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Background: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood. Methods: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients’ clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed. Results: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF. Discussion: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood.

Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is an aggressive cutaneous lymphoma. Bone involvement is rare and poorly described. We present five cases of PCDLBCL-LT with bone localization. In four cases, the bone involvement was diagnosed during the initial staging with positron emission tomography (PET) or computed tomography (CT) scan, and in the fifth case after tibial fracture during treatment with rituximab (RTX) and polychemotherapy (PCT). PCDLBCL-LT can be asymptomatic and involve bone sites distant from cutaneous lesions. None had other extracutaneous involvement. In our series, all patients received RTX-PCT as first-line chemotherapy and all had early relapses or progression. Second-line treatments had poor efficacy. Our series shows that bone involvement seems to be associated with poor prognosis in PCDLBCL-LT. Bone localization is not diagnosed with initial thoracic–abdominal–pelvic CT when asymptomatic and affecting the limbs only. If there is a suspicion of PCDLBCL-LT, patients should undergo systematic investigation with alternative imaging techniques, including PET, both at baseline and if there is any concern during follow-up.

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International audience

Sézary syndrome (SS) is an aggressive cutaneous T cell lymphoma with poor prognosis mainly characterized by the expansion of a tumor CD4+ T cell clone in both skin and blood. So far, the development of new therapeutic strategies has been hindered by a lack of reproducible in vivo models closely reflecting patients’ clinical features. We developed an SS murine model consisting of the intravenous injection of Sézary patients’ PBMC, together with a mixture of interleukins, in NOD-SCID-gamma mice. Thirty-four to fifty days after injection, mice showed skin disorders similar to that observed in patients, with the detection of epidermis thickening and dermal tumor T cell infiltrates. Although experimental variability was observed, Sézary cells could be tracked in the blood stream, confirming that our model could efficiently exhibit both skin and blood involvement. Using this model, we evaluated the therapeutic potential of RT39, a cell-penetrating peptide derived from the survival protein anti-apoptosis clone 11 (AAC-11), that we previously characterized as specifically inducing apoptosis of Sézary patients’ malignant clone ex vivo. Systemic administration of RT39 led to cutaneous tumor T cells depletion, demonstrating efficient malignant cells’ targeting and a favorable safety profile. These preclinical data confirmed that RT39 might be an innovative therapeutic tool for Sézary syndrome.

Background Mogamulizumab is a novel defucosylated monoclonal antibody targeting the C-C chemokine receptor 4 (CCR4) that eradicates Sezary cells via antibody-dependent cellular cytotoxicity. Treatment of Sezary syndrome with mogamulizumab has recently shown an increase in progression-free survival compared to vorinostat in patients previously treated for cutaneous T-cell lymphoma. Objectives To investigate immune side effects of mogamulizumab in patients with Sezary syndrome. Materials & methods Three patients with Sezary syndrome, treated with mogamulizumab, who developed clinically confirmed vitiligo, were investigated. Results Case 1 was a 66-year-old woman from Tunisia. Seven months after the administration of mogamulizumab, she developed vitiligo on her face and hands while still in complete remission for Sezary syndrome. Case 2 was a 72-year-old woman from Martinique, with no history of autoimmune disease, who was diagnosed with Stage IVA1 Sezary syndrome. The patient received multiple lines of treatment with no improvement. After six months of mogamulizumab treatment, while still on treatment, the patient progressively developed well-demarcated depigmented patches on the scalp, upper limbs, and trunk, consistent with vitiligo. Case 3 was a 38-year-old woman from France, who was diagnosed with Sezary syndrome in October 2019. Mogamulizumab therapy was started in December 2019. Eight months later, she developed histologically-confirmed vitiligo on her legs. Conclusion Vitiligo can be another autoimmune manifestation associated with mogamulizumab, and the occurrence of vitiligo could be a favourable predictive factor for response to treatment.

