Archives of pathology & laboratory medicine (Arch Pathol Lab Med)

Publications in this journal

• Article: Renal Lymph Nodes for Tumor Staging: Appraisal of 871 Nephrectomies With Examination of Hilar Fat.

  Vikas Mehta, Kumaran Mudaliar, Ritu Ghai, Marcus L Quek, John Milner, Robert C Flanigan, Maria M Picken
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  ABSTRACT: Context.-Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. Objective.-To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. Design.-We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Results.-Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases. Metastases were seen only in grossly identified lymph nodes (65% hilar, 16% nonhilar); all microscopic nodes were negative. Even with the microscopic examination of fat, hilar lymph nodes were recovered in only 22.5% of patients. A nonhilar route of node metastasis was suspected in 40 patients. Conclusions.-Only grossly identifiable lymph nodes, both hilar and nonhilar, were positive for metastases. Although microscopic examination of the hilar fat increased the number of lymph nodes recovered, the identification rate of these nodes was low (22.5%), and such microscopic nodes were invariably negative. Hence, microscopic examination of the hilar fat may be unnecessary.
  Archives of pathology & laboratory medicine 05/2013;
• Article: Detection of BRAF p.V600E Mutations in Melanoma by Immunohistochemistry Has a Good Interobserver Reproducibility.

  Cristi Marin, Alain Beauchet, David Capper, Ute Zimmermann, Catherine Julié, Marius Ilie, Philippe Saiag, Andreas von Deimling, Paul Hofman, Jean-François Emile
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  ABSTRACT: Context.-Assessment of BRAF p.V600E mutational status has become necessary for treatment of patients with metastatic melanoma. Detection of p.V600E mutation by immunohistochemistry was recently reported in several tumor types. Objective.-To evaluate the interobserver reproducibility of BRAF p.V600E detection by immunohistochemistry in melanoma. Design.-Immunohistochemistry with VE1 antibody was performed on metastatic melanomas of 67 patients. Staining interpretation was performed on digital image virtual slides of tissue microarrays. The p.V600E status was determined by 7 pathologists from 3 European laboratories, blinded for other interpretations and for molecular biology results. Results.-Melanomas had p.V600E (n = 30), p.V600K (n = 4), p.K601E (n = 1), p.600-601delinsE (n = 1), or no p.V600 mutations (n = 31). Staining of p.V600E within mutated cells was cytoplasmic and diffuse, and for each case the staining on the 3 tissue microarray cores was similar. In 53 cases (79.1%) the 7 pathologists had perfect concordance. Agreement of interobserver reproducibility was almost perfect (κ = 0.81 [0.77-0.85]). Only 2 false-positive responses (0.9%) were obtained. The specificities reported were 100% for 5 pathologists (two of whom previously trained for p.V600E interpretation), and 97% for 2 untrained pathologists. Conclusions.-Detection of BRAF p.V600E mutation by immunohistochemistry in melanomas has an excellent interobserver reproducibility. Our results suggest that immunohistochemistry could be used as a first step for detection of BRAF p.V600E mutation, to identify patients with melanoma as candidates for BRAF inhibitors.
  Archives of pathology & laboratory medicine 05/2013;
• Article: The College of American Pathologists' First 3 Years' Experience With High-Risk Human Papillomavirus Proficiency Testing for Cytology and Other Laboratories.

