senior author.  They describe the occurrence of granulomatous bronchiolar disease in patients with asthma.  Although not entirely new to this group, it’s worth taking a look at the consensus statement on IgG4-related diseases by Deshpande et al.  (IgG4-related disease is also explored by Sekiguchi et al in a case report.) Our own Boland, Colby and Folpe report a large series of liposarcomas occurring in the mediastinum and thorax along with molecular studies.  Although the article by Park et al on “ciliated adenocarcinoma of the lung” sounds very intriguing as I didn’t really think such tumors exist, in fact they don’t.  They do, however, present an interesting hypothesis regarding adeno-carcinogenesis along a sequence different from AAH to AIS/BAC.  The article by Kato et al is worth reading as they try to tease out the clinicopathologic characteristics of small adenocarcinomas of the lung.  They focus a lot on what constitutes invasion in small cancers.

There were a number of interesting case reports. Two dealt with granulomatous pathology, so in addition to the article on granulomatous inflammation in asthma, these articles may lead us to expand the differential of granulomatous lung disease:  Tischler et al present a case of crystal precipitation and granulomatous inflammation after foscarnet therapy and a granulomatous pneumonitis associated with a disease I had never heard of, Blau syndrome was reported by Yao et al.  Other case reports include one by Chambers et al on lung fibrosis, premature graying, and macrocytosis; by; a woman with iron pill aspiration and unusual findings in the airways by Grosu et al; and a case of lymphangioleiomyomatosis by Min et al. Urisman et al report on the development of PVOD after the use of oral contraceptives in two patients.

Infectious disease related pathology is explored in a case report of mycobacterial spindle cell tumor by Drs. Philip, Beasley and Dua and Arai et al looked at the effects of cytokine expression on histologic patterns of CMV pneumonia.

Articles in miscellaneous categories address pulmonary hypertension in patients with lymphangioleiomyomatosis by the experienced French group headed by Cottin et al.  The article by Matsuoka et al examines the presence of squamous metaplasia in CPAMs after thoracoamniotic shunt placement.  I found this article most interesting because I did not know about such procedures!  It’s worth taking a look at the editorial by Jim Hogg as he explores a pathologist’s view of airway obstruction in COPD.  It’s always worth reading him and paying attention to an area of intense clinical (and less often pathology related) research.

There seemed to be a host of articles on molecular and other associations in lung cancer (ALK1: Ramalingam, et al; Camidge et al; Pelosi et al; Thunnissen et al);  EGFR (Allegrini et al); microRNA expression by Lee et al; neuropilin-2 expression by Jubb et al; Thymidylate synthase by Herpel et al., and a practical guide to molecular pathology of non-small cell carcinoma by Aisner et al.
Rare and unusual tumor and tumor-like conditions were explored by Cates et al (desmoid type fibromatosis occurring after radiation therapy); DIPNECH by Anevlavis et al; papillary adenoma, Masunaga et al; and solitary fibrous tumor (a majority of these occurred in the chest),  by Demicco et al.

There were some larger studies related to various aspects of pulmonary neoplasia including interobserver agreement in specimens acquired by EBUS-TBNA, by Steinfort et al; cytohistologic correlations in a study by da Cunha Santos et al.; and the long term outcome of 50 cases of limited-resection for patients with pulmonary ground-glass opacities by Nakao et al (bottom line, 5 years is not sufficient follow-up and limited resections should be done only in a trial setting).  Quinn et al evaluate 37 cases of non-small cell carcinoma arising outside of the lung and found TTF expression in a wide variety of these tumors.

Finally, Gordon et al explore the challenging topic of lung allograft rejection and focus on discrepancies identified by a web-based survey.

Hopefully you can listen to the audio file, but if not, this summary should let you know if there is something you need to explore further on your own. Happy reading!

ARTICLE INDEX
Articles for Discussion
Asthmatic granulomatosis: a novel disease with asthmatic and granulomatous features.  Wenzel et al.  Am J Respir Crit Care Med.  2012;186(6):501-7.

Consensus statement on the pathology of IgG4-related disease.  Deshpande et al.  Modern Pathology.  2012;25:1181-92.

Liposarcomas of the mediastinum and thorax: a clinicopathologic and molecular cytogenetic study of 24 cases, emphasizing unusual and diverse histologic features.  Boland et al.  Am J Surg Pathol.  2012;36:1395-1403.

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.  Park et al.  Modern Pathology.  2012;24:1265-74.

Articles for Notation – Diffuse Lung Disease
Lung fibrosis, premature graying, and macrocytosis.  Chambers et al.  Am J Respir Crit Care Med.  2012 Sep;185:e8-e9.

Crystal precipitation and granulomatous inflammation in multiple organs after foscarnet therapy in a lung transplant recipient.  Tischler et al.  J Heart Lung Transplant.  2012;31:1037-40.

