Pulmonary Pathology Review

Welcome to Pulmonary Pathology Review

Welcome to Pulmonary Pathology Review, a blog dedicated to regular and succinct review of articles selected from the peer-reviewed literature that are likely to be of value to anyone interested in diagnostic pulmonary pathology.  This blog has its roots in a monthly journal club that began at Mayo Clinic Rochester in December 2000.  The goal was to regularly review the literature for one another on a rotational basis since none of the founding members were keeping pace with the information that she or he needed in the course of pathology practice, education and research.  We have since adopted a teleconference model that allowed us to expand and include interested faculty at all three Mayo Clinic sites as well as the Universities of Michigan, Manitoba, Calgary and Vermont.  To date we have reviewed thousands of articles!

We currently have 12 participating faculty as listed below.  Each of us, on a rotating basis, reviews a previously selected group of journals (see below) and chooses articles with relevance to pulmonary pathology.  Each article is encapsulated as a summary that is available in PDF format.  The summaries are distributed to all participants and discussed in a free-spirited and open fashion on the last Monday of the month (08:15 CST).  As a group we are dedicated to remaining critical consumers of the peer-reviewed literature while also having fun at our own or others’ expense!  If you are an author coming to this site in the hope of gaining warm fuzzies regarding our view of your work, you might consider walking away!  Things said are not intended to offend (mostly) but rather to stimulate critical review of new information as it tumbles down around us.  Please accept our comments in the constructive spirit with which they are offered.

Purpose of this blog is to allow you access to the content generated in the course of our journal club, which includes not only the monthly summaries but also MP3 audio files of the actual 45 minute teleconferences.  We also provide links to the abstracts in either PubMed or the source journal.  If you have any comments, nasty or nice, we would love to hear from you!  In the meantime, consider this the only stop necessary when it comes to keeping up with the fast-paced world of lung pathology!

PulmPathRev participants
Marie-Christine Aubry (Mayo Clinic Minnesota)
Kelly Butnor (University of Vermont)
Thomas Colby (Mayo Clinic Arizona)
Cherise Cortese (Mayo Clinic Florida)
Margaret Kelly (University of Calgary)
Andras Khoor (Mayo Clinic Florida)
Amir Lagstein (University of Michigan)
Joseph J. Maleszewski (Mayo Clinic Minnesota)
Jeffrey Myers (University of Michigan)
Anja C. Roden (Mayo Clinic Minnesota)
Lindsay Schmidt (University of Michigan)
Henry Tazelaar (Mayo Clinic Arizona)
Joanne Yi (Mayo Clinic Minnesota)

PulmPathRev journal list
Pathology
Advances Anat Pathol
Am J Surg Pathol
A J Clin Pathol
Archives Pathol Lab Med
Histopathology
Human Pathol
J Clin Pathol
Modern Pathol

Pulmonary Medicine and Thoracic Surgery
Am Rev Resp Crit Care Med
Cancer
Chest
European Respiratory Journal
J Thorac Oncology
Thorax

May 2012 Edition

Welcome to the May 2012 edition of Pulmonary Pathology Reviews, this month coming to us from Kelly Butnor at the University of Vermont in beautiful Burlington.  Kelly identified 16 articles worthy of attention, and has summarized them in a succinct Cliff Notes version available as a PDF file by clicking here.  What follows is her OVERVIEW, highlighting the must-knows and the not-so-much including a warning on an unanticipated risk of electronic cigarettes (I know . . . who knew?!).  The ARTICLE INDEX that follows includes links to the PubMed abstracts.  If you want to hear the international, multi-institutional teleconferece as it occurred on Monday, May 21, 2012 at 09:15 EDT click here to download the MP3 file.

OVERVIEW
Springing forth in April 2012 were 16 articles of at least some clinical relevance relating to pulmonary pathology, four of which are selected for discussion.

Furuya et al propose that the pulmonary cysts in Birt-Hogg-Dubé syndrome represent a hamartoma-like cystic alveolar formation associated with deranged mTOR signaling.  They argue that although frequently misdiagnosed as nonspecific cystic disease, the histopathologic features of BHD syndrome-associated pulmonary cysts are distinct from other bullous diseases.
 
Adding to the already impressive array of adverse effects of amiodarone, Larsen along with colleagues that include our very own journal club participants Drs. Colby and Tazelaar, report on 2 newly appreciated patterns of amiodarone lung disease, namely lymphoid hyperplasia and eosinophilic pneumonia.  The former may be diffuse, or manifest as follicular bronchiolitis, LIP, or lymphocytic perivascular cuffing, while the latter may show an acute or chronic pattern. 

Ito et al demonstrate that location isn’t just important in real estate.  For patients with surgically resected T1-2N2M0 NSCLC, primary tumor location is a significant prognostic factor for overall survival.  Peripheral tumors with N2 metastases behave significantly worse than those located more centrally, validating the authors’ hypothesis that mediastinal lymph node metastases from tumors situated farther from the hilum reflect more distant metastases.

In an era of being asked to do more with less, Chowdhuri et al provide data on the quantity of lung adenocarcinoma tumor cells that is sufficient for detecting EGFR and KRAS mutations.  Using laser capture microdissection on cell blocks from cytology samples, mutational results could be consistently obtained from as few as 50 microdissected tumor cells!   

Other articles of interest include a study on the relationship between DAD and chronic allograft lung dysfunction, a topic which has been heretofore surprisingly understudied, as well as an investigation into separating pulmonary neuroendocrine tumors using FoxM1, p27, and p21 immunostaining.  Lastly, included for your perusal is an intriguing case report of exogenous lipoid pneumonia resulting from electronic cigarette use.

ARTICLE INDEX (with PubMed links)
Articles and Abstracts for Discussion
Furuya M et al. Pulmonary cysts of Birt-Hogg-Dubé syndrome: a clinicopathologic and immunohistochemical study of 9 families. Am J Surg Pathol 2012;36:589-600

Larsen B et al. Lymphoid hyperplasia and eosinophilic pneumonia as histologic manifestations of amiodarone-induced lung toxicity. Am J Surg Pathol 2012;36:509-16

Ito M et al. Prognostic impact of the primary tumor location based on the hilar structures in non-small cell lung cancer with mediastinal lymph node metastasis. Lung Cancer 2012;76:93-7

Chowdhuri SR et al. EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma enabled by laser capture microdissection. Mod Pathol 2012;25:548-55

Articles for Notation
Original Articles
Ha SY et al. Differential expression of forkhead box M1 and its downstream cyclin-dependent kinase inhibitors p27kip1 and p21waf1/cip1 in the diagnosis of pulmonary neuroendocrine tumours. Histopathol 2012;60:731-9

Miettinen M et al. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am J Surg Pathol 2012;36:629-39

Noh S et al. Optimal combination of immunohistochemical markers for subclassification of non-small cell lung carcinomas: a tissue microarray study of poorly differentiated areas. Lung Cancer 2012;76:51-5

Ohta-Ogo K et al. CD44 expression in plexiform lesions of idiopathic pulmonary arterial hypertension. Pathol Int 2012;62:219-25

Sato M et al. Revisiting the pathologic finding of diffuse alveolar damage after lung transplantation. J Hearth Lung Transplant 2012:31:354-63

Smith B et al. Lung cancer histologies associated with emphysema on computed tomography. Lung Cancer 2012;76:61-6

Tournoy KG et al. Are EUS-FNA and EBUS-TBNA specimens reliable for subtyping non-small cell lung cancer? Lung Cancer 2012;76:46-50

Zhang L et al. Internal growth of nonsolid lung nodules: radiologic-pathologic correlation. Radiology 2012;263:279-86

Review Articles
Thunnissen E et al. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group. Lung Cancer 2012;76:1-18

Case Reports
Borie R et al. Tracheobronchial amyloidosis: evidence for local B-cell clonal expansion. Eur Respir J 2012l39:1042-5

Chaft J et al. ALK-rearranged lung cancer. Adenosquamous lung cancer masquerading as pure squamous carcinoma. J Thorac Oncol 2012;7:768-9

McCauley L et al. An unexpected consequence of electronic cigarette use. Chest 2012;141:1110-3

April 2012 Edition

Today's monthly journal club from Pulmonary Pathology Reviews comes to you from chilly Ann Arbor where thousands of graduates celebrated celebrated in the Big House just last Saturday.  Jonathon Herbst, pulmonary pathology fellow at the University of Michigan, did most of the work for today's blog with a tiny bit of help from one of several mentors, Jeffrey Myers.  Today's review captures 21 papers that were in print in March 2012 journals, including 4 highlighted for discussion (see ARTICLE INDEX).  For a quick snapshot of what's hot and what's not check out the OVERVIEW.  Click here for an index of the papers reviewed with page numbers that refer to the PDF summary available by clicking here.  If you want to hear the teleconference as it went down at 09:15 EDT on Monday, April 30th, click here to download the MP3 audiofile.

OVERVIEW
The crop of articles culled from the March 2012 print literature again delivers mostly on neoplastic diseases with a bushel of reviews that include no new data (see articles for notation).

Only a handful seemed worthy of discussion, and that was more true before rather than after reading them!  Bishop and colleagues demonstrate that p40 performs with greater specificity than p63 when it comes to separating squamous cell carcinomas from adenocarcinomas (and lymphomas, for what that's worth).  Nelson Ordonez refutes prevous observations suggesting that Napsin A might stain some squamous cell carcinomas, proposing instead that staining of non-neoplastic respiratory epithelium likely accounts for previous claims of napsin immunoreactivity in squamous cancers. Sakr et al somehow managed to publish a paper showing that cytology is less accurate than histology in subclassifying lung carcinoma when using no ancillary studies like . . . you know . . . IHC stains!  Would have been an interesting contribution in about 1984; today, not so much.  And finally, Tanaka and associates describe a couple of lung cancers in a 14-year-old boy and a 7-year-old girl that harbored the t(15;19) translocation associated with so-called NUT carcinomas more commonly described in the midline.  Both were undifferentiated carcinomas, one with associated squamous differentiation.  Interestingly, one of the two expressed TTF-1 . . . hmmmmmmm, the whole NUT thing is getting complicated.

