The Daily Sign-Out

General Surgical Pathologist is Dead

Excellent post from Digital Pathology Blog on the demise of the general surgical pathologist! It's amazing (and worrisome) that this happened so quickly in our field.

What happens to those "orphan" areas that don't really have a subspecialty training or certification or lack sufficient volume-even in some training centers--to "pay for" a full-time subspecialist? Head and neck, neuropathology, cardiac pathology for example? I propose that the general decline in autopsies (providing exposure to general pathology), lack of recognition and reimbursement for clinical pathology (and autopsies), and GI/urology usurpation of pathology practices have contributed mightily to this trend and almost singularly focuses resident training and practice on surgical pathology. I fear "molecular pathology" (and something unique, separate or distinctive from plain-ol' surgical pathology) will only exacerbate this trend. I could see there being molecular pathologists that are uncomfortable signing out surgical pathology--even within a subspecialty.

Kudos to Dr. Kaplan for broaching this subject! This is a complex issue that I'm not sure is even on the radar screens of our representative pathology societies.

CAP Public Comment Period for New Biomarker Reporting Checklists

Take a look at the new cancer biomarker reporting checklists proposed by the College of American Pathologists for breast, colon and lung cancers.  You don't have to be a CAP member to provide comments (but I encourage you to join CAP anyway!).

In an effort to improve consistency and completeness in reporting results of cancer biomarker testing, the College of American Pathologists (CAP) has produced new cancer biomarker reporting templates for Breast, Lung, and Colon. These templates were developed primarily to respond to pathologist user feedback about timing of reporting and structural consistency of ancillary studies data elements in the CAP Cancer Protocols. The development of these templates has been a collaborative effort between the CAP, the Association for Molecular Pathology (AMP), the American Society of Clinical Oncology (ASCO), Centers for Disease Control and Prevention (CDC), the American Joint Committee on Cancer (AJCC), and many other participating organizations.

The cancer biomarker reporting templates are intended to encompass all important data elements for routinely assessed tumor markers for each site, as well as some optional markers. Once these templates are approved by the CAP for general use, they will replace the Ancillary Studies sections of their corresponding CAP cancer protocols.

Prior to the release of these new biomarker reporting templates, the CAP will host a public comment period. You can review the revisions and submit feedback online. The public comment period will run from December 3–31, 2012. Please note that submitted comments are not instantly available for review and will be posted on a weekly basis.

The Cancer Biomarker Reporting Workgroup would appreciate your feedback on these new biomarker reporting templates. Thank you in advance for taking the time to review these and submit your responses.

Multilocular Cystic Renal Cell Carcinoma

Multilocular cystic renal cell carcinoma is an uncommon but diagnostically challenging variant of renal cell carcinoma that fortunately has an excellent prognosis. Histological features of this tumor include thin fibrous septa lined by clear cells with low grade nuclear atypia and small aggregates of similar cells in the septa. Strictly speaking, however, this variant does not have solid nodules in the septa, papillary projections into cystic spaces, or solid masses in an otherwise cystic tumor. Note that conventional clear cell RCC can focally show histologically similar areas. When examining a resected tumor, the recognition of this tumor is relatively straightforward (provided you take and examine multiple sections). But encountering these lesions on needle biopsy (frequently followed by cryoablation!) is not-so straight-forward but important because of the important prognostic differences between this variant and conventional clear cell RCC. A paper by Williamson, Halat, Eble et al in the October 2012 issue of American Journal of Surgical Pathology (2012;36:425-433) present the authors’ experience and data on an immunohistochemical panel that will be helpful to pathologists confronting adult cystic renal tumors.

The authors studied 24 well-characterized multilocular cystic RCCs (ML-RCC) and 24 consecutive matched conventional clear cell RCCs (CC-RCC) with an immunohistochemical panel consisting of CD10, CK7, AMACR(P504S), vimentin, EMA, CAM5.2, carbonic anhydrase IX (CA-IX), PAX-2, smooth muscle actin (SMA), ER, and PR.

Significant differences were found between ML-RCC and CC-RCC with staining for CD10 and CK7. In ML-RCC CD10 showed focal apical membranous staining in cyst-lining cells in 38% of cases, diffuse staining in both cyst-lining and septal cells in 25%, and was negative in 37%. CC-RCC, on the other hand, was positive in 96% of cases with the majority showing diffuse reactivity throughout the tumors. In contrast, CK7 was positive in 92% of ML-RCC cases, usually (63%) showing diffuse staining of the cyst-lining cells, while CK7 was negative in 62% of CC-RCC cases with 38% of these cases showing only focal reactivity (none > 25%).

