FOR A SENSITIVE EXPERIENCE OF INTERNATIONAL RELATIONS. BENEVOLENCE, ACCORDING TO FRÉDÉRIC RAMEL

Interview with Frédéric Ramel (Sciences Po, Centre de recherches internationales (CERI), CNRS, Paris, France), by Miriam Périer

In : Les Entretiens du CERI, 28 March 2022 URL : https://www.sciencespo.fr/ceri/en/content/sensitive-experienceinternational-relations-benevolence-according-frederic-ramel.html

In his book, La bienveillance dans les relations internationales. Un essai politique, published this winter by the CNRS Editions, Frédéric Ramel sets out to examine and analyse international relations through the lens of benevolence. Ramel, a professor of political science and researcher at the CERI explores this notion, which cynical commentators consider naive, looking at its origins and meaning. Through this, he provides an alternative, more sensitive perspective on our contemporary era as well as on past events. He answers our questions below.

You write, "Whether as a disposition or as behaviour, benevolence emphasises relationships based on a kind of solidarity that is particular in that it expresses human sociability, whether horizontal through conviviality between equals, or vertical through protection between non-equals, at a particular moment when faced with a particular tragic situation, which may be lasting or not." So who demonstrates this benevolence in the context of international relations? Diplomats? Senior civil servants in international organisations? Members of a globalised civil society?

Frédéric Ramel: Benevolence is not the prerogative of a select few. But before presenting the agents who are governed by it, it is important to make a distinction between benevolence as a disposition and benevolence as an action. All human beings can recognise behaviour based on benevolence-not causing harm to others (negative benevolence), helping those who are vulnerable, and/or taking reasonable steps to promote the good (positive benevolence). As spectators, we can all evaluate and admire the actions of someone like Denis Mukwege, the gynaecologist who "repairs" women who are victim of rape in conflicts in Africa, or someone like Leymah Gbowee, the Christian leader who promotes non-violence and advocates for the inclusion of women in the peace process is in Liberia. However, taking action (whether planned or spontaneous) is not automatic. What I explore in this book is the existence of this disposition associated with an attention to oneself, to others, and to the natural milieu in which we live, as well as the manifestation of benevolence in its negative and positive forms. The first actors who come to mind are diplomats, who take into account this disposition or even trigger it in immediate response to suffering endured by their counterparts and fellow citizens following terrorist attacks or natural disasters.

I also refer to the resonance these diplomats may experience in their practises by cultivating calm and silence (which might be described as an acoustic reading of their profession 1 which help to make diplomatic relationships more solid (whether in negotiation situations or during commemorations). But I also broaden this exploration of benevolence to other actors: intergovernmental organisations who contribute to cultivating social multilateralism in a spirit of solidarity (improving the living conditions for individuals, such as the International Labour Organisation for example); paradiplomacy cultivates by cities based on cooperation in terms of urban planning, transport, waste management, and which encourages improvements in well-being at the local level 2 ; and NGOs who promote assistance for the most vulnerable. Ordinary individuals are another important link in this chain and can also mobilise actions of benevolence to assist migrants (hospitality), change their forms of consumerism through new ways of managing shared spaces, or the preference for local producers (sobriety).

This exploration encourages us to recognise benevolence not as a substitute for power -still less as the foundation of international politics, that would be totally utopian -but as a kind of glue, a cement that primarily serves to encourage civility. As Pierre Hassner rightly emphasised in La revanche des passions, "if we do not, to varying degrees, have some sense of fraternity, a world that is based exclusively on interests or one exclusively based on identities cannot function." This recognition forces us to concretise our understanding of the conditions that help to liberate benevolence. In this respect, representatives of the English school such as Andrew Linklater, following on from Norbert Elias, have already contributed to the demonstration of the links between self-restraint and interdependence effects. [START_REF] Linklater | Social Standards of Self Restraint in World Politics[END_REF] You mentioned negative benevolence, could you say a little more about that?

Frédéric Ramel: Negative benevolence consists in not hurting others. It goes hand in hand with the principle of doing no harm. In international law, the basis of the due diligence principle, which promotes the idea of refraining from harm even before an action is undertaken, is based on the principle of benevolence itself because it activates concentrated attention to otherness. This negative benevolence must not be confused with the darker sides of benevolence which I explore in my book. Indeed, I do not rule out potential negative side effects of an action conducted in the name of benevolence, of which the effects may come into tension with the basis of its very nature (what Ricoeur called the "affective substance" of respect 4 ). Such negative effects may include instrumentalization for the purposes of reputation, the arrogance that may come from bestowing on beneficiaries assistance they are unable to return, or a lack of recognition from third party actors who may refuse that assistance categorically (which would mean necessarily accepting their refusal).

Let us look at the case of Rwanda as an example of this third phenomenon. Attempts at reconciling with the memory of the Rwandan genocide are present in political discourses and in public policy. They establish a connexion between national cohesion (attachment to a country scarred by the past) and personal resilience (healing by surpassing one's own limits), a dynamic supported by NGOs involved in this cathartic project to break away from hatred. But benevolence is misguided when it imposes a duty for forgiveness on victims who are not yet open to excuses. It "smothers indignation" 5 for some of these victims, and also lacks subtlety in its consideration of them according to a single homogenous profile. In other words, forgiveness entrepreneurs are mistaken in the validity of their own position. An enlightened vision of benevolence accepts these darker sides. It cannot erase them by attempting to impose benevolence. Without necessary steps, such an attempt could derail into the world described by Stanislav Lem at the heart of his book The Futurological Congress, a world in which a totalitarian-leaning government alters citizens' behaviour by releasing bombs of mutual benevolence.

You write that, "benevolence means accepting otherness as another self, as part of a relationship based on equality and not domination": is a foreign policy based on benevolence possible? What would that involve?

Frédéric Ramel: Taking benevolence into account in foreign policy is not necessarily new. Jacqueline de Romilly described this in her excellent book dedicated to gentleness in Greek thought [START_REF] De | La douceur dans la pensée grecque[END_REF] , as did Robert Axelrod in his famous theory on cooperative behaviour (avoiding unnecessary conflicts when the other cooperates, being open if once partner prioritises an end to cooperation and being forgiving after responding to a provocation, being transparent to encourage adaptation from other players). Beyond these classical references, foreign policy based on benevolence implies a certain temperance or strategic restraint. It supposes subscribing to the harm principle through exemplarity as a way of reinforcing the principle of due diligence based on the idea that "he who can intervene to prevent harm, but does nothing, is equally guilty." Foreign policy based on benevolence can be seen in armed conflicts, environmental protection, or human rights. It supposes that reciprocal vulnerabilities are taken into account in the context of transnational issues that expose all societies to the same risks (pandemics or climate change for example). However, these implications remain partly subject to several processes. I will only present two of them here: not succumbing to strategic excesses; and benefiting from full and entire recognition as a state, beyond the legal dimension.

Major powers adopt positions that are liable to succumb to the difficulties of the former and the weaknesses of the latter. Allow me to quote Pierre Hassner again. He compared the foreign policy restraint of Switzerland to that of Russia, invested with a civilising mission against Europe perceived as decadent. The line between "respecting differences, and affirming superiority" is a delicate one, according to him. This difficult balance sometimes provokes resentment, such as in the Russian case after the Cold War. The diplomatic marginalisation of Moscow, associated with the increasingly salient influence of the West in the post-Soviet space generated measures aiming to revive a waning identity (the annexing of Crimea, Russian military offensives in Ukraine etc.). In other words, foreign policy based on benevolence seems a delicate business, but it can by no means be confused with military intervention for the purposes of transforming political regimes-even though detractors of benevolence often use this example to deny its existence in the global space.

In your book, you distance yourself from two popular approaches to international relations. You write "observing and promoting benevolence in the global space also means distancing ourselves from two approaches that are currently popular. The first corresponds to critical theory, grouped under the term international political sociology […]. The second approach is that of care." Can you say more about this?

Frédéric Ramel: These two approaches are particularly stimulating. The first reveals the mechanisms of domination and the second emphasises altruistic behaviour in support of the most vulnerable. I have chosen to not follow either for two reasons. The first stems from my attachment to the sociology of international relations. Although I quote Foucault in the introduction, in order to shed light on benevolence as potential, echoing the idea of moral perfectionism, I am drawing more on What is Enlightenment? than on Discipline and Punish. In other words, I do not exclude the dark sides of benevolence as an instrument of domination, but nor do I make this the guiding line of my demonstration. This does not prevent the possibility of future collaboration because during a conversation with Didier Bigo on this theme, points of convergence appeared, such as the exploration of conditions (social as well as biological) that explain why a terrorist actor may not take action (thus strategic restraint).

As for the second approach, ferocious criticism such as that by Yves Michaud has reduced the philosophy of benevolence to care theory. Yet the first is much broader than the second, although both are built from the same foundation of solicitude. On the one hand, the philosophy of benevolence is based on a conception of humanity that goes beyond vulnerability, and on the other it is not limited to a politics of compassion.

Does an approach to international relations based on benevolence imply accepting a universal history that considers humanity as an indissociable whole? What place might there be for singularity in this? Frédéric Ramel: Georg Simmel emphasised the close correlation between the development of individuality and the broadening of social ties. For him, "that individuality of being and doing increases in general to the extent that the social circle surrounding the individual expands" [START_REF] Simmel | Sociologie, Etudes sur les formes de socialisation[END_REF] In other words, there is a search for universality that operates through the recognition of singularity both of individuals (moving from quantitative individualism to qualitative individualism in the evolution of modernity) and of groups. Paul Ricoeur, a major philosopher of solicitude and hospitality, developed an understanding of universalism that was more in keeping with this perpetually renewed search for recognition. One difficulty appears, however, when we seek to extend benevolence beyond immediate circles because the more action is directed at far away strangers the more benevolence loses intensity. Moreover, it is impossible to maintain benevolence towards everyone all the time. There must be a degree of selectivity. Indeed, as the philosopher Robert Spaermann emphasises, "the receivers of benevolence are so numerous that we cannot possible come to the aid of each in the same way." [START_REF] Spaemann | Essai sur l'éthique[END_REF] You have designed your book as a hybrid project combining references to social and human sciences but also to various arts, a hybridization that was also present in your work on music and diplomacy. How does the work of a political scientist benefit from these various sources? Frédéric Ramel: One aspect of my research in recent decades is somewhat unusual. It explores sensitivity in the global space using images and as you have said music, whether pop music or high culture. But there is something else in this book it is important to rememberthe subtitle. This is a political essay. In other words, I propose an exploration. I invite readers to lift certain veils, to embark upon an adventure. This leads to a freedom of tone that I had not yet experimented with, a style and form that a different from my previous texts. Moreover, the artistic elements are materials that allow us to shed light on political and social reality in less abrupt ways. Drawing on the work of Emeric Lhuisset on global warming or lockdowns ("The sound of Silence"), or by Saype on cooperation between cities ("Beyond Walls"), or more broadly on paintings from Holbein to Lévy-Dhurmer, I have tried to depict benevolence as attention to the other and the natural milieu, based on artistic representations. I am not the first to take this path at Sciences Po. Bruno Latour with the school of political arts, and of course, Laurence Bertrand-Dorléac, the current president of the FNSP, are pioneers in this area. I have modestly set out to follow in their footsteps.