Those articles relegated to Notation status include a number of reviews as well as an interesting study showing c-MET expression as a "good prognostic" finding in patients with diffuse pleural mesothelioma (check it out to see what good prognosis means in this nearly always fatal tumor).  Moran and Suster contributed a couple of papers on thymoma - I know, who knew?! - that are very useful when confused about the WHO classification scheme and Masaoka staging system (good news is you might be able to abandon both if they have their way).  And sticking with the thymoma theme, Valdisaly et al review extrathoracic metastases and offer caution regarding challenges in differential diagnosis for the unsuspecting.  The rest are of less practical value, but you can judge that for yourself by checking them out in either the ARTICLE INDEX or the PDF article summary.  ENJOY!

ARTICLE INDEX
Articles for discussion
Bishop et al. p40 (DNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012;25:405-15.

Ordóñez. A Word of Caution Regarding Napsin A Expression in Squamous Cell Carcinomas of the Lung.  Am J Surg Pathol 2012;36:396-401.

Sakr et al. Cytology-based treatment decision in primary lung cancer: Is it accurate enough?  Lung Cancer 2012;75:293-9.

Tanaka et al.  NUT Midline Carcinoma: Report of 2 Cases Suggestive of Pulmonary Origin.  Am J Surg Pathol 2012;36:381-8.


Articles for notation
Anttila.  Epithelioid Lesions of the Serosa.  Arch Pathol Lab Med. 2012;136:241–252.

Betta et al.  Immunohistochemistry and Molecular Diagnostics of Pleural Malignant Mesothelioma.  Arch Pathol Lab Med. 2012;136:253–261.

Jasani et al.  Mesothelioma Not Associated With Asbestos Exposure.  Arch Pathol Lab Med. 2012;136:262–267.

Attanoos.  Lymphoproliferative Conditions of the Serosa.  Arch Pathol Lab Med. 2012;136:268–276.

Jean et al.  Molecular Changes in Mesothelioma With an Impact on Prognosis and Treatment.  Arch Pathol Lab Med. 2012;136:277–293.

Levallet et al.  Plasma Cell Membrane Localization of c-MET Predicts Longer Survival in Patients with Malignant Mesothelioma A Series of 157 Cases from the MESOPATH Group.  J Thorac Oncol. 2012;7: 599–606.

Moran et al.  Thymomas I:  A Clinicopathologic Correlation of 250 Cases with Emphasis on the World Health Organization Schema.  Am J Clin Pathol 2012;137:444-450.

Moran et al.  Thymomas II:  A Clinicopathologic Correlation of 250 Cases with a Proposed Staging System with Emphasis on Pathologic Assessment.  Am J Clin Pathol 2012;137:451-461.

Vladislav et al.  Extrathoracic metastases of thymic origin: A review of 35 cases.  Modern Pathology 2012;25:370–377.

Ocak et al.  Expression of Focal Adhesion Kinase in Small-Cell Lung Carcinoma.  Cancer 2012;118:1293–301.

Maeda et al.  Number of Circulating Endothelial Progenitor Cells and Intratumoral Microvessel Density in Non-small Cell Lung Cancer Patients: differences in Angiogenic Status between Adenocarcinoma Histologic Subtypes.  J Thorac Oncol. 2012;7: 503–511.

Sterlacci et al.  High transforming growth factor β expression represents an important prognostic parameter for surgically resected non–small cell lung cancer.  Human Pathology 2012;43:339–349.

Corte et al.  Significance of connective tissue disease features in idiopathic interstitial pneumonia.  Eur Respir J 2012;39:661–668.

Nuovo et al.  The distribution of immunomodulatory cells in the lungs of patients with idiopathic pulmonary fibrosis. Modern Pathology 2012;25:416–433.

Mura et al.  Gene Expression Profiling in the Lungs of Associated With Pulmonary Fibrosis Patients With Pulmonary Hypertension.  Chest 2012;141;661-673.

Cheng et al.  Molecular pathology of lung cancer:  key to personalized medicine.  Modern Pathology 2012;25:347–369.

Kerr.  Personalized medicine for lung cancer: new challenges for pathology.  Histopathology 2012;60:531–546.

March 2012 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, an international, multi-institutional journal club focusing on literature of potential interest to those whose practice includes diagnostic pulmonary pathology.  Today's journal club was postponed from it's originally scheduled March date due to a conflict with the annual meeting of the USCAP, and comes to us courtesy of Joanne Yi at Mayo Clinic Minnesota.  What follows below is her OVERVIEW of the articles that emerged in the February 2012 print literature.  Below that is the ARTICLE INDEX, including links to PubMed abstracts (and full text articles for those institutions with access).  Click here for her PDF article summary, short thumbnails of the articles that serve as a handy reference if you want to get her take on the good, the bad and the ugly.  Click here if you want to download the MP3 audiofile of the teleconference as it went down at 08:15 CDT on Monday, April 2nd.

OVERVIEW
On review of the February articles in the journals in our list, I found 25 studies that seem to be relevant.  Please note that there are several JTO papers not included in this cycle because Anja inadvertently reviewed them last month.  As has been the trend for quite some time, there were definitely more studies on neoplastic than non-neoplastic diseases.  I managed to scrape two articles on non-neoplastic diseases for Discussion, however.

Rowan et al reported 5 cases showing diffuse cystic lung disease on HRCT and coexisting small airway diseases (SAD) on examination of surgical lung biopsies.  Tom contributed two cases to this study.  It looks very peculiar especially on imaging.  The authors postulated that the cystic changes in their cases might be associated with SAD and made an analogy with Sjogren’s syndrome (SS) and hypersensitivity pneumonia (HP).  The true nature of this quite striking cystic disease is yet to be determined with more studies and I will certainly keep my eyes out for similar cases. 

Xu et al did a retrospective review on lung adenocarcinomas with prominent lepidic growth and applied newly proposed classification on 87 resected adenocarcinoma in order to assess the impact on tumor staging when using the new criteria.  It is an important subject and requires more data.  I think this study is limited by a small number of cases and also seems to have some critical typos in the figure legends and seemingly mismatching footnote in the table, etc.  It took me quite an effort to read through and still left me with some questions.  The subjectivity of assessing invasion vs. in-situ (lepidic) growth, etc would be another inherent, inevitable problems.

Kadota K et al touched upon a nuclear grading system in epithelioid diffuse malignant pleural mesothelioma.  I guess we all know that not all epithelioid mesotheliomas are created equal.  They did an elaborate study to get into this issue and have shown quite compelling evidences that their nuclear grading system will add a relevant information for the management of this deadly tumor.

Perros F et al did a quite extensive, laborious morphologic study and proposed an attractive hypothesis that circulating pathogenic antibodies in idiopathic pulmonary hypertension (IPAH) pts might be generated in tertiary or ectopic lymphoid tissue in the lung, by comparing with control subjects and flow-induced PAH in pts with Eisenmenger syndrome.  They sought to identify local mechanisms responsible for their formation, perpetuation and function.  They performed an extensive immunostaining using both immunofluorescent method on frozen tissue and regular IHC on paraffin tissue, along with other moleclular study and flowcytomery using peripheral blood.  While their pictures and a schematic diagram are pretty as well as impressive, the real biology and immunologic mechanism are yet to be verified by independent investigators.

All Articles of Notification were on neoplastic diseases and none was on non-neoplastic diseases. 
Ordonez NG showed crystalloid inclusions on electron microscopy in 9 of 59 epithelioid mesotheliomas and stated that they can be used in the diagnosis.  Only problem is that most of us do not look at EM.  Carr et al reported that no difference in mortality, recurrence rates, or 5 year cancer specific survival when comparing segmentectomy and lobectomy for pathologic stage 1A NSCLC when stratified by T stage.  Rare conditions such as metaplastic thymomas and DIPNECH were studied by Liu et al and Gorshtein et al, respectively.  Zahel T et al proposed a grading approach with mitoses and Ki-67 proliferations, which would need a more work than they showed in this study to draw any definite conclusion.  Vilmar A et al have shown an example that IHC is in fact superior to a molecular technique qRT-PCR as methodology for the predictive value of ERCC1, BRCA1, RRM1, and TUBB3 on optimal archival tissue samples from a subgroup of pts in an advanced NSCLC cohort.  These findings are further supported by the lack of correlation between transcript and protein. 

Turner BM et al demonstrated that Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma. While Napsin might be useful in certain situations but I am not entirely convinced if it is any better than TTF1 except for those TTF-1 negative lung adenocarcinomas.  I thought their raw data in a table would be useful since it includes a lot of cases from all important primary sites.  What may not be reflected in all those statistical numbers is whether the cases requiring IHC badly, not those straightforward ones that we really do not need any stain, can be helped by Napsin stain.  Whithaus K et al showed that a combination of p63 and Napsin is the most cost-effective panel for small biopsies to distinguish lung adenocarcinomas from squamous cell carcinomas.  Again, I wonder how useful it will be when IHC is really needed! 

Popat S et al showed the findings that have been well documented previously: ALK rearrangement is strongly associated with ALK IHC and was seen in tumors with pure SRC morphology.  Now we run into another study addressing the size of lung adenocarcinomas.  Lampen-Sachar K et al compared the size of stage I and II lung adenocarcinomas measure by CT and as assessed on gross pathology specimens.  There is a significant difference between the diameters by two methods.  Now, the question is which one is more accurate or appropriate?  I suppose a gross measurement should trump and wonder why it should even be a problem.  Do we tend to underestimate on gross examination as suggested in this study?  Takamochi K et al tried to determine the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras.  There are a number of issues in this assumption.  First of all, it is still not very clear if we can determine the clonality with these mutational status with two genes.  It did not appear very sound to state that “combined mutation pattern analyses of EGFR and KRAS may be useful for making decisions regarding treatment strategies for patients with multifocal lung adenocarcinomas” in their Conclusions. 