The iron lady.  Grosu et al.  Am J Respir Crit Care Med.  2012 Sep;186(5):460.

A 29-year-old woman with an intractable postoperative pleural effusion and pulmonary parenchymal opacification.  Min et al.  Chest.  2012;142(3):791-6.

Granulomatous pneumonitis associated with adult-onset Blau-like syndrome.  Yao et al.  Am J Respir Crit Care Med.  2012;186:465-6.

Pulmonary hypertension in lymphangioleiomyomatosis: characteristics in 20 patients.  Cottin et al.  Eur Respir J.  2012;40:630-40.

Infection
Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.  Arai et al.  Pathology International.  2012;62:628-39.

Mycobacterial spindle cell pseudotumor of the lung.  Philip et al.  Chest.  2012;142(3):783-4.

Miscellaneous
A pathologist’s view of airway obstruction in chronic obstructive pulmonary disease.  Hogg JC.  Am J Respir Crit Care Med.  2012 Sep;186(5):v-398.

IgG4-related systemic disease presenting with lung entrapment and constrictive pericarditis.  Sekiguchi et al.  Chest.  2012;142(3):781-3.

Squamous metaplasia in the cyst epithelium of type 1 congenital pulmonary airway malformation after thoracoamniotic shunt placement.  Matsuoka et al.  Human Pathology.  2012;43:1413-7.

Neoplasms
Lung cancer with translocation in the anaplastic lymphoma kinase gene: a disease within a disease.  Ramalingam et al.  Cancer.  2012 Sep;118(18):4370-1.

Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive non-small cell lung cancer.  Camidge et al.  Cancer.  2012;118:4486-94.

Multiparametric molecular characterization of pulmonary sarcomatoid carcinoma reveals a nonrandom amplification of anaplastic lymphoma kinase (ALK) gene.  Pelosi et al.  Lung Cancer.  2012;77(3):507-14.

EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations.  Thunnissen et al.  Virchows Arch.  2012;461(3):245-57.

Molecular pathology of non-small cell lung cancer: a practical guide.  Aisner et al.  Am J Clin Pathol.  2012;138:332-46.

Epidermal growth factor receptor gene analysis with a highly sensitive molecular assay in routine cytologic specimens of lung adenocarcinoma.  Allegrini et al.  Am J Clin Pathol.  2012;138:377-81.

Altered expression of microRNA miR-21, miR-155, and let-7a and their roles in pulmonary neuroendocrine tumors.  Lee et al.  Pathol Int.  2012;62:583-91.

A 66-year-old woman with dry cough and exertional dyspnea.  Anevlavis et al.  Chest.  2012;142(3):802-5.

Extrapulmonary small cell carcinoma: a clinicopathological study with identification of potential diagnostic mimics.  Quinn et al.  Histopathology.  2012;61:454-64.

Interobserver agreement in determining non-small cell lung cancer subtype in specimens acquired by EBUS-TBNA.  Steinfort et al.  Eur Respir J.  2012;40:699-705.

Cytohistologic agreement in pathologic subtyping of non-small cell lung carcinoma: review of 602 fine needle aspirates with follow-up surgical specimens over a nine year period and analysis of factors underlying failure to subtype.  da Cunha Santos et al.  Lung Cancer.  2012;77(3):501-6.

Long-term outcomes of 50 cases of limited-resection trial for pulmonary ground-glass opacity nodules.  Nakao et al.  J Thorac Oncol.  2012;7:1563-6.

Neuropilin-2 expression in cancer.  Jubb et al.  Histopathology.  2012;61:340-9.

Assessment of thymidylate synthase expression in biopsy specimens and corresponding resection specimens of non-small cell lung cancer.  Herpel et al.  Histopathology.  2012;61:465-72l.

Clinicopathological characteristics of subcentimeter adenocarcinomas of the lung.  Kato et al.  Lung Cancer.  2012;77(3):495-500.

A case of pulmonary papillary adenoma: possible relationship between tumor histogenesis/tumorigenesis and fibroblast growth factor receptor 2 IIIb.  Masunaga et al.  Pathol Int.  2012;62:640-5.

Morphologic and immunophenotypic analysis of desmoid-type fibromatosis after radiation therapy.  Cates et al.  Human Pathology.  2012;43:1418-24.

Solitary fibrous tumor: a clinicopathological study of 110 cases and proposed risk assessment model.  Demicco et al.  Modern Pathology.  2012;25:1298-1306.

Transplantation
SaLUTaRy: a survey of lung transplant rejection.  Gordon et al.  J Heart Lung Transplant.  2012;31:972-9.

Vascular Disease
Rapidly progressive pulmonary venoocclusive disease in young women taking oral contraceptives.  Urisman et al.  J Heart Lung Transplant.  2012;31:1031-6.