To conclude, can you say a few words about the very beautiful map chosen to illustrate the cover of the book?

Frédéric Ramel: This magnificent map was first shown to me by a friend, who is a CNRS researcher in medieval history, with whom I have played the recorder in a group in Lyon for the past twenty years. It is the work of Oronce Fine (1494-1555) who was the first chair of mathematics at the Collège de France and the cartographer of King François I. It is inspired by the cordiform map projections (heart-shaped) invented by the German Johannes Werner in the early 16 th century. Although it is approximative due to the partial knowledge of the era (the connection between North America and Asia for example) it provides the first account of the southern lands not yet explored. Evidently, it has undeniable symbolic weight that resonates with the spirit of the book. One the one hand, bearing in mind the imagination as a human faculty that according to Bachelard "creates a higher reality", and on the other evoking an attachment to the Earth, because to quote Zygmunt Bauman, at the end of his Retrotopia (2017) "we-human inhabitants of Earth-are in the either/or situation: we face either joining hands, or common graves."

Interview by Miriam Périer, translation by Katharine Throssell.

More about this book available here.

Bibliography-

  Hassner P., La revanche des passions, Paris, Fayard, 2015. -Hutcheson F., Système de philosophie morale, Paris, Vrin, 2016. -Jullien F., Fonder la morale. Dialogue de Mencius avec un philosophe des Lumières , Paris, Grasset, 1995. -Linklater A., The Problem of Harm in World Politics, Cambridge, Cambridge University Press, 2011. -Linklater A., Violence and Civilization in the Western States-Systems, Cambridge, Cambridge University Press, 2016. -Michaud Y., Contre la bienveillance, Paris, Stock, 2016.


Alain Dieckhoff

Christophe Jaffrelot

Elise Massicard

Who are the Contemporary Populists in Power?

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WHO ARE THE CONTEMPORARY POPULISTS IN POWER?

Interview with Alain Dieckhoff, Christophe Jaffrelot et Elise Massicard (Sciences Po, Centre de recherches internationales (CERI), CNRS, Paris, France), by Miriam Périer

In : Les Entretiens du CERI, 2 March 2022 URL : https://www.sciencespo.fr/ceri/en/content/who-are-contemporarypopulists-power-interview-alain-dieckhoff-christophe-jaffrelot-and-elis.html Alain Dieckhoff, Christophe Jaffrelot and Elise Massicard are the coeditors of the latest book published as part of the Sciences Po series in International Relations and Political Economy. The book, entitled Contemporary populists in Power, gathers fourteen scholars, who, through their chapters, contribute to a novel analysis of populism, asking how populist leaders govern once they are in power. Through a comparative analysis of cases as diverse as Brazil and Sri Lanka, to name but two, this book offers a pioneering analysis on the practice of populism, from a geographical and analytical perspective. Interview with the editors.

What definition of populism have you collectively adopted in this volume?

Alain Dieckhoff: There are three main theoretical approaches for understanding the phenomenon of populism. The first perspective, well represented by the works of political scientist Cas Mudde (University of Georgia), emphasizes the role of ideas. It characterises populism as a 'thin-centred' ideology that considers society to be ultimately separated into two homogenous and antagonistic camps, 'the pure people', who are mobilized by the populists, versus 'the corrupt elite'. The second perspective, represented, for instance, by Kurt Weyland (University of Texas at Austin), defines populism simply as a political strategy through which a personalistic leader seeks or exercises government power through direct and unmediated support from large numbers of followers. The third perspective is represented by authors like Pierre Ostiguy (University of Valparaiso) and Pierre-André Taguieff (Cevipof, Sciences Po) who approach populism as a political style based on the appeal to a 'true people' defined either on an ethno-cultural basis (right-wing populism) or on a social basis (left-wing populism). We have decided to adopt this last approach to populism in this book. However, the divide between the three theoretical trends should not be overstated; the political style approach cannot be radically severed from the thinideology approach. Promoting a vision of the 'pure' people versus the 'corrupt' elite leads inevitably to the development of a certain political style based on emotion and affect, which stresses the virtues of the people defended by the heroic leader.

Is populism a concept?

Alain Dieckhoff: Back in 1969, in their seminal work , Populism, Its Meanings and National Characteristics Ernest Gellner and Ghiţa Ionescu called populism an "elusive and protean concept" because it came in so many forms. However, while acknowledging the variety of populist configurations, they nevertheless concluded that populism could be used as a concept. We take the same path. We don't share the view of some scholars who completely dismiss the word populism because of the diversity of contexts to which it is applied. It should be strongly stated that many social science concepts are applied to a wide range of concrete situations. There are many forms of capitalism, nationalism, or socialism but this heterogeneity does not lead us to reject these terms-and rightly so. Here we are speaking of an ideal type, i.e. a construct designed to help us understand reality. There are two main features of populism as a concept. Firstly, populism is based on a vision of the people as an absolute. Just as authoritarianism emerges due to an abuse of authority, populism occurs when one uses and abuses the word "people," pronounced as if the referent were sacred. That is the mark of its specific political style. Secondly, populism promotes a direct unmediated relationship between people and leadership. That is why populism is so critical of representative democracy; it is seen as a forgery of the popular will. The paradox of populism is that the promotion of the "true people" ends up by exalting the unique leader.

You consider populist leaders as Janus-like figures, in terms of policy. Can you develop this idea? Is this something that is mostly visible once they are in power?

Elise Massicard: Before being in office, populists claim that they represent the people against the establishment-and they claim to be part of the masses. However, once elected, they become part of the elite. How do they deal with this paradox? Do they completely drop populism once in power, or do they try to maintain it? This questioning is the reason we wanted to explore the possible transformations of populists once they gain power. The book shows that in general, when they gain office, populists tend to maintain their claim to represent the poor and the weak against the establishment, and try to maintain this populist appeal-precisely because its goal is to please the majority. However, more often than not, the economic policy (especially rightwing) that populists defend and implement once they are in power is conservative in socio-economic terms and pro-business-leading some scholars to stress the affinity of right-wing populists with neo-liberalism.

A more sophisticated approach shows that sometimes they maintain their appeal in other ways, reframing the categories of "the people" vs. "the elite". For example, national-populists tend to emphasize sociocultural issues and reframe the people they claim to represent in identity (religious or ethnic) terms; or national-populists might reframe the loathed elite as "cosmopolitan" or as incarnated by non-elected powerful circles (bureaucrats, judiciary elites, media elites)-while, in socio-economic terms, they tend to defend the social status quo or, more often than not, deliberately choose to remain vague on economic issues-in order to have a large cross-class appeal.

The various contributions of this edited volume focus on the populists in power, i.e. populist governments. Are there regions that stand out as particularly "unique" cases?

Elise Massicard: Most research on populism has focused on three areas, Europe, Latin America, and the United States. This is not a coincidence; populism has existed in these regions for a long time, even if its reemergence has been cyclical. However, the populist phenomenon-and populists in power-tend to spread on a global scale, in Northern countries but also in the global South. Therefore, in this collection we have tried to include these textbook cases but also cases from other parts of the world where populism has gained momentum-especially the Middle East and Asia-but where this phenomenon is much less researched. Taking an overall perspective on the populists in power in established democracies, in recent democracies, and in less liberal regimes, in both the global North and South allows us to question the categories with which we generally divide the world-they do not necessarily make sense here. However, the collection of chapters is not big enough to offer a comprehensive overview of populism in power all over in the world. Still, it offers a wide range of contrasting cases and case studies.

At the end of the day, I would not argue that there are strong regional specificities-other than the fact that left-wing populism is much more rooted in Latin America than elsewhere in the world. On the contrary, this wide range of cases provides the opportunity to draw some interesting and surprising parallels, for example between populists in Turkey and Thailand, or between India and Israel.

Can regimes be populist?

Christophe Jaffrelot: To some extent, yes. Today, a new type of regime is taking shape, in which populism plays a big part-but not an exclusive part. This new political regime results from a trajectory, a process whose matrix is populism. The starting point lies in the rise of a populist leader who exploits the fear and the anger of the people and mobilises voters against elite groups. Once elected, this leader-who is usually endowed with some charisma-enjoys such popular legitimacy that he is in a position to prevail over his party, the parliament, and even, eventually, the bureaucracy and the judiciary. Populism leads, therefore, to forms of authoritarianism. But in most of the cases when such developments occur, elections remain an important component in the political life of the country, precisely because every four or five years they give a new popular mandate to the leader. These may not be fully free and fair elections, but the leader could nevertheless be defeated, and by winning, he reasserts his authority through an election campaign with a populist style a populist style. Most of the time, the leader adopts a national-populist repertoire because he claims to represent the "sons of the soil" against foreigners. This new regime, therefore, relies on populism, nationalism, and authoritarianism. It can be sustainable and sometimes lasts for years or even decades, like in Turkey, in Israel under Netanyahu, and in India. Christophe Jaffrelot: Yes, precisely in the perspective that I have just outlined above. Until recently, populism was seen as ephemeral, related to social and economic crises, and even somewhat elusive. It seemed to be an opposition repertoire rather than a mode of government. If it becomes part and parcel of a particular kind of political regime, researchers need to adjust to this new situation and study the transition from opposition populism to populist (or electoral) authoritarianism. What are the mechanisms responsible for this structural transformation? Some of the hypotheses to explore pertain to the role of political communication, including social media, and to the connection between populist rulers and their capitalist cronies who fund the saturation of the public space by populist leaders. The political economy of populist authoritarianism needs to be investigated more.

