Publications by authors named "David Lucas"

264 Publications

COVID-19: rethinking seafarers' temporality to improve healthcare and prevention practices?

Int Marit Health 2021 ;72(1):84-85

Centre for Professional and Environmental Pathologies, Morvan Teaching Hospital (CHRU), Brest, France.

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http://dx.doi.org/10.5603/IMH.2021.0015DOI Listing
January 2021

Phase 2 Study of Ibrutinib in Classic and Variant Hairy Cell Leukemia.

Blood 2021 Mar 22. Epub 2021 Mar 22.

Ohio State University, Colmubus, Ohio, United States.

Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for patients who do not benefit from purine analogues. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown. Therefore, we conducted a multisite phase 2 study (NCT01841723) of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate at 32 weeks with response at 48 weeks and best response during treatment also assessed. Key secondary objectives were characterization of toxicity and determination of progression-free and overall survival. Thirty-seven patients were enrolled (24 at 420mg, 13 at 840mg). The median duration of follow-up was 3.5 years (range 0-5.9). The overall response rate at 32 weeks was 24% which increased to 36% at 48 weeks. The best overall response rate was 54%. The estimated 36-month progression-free and overall survivals were 73% and 85%, respectively. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common with anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to hairy cell leukemia patients with objective responses and results in prolonged disease control. While the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable progression-free survival suggest that ibrutinib may be beneficial in these patients.
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http://dx.doi.org/10.1182/blood.2020009688DOI Listing
March 2021

Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors.

JAMA Oncol 2021 Feb 25. Epub 2021 Feb 25.

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor.

Importance: Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain.

Objective: To determine which patients derived the greatest degree of clinical benefit from NGS profiling.

Design, Setting, And Participants: Patients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020.

Main Outcomes And Measures: Patients' subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer.

Results: During the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses.

Conclusions And Relevance: The high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.
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http://dx.doi.org/10.1001/jamaoncol.2020.7987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907987PMC
February 2021

Seafarers' Occupational Noise Exposure and Cardiovascular Risk. Comments to Bolm-Audorff, U.; et al. Occupational Noise and Hypertension Risk: A Systematic Review and Meta-Analysis. 2020, , 6281.

Int J Environ Res Public Health 2021 01 28;18(3). Epub 2021 Jan 28.

French Society of Maritime Medicine Brest, F-29200 Brest, France.

A German team published a new meta-analysis on the topic, "Occupational noise and hypertension risk: A systematic review and meta-analysis" in the International Journal of Environmental Research and Public Health [...].
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http://dx.doi.org/10.3390/ijerph18031149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908589PMC
January 2021

Medical unfitness for work at sea: causes and incidence rate over a 12-year period in France.

J Occup Med Toxicol 2021 Jan 21;16(1). Epub 2021 Jan 21.

Société Française de Médecine Maritime, Brest, France.

Background: The purposes of the study were first to determine the incidence rate of medical unfitness for work at sea among French seafarers, second to identify the conditions (diseases or accidents) causing such incapacity so as to set up prevention measures where possible and third to ascertain whether there were any overrepresentations of diseases according to category of unfit seafarers (fishers, merchant seafarers, shellfish farmers and professional sailors).

Methods: An exhaustive, observational, descriptive, retrospective epidemiological and nosological study was carried out based on the medical coding of files stored in the Aesculapius® national database, which registers all medical data regarding seafarers presenting at the French seafarers' health services. The increasing rate of permanent medical unfitness for work at sea was calculated in relation to the annual number of registered seafarers. A 12-year span was chosen in an attempt to ascertain the different sociodemographic categories associated with incapacity.

Results: In all, 2392 seafarers were declared unfit for work at sea. This represents a permanent medical unfitness for work at sea incidence rate of below 1% for all French seafarers examined for medical fitness between 2005 and 2016. The average age of the population of unfit seafarers was 48. The average time spent at sea before being declared unfit for work at sea was 15.5 years. Sixty-seven percent of the seafarers declared unfit had been working in the fishing sector. The main reasons for deciding permanent unfitness for work at sea were: rheumatological conditions associated specifically with the spine; injuries relating to accidents or other external causes, mostly affecting the upper limbs; mental and behavioural disorders, including mood disorders and particularly addictions; and diseases of the circulatory system, namely coronopathies. The incidence rate of medical unfitness for work at sea was seen to increase between 2005 and 2016, but a decrease due to the dilution effect was noted in 2015.