September 2012 Edition

Welcome to another edition of Pulmonary Pathology Reviews, this one coming to us courtesy of Margaret Kelly, with help from pulmonary pathology fellow Salwa Bakhsh, in the spectacularly beautiful city of Calgary in the great province of Alberta, Canada.  You may think it a cold place, but at 05:52 MDT on Monday, September 24, 2012 it is a full 7 degrees Fahrenheit warmer than Ann Arbor, MI and 3 degrees warmer than Rochester, MN.  What follows is Margaret's OVERVIEW of what's hot and what's not in articles that appeared in the print peer reviewed literature in August 2012.  The OVERVIEW is followed by the ARTICLE INDEX with links to PubMed abstracts and full text articles for those who have institutional agreements in place.  Click here if you want to see her summary of articles, a quick reference for those who haven't the time or inclination to read the full articles.  Click here if you want to download an MP3 file if you want to hear the teleconference as it unfolded at 7:15 MDT on Monday, September 24th.

OVERVIEW
This months journal club comes to you from the sunny (and presently warm!) city of Calgary, Alberta, with its own unique and never boring microclimate.

I have been helped enormously this month by Dr. Salwa Bakhsh, pulmonary pathology fellow, who has reviewed the lions’ share of the papers. Articles published in August 2012 were critically reviewed and we selected 19 articles we thought would be of interest to pulmonary and thoracic pathologists.

The first two discussion articles deal with the value of various clinical and pathological features that may allow stratification of patients with stage I NSCLC into those that may have a high recurrence rate and hence be entered into trials for adjuvant therapy. In the first, Kadota et al, (Travis is the last author), examined the value of the nuclear features in NSCLC in prediciting recurrence, whilst the second article looked critically at the implications of lymph/vascular invasion and tumor differentiation. A third paper, included in the notation only section, by Koike et al., looks at predictors for mediastinal lymph node metastasis in stage IA NSCLC. Whether the various features described should be included in stratification of patients clinically is for you to decide.  I find it heartening that the features we doggedly record may eventually be of some use to our patients.
 
The last two discussion articles deal with rare entities, NUT midline carcinoma and pleuroparenchymal fibroelastosis, both fascinating papers.

In the articles for notation, we found two papers dealing with the application of diagnostic interventions, classical bonchoscopy and EBUS-TBNA respectively. The former deals with the knotty problem of what to do with patients with CT screen detected pulmonary nodules, and concludes that conventional bronchoscopy should not be routinely applied for these patients. An interesting editorial related to this is included, by Dr. Gerard Silvestri, who states that it is only of use in patients who have a bronchus sign leading to the nodule. Instead, various forms of ‘navigational’ bronchoscopy should be used instead of the conventional kind.  Navani et al. show that EBUS-TBNA is a useful initial investigation in patients with isolated mediastinal lymphadenopathy,  making the more invasive medistinoscopy obsolete in many cases. Lastly, on this theme, an interesting case report describing an unusual cause of a solitary pulmonary nodule is included.

The remainder of the original papers vary from sarcomatous overgrowth in SFT’s, to stem cell markers in pulmonary sclerosing hemangioma, to the description of a new form of silicosis, the exotically named ‘CaesarStone silicosis’.

 The role of surgical lung biopsy in HP is discussed by our very own Dr. Jeff Myers and co, and new insights into HP are described by Drs Selman, Pardo and King. Reviews on IPF, mesothelioma and vasculitis are also included. Lastly, an unusual cause of airway stricture is described, reminding us of the central importance of taking a good history although in this case sleuthing of Sherlock Holmes proportions was applied. Who knew that sweet smelling talcum powder routinely applied to babies bums and ladies noses could be so nasty!

ARTICLE INDEX
Articles for Discussion
Kadota K et al .A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma. Mod Pathol. 2012 Aug; 25(8):1117-27.

Shimada Y et al. Pathological vascular invasion and tumor differentiation predict cancer recurrence in stage IA non-small-cell lung cancer after complete surgical resection. J Thorac Oncol. 2012 Aug; 7(8):1263-70.

Evans AG et al. Pathologic Characteristics of NUT Midline Carcinoma Arising in the Mediastinum. Am J Surg Pathol. 2012 Aug; 36(8):1222-7.

Reddy TL et al. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J. 2012 Aug; 40(2):377-85.

Articles for Notation
Original Articles
A. Neoplastic
Lin XY et al. Expression and significance of stem cell markers in pulmonary sclerosing haemangioma. Histopathology. 2012; 61(2):178-85.

Van‘t Westeinde SC et al. The role of conventional bronchoscopy in the work-up of suspicious CT screen detected pulmonary nodules. Chest 2012; 142(2):377–384.

