Publications by authors named "Julien Calvani"

11 Publications

  • Page 1 of 1

A Comprehensive Clinicopathologic and Molecular Study of 19 Primary Effusion Lymphomas in HIV-infected Patients.

Am J Surg Pathol 2021 Sep 23. Epub 2021 Sep 23.

Departments of Pathology Clinical Immunology Hematological Cytogenetics Laboratory Hematology Laboratory, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) University of Paris, Paris Department of Pathology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) INSERM U955, University Paris-Est Créteil, Créteil, France.

Primary effusion lymphoma (PEL) is associated with human herpesvirus 8 and frequently with Epstein-Barr virus (EBV). We report here a single-center series of 19 human immunodeficiency virus-associated PELs, including 14 EBV+ and 5 EBV- PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV+ and EBV- cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed low expression levels of B-cell markers, including CD19 (0/19), CD20 (1/19), CD79a (0/19), PAX5 (1/19), BOB1 (3/19), and OCT2 (4/19), contrasting with a common expression of CD38 (10/19), CD138 (7/19), and IRF4/MUM1 (18/19). We observed a frequent aberrant expression of T-cell markers, especially CD3 (10/19), and less frequently CD2 (2/19), CD4 (3/19), CD5 (1/19), and CD8 (0/19). Only 2 cases were PD-L1 positive on tumor cells and none PD-1 positive. With respect to immune cells, 3 samples tested positive for PD-L1 and 5 for PD-1. Our 36-gene lymphopanel revealed 7 distinct variants in 5/10 PELs, with either a single or 2 mutations per sample: B2M (n=2), CD58 (n=1), EP300 (n=1), TNFAIP3 (n=1), ARID1A (n=1), and TP53 (n=1). Finally, we did not observe any major clinical, pathologic, or immunohistochemical differences between EBV+ and EBV- PELs and the outcome was similar (2-y overall survival probability of 61.9% [95% confidence interval, 31.2-82.1] vs. 60.0% [95% confidence interval, 12.6-88.2], respectively, P=0.62).
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http://dx.doi.org/10.1097/PAS.0000000000001813DOI Listing
September 2021

[An unusual digestive complication under anti-PD-1 (pembrolizumab)].

Ann Pathol 2020 Jul 24;40(4):320-323. Epub 2020 Feb 24.

Département de pathologie, université de Paris, hôpital Saint-Louis, Assistance publique-Hôpitaux de Paris (AP-HP), Paris, France; Inserm U976, Paris, France.

The most commonly reported pattern of anti-PD-1 induced colitis is an active colitis characterized by neutrophilic inflammation and prominent apoptosis. On the other hand, reports of collagenous colitis (which is a microscopic colitis) are exceptional. In this report, we describe an unusual case of anti-PD1-associated collagenous colitis in a 76-year-old man, treated with pembrolizumab for a stage IV cutaneous melanoma. Fourteen months after the start of pembrolizumab, the patient developed a grade 3 diarrhea (up to 9 stools per day) associated with profound hypokalemia. No bacterial, viral or parasitological infectious agents were found from stool analysis. The rectosigmoidoscopy showed colonic diffuse congestion with no ulceration. Systematic biopsies were performed during endoscopy. Histologically, the fragments analyzed revealed a moderately thickened subepithelial collagen layer (20-30μm thick) associated with a mild mixed inflammatory infiltrate within the lamina propria. There were no granuloma lesions, ulcerations or viral inclusion bodies. The patient was initially successfully treated with corticosteroids (prednisone) and temporary interruption of pembrolizumab. However, during corticosteroids tapering, a relapse was observed. The treatment was switched to budesonide, leading to a complete and definitive resolution of diarrhea. To date, budesonide has been stopped and pembrolizumab has not been restarted. Currently, there is a bone progression treated by radiotherapy alone. In case of a more important progression, a systemic treatment will be secondarily discussed.
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http://dx.doi.org/10.1016/j.annpat.2020.02.001DOI Listing
July 2020

[Erratum to "A better characterization of kidney allograft rejection infiltrates using in situ multiplex immunofluorescence" [Nephrol. Ther. 15S (2019) S43-S52]].

Nephrol Ther 2019 12;15(7):553

Laboratoire d'anatomie et cytologie pathologiques, hôpital Necker-enfants malades, 149, rue de Sèvres, 75015 Paris, France; Inserm, U1151, institut Necker-enfants-malades, 149, rue de Sèvres, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris cité, 12, rue de l'École-de-Médecine, 75006 Paris, France; Paris translational research center for organ transplantation, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.nephro.2019.11.001DOI Listing
December 2019

In situ multiplex immunofluorescence analysis of the inflammatory burden in kidney allograft rejection: A new tool to characterize the alloimmune response.

Am J Transplant 2020 04 11;20(4):942-953. Epub 2019 Dec 11.

Department of Pathology, Necker Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.