Conclusions: Permanent unfitness seldom occurs among French professional seafarers. Prevention measures must be focused on musculoskeletal disorders, psychiatric affections and coronary conditions as well as on combatting maritime accidents, especially in the professional fishing sector, where such affections and accidents are overrepresented.
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http://dx.doi.org/10.1186/s12995-021-00291-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818926PMC
January 2021

About the relationship between ship noise and the occurrence of arterial hypertension in seafarers.

Int Marit Health 2020 ;71(4):301

Centre for Professional and Environmental Pathologies, Morvan Teaching Hospital (CHRU), Brest, France.

No abstract because letter to editor.
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http://dx.doi.org/10.5603/IMH.2020.0053DOI Listing
January 2020

Outdoor air pollution from industrial chemicals causing new onset of asthma or COPD: a systematic review protocol.

J Occup Med Toxicol 2020 Dec 28;15(1):38. Epub 2020 Dec 28.

Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.

Background: Until today, industrial sources contribute to the multifaceted contamination of environmental air. Exposure to air pollutants has the potential to initiate and promote asthma and chronic obstructive pulmonary disease (COPD). At global scale, both entities cause the majority of about 4 million annual deaths by respiratory disease. However, we identified industrial contamination as a subgroup of air pollution that may be associated with this burden and is underinvestigated in research. Therefore, the aim of this study is to investigate associations between substances industrially released into environmental air and the occurrence of asthma and COPD in the human population. Here we present the protocol for our systematic review of the current evidence.

Methods: The following determinations will be applied during the systematic review process and are specified in the protocol that complies with the PRISMA-P statement. Populations of children and adults, as well as outdoor workers, exposed to industrially released air pollutants are of interest. Eligible studies may include subjects as controls who are non- or less exposed to the investigated air pollutants. The outcomes new-onset asthma and/or COPD investigated with risk ratio, odds ratio, hazard ratio, incidence rate ratio, cumulative incidence, and incidence rate are eligible. We will search the electronic literature databases EMBASE, MEDLINE, and Web of Science for peer-reviewed reports of incidence studies and incidence case-control studies. After systematic sorting of initial records, included studies will be subjected to quality assessment. Data will be synthesized qualitatively and, if appropriate, quantitatively for risk ratio and odds ratio. We will maintain and provide a PRISMA report.

Discussion: Results of this systematic review may indicate alterations of incidence and risk of asthma and/or COPD in populations within industrial exposure radiuses including outdoor workplaces. Specific causal substances and compositions will be identified, but results will depend on the exposure assessment of the eligible studies. Our approach covers effects of industrial contributions to overall air pollution if studies reportedly attribute investigated emissions to industry. Results of this study may raise the question wether the available higher-level evidence sufficiently covers the current scale of industrial exposure scenarios and their potential harm to respiratory health.

Trial Registration: This protocol was registered in PROSPERO, registration number CRD42020151573 .
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http://dx.doi.org/10.1186/s12995-020-00289-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768640PMC
December 2020

Transducin β-like protein 1 controls multiple oncogenic networks in diffuse large B-cell lymphoma.

Haematologica 2020 Sep 14;Online ahead of print. Epub 2020 Sep 14.

Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH.

Diffuse large B-cell lymphoma (DLBCL) is the most common Non-Hodgkin's lymphoma and is characterized by a remarkable heterogeneity with diverse variants that can be identified histologically and molecularly. Large-scale gene expression profiling studies have identified the germinal center B-cell (GCB-) and activated B-cell (ABC-) subtypes. Standard chemo-immunotherapy remains standard front line therapy, curing approximately two thirds of patients. Patients with refractory disease or those who relapse after salvage treatment have an overall poor prognosis highlighting the need for novel therapeutic strategies. Transducin β-like protein 1 (TBL1) is an exchange adaptor protein encoded by the TBL1X gene and known to function as a master regulator of the Wnt signalling pathway by binding to β-CATENIN and promoting its downstream transcriptional program. Here, we show that, unlike normal B-cells, DLBCL cells express abundant levels of TBL1 and its overexpression correlates with poor clinical outcome regardless of DLBCL molecular subtype. Genetic deletion of TBL1 and pharmacological approach using tegavivint, a first-in-class small molecule targeting TBL1 (Iterion Therapeutics), promotes DLBCL cell death in vitro and in vivo. Through an integrated genomic, biochemical, and pharmacologic analyses, we characterized a novel, β-CATENIN independent, post-transcriptional oncogenic function of TBL1 in DLBCL where TBL1 modulates the stability of key oncogenic proteins such as PLK1, MYC, and the autophagy regulatory protein BECLIN-1 through its interaction with a SKP1-CUL1-F-box (SCF) protein supercomplex. Collectively, our data provide the rationale for targeting TBL1 as a novel therapeutic strategy in DLBCL.
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http://dx.doi.org/10.3324/haematol.2020.268235DOI Listing
September 2020

Sexually transmitted infections in seafarers: 2020's perspectives based on a literature review from 2000-2020.

