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Mesothelioma: HELP
Articles by William D. Travis
Based on 13 articles published since 2008
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Between 2008 and 2019, William Travis wrote the following 13 articles about Mesothelioma.
 
+ Citations + Abstracts
1 Guideline Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group. 2018

Husain, Aliya Noor / Colby, Thomas V / Ordóñez, Nelson G / Allen, Timothy Craig / Attanoos, Richard Luther / Beasley, Mary Beth / Butnor, Kelly Jo / Chirieac, Lucian R / Churg, Andrew M / Dacic, Sanja / Galateau-Sallé, Françoise / Gibbs, Allen / Gown, Allen M / Krausz, Thomas / Litzky, Leslie Anne / Marchevsky, Alberto / Nicholson, Andrew G / Roggli, Victor Louis / Sharma, Anupama K / Travis, William D / Walts, Ann E / Wick, Mark R. ·From the Department of Pathology, University of Chicago Medical Center, Chicago, Illinois (Drs Husain and Krausz) · the Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona (Dr Colby, emeritus) · the Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston (Dr Ordóñez) · the Department of Pathology, University of Texas Medical Branch, Galveston (Dr Allen) · the Department of Cellular Pathology, University Hospital of Wales and Cardiff University, Cardiff, South Glamorgan, Wales (Dr Attanoos) · the Department of Pathology, Mount Sinai Medical Center, New York, New York (Dr Beasley) · the Department of Pathology, University of Vermont College of Medicine, Burlington (Dr Butnor) · the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Dr Chirieac) · the Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Dr Churg) · the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Dacic) · Centre National Référent MESOPATH Departement de Biopathologie, Lyon Cedex, France (Dr Galateau-Sallé) · the Department of Pathology, University Hospital of Wales, Penarth, South Glamorgan, Wales (Dr Gibbs) · the Department of Pathology, PhenoPath Laboratories, Seattle, Washington (Dr Gown) · the Department of Pathology & Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, (Dr Litzky) · the Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California (Drs Marchevsky and Walts) · the Department of Histopathology, Royal Brompton & Harefield National Health Service Foundation Trust and the National Heart and Lung Institute, Imperial College, Chelsea, London, England (Dr Nicholson) · the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Roggli) · the Department of Pathology, University of Pittsburgh, and the VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania (Dr Sharma) · the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (Dr Travis) · and the Department of Pathology, University of Virginia Medical Center, Charlottesville (Dr Wick). ·Arch Pathol Lab Med · Pubmed #28686500.

ABSTRACT: CONTEXT: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. OBJECTIVE: - To provide updated, practical guidelines for the pathologic diagnosis of MM. DATA SOURCES: - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. CONCLUSIONS: - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.

2 Guideline Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. 2013

Husain, Aliya N / Colby, Thomas / Ordonez, Nelson / Krausz, Thomas / Attanoos, Richard / Beasley, Mary Beth / Borczuk, Alain C / Butnor, Kelly / Cagle, Philip T / Chirieac, Lucian R / Churg, Andrew / Dacic, Sanja / Fraire, Armando / Galateau-Salle, Francoise / Gibbs, Allen / Gown, Allen / Hammar, Samuel / Litzky, Leslie / Marchevsky, Alberto M / Nicholson, Andrew G / Roggli, Victor / Travis, William D / Wick, Mark / Anonymous2710735. ·Department of Pathology, University of Chicago, Chicago, IL 60637, USA. aliya.husain@uchospitals.edu ·Arch Pathol Lab Med · Pubmed #22929121.

ABSTRACT: CONTEXT: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. OBJECTIVE: To provide updated practical guidelines for the pathologic diagnosis of MM. DATA SOURCES: Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. CONCLUSIONS: There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. It is recommended that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

3 Guideline Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group. 2009

Husain, Aliya N / Colby, Thomas V / Ordóñez, Nelson G / Krausz, Thomas / Borczuk, Alain / Cagle, Philip T / Chirieac, Lucian R / Churg, Andrew / Galateau-Salle, Francoise / Gibbs, Allen R / Gown, Allen M / Hammar, Samuel P / Litzky, Leslie A / Roggli, Victor L / Travis, William D / Wick, Mark R. ·Department of Pathology, University of Chicago, Chicago, IL 60631, USA. ahusain@bsd.uchicago.edu ·Arch Pathol Lab Med · Pubmed #19653732.