Almost all cases of both types show positivity for EMA, CAM5.2, CA-IX, and PAX-2 but, notably, CA-IX most clearly highlighted individual clear cells and septal aggregates in ML-RCC and showed diffuse, strong, uniform membranous staining in the cyst-lining cells.

The authors conclude that none of the markers show sufficient positive or negative predictive value to supplant rigorous sampling and light microscopic examination. Indeed, I have discussed this very situation with Dr. John Cheville at Mayo Clinic Rochester, who has published extensively on renal pathology and has studied ML-RCC in particular, and he stressed the importance of careful microscopic examination without relying on IHC to identify or characterize clear cells, especially those in septal aggregates. The authors point out the unexpected finding of CK7 reactivity in ML-RCCs, which raises the possibility of cystic papillary RCC—a tumor that also shows prominent cystic architecture, albeit with at least focal papillary structures. This tumor, however, also typically shows a rather unique finding of solid acinar areas composed of branching ductular or tubular structures.

To me, the most useful finding is the use of CA-IX to highlight septal aggregates, which would be especially useful in CT-guided needle biopsies. It seems tempting to add CD10 and CK7 but these don’t seem hardy enough to be very helpful and might actually be confusing. Perhaps this article isn’t one that you want to rush out and read but keep it in mind next time you get one of these cystic renal tumors.

Impact of the Integrin Signaling Adaptor Protein NEDD9 on Prognosis and Metastatic Behavior of Human Lung Cancer

Thought this was an intriguing abstract. Signaling crosstalk between EGFR and integrins was a hot topic at AACC meeting earlier this year.




From Evernote:




Impact of the Integrin Signaling Adaptor Protein NEDD9 on Prognosis and Metastatic Behavior of Human Lung Cancer
Clipped from: http://clincancerres.aacrjournals.org/content/early/2012/10/19/1078-0432.CCR-11-2162.abstract?papetoc



Impact of the Integrin Signaling Adaptor Protein NEDD9 on Prognosis and Metastatic Behavior of Human Lung Cancer

Shunsuke Kondo1,Satoshi Iwata2, Taketo Yamada4, Yusuke Inoue7, Hiromi Ichihara3, Yoshiko Kichikawa2, Tomoki Katayose2, Akiko Souta-Kuribara2, Hiroto Yamazaki2, Osamu Hosono2, Hiroshi Kawasaki2, Hirotoshi Tanaka2, Yuichiro Hayashi4, Michiie Sakamoto4, Kazunori Kamiya5, Nam H. Dang8, and Chikao Morimoto6+
Authors' Affiliations: 1Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital; 2Department of Rheumatology and Allergy, Research Hospital, 3Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo; 4Department of Pathology, School of Medicine, 5Department of Pathology and Department of Surgery, Division of General Thoracic Surgery, School of Medicine, Keio University;
6Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University,
Tokyo; 7Department of Diagnostic Radiology, Kitasato University Hospital, Kanagawa, Japan; and 8Division of Hematology and Oncology, University of Florida Shands Cancer Center, Gainesville, Florida


Corresponding Author:
Chikao Morimoto, Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine,
Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Phone: 81-3-3868-2310; Fax: 81-3-3868-2310; E-mail: morimoto@ims.u-tokyo.ac.jp


Abstract

Purpose: In a substantial population of non–small cell lung cancer (NSCLC), expression and activation of EGF receptor (EGFR) have been reported and is regarded as a novel molecular target. A growing body of evidence has shown the signaling crosstalk between EGFR and integrins in cellular migration and invasion. NEDD9 is an integrin signaling adaptor protein composed of multiple domains serving as substrate for a variety of tyrosine kinases. In the present study, we aimed at elucidating a role of NEDD9 in the signaling crosstalk between EGFR and integrins.


Experimental Design: Using NSCLC cell lines, we conducted immunoblotting and cellular migration/invasion assay in vitro. Next, we analyzed metastasis assays in vivo by the use of xenograft transplantation model. Finally, we retrospectively evaluated clinical samples and records of patients
with NSCLCs.


