Case Reports of Fatal or Metastasizing Melanoma in Children and Adolescents: A Systematic Analysis of the Literature

Childhood melanoma (ChM) is rare, with clinical and epidemiologic characteristics that differ from those of adult melanomas. The objective of the current study was to systematically identify and analyze case reports and case series of fatal and metastasizing ChM in the medical literature. ChM case reports with a fatal outcome or metastases were identified using a Medline search and subdivided into ChM developing in the absence of a congenital melanocytic nevus (ChM without CMN) and ChM associated with a CMN (ChM with CMN); 258 cases of ChM without CMN (206 cutaneous, 52 noncutaneous) were identified. In cutaneous ChM without CMN with a fatal outcome (n = 155), the mean age at diagnosis was 13.1 years (median 14 yrs). The mean Breslow index in this group was 8.5 mm for children ages 0 to 10 years and 3.7 mm for children ages 11 to 18 years. In ChM with CMN (n = 178; 112 cutaneous, 66 central nervous system [CNS]), the mean age at diagnosis was 5.8 years for cutaneous melanoma (median 3 yrs) and 5.5 years for CMN‐associated CNS melanoma (median 3 yrs). The majority of CMN‐associated cutaneous melanomas developed in small and giant CMN (vs medium and large); 53.9% of CNS melanomas developed in patients with multiple medium CMN. This study represents the largest and most complete synopsis of ChM case reports in the medical literature. Our analysis supports the view that cutaneous ChM without CMN (or associated with smaller CMN) differs in several important aspects from ChM associated with large or giant CMN.     

CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis

We investigated a patient who developed multiple sclerosis (MS) during treatment with the CTLA4‐blocking antibody ipilimumab for metastatic melanoma. Initially he showed subclinical magnetic resonance imaging (MRI) changes (radiologically isolated syndrome). Two courses of ipilimumab were each followed by a clinical episode of MS, 1 of which was accompanied by a massive increase of MRI activity. Brain biopsy confirmed active, T‐cell type MS. Quantitative next generation sequencing of T‐cell receptor genes revealed distinct oligoclonal CD4⁺ and CD8⁺ T‐cell repertoires in the primary melanoma and cerebrospinal fluid. Our results pinpoint the coinhibitory molecule CTLA4 as an immunological checkpoint and therapeutic target in MS. Ann Neurol 2016;80:294–300     

Psoriasis: to treat or to manage?

The recognition of psoriasis as a systemic disorder with characteristic skin symptoms and associated diseases has changed treatment concepts substantially. The complexity of psoriasis disease not only requires appropriate therapy but also weight‐loss and smoking cessation programmes as well as trigger factor elimination. The term ‘management’ may better reflect the aim for a holistic approach of disease control. Comorbidity and the presence of psoriatic arthritis are important denominators for drug selection. However, there is a lack of prospective data substantiating a benefit of associated diseases by antipsoriatic therapy. Securing success using treatment goals helps to establish an efficacious therapy and to control inflammation. A regular scoring of disease severity, patients’ quality of life and assessment of other clinically relevant conditions are mandatory to closely follow the disease course. There is debate whether an early treatment may modulate the future course of psoriasis. Concepts of minimal disease activity have not been implemented in psoriasis yet. There is a lack of evidence how long any treatment should be given and when and how to terminate. Finally, outcome tools should specifically be tailored for psoriasis to evaluate disease‐related items as well as the benefit of management from the patient's perspective.     

Is the knowledge of contact force beneficial in pulmonary vein antrum isolation?

Objective: To investigate the effect of the operator knowing the real-time contact force (CF) on the efficacy of pulmonary vein antrum isolation (PVAI).

Methods: Fifty patients with paroxysmal atrial fibrillation (AF) or short lasting persistent AF were randomized to CF guided PVAI (n?=?25) or conventional PVAI (n?=?25). In the CF guided group, CF between 10 and 40?g was aimed at. Efficacy of PVAI was measured as reduction in AF burden (AFB) and time to AF recurrence detected by implantable cardiac monitor (ICM), inserted three months before PVAI. Blanking period was three months and follow-up 12 months.

Results: All pulmonary veins were isolated in the CF guided group and all but one in the conventional group. Mean CF was 25?g in the CF guided group and 24?g in the conventional group (p?=?0.75). Compared to pre-ablation, median [IQR] relative reduction in AFB 3–12 months after ablation was 100 [99–100]% in the CF guided group (p?p?p?=?0.09). Nine patients (36%) had AF recurrence in the CF guided group and 13 (52%) in the conventional group (p?=?0.21, log-rank test). CF differed between operators. When adjusted for operator by regression analysis, patients without recurrent AF had lower proportion of ablation time with CF <10?g than recurrent patients (p?=?0.034). No complications occurred.

Conclusions: Operator knowledge of real-time CF had no significant effect on AFB reduction or time to AF recurrence. Larger trials should be done to study benefit of real-time CF.     

Cardiovascular biomarkers in patients with psoriasis

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C‐reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low‐density lipoprotein (ox‐LDL), human matrix Gla protein (MGP) and fetuin‐A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin‐A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox‐LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin‐A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high‐need patients with psoriasis.     

Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma

Hereditary papillary renal carcinoma (HPRC) is a highly penetrant hereditary renal cancer syndrome caused by germline missense mutations in the c-MET proto-oncogene. HPRC is clinically characterized by multiple bilateral papillary renal-cell carcinomas. Here we report a family with a novel missense mutation in c-MET. The original pathology report of four primary kidney cancers (1988–1997) revealed renal-cell carcinoma. A revised report described multiple adenomas and papillary renal-cell carcinomas with focal clear cells and a mixture of type 1 and type 2 pattern, emphasizing the importance of revised pathology examinations in possible hereditary renal-cell carcinomas especially when described before 1997.