ABSTRACT: CONTEXT: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. OBJECTIVE: To develop practical guidelines for the pathologic diagnosis of MM. DATA SOURCES: A pathology panel was convened at the International Mesothelioma Interest Group biennial meeting (October 2006). Pathologists with an interest in the field also contributed after the meeting. CONCLUSIONS: There was consensus opinion regarding (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the differential diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. The International Mesothelioma Interest Group recommends that markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

4 Review The 2015 World Health Organization Classification of Tumors of the Pleura: Advances since the 2004 Classification. 2016

Galateau-Salle, Francoise / Churg, Andrew / Roggli, Victor / Travis, William D / Anonymous531111. ·Department of Pathology, Centre Hospitalier Universitaire Caen, Caen, France; Department of Biopathology, Centre Leon Berard, Lyon, France. · Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada. · Department of Pathology, Duke University Medical Center, Durham, NC, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: travisw@mskcc.org. ·J Thorac Oncol · Pubmed #26811225.

ABSTRACT: A new World Health Organization (WHO) Classification of Tumors of the Pleura has recently been published. While the histologic classification of pleural malignant mesothelioma remains the same in the 2015 WHO classification as it was in the 2004 classification, multiple new observations have been recorded. First, more detailed study has been performed of histologic subtyping of epithelioid mesothelioma. In particular, it has been recognized that the pleomorphic subtype is associated with a poor prognosis, similar to that of sarcomatoid malignant mesothelioma. Second, there is improved understanding of the role of immunohistochemistry in distinguishing mesothelioma from carcinomas of various sites. Third, the criteria for distinguishing malignant mesothelioma from reactive mesothelial proliferations has been further refined. Fourth, additional studies of sarcomatoid mesothelioma have defined the frequency and spectrum of various histologic and immunohistochemical features, including heterologous elements. Finally, pleural well-differentiated papillary mesotheliomas are better defined and cases with invasive foci are recognized. In addition, several promising observations in mesothelioma pathology and genetics have been made in the past decade. These are now the subject of further investigation to determine if they can be validated in ways that will significantly impact clinical practice. These include a preliminary study of grading, suggesting that nuclear atypia and mitotic count are independent prognostic markers. The discovery of inactivating mutations in the BRCA1-associated protein 1 gene in sporadic and hereditary mesothelioma has opened up a variety of novel molecular, clinical, and diagnostic investigations. One possible diagnostic application includes the setting of separating mesothelioma from reactive mesothelial proliferations, where it may play a role in conjunction with p16 FISH. Another useful discovery was that the NAB2-STAT6 fusion is characteristic of solitary fibrous tumors. This led to development of a STAT6 antibody that is a reliable immunohistochemical marker for solitary fibrous tumors. Genetic studies also led to the finding that WWTR1-CAMTA1 fusions are useful diagnostic markers for epithelioid hemangioendotheliomas, which can present as pleural-based masses. Finally, desmoid type fibromatosis, a locally aggressive tumor that can present in the pleura, has been shown to frequently have CTNNB1 gene mutations and express β-catenin by immunohistochemistry.

5 Clinical Trial Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma. 2011

Kadota, Kyuichi / Suzuki, Kei / Sima, Camelia S / Rusch, Valerie W / Adusumilli, Prasad S / Travis, William D. ·Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York City, New York 10065, USA. ·J Thorac Oncol · Pubmed #21358344.

ABSTRACT: INTRODUCTION: In patients with epithelioid diffuse malignant pleural mesothelioma (DMPM), clinical stage is the current primary prognostic factor. We sought to investigate whether histologic subtyping can prognostically stratify patients with epithelioid DMPM. METHODS: Hematoxylin and eosin-stained slides of 232 patients with epithelioid DMPM (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed. We classified the tumors into five subtypes, according to the predominant histological pattern: trabecular, tubulopapillary, micropapillary, solid, and pleomorphic (≥10% of tumor). RESULTS: Median overall survival (OS) of all patients with epithelioid DMPM was 16.2 months. Patients with pleomorphic subtype (n = 34) had the worst median OS (8.1 months), followed by solid (n = 89, 13.7 months), micropapillary (n = 20, 15.8 months), tubulopapillary (n = 51, 17.9 months), and trabecular (n = 38, 24.9 months). The pleomorphic subtype was associated with lymphatic and vascular invasion (p < 0.001). The micropapillary subtype was associated with lymphatic invasion (p < 0.001). In univariate analyses, pleomorphic subtype was significantly associated with poor OS (p = 0.003). The pleomorphic subtype showed no significant difference on OS compared with biphasic and sarcomatoid DMPM. In a multivariate analysis, the pleomorphic subtype was an independent predictor of poor OS (p = 0.031). In patients who underwent R1 resection, pleomorphic subtype had the shortest median time to recurrence (13.7 months). CONCLUSION: Our finding that the pleomorphic subtype is a predictor of aggressive behavior in epithelioid DMPM with no survival difference from biphasic or sarcomatoid DMPM suggests that it may be best regarded as a sarcomatoid pattern rather than a subtype of epithelioid DMPM.

