Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

Dramatic response to brentuximab vedotin in refractory nontransformed CD30- mycosis fungoides allowing allogeneic stem cell transplant and long-term complete remission.

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.

Cutaneous presentation of adult T-cell leukemia/lymphoma (ATLL). Single-center study on 37 patients in metropolitan France between 1996 and 2016.

INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a hematological malignancy associated with chronic HTLV-1 infection. AIM: To describe skin lesions in ATLL. METHODS: A descriptive, retrospective study between 1996 and 2016, including all patients diagnosed with ATLL at Saint-Louis Hospital (Paris, France). RESULTS: Thirty-seven ATLL patients were included. Fifteen patients (41%) had a cutaneous localization of the disease, which was present from the beginning of the disease for two thirds of them. ATLL types in patients with cutaneous localization of the disease were as follows: lymphoma, n=5, chronic, n=4, smoldering, n=4, acute, n=2. Half the patients had 2 or more cutaneous manifestations. The cutaneous localizations observed were as follows: nodulotumoral (n=8), plaques (n=7), multipapular (n=6), macular (n=4), purpuric (n=2). Among the 15 patients with cutaneous localization, median overall survival was significantly shorter in the acute and lymphoma types compared to the smoldering and chronic types (8.7 months vs. 79 months, P=0.003). DISCUSSION: ATLL is a hematologic malignancy with variable expression that is diagnosed only very rarely in metropolitan France, but that should be sought in patients from countries with high HTLV-1 prevalence in the event of a chronic eruption with patches, papules, plaques and/or tumors. The chronic and smoldering types are relatively indolent, whereas the acute and lymphoma forms have a poor prognosis.

[Granulomatous slack skin associated with metastatic testicular seminoma]. / Mycosis fongoïde chalazodermique associé à un séminome testiculaire métastatique.

BACKGROUND: Granulomatous slack skin (GSS) is an extremely rare subtype of T-cell lymphoma, a variant of mycosis fungoides (MF). Herein, we describe the first reported case of GSS associated with metastatic testicular seminoma. PATIENTS AND METHODS: A 28-year-old male patient presented with circumscribed erythematous loose skin masses, especially in the body folds and which had been relapsing for 4years. Skin biopsy showed a loss of elastic fibers and an atypical granulomatous T-cell infiltrate with epidermotropism, enabling a diagnosis of GSS to be made. A biopsy of a retroperitoneal lymphadenopathy showed testicular seminoma metastasis. DISCUSSION: Patients suffering from GSS have a statistically higher risk of developing a second primary cancer, especially Hodgkin's lymphoma. The association found between GSS and a lymphoproliferative malignancy requires long-term follow-up and determines the patient's prognosis. CONCLUSION: It is not possible to prove a formal link between GSS and testicular seminoma. However, this case illustrates the value of screening for a second cancer, particularly where extra-cutaneous lesions appear during GSS treatment. Lymph node biopsy should be performed routinely in the event of GSS with possible lymph node involvement.

[Post-radiation atypical vascular lesions and angiosarcoma: 11 cases]. / Lésions vasculaires atypiques et angiosarcomes post-radiothérapie : 11 cas.

BACKGROUND: Post-radiation atypical vascular lesions of the skin display clinical and morphological overlap with well-differentiated angiosarcomas, and correct diagnosis may be difficult. PATIENTS AND METHODS: We studied clinical, histological and immuno-histochemical aspects (CD31, CD34, D2-40 and VEGFR-3) of eight post-radiation atypical vascular lesions comparatively with three post-radiation angiosarcomas. RESULTS: All patients were female and received radiation therapy for breast carcinoma. On average, atypical vascular lesions occurred 4.3 years after radiation therapy and presented as small papulonodules or erythematous plaques. The clinical course after simple excision was benign. Histologically, they were relatively circumscribed lesions and showed slit-like vessels dissecting dermal collagen in all cases. On average, angiosarcomas occurred 5 years after radiation therapy and presented as more extensive lesions with a more aggressive clinical course. The lesions showed histological overlap with atypical vascular lesions, but were poorly circumscribed, with deeper invasion, cytological atypia and mitosis. Although the immuno-histochemical profiles were similar, expression of VEGFR-3 was greater in two cases of angiosarcoma. CONCLUSION: Post-radiation atypical vascular lesions are benign lesions that display clinical, histological and immuno-phenotypic overlap with well-differentiated angiosarcoma, and diagnosis requires good clinicopathological correlation. VEGFR-3 may be useful for differential diagnosis, as well as amplification of the MYC gene.

[Multiple cutaneous osteomas of the face in a setting of chronic acne]. / Ostéomes cutanés multiples de la face dans un contexte d'acné chronique.

BACKGROUND: Multiple cutaneous osteomas are a rare complication of chronic inflammatory acne that often goes unrecognized. We report a case concerning a 35-year-old woman. PATIENTS AND METHODS: A 35-year-old woman had been treated for acne since the age of 22 years, as part of which she received two courses of oral isotretinoin. We noted the secondary appearance of several microcysts on the face for which the excision was very difficult. Curiously, these small formations did not contain keratin but were very callous. Histological examination revealed foci of osseous metaplasia, probably of postinflammatory origin. Treatment consisted solely of excision of the lesions. DISCUSSION: Osteoma cutis comprises two distinct groups (primary and secondary). In our case, there were multiple cutaneous osteomas of the face resulting from chronic acne. The differential diagnosis was idiopathic miliary osteomatosis of the face, but this was ruled out by the young age of the patient, the improvement of the acneiform lesions under isotretinoin (confirming the initial diagnosis of acne) and the subsequent appearance of microcysts. Although there are as yet no codified treatments, excision appears to yield good results.

Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs.

The chimeric oncogene Bcr-Abl is known to induce autonomous motility of leukemic cells. We show here that p210(bcr-abl) responsible for chronic myelogenous leukemia induces an amoeboid type of motility while p190(bcr-abl), associated with acute lymphoid leukemia, induces a rolling type of motility. We previously reported that p210(bcr-abl) activates RhoA and Rac1, while p190(bcr-abl) although devoid of a Dbl-homology (DH) domain activates Rac1, but not RhoA. We investigated the regulation of GDP/GTP exchange factor (GEF) activities in the Bcr-Abl complex. For that purpose, different GEF activity mutants of Vav and of Bcr-Abl were constructed and stably transfected in Ba/F3 cells. Using these mutants, we demonstrate that RhoA is exclusively activated by the DH domain of p210(bcr-abl), while Rac1 activation is mostly due to Vav. Inhibition of Rac1 by Vav GEF mutant leads to immobilization of cells. Vav depletion using shRNA also induces immobilization of cells and suppression of GTP-bound Rac1. RhoA inactivation induces the specific loss of amoeboid movements. These results suggest that Rac1 activation by Vav triggers the motility of Bcr-Abl-expressing Ba/F3 cells, while the specific amoeboid mode of motility induced by p210(bcr-abl) is a consequence of RhoA activation.