Infantile fibrosarcoma with an EGFR kinase domain duplication: Underlining a close relationship with congenital mesoblastic nephroma and highlighting a similar morphological spectrum.

Infantile fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) are locally aggressive tumors primarily occurring in infants. Both IFS and the cellular subtype of CMN show overlapping morphological features and an ETV6-NTRK3 fusion, suggesting a close relationship. An activating alteration of EGFR, based on an EGFR kinase domain duplication (KDD), occurs in a subset of CMNs lacking an NTRK3 rearrangement, especially in the classic and mixed type. So far no EGFR-KDDs have been detected in IFS. We describe four pediatric tumors at the extremities (leg, n = 2; foot and arm n = 1) with histological features of IFS/CMN. Two cases showed classic IFS morphology while two were similar to classic/mixed type CMN. In all cases, an EGFR-KDD was identified without detection of a fusion gene. There were no abnormalities of the kidneys in any of the patients. This is the first description of IFS with an EGFR-KDD as driver mutation, supporting that IFS and CMN are similar lesions with the same morphological and genetic spectrum. Pathologists should be aware of the more fibrous variant of IFS, similar to classic/mixed type CMN. Molecular analyses are crucial to treat these lesions adequately, especially with regard to the administration of tyrosine kinase inhibitors.

Parenting Children With a Cleft Lip With or Without Palate or a Visible Infantile Hemangioma: A Cross-Sectional Study of Distress and Parenting Stress.

OBJECTIVE: Parents of children with a medical condition and a visible difference can experience challenging situations. We evaluated distress and parenting stress in parents of children with a cleft lip with or without cleft palate (CL±P) or a visible infantile hemangioma (IH). SETTING: This cross-sectional study took place in an academic medical hospital in Rotterdam, the Netherlands. PARTICIPANTS: Three-hundred nine parents (mean age = 40.30, 56.00% mothers) of children with CL±P and 91 parents (mean age = 36.40, 58.24% mothers) of children with IH. MAIN OUTCOME MEASURES: The Dutch version of the Parenting Stress Index - Short Form and the subscales Anxiety, Depression, and Hostility of the Symptom Checklist - 90. RESULTS: One sample t tests and mixed linear modeling were used. On average, parents of children with CL±P and of children with IH showed significantly lower parenting stress compared to normative data. Anxiety was significantly lower in parents of children with CL±P than that in the norm group. Visibility of the condition was not related to distress or parenting stress. Child behavioral problems were positively related to parenting stress, depression, and hostility. CONCLUSIONS: Parents of children with CL±P and IH report less distress and parenting stress compared to the norm. On average, these parents seem well adjusted. A practical implication is to monitor parents of children with behavioral problems.

Intractable vascular autonomic dysregulation (Harlequin phenomenon) in two brothers: another indication for propranolol?

Vascular autonomic dysregulation, in the most extreme presentation known as Harlequin phenomenon, is a rare condition. It manifests as a sudden and brief paroxystic change in skin color, resulting in two different colors on the body. It is supposed that this condition occurs due to a vasomotor instability. This again is caused by sympathetic disautonomy, which is a consequence of hypothalamic peripheral vascular tone control immaturity in the newborn. Typically, there is spontaneous regression. We describe two brothers who both had this condition in their first life years. Clinical symptoms included frequent attacks of discoloration of extremities (up to four times per day) accompanied with terrifying crying fits, interpreted by the parents as pain. These patients were treated with propranolol, a nonselective beta-blocker, resulting in improvement of symptoms: only occasional attacks were seen. Beta-blockers act on ß1 -adrenoceptors in the heart, thereby preventing the positive chronotropic and inotropic effects mediated by these receptors. We hypothesize that propranolol, which is very lipophilic and therefore also acts on ß-receptors of the central nervous system, acts on the sympathetic system.

Treatment of small superficial haemangioma with timolol 0.5% ophthalmic solution: a series of 20 cases.

BACKGROUND: Haemangioma of infancy (HOI) on the face may be disfiguring and alarming for parents. Usually they are not treated when they are small. Treatment of HOI with propranolol is a breakthrough. Timolol (topical treatment) and propranolol are closely related. METHODS: We considered topical treatment with timolol 0.5% ophthalmic solution 3-4 times daily in patients with small HOI. Twenty patients with small mostly superficial HOI were included. RESULTS: A series of 20 patients with HOI treated with timolol 0.5% ophthalmic solution are described. The treatment was effective in all superficial HOIs after 1-4 months. A quick direct inhibitory effect on the growth of the HOI followed by slower regression was observed. The children had to be treated during the whole proliferative phase. Deep HOIs on the nose (2 cases) and lower eyelid (1 case) showed no response. CONCLUSION: Topical timolol 0.5% ophthalmic solution is effective in HOI. Safety and effectiveness of drugs like topical timolol and topical propranolol require further investigation but they seem very safe when used in small HOIs. We recommend that small superficial HOIs should be treated in an early proliferative phase.

Haemangioma of infancy: two case reports with an overdose of propranolol.

An 8-week-old infant was treated with oral propranolol for a haemangioma of infancy. The standard dose (according to protocol) is 2 mg/kg/day but, because of a mistake by the pharmacist, the child was treated with 8 mg/kg/day without any side effects (pulse, blood pressure and glucose stayed normal).

Scoring the proliferative activity of haemangioma of infancy: the Haemangioma Activity Score (HAS).

BACKGROUND: Haemangioma of infancy (HOI) is the most frequently occurring benign tumour of infancy. A good, reliable and objective scoring system for haemangioma activity is not yet available. AIM: We have developed a simple system called the Haemangioma Activity Score (HAS) for scoring the (disease) proliferative activity of haemangiomas. The current study was undertaken to validate this system. METHODS: We validated the HAS in a comparative study of photographs taken during consultations from 2000 until 2008 (n = 78). Agreement between three observers was assessed at two different time points (t(0) and t(1)) with a minimum interval of 6 months between them, using interclass correlation coefficients (ICC). RESULTS: Agreement between observers was good. The average ICC of the HAS at t(0) and t(1) was 0.72 and 0.76, respectively. The average ICC of the HAS for the changes from baseline (HAS at t(0) minus HAS at t(1) ) was 0.69. CONCLUSIONS: We conclude that the HAS is a good system for scoring the proliferative activity of haemangiomas, and believe it to be useful in future investigations. The number of studies comparing different therapies for treating haemangiomas is steadily increasing, and the HAS (before and after treatment) may provide a valuable scoring system for evaluating such therapies.

Collodion baby: a follow-up study of 17 cases.

Seventeen cases of collodion baby are reported. Clinical aspects, complications, treatment, final outcome and family history were studied. We did not observe any clinical features in the collodion baby that could serve as a clue in predicting the final diagnosis. Infections were observed in nine, hypothermia in five and hypernatraemic dehydration in four cases. Skin infection mainly occurred in babies treated with emollients (petrolatum, lanolin and cetomacrogolis cream were used). We therefore recommend treating the collodion baby in a humidified incubator, if necessary with intravenous rehydration, but not to use emollients. The final outcome of these study patients was erythrodermic autosomal recessive lamellar ichthyosis in seven cases (41%), non-erythrodermic autosomal recessive lamellar ichthyosis in three cases (18%), Sjögren-Larsson in one case (6%), epidermolytic hyperkeratosis in one case (6%), acute neonatal variant of Gaucher disease in one case (6%) and normal skin in four cases (24%).