  Ann T Moriarty, Joel S Bentz, Barbara Winkler, Andrew H Fischer, Rodolfo Laucirica, Rhona J Souers, Nicole Thomas, Chengquan Zhao
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  ABSTRACT: Context.-The College of American Pathologists (CAP) Human Papillomavirus (High-Risk) Survey for Cytopathology and Other Laboratories (CHPV) meets the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) requirements for 5 proficiency testing challenges analyzed 3 times per year. This study reports laboratory performance for CHPV from 2008 through 2010. Objective.-To identify trends in proficiency testing performance for subscribers to the CAP CHPV. Design.-CHPV responses were evaluated by using a nonlinear mixed model (significance level of .05) with a 2-factor interaction term and repeated measures component, comparing year, media, method, and intended response. Media types included Digene transport, SurePath, ThinPrep media, or a mixture of media types. Proficiency testing challenges validated at 80% consensus. Results.-All challenges validated; 476 laboratories submitted 14 911 responses with 14 620 correct responses (98%). There were no differences between positive or negative challenges, or rate of correct responses; significant differences existed between media types by year and methods. Digene and ThinPrep media performed better than SurePath (P < .001; P = .03). There was a statistically significant difference between methods (P < .001); "other commercial kits," "other (noncommercial)" tests, and Third Wave performed more poorly than others. Conclusions.-Laboratories performed well when testing for human papillomavirus in CHPV during a period of 3 years. All challenges performed to the 80% threshold. Significant differences were found between methods and media. The CAP CHPV survey provides useful information for laboratories choosing human papillomavirus testing methods.
  Archives of pathology & laboratory medicine 05/2013; 137(5):606-609.
• Article: Transformation of pathologists: responding in a volatile, uncertain, complex, and ambiguous environment.

  James S Hernandez, Timothy Craig Allen
  Archives of pathology & laboratory medicine 05/2013; 137(5):603-5.
• Article: Inflammatory fibroid polyp of the gallbladder bearing a platelet-derived growth factor receptor alpha mutation.

  Maurizio Martini, Luisa Santoro, Pietro Familiari, Guido Costamagna, Riccardo Ricci
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  ABSTRACT: The inflammatory fibroid polyp (IFP) is a benign lesion occurring in the digestive tract, mostly in the stomach and small bowel, composed of fibrovascular tissue infiltrated by inflammatory cells including eosinophils and mastocytes. Its pathogenesis has been controversial (reactive versus neoplastic). The recent finding of mutations in platelet-derived growth factor receptor α (PDGFRA) in most gastric and small intestinal IFPs supported their neoplastic etiology, moreover helping in their differential diagnosis. In the only gallbladder IFP reported so far, the diagnosis was based on morphologic and immunohistochemical grounds, which in current standards would probably be considered not fully conclusive. Conversely, the gallbladder IFP we report shows typical pathologic features supported by a PDGFRA mutation, similar to its usual gastric and small intestinal counterparts, constituting the first report of an unequivocal IFP at gallbladder level. Thus, IFPs must be considered in the differential diagnosis of gallbladder mesenchymal masses, and genetic analysis of PDGFRA is a helpful tool for this purpose.
  Archives of pathology & laboratory medicine 05/2013; 137(5):721-4.
• Article: Robert e. Scully, MD.

  Eugene J Mark, Esther Oliva, Robert H Young
  Archives of pathology & laboratory medicine 05/2013; 137(5):599-600.
• Article: p16 Deletion in Sarcomatoid Tumors of the Lung and Pleura.

  Naobumi Tochigi, Richard Attanoos, Lucian R Chirieac, Timothy Craig Allen, Philip T Cagle, Sanja Dacic
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  ABSTRACT: Context.-The diagnosis of sarcomatoid neoplasms of the lung and pleura can be challenging. Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as the most common genetic alteration in malignant mesotheliomas that is of potential diagnostic and prognostic significance. Objectives.-To evaluate the frequency of 9p21 deletion by fluorescence in situ hybridization in the primary sarcomatoid neoplasms of the lung and pleura and to determine its potential diagnostic utility. Design.-Ninety-two sarcomatoid neoplasms of the lung and pleura (32 sarcomatoid mesotheliomas, 15 sarcomatoid carcinomas, 32 solitary fibrous tumors, and 13 high-grade sarcomas) were examined for 9p21 deletion by fluorescence in situ hybridization. Results.-Deletion of 9p21 was most frequently seen in malignant mesotheliomas (81%), followed by sarcomatoid carcinomas (53%), sarcomas (25%), and solitary fibrous tumors (12.5%). Malignant mesotheliomas showed mostly homozygous deletion, whereas sarcomatoid carcinomas showed either homozygous or hemizygous deletion. None of the sarcomas showed homozygous deletion. There was a trend toward more frequent occurrence of 9p21 deletion in recurrent solitary fibrous tumors, but this did not reach statistical difference. Conclusions.-Deletion of 9p21 is common in sarcomatoid tumors of the lung and pleura. Despite statistically significant differences in the frequency of 9p21 deletion, and because of the large overlap among the study groups, this genetic abnormality cannot be used as a reliable diagnostic tool in the assessment of sarcomatoid lesions of the lung and pleura. A potential use of p16 deletion in predicting the biology of solitary fibrous tumors should be further explored.
  Archives of pathology & laboratory medicine 05/2013; 137(5):632-636.
• Article: Increased thickness of abdominal subcutaneous adipose tissue occurs more frequently in steatohepatitis than in simple steatosis.