The exact composition of leukocyte infiltration during kidney allograft rejection is difficult to comprehend and visualize on the same biopsy slide. Using an innovative technology of multiplex immunofluorescence (mIF), we were able to detect simultaneously NK cells, macrophages, and T cells and to determine their intra- or extravascular localization using an endothelial marker. Twenty antibody-mediated rejection (ABMR), 20 T cell-mediated rejection (TCMR), and five normal biopsies were labeled, with automatic leukocyte quantification and localization. This method was compared to a classic NKp46 immunohistochemistry (IHC) with manual quantification and to mRNA quantification. mIF automatic quantification was strongly correlated to IHC (r = .91, P < .001) and to mRNA expression levels (r > .46, P < .021). T cells and macrophages were the 2 predominant populations involved in rejection (48.0 ± 4.4% and 49.3 ± 4.4%, respectively, in ABMR; 51.8 ± 6.0% and 45.3 ± 5.8% in TCMR). NK cells constituted a rare population in both ABMR (2.7 ± 0.7%) and TCMR (2.9 ± 0.6%). The intravascular compartment was mainly composed of T cells, including during ABMR, in peritubular and glomerular capillaries. However, NK cell and macrophage densities were significantly higher during ABMR in glomerular and peritubular capillaries. To conclude, this study demonstrates the feasibility and utility of mIF imaging to study and better understand the kidney allograft rejection process.
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http://dx.doi.org/10.1111/ajt.15699DOI Listing
April 2020

In situ multiplex immunofluorescence analysis of the inflammatory burden in kidney allograft rejection: A new tool to characterize the alloimmune response.

Nephrol Ther 2019 04;15 Suppl 1:S43-S52

Université Paris Descartes, Sorbonne Paris Cité, 12, rue de l'École-de-Médecine, 75006 Paris, France; Inserm, UMR-S970, 20, rue Leblanc, 75015 Paris, France; Laboratoire d'anatomie et cytologie pathologiques, hôpital européen Georges-Pompidou, 20 rue Leblanc, 75015 Paris, France.

Background: The exact composition and localization of the inflammatory burden during allograft rejection is difficult to analyse on the same biopsy slide. We tested the feasibility of detecting four distinct markers in a same paraffin-embedded tissue section from human kidney allograft rejection by using an innovative process of multiplex immunofluorescence. Methods: Kidney allograft biopsies from 20 antibody-mediated rejection, 20 T cell-mediated rejection and five non rejection were labelled against NKp46, CD163, CD3, and CD34 respectively for NK cells, macrophages, T cells and endothelial cells. Images were scanned and cells were automatically quantified and their extra- or intravascular location determined. Conventional immunohistochemistry against NKp46 with manual quantification and real time quantitative polymerase chain reaction for evaluation of the relative messenger ribonucleic acid (mRNA) expression levels of NK, T cell and macrophage transcripts were simultaneously performed. Results: Multiplex immunofluorescence cell quantification was strongly correlated to manual quantification by immunohistochemistry (r = 0.91, P < 0.001) and to mRNA expression levels (r > 0.46, P < 0.021). T cells and macrophages were the two predominant populations involved in rejection (48.0 ± 4.4% and 49.3 ± 4.4% in antibody-mediated rejection; 51.8 ± 6.0% and 45.3 ± 5.8% in T cell-mediated rejection respectively) despite an important heterogeneity in the composition of the inflammatory burden. NK cells constituted a rare population for both T cell-mediated rejection (2.9 ± 0.6%) and antibody-mediated rejection (2.7 ± 0.7%). The intravascular compartment was mainly composed of T cells, including during antibody-mediated rejection. However, NK cells and macrophages densities were significantly higher in capillaries during antibody-mediated rejection. Conclusion: Multiplex immunofluorescence staining is a reliable technology allowing studying the exact composition and localization of the inflammatory burden during kidney allograft rejection..
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http://dx.doi.org/10.1016/j.nephro.2019.03.008DOI Listing
April 2019

[Large scale teaching in pathology].

Ann Pathol 2019 Apr 30;39(2):144-150. Epub 2019 Jan 30.

Université de Franche-Comté, CHU de Besançon, 25030 Besançon, France.

Medical education is currently facing great changes that affect all medical specialties, including anatomical pathology. Due to rapidly increasing medical knowledge and diagnostic complexity, we are living an era of teaching resources mutualization. We present different tools that allow large numbers of students to access courses, self-evaluations, and competencies assessments. MOOC platforms and e-learning platforms are central to these new online tools, which include the French National Platform of Medical Specialties, dedicated to the teaching of 50,000 medical residents in France. We also discuss "serious games" and the use of images and virtual slides in anatomical pathology teaching. These new modalities can deliver essential knowledge to large student populations, but they must be used in conjunction with adapted teacher-led courses focusing on competencies and professional skills in order to be fully effective.
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http://dx.doi.org/10.1016/j.annpat.2018.12.009DOI Listing
April 2019

Solid pseudopapillary neoplasms of the pancreas do not express major pancreatic markers in pediatric patients.

Hum Pathol 2019 01 18;83:29-35. Epub 2018 Aug 18.