Kim HR et al showed genetic abnormalities of EGFR, KRAS and ALK in never-smokers with non-small cell lung cancers in East Asians (Korean) and found more or less predictable results.  Kim HJ et al, another Korean investigators compared peptide nucleic acid-mediated real-time polymerase chain reaction clamping and direct gene sequencing for epidermal growth factor receptor mutations in patients with non-small cell lung cancer showed that RT-PCR is a simpler and more sensitive method than direct DNA sequencing in clinical setting.  Finally, de Lima Lopes et al, a group in Singapore, showed that EGFR testing and first-line treatment with gefitinib are better with lower costs and greater effectiveness compared with standard care, a promising new standard, at least in Asia.

I included several reviews, editorials and case reports that looked intriguing and I hope those are useful in your practice and for a good reference when needed.

ARTICLE INDEX
Articles for Discussion
Rowan C et al. Diffuse cystic lung disease of unexplained cause with coexistent small airway disease: a possible causal relationship. Am J Surg Pathol 2012;36:228-34

Xu et al. Adenocarcinomas with prominent lepidic spread: Retrospective review applying new classification of the American Thoracic Society. Am J Surg Pathol 2012;36:273-282

Kadota K et al. A nuclear grading system is a strong predictor of survival in epithelioid diffuse malignant pleural mesothelioma. Mod Pathol 2012;25:260-71

Perros F et al. Pulmoary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2012;185:311-21

Articles for Notation-Neoplastic
Carr SR et al. Impact of tumor size on outcomes after anatomic lung resection for stage 1A non-small cell lung cancer based on the current staging system. J Thorac Cardiovsc Surg 2012;143:390-7

Ordonez NG. Mesotheliomas with crystalloid structures: report of nine cases, including one with oncocytic features. Mod Pathol 25:272-81

Liu B et al. Metaplastic thymoma of the mediastinum. A clinicopathologic, immunohistochemical and genetic analysis. Am J Clin Pathol 2012;137:261-9

Zahel T et al. Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. Virchows Arch epub 01 Feb 2012 

Gorshtein A et al. Diffuse idiopathic pulmonary neuroencdocrine cell hyperplasia and the associated lung neuroendocrine tumors. Cancer 2012;118:612-9

Vilmar A et al. RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRAC1, TUBB3 and RRM1 in NSCLC. Lung Cancer 2012;75:306-12

Turner BM et al. Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma. Arch Pathol Lab Med 2012;136:163-71

Whithaus K et al. Evaluation of Napsin A, cytokeratin 5/6, p63, and thyroid transcription factor 1 in adenocarcinoma versus squamous cell carcinoma of the lung. Arch Pathol Lab Med 2012;136:155-62

Popat S et al. ALK translocation is associated with ALK immunoreactivity and extensive signet-ring morphology in primary lung adenocarcinoma. Lung Cancer 2012;75:300-5

Lampen-Sachar K et al. Correlation between tumor measurement on computed tomography and reseted specimen size in lung adenocarcinomas. Lung Cancer 2012;75:332-5

Takamochi K et al. Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. Lung Cancer 2012;75:313-20

Kim HR et al. Distinct clinical features and outcomes in never-smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutation on ALK rearrangement. Cancer 2012;118:729-39

Kim HJ et al. Detection and comparison of peptide nucleic acid-mediated real-time polymerase chain reaction clamping and direct gene sequencing for epidermal growth factor receptor mutations in patients with non-small cell lung cancer. Lung Cancer 2012;75:321-5

de Lima Lopes et al. Cost-effectiveness of epidermal growth factor receptor mutation testing and first-line treatment with gefitinib for patients with advanced adenocarcinoma of the lung. Cancer 2012;118:1032-9

Reviews/editorials
Ost DE et al. Decision making in patients with pulmonary nodules. Am J Respir Crit Care Med 2012;185:363-72

Cullinan P et al. The asbestos disease epidemic: here today, here tomorrow. Thorax 2012;67:98-9

Stoller JK et al. A review of alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2012;185:246-59

Tuder RM et al. Targeting energetic metabolism. A new frontier in the pathogenesis and treatment of pulmonary hypertension. Am J Respir Crit Care Med 2012;185:260-6

Case reports
Hariri LP et al. Progressive granulomatous pneumonitis in response to cosmetic subcutaneous silicone injections in a patient with HIV-1 infection. Case report and review of the literature. Arch Pathol Lab Med 2012;136:204-7

ter Heine R et al. Fatal interstitial lung diseae associate with high erlotinib and metabolite levels. A case report and a review of the literature. Lung Cancer 2012;75:391-7

Singh et al. Tumor of the heart in a young woman; a rare manifestation of Wegener granulomatosis. Hum Pathol 2012;43:289-92

February 2012 Edition

Today's edition of Pulmonary Pathology Reviews comes to us from the Mayo Clinic in balmy Rochester, MN where global warming is embraced by those for whom snow is something less than the wintery wonderland celebrated by other hard core Minnesotans.  Anja Roden is Assistant Professor of Pathology and gives us her views of what's new and hot in the fast paced world of academic pulmonary pathology as reflected in the peer reviewed print media published in January 2012.  What follows is her OVERVIEW followed by an Article Index that includes links to PubMed abstracts (and full text versions of the articles if supported by your institution).  Click here for a list of articles including page references to her PDF "Crib Notes" summary of the articles.  Click here to download an MP3 audiofile of the multi-institutional teleconference as it went down at 08:15 CST on Monday morning, February 27th.

OVERVIEW
The majority of the 24 articles that were selected from the January editions of our journals discussed neoplastic lung diseases, a few focused on non-neoplastic processes. There was a nice mix of themes that are continuously discussed in the pulmonary community including: (i) The best algorithm to identify the ALK rearrangement status of lung adenocarcinomas; (ii) clinical characteristics of patients with lung adenocarcinomas that harbor ALK gene rearrangements; (iii) postmortem histopathologic and immunophenotypical findings in lungs and other organs from patients who died from complications of H1N1 influenza; and (iv) potential prognostic factors for patients with adenocarcinoma. Other studies focused on issues that come up in our daily practice, such as (i) the usefulness of high risk HPV testing of the tumor to distinguish primary lung squamous cell carcinomas (SQCC) from metastases from the head & neck area; (ii) the practical value of ΔNp63 (p40) to diagnose squamous differentiation; or (iii) the sensitivity and specificity of EGRF mutation specific antibodies for IHC use in comparison to molecular studies, amongst others. Some groups looked into the pathogenesis of IPF and temporal evolution of NSIP. 

For discussion I have chosen four articles that I thought might be of interest for our day-to-day practice and one that appeared intriguing to me in regards to the pathogenesis of IPF.

The first article by Bishop JA et al shows that high-risk HPV by ISH in lung SQCC might be restricted to patients with HPV-related oropharyngeal HNSQCC and that high-risk HPV ISH could help to distinguish metastases from oropharyngeal SQCC from primary lung tumors. P16, in contrast to other sites, appears not useful as a surrogate marker for HPV infection in lung SQCC because of false positive tumors in the lung. Furthermore, basaloid growth pattern might be a hint for the possibility of metastasis in patients with history of oropharyngeal HNSQCC. However, the study does not include metastases of SQCC from other sites such as cervical cancer that might also be related to HPV.

The second article is from Pelosi G et al and evaluates the usefulness of p40 and TTF1 on small amount of tissue for typing NSCLC. P40 is a marker of squamous differentiation that is related to isoforms of p63 but is more specific than p63. However, as all squamous markers, p40 does not help to distinguish the organ of origin. The article shows that p40 is diagnostic useful either if it is positive indicating SQCC or negative indicating non-SQCC in contrast to TTF-1 which only can be used if it is positive indicating lung adenocarcinoma.

The third article is by Azuma K et al and studied the practical use of EGFR mutation-specific antibodies in regards to their efficacy of gefitinib treatment. The authors concluded that a combination of proportion and intensity score for EGFR antibodies might be useful for predicting efficacy of EGFR-TKIs in NSCLC patients harboring EGFR mutations. However, the authors also found that the sensitivity for the IHC detection of exon 19 deletions was lower than the L858R mutation (exon 21). Overall, negative IHC does not exclude EGFR mutation.

The fourth article by Yang P et al confirms previous recommendation that ALK IHC scores 3+ and 0 results are concordant with FISH+ and FISH-, and cases with IHC score 2+ need confirmation by FISH. Although IHC score 1+ can usually be regarded as ALK-, confirmation by FISH is recommended in patients with characteristics that have been associated with ALK positivity (e.g. never-smoker, young, signet ring morphology, no EGFR / Kras mutations). Furthermore, the prevalence of ALK+ tumors in a population enriched for never-smokers with adenocarcinomas is 6% if only tested by IHC score 3+ and 12.2% if either FISH+, or IHC score 3+, or IHC score 2+ are allowed. ALK+ cases had worse outcome than ALK- cases.

The last article is by Mubarak KK et al and discusses an interesting potential pathogenesis for IPF that includes pleural mesothelial cells that can transition into a myofibroblast phenotype and undergo haptotactic migration in response to TGF1 (“mesothelial-mesenchymal transition”). They found that pleural mesothelial cells might be attracted to areas of fibrosis and correlate with degree of fibrosis and concluded that dysregulated pleural mesothelial cells might be involved in the pathogenesis of IPF.  
 
