Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations.

BACKGROUND: Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients' genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)]. RESULTS: We identified a somatic PIK3CA mutation in resected lesions of 108 out of 143 patients (75.5%). The frequency of the variant allele ranged from 0.54 to 25.33% in tissues, and up to 47% in isolated endothelial cells. We detected a statistically significant difference in the distribution of mutations between patients with common and combined LM compared to the syndromes, but not with KTS. Moreover, the variant allele frequency was higher in the syndromes. CONCLUSIONS: Most patients with an common or combined lymphatic malformation with or without overgrowth harbour a somatic PIK3CA mutation. However, in about a quarter of patients, no such mutation was detected, suggesting the existence of (an)other cause(s). We detected a hotspot mutation more frequently in common and combined LMs compared to syndromic cases (CLOVES and PROS). Diagnostic genotyping should thus not be limited to PIK3CA hotspot mutations. Moreover, the higher mutant allele frequency in syndromes suggests a wider distribution in patients' tissues, facilitating detection. Clinical trials have demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. Genotyping might lead to an increase in efficacy, as treatments could be more targeted, and responses could vary depending on presence and type of PIK3CA-mutation.

Quality of life and clinical results after endovascular sclerotherapy: A comparison between intra- and extramuscular low-flow venous malformations.

BACKGROUND: Based on clinical observations we hypothesized that patients with intramuscular venous malformations (VMs) did worse or needed more sclerotherapy sessions than patients with extramuscular VMs. PURPOSE: To evaluate the difference in treatment and quality of life (QOL) results after Polidocanol sclerotherapy of intra- and extramuscular low-flow VMs. MATERIAL AND METHODS: Forty-one patients with a VM were treated with Polidocanol in two university hospitals. The results were retrospectively analyzed. Pre- and post-treatment magnetic resonance imaging (MRI) scans were compared. All patients completed a self-evaluating form on symptoms as well as a QOL questionnaire. The results were compared between two groups: intra- and extramuscular VM's. RESULTS: No statistically significant differences between intra- and extramuscular groups concerning QOL and specific dimensions pain, functional problems or cosmetic appearance were found. Radiological changes in MRI examinations did not correlate with any of the subjective symptoms. 56% of the patients benefitted from the treatment according to patient self-evaluation. CONCLUSION: In this material intramuscular VM's responded to the treatment comparably to extramuscular malformations. Post-treatment MRI findings do not correlate with subjective symptoms or QOL results and thus, a routine post-treatment examination seems to be unwarranted. Subjective symptoms and QOL results are the most important parameters in evaluating the effectiveness of sclerotherapy.

Quality of life after endovascular sclerotherapy of low-flow venous malformations: the efficacy of polidocanol compared with ethanol.

Background Limited information is available on mid-term results and quality of life (QOL) after endovascular sclerotherapy of venous malformations. Purpose To compare two agents-polidocanol and ethanol-with a focus on the influence on QOL after sclerotherapy. Material and Methods Forty-one consecutive patients with a venous malformation in the head and neck area or in the extremities were treated with polidocanol between 2008 and 2013. Pre- and post-treatment magnetic resonance imaging (MRI) scans were compared. All patients completed a self-evaluation form on symptoms as well as a QOL questionnaire. The results were compared with previously obtained material during 1991-2001, comprising 44 consecutive, similarly located venous malformation patients subject to ethanol sclerotherapy. Results No significant clinical complications were observed. Subjectively, 19 (46%) of the patients benefitted from the treatment. QOL results showed that 85% of patients had an index < 39 - where 0 represents the highest and 100 the lowest QOL. Patients in the ethanol group had marginally better overall post-treatment QOL results. Post-treatment MRI in 35 patients showed the size of the malformation unchanged in 19 (54%) patients, in ten (29%) there was a decrease (<50%) while in six (17%) the decrease was more significant (>50%). Post-treatment MRI results did not correlate with either subjective symptoms or QOL results. Conclusion Polidocanol sclerotherapy were found to be an effective, safe, and well tolerated treatment option for low flow venous malformations. Routine MRI for follow-up appears redundant and may be omitted.

Unilateral common cavity deformity: Recurrent meningitis due to insufficient newborn hearing screening.

Insufficient newborn hearing screening may leave the other ear with undetected hearing loss. Subsequently, the missed pathology behind the impairment may have potential risk for severe infections. We describe a case of recurrent Streptococcus pneumoniae meningitis in an infant with unilateral common cavity deformity. The diagnosis of the deaf left ear was delayed due to insufficient newborn hearing screening and not until the second meningitis the pathology behind the deafness was confirmed. Subtotal petrosectomy was performed unsuccessfully and resulted in another meningitis. We highlight the importance of proper newborn hearing screening and surgical technique to treat cochlear malformations.

[Tongue abscess]. / Kielipaise.

Tongue abscess is a rare and sometimes life-threatening condition, as swelling of the tongue may rapidly occlude the airways. In a patient described by us swelling of the tongue was found in MR imaging to be caused by an abscess of the anterior part of the tongue, extending to the floor of the mouth, beside the submandibular gland. It was only after recanalization of the compartmentalized abscess of the tongue and removal of the salivary gland that the patient recovered.

Efficacy of OK-432 sclerotherapy in treatment of lymphatic malformations: long-term follow-up results.

Lymphatic malformations (LMs) are rare congenital tumors of the lymphatic system often affecting the head and neck area. Because of cosmetic and functional symptoms most patients need to be treated. Traditionally surgical treatment has been considered to be the first-line treatment for LM. However, it is challenging because of the need for complete excision. The risk of poor cosmetic result and damage to surrounding structures is high. Since Ogita presented OK-432 as a treatment for LM in 1987, it has been widely used as the primary treatment. Many papers have been published on this topic but with relatively short follow-up times. We present a material of 36 LMs treated with OK-432 during the period of 1999-2009 and with an average follow-up time of 6 years. Immediate post-treatment results were compared with the late follow-up findings. Primary and late response to therapy was evaluated with an MRI scan by measuring the change in lesion size. At the follow-up visit, all patients were clinically examined and they answered a symptom questionnaire. Later 26/36 patients were also available for a quality of life questionnaire. Primarily 67% demonstrated a complete or marked response. At the follow-up 64% showed a complete or marked response, in 11% the final response was better than the initially observed and only 2 patients had relapsed. The initial response predicted the long-term outcome accurately and the effect of OK-432 sclerotherapy seems to be long lasting. According to the MRI evaluation 80% and subjectively 94% of the patients benefitted from the treatment. Quality of life questionnaire showed high post-treatment satisfaction. We found OK-432 sclerotherapy to be a safe and effective treatment with a long lasting effect in the management of macrocystic LMs.

[Chronic sclerosing sialadenitis - Küttner tumor]. / Krooninen sklerosoiva sylkirauhastulehdus - küttnerin tuumori.

Chronic sclerosing sialadenitis i.e. Küttner tumor is a rare inflammatory disease most commonly affecting the submandibular gland, due to clinical findings easily interpreted even as a malignant tumor. Our 45-year-old patient sought medical care due to a solid lump that had appeared under the right mandibular angle. The submandibular gland and associated hard mass were excised in a surgical operation conducted after the investigations. Histologic examination proved that the seldom diagnosed reactive Küttner tumor was in question.