Koike T et al. Predictive Risk Factors for Mediastinal Lymph Node Metastasis in Clinical Stage IA Non-Small-Cell Lung Cancer Patients. J Thorac Oncol. 2012 ;7(8):1246-51.

Collini P et al. High-grade Sarcomatous Overgrowth in Solitary Fibrous Tumors: A Clinicopathologic Study of 10 Cases. Am J Surg Pathol. 2012;36(8):1202-15.

Navani N et al. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Prevents Mediastinoscopies in the Diagnosis of Isolated Mediastinal Lymphadenopathy: A Prospective Trial. Am J Respir Crit Care Med. 2012 Aug 1; 186(3):255-260.

B. Non-neoplastic
Tsujino K et al. Tetraspanin CD151 Protects against Pulmonary Fibrosis by Maintaining Epithelial Integrity. Am J Respir Crit Care Med. 2012 15; 186(2):170-80.

Kramer MR et al. CaesarStone Silicosis: Disease Resurgence among Artificial Stone Workers. Chest. 2012; 142: 419-24.

Review Articles and Editorials
Bronchoscopy for the Solitary Pulmonary Nodule: Friend or Foe? Chest 2012; 142: 276-7.

Selman M et al. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med. 2012 Aug 15; 186(4):314-24.

Herbst JB et al. Hypersensitivity pneumonia: role of surgical lung biopsy. Arch Pathol Lab Med. 2012; 136(8):889-95.

Hoo ZH et al. Idiopathic pulmonary fibrosis. Thorax. 2012 ;67(8):742-6.

Frankel S. Et al. The Pulmonary Vasculitides. Am J Respir Crit Care Med 2012 ;Aug (186)( 3), 216–224.

Case Reports
Seif Fet al. A solitary pulmonary nodule mimicking lung cancer. Am J Respir Crit Care Med. 2012 Aug 1;186(3):e4.

Oviedo SP et al. Diffuse malignant mesothelioma. Arch Pathol Lab Med. 2012; 136(8):882-8.

Ong TH et al.Severe endobronchitis and airway stricture caused by inhalation of cosmetic talc. Chest. 2012 1;142(2):511-3.

August 2012 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, a multi-institutional project intended to help all of us keep pace with the rapidly evolving peer reviewed literature relevant to pulmonary pathology.  Today's journal club comes to us from Lindsay Schmidt and Chen Zhang, faculty and pulmonary pathology fellow, respectively, at the University of Michigan in a grey and rainy Ann Arbor.  What follows is their high level OVERVIEW.  Below the OVERVIEW is the ARTICLE INDEX including links to PubMed abstracts and full text articles if your institutional license allows it.  Click here if you want to see the PDF thumbnail of the articles included, and click here if you want to download the MP3 audiofile to hear exactly how it unfolded by teleconference at 9:15 EDT on Monday, August 27, 2012.

OVERVIEW
This month we combed the literature and found 20 articles we thought would be of interest to pulmonary and thoracic pathologists. Many thanks to the pulmonary pathology fellow here at the University of Michigan, Chen Zhang, who contributed a lot of hard work to preparing this journal club!

Two of the articles we chose for discussion deal with the budding and increasingly important field of molecular diagnostics in nonsmall cell lung carcinoma. In the first, Wallander et al report a series of 46 cases tested for the ALK gene rearrangement using three different methods: immunohistochemistry, FISH, and RT-PCR. They sought to determine both concordance between methods as well as interobserver variability when reading out the tests. The second article for discussion comes from the European Respiratory Journal, from Scoccianti et al, who sought to use a huge cohort of lung carcinoma patients to investigate the prognostic value of TP53, KRAS, and EGFR mutations. Our third article for discussion comes to use from Higgins et al, and is a large series which sought to determine the implications of lymphovascular invasion in NSCLC in terms of staging and its possible impact on adjuvant therapy.

Our last article for notation is a departure from the neoplastic theme, and deals with lung transplant patients. This article comes from Sam Yousem at Pitt, and looked at the histology of antibody-mediated rejection. This may be a somewhat esoteric topic, but this article has come in handy for our group on more than one occasion recently as we begin to deal with the question from clinicians on a regular basis.

For our notation articles, we found several papers dealing with prognostic factors in lung cancer, including Sun et al’s discussion of astrocyte-elevated gene-1, Kohler et al’s discussion of FGFR1, Hung et al’s paper on the prognostic significance of visceral pleural invasion, and Ito et al’s look into cancer associated stromal cells. Toffalorio et al provided us with an overview of large node negative NSCLC that shifted from stage IB to stage II when the new TNM staging guide came out. There is also an interesting look at the possibility of using breath sampling in diagnosing lung cancer from Santonico et al. Michels et al look at the use of cytology in diagnosing lung diseases. And last in our notation cases for lung neoplasms, we found a look at staining patterns in sclerosing hemangiomas from Lin et al.