Results: We showed that tyrosine phosphorylation of NEDD9 was reduced by the inhibition of EGFR in NSCLC cell lines. Overexpression of constitutively active EGFR caused tyrosine phosphorylation of NEDD9 in the absence of integrin stimulation. By gene transfer and gene knockdown, we showed that NEDD9 plays a pivotal role in cell migration and invasion of those cells in vitro. Furthermore, overexpression of NEDD9 promoted lung metastasis of an NSCLC cell line in NOD/Shi-scid, IL-2Rγnull mice (NOG) mice. Finally, univariate and multivariate Cox model analysis of NSCLC clinical specimens revealed a strong correlation
between NEDD9 expression and recurrence-free survival as well as overall survival.


Conclusion: Our data thus suggest that NEDD9 is a promising biomarker for the prognosis of NSCLCs and its expression can promote NSCLC
metastasis. Clin Cancer Res; 1–13. ©2012 AACR.



Footnotes

Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).



Received August 23, 2011.
Revision received August 20, 2012.
Accepted August 28, 2012.

©2012 American Association for Cancer Research.

Lack of NKX2-1 (TTF-1) expression in lung adenocarcinoma and EGFR mutations

My last post discussed one of the two papers I thought were notably in the October 2012 Journal of Thoracic Oncology. Here's my take on the other paper by Vincentin et al (J Thorac Oncol 2012;7:1522-1527). NK2 homeobox 1 is the "proper" name that we pathologists more affectionately call "TTF-1." NKX2-1 is normally expressed in type 2 pneumocytes and non-ciliated bronchiolar epithelial cells and has been shown to play an active role in sustaining lung adenocarcinoma. Since NKX2-1 is found in about 95% of lung adenocarcinomas with EGFR mutations, the authors studied whether NKX2-1 IHC staining is a useful provisional marker for guiding EGFR-TKI therapy in advanced stage lung adenocarcinoma while EGFR mutation analysis is being completed.

This is a large study including 810 consecutive NSCLC tumor specimens referred for routine diagnostic EGFR mutation testing. While one may debate the ultimate practicality of this study with respect to it's purpose, what recommends it to me is that the study population more closely mirrors what a general pathologist encounters in routine practice. The study includes biopsies (N=594), resections (N=162), and cytology specimens (N=54) and the overall incidence of EGFR mutations was 14%. It is important to note that the authors used the TTF-1 8G7G3/1 antibody clone for IHC testing. There are substantial differences between the different antibody clones for TTF-1 that have been recently noted in the literature and it is important to take note of this detail when analyzing articles that test NKX2-1 or determining the best antibody to use in your lab.

Results and Authors' Conclusions

NKX2-1 was evaluable in 98% of cases and was positive in 68%, negative in 32%. NKX2-1 positive immunostaining showed a strong correlation with EGFR mutations: in the EGFR-mutated cases, NKX2-1 was positive in 92% and negative in 8%. The probability of absent of EGFR mutation in all adenocarcinomas is 80%; in NKX2-1-negative adenocarcinomas that probability rises to 96%. The authors found a negative predictive value of negative NKX2-1 IHC for EGFR mutation to be >95%.

The authors conclude that if treatment is clinically urgent, the NPV of NKX2-1 expression is appropriate to use as a surrogate marker to choose conventional chemotherapy as starting treatment pending EGFR mutation analysis. The PPV of NKX2-1 is not sufficient to warrent adding an EGFR-TKI. Also, the result of NKX2-1 is not specific enough to exclude a specimen from EGFR-mutation analysis.

My take-aways

While the clinical situation in which NKX2-1 testing would influence an urgent treatment decision may uncommon, I think it is important to note this paper because when it does occur, the pathologist can play a vital role in assisting the clinician determine the management for such a patient. If one is following the diagnostic algorithm from the 2011 IASLC guidelines, one would not routinely test either histologically diagnostic adenocarcinomas or squamous cell carcinomas for NKX2-1 (TTF-1). Another point is that the SPT24 clone for TTF-1 is a more sensitive antibody for TTF-1/NKX2-1 (a point that the authors make as well) and, therefore, one would expect the percentage of NKX2-1-negative cases to be fewer and the NPV to be higher. Finally, the authors used direct sequencing of EGFR exons 19-21, followed by HRM screening, and PCR-sequencing for identifying EGFR mutations; another methodology could influence the denominator of EGFR-mutated cases and, thus, the predictive value of NKX2-1 IHC testing.