Department of Pathology, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, and Université Paris Descartes, 75015 Paris, France. Electronic address:

Solid pseudopapillary neoplasms (SPNs) of the pancreas are classified as "exocrine" pancreatic tumors by the World Health Organization. However, despite numerous studies using immunohistochemistry, electron microscopy, animal models, and molecular biology, the histogenesis of SPN remains unclear. At the same time, our knowledge of human pancreas development has significantly increased. It is now well known that the undifferentiated PDX1+ pancreatic progenitors proliferate and differentiate into endocrine, ductal, and acinar cells, thanks to the expression of numerous transcription factors, which can be used to better characterize pancreatic tumors. In a series of 14 pediatric SPN, we investigated the expression of 4 transcription factors associated with pancreatic development (PDX1, SOX9, PTF1A, and NKX2.2) to obtain new insights into the pathogenesis of SPN. In addition, we tested the expression of different markers of epithelial, endocrine, exocrine, and neural differentiation using both immunohistochemical and immunofluorescence analyses. All tumors displayed the typical histologic features of SPN, with both pseudopapillary and solid patterns. The immunoprofile was characterized by immunoreactivity for β-catenin (100%), progesterone receptor (100%), cyclin D1 (100%), synaptophysin (65%), and S100 (15%). In all cases, tumor cells were negative for the following markers: PDX1, SOX9, PTF1A, NKX2.2, chromogranin A, glucagon, insulin, somatostatin, ghrelin, pancreatic polypeptide, amylase, GFAP, calretinin, EPCAM, and estrogen receptor α. To conclude, SPNs do not express major transcription factors involved in pancreatic development and differentiation, which does not allow for precise pancreatic lineage of tumor cells. Thus, additional studies are still required to determine the origin of SPN.
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http://dx.doi.org/10.1016/j.humpath.2018.08.010DOI Listing
January 2019

[A case of lung infection imported from the United-States].

Ann Pathol 2017 Apr 17;37(2):202-205. Epub 2017 Mar 17.

Service d'anatomie et de cytologie pathologiques, hôpital Marie-Lannelongue, 133, avenue de la Résistance, 92350 Le Plessis-Robinson, France. Electronic address:

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http://dx.doi.org/10.1016/j.annpat.2017.01.007DOI Listing
April 2017

[Results of the Massive Open Online Course (MOOC) on cancer diagnosis and evaluation of its impact on the perception of the pathology specialty].

Ann Pathol 2017 Apr 17;37(2):144-150. Epub 2017 Mar 17.

Université Paris Diderot, Sorbonne-Paris-Cité, 75013 Paris, France; Service d'anatomie et cytologie pathologiques, CHU Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris, France. Electronic address:

The Massive Open Online Course (or MOOC) "Diagnostic Strategies Cancers", was hosted in autumn 2016 on the platform "France Université Numérique" and had two levels of learners: students in the field of health and biology and the general public. Of the 5285 learners in 81 different countries, 1237 (23%) were successfully certified. This MOOC was also integrated into the teaching program of medical students of Paris Diderot University and Paris 13 University. Using anonymous questionnaires before and after MOOC, it has been shown that pathology is less known than other medical specialties. Participation in this MOOC led to a marked improvement in participants' knowledge of the place and role of the pathologist in the diagnosis of cancers. Regarding the students who have followed the MOOC as part of their university course, their comments were very positive, but it is necessary to make substantial adjustments in the amounts and contents of the campus-based courses.
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http://dx.doi.org/10.1016/j.annpat.2017.02.001DOI Listing
April 2017

[Backstage of a massive open online course (MOOC) on cancer diagnosis].

Ann Pathol 2016 Oct 14;36(5):305-311. Epub 2016 Sep 14.

Université Paris Diderot, Sorbonne Paris Cité, 10, rue Françoise-Dolto, 75013 Paris, France; Service d'anatomie et cytologie pathologiques, CHU Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris, France. Electronic address:

Massive open online course (or MOOC) is a new online and open access teaching approach aimed at unlimited participation and providing interactions among students and teaching staff. These academic courses, often still free, lead to the delivery of a certificate of attendance and could soon also deliver a diploma. The MOOC "Stratégies diagnostiques des cancers" will be hosted in autumn 2016 on the platform "France Université Numérique" and will have two levels of learners: students in the field of health and biology and the general public. This MOOC will also be integrated into the teaching program of medical students of Paris Diderot University and Paris 13 University. The educational objective of this MOOC is to convey to all participants an overview of the diagnostic steps of cancers and of the various medical specialties involved in this diagnosis. The second week of the MOOC, entitled "tumor samples, macroscopic and microscopic analysis", presents the pathology specialty with the technical treatment of tissue or cell samples and the basic elements of the tissue section analysis to get a diagnosis of benign or malignant tumor. After this MOOC, it is planned to assess the impact of this new modality of teaching the pathology specialty or pathology, especially by the general public.
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http://dx.doi.org/10.1016/j.annpat.2016.08.013DOI Listing
October 2016
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