Int Marit Health 2020 ;71(3):166-173

Centre for Professional and Environmental Pathologies, Morvan Teaching Hospital (CHRU), Brest, France.

Background: Seafarers are a special population. The issue of sexually transmitted diseases among seafarers is as old as navigation itself, and is a public health issue and a matter of concern for seafarers themselves. The purpose of this article is to review the literature on sexually transmitted infections (STIs) in professional seafarers in the 21st century, with a view to guiding maritime physicians in their practice.

Materials And Methods: This is a Medline® and Scopus® literature review covering publications between 01/01/2000 and 31/12/2019. Out of the 224 articles, 26 were selected.

Results: This review showed that at the beginning of the 21st century, attention has been focused mainly on human immunodeficiency virus (HIV). Few seroprevalence data were available. Between 10% and 91% of seafarers had been tested for STIs. Several risk behaviours were identified: out of 4022 seafarers surveyed, 34.3% said they had several sexual partners; out of 3722 seafarers surveyed, 19.5% engaged with sex workers; out of 3493 seafarers surveyed, 63.3% did not always use condoms, while 58.0% were aware of the relevance of this protection. There was a lot of misunderstanding about STIs: 28.3% of seafarers believed that a healthy-looking person could not be HIV-positive.

Conclusions: The main pathology studied was HIV. Many seafarers had no specific training and only learned about STIs and HIV through media such as television. Maritime doctors could use new technologies to disseminate the right information on STI prevention.
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http://dx.doi.org/10.5603/IMH.2020.0030DOI Listing
January 2020

Seasickness and its impact on researchers' work on board French oceanographic vessels.

Int Marit Health 2020 ;71(3):160-165

French Society for Maritime Medicine, Faculty of Medicine and Health Sciences, University of Western Brittany, Brest, France.

Background: Seasickness (SS) is an often hidden pathology, but one that can significantly disrupt work on board. The aim of the study is to evaluate the influence of SS on the workability of workers on board vessels.

Materials And Methods: We performed a cross-sectional questionnaire study conducted on 250 oceanographers in 2015 during 3 months. Based on the "Bos seasickness susceptibility questionnaire", we created a specific questionnaire with 49 questions.

Results: 151 men and 72 women responded to the survey. 188 of them (91.7% of women and 80.8% of men) report being seasick, either occasionally (69%) or at each boarding where there is female predominance (23.6% vs. 11.3% for men). The major symptoms are nausea (82%) and vomiting (56%). 60% of the workers think that SS has an influence on the success of their mission, by first affecting their mood (50%), relationship (23%), and increased risk of accidents such as falls, accidents on machines or in laboratories (40%). Antinaupathic treatments also produce deleterious effects on their workstation. Women have higher risk of developing SS (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.03-6.6; p = 0.04), more frequently taking medicines when ill (OR 4.1; 95% CI 1.27-13.2; p = 0.004) and coming with her own tablets (OR 2.3; 95% CI 1.3-4.1; p = 0.04).

Conclusions: Gender is a trending factor of SS. Information on SS clinical signs, impact and therapeutics could be prone to prevent sickness and impact of it on workability.
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http://dx.doi.org/10.5603/IMH.2020.0029DOI Listing
January 2020

Acute occupational phosphine intoxications in the maritime shipping sector: Belgian and French reported cases.

Int Marit Health 2020 ;71(3):151-159

Centre of Maritime Health and Society, Institute of Public Health, University of Southern Denmark, N Bohrs Vej, 6700 Esbjerg, Denmark.

Background: During ship transport of organic cargo e.g. soybeans in bulk or textiles in containers, there is a risk of pests damaging the cargo during transport as well as of unwanted global spread of organisms. Consequently, fumigation of the shipped goods is recommended. While aiming to protect the cargo from being damaged by pests during the transport time, fumigation constitutes a risk to the health of seafarers and port workers and even fatal cases are seen. Phosphine gas is increasingly applied for fumigation. Based on former experiences this article aims to describe the risk and to provide recommendations for prevention.