6 Clinical Trial WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer. 2010

Krug, Lee M / Dao, Tao / Brown, Andrew B / Maslak, Peter / Travis, William / Bekele, Sara / Korontsvit, Tatyana / Zakhaleva, Victoria / Wolchok, Jedd / Yuan, Jianda / Li, Hao / Tyson, Leslie / Scheinberg, David A. ·Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, 1275 York Ave, New York, NY, 10065, USA. krugl@mskcc.org ·Cancer Immunol Immunother · Pubmed #20532500.

ABSTRACT: BACKGROUND: The transcription factor, WT1, is highly overexpressed in malignant pleural mesothelioma (MPM) and immunohistochemical stains for WT1 are used routinely to aid in its diagnosis. Using computer prediction analysis we designed analog peptides derived from WT1 sequences by substituting amino acids at key HLA-A0201 binding positions. We tested the safety and immunogenicity of a WT1 vaccine comprised of four class I and class II peptides in patients with thoracic neoplasms expressing WT1. METHODS: Therapy consisted of six subcutaneous vaccinations administered with Montanide adjuvant on weeks 0, 4, 6, 8, 10, and 12, with 6 additional monthly injections for responding patients. Injection sites were pre-stimulated with GM-CSF (70 mcg). Immune responses were evaluated by DTH, CD4 T-cell proliferation, CD8 T-cell interferon gamma release, intracellular cytokine staining, WT1 peptide MHC-tetramer staining, and cytotoxicity against WT1 positive tumor cells. RESULTS: Nine patients with MPM and 3 with NSCLC were vaccinated, with 8 patients receiving at least 6 vaccinations; in total, 10 patients were evaluable for immune response. Six out of nine patients tested demonstrated CD4 T-cell proliferation to WT1 specific peptides, and five of the six HLA-A0201 patients tested mounted a CD8 T-cell response. Stimulated T cells were capable of cytotoxicity against WT-1 positive cells. Vaccination also induced polyfunctional CD8 T cell responses. CONCLUSIONS: This multivalent WT1 peptide analog vaccine induces immune responses in a high proportion of patients with thoracic malignancies with minimal toxicity. A randomized trial testing this vaccine as adjuvant therapy in MPM is planned.

7 Article Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study. 2018

Rosen, Lauren E / Karrison, Theodore / Ananthanarayanan, Vijayalakshmi / Gallan, Alexander J / Adusumilli, Prasad S / Alchami, Fouad S / Attanoos, Richard / Brcic, Luka / Butnor, Kelly J / Galateau-Sallé, Françoise / Hiroshima, Kenzo / Kadota, Kyuichi / Klampatsa, Astero / Stang, Nolween Le / Lindenmann, Joerg / Litzky, Leslie A / Marchevsky, Alberto / Medeiros, Filomena / Montero, M Angeles / Moore, David A / Nabeshima, Kazuki / Pavlisko, Elizabeth N / Roggli, Victor L / Sauter, Jennifer L / Sharma, Anupama / Sheaff, Michael / Travis, William D / Vigneswaran, Wickii T / Vrugt, Bart / Walts, Ann E / Tjota, Melissa Y / Krausz, Thomas / Husain, Aliya N. ·Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA. · Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA. · Department of Pathology, Loyola University Medical Center, Chicago, IL, USA. · Department of Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK. · Department of Cellular Pathology, University Hospital of Wales and Cardiff University, Cardiff, UK. · Medical University of Graz, Institute of Pathology, Graz, Austria. · Department of Pathology, University of Vermont Medical Center, Burlington, VT, USA. · Centre Léon Bérard, BioPathologie, Lyon, France. · Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan. · Department of Diagnostic Pathology, Kagawa University, Takamatsu, Japan. · Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Division of Thoracic and Hyperbaric Surgery, Department of Surgery,Medical University of Graz, Graz, Austria. · ,Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Basildon & Thurrock University Hospital, Department of Pathology, Basildon, UK. · Department of Histopathology, Royal Brompton and Harefield Hospitals Imperial College of London, London, UK. · Department of Cancer Studies, University of Leicester, Leicester, UK. · Fukuoka University, Department of Pathology, Fukuoka, Japan. · Department of Pathology, Duke University Medical Center, Durham, NC, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, University of Pittsburgh Medical Center and VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. · Department of Pathology, Barts Health NHS Trust, London, UK. · Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Chicago, IL, USA. · University Hospital Zurich, Institute for Pathology and Molecular Pathology, Zurich, Switzerland. ·Mod Pathol · Pubmed #29327706.