This was a big month for mesotheliomas in the literature as well. First is a series from Lagana et al looking at the utility of GLUT-1, a new immunohistochemical marker, in separating benign from malignant mesothelial proliferations. Ordonez provides us with a look at a series of 10 cases of pleomorphic mesothelioma, including morphology, immunohistochemistry, and electron microscopy. Kadota et al performed a study to correlate FDG-PET findings with pleomorphic mesotheliomas.

And to round out our neoplasms, this was a bumper month for thymic carcinoma articles for some reason, all from Weisferdt and Moran. Their first article was a case series of micronodular thymic carcinomas with lymphoid hyperplasia. They then gave us a two part series of articles in AJCP, the first looking at clinicopathologic features of thymic carcinomas and the second proposing a new staging system for thymic carcinomas.

Only two non-neoplastic articles to point out this month. The first comes from Cha et al, using lung mast cell density to characterize IPF patients. And the last (and perhaps my personal favorite) an article from the only radiology journal on our list from Ross et al, describing the feasibility of performing “virtual autopsy” using CT imaging and biopsy.

That’s all the articles we culled from the pages of our journals. Hope you all are this excited about journal club:

 

 

 

 

 

ARTICLE INDEX
Discussion articles
Yousem SA, Zeevi A. “The histopathology of lung allograft dysfunction associated with the development of donor-specific HLA alloantibodies.” Am J Surg Path 36(7): 987-992.

Wallander ML, Geiersback KB, Tripp SR, Layfield LJ. “Comparison of reverse transcription-polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization methodologies for detection of echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase fusion-postive non-small cell lung carcinoma.” Arch Pathol Lab Med 136: 796-803.

Scoccianti C, Vesin A, Martel G, Olivier M, Brambilla E, Tmsit JF, Tavecchio L, Brambilla C, Field JK, Hainaut P. “Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: the EUELC cohort.” Eur Respir J 40: 177-184.

Higgins KA, Chino JP, Ready N, D’Amico TA, Berry MF, Sporn T, Boyd J, Kelsey CR. “Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy.” J Thorac Oncol 2012 7: 1141-1147.

Articles for notation
Neoplastic diseases
Sun S, Ke Z, Wang F, Li S, Chen W, Han A, Wang Z, Shi H, Wang L, Chen X. “Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression.” Hum Pathol 43: 1051-1060.

Michels G, Topalidis T, Buttner R, Engels M, Pfister R. “Usefulness of imprint and brushing cytology in diagnosis of lung diseases with flexible bronchoscopy.” J Clin Pathol 65: 649-653.

Kohler LH, Mireskandari M, Knosel T, Altendorf-Hofmann A, Kunze A, Schmidt A, Presselt N, Chen Y, Petersen I. “FGFR1 expression and gene copy numbers in human lung cancer.” Virchows Arc 461:49-57.

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 136:804-809.

Santonico M, Lucantoni G, Pennazza G, Capuano R, Galluccio G, Roscioni C, La Delfa G, Consoli D, Martinelli E, Paolesse R, Di Natale C, D’Amico A. “In situ detection of lung cancer volatile fingerprints using bronchoscopic air-sampling.” Lung Cancer 77:46-50.

Weissferdt A, Moran CA. “Micronodular thymic carcinoma with lymphoid hyperplasia: a clinicopathological and immunohistochemical study of five cases.” Mod Pathol 25:993-999.

Ordonez NG. “Pleomorphic mesothelioma: report of 10 cases.” Mod Pathol 25: 1011-1022.

Hung JJ, Jen WJ, Hsu WH, Chou TY, Lin SF, Wu YC. “Prognostic significance of the extent of visceral pleural invasion in completely resected node-negative non-small cell lung cancer.” Chest 142(1):141-150.

Lin XY, Zhang D, Zhang Y, Fan CF, Dai SD, Wang EH. “In pulmonary sclerosing hemangioma expression of B-catenin, axin, and c-myc differs between the two cell types.” Virchows Arch 461: 59-65.

Weisferdt A, Moran CA. “Thymic carcinoma, part 1: a clinicopathologic and immunohistochemical study of 65 cases.” Am J Clin Pathol 138: 103-114.

Weissferdt A, Moran CA. “Thymic carcinoma, part 2: A clinicopathologic correlation of 33 cases with a proposed staging system.” Am J Clin Pathol 138: 115-121.   

Toffalorio F, et al “Features and Prognostic Factors of Large Node-Negative Non–Small-Cell Lung Cancers Shifted to Stage II.”  J Thorac Oncol. 2012; 7: 1124–1130.