But we also need to understand voters' behaviour. Why do people (including the poor) support populist leaders (who are often pro-rich) in spite of their often bad economic results? Because of their resentment against the old, cosmopolitan elite? Because of identity politics stigmatizing minorities? Or because they crave security and do not care much for liberty? Supply and demand on the political market need to be scrutinized in parallel of course-they are two sides of the same coin. And to make sense of this new polity, we need to use survey-based methods as well as ethnographic studies, and draw on an interdisciplinary approach combining political science, sociology, geography (the fact that rural areas feel abandoned matters a lot), psychology, and so forth. There is much to do! Interview by Miriam Périer, CERI.

The Sciences Po Series in International Relations and Political Economy on our website

  Anti EU sign during Matteo Salvini's speech in Piazza del Popolo, Rome, Italy, 8 December 2018. Photo by Giuseppe Barletta for Shutterstock Does this collective project open up new avenues for future research?


Solene-Florence Kammerer-Jacquet
email: soleneflorence.kammerer-jacquet@chu-rennes.fr

Camille Gandon

Frederic Dugay

Brigitte Laguerre

Benoit Peyronnet

Romain Mathieu

Gregory Verhoest

Karim Bensalah

Xavier Leroy

Sebastien Aubert

Florence Kammerer

Jacquet Solene

Solène-Florence Kammerer-Jacquet

Grégory Verhoest

Catherine Vermaut

Fabienne Escande

Virginie Verkarre

Eva Compérat

Damien Ambrosetti

Flor- Ence Pedeutour

Marc-Antoine Belaud-Rotureau

Nathalie Rioux-Leclercq

Solene-Florence Kammerer-Jacquet

Comprehensive study of nine novel cases of TFEB-amplified renal cell carcinoma: an aggressive tumour with frequent PDL1 expression

Keywords: renal cell carcinoma, TFEB gene, amplification, MITF -8p, -8q, -13, -14, -18, -Y Case 2 +6p, +8p, +8q, +9p -3p (VHL), -4q, -6p, -6q, -8p, -9p, -11p, -13q, -17p, -18q Case 3 +6q, +6p -1p, -2q, -3p (VHL), -6p, -6q, -9p, -12p, -16q, -18q, -19q Case 4 +1q, +2q, +8,+16, Case 5 +1q, +6q -1p, -2q, -3 (VHL), -6p, -19q, -22 Case 6 +6p, +7p, +8p, +8q, +17q -1p, -2q, -8p, -8q, -10q, -15q, -17p, -18, -21q, -22q Case 7 +4p, +4q, +6p

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INTRODUCTION

Historically, renal cell carcinoma (RCC) classification was mainly based on morphology [START_REF] Moch | The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours[END_REF]. Over the past few years, genetic aberrations have contributed to define new entities [START_REF] Udager | Morphologic, molecular, and taxonomic evolution of renal cell carcinoma: a conceptual perspective with emphasis on updates to the 2016 World Health Organization classification[END_REF]. Microphthalmia transcription factor family (MITF) translocation RCC is now considered as a separate entity among RCC in the current 2016 WHO Classification of Tumors of the Urinary System [START_REF] Moch | The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours[END_REF]. Four transcription factors are described as members of this family: MITF, TFEC, TFEB and TFE3. The rearrangement of TFE3 (Xp11) and TFEB (6p21) have been involved in the development of RCC [START_REF] Xie | Microphthalmia family of transcription factors associated renal cell carcinoma[END_REF]. TFE3 translocated RCC are found in about 20-40% of pediatric and 1-4% of adult RCC [START_REF] Kmetec | Xp 11.2 translocation renal carcinoma in young adults; recently classified distinct subtype[END_REF][START_REF] Sukov | TFE3 rearrangements in adult renal cell carcinoma: Clinical and pathologic features with outcome in a large series of consecutively treated patients[END_REF], whereas TFEB translocated carcinomas are very rare with approximatively one hundred cases reported in the literature [START_REF] Wyvekens | Histological and molecular characterization of TFEB-rearranged renal cell carcinomas[END_REF].

TFEB plays an important role in organelle biogenesis and metabolic processes. In particular, it participates to the regulation of lysosomal biogenesis, lysosomal acidification, lysosomal exocytosis, endocytosis, autophagy and membrane repair [START_REF] Sardiello | A gene network regulating lysosomal biogenesis and function[END_REF]. Recently, TFEB dysregulation was found to play a crucial pathogenic role in different tumors by modulating tumor cell autophagy [START_REF] Perera | Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism[END_REF]. Because autophagy is activated in hypoxic areas of tumors in order to maintain cancer cell growth [START_REF] Degenhardt | Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis[END_REF], it is not surprising that overexpression of TFEB potentiates its intrinsic pro-oncogenic activity [START_REF] Kauffman | Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers[END_REF].

In the vast majority of TFEB translocated RCC, the partner is MALAT1 (11q12) (which has a stronger promoter resulting in the overexpression of TFEB [START_REF] Davis | Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation[END_REF][START_REF] Kuiper | Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution[END_REF][START_REF] Caliò | MiT Family Translocation Renal Cell Carcinoma: from the Early Descriptions to the Current Knowledge[END_REF]. This entity was initially described in 2001 [START_REF] Argani | A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation[END_REF]. It is classically composed of nests of epithelioid cells with clear to eosinophilic cytoplasm, associated with a subpopulation of smaller cells surrounding hyaline basement membrane material [START_REF] Peckova | Aggressive and nonaggressive translocation t(6;11) renal cell carcinoma: comparative study of 6 cases and review of the literature[END_REF]. Despite an epithelioid morphology, these tumors under express epithelial markers and PAX8 relative to typical RCC [START_REF] Smith | t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases[END_REF]. However, they frequently express melanocytic markers such as Melan-A and HMB45 that are downstream targets of TFEB [START_REF] Argani | A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation[END_REF]. A frequent expression of PDL1 was recently described [START_REF] Caliò | TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1[END_REF].

Because TFEB is supposed to drive oncogenesis in this molecular subgroup, other mechanisms increasing its expression, such as amplification, could generate a similar phenotype. Several studies have reported cases of TFEB-amplified RCC that share in common with TFEB-translocated RCC the expression of TFEB and downstream targets HMB45 and Melan-A but with morphological discrepancies and a worse clinical prognosis for TFEB-amplified RCC [START_REF] Durinck | Spectrum of diverse genomic alterations define nonclear cell renal carcinoma subtypes[END_REF][START_REF] Lilleby | Translocational renal cell carcinoma (t(6;11)(p21;q12) with transcription factor EB (TFEB) amplification and an integrated precision approach: a case report[END_REF][START_REF] Linehan | Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma[END_REF][START_REF] Argani | TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity[END_REF][START_REF] Qu | TFEB amplification renal cell carcinoma detected by chromosome genomic array testing: A case report for diagnosis of a novel entity[END_REF][START_REF] Williamson | Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?[END_REF][START_REF] Gupta | TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management[END_REF][START_REF] Mendel | Comprehensive study of three novel cases of TFEB-amplified renal cell carcinoma and review of the literature: Evidence for a specific entity with poor outcome[END_REF][START_REF] Guisado | Carcinoma de células renales asociado a amplificación del gen TFEB. Presentación de un caso y revisión de la literatura [TFEB-amplified renal cell carcinoma. A case report and review of the literature[END_REF][START_REF] Martin | Renal cell carcinoma With TFEB translocation versus unclassified renal cell carcinoma with TFEB amplification[END_REF][START_REF] Skala | Detection of 6 TFEB-amplified renal cell carcinomas and 25 renal cell carcinomas with MITF translocations: systematic morphologic analysis of 85 cases evaluated by clinical TFE3 and TFEB FISH assays[END_REF][START_REF] Caliò | VEGFA amplification/increased gene copy number and VEGFA mRNA expression in renal cell carcinoma with TFEB gene alterations[END_REF][START_REF] Kojima | Aggressive TFEB-rearranged renal cell carcinoma mimicking chromophobe and clear cell renal cell carcinoma[END_REF][START_REF] Wyvekens | Histological and molecular characterization of TFEB-rearranged renal cell carcinomas[END_REF][START_REF] Gupta | TFEB Expression Profiling in Renal Cell Carcinomas: Clinicopathologic Correlations[END_REF][START_REF] Vormittag-Nocito | A unique case of TFEB amplified renal cell carcinoma[END_REF].

Here, we report 9 novel cases, with clinical, morphological, immunohistochemical (PDL1 status for the first time) and genomic features. We also performed an exhaustive review of the literature and confronted our data with the previously reported cases.

METHODS

Patients

Pathological analysis

Fresh surgical specimens were received at the departments of Pathology and tumors were described at gross examination. Samples were formalin fixed and paraffin embedded with hematoxylin and eosin-safran staining (HES). The HES slides were addressed for second opinion and then centrally reviewed by two uropathologists (NRL and SFJK).

Immunohistochemistry

Four-μm thick whole tissue sections were cut and mounted on glass slides (Superfrost+, Menzel Gläser, Thermo Fisher Scientific, Waltham, Massachusetts, USA). The preparations were dried for 1 hour at 58°C, and then overnight at 37°C. The sections were deparaffinized with toluene and rehydrated with ethanol.