ABSTRACT: A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

8 Article A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions. 2017

Desmeules, Patrice / Joubert, Philippe / Zhang, Lei / Al-Ahmadie, Hikmat A / Fletcher, Christopher D / Vakiani, Efsevia / Delair, Deborah F / Rekhtman, Natasha / Ladanyi, Marc / Travis, William D / Antonescu, Cristina R. ·*Department of Pathology §Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY †Department of Pathology, Quebec Heart and Lung Institute, Quebec, QC, Canada ‡Department of Pathology, Brigham and Women's Hospital, Boston, MA. ·Am J Surg Pathol · Pubmed #28505004.

ABSTRACT: Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality. As both index cases occurred as intra-abdominal tumors in young adults, we searched our files for pleural and peritoneal MM occurring in adults younger than age of 40. All cases were tested by fluorescence in situ hybridization using custom bacterial artificial chromosomes probes for EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was performed. A total of 25 MM from patients aged 40 or less were screened, either from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40 y). Two additional ATF1-rearranged tumors were identified at pleural and peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100. BAP1 expression was retained in the 3 fusion-positive cases with available material, and in 80% (12/15) of the fusion-negative cases. Our results expand the spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a subgroup of conventional epithelioid MM. Other features of this unique MM subset include young age at presentation, lack of asbestos exposure and retained BAP1 expression.

9 Article Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma. 2015

Kadota, Kyuichi / Villena-Vargas, Jonathan / Nitadori, Jun-Ichi / Sima, Camelia S / Jones, David R / Travis, William D / Adusumilli, Prasad S. ·Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Ann Surg Oncol · Pubmed #25608772.

ABSTRACT: BACKGROUND: Currently, tumor-node-metastasis stage and histologic type are the established prognostic factors for malignant pleural mesothelioma, whereas no prognostic markers have been established for clinical practice. We investigated the prognostic value of CD10, a metalloproteinase that can promote cancer aggressiveness through enzymatic degradation and intracellular signaling crosstalk, in malignant pleural mesothelioma. METHODS: CD10 immunostaining was performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148; biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative (no staining) or positive (any staining). Epithelioid tumors were classified as pleomorphic subtype when cytologic pleomorphism was ≥10 % of the tumor. Overall survival (OS) was analyzed by log-rank tests and Cox proportional hazard models. RESULTS: Tumoral CD10 expression was identified in 42 % of epithelioid non-pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was correlated with higher mitotic count (p = 0.002). Overall survival for patients with positive CD10 expression was significantly shorter than that for patients with negative CD10 expression in all patients (p = 0.001) and in patients with epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019). CONCLUSIONS: Tumoral CD10 expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma.

10 Article High SUVmax on FDG-PET indicates pleomorphic subtype in epithelioid malignant pleural mesothelioma: supportive evidence to reclassify pleomorphic as nonepithelioid histology. 2012

Kadota, Kyuichi / Kachala, Stefan S / Nitadori, Jun-Ichi / Suzuki, Kei / Dunphy, Mark P S / Sima, Camelia S / Travis, William D / Rusch, Valerie W / Adusumilli, Prasad S. ·Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·J Thorac Oncol · Pubmed #22617244.