Kadota K, Kachala SS, Nitadori J, Suzuki K, Dunphy MPS, Sima CS, Travis WD, Rusch VW, Adusumilli PS. “High SUVmax on FDG-PET indicates pleomorphic sybtype in epithelioid malignant pleural mesothelioma.” J Thoracic Oncol 7:1192-1197.

Ito M, Ishii G, Nagai K, Maeda R, Nakano Y, Ochiai A. “Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma.” Chest 142(1): 151-158.

Non-neoplastic diseases
Cha SI, Chang CS, Kim EK, Lee JW, Matthay MA, Golden JA, Elicker BM, Jones K, Collard HR, Wolders PJ. “Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis.” Histopathology 61:98-106.

Ross SG, Thali MJ, Bolliger S, Germerott T, Ruder TD, Flach PM. “Feasibility of virtual autopsy with postmortem CT angiography and biopsy.” Radiology 264(1): 250-259.

July 2012 Edition

Welcome to the July 2012 Edition of Pulmonary Pathology Reviews, a collaborative, multi-institutional journal club focusing on diagnostic and academic pulmonary pathology.  Today's entry comes from Cherise Cortese at the beautiful Mayo Clinic Florida.  What follows is her OVERVIEW, highlighting the good, bad, and the ugly in peer reviewed literature in print in June 2012.  Below the OVERVIEW is an ARTICLE INDEX with links to PubMed abstracts (and full text articles if your institution allows it) for both discussion and notation articles.  Click here for the list of articles included in this week's journal club, along with page listing corresponding to the PDF summary providing thumbnails for quick reference.  And click here if you want to download the MP3 audiofile (may take awhile to download - it's a big file!) of the actual teleconference as it occurred at 9:15 EDT on Monday, July 30, 2012.

OVERVIEW
There was no lack of articles in the month of June this year. I found over 30 but weeded out several of the clinical and research articles. I have chosen an interesting handful to discuss and will mention some of the more educational articles below.
    The first article by Yserbyt et al takes a look at lung cancer rates after transplantation, which is an interesting topic. They found that bilateral lung transplants have a better outcome than single lung because the remaining native lung is more likely to develop cancer, especially in emphysema or IPF.  The second article breaks down p63 into its different termini and looks at the sensitivity and specificity of those antibodies. It looks as though p40 is the better of the termini. Tumor budding and its prognosis is discussed in the third article. An immunohistochemical profile of the cells that bud are examined and found to lack cellular adhesion molecules, which is fairly intuitive but interesting. Solis et al looked at different histologic patterns of adenocarcinomas and their respective clinical outcomes, suggesting that it may be important to list all of those different histologies that we discover. And the last article looks at the new IASLC/ATS/ERS classification of adenocarcinomas to see if it is clinically relevant. They also promoted an immunohistochemical profile to use on NSCLC for diagnostic purposes.
    Several articles for notation are worth mentioning here. One examines survival in NSCLC out to 18 years and found that “five year survival does not equal cure”.  They had a large cohort of patients that were included in the study. Leslie discusses his tractional injury theory on IPF in an Archives article this month with illustrations to make his points more clear. An article on Indium lung disease is worth reviewing, especially since we will probably see more of this in the future with the electronics being as popular as they are. United States is a big player in this industry, so it might be seen here.
    There were three yearly updates, one for vascular disease, one for environmental and occupational medicine and one for COPD.
    Case reports were not scarce this month. Several of these are of rare tumors not usually found in the lungs.
    Hope you enjoy the discussion and articles in this very busy month!

ARTICLE INDEX
ARTICLES FOR DISCUSSION
Bronchial carcinoma after lung transplantation: A single-center experience. Yserbyt et al. J Heart Lung Transplant 2012;31:585-90.

A Study of ΔNp63 Expression in Lung Non-Small Cell Carcinomas. Nonaka. Am J Surg Pathol 2012;36:895-899.

Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung. Taira et al. Lung Cancer 2012;76:423-430.

Histologic Patterns and Molecular Characteristics of Lung Adenocarcinoma Associated with Clinical Outcome. Solis et al. Cancer 2012;118:2889-99.

Tissue-Sparing Application of the Newly Proposed IASLC/ATS/ERS Classication of Adenocarcinomas of the Lung Shows Practical Diagnostic and Prognostic Impact. Sterlacci et al. Am J Clin Pathol 2012;137:946-956.

ARTICLES FOR NOTATION
Neoplastic
Aquaporin 1 is an Independent Prognostic Factor in Pleural Malignant Mesothelioma. Kao et al. Cancer 2012;118:2952-61. 

Ectopic Expression of TIM-3 in Lung Cancers: A Potential Independent Prognostic Factor for Patients with NSCLC. Zhuang et al. Am J Clin Pathol 2012;137:978-985.

Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma. Enomoto et al. J Clin Pathol 2012;65:522-527.

Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: Spatial distribution and prognostic value of GLUT1 and MCT4. Meijer et al. Lung Cancer 2012;76:316-323.

Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALK-rearrangement in lung cancer: A comprehensive study of Caucasian non-smokers. Just et al. Lung Cancer 2012;76:309-315.

Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas. Kayser et al. Lung Cancer 2012;76:445-451.

EGFR mutations detection on liquid-based cytology: is microscopy still necessary?  Malapelle et al. J Clin Pathol 2012;65:561-564.

Effusion Immunocytochemistry as an Alternative Approach for the Selection of First-Line Targeted Therapy in Advanced Lung Adenocarcinomas. Tsai et al. J Thorac Oncol 2012;7:993-1000.

Early Detection of Lung Cancer by Molecular Markers in Endobronchial Epithelial-Lining Fluid. Kahn et al. J Thorac Oncol 2012;17:1001-1008.

Positive pre-resection pleural lavage cytology is associated with increased risk of lung cancer recurrence in patients undergoing surgical resection: a meta-analysis of 4450 patients. Saso et al. Thorax 2012;67:526-532.

Five-year survival does not equal cure in non-small cell lung cancer: A Surveillance, Epidemiology, and End Results-based analysis of variables affecting 10- to 18-year survival. Hubbard et al. J Thorac Cardiovasc Surg 2012;143:1307-13.

Non-Neoplastic
Idiopathic Pulmonary Fibrosis May Be a Disease of Recurrent, Tractional Injury to the Periphery of the Aging Lung. Leslie. Arch Pathol Lab Med 2012;136:591-600.

MUC5AC, cytokeratin 20 and HER2 expression and K-ras mutations with mucinogenic growth in congenital pulmonary airways malformations. Rossi et al. Histopathology 2012;60:1133-1143.

Prospective study of endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes versus transbronchial lung biopsy of lung tissue for diagnosis of sarcoidosis. Oki et al. J Thorac Cardiovasc Surg 2012;143:1324-29.

Indium Lung Disease. Cummings et al. Chest 2012;141(6):1512-1521.


Review Articles
Anaplastic thymic carcinoma: a clinicopathologic and immunohistochemical study of 6 cases. Weissferdt et al.  Human Pathology 2012;43:874-877.

Update in Pulmonary Vascular Diseases 2011. Hassoun et al. Am J Respir Crit Care Med 2012;185(11):1177-1182.

Update in Environmental and Occupational Medicine 2011. Blomberg. Am J Respir Crit Care Med 2012;185(11):1166-1170.

Update in Chronic Obstructive Pulmonary Disease 2011. Barnes et al. Am J Respir Crit Care Med 2012;185(11):1171-1176.


Case Reports
Endobronchial Pulmonary Angiomatoid Fibrous Histiocytoma: Two Cases with EWSR1-CREB1 and EWSR1-ATF- Fusions. Thway et al. Am J Surg Pathol 2012;36:883-883.

Case 182: Pulmonary Amyloidosis. Lee et al. Radiology 2012;263:929-932.
       
Primary pulmonary epithelioid angiosarcoma presenting as a solitary pulmonary nodule on image. Yang et al. Pathology International 2012;62:424-428.

A 64-Year-Old Man With Progressive Dyspnea and Cough Productive of Copious Amounts of Clear Sputum. Kloesel et al. Chest 2012;141(6):1622-1625.

Whipple Disease Revealed by Lung Involvement. Urbanski et al. Chest 2012;141(6):1595-1598.

An ectopic ACTH-producing small cell lung carcinoma associated with enhanced corticosteroid biosynthesis in the peritumoral areas of adrenal metastasis. Satoh et al. Lung Cancer 2012;76:486-490.

June 2012 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, an international multi-institutional journal club intended to help all of us keep pace with the latest print literature touching on issue relevant to diagnostic pulmonary pathology.  This week's journal club comes to us from Marie-Christine Aubry at Mayo Clinic Minnesota.  What follows is her OVERVIEW of those articles that made the cut, followed by an ARTICLE INDEX with links to PubMed abstracts (and full text of articles if your institutional access allows it).  Click here if you want to see her PDF summary of not only the articles chosen for discussion but also those included as note items only.  Click here if you want to hear the teleconference recorded at 08:15 CDT on Monday, June 25, 2012.

OVERVIEW
May 2012 generated 18 articles.  Amongst the most interesting were 3 great review articles on targeted therapy in lung cancers including one focusing on resistance to EGFR-TKI and potential alternative strategies, and one review exclusively on the genetic alterations of squamous cell carcinoma and potential therapeutic targets, the often forgotten cancer in the world of novel therapy!   For discussion, I usually try to identify articles that have immediate clinical relevance and there were few of those. So I added one for personal reasons which I admit will be more of interest to folks in Rochester but hopefully, we will all learn from it.

