E. Tournier

Double‐positive CD4/CD8 mycosis fungoides: a rarely reported immunohistochemical profile

Mycosis fungoides (MF) represents the most common epidermotropic cutaneous T‐cell lymphoma (CTCL), and tumor cells typically express a mature T‐helper memory phenotype. A minority of MF patients display an unusual phenotype, which may be either CD4(−)/CD8(+) or double negative. Herein, we report a case of biopsy‐proven MF in a 31‐year‐old woman who presented with infiltrated plaques involving photoprotected areas of the skin. Immunohistochemical study combined with confocal microscopy revealed co‐expression of CD4 and CD8 in a subset of atypical T lymphocytes. To our knowledge, this is the second report of a CD4/CD8 dual‐positive MF.

Highly Concordant Results Between Immunohistochemistry and Molecular Testing of Mutated V600E BRAF in Primary and Metastatic Melanoma.

This study tested the sensitivity and specificity of VE1 antibody raised against BRAFV600E protein, on 189 melanoma samples, compared with molecular testing. In addition, the therapeutic response to BRAF inhibitors was analysed in 27 patients, according to staining intensity (scored from weak to strong) and pattern (homogeneous or heterogeneous). BRAFV600E status during melanoma progression was evaluated in a cohort of 54 patients with at least paired-samples. High sensitivity (98.6%) and specificity (97.7%) of VE1 were confirmed. During melanoma progression different samples showed concordant phenotypes. Heterogeneous VE1 staining was observed in 28.5% of cases, and progression-free survival was higher in patients with tumour samples displaying such staining. These findings suggest that only VE1-negative tumours would be genotyped to detect other BRAFV600 mutations, and that either primary melanoma or metastasis can be tested using immunohistochemistry, according to the material available.

Tumour lysis syndrome: an unexpected adverse event associated with ipilimumab

gangrenosum in the biologic era, the response to therapy. Aliment Pharmacol Ther 2013; 38: 563–572. 4 Jaimes-L opez N, Molina V, Arroyave JE et al. Development of pyoderma gangrenosum during therapy with infliximab. J Dermatol Case Rep 2009; 3: 20–23. 5 Fiorino G, Danese S, Pariente B et al. Paradoxical immune-mediated inflammation in inflammatory bowel disease patients receiving antiTNF-a agents. Autoimmun Rev 2014; 13: 15–19. 6 Rozenbaum M, Boulman N, Slobodin G et al. Polyarthritis flare complicating rheumatoid arthritis infliximab therapy: a paradoxic adverse reaction. J Clin Rheumatol 2006; 12: 269–271. 7 Takahashi T, Asano Y, Shibata S et al. Arthritis possibly induced and exacerbated by TNF antagonist in a patient with psoriasis vulgaris. Br J Dermatol 2015; 172: 1458–1460. 8 Lee M, Petroniene R, Thorne C. New onset of inflammatory polyarthritis in a patient taking adalimumab. J Rheumatol 2009; 36: 660. 9 Van RD, Mooij JE, Baeten DL et al. New-onset polyarthritis during successful treatment of hidradenitis suppurativa with infliximab. Br J Dermatol 2011; 165: 194–198. 10 Villani AP, Weiler L, Jullien D et al. Paradoxical psoriatic arthritis in a patient with rheumatoid arthritis treated by TNFa blocker. Joint Bone Spine 2014; 81: 455–456.

Telangiectasia macularis eruptiva perstans (TMEP): A form of cutaneous mastocytosis with potential systemic involvement

BACKGROUND Telangiectasia macularis eruptiva perstans (TMEP) has not been fully characterized. OBJECTIVE We sought to estimate the frequency and clinical characteristics of TMEP in a cohort of adult patients with cutaneous mastocytosis, and to assess the presence of systemic involvement. METHODS We included all consecutive patients evaluated for cutaneous mastocytosis in 2 centers: the Mastocytosis Competence Center of the Midi-Pyrénées from May 2006 to December 2013, and the French Reference Center for Mastocytosis from January 2008 to September 2013. Skin phenotype, histopathology, presence of KIT mutation in the skin, and assessment of systemic involvement according to World Health Organization (WHO) criteria were prospectively investigated. RESULTS Of 243 patients with cutaneous mastocytosis, 34 (14%) were given a diagnosis of TMEP. The diagnosis of systemic mastocytosis was established in 16 patients (47%) with TMEP. Three patients (9%) had aggressive systemic mastocytosis (C-findings according to WHO). In all, 32 patients (94%) exhibited at least 1 mast cell activation-related symptom. LIMITATIONS Patient recruitment was undertaken at 2 referral centers with expertise in the diagnosis and treatment of mastocytosis so that the clinical findings and incidence of systemic involvement may be overestimated in comparison with the overall population of patients with TMEP. CONCLUSION TMEP accounts for about 14% of patients with cutaneous mastocytosis. The disease manifests as mast cell activation symptoms in almost all patients and can be associated with systemic involvement in about 50% of cases.