The preparations were pretreated and immunostained using Ventana Benchmark XT, Ventana Medical Systems, Oro Valley, Arizona, USA. Immunohistochemical analyses were carried out using the following antibodies: anti-PAX8 (clone MRQ50, Ventana Medical Systems), anti-CD117 CKit (monoclonal, Ventana Medical Systems), anti-Melan-A (clone A103, Ventana Medical Systems), anti-HMB45 (monoclonal, Dako, Agilent, Santa Clara, California, USA), anti-CD10 (monoclonal, Leica, Wetzlar, Germany), anti-CKAE1-AE3 (clone PCK26, Ventana Medical Systems), anti-CAIX (Abcam, Cambrige, UK), anti-CK7 (monoclonal, Dako, Agilent), anti-AMACR (monoclonal, Dako, Agilent), anti-TFE3 (Cell Marque Corporation, Rocklin, California, USA), anti-PDL1 (28-8 clone, Dako, Agilent Technologies), anti-PD1 (Dako, Agilent Technologies) and CD8 (clone C8/144B, Dako, Agilent Technologies). The clone 28-8 was choosen because it is the companion testing of Novolumab with a good reproductibility with 22C3 the companion of Pembrolizumab also widely used in RCC [START_REF] Kammerer-Jacquet | Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma[END_REF][START_REF] Krigsfeld | Analysis of real-world PD-L1 IHC 28-8 and 22C3 pharmDx assay utilisation, turnaround times and analytical concordance across multiple tumour types[END_REF]. The detection was performed using horseradish peroxidase-labeled polymer conjugated secondary antibodies using diaminobenzidine as chromogen (Sigma-Aldrich, Saint Louis, Missouri, USA). The PD1 and CD8 expressions were semi-quantitatively assessed with either absent (0), low (1), moderate (2) or high (3) infiltrate as previously described [START_REF] Wyvekens | Histological and molecular characterization of TFEB-rearranged renal cell carcinomas[END_REF]. The tumor expressions of each antibody were independently evaluated by 2 uropathologists (NRL and SFJK). Negative controls were performed by omitting the primary antibody.

Fluorescence in situ hybridization (FISH)

FISH analysis was performed as previously described [START_REF] Kammerer-Jacquet | Independent association of PD-L1 expression with noninactivated VHL clear cell renal cell carcinoma-A finding with therapeutic potential[END_REF]. Briefly, the 5-µm thick, paraffin-embedded sections fixed on slides were deparaffinized and pre-treated using pre-treatment solution (Dako). Pepsin solution was added on preparations for 6 minutes (Sigma, 100 mg/l) and then dehydrated in ethanol 70°, 85°, and 100° (2 minutes each). Specimens and probes were codenatured (10 minutes at 75°C +/-2°C) and hybridized overnight at 37°C. The TFEB gene status was assessed using the TFEB Break apart Probe 6p21.1 (Empire Genomics, Buffalo, United States). After hybridization, slides were washed according to the manufacturers' instructions, and the nuclei were counterstained by DAPI (Dako). Cells were viewed using a fluorescent Axioplan II microscope (Zeiss, Le Pecq, France) or the automatized microscope Bioview Encore (Bioview, Rehovot, Israel) with appropriate filters and 100 non-overlapped nuclei were analysed for each tumor by 2 independents observers (FD and MABR). According to the definition set by Gupta and al [START_REF] Gupta | TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management[END_REF], a low-level amplification was defined by 5-10 copies and a high-level amplification by more than 10 copies.

Comparative Genomic Hybridization array study (CGH)

Copy number alterations were analyzed by array-CGH using the standard version of Agilent Human Genome CGH microarray 180K (Agilent Technologies, Santa Clara, CA, USA) according to the manufacturer's instructions. Microarrays were scanned using the Agilent G2565BA Microarray Scanner System. The images were extracted using Agilent Feature Extraction software, and data were analyzed with Agilent Cytogenomics v.2.5.8.11 software to identify chromosome imbalances.

Review of the literature

We exhaustively gathered all the published cases of TFEB-amplified RCC and noted their clinical, pathological and molecular details. We used Mann-Whitney test and χ² or Fisher's exact test to compare if there were significant differences within subgroups (between TFEB-amplified RCC with low or high-level amplification, and between TFEB-amplified RCC with or without concomitant translocation).

RESULTS

Clinical features

The clinical features of the 9 patients of our cohort are detailed in Table 1. They were adults with a male predominance (n=7, 78%), with an age range from 31 years to 86 years (mean: 60 years). The tumors presented at variable stages, from pT1a to pT3b with a majority of pT3 (n=6, 67%), with a size ranging from 3 cm to 20 cm. A majority of patients presented with metastasis, located in distant lymph nodes, liver, lungs, adrenal gland and bone at the diagnosis or during the follow-up. The delivered therapies were sunitinib, cabozantinib, mTOR inhibitor or nivolumab. The 2 patients treated by sunitinib showed progression, while no recurrence was observed after the introduction of nivolumab (after 2 and 5 months of treatment). The non-metastatic patients were free of recurrence at 18 months and 24 months.

Morphologic features

The morphologic features are illustrated in Figure 1 and detailed in Table 2. The type of architecture was variable with papillary, trabecular, alveolar and solid patterns. The cytoplasm were either eosinophilic or clear. High-grade features such as prominent nucleoli and necrosis were frequently observed, but no sarcomatoid component. No case showed the biphasic appearance of the TFEB-translocated RCC. The diagnosis originally mentioned were papillary RCC, oncocytoma and clear cell RCC, Table 2.

Immunohistochemistry

The immunohistochemical results are illustrated in Figure 2 and presented in Table 3. All cases demonstrated immunoreactivity for AMACR and for PAX8. Whereas all cases expressed Melan A, only 5 of them (56%) expressed HMB45 with only focal expression. Misleading to a differential diagnosis, 4 cases (44%) focally expressed CK7, 6 cases (67%) expressed membranous CA-IX and 4 cases (44%) expressed CD117.

No cases demonstrated expression of TFE3. We observed a membranous staining for PDL1 in tumor cells in 6 out of 7 samples tested (86%) with a mean percentage of 32% (5-80%). The immune infiltrate assessed with CD8 was variable but a positivity for PD1 was observed in all cases.

FISH

FISH results are illustrated in Figure 3 and detailed in Table 4, along with CGH results. All cases included in the study showed amplification of TFEB with a high level in 6 cases. One of the cases demonstrated both TFEB amplification and rearrangement. As expected, no rearrangement of TFE3 was identified.

CGH

The gains and losses are gathered in Table 5. A profile is presented in Figure 3. Most frequents gains were identified on chromosomes 6 (78%), 8 (56%), 1 and 17 (33%) and the most frequent losses impacted chromosomes 1, 2, 6 (78%), 18 (67%), 5 including VHL (56%), 13, 19, 22 (44%), 8, 9, 17 (33%). Moreover, VEGFA was found co-amplified with TFEB in all cases but always with a lower level than TFEB.

Review of the literature

To the best of our knowledge, 73 cases of TFEB-amplified RCC have been previously reported [START_REF] Peckova | Aggressive and nonaggressive translocation t(6;11) renal cell carcinoma: comparative study of 6 cases and review of the literature[END_REF][START_REF] Smith | t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases[END_REF][START_REF] Caliò | TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1[END_REF][START_REF] Durinck | Spectrum of diverse genomic alterations define nonclear cell renal carcinoma subtypes[END_REF][START_REF] Lilleby | Translocational renal cell carcinoma (t(6;11)(p21;q12) with transcription factor EB (TFEB) amplification and an integrated precision approach: a case report[END_REF][START_REF] Linehan | Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma[END_REF][START_REF] Argani | TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity[END_REF][START_REF] Qu | TFEB amplification renal cell carcinoma detected by chromosome genomic array testing: A case report for diagnosis of a novel entity[END_REF][START_REF] Williamson | Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?[END_REF][START_REF] Gupta | TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management[END_REF][START_REF] Mendel | Comprehensive study of three novel cases of TFEB-amplified renal cell carcinoma and review of the literature: Evidence for a specific entity with poor outcome[END_REF][START_REF] Guisado | Carcinoma de células renales asociado a amplificación del gen TFEB. Presentación de un caso y revisión de la literatura [TFEB-amplified renal cell carcinoma. A case report and review of the literature[END_REF][START_REF] Martin | Renal cell carcinoma With TFEB translocation versus unclassified renal cell carcinoma with TFEB amplification[END_REF][START_REF] Skala | Detection of 6 TFEB-amplified renal cell carcinomas and 25 renal cell carcinomas with MITF translocations: systematic morphologic analysis of 85 cases evaluated by clinical TFE3 and TFEB FISH assays[END_REF][START_REF] Caliò | VEGFA amplification/increased gene copy number and VEGFA mRNA expression in renal cell carcinoma with TFEB gene alterations[END_REF][START_REF] Kojima | Aggressive TFEB-rearranged renal cell carcinoma mimicking chromophobe and clear cell renal cell carcinoma[END_REF][START_REF] Wyvekens | Histological and molecular characterization of TFEB-rearranged renal cell carcinomas[END_REF][START_REF] Gupta | TFEB Expression Profiling in Renal Cell Carcinomas: Clinicopathologic Correlations[END_REF][START_REF] Vormittag-Nocito | A unique case of TFEB amplified renal cell carcinoma[END_REF].

Including our cases, the mean age was 63 years with a male predominance. The size of the tumors ranged from 1.8 cm to 19.5 cm (mean 9 cm). Most patients presented aggressive tumors with advanced stage and frequent metastases, Supplementary data Table 1. Most TFEB-amplified RCC share high grade features, with prominent nucleoli and necrosis. They exhibited variable morphology with a tubulopapillary, pseudopapillary or nested architecture and large eosinophilic cells, Supplementary data Table 2. They frequently expressed melanocytic markers, with a frequent expression of Melan-A and a more variable expression of HMB45, Supplementary data Table 3. A majority of the reported cases showed high-level amplification, Supplementary data Table 4. Concerning the genomic profile of TFEB-amplified RCC, data were rather limited, Supplementary data Table 5. The more frequent gains remained on chromosome 6 and losses on chromosomes 1, 2, 3 and 6. No significant differences between TFEB-amplified RCC with low or highlevel of amplification were identified with the exception of Melan-A positivity less expressed in TFEB low-amplified RCC (p<0.01), Supplementary data Table 6. Moreover, we found 11 cases with concomitant TFEB-amplification and translocation. None of them demonstrated the biphasic morphology usually seen in TFEB-translocated RCC. The RCC with both TFEB translocation and amplification did not present significant clinical or pathological differences Supplementary data Table 7.