  M Isabel Fiel, Hamid Reza Sima, Garrett Desman, Amirabbas Azarian, Patrick Lento, Thomas D Schiano
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  ABSTRACT: Context.-The incidence of obesity is increasing and contributes to the rising incidence of fatty liver. Body mass index (BMI) is used to assess the degree of obesity but does not take into account the pattern of body fat distribution. Objectives.-To confirm the increasing incidence of fatty liver in an autopsy study. We hypothesized that a standardized measurement of abdominal subcutaneous adipose tissue (ASAT) might be a good noninvasive method for differentiating steatohepatitis from steatosis. Design.-Consecutive complete adult postmortem cases were studied and liver sections were assessed with a steatohepatitis scoring system. Spleen weight, ASAT, and clinical information were obtained. Spleen histology was assessed in a subset of patients having splenomegaly in the absence of cirrhosis. Results.-Patients with human immunodeficiency virus, hepatitis C virus, and appreciable alcohol use were excluded. Of 306 cases, the frequency of fatty liver was 51.6% with 33.3% having simple steatosis and 18.3%, having steatohepatitis. Mean ASAT was 3.7 cm in the steatohepatitis group versus 2.6 cm in the steatosis group (P < .001); this difference was greater in patients with a BMI less than 25 kg/m(2) (P = .05). Fibrocongestive splenomegaly was noted in 9 of 38 patients with nonalcoholic steatohepatitis (24%) in the absence of cirrhosis. Conclusions.-In this series of autopsy cases, a dramatic increase in the prevalence of fatty liver disease is demonstrated. Thicker ASAT is associated more with steatohepatitis than with simple steatosis, especially in patients with BMI below 25 kg/m(2). Fibrocongestive splenomegaly may occur in the absence of cirrhosis in the presence of steatohepatitis.
  Archives of pathology & laboratory medicine 05/2013; 137(5):642-6.
• Article: Accurate diagnosis of mesothelioma: more important than ever.

  Timothy Craig Allen
  Archives of pathology & laboratory medicine 05/2013; 137(5):601-2.
• Article: Hypoxic patterns of placental injury: a review.

  Jerzy Stanek
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  ABSTRACT: Context.-In utero hypoxia is an important cause of perinatal morbidity and mortality and can be evaluated retrospectively to explain perinatal outcomes, to assess recurrence risk in subsequent pregnancies, and to investigate for medicolegal purposes by identification of many hypoxic placental lesions. Definitions of some placental hypoxic lesions have been applied relatively liberally, and many of them are frequently underreported. Objectives.-To present a comprehensive assessment of the criteria for diagnosing acute and chronic histologic features, patterns, and lesions of placental and fetal hypoxia and to discuss clinicopathologic associations and limitations of the use thereof. The significance of lesions that have been described relatively recently and are not yet widely used, such as laminar necrosis; excessive, extravillous trophoblasts; decidual multinucleate extravillous trophoblasts; and, most important, the patterns of diffuse chronic hypoxic preuterine, uterine, and postuterine placental injury and placental maturation defect, will be discussed. Data Sources.-Literature review. Conclusions.-The placenta does not respond in a single way to hypoxia, and various placental hypoxic features should be explained within a clinical context. Because the placenta has a large reserve capacity, hypoxic lesions may not result in poor fetal condition or outcome. On the other hand, very acute, in utero, hypoxic events, followed by prompt delivery, may not be associated with placental pathology, and many poor perinatal outcomes can be explained by an etiology other than hypoxia. Nevertheless, assessment of placental hypoxic lesions is helpful for retrospective explanations of complications in pregnancy and in medicolegal investigation.
  Archives of pathology & laboratory medicine 05/2013; 137(5):706-20.
• Article: Tracking in Anatomic Pathology.