ABSTRACT: BACKGROUND: We have recently proposed to reclassify the pleomorphic subtype of epithelioid malignant pleural mesothelioma (MPM) as nonepithelioid (biphasic/sarcomatoid) histology because of its similarly poor prognosis. We sought to investigate whether preoperative maximum standardized uptake value (SUVmax) on F-fluorodeoxyglucose (FDG) positron emission tomography (PET) correlates with histologic subtype in MPM. METHODS: Clinical data were collected for 78 patients with MPM who underwent preoperative FDG-PET. We retrospectively classified the epithelioid tumors into five subtypes: trabecular, tubulopapillary, micropapillary, solid, and pleomorphic. Tumors were categorized by SUVmax into two groups: low (<10.0) and high (≥10.0). RESULTS: The median overall survival of epithelioid tumors with high SUVmax (n = 12) was significantly shorter (7.1 months) than that of epithelioid tumors with low SUVmax (n = 54, 18.9 months, p < 0.001) and comparable to nonepithelioid tumors (n = 12, 7.2 months). Epithelioid tumors with pleomorphic subtype (n = 9) had marginally higher SUVmax (mean ± SD: 10.6 ± 5.9) than epithelioid nonpleomorphic subtype (n = 57, 6.5 ± 3.2, p = 0.050), and were comparable to that of nonepithelioid tumors (n = 12, 9.1 ± 4.8). Among the epithelioid tumors with high SUVmax (n = 12), 50% (n = 6) showed pleomorphic subtype. In contrast, among epithelioid tumors with low SUVmax (n = 54), 6% (n = 3) showed epithelioid pleomorphic subtypes (p = 0.001). A positive correlation between mitotic count and SUVmax was observed (r = 0.30, p = 0.010). CONCLUSIONS: Pleomorphic subtype of epithelioid MPM showed higher SUVmax than the epithelioid nonpleomorphic subtype and was similar to nonepithelioid histology. Preoperative SUVmax on FDG-PET in epithelioid MPM can indicate patients with pleomorphic subtype with poor prognosis, supporting their reclassification as nonepithelioid.

11 Article A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma. 2012

Kadota, Kyuichi / Suzuki, Kei / Colovos, Christos / Sima, Camelia S / Rusch, Valerie W / Travis, William D / Adusumilli, Prasad S. ·Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·Mod Pathol · Pubmed #21983936.

ABSTRACT: Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival=28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors.

12 Article The fake fat phenomenon in organizing pleuritis: a source of confusion with desmoplastic malignant mesotheliomas. 2011

Churg, Andrew / Cagle, Philip / Colby, Thomas V / Corson, Joseph M / Gibbs, Allen R / Hammar, Samuel / Ordonez, Nelson / Roggli, Victor L / Tazelaar, Henry D / Travis, William D / Wick, Mark / Anonymous3630706. ·Department of Pathology, University of British Columbia, Vancouver, BC, Canada. achurg@interchange.ubc.ca ·Am J Surg Pathol · Pubmed #21959310.

ABSTRACT: We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.

13 Article Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients. 2011

Suzuki, Kei / Kadota, Kyuichi / Sima, Camelia S / Sadelain, Michel / Rusch, Valerie W / Travis, William D / Adusumilli, Prasad S. ·Division of Thoracic Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. ·Cancer Immunol Immunother · Pubmed #21769693.

ABSTRACT: This study aims to determine whether a semi-quantitative assessment of inflammatory response in tumor and stroma on routine hematoxylin and eosin-stained (H&E) slides can predict survival in patients with epithelioid malignant pleural mesothelioma (MPM). H&E sections of 175 epithelioid MPM specimens from a single institution (1989-2009) were reviewed. Patients who received neoadjuvant chemotherapy were excluded from analysis. Each tumor was histologically assessed for acute and chronic inflammatory response both within the tumor and the stromal component. Inflammatory response was graded: low (none to mild infiltrate) or high (moderate to severe infiltrate). Log-rank test and Cox proportional hazards regression were used to investigate the association between the degree of inflammation (acute/tumor, acute/stroma, chronic/tumor, and chronic/stroma) and overall survival (OS). Patients with high chronic inflammatory response in stroma (n = 59) had improved survival compared to low (n = 116) (median OS = 19.4 vs. 15.0 months, P = 0.01). This prognostic stratification remained significant in stage III patients (median OS = 16.0 vs. 9.3 months, P = 0.03). In multivariate analysis, chronic inflammation in stroma was an independent predictor of survival (HR = 0.659, 95% CI 0.464-0.937, P = 0.02). While high degree of chronic inflammatory cell infiltration in the stromal component was associated with improved overall survival, degree of other inflammatory responses did not show significant correlation with OS. Our study for the first time investigates inflammatory response in tumor and stroma and not only suggests the prognostic value of inflammatory response in epithelioid MPM but also provides rationale for investigation of immunotherapy to benefit epithelioid MPM patients.