Chemotherapy-Related Reticulate Hyperpigmentation: A Case Series and Review of the Literature

Background: Inherited or acquired reticulate hyperpigmentation represents a heterogeneous group of infrequent dermatological conditions. The development of reticulate hyperpigmentation has so far been rarely reported to be associated with chemotherapeutic agents, including fluorouracil, bleomycin or a combination of cytarabine and idarubicin. Case Reports: We describe 5 cases of chemotherapy-related reticulate hyperpigmentation in patients treated with different chemotherapeutic regimens, in particular paclitaxel or cytarabine. The lesions were similar in all cases, with reticulate and/or linear hyperpigmented streaks, which were mainly located to the back and buttocks. Histology showed increased melanogenesis, which suggests a direct toxic effect of chemotherapy on melanocytes. Reflectance confocal microscopy was performed in 2 patients showing a similar pattern, with an increased amount of melanin in basal keratinocytes. These features have been compared with the available data through a literature review. Conclusion: Reticulate hyperpigmentation is an underestimated but characteristic complication of chemotherapy. Neither specific management nor discontinuation of the chemotherapeutic regimen is required.

Efficacy of anti-programmed cell death-1 immunotherapy for skin carcinomas and melanoma metastases in a patient with xeroderma pigmentosum

Xeroderma pigmentosum (XP) is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti‐programmed cell death‐1 (PD‐1) antibody on both melanoma and skin carcinoma in a patient with XP. A 17‐year‐old patient presented with metastatic melanoma and multiple nonmelanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti‐PD‐1 antibody, at a dose of 2 mg kg−1, every 3 weeks. Parallel therapeutic efficacy of anti‐PD‐1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24. This observation suggests anti‐PD‐1 may be considered in patients with XP and metastatic melanoma in addition to advanced nonmelanoma skin cancer.This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bjd.16270 This article is protected by copyright. All rights reserved. PROFESSOR CARLE F PAUL (Orcid ID : 0000-0003-0165-5263)

Bone marrow tryptase as a possible diagnostic criterion for adult systemic mastocytosis

Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ.

Panniculitis Associated with MEK Inhibitor Therapy: An Uncommon Adverse Effect

The combination of MEK inhibitor (cobimetinib, trametinib) and BRAF inhibitor (vemurafenib, dabrafenib) is now the first-line treatment in patients with BRAF V600-mutated metastatic melanoma. This association reduces cutaneous adverse events induced by BRAF inhibitors alone, including photosensitivity, hand-foot syndrome, hyperkeratosis, alopecia, skin papillomas, keratoacanthomas, and squamous-cell carcinomas. While panniculitis has exceptionally been reported with BRAF inhibitors, this rare side effect has never been described with the use of MEK inhibitors. We present here the first observation of panniculitis strictly induced by MEK inhibitors. Indeed, 10 days after the initiation of combined treatment with cobimetinib and vemurafenib for metastatic melanoma, our patient developed panniculitis predominantly on the upper and lower extremities. These cutaneous nodules disappeared during cobimetinib intermissions and recurred while the molecule was resumed. Recurrence of cutaneous nodules was observed after initiation of trametinib combined with dabrafenib, and resolved once again with trametinib discontinuation. We believe that clinicians should be aware of this cutaneous adverse event in patients treated with combined therapy, which can lead to unfounded BRAF inhibitor treatment discontinuation and compromise the antitumor response. Our case suggests a class effect linked with the MEK inhibition pharmacodynamic activity. Finally, laboratory investigation and histopathological examination are mandatory to exclude other panniculitis etiologies and subcutaneous metastasis of melanoma.

Prevalence and risk factors for fragility fracture in systemic mastocytosis

OBJECTIVES Systemic mastocytosis (SM) is characterized by the accumulation of mast cells in tissues other than the skin. Bone involvement although frequent has not been thoroughly evaluated. Primary objective was to determine risk factors associated with fragility fractures (FF) in SM. Secondary objectives were to evaluate the ability of bone marrow tryptase (BMT) level to identify patients with FF, and to describe bone involvement in SM. METHODS We analyzed retrospectively all consecutive patients seen in our expert center, with a diagnosis of SM according to the 2001 WHO criteria, and with complete bone assessment. We collected data about lifetime fractures, types of cutaneous manifestations, degranulation symptoms, blood and BMT levels, bone mineral density assessed by densitometry and KIT mutation. We performed a univariate analysis investigating the factors associated with FF and then a logistic multivariable regression analysis. We assessed the ability of bone marrow tryptase to identify patients with FF. RESULTS Eighty-nine patients with SM were included. Thirty-six patients (40.4%) suffered from osteoporosis and twenty-five (28.1%) experienced lifetime FF. Univariate analysis identified age at diagnosis and disease onset, presence of telangiectasia macularis eruptiva perstans, digestive symptoms, mast cells activation symptoms, elevated BMT, low femoral and lumbar BMD, as associated with FF. Multivariate analysis identified elevated BMT, low femoral T score and older age at diagnosis as independently associated with FF. CONCLUSIONS Low femoral T-score, BMT level, and older age at diagnosis are markers associated with FF in SM. BMT may represent an important biomarker to predict FF in SM patients.

Cutaneous inflammatory myofibroblastic tumours can be anaplastic lymphoma kinase-positive: report of the first four cases.

Inflammatory myofibroblastic tumours (IMTs) usually have a soft tissue and visceral localization, but have been rarely reported in skin. The aim of this study was to characterize the histological and immunohistochemical features of a series of cutaneous IMTs.