Materials And Methods: All reports of acute occupational exposures to phosphine in the maritime shipping industry to the Belgian Poison Centre were analysed and compared to reports in a study by ANSES (Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail), which collected data from the French Poison Centres. Data were registered and analysed between the 1st of January 1999 and the 31 of December 2018.

Results: The reported incidents have so far been rather few but seem to have increased over the last years. Symptoms are gastro-intestinal, neurologic and respiratory and often seem "vague" and non-specific and are often difficult to recognise for first responders. In the cases where the aetiology of the incident is known, there often seems to be a lack of clear information about the risk and options for mitigation in workplaces and among the workers. Twelve publications of case reports were included from the literature review that showed the same patterns as found in the registered incident reports.

Conclusions: There seems to be an increase in incidents of acute poisoning from phosphine worldwide. This increase could be linked to the phasing out of methyl bromide in the Montreal Protocol but may also have other explanations. Strict precautions are needed when using phosphine for fumigation of ship cargoes and containers. Since symptoms are often vague, first-responders need to pay attention to the possible occurrence of acute phosphine intoxication as it may be life threatening. Phosphine intoxication remains a diagnosis nor to underestimate not to miss. Further monitoring and research is needed. Preventive actions are mandatory. It is essential to implement in a strict way the existing legislation of an in-transit fumigation with phosphine. Training of the crew and good communication between the different actors during an in-transit fumigation (ship-owner, captain, fumigator, crew, longshoremen) is the key of a good prevention of accidents.
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http://dx.doi.org/10.5603/IMH.2020.0028DOI Listing
January 2020

COVID-19 on cruise ships: preventive quarantine or abandonment of patients?

Int Marit Health 2020;71(2):147-148

French Society for Maritime Medicine, Faculty of Medicine and Health Sciences, University of Western Brittany, Brest, France.

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http://dx.doi.org/10.5603/IMH.2020.0025DOI Listing
July 2020

A genomic survey of sarcomas on sun-exposed skin reveals distinctive candidate drivers and potentially targetable mutations.

Hum Pathol 2020 08 12;102:60-69. Epub 2020 Jun 12.

Department of Pathology, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA; Department of Dermatology, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA; Rogel Cancer Center, University of Michigan, 1500 E. Medical Center Drive Ann Arbor, MI, 48109, USA. Electronic address:

Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping microscopic and immunophenotypic features. Improved understanding of molecular alterations in these tumors may provide diagnostic and therapeutic insights. We characterized 111 cutaneous sarcomatoid malignancies and their counterparts, including primary cutaneous angiosarcoma (n = 7), atypical fibroxanthoma (AFX) (n = 21), pleomorphic dermal sarcoma (PDS) (n = 17), extracutaneous undifferentiated pleomorphic sarcoma (n = 8), cutaneous leiomyosarcoma (LMS) (n = 5), extracutaneous LMS (n = 9), sarcomatoid squamous cell carcinoma (spindle cell squamous cell carcinoma) (S-SCC) (n = 24), and conventional cutaneous squamous cell carcinoma (SCC) (n = 20), by next-generation sequencing (NGS) using the StrataNGS panel for copy number variations, mutations, and/or fusions in more than 60 cancer-related genes. TP53 mutations were highly recurrent in most groups. Angiosarcoma displayed previously reported MYC amplifications, as well as CCND1 gains. RB1 mutations were relatively restricted to cutaneous LMS. As previously reported, PIK3CA mutations occurred in AFX, whereas RAS activation was more frequent in PDS. CDKN2A mutations were recurrent in AFX and S-SCC, whereas PDS displayed frequent CDKN2A deletion. S-SCC displayed mutational similarity to conventional SCC. BRCA1/2 mutations were specific to tumors with disease progression. In a subset, we detected potential driver events novel to these tumor types: activating mutations in IDH2 (PDS), MAP2K1 (angiosarcoma, PDS), and JAK1 (S-SCC) and copy gains in FGFR1 (angiosarcoma, S-SCC), KIT (AFX), MET (PDS), and PDGFRA (PDS). Our findings confirm and expand the spectrum of known genomic aberrations, including potential targetable drivers, in cutaneous sarcomatoid malignancies. In addition, certain events are relatively specific to particular tumors within this differential diagnosis and hence might be diagnostically informative.
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http://dx.doi.org/10.1016/j.humpath.2020.06.003DOI Listing
August 2020

Temporary and permanent unfitness of occupational divers. Brest Cohort 2002-2019 from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

Int Marit Health 2020 ;71(1):71-77

Centre for Professional and Environmental Pathologies (Centre de Ressource en Pathologie Professionnelle et Environnementale CRPPE), Brest University Hospital (CHRU), Brest, France.

