Leser-Trélat sign presenting in a patient with ovarian cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Seborrheic keratoses are very common findings in elderly patients. However, a sudden onset and dramatic increase in the number and size of these benign lesions deserves special attention, since this may represent the Leser Trélat sign, a rare paraneoplastic cutaneous syndrome.</p> <p>Case presentation</p> <p>A 92-year-old female presented to our clinic with multiple eruptive seborrheic keratoses, which had dramatically increased in size and number over the past two years. A diagnostic work-up revealed an ovarian carcinoma. Hence, cutaneous findings in our patient were consistent with the diagnosis of the Leser-Trélat sign.</p> <p>Conclusion</p> <p>The Leser-Trélat sign may coincide with the diagnosis of occult cancer or follow or precede it by months or years. Practitioners should take cases of eruptive seborrheic keratoses seriously and perform thorough patient examinations.</p

Effects of Radiotherapy in the treatment of multiple myeloma: a retrospective analysis of a Single Institution

Background: Palliative irradiation of osteolytic lesions is a considerable component in the treatment for patients with multiple myeloma. In this study, we analyzed the efficacy of irradiation in these patients. Patients and methods: We retrospectively analyzed 153 patients with multiple myeloma who were admitted to our department between 1989 and 2013. According to the staging system of Durie & Salmon 116 patients were classified as stage III. 107/153 patients were treated with radiotherapy of at least one and up to 6 bony lesions at different times. In order to evaluate the effect of local radiotherapy on pain relief and bone recalcification a uni-and multivariate analysis was performed using a binary logistic regression model to correct for multiple measurements. Complete information on dose, fractionation and volume of radiotherapy was available from 81 patients treated in 136 target volumes for pain relief, and from 69 patients treated in 108 target volumes for recalcification. Total radiation doses varied between 8 Gy to 50 Gy (median dose 25 Gy in 2.5 Gy fractions, 5 times a week). Results: Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. In the univariate analysis, higher total radiation doses (p = 0.023) and higher age (p = 0.014) at the time of radiotherapy were significantly associated with a higher likelihood of pain relief, whereas no significant association was detected for concurrent systemic treatment, type and stage of myeloma and location of bone lesions. The same variables were independent predictors for pain relief in the multivariate analysis. Recalcification was observed in 48% of irradiated bone lesions. In the uni-and multivariate analysis higher radiation doses were significantly associated (p = 0.048) with an increased likelihood of recalcification. Side effects of radiotherapy were generally mild. Conclusions: Higher total biological radiation doses were associated with better pain relief and recalcification in this retrospective evaluation of multiple myeloma patients. In addition, in the elderly the therapeutic measures appear to develop a better analgesic effect

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations

Mutations in LAMA1 Cause Cerebellar Dysplasia and Cysts with and without Retinal Dystrophy

Cerebellar dysplasia with cysts (CDC) is an imaging finding typically seen in combination with cobblestone cortex and congenital muscular dystrophy in individuals with dystroglycanopathies. More recently, CDC was reported in seven children without neuromuscular involvement (Poretti-Boltshauser syndrome). Using a combination of homozygosity mapping and whole-exome sequencing, we identified biallelic mutations in LAMA1 as the cause of CDC in seven affected individuals (from five families) independent from those included in the phenotypic description of Poretti-Boltshauser syndrome. Most of these individuals also have high myopia, and some have retinal dystrophy and patchy increased T2-weighted fluid-attenuated inversion recovery (T2/FLAIR) signal in cortical white matter. In one additional family, we identified two siblings who have truncating LAMA1 mutations in combination with retinal dystrophy and mild cerebellar dysplasia without cysts, indicating that cysts are not an obligate feature associated with loss of LAMA1 function. This work expands the phenotypic spectrum associated with the lamininopathy disorders and highlights the tissue-specific roles played by different laminin-encoding genes