Mogamulizumab, an anti-CCR4 monoclonal antibody, has been shown to increase progression-free survival in cutaneous T-cell lymphoma.We hypothesized that besides the targeted depletion of Sézary cells (SCs), mogamulizumab may reshape the immune tumour microenvironment.Both malignant and benign compartments from 26 patients with B2 stage Sézary syndrome before mogamulizumab initiation were prospectively analysed using KIR3DL2 and TCRVβ markers, serological markers and molecular assessments of clonality.Prior to mogamulizumab, the benign subset of CD4Mogamulizumab likely contributes to the restoration of efficient immunity and reshapes not only the malignant lymphocyte subset but also the benign subset. These results have potential implications for optimal therapeutic sequences and/or combinations. What is already known about this topic? Management of Sézary syndrome (SS) involves successive therapies that participate as cause and consequence in the emergence of resistant clones, on a background of immunodeficiency. We and others have reported the complex and dynamic heterogeneity of Sézary cells (SCs) during disease progression. Mogamulizumab therapy, by targeting the skin-homing receptor CCR4, mainly expressed by SCs, has been shown to increase progression-free survival in patients with SS. What does this study add? Using multicolour flow cytometry, we provide quantification of CCR4 and immune checkpoint molecules on malignant SCs and benign CD4

Applying next-generation sequencing to paired skin and marrow biopsies, Delaleu et al describe an entity they term “myelodysplasia cutis,” comprising histologic features of histiocytoid Sweet syndrome in the skin and a clonally related myelodysplasia in the bone marrow. This can be distinguished from forms of histiocytoid Sweet syndrome not associated with myelodysplastic syndromes, as well as classical neutrophilic Sweet syndrome associated with various malignant and nonmalignant diseases and leukemia cutis where the infiltrating cells are myeloblasts.

Cutaneous T-cell lymphomas (CTCLs) are rare malignancies involving primarily the skin. Responses to treatment are usually short-lived in advanced CTCL. The determinants of long-term CTCL control are unclear. Mogamulizumab, an anti-human CCR4 antibody that acts by antibody-dependent cell cytotoxicity against CCR4+ CTCL tumor cells and peripheral memory blood regulatory T cells, has been associated with long-lasting remissions and immune adverse events. Here, we reported skin rashes in 32% of 44 patients with CTCL treated with mogamulizumab, associated with significantly higher overall survival (hazard ratio, 0.16; 0.04-0.73; P = .01). Rash occurred in patients with Sézary syndrome and was associated with longer time to progression. These rashes were characterized by a CD163+ granulomatous and/or CD8+ lichenoid skin infiltrate. High-throughput sequencing analysis of T-cell receptor β genes in skin and blood flow cytometry confirmed the depletion of CTCL tumor cells, as well as the recruitment of new reactive T-cell clones in skin at the time of skin rash. CXCL9 and CXCL11, two macrophage-derived chemokines that recruit CXCR3+ T cells to skin, were overexpressed in skin rashes. A higher frequency of TIGIT+ and PD1+ exhausted reactive blood T cells was observed at baseline in patients with rash, and this frequency decreased with mogamulizumab treatment. These data are consistent with mogamulizumab-induced long-term immune CTCL control by activation of the macrophage and T-cell responses in patients with rash.