Amongst articles for notation, under the category neoplasia, Rossi G et al show that in pulmonary sclerosing hemangiomas, Napsin A stains only the cuboidal surface cells similar to cytokeratin and surfactant apoprotein, further supporting the hypothesis that this tumor differentiates towards the peripheral respiratory epithelium. Kachroo P et al conclude that image-guided core needle biopsy of chest wall sarcomas is an accurate method to determine malignancy, histological subtype, and high grade differentiation. Fassina A et al investigate the role of epithelial-mesenchymal transition in the histologic subtyping of malignant mesothelioma and find that markers are consistent with epithelial-to-mesenchymal trend and that morphologic patterns of malignant mesotheliomas are part of a continuous spectrum determined by epithelial-mesenchymal transition. Since our GI colleagues often ask us about our opinion on malignant mesotheliomas in the abdominal cavity I included the article by Malpica A et al on the clinicopathologic features of well-differentiated papillary mesothelioma of the female peritoneum. These tumors are usually discovered incidentally, are small and have a good prognosis and, in contrast to their pleural counterpart, patients have no history of asbestos exposure.  Kido T et al show that MALT1 gene rearrangements can be detected by FISH in BAL cells in 80% of patients with p-MALT and is useful in the diagnosis of p-MALT. Won KY et al studied the expression of the Bcl-2 interacting protein, Beclin-1, in lung SQCC and adenocarcinomas and concluded that autophagocytosis induced by Beclin-1 expression contributes to tumorigenesis and might suppresses tumor development. Fang HY et al found that optic atrophy 1 protein (OPA1) is frequently overexpressed in lung AdCa, correlates with male gender and tumor characteristics that are associated with poor prognosis and reduced drug sensitivity. Another study to determine best daily practice for diagnosing ALK rearrangements in lungs cancers was published by McLeer-Florin A et al and confirmed that ALK IHC is good as screening tool but the authors also recommend FISH in doubtful cases and/or to check if patients are definitely eligible for crizotinib therapy. Furthermore, in that study, FISH was deficient in a considerable number of cases, either because of inappropriate fixation, decalcification, or <20% of malignant cells on the slide. Dziadziuszko R et al and Tsuta K et al independently had studied MET gene copy number in NSCLC because MET amplification is proposed as a mechanism of acquired resistance to anti-EGFR therapy. Dziadziuszko R et al found that SISH and IHC correlate for MET but were not associated with clinical / pathologic variables and that MET protein expression or gene copy number had no prognostic significance in a cohort of surgically treated patients with NSCLC. Tsuta K used a different method for MET gene copy # analysis – BISH - and found that MET gene amplification is more prevalent in poorly differentiated than in well differentiated adenocarcinoma, that MET BISH positivity is an independent prognostic factor in non-SQCC and that c-MET expression and MET gene amplification are differentiation markers between adenocarcinoma and SQCC. Sun PL et al analyzed histologic subtypes of adenocarcinoma and NSCLC solely in Korean patients and found that EGFR mutations seem more prevalent in NSCLC of Korean patients than in NSCLC from Japanese and Chinese, that a significant number of men and ever-smokers had EGFR mutations, and that there was a relatively high incidence of EGFR mutations in men who smoked with adenocarcinomas. Therefore, EGFR mutation tests should be performed in all adenocarcinoma patients regardless of gender or smoking history. Rades D et al looked into the prognostic role of tumor cell expression of ER-alpha, PR, and AR in patients who received radiation for NSCLC and found that only ER-alpha expression by the tumor cells is an independent prognostic factor with respect to locoregional control, overall survival and a negative prognostic factor for treatment outcomes in both, women and men who received radiation for stage II/III NSCLC, not PR or AR. Li C et al found that HER2 mutations are more common in Asians, lung adenocarcinomas, women, and never smokers and that EGFR, KRAS, and HER2 were all mutually exclusive. Their study suggests that small molecule agents targeting both EGFR and HER might be useful for both EGFR-TKI-resistant and HER-mutated tumors.

The original articles for notation in the non-neoplastic category included two studies concerning H1N1 casualties. Bal A et al confirmed H1N1 involvement of predominantly the upper respiratory tract. They also showed that transplacental virus transmission to the fetus seems unlikely. Nakajima N et al showed that multiple people actually did not die of respiratory failure but of encephalopathy, cerebral hemorrhage, or myocardial dysfunction and that influenza A nucleoprotein antigen was detected in the respiratory tract in type II and I pneumocytes, in alveolar epithelial cells, bronchioles, glands, bronchi, trachea and macrophages. In a case series, Schneider F et al shows that fibrotic NSIP can evolve into UIP and cellular NSIP can evolve into fibrotic NSIP.

Jankowich MD et al review the topic of combined pulmonary fibrosis and emphysema syndrome (CPFE) and comment on definition, imaging, demographics, etiology, pathological findings and treatment of this entity. Ryu JH et al review clinical, radiological, and histopathologic features of IgG4-related sclerosing disease (ISD) in the lung.

A case report by Yang CJ et al describes a 52 yo previously healthy smoker with fever (38°C) and cough for 1 mo and was found to have palpable fixed supraclavicular LNs and a large mass in RUL with the lower trachea narrowed and displaced, mediastinal invasion, SVC encasement and multiple nodules over both lung fields. PET positive. This was a case of pulmonary Langerhans cell sarcoma.

Modern Pathology also published the Pulmonary Pathology Long Course material from 2011 USCAP.

Enjoy the reading!

ARTICLE INDEX
Articles for discussion
Bishop JA et al. HPV analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2012 Jan;36(1):142-8.

Pelosi G et al. ΔNp63 (p40) and Thyroid Transcription Factor-1 Immunoreactivity on Small Biopsies or Cellblocks for Typing Non-small Cell Lung Cancer: A Novel Two-Hit, Sparing-Material Approach. J Thorac Oncol. 2012 Feb;7(2):281-290.

Azuma K et al. Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment. J Thorac Oncol. 2012 Jan;7(1):122-7.

Yang P et al. Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. J Thorac Oncol. 2012 Jan;7(1):90-7.

Mubarak KK et al. Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis. Eur Respir J. 2012 Jan;39(1):133-40.

Articles for notation – Neoplastic
Rossi G et al. Napsin A expression in pulmonary sclerosing haemangioma. Histopathology. 2012 Jan;60(2):361-3.

Kachroo P et al. Chest wall sarcomas are accurately diagnosed by image-guided core needle biopsy. J Thorac Oncol. 2012 Jan;7(1):151-6.

Fassina A et al. Epithelial-mesenchymal transition in malignant mesothelioma. Mod Pathol. 2012 Jan;25(1):86-99.

Malpica A et al. Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases. Am J Surg Pathol. 2012 Jan;36(1):117-27.

Kido T et al. Detection of MALT1 gene rearrangements in BAL fluid cells for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma. Chest. 2012 Jan;141(1):176-82.

Won KY et al. Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung. Hum Pathol. 2012 Jan;43(1):62-8.

Fang HY et al. Overexpression of optic atrophy 1 protein increases cisplatin resistance via inactivation of caspase-dependent apoptosis in lung adenocarcinoma cells. Hum Pathol. 2012 Jan;43(1):105-14.

McLeer-Florin A et al. Dual IHC and FISH Testing for ALK Gene Rearrangement in Lung Adenocarcinomas in a Routine Practice: A French Study. J Thorac Oncol. 2012 Feb;7(2):348-54.

Dziadziuszko R et al. Correlation between MET Gene Copy Number by Silver In Situ Hybridization and Protein Expression by Immunohistochemistry in Non-small Cell Lung Cancer. J Thorac Oncol. 2012 Feb;7(2):340-7.

Tsuta K et al. c-MET/Phospho-MET Protein Expression and MET Gene Copy Number in Non-small Cell Lung Carcinomas. J Thorac Oncol. 2012 Feb;7(2):331-9.

Sun PL et al. High Incidence of EGFR Mutations in Korean Men Smokers with No Intratumoral Heterogeneity of Lung Adenocarcinomas: Correlation with Histologic Subtypes, EGFR/TTF-1 Expressions, and Clinical Features. J Thorac Oncol. 2012 Feb;7(2):323-330.

Rades D, Setter C, Dahl O, Schild SE, Noack F. The prognostic impact of tumor cell expression of estrogen receptor-α, progesterone receptor, and androgen receptor in patients irradiated for nonsmall cell lung cancer. Cancer. 2012 Jan 1;118(1):157-63.

Li C, Sun Y, Fang R, Han X, Luo X, Wang R, Pan Y, Hu H, Zhang Y, Pao W, Shen L, Ji H, Chen H. Lung adenocarcinomas with HER2-activating mutations are associated with distinct clinical features and HER2/EGFR copy number gains. J Thorac Oncol. 2012 Jan;7(1):85-9.

Non-Neoplastic
Bal A, et al: Pathology and virology findings in cases of fatal influenza A H1N1
virus infection in 2009-2010. Histopathology. 2012 Jan;60(2):326-35.

Nakajima N, et al. Histopathological and immunohistochemical findings of 20
autopsy cases with 2009 H1N1 virus infection. Mod Pathol. 2012 Jan;25(1):1-13.

Schneider F, Hwang DM, Gibson K, Yousem SA. Nonspecific interstitial
pneumonia: a study of 6 patients with progressive disease. Am J Surg Pathol. 2012 Jan;36(1):89-93.

Current Topics/Review Articles:
Jankowich MD, et al. Combined pulmonary fibrosis and emphysema syndrome: a
review. Chest. 2012 Jan;141(1):222-31.

Ryu JH, Sekiguchi H, Yi ES. Pulmonary manifestations of immunoglobulin G4-related sclerosing disease. Eur Respir J. 2012 Jan;39(1):180-6.

Case reports
Yang CJ, et al. An unusual pulmonary mass with mediastinal invasion and
multiple intrapulmonary nodules in a 52-year-old man. Chest. 2012 Jan;141(1):253-8

January 2012 Edition

Hard to believe that it's 2012!  And with the New Year comes our first 2012 Edition of Pulmonary Pathology Reviews, a blog that shares with whomever is interested materials and discussion generated by a multi-institutional North American journal club held once a month by teleconference (you can learn more by reading first April 2006 post, Welcome to Pulmonary Pathology Review).  Today's journal club comes to us courtesy of Dr. Tom Colby of Mayo Clinic fame in sunny Scottsdale, Arizona.  What follows is his OVERVIEW intended to highlight peer reviewed publications that appeared in print in December 2011.  Click here for his PDF summary of the articles reviewed.  Click here for the MP3 audiofile if you want to hear the discussion as it occurred at 07:15 MST on Monday, January 30th.

OVERVIEW
It seems some investigators took time off for vacation since I found the papers in the December issues of the journals somewhat less interesting than in other months. 