Loss of PTEN as a poor prognostic marker for lung adenocarcinoma

The October 2012 Journal of Thoracic Oncology presents two papers of interest to pathologists.

The first study is a paper by Yanagawa et al. that correlates PTEN expression with gene copy number, P53 expression, EGFR and KRAS mutations in surgically resected NSCLCs and examines the relationship between PTEN status, clinicopathologic characteristics and survival.

Recall that PTEN functions as a lipid phosphatase that negatively regulates the PI3K/AKT anti-apoptotic and proliferation pathway, which is a key downstream component of the EGFR pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with LOH seem to be uncommon.

PTEN expression was examined by immunohistochemistry in a tissue microarray constructed from 152 patients with a median follow-up time of 2.3 years. The study consisted of 62% adenocarcinomas, 29% squamous cell carcinomas and 9% of tumors called “other.” Since this is a study of surgically resected patients, there is obviously an overrepresentation of stage one tumors compared to all patients typically diagnosed with lung cancer. Smokers comprised 79% of the study population. EGFR mutations were found in 15% and KRAS mutations and 22%. The authors defined loss of PTEN as complete absence of cytoplasmic staining in tumor cells.

Loss of PTEN was found in 63 out of 152 cases (41.4%). No significant differences were found between loss of PTEN and smoking, EGFR mutations, KRAS mutations, or p53 expression.

Patients with loss of PTEN expression had significantly worse disease-free survival compared with patients with retained PTEN expression (HR 1.76, log-rank p=0.038) but the prognostic effect was related directly to tumor histology: loss of PTEN was significantly associated with shorter DFS in adenocarcinoma only (HR 2.72, log-rank p=0.002). This association was also significant in multivariate analysis controlling for sex, age, histology and stage.

Recent data suggest that loss of PTEN may contribute to EGFR TKI resistance in NSCLC. PIK3CA mutations only account for 2% to 4% of NSCLC but loss of PTEN would result in constitutive activation of the PI3K pathway. This study suggests that lung adenocarcinomas selected for PTEN status may be susceptible to PI3KCA inhibitors that are currently under investigation.

My next post will discuss the other interesting paper in JTO this month.

All the RAGE in Asthma

My lab's CAP inspection is finally over!!! Now I can get back to more regular blogging (without guilt).

This month's American Journal of Pathology features an intriguing article that proposes a central role for receptor for advanced glycation end products (RAGE) in the pathogenesis of asthma (abstract).  

First, some background.  RAGE is a multiligand receptor for ligands including S100 proteins, HMGB1, amyloid beta, and heparin.  There are two forms of RAGE: membrane RAGE (mRAGE) which is thought to be proinflammatory, and soluble (i.e., cytoplasmic) RAGE (sRAGE) considered to be anti-inflammatory.  RAGE transcripts and proteins are preferentially expressed in lung.

This study uses a house dust mite (HDM) antigen sensitization/challenge model in RAGE knockout (RAGE-ko) mice to directly assess the role of RAGE in asthma/allergic airway disease (A3D).  The authors confirm these results using a different model, ovalbumin, to confirm that the same effects of RAGE are independent of the antigen challenge.

The authors measured cell counts in BALF obtained from Diff-Quik stained sections; they measured BALF for levels of eotaxin, eotaxin-2, IL-4, IL-5, and IL-13 by ELISA.  The prepared RNA from whole lung and performed qRT-PCR for RAGE, IL-5, and IL-13.  FFPE lung was examined for RAGE by immunofluorescence and tissue eosinophilia. Finally (if you can picture this), they measured respiratory mechanics in both wt and RAGE-ko mice.

Most of the measures of A3D are not seen in RAGE-knockout mice after HDM challenge compared to wt mice.  Following HDM challenge, RAGE-knockout mice showed no significant changes in pulmonary function testing; no increased eosinophilic infiltrates, goblet cell hyperplasia, or increased mucin expression; no increases in IL-5, IL-13, eotaxin, or eotaxin-2.  The latter suggests that canonical mediators of eosinophil recruitment and airway remodeling are abrogated in the absence of RAGE and that RAGE likely acts as a proximal mediator in one or more proinflammatory pathways that lead to the functional and pathologic changes seen in A3D.  However, IL-4, IgE, and HDM-specific IgG1 are the same between wt and RAGE-knockout mice--indicating that humoral immunity remains intact in the absence of RAGE and that IgE alone does not appear to play a significant role in this model.  The ovalbumin model showed similar data indicating that the role of RAGE in murine A3D is independent of the particular epitopes involved in antigen sensitization and challenge.