DISCUSSION

We reported 9 novel cases of TFEB-amplified RCC with detailed immunohistochemical including for the first time PDL1 status and chromosomic profiles. We compared them to the previously published cases.

Our study confirms the emerging data suggesting that TFEB-amplified RCC occurs in older patients than TFEB-translocated RCC and demonstrates variable morphology (although frequently papillary) with high grade features. None of the cases showed the biphasic morphology classically seen in TFEB-translocated RCC [START_REF] Peckova | Aggressive and nonaggressive translocation t(6;11) renal cell carcinoma: comparative study of 6 cases and review of the literature[END_REF]. The expression of melanocytic markers is essential to the diagnosis, with a frequent expression of Melan-A and a more variable expression of HMB45. Those markers are downstream targets of TFEB, and are therefore correlated with its degree of expression. Indeed, they are more consistently expressed in TFEB-translocated RCC, which has a higher TFEB expression [START_REF] Gupta | TFEB Expression Profiling in Renal Cell Carcinomas: Clinicopathologic Correlations[END_REF]. This explained that Melan-A was significant less expressed in low-level amplification than in high-level TFEB-amplification. The diagnosis of this new molecular subgroup relies on FISH, demonstrating an amplification of TFEB. Rarely, a concomitant translocation of TFEB can be found but this does not seem to confer any clinical, or immunohistochemical particularities, within the limit of a low number of cases. The clinical course is usually aggressive, contrary to TFEB-translocated RCC, which is frequently indolent. When the 2 events are present, the tumor is therefore classified as TFEB-amplified RCC. The chromosomic profile show many alterations, which correlates with a poor prognosis. No specific genomic pattern was identified contrary to other entities [START_REF] Udager | Morphologic, molecular, and taxonomic evolution of renal cell carcinoma: a conceptual perspective with emphasis on updates to the 2016 World Health Organization classification[END_REF][START_REF] Gowrishankar | A genomic algorithm for the molecular classification of common renal cortical neoplasms: development and validation[END_REF], which highlights the driving role played by TFEB in the oncogenesis.

The differential diagnosis of a TFEB-amplified RCC mainly include clear cell RCC, papillary RCC, oncocytoma/chromophobe RCC and TFE3/TFEB-translocated RCC. First, the solid or trabecular architecture associated with clear and eosinophilic cytoplasm and prominent nucleoli raises the differential diagnosis of clear cell RCC, which frequently shows cells with eosinophilic cytoplasm in high grade tumors [START_REF] Leibovich | Carbonic anhydrase IX is not an independent predictor of outcome for patients with clear cell renal cell carcinoma[END_REF]. The positivity of carbonic anhydrase 9 (CA-IX) could be misleading and needs to be interpreted with caution especially next to necrosis. Also, the deletion of VHL is not uncommon but no VHL mutations were identified. Secondly, the papillary architecture as well as the positivity for AMACR could argue for the differential diagnosis of papillary RCC so as the gains in chromosomes 7 and 17 that can be identified by FISH. Furthermore, the eosinophilic tumor cells could raise the diagnosis of oncocytoma or chromophobe RCC.

However, the prominent nucleoli in TFEB-amplified RCC are not in favor of these diagnoses. The differential diagnosis with TFE3 and TFEB-translocated RCC is difficult as they demonstrate variable morphology, even though the biphasic pattern is more specific of the last entity. The key to the diagnosis of TFEBamplified RCC is the expression of melanocytic markers that we suggest to perform in every unclassified RCC. FISH analysis is required to confirm TFEB amplification.

Genomic amplification is a very rare event in RCC, even less frequent than translocation [START_REF] Myllykangas | Specificity, selection and significance of gene amplifications in cancer[END_REF]. Recent studies have been focusing on TFEB, which is implicated in mTORC1 pathway, a key to the oncogenesis of many cancers. TFEB is an important regulator of lysosomal biogenesis and autophagy, and its activity is inhibited by mTORC1 to promote anabolic pathways [START_REF] Sardiello | A gene network regulating lysosomal biogenesis and function[END_REF][START_REF] Settembre | TFEB links autophagy to lysosomal biogenesis[END_REF][START_REF] Martina | The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris[END_REF][START_REF] Steingrimsson | Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development[END_REF][START_REF] Settembre | A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB: Self-regulation of the lysosome via mTOR and TFEB[END_REF][START_REF] Roczniak-Ferguson | The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis[END_REF]. The overexpression of TFEB influences mTORC1 as well by increasing its activation [START_REF] Malta | TFEB-mTORC1 feedback loop in metabolism and cancer[END_REF]. In addition, TFEB amplification is often combined with amplification of VEGFA [START_REF] Gupta | TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management[END_REF], but with a lower number of copies than for TFEB [START_REF] Caliò | VEGFA amplification/increased gene copy number and VEGFA mRNA expression in renal cell carcinoma with TFEB gene alterations[END_REF], suggesting that TFEB rather than VEGFA drives the oncogenesis. However, amplifications of VEGFA have been associated with a poor prognosis [START_REF] Gupta | TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management[END_REF][START_REF] Yang | Genetic amplification of the vascular endothelial growth factor (VEGF) pathway genes, including VEGFA, in human osteosarcoma[END_REF]. Indeed, VEGFA has a well know angiogenic effect on endothelial cells, leading to increased tumor growth despite hypoxia. Moreover, emerging data show that VEGFA may also have an autocrine effect on tumors cells with the subsequent activation of the AKT/mTOR signalling pathway [START_REF] Trinh | The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer[END_REF].

The amplification of both TFEB and VEGFA could have a synergic effect through mTOR signaling pathway. Consequently, mTOR inhibitors and antiangiogenics could be proposed. Indeed, many patients received a treatment with mTOR inhibitors, but generally with a poor response [START_REF] Lilleby | Translocational renal cell carcinoma (t(6;11)(p21;q12) with transcription factor EB (TFEB) amplification and an integrated precision approach: a case report[END_REF][START_REF] Qu | TFEB amplification renal cell carcinoma detected by chromosome genomic array testing: A case report for diagnosis of a novel entity[END_REF][START_REF] Gupta | TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management[END_REF][START_REF] Mendel | Comprehensive study of three novel cases of TFEB-amplified renal cell carcinoma and review of the literature: Evidence for a specific entity with poor outcome[END_REF]. On this point, a study showed that TFEB induced PDL1 expression, and this could mediate resistance to mTOR inhibit io n [START_REF] Zhang | TFEB Mediates Immune Evasion and Resistance to mTOR Inhibition of Renal Cell Carcinoma via Induction of PD-L1[END_REF]. In this study, we assessed PDL1 status along with quantification of the immune infiltrate and demonstrate that a vast majority of cases showed positivity. This suggests the use of immunotherapies alone or in combination with mTOR inhibitors or antiangiogenics. A few patients received nivolumab, with promising results, although long-term data were very limited. Collective efforts are needed to reach optimal treatment in this very rare molecular subgroup.

In conclusion, we strongly recommend the use of melanocytic markers in unclassified RCC to detect TFEBamplified RCC that need to be confirmed by FISH analysis. The diagnosis of this molecular subgroup is important because the tumors are particularly aggressive. Additional studies are needed to define the best treatment strategy.

  ' selection Patients originated from Rennes University Hospital or others French medical centers. Most of them were addressed for second opinion. They were all included in the French CARARE network (Rare Renal Cancer in Adults) of the INCa (National Institute of Cancer, France), which focuses on rare subtypes of RCC or RCC occurring in young people (≤ 40 years). All procedures were performed in accordance with the ethical standards of the Helsinki Declaration. The study was approved by the Ethical Committee (CNIL DR-2013-206).

FIGURES LEGENDSFigure 1 :

 1 FIGURES LEGENDS

Figure 2 :

 2 Figure 2: Immunohistochemistry. A, focal positivity of Melan-A (case 9); B, rare positivity of HMB45 (case 8); C, nuclear expression of PAX8 (case 3); D, diffuse positivity of AMACR (case 6); E, expression of CAIX at the edge of necrosis area (case 7), F, diffuse expression of PDL1 (case 2).

Figure 3 :

 3 Figure 3: A, Array-CGH showing complex quantitative whole genome profile : losses of chromosome segments 1p, 2q, 3p, 4p, 4q, 6p, 17p, 18q, 19p and whole chromosomes 21 and 22 and gains of chromosome segments 4p, 4q, 6p and 17q, including amplification of TFEB gene at 6p21.1; B, zoom on chromosome 6 and TFEB amplification; C, interphase FISH analysis using a TFEB break-apart probe, showing amplification of TFEB (more than 5 copies of non-rearranged TFEB/cell ).

Acknowledgements

The authors would like to thank the members of CARARE French network and the French Institute of Cancer (INCa) for their financial support. The contribution of each author was redaction of the paper (SFKJ, CG), interpretation of the data (FD, NRL, MABR, SA, CV, FP, DA, XL, FE, VV, EC) and the collection of data (BL, BP, RM, KB). All authors edited the manuscript. The authors would also like to thank Pascale Bellaud and Roselyne Viel from the Histopathology platform H2P2-BIOSIT at the Faculty of Medicine in Rennes for their technical support.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

TABLES Table 1 Clinical features of TFEB-amplified renal cell carcinoma


1

Objectif

Les scarifications, en tant que coupures cutanées superficielles et répétées, souvent effectuées en secret à l'adolescence, sont fréquemment présentées comme une manière de pallier un déficit de l'enveloppe psychique par une enveloppe de souffrance. Face à ces pratiques, le rôle du clinicien consisterait à favoriser la restauration d'une fonction contenante chez le patient qui pourrait alors abandonner ces conduites transgressives. Cette description, souvent juste et validée par la clinique, est cependant insuffisante pour comprendre la dimension relationnelle des scarifications et le choix spécifique de cette pratique particulièrement dérangeante.

Méthode

A partir de l'exposition d'un cas clinique et de son évolution après un ratage interprétatif, cet article développe plusieurs pistes théoriques et questionne la représentation hégémonique des scarifications comme ersatz d'une enveloppe psychique défaillante.