  Liron Pantanowitz, Alexander C Mackinnon, John H Sinard
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  ABSTRACT: Bar code-based tracking solutions, long present in clinical pathology laboratories, have recently made an appearance in anatomic pathology (AP) laboratories. Tracking of AP "assets" (specimens, blocks, slides) can enhance laboratory efficiency, promote patient safety, and improve patient care. Routing of excess clinical material into research laboratories and biorepositories are other avenues that can benefit from tracking of AP assets. Implementing tracking is not as simple as installing software and turning it on. Not all tracking solutions are alike. Careful analysis of laboratory workflow is needed before implementing tracking to assure that this solution will meet the needs of the laboratory. Such analysis will likely uncover practices that may need to be modified before a tracking system can be deployed. Costs that go beyond simply that of purchasing software will be incurred and need to be considered in the budgeting process. Finally, people, not technology, are the key to assuring quality. Tracking will require significant changes in workflow and an overall change in the culture of the laboratory. Preparation, training, buy-in, and accountability of the people involved are crucial to the success of this process. This article reviews the benefits, available technology, underlying principles, and implementation of tracking solutions for the AP and research laboratory.
  Archives of pathology & laboratory medicine 05/2013;
• Article: Plasma cell enrichment enhances detection of high-risk cytogenomic abnormalities by fluorescence in situ hybridization and improves risk stratification of patients with plasma cell neoplasms.

  Gary Lu, Ramya Muddasani, Robert Z Orlowski, Lynne V Abruzzo, Muzaffar H Qazilbash, M James You, Yaping Wang, Ming Zhao, Su Chen, Isabella Claudia Glitza, L Jeffrey Medeiros
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  ABSTRACT: Context.-Methods for plasma cell enrichment of bone marrow (BM) specimens can increase the sensitivity of fluorescence in situ hybridization (FISH) for detecting cytogenomic abnormalities. There are no published reports using these methods to evaluate high-risk cytogenomic abnormalities in patients with plasma cell neoplasms (PCNs) after therapy. Objective.-To evaluate the utility of plasma cell enrichment combined with FISH for detection of high-risk cytogenomic abnormalities in patients with PCNs after therapy. Design.-Twenty-eight patients with PCNs, of whom 22 received treatment, were included in this study. Plasma cells were enriched in BM aspirates by using a magnetic cell-sorting procedure to select CD138(+) cells. Probes were chosen to assess for del(17p13/TP53), del(13q14/RB1), 1q21/CKS1B gain, IgH/FGFR3, and IgH/MAF. Clinicopathologic data were collected during clinical follow-up after plasma cell enrichment. Results.-Plasma cells in nonenriched BM specimens ranged from 1% to 28% (median, 8%) compared with 28% to 96% (median, 73%) in enriched BM specimens (P < .001). In a subset of treated patients in clinical remission, FISH detected high-risk cytogenomic abnormalities only in plasma cell-enriched samples. This approach also detected abnormalities in cases of solitary plasmacytoma and monoclonal gammopathy of undetermined significance. Conclusions.-Plasma cell enrichment of BM specimens increases FISH sensitivity for detecting high-risk cytogenomic abnormalities, particularly in treated patients, and these results, in combination with clinical follow-up data, can be of value to improve risk stratification and patient management.
  Archives of pathology & laboratory medicine 05/2013; 137(5):625-31.
• Article: Raising the quality of care during medical missions: a survey to assess the need for clinical and anatomic pathology services in international medical missions.