This is a very interesting paper that challenges some longstanding ideas about the understanding of the pathogenesis of asthma.  Certainly worth noting as follow-up studies come out.

 

Hypersensitivity Pneumonitis: recent updates

There have been two recent papers reviewing hypersensitivity pneumonitis (HP) that I had to summarize for myself and am sharing with you. While idiopathic pulmonary fibrosis/usual interstitial pneumonitis (IPF/UIP) may be the prototype for interstitial lung disease, I think that hypersensitivity pneumonitis is more frequently encountered or strongly considered in the differential diagnosis as a non-neoplastic lung biopsy specimen in “the daily sign-out,” at least in community-based general surgical pathology practice, and especially since the majority of IPF cases are now diagnosed by high-resolution CT scans without biopsy. Thus, being a practical sort, I suggest that a solid appreciation for the clinical, radiographic and pathological features of HP would help resolve many cases you might encounter in practice.

The paper by Selman, Pardo and King in the August 15, 2012 Am J Respir Crit Care Med (abstract) is more clinically oriented, while the paper by Herbst and Myers in the August 2012 Arch Pathol Lab Med (abstract) focuses on the role of surgical biopsy in the diagnosis of HP. I refer (defer?) to the Dail and Hammar Pulmonary Pathology textbook for the definitive description of the pathological findings in HP. (I also suggest that curling that textbook--volume 1--with 10 reps for each arm will give you beastly biceps in a few weeks’ time (hey--Kindle version anytime soon?).

One of the interesting aspects of the AJRCCM paper is the discussion on pathogenesis. The authors review the “2-hit” hypothesis: that there is a pre-existing genetic susceptibility and/or environmental factors, followed by exposure to one of the many antigens associated with HP. The antigens can be roughly divided into 3 groups: 1) thermophilic actinomycetes (Saccharopolyspora rectivirgula) as well as a variety of other fungi (Aspergillus, Penicillium spp); 2) a complex mixture of high- and low-molecular weight proteins from avian serum, feces, and feathers; 3) water-borne non-tuberculous mycobacteria. Importantly, no genetic factors have been consistently associated with HP. But certain polymorphisms have been identified that are associated with increased risk, including HLA-DR and -DQ polymorphisms, polymorphisms in the genes coding for TAP transport peptides MHC molecules for presentation to cytotoxic T cells, and polymorphisms in β type 8 (PSMB8)--an immunoproteasome catalytic subunit that participates in degradation of ubiquinated proteins to generate peptides for antigen presentation by class I MHC molecules. Finally, the authors discuss the role of cigarette smoking in HP. It is somewhat curious but known clinically that HP is less frequent in smokers compared to non-smokers. It is hypothesized that nicotine blunts the response to antigen exposure by its effects on decreasing macrophage activation, decreasing lymphocyte proliferation, and impairing T-cell function. However, when HP does occur in smokers, they tend to develop a chronic clinical course characterized by more recurrent episodes of disease and have a poorer survival rate compared with HP in non-smokers.

Classically (“”), HP is divided into acute, subacute, and chronic forms. However, there are no accepted clinical criteria that distinguish the various forms. Moreover, there is little information regarding the latency period between antigen exposure and disease onset. Indeed, it is uncertain that these divisions truly represent different stages of the disease.

Recently, cluster analysis studies suggest a two-cluster model for HP that correlates with observed clinical profile and the type of antigen exposure. Cluster 1 corresponds to the clinically “acute” form of HP. It is associated with an influenza-like syndrome occurring a few hours after a substantial exposure, more recurrent systemic symptoms, and a normal chest xray. Cluster 1 tends to occurs in individuals exposed to thermophilic actinomyces or fungi (≈”farmer’s lung”). Cluster 2 corresponds to the clinically “chronic” form of HP. It is associated with more features of severe, chronic disease (e.g. digital clubbing, hypoxemia, restrictive pattern by PFTs, fibrosis on HRCT scans) as well as slowly progressive chronic respiratory disease. This cluster tends to occur in individuals with bird antigen exposure. As pointed out by Herbst and Myers, this is the form one would be more likely to encounter in a biopsy situation as it mimics IPF/UIP or fibrotic NSIP. Of note, HRCT features that would favor HP over UIP/NSIP include lobular areas with decreased attenuation and air trapping, centrilobular nodules, and lack of lower zone predominance. The cluster analysis by 