Discussion

En considérant les scarifications comme la conséquence d'une défaillance de la capacité de contenance des éprouvés corporels à l'adolescence, le thérapeute peut, au fil des séances, et par l'intermédiaire de l'enveloppe sonore formé par ses mots, proposer à l'adolescent un étayage sensoriel favorisant la consolidation d'une fonction contenante.

Néanmoins, à trop se représenter le patient sur un mode déficitaire, le thérapeute risque de négliger l'interpellation que recèlent ces conduites de scarifications. En effet, les pratiques d'entailles cutanées résultent aussi souvent d'une résistance de l'environnement à accueillir les mouvements pulsionnels, érotiques et agressifs, de l'adolescent, les coupures permettant alors de « forcer le passage ». Pour éviter de reproduire cette rigidité de l'environnement, le thérapeute doit alors être particulièrement attentif à ce que les conduites de scarification tentent de modifier chez lui et de ne pas les réduire à des comportements qui ne concerneraient que le patient.

Conclusion

En sus de former une enveloppe de souffrance contenante, les scarifications à l'adolescence, en tant que pratiques transgressives particulièrement dérangeantes, peuvent être comprises comme des tentatives, souvent efficaces, de forcer le changement de regard et de position d'un environnement qui résiste à accueillir les mouvements pulsionnels pubertaires.

Mots clés : automutilation, scarification, Moi-peau, contenance, enveloppe, langage, adolescence Objective Scarifications, as superficial and repeated skin cuts, often carried out in secrecy during adolescence, are frequently described as a way to compensate for a deficit in the psychic envelope by an envelope of suffering. Confronted with these practices, the clinician's role would be to promote the restoration of a containing function in the patient who could then abandon these transgressive behaviors. This description, often accurate and validated by the clinic, is however insufficient to understand the relational dimension of scarification and the specific choice of this particularly disturbing practice to form an envelope of suffering.

Method

Based on the exposure of a clinical case together with its evolution following an interpretative failure, this article develops several theoretical approaches and questions the hegemonic representation of scarification as a substitute for a deficient psychic envelope.

Discussion

If the scarifications result from a deficiency of the containing function due to the overwhelmed body sensations triggered during puberty, then the therapist can provide a sensory envelope to the adolescent through the sound envelope formed by his words.

However, if the therapist considers the patient only from a deficiency point of view, he may overlook the interpellation that these scarification behaviours conceal. Indeed, the practices of skin cuts also often result from a resistance of the environment to accommodate the adolescent's impulsive, erotic and aggressive movements. In this context, skin cuts may be an attempt to "force the passage". To avoid reproducing this rigidity of the environment, the therapist must therefore be particularly attentive about what the scarifications try to modify in him and not limiting them to behaviours that would only concern the patient.

Conclusion

In addition to forming an envelope of suffering, scarifications in adolescence, as particularly disturbing transgressive practices, can be understood as attempts, often effective, to force a change of gaze, especially when the adolescent feels confined to the role of a child whose physical experiences are disavowed. Durant les séances, elle ne supporte pas les silences et verbalise de façon répétitive une envie de dormir. J'éprouve plusieurs fois la sensation d'un temps qui s'étire indéfiniment et je m'attends presque à la voir tomber de sa chaise, son corps se liquéfiant sur le sol et y disparaissant.

Keywords

Fonction contenante et limites du corps

Fonction contenante et éprouvés corporels

A un stade préverbal, la voix, le regard et le toucher de l'être prenant soin (qu'il soit appelé Nebenmensch [START_REF] Freud | Projet d'une psychologie[END_REF] ou good enough mother [START_REF] Winnicott | La mère suffisamment bonne[END_REF]) permettent de prodiguer à l'infant cette sensation de contenance, notamment en lui fournissant un environnement suffisamment sécurisant dans lequel ses affects peuvent être reçus puis restituer d'une façon qui ne soit pas menaçante. Bion [START_REF] Bion | Aux sources de l'expérience[END_REF] décrit ainsi la fonction alpha de l'être prenant soin qui accueille des sensations et éprouvés corporels inassimilables psychiquement pour le bébé (appelés éléments béta). L'être prenant soin détoxique et transforme ensuite ces éprouvés insupportables et les retransmet au bébé sous forme d'éléments alpha, assimilables psychiquement. Le bébé peut alors reconnaître ces éprouvés corporels comme faisant partie de lui et en assurer la contenance au sein de son corps et de son psychisme. Cette détoxification se produit via la capacité de rêverie de l'être prenant soin et se communique au bébé au travers d'un tissu de soins sensoriels. Si ce tissu est suffisamment dense et adapté aux sollicitations du bébé, ce dernier pourra alors dans un second temps introjecter cette fonction alpha. Anzieu reprendra les travaux de Bion [START_REF] Bion | Aux sources de l'expérience[END_REF], d'Esther Bick [START_REF] Bick | The Experience of the Skin in Early Object-Relations[END_REF], de Freud [START_REF] Freud | Projet d'une psychologie[END_REF][START_REF] Freud | Essais de psychanalyse[END_REF], de Winnicott [START_REF] Winnicott | Intégration du moi au cours du développement de l'enfant[END_REF][START_REF] Winnicott | La capacité d'être seul[END_REF], et d 'Abraham et Torok [START_REF] Abraham | L'écorce et le noyau[END_REF] pour proposer le concept de Moi-peau [START_REF] Anzieu | Le moi-peau[END_REF]. Il décrit neuf fonctions du Moi-peau mais nous nous concentrerons ici sur la fonction contenante. Cette fonction du Moi-peau prend alors la forme d'une enveloppe psychique, écorce capable de contenir les pulsions internes, apparentées à un noyau. La défaillance de cette fonction contenante peut alors se manifester par la formation d'un « Moi-peau passoire » caractérisé par une porosité entre limite interne et externe et l'angoisse « d'avoir un intérieur qui se vide ».

Lorsque ce sentiment de contenance vacille, il est alors possible de faire appel de nouveau à des sollicitations sensorielles pour le renforcer. Ainsi, l'augmentation drastique des pratiques sensorielles à l'adolescence vise en partie à renforcer une capacité de contenance mise à mal d'une part par des modifications constantes des limites du corps et d'autre part par une poussée pulsionnelle impossible à contrôler [START_REF] Gutton | [END_REF]. On comprend alors mieux le temps passé par certains adolescents devant le miroir (contenance visuelle), l'importance d'un fond sonore constant et souvent l'envie de chanter soi-même à tue-tête (contenance sonore) et enfin le désir régulier de toucher son propre corps, que ce soit pour des motifs sexuels ou esthétiques (contenance cutanée).

A défaut de mots, une enveloppe sonore, tactile et visuelle

Lorsque ces modes de contenance ne sont pas suffisants, soit parce que les changements psychiques et corporels liés à la puberté sont trop brutaux, soit parce que la capacité de contenance n'a pas pu être suffisamment introjectée durant l'enfance, il est nécessaire pour l'entourage de renforcer dans un premier temps cette capacité de contenance.

L'interdit du toucher étant en vigueur dans les psychothérapies d'inspiration analytique, c'est, en dehors des poignées de main rituelles qui scandent les débuts et fin de séance, principalement au travers du regard et de la voix que le thérapeute peut remplir cette fonction de contenance.

Je perçois ainsi un faible intérêt pour le langage durant les séances avec Lucie où le sens des mots se perd mais où elle insiste néanmoins pour que je continue de lui parler. Selon Anzieu, « l'espace sonore est le premier espace psychique » [START_REF] Anzieu | Le moi-peau[END_REF], l' « enveloppe sonore » préfigurant la construction du Moi-Peau. L'existence de cette enveloppe sonore, formée à la fois par les sons du bébé et de son environnement est un pré-requis pour envisager dans un second temps un espace commun de communication. Anzieu explique que la plus efficace des réponses au cri de détresse du bébé est d'abord la voix maternelle, qui rassure et contient avant même la présence de l'être prenant soin ou l'action spécifique atténuant la souffrance à l'origine de ce cri.

Comme elle parle peu et me reproche mes silences, qui semblent générer chez elle une angoisse insupportable, je me retrouve à lui poser des questions, à lui proposer des hypothèses et à lui décrire ce que je ressens moi-même. Si mes mots n'ont que peu d'importance (elle oubliera d'ailleurs mes paroles d'une séance à l'autre), le ton de ma voix et mon regard sur elle la contiennent et la rassurent. Durant une séance, alors que je parle depuis plusieurs minutes (je serai incapable de me souvenir de mes paroles à la fin de la séance), elle finit ainsi par enlever son manteau, décroiser les bras, elle se redresse et son regard croise le mien. Il me semble que la sonorité de ma voix et mon regard font office de contenant et de limite face au sentiment d'un corps qui ne tient pas, se délite et s'affaisse.

Les scarifications de Lucie ne sont pas un support de discussion, une pratique autour de laquelle des mots et un sens pourraient se tisser. Son insistance sur l'importance de la douleur et de la vue du sang coulant sur ses bras me met sur la voie de la formation d'une « enveloppe de souffrance » [START_REF] Anzieu | Le moi-peau[END_REF] utilisée pour pallier le défaut de contenance et révélatrice de sa difficulté à s'appuyer sur d'autres sensorialités que la douleur. Lucie n'aime en effet ni sa voix, ni son image dans le miroir et se considère incapable de « bien s'habiller » ou de se maquiller. Les sensations provoquées par la douleur de la coupure et l'investissement du regard sur son corps mutilé lui permettent de s'assurer d'un sentiment d'existence à minima et d'une enveloppe contenante qui la distingue du monde extérieur, la maintient éveillée et évite à son corps de disparaître. Nous pouvons ici rappeler que la peau établit une ligne de démarcation entre l'extérieur et soi-même, tandis que l'action musculaire est le test indiquant de quel côté de la ligne on se trouve (comme le rappelle Fanny Dargent en s'appuyant sur Freud [START_REF] Dargent | Blessures de l'adolescence[END_REF]). Les scarifications peuvent alors être une tentative de retracer une frontière vacillante et, en ayant une position active, de lutter contre une expérience de passivation extrême provoquée par les modifications corporelles pubertaires, ce qui explique en partie la forte prévalence, estimée à 17% [START_REF] Swannell | Prevalence of nonsuicidal self-injury in nonclinical samples: Systematic review, meta-analysis and metaregression[END_REF], de ces pratiques à l'adolescence.

