Low risk of embryonic and other cancers in PIK3CA-related overgrowth spectrum: Impact on screening recommendations.

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.

Long-term adverse event: inflammatory orbitopathy induced by pembrolizumab in a patient with metastatic melanoma.

The recent advent of immune checkpoint inhibitors (ICI), including anti-programmed cell death 1 protein (anti-PD-1) agents has revolutionized the therapeutic approach of metastatic malignancies. Yet, ICI can disrupt immune tolerance resulting in enhanced immune activation in normal tissues with significant toxicity. A dysregulated activation of T-cells directed to normal tissues stands as the main mechanism of immune-related adverse events (irAE). To date, only two cases of immune-related inflammatory orbitopathy related to anti-PD-1 agents have been reported. This rare immune adverse event usually occurred early after ICI initiation. Here, we report the first case of late inflammatory orbitopathy occurring in a melanoma patient treated with pembrolizumab. Consequently, the occurrence of irAE under ICI should be monitored, even late after treatment instauration.

The scalp hair collar and tuft signs: A retrospective multicenter study of 78 patients with a systematic review of the literature.

BACKGROUND: Hair collar sign (HCS) and hair tuft of the scalp (HTS) are cutaneous signs of an underlying neuroectodermal defect, but most available data are based on case reports. OBJECTIVE: We sought to define the clinical spectrum of HCS and HTS, clarify the risk for underlying neurovascular anomalies, and provide imaging recommendations. METHODS: A 10-year multicenter retrospective and prospective analysis of clinical, radiologic, and histopathologic features of HCS and HTS in pediatric patients was performed. RESULTS: Of the 78 patients included in the study, 56 underwent cranial and brain imaging. Twenty-three of the 56 patients (41%) had abnormal findings, including the following: (1) cranial/bone defect (30.4%), with direct communication with the central nervous system in 28.6%; (2) venous malformations (25%); or (3) central nervous system abnormalities (12.5%). Meningeal heterotopia in 34.6% (9/26) was the most common neuroectodermal association. Sinus pericranii, paraganglioma, and combined nevus were also identified. LIMITATIONS: The partial retrospective design and predominant recruitment from the dermatology department are limitations of this study. CONCLUSIONS: Infants with HCS or HTS are at high risk for underlying neurovascular anomalies. Magnetic resonance imaging scans should be performed in order to refer the infant to the appropriate specialist for management.

Nail Psoriasis: A Systematic Evaluation in 313 Children with Psoriasis.

BACKGROUND/OBJECTIVES: Little information is available on the prevalence and clinical aspects of nail involvement in children with psoriasis. The objective of this study was to evaluate the prevalence and clinical aspects of and the risk factors for nail involvement in French children with psoriasis. METHODS: We performed a multicenter, cross-sectional study in 23 French dermatology centers. All children seen during the 1-year study were systematically included. Clinical features of the nails were collected. Association with clinical aspects of the disease and comorbidities were evaluated. RESULTS: Of 313 children with psoriasis (mean age 9.1 ± 4.2 yrs; 149 boys, 164 girls), 31.1% had familial psoriasis and 30% had severe psoriasis. The mean age at onset was 6.1 ± 3.7 years. Nails were involved in 32.3% of children. The main clinical aspects were pitting (69.1%) for fingernails and onycholysis (40.0%) and pachyonychia (27.5%) for toenails. All of the fingers were involved at similar frequencies, whereas the big toe was involved twice as often as the others (p < 0.005). Nail involvement was associated with male sex (p < 0.001), palmoplantar psoriatic (p < 0.001), severity of disease (p = 0.003), and psoriatic arthritis (p = 0.03). CONCLUSION: The prevalence of nail involvement was 32.3% in children with psoriasis. Clinical aspects in children are reported, as well as clinical associations. As in adults, nail psoriasis is closely associated with psoriatic arthritis.

Skin Patterns Associated with Upper Airway Infantile Haemangiomas: A Retrospective Multicentre Study.

The aim of this study was to define the skin patterns at high risk for upper airway infantile haemangioma. A retrospective multicentre French observational study was conducted between January 2006 and January 2015 and all confirmed airway haemangioma were included. Thirty-eight patients with airway haemangioma from 9 centres were included. Thirty-one patients had a cutaneous or mucosal haemangioma: 21 with a location considered at high risk for airway haemangioma (large segmental mandibular haemangioma), 4 with a very mild facial involvement (lower lip or S1 (frontotemporal segment according to Haggstrom and Frieden)) and 6 with either lesions of the neck or body, or association of both. We report here the largest cohort of airway haemangioma. A third of patients do not completely fit with the definition of the high-risk area of airway haemangioma. Segmental lower lip and neck involvement also seem to be very suggestive areas. Clinicians must be able to recognize these areas.

Intracranial hemorrhage caused by dabrafenib and trametinib therapy for metastatic melanoma.

Although generally well tolerated compared with chemotherapy, molecular targeted therapy used in metastatic melanoma may be associated with life-threatening toxicity. We report the case of a patient with metastatic melanoma treated by dabrafenib plus trametinib who developed intracranial hemorrhage. Physicians should be aware of this rare but life-threatening adverse event of B-rapidly accelerated fibrosarcoma (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. However, they should be also careful about the bleeding origin, which can prove to be a new onset of melanoma metastasis or anticoagulation overdose, or even an uncontrolled arterial hypertension.

Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis.

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.