The paper by Von Der Thusen, et al. describes pleuroparenchymal fibroelastosis in patients with a history of bone marrow transplantation.  I found this interesting for a number of reasons.  PPFE is often an upper lobe process which allows its radiologic distinction from other fibrosing processes.  The histology is dominated by fibroelastosis and an idiopathic version has been described, first in Japan as idiopathic upper lobe fibrosis and more recently in North America and Great Britain as idiopathic pleuroparenchymal fibroelastosis (IPPFE).  This series correlates this change with the history of bone marrow transplantation.  Interestingly, there are reports in the literature of upper lobe fibrosis related to chemotherapy and in retrospect some of these cases may actually represent PPFE associated with bone marrow transplantation.  How one separates one cause from another in cases with multiple possible etiologies remains a difficult problem.

There is a large series from China by Zhang, et al. which essentially is all you ever wanted to know about the micropapillary pattern in pulmonary adenocarcinoma.  They studied a large series of cases (886 resected adenocarcinomas) and then did various immunohistochemical stainings, and mutation analyses to correlate with the histology.  Not surprisingly a micropapillary pattern conveyed a worse prognosis and was more likely to be correlated with higher stage and lymphatic invasion and the correlation was better as the degree of micropapillary change increased.

There is a small series from the Cleveland Clinic by Dyhdalo and Farver of histologic changes in Marfan’s syndrome.  Five patients are studied, the majority of which had cardiac problems and incidental findings on lung tissue.  The changes described were labeled “distal acinar emphysema” but to my eye they look more like cystic change in the peripheral regions of the lung.  I am not sure the precise label is as important as the fact that cystic/emphysematous change may be encountered in patients with Marfan’s syndrome.  This could be a conceivable explanation for spontaneous pneumothorax.

Among the articles for notation, there are some that were quite interesting.

The series by Hayashi, et al. showed that patients with sporadic pulmonary LAM were very like to have uterine involvement by LAM cells and the authors postulated that these could be a primary site for LAM cells in patients with LAM.

Dr. Raghu has been touting the potential influence of GERD and micro-aspiration in the pathogenesis of IPF for years and for the most part he has been a voice in the dark.  The article by Lee, et al. suggests that therapy for GERD reflux may actually be associated with a longer survival suggesting that it may in fact be a significant factor in these patients.

And finally if you didn’t know it yet, sex matters.  In a review of 848 patients with adenocarcinoma of the lung, Nagy-Mignotte, et al. found that there were significant differences among patients when stratified according to sex and smoking history.  Female smokers were significantly younger when they were diagnosed with cancer than female never smokers, whereas in men such a finding was not identified.

December 2011 Edition

Welcome to the last 2011 Edition of Pulmonary Pathology Reviews, a blog that supports a multi-institutional journal club focusing on problems in diagnostic pulmonary pathology.  Today's holiday edition comes to us from Andras Khoor ("Tebow" to his friends) at Mayo Clinic Jacksonville, home of the 4 and 10 Jaguars.  Read his OVERVIEW to see what's hot and what's not.  Below that is the ARTICLE INDEX with links to PubMed abstracts, and full text articles if your institution allows it.  Click here to see the list of articles chosen for discussion and notation, and here if you want to see his thumbnail summaries of today's articles.  If you want to listen to the teleconference as it unfolded at 09:15 EST on Monday, December 19, 2011, click here to download MP3 audiofile.

OVERVIEW
Thirteen pulmonary pathology-related articles were selected from our usual journals from the month of November, 5 for discussion and 8 for notation only.  Diagnostic tools to further classify non-small cell carcinomas of the lung remain a hot topic.  This is, at least partially, due to the fact that oncologists need accurate subtyping of these tumors to provide patients with optimal targeted chemotherapy.  From among the 3 articles related to this topic this month, I chose the one written by Barbareschi et al for discussion.  These authors used immunohistochemistry and, then, microRNA-205 analysis to subtype surgically removed large cell carcinomas.

An article by Won et al compares the clinical outcome of non-small cell carcinoma patients with the 2 most common epidermal growth factor mutations: deletion of exon 19 and the L858R mutation of exon 21.

Thway et al describe a new entity: primary pulmonary myxoid sarcoma.  It turns out that most of these tumors contain a fusion gene (EWSR1-CREB1), which has previously been found only in clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas.  You cannot say that there are no new entities to describe in Surgical Pathology!

Vij et al report a series of patients with “autoimmune-featured interstitial lung disease.”  My feeling is that these patients have idiopathic pulmonary fibrosis and some abnormal lab results (they do not meet the American College of Rheumatology criteria for connective tissue disease).  I can hardly wait to hear what my esteemed colleagues think!

Finally, we will discuss an article by Wright et al, who describe a fatal, inhalation anthrax-like infection, which was caused by a previously unknown strain of Bacillus cereus.  Enjoy!

ARTICLE INDEX
ARTICLES FOR DISCUSSION:
Barbareschi M, et al. Heterogeneity of large cell carcinoma of the lung: an immunophenotypic and miRNA-based analysis. Am J Clin Pathol. 2011 Nov;136(5):773-82.

Won YW, et al. Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations. J Clin Pathol. 2011 Nov;64(11):947-52.

Thway K, et al. Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity. Am J Surg Pathol. 2011 Nov;35(11):1722-32.

Vij R, et al. Autoimmune-featured interstitial lung disease: a distinct entity. Chest. 2011 Nov;140(5):1292-9.

Wright AM, et al. Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case report, pathogen genome sequencing, pathology, and coordinated response. Arch Pathol Lab Med. 2011 Nov;135(11):1447-59.

ARTICLES FOR NOTATION:
Neoplastic:
Sigel CS, et al. Subtyping of non-small cell lung carcinoma: a comparison of small biopsy and cytology specimens. J Thorac Oncol. 2011 Nov;6(11):1849-56.

Fassina A, et al. Classification of non-small cell lung carcinoma in transthoracic needle specimens using microRNA expression profiling. Chest. 2011 Nov;140(5):1305-11.

Weissferdt A, Moran CA. Pulmonary salivary gland-type tumors with features of malignant mixed tumor (carcinoma ex pleomorphic adenoma): a clinicopathologic study of five cases. Am J Clin Pathol. 2011 Nov;136(5):793-8.

Kalhor N, et al. Primary pulmonary chondrosarcomas: a clinicopathologic study of 4 cases. Hum Pathol. 2011 Nov;42(11):1629-34.

Boxer MM, et al. Do multidisciplinary team meetings make a difference in the management of lung cancer? Cancer. 2011 Nov 15;117(22):5112-20.

Non-neoplastic:
Bakan ND, et al. Silicosis in denim sandblasters. Chest. 2011 Nov;140(5):1300-4.

Matsukuma S, Sato K. Pulmonary capillary haemangiomatosis-like lesions in severely congested lungs. Histopathology. 2011 Nov;59(5):876-81.

Kumasaka T, et al. Rare pneumoconiosis induced by long-term amorphous silica exposure: the histological characteristics and expression of cyclooxygenase-2 as an antifibrogenic mediator in macrophages. Pathol Int. 2011 Nov;61(11):667-71.

November 2011 Edition

Welcome to a delayed November edition of Pulmonary Pathology Reviews, a monthly journal club supported by pathologists from multiple North American academic medical centers in order to share the work of keeping pace with the print literature of interest to the pulmonary pathology community.  Today's journal club comes to us from beautiful Alberta through the hard work of Margaret Kelly at the University of Calgary.  Click here to see her list of reviewed articles, and here for her "Cliff Notes" summary of those that were discussed and those that were included for notation only.  Her OVERVIEW is below and is followed by an ARTICLE INDEX with links to PubMed citations.  If you want to hear how it actually happened at 08:15 CST click here to download the MP3 audiofile (may take awhile given file size - be patient!).  As always, your comments are welcome.

OVERVIEW
I selected 25 articles from those published in October 2011 (including editorials) reviwing 4 in detail. Most of the articles deal with neoplasia, including validation of immunohistochemical stains for differentiating adenocarcinoma from squamous carcinoma, taking a closer look at precursor cells of carcinoids, identifying histologic correlates of tumors with epidermal growth factor receptor mutations and attempting to identify markers predictive of lung cancer in squamous metaplastic lesions. Other articles examined pulmonary sequelae in survivors of childhood cancer, found that the elderly can tolerate major pulmonary cancer surgery better than expected and outcomes after pulmonary metastectomy are encouraging.

Case reports illustrate the importance of being unbiased when looking at histopathology, with benign metastasizing leiomyoma having a very similar presentation to LAM (multiples cysts and some overlapping immunohistochemical results) and pulmonary malakoplakia mimicking stage IV lung cancer. Other case reports emphasize the varied manifestations of the fungal kingdom. Another paper raises the possibility of IgG4-related disease being associated with yet another disease, this time sarcoid. Using molecular techniques rather than cultures, one paper provided convincing evidence that the lower respiratory tract is not sterile in healthy subjects, due to apparent chronic microaspiration, which opens up several new questions about tolerance to micro-organisms in the lung, similar to those being studied in the gastrointestinal tract.  New molecular techniques (genome wide association studies) and new endomicroscopic techniques (confocal laser endomicroscopy) are comprehensively explained and their application to lung disease outlined. Interesting and thorough reviews on the histopathology of drug abuse and a primer on the utility of bronchoalveolar lavage are also included.

ARTICLE INDEX
Articles for discussion:
1. Rekhtman N, Ang DC, Sima CS, Travis WD and Moreira AL. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens Mod. Pathol. 2011; 24: 1348–1359.

2. Gosney JR, Williams  IJ, Dodson AR and Foster CS. Morphology and antigen expression profile of pulmonary neuroendocrine cells in reactive proliferations and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Histopathol. 2011; 59: 751-762.

3. Shim HS, Lee DH, Park EJ, and Kim SE, Histopathologic Characteristics of Lung Adenocarcinomas With Epidermal Growth Factor Receptor Mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Lung Adenocarcinoma Classification. Arch Pathol & Lab Med. 2011;135: 1329-1334.

4. Editorial: Dajic S. Lung Carcinoma Morphology or Mutational Profile: That is the Question. Arch Pathol & Lab Med. 2011;135: 1242-1243.