En début de thérapie, j'analyse ainsi les scarifications de Lucie comme des pratiques sensorielles qui n'ont d'autre visée que de lui procurer une fonction contenante à minima, contenance rehaussée par un regard et une voix extérieure que ses pratiques lui permettent de convoquer. Je considère que ces pratiques ne me sont pas adressées, qu'elles ne sont pas une tentative de représentation de motions pulsionnelles refoulées et en conséquence, je ne leur cherche pas un sens caché. Le début de la thérapie est ainsi marqué par des séances laborieuses où mes paroles semblent diminuer l'angoisse et permettre à Lucie de progressivement prendre le risque d'entrer en relation, de croiser mon regard et parfois, de me répondre. Le soir même, elle avale l'ensemble des médicaments de la pharmacie et s'évanouit ensuite devant la chambre de ses parents. Ces derniers l'emmènent à l'hôpital où elle sombrera dans le coma quelques minutes avant d'être réanimée. Cette fois bien inquiété, je lui rends visite quelques jours plus tard à l'hôpital, où un bureau m'est prêté pour faire une séance de psychothérapie. Elle a l'air contente de me voir, semble pour sa part très peu inquiète, me raconte avec beaucoup de détail cette deuxième tentative de suicide et m'explique ensuite qu'elle a un copain depuis un mois mais qu'elle n'avait pas « osé en parler avant ».

Brouiller les représentations, forcer le regard

Une entrée dans la puberté invisibilisée

Je suis surpris par cette tentative de suicide plus sérieuse mais plus encore par mon incapacité à anticiper cette dernière, malgré tous les signes avant-coureur. Je prends conscience que depuis le début de la thérapie, je me représente Lucie comme une petite fille A la fin de cette séance, je me dis que la fonction de contenance que j'assurais en début de thérapie était probablement plus ambivalente que je ne le pensais. En effet, si je m'efforçais de combler les silences qu'elle jugeait insupportables, c'était peut-être aussi dans l'objectif d'étouffer certains mouvements pulsionnels qui nous semblaient, à elle comme à moi, trop dangereux. Autrement dit, plutôt que de laisser se déployer, de manière contenue et encadrée, certaines manifestations et représentations de pulsions agressives et érotiques, j'ai plutôt choisi de leur barrer l'accès, me laissant happer par les propres angoisses de Lucie et celles de ses parents, le père de Lucie déclarant notamment en entretien familial qu'il avait « très peur de ce que Lucie pourrait faire ». Ce n'est qu'après sa tentative de suicide que je mesure alors la nécessité non seulement de continuer à contenir ces mouvements pulsionnels mais surtout de leur laisser une porte d'entrée. Mon rôle de thérapeute consiste alors à rassurer Lucie sur ma propre capacité à contenir ses mouvements pulsionnels, lui indiquant ainsi que ces derniers sont supportables, et qu'elle pourra elle-même, dans un second temps, leur laisser une place dans sa propre dynamique pulsionnelle.

Cet épisode m'évoque un article de Jacques Laget qui a travaillé deux ans avec Benoit, un adolescent se scarifiant, qui réalise au cours de sa thérapie une peinture au/avec son sang.

L'évocation de celle-ci en séance permet de faire émerger des problématiques liées au regard de l'autre et aux rapports que Benoit, entretien avec sa jumelle et ses parents. Jacques Laget écrit alors à propos de la créativité adolescente et de ses formes morbides qu'« au-delà des fantasmes d'omnipotence voire d'auto-engendrement qu'elle sous-tend, cette créativité reste aussi potentiellement vivante pour peu qu'elle achoppe à un point de rencontre -un point de mise au point au sens photographique, peut-être ! » [START_REF] Laget | Coupure, peinture au sang, regard du thérapeute[END_REF], la question de l'autre et de son regard étant ici centrale. Dans ce cas, la capacité de Jacques Laget à accueillir les fantasmes de Benoît mis en image de façon assez crue permet à ce dernier, en passant par le regard du thérapeute et sa capacité à contenir et à supporter la brusque émergence pulsionnelle, de poursuivre une élaboration fantasmatique douloureuse. A l'inverse, Vered Bar-On décrit avec beaucoup de courage son incapacité à supporter la vision de photos de scarifications que lui montre une patiente lors d'une séance. L'impossibilité de se connecter à ses éprouvés lors de cette vision et la barrière émotionnelle qu'il dresse entre lui et la patiente se manifestent par une tendance à sur-interpréter et à « trop parler » pour se protéger des motions pulsionnelles agressives et érotiques provoquées par cette vision [START_REF] Bar-On | It Cuts Both Ways: An Analysis of the Psychological Discourse on Self-Injury from a Linguistic Point of View[END_REF].

Les scarifications pour tracer des frontières

Frontières corporelles, temporelles et relationnelles

Je souhaite maintenant revenir sur cette notion de changement et de différenciation qui éclaire fortement les scarifications de Lucie. En effet, ces pratiques visent à établir une distinction à même le corps de Lucie sous plusieurs aspects. Tout d'abord, comme je l'avais noté dans la première partie de cet article, les scarifications, au travers de la sensation douloureuse et de la vue du sang, renforcent la capacité contenante de la peau et donc la distinction entre l'extérieur et l'intérieur. Pour éviter de disparaître et de se répandre dans le monde et pour maintenir un sentiment vacillant d'existence corporelle, les coupures tracent et retracent la ligne de démarcation entre intérieur et extérieur [START_REF] Breton | La peau et la trace[END_REF][START_REF] Lamotte | Apport de la théorie des enveloppes psychiques à la compréhension des conduites de scarifications à l'adolescence[END_REF].

Par ailleurs, ces marques effectuées par Lucie elle-même permettent de distinguer le corps de l'enfance du corps de l'adolescence, distinction qui avait été ressentie et subie à même le corps lors de la puberté mais n'avait pu être ni reconnue par d'autres, ni intégrée psychiquement. Les processus pubertaires [START_REF] Gutton | [END_REF], en tant que transformations psychiques qui accompagnent la puberté, avaient été entravés puisqu'aucune parole, aucun changement Le corps et plus particulièrement la cicatrice deviennent alors témoins « historiques de l'évènement psychique traversé » [START_REF] Dargent | Blessures de l'adolescence[END_REF] : support de discussion entre le sujet et l'autre, qui atteste de la souffrance vécue sans que le sujet doive se risquer à une adresse directe.

Catherine Matha explique ainsi comment les scarifications peuvent être un moyen de forcer l'empathie de l'autre et de situer en dehors de soi la demande de lien : c'est l'autre qui s'inquiète et se rapproche, l'autre qui désire et devient dépendant du lien mais absolument pas le sujet scarificateur. Lorsque l'angoisse d'être sous l'emprise de l'objet est trop forte, l'entame force le lien en contournant la terreur d'être rejetée, la réaction faisant alors partie intégrante du processus scarificatoire et paradoxalement aussi du processus suicidaire où la « dimension ordalique équivaut à un appel à l'objet humain qui a fait défaut, plus qu'à une divinité arbitraire ou au hasard » [START_REF] Corcos | Conduites à risque et de dépendance à l'adolescence : la force et le sens[END_REF]. En effet, le spectateur donne sens à l'entame et celle-ci ne peut être comprise indépendamment de son adresse, comme si la charge affective suscitée par le recours au corps était trop lourde, trop chargée de sens pour être appréhendée par un seul individu et nécessitait forcément un appoint externe d'élaboration psychique. Si les scarifications sont une manière de rejouer un épisode traumatique, l'aboutissement de cette scène est modifié par la présence d'un autre contenant et capable de remplacer une simple répétition par une élaboration potentielle. Ainsi « l'automutilation prend un autre sens du moment où quelqu'un s'émeut, et contient, répond à l'acte » [START_REF] Douville | L'automutilation, mise en perspectives de quelques questions[END_REF]. En faisant voler en éclat l'image d'enfant à laquelle elle était associée Lucie peut dans un second temps s'autoriser à occuper d'autres positions. Elle oblige son entourage à réfléchir avec elle à ce qui lui arrive, à l'accompagner dans ce cheminement identitaire douloureux et angoissant. Ses parents acceptent finalement de participer à une thérapie familiale qu'ils avaient jusque-là refusée et du côté institutionnel, plusieurs réunions de synthèse s'articulent autour de sa situation. Si nous partageons avec Nathalie de Kernier l'idée que « « le devenir à moyen terme du fonctionnement psychique de l'adolescent est probablement tributaire […] de la réponse de l'autre à qui le geste a été adressé » [START_REF] De Kernier | Penser le geste suicidaire à l'adolescence et observer l'évolution à moyen-terme du fonctionnement psychique[END_REF], nous insistons néanmoins sur la capacité des adolescents à provoquer la réponse désirée et à être ainsi acteurs de cette réponse plutôt qu'à la merci des réponses ou non réponses de leur environnement.

Conclusion

En conclusion, les pratiques de scarification servent bien à assurer à leur auteur une enveloppe sensorielle visuelle et tactile lorsque les interactions précoces n'ont pas permis l'introjection d'une séparation nette entre l'extérieur et l'intérieur [START_REF] Lamotte | Apport de la théorie des enveloppes psychiques à la compréhension des conduites de scarifications à l'adolescence[END_REF][START_REF] Perret-Catipovic | Blessures auto-infligées à l'adolescence : un survol de la littérature[END_REF][START_REF] Gaspard | Marques corporelles, tatouages et solutions subjectives à l'adolescence[END_REF]

Références

  : self-mutilation, self-injury, self-harm, scarification, Ego-skin, containing, envelope, language, adolescence 1. Premiers contacts Lucie, seize ans, est adressée au Centre Médico-Psychologique où je travaille après que l'infirmière scolaire ait découvert sur ses bras des traces rectilignes, horizontales, rouges ou blanches selon l'ancienneté de la coupure. C'est la première fois que Lucie rencontre un psychologue. Durant toutes les premières séances, elle garde son manteau et reste les bras croisés. Elle parle peu et ne peut rien dire de ses coupures, que j'appellerai dans le reste de cet article « scarifications » pour reprendre sa propre dénomination. Elle insiste toutefois sur l'importance de la douleur et la vue de l'écoulement de sang. Une fois ces deux conditions remplies, elle arrête et peut passer plusieurs minutes à regarder le sang se répandre lentement sur son bras. Elle explique recourir à cette pratique de scarification lorsqu'elle a « le sentiment de ne pas exister » et ne pas « se sentir à [s]a place » et rapporte aussi l'existence de courts épisodes de boulimie et de « crises d'angoisse » liées à ce même sentiment. Concernant ses relations aux autres, Lucie se décrit comme secrète et réservée et dit qu'elle « garde beaucoup de choses pour elle » et ne sait pas ce qui se passerait si elle « laissait tout sortir ». Elle dit aussi ne pas supporter son corps et ne pas se reconnaître quand elle se regarde dans le miroir.