Summary Background IPH4102 is a first-in-class monoclonal antibody targeting KIR3DL2, a cell surface protein that is expressed in cutaneous T-cell lymphoma, and predominantly in its leukaemic form, Sezary syndrome. We aimed to assess the safety and activity of IPH4102 in cutaneous T-cell lymphoma. Methods We did an international, first-in-human, open-label, phase 1 clinical trial with dose-escalation and cohort-expansion parts in five academic hospitals in the USA, France, the UK, and the Netherlands. Eligible patients had histologically confirmed relapsed or refractory primary cutaneous T-cell lymphoma, an Eastern Cooperative Oncology group performance score of 2 or less, were aged 18 years or older, and had received at least two previous systemic therapies. Ten dose levels of IPH4102, administered as an intravenous infusion, ranging from 0·0001 mg/kg to 10 mg/kg, were assessed using an accelerated 3 + 3 design. The primary endpoint was the occurrence of dose-limiting toxicities during the first 2 weeks of treatment, defined as toxicity grade 3 or worse lasting for 8 or more days, except for lymphopenia. Global overall response by cutaneous T-cell lymphoma subtype was a secondary endpoint. Safety and activity analyses were done in the per-protocol population. The study is ongoing and recruitment is complete. This trial is registered with ClinicalTrials.gov , number NCT02593045 . Findings Between Nov 4, 2015, and Nov 20, 2017, 44 patients were enrolled. 35 (80%) patients had Sezary syndrome, eight (18%) had mycosis fungoides, and one (2%) had primary cutaneous T-cell lymphoma, not otherwise specified. In the dose-escalation part, no dose limiting toxicity was reported and the trial's safety committee recommended a flat dose of 750 mg for the cohort-expansion, corresponding to the maximum administered dose. The most common adverse events were peripheral oedema (12 [27%] of 44 patients) and fatigue (nine [20%]), all of which were grade 1–2. Lymphopenia was the most common grade 3 or worse adverse event (three [7%]). One patient developed possibly treatment-related fulminant hepatitis 6 weeks after IPH4102 discontinuation and subsequently died. However, the patient had evidence of human herpes virus-6B infection. Median follow-up was 14·1 months (IQR 11·3–20·5). A confirmed global overall response was achieved in 16 (36·4% [95% CI 23·8–51·1]) of 44 patients, and of those, 15 responses were observed in 35 patients with Sezary syndrome (43% [28·0–59·1]). Interpretation IPH4102 is safe and shows encouraging clinical activity in patients with relapsed or refractory cutaneous T-cell lymphoma, particularly those with Sezary syndrome. If confirmed in future trials, IPH4102 could become a novel treatment option for these patients. A multi-cohort, phase 2 trial (TELLOMAK) is underway to confirm the activity in patients with Sezary syndrome and explore the role of IPH4102 in other subtypes of T-cell lymphomas that express KIR3DL2. Funding Innate Pharma

The erythrodermic ulcerated form of mycosis fungoides (MF) is exceptional, and treatment of refractory cases is challenging. Brentuximab vedotin (BV) is a monoclonal antibody combined with monomethyl auristatin E, recently approved for the treatment of refractory CD30+ cutaneous T-cell lymphoma. We report a case of refractory MF in a 56-year-old man with a long history of large-plaque parapsoriasis, as revealed by psoriasiform erythroderma, treated initially with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) polychemotherapy, inducing a 2-year complete response. After relapse, interferon and gemcitabine were unsuccessful. Finally, treatment with BV was decided upon, despite the absence of CD30 expression. After three infusions of BV 1·8 mg kg-1 , we achieved a complete and stable response, allowing an allogeneic stem cell transplant. The patient is still in complete remission, 19 months after the graft. This case illustrates the possibility of using BV in refractory CD30- MF as a salvage therapy.

The prognosis of erythrodermic cutaneous T-cell lymphomas (ECTL) depends upon lymph node (N), visceral (M) involvement, and blood stage (B, i.e circulating Sezary cells, identified upon peripheral blood immunophenotyping, B0: absolute count 60 years, an elevated rate of lactate dehydrogenase (LDH), and histologic large-cell transformation (LCT).1-3 ECTL progression is usually homogeneous and simultaneously involves all compartments of the disease. We report nine patients with B1 or B2 ECTL displaying an unusually discrepant outcome profile with the rapid onset of N or M involvement contrasting with the lack of progression of cutaneous and blood involvement.

BACKGROUND Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

Background: The prognosis of Sezary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated. Objectives: To determine the prognostic value of LN CNB in MF/SS. Methods: A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus. Results: We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26–not reached) vs. 14 months (range 5–30), respectively (p 75 years, LN short-axis diameter >15 mm, N3 stage, presence of large-cell transformation, TOX >60%, PD1 >25%, Ki67 >30%, KIR3DL2 >15%, CD30 >10% and TCF >25% were identified as adverse prognostic factors. In multivariate analyses, only an age >75 years and Ki67 index >30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis. Conclusions: CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis.

Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders characterized by dysplastic and ineffective blood cell production leading to blood cytopenias, and a risk of transformation to acute myeloid leukemia (AML). Skin lesions in patients with MDS include Sweet syndrome (SS), leucocytoclastic vasculitis, leukemia cutis and histiocytoid SS (H-SS), among others,.1,2 H-SS is a histological variant of SS differing from classical neutrophilic SS by a dermal infiltrate mostly made of immature cells of the myeloid lineage, that has been associated with myeloid malignancies.

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International audience; Skin involvement in Waldenström's macroglobulinaemia is poorly described, and diagnosis of this disorder may be difficult. Many differential diagnoses are possible (other lymphomas, primary cutaneous lymphoma, etc.). Describing 2 aspects of Waldenström's macroglobulinaemia (infiltration by lymphoplasmacytic tumour cells or histological transformation into diffuse large B-cell lymphoma) allows the identification of clinical, histological and immunohistochemical diagnostic aids. Detection of the MYD88 L265P mutation is of interest. This study identified a characteristic clinical picture in non-transformed cases, and was able to distinguish between transformed and non-transformed cases by their severity and poor prognosis. Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the followup of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation).

International audience; In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with impaired survival. Finally, the double-hit assessment does not appear clinically relevant in primary cutaneous large B-cell lymphoma.

BACKGROUND Primary cutaneous B-cell lymphomas represent approximately 25% of primary cutaneous lymphomas. Follicular centre cell lymphomas (PCFCL) and marginal zone lymphomas (PCMZL) are the two histological subtypes that present an indolent evolution. Radiotherapy is one of the recommended treatment options with few series reported. OBJECTIVE This study aimed to evaluate radiotherapy outcomes in term of overall survival (OS) and disease-free survival (DFS) for patients suffering from a PCMZL or PCFCL, to search for predictive factors of recurrence, and to evaluate chronic and aesthetics adverse events and patient's satisfaction. METHODS Patients treated with contact low energy radiotherapy for a PMZCL or PCFCL from April 2009 to June 2017 in Saint Louis hospital were retrospectively analysed. Total dose ranged from 18 to 30 Gy. Objective response (OR) rates, DFS and OS as patterns of recurrence according to radiation fields were analysed. Univariate analysis of DFS has been performed according to clinical and biological parameters. Acute toxicity, long-term adverse events and satisfaction were collected via individualized questionnaires. RESULTS Forty-six patients were included. Median follow-up was 43.5 months. OR was achieved for 100% of cases. Recurrence occurred in 39% of cases. Median DFS was 44 months. Three-year DFS and 5-year DFS were 56% and 51%, respectively. OS at 3 and 5 year was 100%. Only sex was significantly associated with DFS. Acute AEs occurred in 48% of cases without grade 3 and 4. 55% reported some moderate aesthetic sequelae for long-term AEs. 97% were satisfied with treatment. CONCLUSION This study confirms the good risk-benefit of radiotherapy for the treatment of primary cutaneous indolent B-cell lymphomas due to the high response rate and a long DFS. No significant factor for recurrence was identified, except female sex. Long-term aesthetic evaluation was good or excellent for most of the patients.