  Agne Naujokas
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  ABSTRACT: Context.-Providing basic medical care to patients in underserved communities around the world is a valuable service and should not be compromised. Limited publicly available information on the use of pathology services during short-term medical missions (STMMs) shows a dire need for the improved quality of care being provided. Objective.-To assess the need for clinical and anatomic pathology services in international medical missions by conducting an online survey. Design.-A survey containing 35 questions aimed to understand the current use and availability of routine laboratory tests during STMMs, identify the need for particular tests that would improve quality of care, and determine the perceived obstacles preventing the delivery of the care to underserved communities worldwide. Answers from 21 health care providers who served on 50 medical missions were assessed. Results.-Survey results revealed a significant discrepancy between the availability of pathology services in the United States and during STMMs. Statistical significance (P< .001) was found in areas of routine blood work, cytopathology, and histologic evaluation, among many others. More than half of the STMMs did not have access to basic metabolic panel, rapid hepatitis B test, and microbial cultures. Another 28% of health care providers indicated that having human immunodeficiency virus testing would have improved health care quality. Conclusions.-Survey results show the need for improved pathology support during STMMs. The lack of precise diagnosis and disease monitoring has a negative effect on the quality of care provided during missions and the ability to enhance global health.
  Archives of pathology & laboratory medicine 05/2013; 137(5):637-41.
• Article: Adenomyoepithelioma of the breast: a brief diagnostic review.

  Ji Yoon Yoon, Dhananjay Chitale
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  ABSTRACT: Adenomyoepithelioma of the breast is an uncommon tumor characterized by dual differentiation into luminal cells and myoepithelial cells. A spectrum of histologic patterns is observed among these tumors and even in different areas of individual tumors. These lesions can be diagnostically challenging, especially when a core needle biopsy is performed, because of the heterogeneity of adenomyoepitheliomas. Recognition of the biphasic cellular elements and the characteristic overall architecture of the tumors in combination with immunohistochemistry are essential to establish the correct diagnosis. Although most tumors have a benign clinical course, local recurrences, malignant transformations, and distant metastases have been reported. All the reported malignant adenomyoepitheliomas with metastases have shown significant cytologic atypia and brisk mitotic rates. Therefore, adequate sampling of the tumor to identify these features is necessary. A complete excision with adequate margins would lower the chance of local recurrence or potential for metastasis.
  Archives of pathology & laboratory medicine 05/2013; 137(5):725-9.
• Article: Gleason score 7 adenocarcinoma of the prostate with lymph node metastases: analysis of 184 radical prostatectomy specimens.

  Oleksandr N Kryvenko, Nilesh S Gupta, Nilam Virani, Daniel Schultz, Juan Gomez, Ali Amin, Zhaoli Lane, Jonathan I Epstein
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  ABSTRACT: Context.-Prostate cancer (PC) with lymph node metastases (LN(+)) is relatively rare, whereas it is relatively common in disease with a Gleason score (GS) 8 to 10 and virtually never seen in PC with GS 6 or less. It is most variable in GS 7 PC. Objective.-To determine clinicopathologic features associated with GS 7 PC with LN(+) compared with a control group without lymph node metastases (LN(-)). Design.-We analyzed 184 GS 7 radical prostatectomies with LN(+) and the same number of LN(-) Gleason-matched controls. The LN(+) cases were GS 3 + 4 = 7 (n = 64; 34.8%), GS 4 + 3 = 7 (n = 66; 35.9%), GS 3 + 4 = 7 with tertiary 5 (n = 10; 5.4%), and GS 4 + 3 = 7 with tertiary 5 (n = 44; 23.9%). Results.-The LN(+) cases demonstrated higher average values in preoperative prostate-specific antigen (12.2 versus 8.1 ng/mL), percentage of positive biopsy cores (59.1% versus 42.9%), prostate weight (54.4 versus 49.4 g), number of LNs submitted (12.7 versus 9.4), incidence of nonfocal extraprostatic extension (82.6% versus 63.6%), tumor volume (28.9% versus 14.8%), frequency of lymphovascular invasion (78.3% versus 38.6%), intraductal spread of carcinoma (42.4% versus 20.7%), incidence of satellite tumor foci (16.4% versus 4.3%), incidence of pT3b disease (49.5% versus 14.7%), and lymphovascular invasion in the seminal vesicles (52% versus 30%). There were differences in GS 4 patterns and cytology between LN(+) and LN(-) cases, with the former having higher volumes of cribriform and poorly formed patterns, larger nuclei and nucleoli, and more-frequent macronucleoli. All P ≤ .05. Conclusion.-Gleason score 7 PC with LN(+) has features highlighting a more-aggressive phenotype. These features can be assessed as prognostic markers in GS 7 disease on biopsy (eg, GS 4 pattern, intraductal spread, cytology) or at radical prostatectomies (all variables), even in men without LN dissection or LN(-) disease.
  Archives of pathology & laboratory medicine 05/2013; 137(5):610-7.
• Article: Recalled Items and the American Board of Pathology Certification Examinations: What Constitutes Cheating?