3. 1 .

 1 Léthargie de l'environnement et passage à l'acte suicidaire Deux mois après le début de la thérapie, Lucie avale une quantité importante de somnifère avant de s'endormir. Elle se réveillera néanmoins le lendemain et ira au lycée, mais, incapable de se concentrer pendant les cours, elle parlera de cette ingestion excessive de médicaments à son amie en utilisant le terme « tentative de suicide » et, après un passage auprès de l'infirmière scolaire, retournera chez elle pour se reposer. La séance suivante, elle manifeste une vive colère envers ses parents qui, selon elle, agissent « comme avant », lui demandent de continuer à aller à l'école même si elle se sent mal, et expliquent que ses scarifications et ses crises d'angoisse « ne sont pas une raison d'avoir de moins bonnes notes ». Elle insiste notamment sur le fait que les couteaux dont elle se sert pour se scarifier restent à disposition dans la cuisine et que l'armoire à pharmacie n'est « même pas verrouillée ». J'échoue alors à entendre ce qui m'est adressé, le manque d'inquiétude et d'affolement qui m'est aussi reproché et j'interviens seulement pour lui demander comment elle souhaiterait que ses parents réagissent.

  ayant besoin d'être protégée, rassurée et contenue. Je nie toute dimension sexuelle et agressive de sa relation à elle-même et aux autres, comme le font ses parents à qui elle reproche de la voir toujours comme « une petite fille sage et modèle ». Sa deuxième tentative de suicide m'oblige à m'interroger sur cette représentation et sur mon incapacité à anticiper son acte. En m'inquiétant et en faisant voler en éclat la représentation figée que j'avais d'elle, elle peut dans un second temps se permettre de proposer autre chose et d'évoquer un corps sexualisé, désirable et désirant. Je réalise que ses pratiques de scarification cherchent non seulement à assurer une fonction de contenance mais probablement aussi à attirer le regard des autres sur son corps mutilé, dans une visée à la fois excitatrice et agressive. A partir de cet évènement, elle parlera de plus en plus pendant les séances et décrira notamment la sensation d'avoir été kidnappée et violée pendant son enfance. Elle a en parlé à ses parents qui lui ont assuré qu'un évènement de ce type ne s'était jamais produit. Elle évoque aussi une puberté précoce, avec un début de menstruation à onze ans, qu'elle a très mal vécue, ayant l'impression d'être toujours considérée exactement de la même manière, comme une enfant, alors même qu'elle subissait de nombreux changements corporels et pulsionnels qu'elle était incapable de comprendre et de maîtriser. Il me semble que l'entrée dans la sexualité adolescente a été particulièrement traumatique pour Lucie et se cristallise autour de cette sensation d'avoir été kidnappée et violée, traumatisme d'autant plus fort qu'il a été dénié par son entourage. J'ai moi-même reproduit ce déni au début de la thérapie et ce n'est que dans un second temps qu'elle s'autorisera à me parler de ses relations amoureuses et de ce fantasme sexuel. Je serai aussi en mesure de reconnaître et d'accueillir de timide tentatives de séduction de sa part au cours de la thérapie, Lucie arrivant de plus en plus maquillée et apprêtée aux séances, et croisant bien plus souvent mon regard en souriant. Il ne me semble alors pas qu'elle attende de réponse de ma part mais plutôt qu'elle expérimente la possibilité de séduire dans un cadre sécurisé, cette séduction pouvant être reconnue et accueillie sans mettre en danger ni la relation thérapeutique ni l'intégrité des protagonistes. Je me permets donc de remarquer à voix haute ces changements entre sa présentation lors des premières séances et celle qu'elle montre depuis sa sortie d'hospitalisation. Elle me répond « oui, je crois que je suis en train de grandir ».

  d'attitude significatif n'avaient, selon Lucie, accompagné ses modifications corporelles. Vers la fin de la thérapie, elle sera aussi capable d'exprimer clairement qu'elle a commencé à se scarifier pour que ses parents se rendent compte qu'elle allait mal car elle n'arrivait pas à leur faire comprendre autrement qu'elle « n'étai[t] plus la même ». Elle avait en effet l'impression de n'être « ni vue ni entendue » par ses parents tout en reconnaissant qu'ils se préoccupaient d'elle et effectuaient de nombreuses démarches matérielles. Ses parents écoutaient et voyaient bien quelqu'un mais il s'agissait de la « petite fille sage et modèle » dans laquelle elle ne se reconnaissaient plus. Elle raconte ainsi avec un grand sourire au cours d'une séance que ses grands parents l'ont vu après qu'elle se soit scarifiée et « ne [l]'ont pas reconnue ». On rejoint ici les réflexions de Catherine Matha selon qui les scarifications permettent notamment de « mourir au passé pour accéder à un statut plus enviable » [17], en détruisant fantasmatiquement le corps dépendant de l'enfance pour advenir au corps de l'adolescence. Enfin, Lucie a une soeur jumelle, avec laquelle la relation est très conflictuelle. Elle explique que lorsqu'elles étaient enfants, sa soeur faisait beaucoup de bêtise et nécessitait beaucoup d'attention de la part de ses parents. Elle a ainsi souvent reproché à ses parents d'avoir une préférence envers sa soeur jumelle, ses parents de rétorquer qu'ils « ne font pas de différence » et elle alors d'affirmer en séance avec colère qu'« il y a forcément une différence ». Durant la thérapie, elle exprime une forte angoisse que sa soeur « fasse comme [elle] », c'est-à-dire se scarifie aussi et insiste sur le fait que ses marques permettent maintenant à leurs amis de bien les distinguer. Elle s'appuie aussi sur ses scarifications pour exiger une chambre séparée de celle de sa soeur jumelle et l'obtiendra. Nous rejoignons ici les travaux de Matthew Nock selon qui les scarifications proviennent souvent d'une frontière diffuse entre soi et l'autre [18].

4. 2 .

 2 Une reconnaissance nécessaire Néanmoins, ces tentatives de créer une distinction entre l'intérieur et l'extérieur, entre son corps d'enfant et son corps d'adolescent et entre sa soeur et elle-même ne peuvent s'inscrire de manière durable que si elles sont reconnues par son entourage. Elle semble en effet incapable de s'identifier elle-même à un corps d'adolescent et a donc besoin que la fin de l'enfance et le passage à l'adolescence soient reconnus par l'entourage. Elle raconte ainsi un rêve qu'elle fait durant son hospitalisation où elle est maquillée, coiffée et bien habillée mais où tout le monde la trouve ridicule et se moque d'elle. Elle déclare ensuite qu'elle ne se sent pas légitime quand elle se maquille, que ça lui parait faux et qu'elle a donc besoin que ce changement soit d'abord validé par un regard extérieur pour y croire ensuite elle-même. Ses scarifications et ses tentatives de suicide servent à forcer le changement de regard. Elle se protège d'un éventuel refus ou d'une éventuelle agressivité en réaction à ce passage en force en plaçant ce changement hors de sa volonté, hors de son contrôle puisque ces pratiques se font malgré elle (« c'est plus fort que moi », « je ne sais pas ce qui m'est arrivée »).

  . Elles forment une enveloppe de souffrance qui assure un sentiment d'existence minimum et évite une dissolution du corps dont les limites semblent inexistantes. Elles tentent aussi d'instaurer une distinction entre soi et l'autre et de remettre en route une temporalité qui a pu se figer à la suite d'un évènement traumatique. Pour Lucie, ses coupures visent ainsi à établir une séparation nette avec sa soeur tout en montrant la douleur de cette séparation et aussi à se réapproprier un corps malmené par des changements pubertaires précoces et vécus sur un mode traumatique. Néanmoins, ces opérations de coupure entre le monde extérieur et le monde intérieur d'une part et entre soi et l'autre d'autre part ne peuvent s'inscrire dans la durée que si elles passent par un regard extérieur. Ce que montre ce cas clinique est qu'un des objectifs principaux des scarifications et des tentatives de suicide de Lucie est bien de convoquer ce regard et que la coupure de la peau vise ici à transformer le lien à l'autre parental (et aussi au thérapeute qui en accueille la projection). Le choix de pratiques transgressives et générant des sentiments particulièrement difficiles à supporter par l'entourage [24,25] est loin d'être anodin et permet de s'assurer d'une réaction et d'une remise en mouvement des relations et des représentations existantes. Les scarifications et les tentatives de suicide à l'adolescence peuvent alors être comprises comme des tentatives, souvent efficaces, de forcer le changement de regard, notamment lorsque l'adolescent se sent cantonné à une place d'enfant qui désavoue ses éprouvés corporels. Dans ce contexte, l'élaboration de la fonction contenante d'un patient qui se scarifie passe en partie par la capacité du thérapeute à laisser émerger et à supporter l'émergence de motions pulsionnelles agressives et érotiques. Si le thérapeute se représente le patient principalement sur un mode déficitaire, comme un individu dont il faudrait « réparer » la fonction contenante pour diminuer les angoisses et prévenir les agirs auto-agressifs, il échoue alors à voir ce qui lui est adressé. Les agirs auto-agressifs peuvent alors devenir une façon de convoquer le spectateur, d'exiger son attention et de mettre sur le devant de la scène des motions pulsionnelles que l'environnement peine à supporter mais qui n'en existent pas moins pour le sujet. Déclaration d'intérêts : Les auteurs déclarent ne pas avoir de conflits d'intérêts en relation avec cet article.