The articles for discussion include:

Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis by Hariri et al. In this article, investigators from Boston and Japan describe the histologic appearance of acute HSP either as a de novo presentation or as an exacerbation of a known chronic HSP.  All had features of chronic HSP but the distinctive acute features included airspace fibrin and interstitial neutrophils.

Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy by Pataer et al. This study from MD Anderson is well executed and thorough with detailed histopathologic examination of a group of patients who had neo-adjuvant therapy.  They added the equivalent of a control group of patients who did not get therapy which really didn’t had much as these patients were significantly different based on histologic subtype and of course stage.  But they wanted to show that features such as necrosis/% viable cells did not have the same impact on outcome in each group.  Indeed, this study nicely demonstrated that post adjuvant therapy tumors with few viable cells did much better and survival also correlated with the downstaged effect of the therapy, findings not seen in the group of patients who did not undergo adjuvant therapy.

Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure by Knowles et al.  In Rochester, we get numerous EM studies for cilia and this article caught my attention.  It is an example of normal phenotype with abnormal genotype.  And this will have impact on the way patients with PCD will be diagnosed.  Currently, much emphasis is put on the ultrastructure however, over the last few years, it became clear patients may have had normal EM yet have significant clinical manifestations of PCD, thus the introduction of new tests in the diagnostic algorithm such as high-speed videomicroscopy to evaluate ciliary beat pattern. However, as highlighted by Knowles et al, this test requires significant expertise and not performed in many centers, thus the potential need for genetic testing.  Indeed, as previously shown and confirmed in this study, patients with normal cilia by EM yet clinical manifestations of PCD do have distinct mutation in DNAH11 not seen in patient with PCD with abnormal ciliary ultrastructure.  This could be the basis of a genetic testing to identify these patients.

I guess no pulmonary journal club would be complete without discussing an article on malignant mesotheliomas. Mesotheliomas with small cell features: report of eight cases by Ordonez is just that, a report of few cases where the mesothelioma cells are small and raise a differential diagnosis with small cell carcinoma and small blue round cell tumors.

Enjoy!

ARTICLE INDEX
ARTICLES FOR DISCUSSION
1- Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis. Hariri et al. Hum Pathol 2012; 43: 660

2- Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy.  Pataer et al.  JTO 2012; 7: 825

3- Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure.  Knowles et al.  Thorax 2012; 67:433

4- Mesotheliomas with small cell features: report of eight cases.  Nelson G Ordonez.  Mod Pathol 2012; 25:689

ARTICLES FOR NOTATION
Original articles
1- Airway Smooth Muscle Hypertrophy and Hyperplasia in Asthma. James et al. Am J Respir Crit Care Med 2012; 185: 1058

2- Lung Manifestations in an Autopsy-Based Series of Pulmonary or Disseminate Nontuberculous Mycobacterial Disease. O’Connell et al. Chest 2012; 141:1203

3- Hyaluronidase splice variants are associated with histology and outcome in adenocarcinoma and squamous cell carcinoma of the lung.  De Sa et al.  Hum Pathol 2012; 43: 675

4- Gene expression signatures differentiate adenocarcinoma of lung and breast origin in effusions. Davidson et al. Hum Pathol 2012; 43: 684

5- RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations.  Iwakoshi et al.  Int J of Pathol 2012; 62:324

6- NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation.
Dimitrakopoulos et al. Virchows Arch 2012; 460 :515

7- CCL2, Galectin-3, and SMRP Combination Improves the Diagnosis of Mesothelioma in Pleural Effusions. Blanquart et al. JTO 2012; 7: 883

8- Exploratory analysis of activation of PTEN–PI3K pathway and downstream
proteins in malignant pleural mesothelioma (MPM).  Cedrésa et al. Lung Cancer 2012; 77:192

Case reports
1- Pulmonary Hyalinizing Granuloma With Associated Elevation in Serum and Tissue IgG4 Occurring in a Patient With a History of Sarcoidosis. Chapman et al. AJSP 2012; 36: 774

2- A 52-Year-Old Smoker With an Incidental Pulmonary Nodule. Das et al.  Chest 2012; 141: 1346

3- Difference in Clonality as a Tool for Differential Diagnosis of Primary Versus Secondary Lung Neoplasms. Leuzzi et al. JTO 2012 ; 7 :934

Review articles
1- Advances in Treatment of Lung Cancer With Targeted Therapy.  Cagle and Chirieac. Arch Pathol Lab Med 2012; 136:504

2- Genetic Changes in Squamous Cell Lung Cancer – A Review.  Heist et al. JTO 2012; 7:924

3- EGFR–TKI resistant non-small cell lung cancer (NSCLC): New developments and implications for future treatment.  Bruggera and Thomasb. Lung Cancer 2012; 77:2