Articles for Notation
Neoplastic
1. van Boerdonk RA, Sutedja TG, Snijders PJF, et al. DNA Copy Number Alterations in Endobronchial Squamous Metaplastic Lesions Predict Lung Cancer. Am J Respir Crit Care Med. 2011;184: 948–956.

2. Editorial: Coldren CD and Miller YE. Progressive Endobronchial Premalignancy: Marked by Original CIN. Am. J. Respir. Crit. Care Med. 2011 184: 869-870.

3. Salto-Tellez M, Tsao M-T; Shih JY; Thongprasert S, Shun L; Chang G-C; Au JS; Chou T-Y, Lee J-S,  et al. Clinical and Testing Protocols for the Analysis of Epidermal Growth Factor Receptor Mutations in East Asian Patients with Non-small Cell Lung Cancer: A Combined Clinical-Molecular Pathological Approach. J Thor Oncol; 6:1663-1669.

4. Wallace WAH and Rassl DM. Accuracy of cell typing in nonsmall cell lung cancer by EBUS/EUS–FNA cytological samples. Eur Respir J. 2011 38:911-917.

5. Rivera C, Falcoz P-E, Bernard A, Thomas PA, Dahan M. Surgical Management and Outcomes of Elderly Patients With Early Stage Non-small Cell Lung Cancer; A Nested Case-Control Study. Chest. 2011; 140: 874-880.

6. Editorial: Johnson RG. The Elderly Are Different, Resection for Non-small Cell Lung Cancer. Chest. 2011; 140: 839-840.

7. Huang T-T, Hudson MM, Stokes DC, Krasin MJ, Spunt SL and Ness KK. Pulmonary Outcomes in Survivors of Childhood Cancer, A Systematic Review. Chest; 140: 881-901.

8. Aboualfa K, Calandriello L, Dusmet M, Ladas G, Hansell DM and Nicholson AG.  Benign metastasizing leiomyoma presenting as cystic lung disease: a diagnostic pitfall. Histopathology;59:796–799.

9. Lang-Lazdunski L, Bille A, Belcher E, Cane P, Landau D, Steele J, Taylor H, and Spicer J. Pleurectomy/Decortication, Hyperthermic Pleural Lavage with Povidone-Iodine Followed by Adjuvant Chemotherapy in Patients with Malignant Pleural Mesothelioma. J Thor Oncology. 2011; 6: 1746-1752.

10. Hornbech K, Ravn J and Steinbrüchel DA. Outcome after Pulmonary Metastasectomy: Analysis of 5 Years Consecutive Surgical Resections 2002–2006. J Thor Oncology. 2011; 6:1733-1740.

11. Grogan EL, Weinstein JJ, Deppen SA, Putnam JB, Nesbitt JC et al. Thoracic Operations for Pulmonary Nodules Are Frequently Not Futile in Patients with Benign Disease. J Thor Oncology. 2011; 6:1720-1725.

12. Mandal P, Wallace WA, and Skwarski KM. Pulmonary malakoplakia: a rare presentation mimicking extensive stage IV lung cancer. Eur Respir J. 2011 38:983-985.

Non-neoplastic
1. Ono S, Tanaka T, Ishida M, Kinoshita A, Fukuoka J, Takaki M, Sakamoto N et al. Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred. Eur Respir J 2011 38:861-869.

2. Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, Bushman FD, and Collman RG.Topographical Continuity of Bacterial Populations in the Healthy Human Respiratory Tract Am. J. Respir. Crit. Care Med. 2011;184:957-963.

 Case Reports:

3. Michel L, Clair R, Ne´el A, Masseau A,1 Eric Frampas E and  Hamidou M. Association of IgG4-related disease and sarcoidosis. Thorax. 2011; 66:920-921.

4. Kairalla R, Kawano-Dourado L, Baldi B and Carvalho C. Diffuse Micronodules with Spontaneous Resolution. Am J Respir Crit Care Med. 2011; 184:859.

5. Tsai M-J, Chang W-A, Tsai K-B, Chen H-C, Hwang J-J and Huang M-S. Probable Invasive Pulmonary Trichosporonosis in a Diabetic Patient. Am J Respir Crit Care Med. 2011; 184: 982.

Reviews
1. Meyer KC and Raghu G. Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful? Eur Respir J. 2011 38:761-769.

2. Milroy CM and Parai JL The histopathology of drugs of abuse. Histopathology. 2011; 59: 579–593.

3. Todd JL, Goldstein DB, Ge D, Christie J and Palmer SM.  The State of Genome-Wide Association Studies in Pulmonary Disease: A New Perspective. Am. J. Respir. Crit. Care Med. 2011 184: 873-880.

4. Paull PE, Hyatt BJ, Wassef W and Fischer AH. Confocal Laser Endomicroscopy: A Primer for Pathologists. Archives of Pathology & Laboratory Medicine. 2011; 135: 1343-1348. 

October 2011 Edition

Welcome to a Halloween edition of Pulmonary Pathology Reviews, a journal club blog intended to keep those interested in diagnostic pulmonary pathology up to speed with the relevant and sometimes spooky peer reviewed print literature.  Today's journal club comes to us courtesy of Dr. Henry Tazelaar at Mayo Clinic Arizona where he's all set to go in a costume that looks oddly appropriate to the Scottsdale desert envirnoment.  Click here if you want a PDF version of his summary of articles chosen for discussion as well as those worthy of notation.  If you want to hear the teleconference as it happened at 06:15 MST (yup, no daylight savings in Arizona), click here and wait the few minutes it might take to download the MP3 file.  Below is the ARTICLE INDEX including links to PubMed abstracts, and full text articles for those whose institutions have access.  And as always, we welcome your comments should you wish to engage in the dialogue generated by this month's crop of scientific discoveries, reviews and case reports.

OVERVIEW
Happy Halloween, everyone - no need to be afraid of the articles this month.  There’s only one or two that are a bit scary.  The selection perhaps is a bit odd in that some of the papers have very little pathology (or none at all!), but since there weren’t very many articles with pathology I thought worth discussing, I just picked my favorite articles overall.

An article by Valliéres, et al. reviews the significance of carcinoma in situ at the bronchial margin as reported in 13 articles over the last five years.  The bottom line is that a positive margin has many different forms and true carcinoma in situ at the bronchial margin likely has little long term prognostic significance.  Other forms of carcinoma at the margin, however, are significant, e.g. peribronchial or lymphatic involvement.  Nishino, working with Drs. Eugene Mark, Osama Matsubara, and Richard Kradin, describe a form of variant alveolar proteinosis, characterized by the presence of abundant histiocytes, and mixed with the alveolar exudate.  Some of these patients appear to have steroid responsive disease and, in fact, whole lung lavage may exacerbate rather than cure them.  Although the paper on mycobacterial disease by Maekawa has no pathology, since many of us have an interest in non-tuberculous microbacterial disease, you might want to know that if you muck around in the soil and have bronchiectasis, you may be setting yourself up for this nasty bug to take over your lungs. The results of a major clinical trial for the treatment of IPF are reported in the New England Journal.  As the accompanying editorial so eloquently states, the beneficial effects of BIBF 1120 shine like a beacon over a turbulent sea of unfulfilled promises and failed clinical trials.  Might want to check this out as our clinical colleagues will likely be talking about this trial.  Interestingly, it appeared as though instances of acute exacerbation were lower in one treatment group and that they had an improvement in quality of life compared with the placebo group.

Articles for notation include a review by Salgia, et al. on angiogenesis and angiogenic growth factors in non-small cell lung cancer, an analysis of spindle-cell carcinoids by Tsuta, an analysis of Frat1 overexpression in advanced stage non-small cell lung cancer (it appears to be associated with invasiveness and dissemination), an analysis of the genetics of MALT lymphomas by Xia, et al. (a paper beyond my genetic capabilities!), and a large study looking at KRAS mutations in lung adenocarcinoma (by Kakegawa; it seems there is little new in this paper, however). Diaz de Leon, et al. identified that TERT mutation carriers exhibit preclinical signs of lung fibrosis, bone marrow dysfunction, and premature aging, a disease association highlighted at the Pulmonary Pathology Society Meeting.
There were a child’s bag of Halloween candy worth of case reports and small case series.  These include the occurrence of a mediastinal cystic teratoma by Suwatanapongched, microcystic squamous cell carcinoma of the lung (Weissferdt), and the development of miliary mesothelioma following multimodality therapy by Purek, et al.  Cryptococcus gattii infection, an emerging pathogen in the Pacific Northwest and western United States, is highlighted in a case report by Garrett.  Those of you who were at the Pulmonary Pathology Society Meeting in New York will undoubtedly remember this bug.  Gravdahl, et al. described the development of a spindle cell pseudotumor due to histoplasmosis.  Ishii et al described a patient with sarcoidosis and vasculitis who was thought to have Takayasu arteritis because of the involvement of large vessels.  Finally, Das described the development of alveolar hemorrhage due to sirolimus.

There were several articles dealing with thymic epithelial neoplasms.  Weissferdt and Moran analyzed the significance of Pax8 and found that it might be helpful in distinguishing thymomas from other mediastinal neoplasms, while Yamada et al. evaluated expression of proteasome β5t in thymomas and thymic carcinomas (it might be helpful in distinguishing Type B3 from thymic carcinomas).

ARTICLE INDEX
Articles for Discussion
Vallieres E, Van Houtte P, Travis WD, Rami-Porta R, Goldstraw P.  Carcinoma In Situ at the Bronchial Resection Margin: A Review.  J Thorac Oncol. 2011 Oct;6(10):1617-1623.

Nishino M, Medoff BD, Mark EJ, Matsubara O, O'Donnell WJ, Currier PF, Kradin RL.  Variant alveolar lipoproteinosis: a syndrome with distinct clinical and pathological features.  Pathol Int. 2011 Sep;61(9):509-17.

Maekawa K, Ito Y, Hirai T, Kubo T, Imai S, Tatsumi S, Fujita K, Takakura S, Niimi A, Iinuma Y, Ichiyama S, Togashi K, Mishima M.  Environmental risk factors for pulmonary Mycobacterium avium-intracellulare complex disease.  Chest 2011 Sep;140(3):723-9.

Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Klüglich M, du Bois RM.  Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87.