Introduction Le syndrome de Sezary (SS) est un lymphome T cutane rare de mauvais pronostic caracterise par une phase leucemique et rattache au mycosis fongoide (MF) dans la classification internationale. La transformation en grandes cellules (LCT) est un facteur pronostique independant defavorable bien decrit dans le MF. Cependant, la LCT n’a jamais ete etudiee specifiquement sur une large cohorte de patients avec SS. L’objectif principal de notre etude est de decrire la frequence et la valeur pronostique de la LCT dans le SS. Materiel et methodes Nous avons collecte retrospectivement les donnees cliniques, histologiques, biologiques et cytometriques au diagnostic et au cours du suivi de tous les patients ayant un syndrome de Sezary diagnostiques entre 1998 et 2020 selon les criteres OMS/EORTC et suivis a l’hopital Saint-Louis (AP–HP, PARIS). Chaque biopsie cutanee a ete analysee independamment par deux pathologistes puis scannee et analysee numeriquement (Innate Pharma, Marseille). Resultats Un total de 117 patients ont ete inclus dans l’etude. Le suivi median etait de 41 mois [IQR : 1–81]. La LCT diagnostiquee sur biopsie cutanee etait observee chez 6 % (6/100) et 20% (18/91) des patients, respectivement au diagnostic et au cours du suivi. L’etude de la reproductibilite inter-observateur pour le diagnostic de la LCT montrait un coefficient Kappa de Cohen a 0,88 (IC95[0,78–0,98]). L’analyse d’image sur lames scannees (n = 190) retrouvait une surface moyenne des 25 % des cellules les plus grandes egale a 33 μm2 [SD = 4,7] sur les biopsies LCT+ vs 26 μm2 [SD = 3,2] sur les biopsies LCT− ; p 60 ans, le taux de LDH eleve, le taux de cellules circulantes CD3 + CD4 + CD26− ≥ 10 000/mm3 et une LCT au diagnostic etaient associes independamment a une diminution de la survie globale. Discussion La LCT dans le syndrome de Sezary est un facteur pronostique defavorable, independant de la taille des cellules tumorales circulantes, dont l’evaluation histologique est fiable, en utilisant les criteres definis pour le MF, et recommandee au cours du suivi. Notre etude comparant des donnees cliniques, histologiques, biologiques et cytometriques est, a notre connaissance, la premiere decrivant la frequence et la signification pronostique de la LCT dans une large cohorte homogene de SS.

Introduction Les lymphomes T gamma delta primitivement cutanes (PCGDTCL) sont rares, representent moins de 1 % de tous les lymphomes cutanes, et ont classiquement une evolution clinique agressive. L’etiologie est incertaine mais implique une stimulation antigenique chronique et une immunosuppression. C’est une entite de la classification EORTC-OMS de 2018 dont la presentation clinique peut etre tres variee, le plus souvent des nodules ou des placards infiltres et l’evolution des lesions est imprevisible avec progression ou apparition d’un syndrome d’activation macrophagique. Le traitement est habituellement agressif avec une resistance a la chimiotherapie ou a la radiotherapie, et rechutes frequentes, necessitant une allogreffe. Le pronostic global est generalement mauvais avec une survie a 5 ans ne depassant pas 20 %. Cependant, des cas d’evolution plus indolente ont ete rapportes dans la litterature depuis 2005, traites avec succes par corticoides systemiques, methotrexate, bexarotene ou phototherapie. Nous en rapportons 4 nouveaux cas. Materiel et methodes Nous rapportons quatre cas de patients atteints de PCGDTCL avec des presentations cliniques heterogenes : un homme de 81 ans ayant presente des plaques infiltrees du visage, et trois femmes de 25, 36 et 66 ans, ayant presente respectivement des lesions nodulaires localisees des membres inferieurs (cas 2), des lesions urticariennes du tronc (cas 3) et des lesions nodulaires et necrotiques par endroits des membres inferieurs (cas 4). Malgre un diagnostic confirme de PCGDTCL, l’evolution clinique etait indolente avec une reponse partielle a complete aux traitements par bexarotene ou methotrexate, avec un suivi clinique entre 7 et 24 mois. Cependant, la patiente de 66 ans (cas 4) a progresse vers une atteinte diffuse et agressive au bout de 3 ans de suivi, ayant necessite l’introduction de traitements plus agressifs (chimiotherapie et autogreffe). Quelques cas de formes egalement indolentes ont deja ete decrits dans la litterature (cas 5 a 8 du tableau), avec des presentations variees de lesions localisees ou diffuses, ayant favorablement evolue sous traitements conventionnels par phototherapie, radiotherapie, corticotherapie systemique ou meme ont ayant regresse spontanement. Discussion Nos quatre cas soulignent l’importance de connaitre la possibilite d’une forme indolente de PCGDTCL, qui serait caracterisee par une evolution plutot favorable sous des traitements immunomodulateurs avec maintien d’une remission clinique, ce qui permettrait d’eviter les traitements lourds tels qu’une chimiotherapie. Toutefois, il est prudent de maintenir une surveillance rapprochee pour detecter precocement toute evolution secondairement agressive, comme pour le cas 4 de notre serie.