Background: In France, the monitoring of professional divers is regulated. Several learned societies (French Occupational Medicine Society, French Hyperbaric Medicine Society and French Maritime Medicine Society) have issued follow-up recommendations for professional divers, including medical follow-up. Medical decisions could be temporary unfitness for diving, temporary fitness with monitoring, a restriction of fitness, or permanent unfitness. The aim of study was to point out the causes of unfitness in our centre.

Materials And Methods: The divers' files were selected from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P). Only files with a special medical decision were selected, between 2002 and 2019.

Results: Three hundred and ninety-six professional divers are followed-up in our centre and 1371 medical decisions were delivered. There were 29 (7.3%) divers with a special medical decision, during 42 (3.1%) medical visit. Twelve (3.0%) had a permanent unfitness. The leading cause of unfitness was pulmonary diseases: emphysema (3), chronic obstructive pulmonary disorder (2), asthma (2). Sixteen (4.0%) divers had temporary unfitness. The leading causes were cardiovascular (4 times) and neurological (6 times). Twelve (3.0%) divers had had at least one decompression sickness.

Conclusions: Judgments of permanent unfitness for diving were rare (3.0% of divers), but were because of life-threatening disease. Medical follow-up of occupational divers was justified to decrease the risk of fatal event during occupational dives.
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http://dx.doi.org/10.5603/IMH.2020.0014DOI Listing
December 2020

Comment on Oldenburg, M., Jensen, H.J. Stress and Strain among Seafarers Related to the Occupational Groups. 2019, doi:10.3390/ijerph16071153.

Int J Environ Res Public Health 2020 02 11;17(4). Epub 2020 Feb 11.

French Society of Maritime Medicine Brest, F-29200 Brest, France.

Recently, Oldenburg M published an article in the journal "Communication" titled "Stress and Strain among Seafarers Related to the Occupational Groups" [...].
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http://dx.doi.org/10.3390/ijerph17041141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068386PMC
February 2020

Exposure to fumigants in containers: a questionnaire assessment on 125 French dockers.

Int Marit Health 2019 ;70(4):195-201

European Society for Environmental and Occupational Medicine, Berlin, Germany.

Background: Cases of intoxications to gas from container's atmosphere have been described. For diagnosis, Fum Ex 2 questionnaire has been developed by the European Society for Environmental and Occupational Medicine. The aim of this study was to enhance knowledge on health effects of toxic substances in containers and to validate this questionnaire in medical follow-up and diagnosis.

Materials And Methods: In 2014, 125 French dockers answered the questionnaire in a face-to-face interview.

Results: 83.5% declared no exposure to fumigants or pesticides. Most frequently declared symptoms were fatigue and neurological disorders for dockers and respiratory irritation for refrigeration technicians. Only 28 workers wore regularly individual protection equipment.

Conclusions: A "healthy worker" effect could explain low level of symptoms. Fum Ex 2 questionnaire is relevant for diagnosis. Workers in all steps of the logistic transport chain and consumers are exposed to containers' atmosphere.
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http://dx.doi.org/10.5603/IMH.2019.0031DOI Listing
May 2020

Primary Leiomyosarcoma of Bone: Review and Update.

Arch Pathol Lab Med 2019 11;143(11):1332-1337

From the Department of Pathology, University of Michigan, Ann Arbor.

Context.—: Leiomyosarcoma of bone is a rare primary osseous sarcoma characterized by smooth muscle differentiation and absence of malignant osteoid formation. Leiomyosarcoma of bone is diagnostically challenging; this can be improved with greater awareness of this entity and the ability to differentiate it from its histologic mimics. Because of its rarity, only a small number of studies are available in the literature. These factors contribute to our limited understanding of its pathology, prognosis, and treatment.

Objective.—: To review the clinicopathologic features of leiomyosarcoma of bone and present the most up-to-date understanding of its behavior and management in accordance with the current literature.

Data Sources.—: Review of pertinent literature on the major features, current knowledge thereof, and the authors' experience in the diagnosis and management of leiomyosarcoma of bone.

Conclusions.—: Leiomyosarcoma of bone is a rare but well-recognized primary osseous sarcoma that may arise de novo or in association with radiation. Although it is diagnostically challenging, awareness of this rare sarcoma and knowledge of its key histomorphologic and immunohistochemical features allow for accurate diagnosis.
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http://dx.doi.org/10.5858/arpa.2019-0375-RADOI Listing
November 2019

Contributions From University of Michigan 2018 New Frontiers in Pathology Conference.

