Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) preferentially involves the lower limb in elderly subjects. A combination of polychemotherapy and rituximab has improved prognosis. However, about 50% of patients will experience progression or relapse without any predictive biologic marker of therapeutic response. The mutational profile of PCLBCL-LT has highlighted mutations contributing to constitutive NF-kB and B-cell receptor (BCR) signaling pathways but has not demonstrated clinical utility. Therefore, the mutational status of 32 patients with PCLBCL-LT (14 patients with complete durable response and 18 patients with relapsing or refractory disease) was determined with a dedicated lymphopanel. Tumor pairs at diagnosis and relapse or progression were analyzed in 14 relapsing or refractory patients. Patients with PCLBCL-LT harboring one mutation that targets one of the BCR signaling genes, CD79A/B or CARD11, displayed a reduced progression-free survival and specific survival (median 18 months, P ¼ 0.002 and 51 months, P ¼ 0.03, respectively, whereas median duration in the wild-type group was not reached) and were associated with therapeutic resistance (P ¼ 0.0006). Longitudinal analyses revealed that MYD88 and CD79B were the earliest and among the most mutated genes. Our data suggest that evaluating BCR mutations in patients with PCLBCL-LT may help to predict first-line therapeutic response and to select targeted therapies.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. Combination of ICI with ipilimumab cytotoxic T-lymphocyte antigen-4 and nivolumab [anti-programmed cell death-1 (PD-1)] improves tumoral response compared to anti-PD1 monotherapy in melanoma patients, but is associated with more severe and multiple immune-related adverse events. We report the first case of aseptic cystitis induced by ipilimumab and nivolumab combination in a 61-yearold melanoma patient. She described after two infusions, diarrhea, pollakiuria, intense bladder pain, urinary urgency, and nocturia. Repeated negative urine culture tests led to perform cystoscopy. Mucosal bladder biopsies showed lymphocytic T-cells infiltration in intraepithelial and in subepithelial connective tissue, which were consistent with the diagnosis of immune-related aseptic cystitis. Aseptic cystitis is a rare and poorly known side-effect related to ICI. Only four other cases with anti-PD1 monotherapy were found in literature, only in Japanese patients. It simulates bacterial cystitis with negative urinary tests, and is often associated with atypical symptoms like diarrhea, which may delay the diagnosis. Oral steroids appear to be the most efficient therapeutic options. Melanoma Res 31: 487
K E Y W O R D S : allergic contact dermatitis, case report, children, fingertip dermatitis, methylchloroisothiazolinone, methylisothiazolinone, noise putty, slime Methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) are the main allergens of the last decade in adults, and cases are being increasingly reported in children. We present a case of fingertip dermatitis in a young boy caused by exposure to a "noise putty" related to contact allergy to MCI/MI. CASE REPORTA 7-year-old boy was referred because of a 1-year history of recalcitrant chronic hand dermatitis. He had a history of asthma and familial atopy, but not of atopic dermatitis. Clinical examination showed FIGURE 1 (A), Fingertip dermatitis with erythematous and fissured lesions. (B), Positive reactions to methylchloroisothiazolinone (MCI) (++), methylisothiazolinone (MI) (++), "noise putty" (red circle) (++), and fragrance mix I (+) DUCHARME ET AL. 393eczema involving all fingertips ( Figure 1A). This was not influenced by school or sport activities. He had been treated with topical steroids, achieving partial improvement but with many relapses. Patch testing was performed by the use of IQ Ultimate chambers (Chemotechnique Diagnostics, Vellinge, Sweden) fixed on the upper back with an occlusion time of 48 hours with Urgoderm (URGO, Chenove, France). The patient was tested with the European baseline series adapted for children 1 and with his hygiene and cosmetic products, topical drugs applied, school materials, and various toys. Readings were performed on day (D) 2 and D3. Patch test results were strong positive on D2 (+ +) and D3 (++) for MI 2000 ppm aq., MCI/MI 200:100 ppm aq., and1 of the patient's toys: a manufactured "noise putty" ( Figure 1B). We also observed a weak positive reaction to fragrance mix I 8% pet. The "noise putty" was deemed to be of probable clinical relevance. Indeed, the patient's father noticed that the fingertip dermatitis worsened after the boy handled it. We instructed the parents and the boy to stop using this paste, and to avoid MCI and MI as preservatives. At a 1-year follow-up, resolution of symptoms with no relapse was documented. DISCUSSIONBoth preservatives, MCI and MI, are well-known causes of allergic contact dermatitis resulting from the use of cosmetics, detergents, and industrial products. In small children, the main sources are nappies and wet wipes. 2,3 "Noise putty" is a manufactured playdough that has become very popular among children, and that makes amusing noises.The "noise putty" in the present case had been bought at a fairground, with the information on the packaging stating "produced in China", but containing no ingredients list. Therefore, we contacted one of the biggest French importers of "noise putty" to inquire about the usual composition; it gave us a non-exhaustive list, despite our repeated requests: "polyvinyl alcohol, glycerine, borax, ethyl paraben, deionized water and various dyes". The regional Poison Control Centre confirmed that isothiazolinones are used in dyes contained in man...
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