  Diane Davis Davey
  Archives of pathology & laboratory medicine 04/2013;
• Article: Lung Cancer in the Era of Targeted Therapy: A Cytologist's Perspective.

  Maureen F Zakowski
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  ABSTRACT: Context.-The diagnosis and treatment of non-small cell lung cancer have changed dramatically in the past few years. The discovery of activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor and the use of drugs that successfully target those mutations are among the key advances that have led to a shift in the practice of oncology and pathology, with perhaps the greatest effect on the field of cytology. Objectives.-To present the perspective of a practicing thoracic pathologist and cytopathologist on the developments that have changed practice and to place those changes in a broader context. Data Sources.-Literature review, studies undertaken or participated in by the author, and personal experience. Conclusions.-Cytologists are in an ideal position to influence appropriate testing and treatment in the era of targeted therapy. Lung pathology has led the way in the era of targeted therapy, in no small part due to cytology.
  Archives of pathology & laboratory medicine 04/2013;
• Article: Interobserver Agreement and Assay Reproducibility of Folate Receptor α Expression in Lung Adenocarcinoma: A Prognostic Marker and Potential Therapeutic Target.

  Ryan E Bremer, Tatiana S Scoggin, Elizabeth B Somers, Daniel J O'Shannessy, David E Tacha
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  ABSTRACT: Context.-Lung cancer is the leading cause of cancer deaths in the United States and globally. Folate-targeted drugs are among the promising new targeted therapies for lung cancer, provided predictive biomarkers can be identified for optimal patient selection. Objective.-To evaluate the interobserver agreement and reproducibility of an immunohistochemistry assay for folate receptor α as a potential predictive marker for folate-targeted therapies. Design.-Immunohistochemistry using anti-folate receptor α antibody 26B3 was performed on formalin-fixed, paraffin-embedded tissues. The M-score, a semiquantitative measure of staining intensity and proportion of tumor cells staining, was determined for each specimen. Interobserver agreement was assessed using lung adenocarcinoma specimens stained at a single site and evaluated by 3 independent pathologists. Interinstrument reproducibility assessed 20 specimens stained by 3 different automated stainers. Interlaboratory agreement was determined on 5 specimens, repeatedly stained on each of 5 days, at 3 different study sites. Results.-Folate receptor α expression was identified in 39 of 54 cases of lung adenocarcinoma (72%) and 4 of 37 cases of lung squamous cell carcinoma (11%). Agreement among 3 pathologists was found in 24 of 26 cases (92%). Interinstrument reproducibility was observed in 19 of 20 cases (95%). Agreement among 3 laboratories was found for 49 of 50 specimens (98%). Conclusions.-Immunostaining of folate receptor α in lung adenocarcinomas is reproducible across staining platforms and among laboratories. Agreement among pathologists is achieved using a semiquantitative scoring method. An accurate and convenient method for determining folate receptor α expression offers a potentially invaluable tool for selecting patients for folate-targeted therapies.
  Archives of pathology & laboratory medicine 04/2013;
• Article: Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology.

  Neal I Lindeman, Philip T Cagle, Mary Beth Beasley, Dhananjay Arun Chitale, Sanja Dacic, Giuseppe Giaccone, Robert Brian Jenkins, David J Kwiatkowski, Juan-Sebastian Saldivar, Jeremy Squire, Erik Thunnissen, Marc Ladanyi
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  ABSTRACT: Objective.-To establish evidence-based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Participants.-Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies. Evidence.-Three unbiased literature searches of electronic databases were performed to capture articles published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation. Consensus Process.-Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4). Conclusions.-The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines.
  Archives of pathology & laboratory medicine 04/2013;