Arch Pathol Lab Med 2019 11;143(11):1302-1303

From the Department of Pathology, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.5858/arpa.2019-0389-EDDOI Listing
November 2019

Are we underestimating the cardiovascular risks of seafarers?

Int Marit Health 2019 ;70(3):193

French Society of Maritime Medicine (Société Française de Médecine Maritime [SFMM]), Brest, France.

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http://dx.doi.org/10.5603/IMH.2019.0030DOI Listing
March 2020

Evolution of the respiratory function of professional divers over 15 years.

Int Marit Health 2019 ;70(2):119-124

French Society of Maritime Medicine (Société Française de Médecine Maritime [SFMM]), Brest, France.

Background: The study was aimed at assessing changes in respiratory function after 15 years of profes- sional diving, among scientific divers.

Materials And Methods: A retrospective study was performed on divers who underwent an initial visit and a visit 15 years later at the same medical centre, among divers who had a scientific activity (monitoring the coastline, fauna and flora). Pulmonary function tests were performed in the same laboratory with the same operating standards and using a Jaeger MasterBody plethysmograph. Each subject acted as his or her own control. The data were analysed by Student's t-test and Spearman's correlation coefficient.

Results: Twenty-six divers were included. Changes over 15 years included: a decrease in the forced expired volume in 1 second/functional vital capacity (FEV1/FVC) ratio (-6 for absolute value, p < 0.01; and -5% for theoretical value, p = 0.02); a decrease in forced expiratory flow (FEF)25% (-1.1 for absolute value, p < 0.01; and -21% for theoretical value, p < 0.01); a decrease in transfer factor for carbon monoxide (TLCO) (-0.7 for absolute value, p = 0.04); and an increase in vital capacity (VC) (+8% for theoretical value, p = 0.03). A significant correlation was found between the consumption of tobacco in packs per year (PY) and the variations in VC (r = 0.89; p < 0.01) and the variations in the theoretical FEV1 (r = 0.76; p = 0.03). There was a significant relationship between the number of dives and the variations in the percentage of the theoretical FEV1/FVC ratio (r = -0.42; p = 0.04). The same relationship was found for the average of dive duration (r = -0.59; p < 0.01) Conclusions: With increasing length of diving activities service, the pulmonary function displays a trend toward both a decrease in TLCO and a decrease in FEF25%.
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http://dx.doi.org/10.5603/IMH.2019.0019DOI Listing
December 2019

Don't forget about seafarer's boredom.

Int Marit Health 2019 ;70(2):82-87

French Society of Maritime Medicine (Société Française de Médecine Maritime [SFMM]), Brest, France.

Background: The question we asked was whether it is worthwhile screening for seafarers who are prone to boredom, and whose mental health might deteriorate on board because of the particular character of life at sea.

Materials And Methods: We used the Farmer and Sundberg Boredom Proneness Scale (BPS), validated in French, as well as the Zigmond and Snaith Hospital Anxiety and Depression Scale (HADS). The survey was voluntary and responses were collected by means of questionnaires which were returned by post.

Results: Eighty seafarers (40 officers and 40 crew) as well as 63 office staff from the same shipping company were included in the survey. We found a significant difference between officers and operational personnel: average score of 8.4 ± 5 (median = 7) for officers and 10.2 ± 4.8 (median = 10) for operational personnel. 21% of the officers have scores greater than or equal to 12 compared with 41% of the crew. There is a significant correlation between the BPS and HADS test scores, in terms of depression, for the office staff and the seafarers taken as a whole; this correlation being highly significant among officers (r = +0.85), but only marginally significant among crew members (r = +0.54).

Conclusions: The BPS may be useful in screening for seafarers prone to boredom and depression for their fitness for embarkation.
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http://dx.doi.org/10.5603/IMH.2019.0013DOI Listing
December 2019

EWSR1-NFATC2 Translocation-associated Sarcoma Clinicopathologic Findings in a Rare Aggressive Primary Bone or Soft Tissue Tumor.

Am J Surg Pathol 2019 08;43(8):1112-1122

Departments of Pathology.