Introduction Les leucemies a grands lymphocytes granuleux (LGL) font partie des syndromes lymphoproliferatifs T (SLPT) matures, maladies clonales rares dont le diagnostic repose sur une signature phenotypique particuliere. L’association de deux SLPT est rare. Nous rapportons le premier cas de LGL chez un patient suivi pour un syndrome pre-Sezary aux caracteristiques phenotypiques atypiques. Materiel et methodes Un homme de 77 ans suivi pour une gammapathie monoclonale etait adresse en dermatologie pour une erythrodermie prurigineuse associee a un ectropion bilateral, une ichtyose et une keratodermie palmoplantaire. On ne palpait aucune adenopathie et le scanner montrait un nodule pulmonaire isole (adenocarcinome pT1aN0M0 traite chirurgicalement). Le phenotypage lymphocytaire (PLy) revelait une population lymphoide TCD3+ suspecte CD4+CD7-CD26-TCRαβ CD158k- representant 34 % des lymphocytes totaux. L’histologie cutanee compatible avec une localisation d’un lymphome T epidermotrope (CD4/CD8 > 10) et la presence d’un clone T sanguin important identique au clone T cutane faisaient porter le diagnostic de syndrome pre-Sezary (stade IIIB T4N0B1). Debute en 2016 et arrete en 2019, un traitement par bexarotene entrainait une remission complete. Hospitalise en 2020 pour asthenie et bicytopenie (anemie, neutropenie) associees a une splenomegalie sans erythrodermie, le PLy retrouvait une population CD8+ a 3277/mm3 (80,9 %) dont 86 % CD158k+ majoritairement TCRαβ(98,5 %) CD26-(75 %) et CD57+(CD3+CD8+CD57+ 79,1 % soit 2592/mm3). Il existait un clone T circulant distinct de 2016. L’etude next generation sequencing (NGS) confirmait le diagnostic de T-LGL par la presence de mutations caracteristiques STAT3 (Asp661Val et Asp661Tyr) et une mutation TET2 (Phe1287Ser). Une surveillance simple etait recommandee. Discussion Notre malade presentait un syndrome pre-Sezary atypique par l’absence d’expression de KIR3DL2 et la reponse complete rapide et durable induite par le bexarotene. Il s’agit du 1er cas de LGL chez un patient suivi pour un syndrome pre-Sezary. Les CTCL et les LGL partagent des voies de signalisations pathogeniques telles que IL15/IL15R. Le syndrome de Sezary, quasi exclusivement CD3+CD4+, exprime dans 90 % des cas le marqueur CD158k (KIR3DL2). La LGL est une proliferation monoclonale de lymphocytes de phenotype CD3+CD8+ dans plus de 80 % des cas ou CD3- CD56+ (NK) plus rarement CD4+. L’expression de KIR3DL2 par les LGL n’a jamais ete rapportee. Conclusion La survenue d’une double population clonale CD4 puis CD8 peut faire suspecter l’apparition au sein d’un progeniteur T d’une mutation commune telle que sur la voie JAK/STAT deja retrouvee dans ces maladies. L’expression de KIR3DL2 par les cellules de LGL merite d’etre etudiee sur un plus grand nombre de cas et pourrait ouvrir la voie a un traitement par l’anticorps monoclonal anti-KIR3DL2, le lacutamab.