Downey GP.  Resolving the scar of pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1140-1.

Articles for Notation
Neoplastic
Salgia R.  Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall cell lung cancer. Cancer. 2011 Sep 1;117(17):3889-99.

Tsuta K, Kalhor N,Wistuba II, Moran CA. Clinicopathological and immunohistochemical analysis of spindle-cell carcinoid tumour of the lung.  Histopathology.  2011; 59, 526–536.

Zhang Y, Yu JH, Lin XY, Miao Y, Han Y, Fan CF, Dong XJ, Dai SD, Wang EH. Overexpression of Frat1 correlates with malignant phenotype and advanced stage in human non-small cell lung cancer.  Virchows Arch. 2011 Sep;459(3):255-63.

Xia H, Nakayama T, Sakuma H, Yamada S, Sato F, Takino H, Okabe M, Fujiyoshi Y, Hattori H, Inagaki H.  Analysis of API2-MALT1 fusion, trisomies, and immunoglobulin VH genes in pulmonary mucosa-associated lymphoid tissue lymphoma.  Hum Pathol. 2011 Sep;42(9):1297-304.

Kakegawa S, Shimizu K, Sugano M, Miyamae Y, Kaira K, Araki T, Nakano T, Kamiyoshihara M, Kawashima O, Takeyoshi I.  Clinicopathological features of lung adenocarcinoma with KRAS mutations.  Cancer. 2011 Sep 15;117(18):4257-66.

Suwatanapongched T, Kiatboonsri S, Visessiri Y, Boonkasem S. A 30-year-old woman with intermittent cough and a mass-like opacity in the right upper lobe. Chest. 2011 Sep;140(3):808-13.

Weissferdt A, Moran CA.  Microcystic squamous cell carcinoma of the lung: a clinicopathologic study of three cases.  Am J Clin Pathol. 2011 Sep;136(3):436-41.

Purek L, Laroumagne S, Dutau H, Maldonado F, Astoul P.  Miliary Mesothelioma, A New Clinical and Radiological Presentation in Mesothelioma Patients with Prolonged Survival After Trimodality Therapy.  J Thoracic Oncol.  2011;6:1753-6.

Weissferdt A, Moran CA.  Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis.  Am J Surg Pathol. 2011 Sep;35(9):1305-10.

Yamada Y, Tomaru U, Ishizu A, Kiuchi T, Marukawa K, Matsuno Y, Kasahara M.  Expression of proteasome subunit β5t in thymic epithelial tumors.  Am J Surg Pathol. 2011 Sep;35(9):1296-304.

 
Non-neoplastic
Garrett L, Marr K, West S, Allada G. 74-year-old man from the pacific northwest with fever and a lung mass. Chest. 2011 Sep;140(3):814-7.

Gravdahl DJ, Gardetto JS, Hurley JR, Tazelaar HD, Koontz PW, Leslie KO.  Pulmonary histoplasmosis producing a spindle cell "pseudotumor".  Am J Clin Pathol. 2011 Sep;136(3):410-5.

Ishii A, Hoshii Y, Nakashima T, Umemoto S, Nakamura H, Tanaka N, Matsuzaki M, Ikeda E.  Sarcoidosis with pulmonary hypertension exacerbated by Takayasu-like large vessel vasculitis. Pathol Int. 2011 Sep;61(9):546-50.

Das S, Cherian SV, Das N, Garcha AS, Lenox R, Sexton J.  Persistent dyspnea in a 59-year-old woman receiving immunosuppressants. Chest. 2011 Sep;140(3):818-22.

Diaz de Leon A, Cronkhite JT, Yilmaz C, Brewington C, Wang R, Xing C, Hsia CC, Garcia CK.  Subclinical lung disease, macrocytosis, and premature graying in kindreds with telomerase (TERT) mutations. Chest. 2011 Sep;140(3):753-63.

September 2011 Edition

Welcome to the latest edition of Pulmonary Pathology Reviews, a vehicle intended to ease the pain of keeping pace with peer reviewed literature likely to be of interest to the pathologist with special interest in thoracic pathology.  This week's journal club came to us from Rochester, MN, home of the World Famous Mayo Clinic and Joe Maleszewski, one of the newest members of Mayo Minnesota's expanding pulmonary pathology team.  Click here if you want to see the beautiful summary that Joe put together to make it quick and easy to see what's new at a glance.  His OVERVIEW follows and beneath that is the ARTICLE INDEX with links to PubMed abstracts (and full text versions for those whose institutions have licensed access).  Click here if you want to hear the teleconference as it went down on Monday morning, September 26th, at 08:15 CDT.

OVERVIEW
This month, 24 articles were found relating to topics in pulmonary pathology. Again, the molecular theme is a hot topic in many of the manuscripts with a dearth of non-neoplastic articles. In addition to the articles for discussion and notation, several excellent review articles/editorials were published. One editorial by Travis et al summarizes the major paradigm shifts in the new IASLC/ATS/ERS lung adenocarcinoma classification system and their potential effects in the approach to the diagnosis of lung cancer.

For discussion, four articles on neoplastic lung disease were chosen. The first one from The National Lung Screening Trial Research Team, published in The New England Journal of Medicine, illustrates the utility of low-dose CT scans reducing the morality from lung cancer. This paper particularly warrants discussion given the attention that it received in the popular press. The second article by Ellis et al provided a rigorous aggregate of lung cancer biomarker data (through March 2010) in an attempt to provide some consensus recommendations for the use of molecular testing in lung cancer. The third article, by Welter et al, lays out evidence from a study of growth patterns of lung metastases from sarcomas in an attempt to help guide resection planning in individuals with metastatic sarcoma. Finally, Yoshida et al, provided a detailed histologic analysis of ALK-rearranged lung carcinomas and provide findings that describe the antigenic expression of these tumors, largely with respect to TTF-1 and p63.

For notation, Casiraghi et al provide a manuscript with data from the “International Registry of Lung Metastases,” where the describe a 10-year, single-center experience with lung metastasectomies. Chung et al provide a more basic-science bent on lung cancer by talking about the role of DNA methylation profiles in the possible step-wise transformation of atypical adenomatous hyperplasia to in-situ and then invasive adenocarcinoma. Shen et al examined the role of leukocyte telomere length in determining the risk of lung cancer. The number of involved lymph nodes in individuals with N1 non-small cell lung cancer are assessed for prognostic significance by Jonnalagadda et al. Murakami et al look at the role of Tyrosine phosphatase SHP-1 expression in Langerhans cells in the setting of single- and multi-organ histiocytosis. The utility of biomarkers in cytology specimens are examined by Righi et al and Hong et al. Finally, Sun et al examined the significance of TTF-1 expression in individuals with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy to determine potential prognostic significance.

With respect to non-neoplastic diseases, Foreman et al provided us with data from a large multi-center epidemiological study, COPDGene, where they find that female gender and maternal factors appear to play substantial roles in the development of early-onset, severe COPD. Plantier et al examine the possible roles for various genes involved in bronchiolization of distal airways in idiopathic pulmonary fibrosis.

Finally, six case reports describing bilateral cystic lesions, polycythemia with organizing pneumonia mimicking tuberculosis, ALK-rearranged NSCLC with markers of both glandular and squamous differentiation, an unusual form of papillary adenoma, a tumor with neuroendocrine and melanocytic differentiation, and a classic example of biphasic pulmonary blastoma (with a nice review of the literature).

We hope you all enjoy the chosen articles this month!

ARTICLE INDEX
Articles for Discussion
The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. NEJM 2011 Aug 4;365(5):395-409. [PAGE 4]

Ellis PM et al. A Systematic Review and Canadian Consensus Recommendations on the Use of Biomarkers in the Treatment of Non-small Cell Lung Cancer. J Thorac Oncol. 2011 Aug;6(8):1379-91. [PAGE 5]

Welter S et al. Growth patterns of lung metastases from sarcomas. Virchows Arch. 2011 Aug;459(2):213-9. Epub 2011 Jul 6. [PAGE 6]

Yoshida A. Comprehensive histologic analysis of ALK-rearranged lung carcinomas. Am J Surg Pathol. 2011 Aug;35(8):1226-34. [PAGE 7]

Articles for Notation
Neoplastic
Casiraghi M et al. A 10-year single-center experience on 708 lung metastasectomies: the evidence of the "international registry of lung metastases". J Thorac Oncol. 2011 Aug;6(8):1373-8. [PAGE 8]

Chung JH et al. DNA methylation profile during multistage progression of pulmonary adenocarcinomas. Virchows Arch (2011) 459:201-211. [PAGE 8]

Jonnalagadda S et al. The number of lymph node metastases as a prognostic factor in patients with N1 non-small cell lung cancer. Chest. 2011 Aug;140(2):433-40. [PAGE 8]

Murakami I et al. Tyrosine phosphatase SHP-1 is expressed higher in multisystem than in single-system Langerhans cell histiocytosis by immunohistochemistry. Virchows Arch. 2011 Aug;459(2):227-34. [PAGE 8]

Righi L et al. Immunohistochemical subtyping of non small cell lung cancer not otherwise specified in fine-needle aspiration cytology: a retrospective study of 103 cases with surgical correlation. Cancer. 2011 Aug 1;117(15):3416-23. [PAGE 9]

Shen M et al. A prospective study of telomere length measured by monochrome multiplex quantitative PCR and risk of lung cancer. Lung Cancer. 2011 Aug;73(2):133-7. [PAGE 9]

Sun JM et al. Significance of Thymidylate Synthase and Thyroid Transcription Factor 1 Expression in Patients with Nonsquamous Non-small Cell Lung Cancer Treated with Pemetrexed-Based Chemotherapy. J Thorac Oncol. 2011 Aug; 6(8): 1392-1399. [PAGE 9]

Hong YJ et al. Analysis of Tumor Markers in the Cytological Fluid Obtained from Computed Tomography-Guided Needle Aspiration Biopsy for the Diagnosis of Non-small Cell Lung Cancer. J Thorac Oncol. 2011 Aug;6(8):1330-5. [PAGE 10]

Non-neoplastic
Foreman MG et al. Early-Onset COPD is Associated with Female Gender, Maternal Factors, and African American Race in the COPDGene Study. Am J Respir Crit Care Med. 2011; 184: 414-420. [PAGE 11]

Plantier L et al. Ectopic respiratory epithelial cell differentiation in bronchiolised distal airspaces in idiopathic pulmonary fibrosis. Thorax. 2011 Aug;66(8):651-7. [PAGE 11]

Review Articles
Halmos B et al. Update in lung cancer and oncological disorders 2010. Am J Respir Crit Care Med. 2011 Aug 1;184(3):297-302.