In recent years, a novel small round cell sarcoma harboring EWSR1-NFATC2 translocation with immunomorphologic overlap with Ewing sarcoma (ES), myoepithelial tumors, and extraskeletal myxoid chondrosarcoma has emerged. There has not been a case series devoted to describing its detailed clinicopathologic and immunohistochemical characteristics. Six sarcomas harboring EWSR1-NFATC2 fusion transcripts by reverse transcription polymerase chain reaction and amplification of the fusion gene by fluorescence in situ hybridization were identified. The patients were 5 adult men and 1 adult woman. Three were primary bone tumors of the radius and 3 were primary soft tissue tumors. Most tumors showed monomorphic round to epithelioid cells in anastomosing cords and abundant myxohyaline to collagenous extracellular matrix. Two tumors had large areas of a solid, matrix-poor histomorphology. All tumors stained for CD99 and NKX2.2; while EMA, dot-like cytokeratin, and focal WT-1 and SMA were present in some tumors. All but 1 tumor showed poor histologic and radiologic responses to neoadjuvant ES-specific chemotherapy. Local or distant recurrences happened in 4 cases. EWSR1-NFATC2 sarcoma is a novel translocation-associated sarcoma. It presents as either a primary bone or soft tissue tumor, usually exhibits distinctive histopathologic features, and has predilection for long bones of adult men. It consistently shows recurrent fusion gene amplification readily detectable by EWSR1 breakapart fluorescence in situ hybridization, which serves as a diagnostic surrogate. It has potential for local and distant recurrence and histologic progression, and is resistant to Ewing sarcoma-specific chemotherapy.
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http://dx.doi.org/10.1097/PAS.0000000000001260DOI Listing
August 2019

Atypical "Sclerosing" Osteoblastic Neoplasm: A Tumor of Intermediate Biological Potential Between Usual Osteoblastoma and Conventional Osteosarcoma.

Am J Surg Pathol 2019 05;43(5):610-617

Departments of Anatomic Pathology.

The existence of "aggressive" osteoblastoma (OB) or malignant transformation of OB is controversial. Over a few decades, we have encountered a group of "borderline" sclerosing osteoblastic lesions that are difficult to classify, tending toward local recurrence, especially following curettage. A search of the consultative and institutional files from 3 co-authors for atypical OB, malignant transformation of OB, well-differentiated osteosarcoma (OS), and OB-like OS diagnoses revealed 8 similar cases. There were 6 males and 2 females, ages 11 to 55 years (mean, 26 y). Three arose in metatarsals, 2 in the fibula, and 1 each in the humerus, tibia, and femur. Radiologically, most were expansile, lytic to sclerotic, with circumscribed and at least partially sclerotic borders. Pathologically, all displayed a predominant, sclerosing sheet-like neoplastic bone growth pattern, associated with minor components of conventional OB. No solid sheets of osteoblasts or permeation of surrounding bone were identified. Six cases were reviewed by >1 expert orthopedic pathologist, often with divergent opinions. Four were initially diagnosed as OB, 2 as low-grade OS, 1 as high-grade OS, and 1 as atypical sclerosing osteoblastic neoplasm. Clinical follow-up for 7 patients ranged from 12 to 138 months (mean, 71 mo). Four underwent curettage only; 2, curettage and en bloc resection with negative margins; 1, en bloc intralesional resection, and 1 amputation. 5 locally recurred, with 3 "reclassified" as OSs. One local recurrence was considered dedifferentiation. Whether these tumors represent low-grade OSs or aggressive forms of OB remains unclear. We recommend classifying these neoplasms as "atypical sclerosing osteoblastic neoplasm" and performing complete resection with negative margins.
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http://dx.doi.org/10.1097/PAS.0000000000001236DOI Listing
May 2019

Phosphaturic Mesenchymal Tumor of the Cerebellopontine Angle.

JAMA Otolaryngol Head Neck Surg 2019 Mar;145(3):287-288

Department of Neurotology, Michigan Ear Institute, Farmington Hills, Michigan.

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http://dx.doi.org/10.1001/jamaoto.2018.4045DOI Listing
March 2019

Canonical Wnt/β-catenin signaling activation in soft-tissue sarcomas: A comparative study of synovial sarcoma and leiomyosarcoma.

Rare Tumors 2018 25;10:2036361318813431. Epub 2018 Nov 25.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Background: Previous studies have shown that aberrant activation of the Wnt/β-catenin pathway is associated with many malignant neoplasms. This includes some soft-tissue sarcoma phenotypes, most notably synovial sarcoma, implicating potential targets for novel molecular therapies.

Objective: We investigate the level of Wnt/β-catenin pathway activation present in leiomyosarcomas relative to synovial sarcomas, using expression of LEF1 and β-catenin as surrogates.