Pathology of HP

As one may have surmised already, “acute” HP is just not biopsied very often so it is not very well-characterized. When specimens have been examined in which patients were diagnosed clinically with acute HP, the histologic findings resemble acute fibrinous organizing pneumonia. The “chronic” form of HP is much better studied and characterized as consists of a histologic triad of chronic interstitial inflammation, nonnecrotizing granulomas, and cellular bronchiolitis.  While this triad is seen in around 80% of patients with the clinical diagnosis of HP, it is not specific for HP.

The chronic interstitial infiltrate consists of a patchy and variably intense lymphoplasmacytic interstitial infiltrate that is frequently most intense around small bronchi and bronchioles. A salient point by Herbst and Myers (that I have noticed myself as well) is that this infiltrate may be accompanied by alveolar macrophages in adjacent alveoli with occasional aggregates of foamy macrophages suggesting lipid pneumonia. They also note that large numbers of foamy macrophages are frequently seen in pigeon-breeder’s disease. Importantly, necrosis and vasculitis are not seen. Nonnecrotizing granulomas may be found around respiratory bronchi or bronchioles as well as in the interstitium or in alveoli (so basically anywhere). These are “poorly-formed” (cf. sarcoidal granulomas) and composed of epithelioid histiocytes and Langhans’ giant cells. One helpful tip is the use of cathepsin K by IHC to help identify microgranulomas, particularly in “subacute” cases, but I think it would probably be helpful when granulomas don’t pop out at you. Another notable point is that the giant cells frequently contain cholesterol clefts, Schaumann bodies, and/or birefringent oxalate crystals. The cellular bronchiolitis is somewhat self-explanatory btu is primarily lymphocytic and extends into adjacent alveolar interstitium.

Herbst and Myers also point out some other significant “soft” findings that can be valuable in the diagnosis of HP. Small foci of organizing pneumonia pattern are found in up to 60% of patients diagnosed with HP. Small airways involvement may be found (more frequently in farmer’s lung than pigeon breeder’s disease) and adds an obstructive component. Mast cells are a constant finding and are frequently found in areas of interstitial fibrosis. And last but not least--interstitial fibrosis. Significant intersitial fibrosis is frequently found in patients who are biopsied months to years after the onset of symptoms as well as in those who have repetitive or persistent exposure to the putative antigen. Histologically, the fibrosis may have a UIP-like pattern identical to IPF.

As a personal note, I have found that the diagnosis of HP is typically made by carefully correlating the biopsy findings with the patient’s clinical history and radiographic findings in collaboration with the pulmonologist and radiologist. The paper by Selman, Pardo and King highlights important clinical findings of which we should be aware in consideration of the histological findings and the paper by Herbst and Myers emphasizes those histological features that might lead one to consider HP perhaps with less than adequate or preliminary clinical information. Both papers are timely and highly recommended but I hope I’ve been able to summarize them adequately for you.

Apps & Smartphones in Medical Education

Medical students across the country are coming into a day and age where technology rules, and in a society where iPads and Android phones are voted king, it is no small wonder that professors at the most highly coveted medical schools in the country are moving forward with technology and bringing it right to their students. 

via www.tissuepathology.com

The always interesting "Digital Pathology Blog" posted a nice summary of current medical schools that have developed apps geared toward students. My recent experience with M2 medical students is that they increasingly seeking their information on the Web and eschewing the assigned textbook and even my course syllabus. So a mobile app makes some sense but it seems that we (as educators) haven't really used social media, such as Twitter or Facebook, to its full potential yet. That being said, a course "app" seems a bit gimmicky.

Pulmonary Arterial Enlargement and Acute Exacerbations of COPD — NEJM

Interesting article more from the radiology perspective but it would be interesting to know if there is an autopsy study of pathological findings that would corroborate the radiographic measurements. Would they be comparable even?

Pulmonary Arterial Enlargement and Acute Exacerbations of COPD — NEJM.