Kulesza P et al. Emerging Concepts in the Pathology and Molecular Biology of Advanced Non-Small Cell Lung Cancer. Am J Clin Pathol 2011;136:228-238.

Stinchcombe TE et al. Annual Review of Advances in Non-small Cell Lung Cancer Research: A Report for the Year 2010. Journal of Thoracic Oncology 2011;6(8): 1443-1450.

Travis WD et al. Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification. Eur Respir J 2011; 38:239-243.

 

Case Reports
Kim SR et al. A 38-year-old Woman with Bilateral Cystic Lesions in Both Lower Lung Lobes. Chest 2011;140;544-548

Kimura Y et al. Case of polycythemia vera with unusual organizing pneumonia mimicking the clinical features of military tuberculosis and possibly caused by the involvement of neoplastic megakaryocytes. Pathology International 2011; 61: 486-490

Klempner SJ et al. ALK Translocation in Non-small Cell Lung Cancer with Adenocarcinoma and Squamous Cell Carcinoma Markers. Journal of Thoracic Oncology 2011; 6(8): 1439-1440.

Nakano T et al. Papillary adenoma of the lung with a peculiar raw macroscopic feature. Pathology International 2011; 61:475-480

Pilozzi E et al. Primary malignant tumour of the lung with neuroendocrine and melanoma differentiation. Virchows Arch 2011; 459: 239-243.

Van Loo S et al. Classic biphasic pulmonary blastoma: A case report and review of the literature. Lung Cancer 2011; 73: 127-132.

August 2011 Edition

Today's edition of Pulmonary Pathology Reviews comes to you from Ann Arbor Michigan, a place in which an autumn chill is insufficient to dampen the enthusiasm with which Wolverines fans everywhere greet the possibility of a return to football dominance - or at least presence - even if only in the Big Ten!  Lindsay Schmidt, a veteran now in her 2nd year as Assistant Professor of Pathology, and Jonathan Herbst, a rookie appointed as this year's Pulmonary Pathology Fellow, did all of the hard work in putting it together.  Check out their PDF summary of this month's bumper crop of articles that showed up in print in July 2011 by clicking here.  What follows below is an OVERVIEW summarizing what's hot 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 hear the teleconference as it went down at 09:15 EDT on Monday, August 29th - may take a few minutes but patience pays off by giving you the spirited dialogue that occured right here at www.pulmpathrev.typepad.com!

OVERVIEW
This month, we found 25 articles of interest to lovers of pulmonary pathology. As has been the case recently, most are regarding neoplastic diseases, with a few non-neoplastic articles as well. Of interest, there are quite a few interesting review articles, including several in pediatric pulmonary pathology, as well as some interesting letters to the editor regarding articles discussed in this group previously.

For discussion, we chose four articles dealing with various aspects of neoplastic lung pathology. First, something that we are all dealing with more and more as molecular diagnostic testing becomes vital to the practice of lung pathology, an article by Kozu et al regarding mutation specific antibodies in EGFR mutation testing for nonsmall cell lung carcinomas—the numbers weren’t quite what I was expecting. We also chose an interesting piece regarding positive urine cytologies in patients with lung carcinoma from Voulgaris et al, a phenomenon with which I was not familiar. Next, Sakai et al took a look at microscopic invasion of hilar peribronchiolar structures, an issue which I must admit I struggle with sometimes when trying to stage resected lung carcinomas accurately using the AJCC staging system. Last, we chose an article from Maeda et al in Chest looking at the impact of histologic subtype in NSCLC.

For notation, we found several excellent review articles, as well as some original research, case reports, and correspondence. First, Shaw et al provide a case report in the NEJM of an ALK-positive adenocarcinoma which contains invaluable information regarding the testing and treatment of those tumors. Ocque et al looked at the usefulness of immunohistochemistry in cytology specimens in subclassifying NSCLC. A more clinical paper from de Sanctis et al describes pulmonary toxicity from lung cancer treatments. Ichinokawa et al provided us with a review of an entity they call goblet-cell predominant adenocarcinomas—an entity which sounds a lot like mucinous BAC/AIS. There are several papers this month—from Wilbertz, Karpathiou, and Donnem—looking at several immunohistochemical markers with regards to prognosis in NSCLC. Weissferdt and Moran provide us with a case series of thymic carcinomas—an entity which we don’t often get to see published in this forum. There were several interesting case reports from Hashimoto, Marquez-Medina, and Krenke regarding tumor-to-tumor metastases, epithelioid hemangioendotheiomas, and primary pulmonary angiosarcoma. Nassar et al provide a very complete and handy review of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, another unusual entity we don’t often get to see published. Wen et al gave a review of genetic and epigenetic changes over time in NSCLC. Lastly in the neoplastic disease articles, we tackled several correspondences, including a trio of letters (from Camesell-Teijeiro, Yatabe, and Sakurai) regarding TTF-1 staining in non-pulmonary carcinomas, and one from Chadarevian regarding an unusual pediatric lung neoplasm termed “fetal lung interstitial tumor”.

In non-neoplastic diseases, King et al describe the phenomenon of constrictive bronchiolitis in soldiers returning from overseas. Kotloff et al gave us a very helpful and complete review of lung transplantation, including indications, outcomes, and a wealth of useful information. Bishop et al gave us another review, this one regarding another pediatric pulmonary entity, alveolar capillary dysplasia. Lastly, another non-pathology article from a radiology journal from van den Burgh et al regarding the long-term effects of screening CT scans.

Hope you all enjoy the articles we chose!

ARTICLE INDEX
Discussion articles
Kozu Y et al. The usefulness of mutation-specific antibodies in detecting epidermal growth factor receptor mutations and in predicting response to tyrosine kinase inhibitor therapy in lung adenocarcinoma. Lung Cancer 73: 45-50.

Voulgaris E et al. Positive urinary cytology in patients with lung cancer in the absence of obvious         urine tract metastases. Lung Cancer 73: 51-58.

Sakai Y et al. Significance of microscopic invasion into hilar peribronchovascular soft tissue in resection specimens of primary non-small cell lung cancer. Lung Cancer, 73: 89-95

Maeda R et al.  Prognostic Impact of Histology on Early-Stage Non-small Cell Lung Cancer.  Chest; 2011; 140; 135-145.


Articles for notation
Neoplastic diseases
Shaw AT et al.  A 31 Year-old Man with ALK-Positive Adenocarcinoma of the Lung.  N Engl J Med 2011; 365: 158-67. 

Ocque R et al.  Usefulness of Immunohistochemical and Histochemical Studies in the Classification of Lung Adenocarcinoma and Squamous Cell Carcinoma in Cytologic Specimens.  Am J Clin Path 2011;136:81-87.

De Sanctis A et al.  Pulmonary Toxicity Related to Systemic Treatment for Non-Small Cell Lung Cancer Cancer 2011; 117: 3069 – 80. 

Ichinokawa H et al. Clinicopathological characteristics of primary lung adenocarcinoma predominantly composed of goblet cells in surgically resected cases. Pathol International; 61: 423-429.

Wilbertz T et al. SOX2 gene amplification and protein overexpression are associated with better outcome in squamous lung cancer. Mod Pathol; 24: 944-953.

Karpathiou G et al. Light-chain 3A autophagic activity and prognostic significance in non-small cell carcinomas. Chest; 140: 127-134.

Donnem T et al. Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer. Cancer; July 15, 2011: 3193-3200.

Weissferdt A and Moran C. Thyrmic carcinoma associated with multilocular thymic cyst: a clinicopathologic study of 7 cases. Am J Surg Pathol; 35: 1074-1079.

Hashimoto K et al. Tumor-to-tumor metastasis: lung adenocarcinoma metastasizing to a follicular variant of papillary thyroid carcinoma. Path International; 61:435-441.

Marquez-Medina D et al. Pleural epithelioid hemangioendothelioma in an elderly patient: a case report and review of the literature. Lung Cancer; 73: 116-119.

Krenke R et al. Hemoptysis and spontaneous hemothorax in a patient with multifocal nodular lung lesions. Chest; 140: 245-251.

Nassar AA et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a systematic overview. Am J Resp Crit Care Med; 184: 8-16.

Wen J et al.  Genetic and Epigenetic Changes in Lung Carcinoma and Their Clinical Implications.  Modern Pathology 2011; 24; 932-943.

Cameselle-Teijeiro J et al. Thyroid transcription factor-1 expression in endometrioid tumors: a note of caution. Hum Pathol; 42: 1053-1055/Yatabe Y et al. Thyroid transcription factor-1 expression in endometrioid tumors: a note of caution—reply. Hum Pathol; 42: 1055-1056/Sakurai A et al. Thyroid transcription factor-1 expression in rare cases of mammary ductal carcinoma. Histopathology; 59: 143-161.

Chadarevian J-P et al. Diagnosis of “fetal lung interstitial tumor” requires a FISH negative for trisomies 8 and 2. Am J Surg Pathol; 35: 1085-1086.

Non-neoplastic diseases
King MS et al.  Constrictive Bronchiolitis in Soldiers Returning from Iraq and Afghanistan.  N Engl J Med 2011; 365: 222 – 30.

Kotloff RM and Thabut G. Lung transplantation. Am J Resp Crit Care Med; 184: 159-171.

Bishop NB et al.  Alveolar Capillary Dysplasia.  Am J Respir Crit Care Med 2011; 184: 172 – 79.

Van den Bergh KAM et al. Long-term effects of lung cancer computed tomography screening on health-related quality of life: the NELSON trial. Eur Resp J; 38: 154-161.