Methods: Cancer outlier profile analysis was performed on messenger RNA expression datasets in Oncomine (70 synovial sarcomas, 178 leiomyosarcomas). Results for LEF1 and β-catenin messenger RNA expression were reported in terms of median-centered intensity. Separate immunohistochemical studies were performed on tissue microarrays created from 77 synovial sarcomas and 89 leiomyosarcomas using antibodies to LEF1 and β-catenin. Tumors with unequivocal strong nuclear staining involving ⩾5% of cells were interpreted as positive.

Results: Cancer outlier profile analysis demonstrated a higher level of LEF1 messenger RNA expression in synovial sarcomas than in leiomyosarcomas ( < 0.0001), but showed no significant difference in β-catenin messenger RNA expression ( = 0.868). Immunohistochemistry showed most synovial sarcomas had strong nuclear expression of LEF1 (79%) and β-catenin (84%), while a small minority of leiomyosarcomas had strong nuclear expression of LEF1 (5%) and β-catenin (6%).

Conclusion: These results provide further evidence that aberrant activation of the Wnt/β-catenin pathway is present in most synovial sarcomas, but not in most leiomyosarcomas. While targeting the constituents of this pathway might be effective in the treatment of synovial sarcomas, it is not likely to be an effective strategy in the treatment of leiomyosarcomas.
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http://dx.doi.org/10.1177/2036361318813431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256314PMC
November 2018

Histiocytic Sarcoma: Review, Discussion of Transformation From B-Cell Lymphoma, and Differential Diagnosis.

Arch Pathol Lab Med 2018 11;142(11):1322-1329

From the Department of Pathology, University of Michigan, Ann Arbor.

Context.—: Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In particular, chronic lymphocytic leukemia/small lymphocytic lymphoma is a very common malignancy in the Western hemisphere, and most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma have an indolent course and behavior. However, 2% to 8% of chronic lymphocytic leukemia/small lymphocytic lymphoma cases transform. Histiocytic sarcomatous transformation is rare and portends poor prognosis.

Objective.—: To review the clinical features, morphology, and key points related to the differential diagnosis for histiocytic sarcoma. We discuss recent understanding of the biology underlying transformation.

Data Sources.—: University of Michigan case and review of pertinent literature about histiocytic sarcoma and morphologic differential diagnosis.

Conclusions.—: Histiocytic sarcoma is a rare histiocytic neoplasm that can arise as a result of transdifferentiation from low-grade B-cell lymphomas, and has a wide differential diagnosis including other histiocytic/dendritic cell neoplasms, myeloid neoplasms, lymphomas, melanoma, and carcinoma. However, some key morphologic and immunohistochemical features allow for accurate classification.
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http://dx.doi.org/10.5858/arpa.2018-0220-RADOI Listing
November 2018

Melanotic Neuroectodermal Tumor of Infancy.

Arch Pathol Lab Med 2018 11;142(11):1358-1363

From the Divisions of Anatomic and Clinical Pathology (Dr Soles) and Anatomic Pathology (Drs Wilson and Lucas), Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor.

Context.—: Melanotic neuroectodermal tumor of infancy, albeit rare and generally regarded as benign, is an important tumor to recognize because of its rapid growth, potential for local recurrence, and small round blue cell morphology, which can lead to misdiagnosis of a malignant neoplasm.

Objective.—: To review its clinical presentation and immunomorphologic findings, and discuss common entities in the differential diagnosis.

Data Sources.—: The study involved PubMed searches, including multiple review articles, case studies, retrospective studies, selected book chapters, and University of Michigan cases.

Conclusions.—: Melanotic neuroectodermal tumor of infancy most commonly occurs in the bones of the head and neck region during the first year of life, but it can also present in other locations, including the central nervous system, testes, ovaries, and subcutaneous soft tissues. Histologically, it is composed of a biphasic population of cells, consisting of epithelioid melanin-producing cells and primitive neurogenic cells in a fibrocollagenous stroma. These microscopic findings, especially in small biopsies, can lead to a broad differential diagnosis that includes malignant small round blue cell tumors and malignant melanoma. Melanotic neuroectodermal tumor of infancy commonly has an infiltrative growth pattern, and anatomic constraints often lead to incomplete resection and local recurrence, requiring multiple surgical operations. Because melanotic neuroectodermal tumor of infancy can mimic a more aggressive and aggressively treated malignancy, recognition of this rare tumor is very crucial for pathologists.
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http://dx.doi.org/10.5858/arpa.2018-0241-RADOI Listing
November 2018