Capillary malformation-arteriovenous malformation syndrome: a multicentre study.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM: To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS: We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS: In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS: Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

Interobserver variability in the classification of childhood maculopapular cutaneous mastocytosis.

BACKGROUND: Maculopapular cutaneous mastocytosis (MPCM) in children is classified in two variants: (i) monomorphic variant, presenting with the small macules or papules typically seen in adult patients; and (ii) polymorphic variant with larger lesions of variable size and shape, typically seen in children. The definition of polymorphic and monomorphic variants is mostly intuitive, and a validation of this classification has not been done. OBJECTIVE: To study interobserver variability in the classification of MPCM in two groups of observers: mastocytosis experts and general dermatologists. MATERIALS AND METHODS: Nineteen cases of childhood MPCM were shown blindly, for classification as monomorphic or polymorphic type, to 10 independent observers (eight dermatologists, one allergist and one haematologist) from Europe and North America with a vast experience in the management of paediatric mastocytosis. Also, the same cases were shown on a screen to 129 general dermatologists attending a meeting; their votes were registered by remote controls. The interobserver variability kappa coefficient (with 95% confidence interval) was calculated to measure the reliability of the correlation. RESULTS: The value of kappa interobserver variability coefficient for the group of 10 experts (95% confidence interval) was 0.39 (0.18-0.63), which is considered as 'fair'. The value of kappa interobserver variability coefficient for the group of 129 general dermatologists (95% confidence interval) was 0.17 (0.06-0.39), which is considered as 'slight'. A complete agreement of all 10 experts was achieved in only four of 19 cases (21.1%) The most voted choice was concordant between the two groups in only 11 of the 19 cases. CONCLUSIONS: We failed to validate the classification system of childhood MPCM in monomorphic and polymorphic types. While the rate of agreement was low for mastocytosis experts, it was nearly the agreement expected by chance in general dermatologists.

Histopathological hallmarks of cutaneous lesions of capillary malformation-arteriovenous malformation syndrome.

IMPORTANCE: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a recently described syndrome with distinctive cutaneous lesions. Very little is known about the histopathology of these lesions. OBJECTIVE: The purpose of the study was to evaluate the histopathological characteristics of the pink macules of the CM-AVM syndrome and to investigate if these pink macules could be classified as capillary malformations or arteriovenous malformations based on their histopathological features. DESIGN-SETTINGS-PARTICIPANTS: We conducted a retrospective multicenter study involving eight hospitals in Spain. Fifteen biopsies from pink macules of the CM-AVM syndrome were analysed and compared with five biopsies of diverse capillary malformations and three stage I arteriovenous malformations. RESULTS: Pink macules' biopsies of the CM-AVM syndrome showed similar features including a high vascular density encompassing capillaries and numerous thick-walled arterioles mainly located in the superficial dermis, a predominance of elongated over round vessels, scarce or absent erythrocytes within the lumina and discrete perivascular inflammation. CMs were characterized by an increased number of capillary-type vessels mostly rounded and located in the upper dermis. AVMs were composed by highly increased numbers of vessels with a branching pattern involving the full thickness of the dermis, without erythrocytes within the lumina. Wilms tumour 1 protein was positive in the endothelial cells both in pink macules of the CM-AVM and in arteriovenous malformations. CONCLUSIONS AND RELEVANCE: Pink macules of the CM-AVM syndrome seem to be different from capillary malformations. Our results suggest that histologically and immunohistochemically they are closer to incipient arteriovenous malformations than to capillary malformations. A deepened knowledge about the nature of these skin lesions will contribute to the better understanding of capillary malformation-arteriovenous malformation syndrome, and will open the possibility of new and more specific treatments in the future.

Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment.

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burden.

Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients.

Ultrafast all-optical temporal differentiators based on CMOS-compatible integrated-waveguide Bragg gratings.

We report the first realization of integrated, all-optical first- and higher-order photonic differentiators operating at terahertz (THz) processing speeds. This is accomplished in a Silicon-on-Insulator (SOI) CMOS-compatible platform using a simple integrated geometry based on (π-)phase-shifted Bragg gratings. Moreover, we achieve on-chip generation of sub-picosecond Hermite-Gaussian pulse waveforms, which are noteworthy for applications in next-generation optical telecommunications.

UV-induced modification of stress distribution in optical fibers and its contribution to Bragg grating birefringence.

This paper discusses the importance of stress-induced contributions to the photo-induced birefringence observed in fiber Bragg gratings. Optical tomography measurements are performed in exposed and unexposed fibers to extract the stress profiles induced by UV-writing of fiber Bragg gratings for various exposure levels. A photoelastic analysis and a high-order isoparametric finite elements method are then used to calculate the birefringence caused by stress profile modifications. The results are compared to the birefringence directly measured by spectral analysis of a chirped fiber grating with multiple phase-shifts. We can therefore estimate the fraction of the photo-induced birefringence due to stress-induced anisotropy following UV exposure.

Tunable dispersion-tolerant picosecond flat-top waveform generation using an optical differentiator.

We study the influence of dispersive propagation on picosecond flat-top pulses, which are generated using long period fiber grating (LPG)-based optical differentiators. We suggest an extremely simple scheme to compensate for the dispersion-induced flat-top pulse distortion; this scheme is based on proper tuning the LPG coupling strength. As this coupling strength may be changed via LPG axial straining, the demonstrated device can be tuned to compensate for different levels of the dispersion in a very easy and straightforward fashion. This allows for very fine flat-top pulse shape adjustment, even after propagation through a relatively long section of dispersive optical fiber. In the experimental demonstration reported here, the dispersion tolerance of 1.8-ps flat-top pulses propagating through a standard telecom fiber (SMF-28) was increased from approximately 2 m to approximately 18 m, giving a 9-fold improvement.

Picosecond and sub-picosecond flat-top pulse generation using uniform long-period fiber gratings.

We propose a novel linear filtering scheme based on ultrafast all-optical differentiation for re-shaping of ultrashort pulses generated from a mode-locked laser into flat-top pulses. The technique is demonstrated using simple all-fiber optical filters, more specifically uniform long period fiber gratings (LPGs) operated in transmission. The large bandwidth typical for these fiber filters allows scaling the technique to the sub-picosecond regime. In the experiments reported here, 600-fs and 1.8-ps Gaussian-like optical pulses (@ 1535 nm) have been re-shaped into 1-ps and 3.2-ps flat-top pulses, respectively, using a single 9-cm long uniform LPG.

Infrequent expression of protein p53 in epidermotropic variants of cutaneous T-cell lymphoma.

Although diverse types of lymphomas have been examined for immunohistochemical detection of p53 protein, little information is available with regard to p53 protein expression in CTCL. We analyzed cutaneous biopsy specimens of 22 patients with the diagnoses of mycosis fungoides or Sézary syndrome with polyclonal rabbit anti-p53 antiserum CM-1. Staining of neoplastic cells was observed only in two patients with advanced disease. Overexpression of p53 protein does not seem to be a major feature of either mycosis fungoides or Sézary syndrome.

Cutaneous metastases from prostatic cancer.

The skin is involved in metastases from 2-9% of malignant tumors. These usually tend to spread to the skin relatively late in the course of the disease. Skin metastases of prostatic origin are quite uncommon and preferentially localized to the lower abdomen and genital area. We present a case of cutaneous metastasis from prostatic adenocarcinoma that preceded diagnosis of the primary tumor and was located on the neck.

CD133 expression in normal skin and in epithelial cutaneous tumors.

BACKGROUND: Expression of human CD133 (human prominin-1) in cancer cells has been postulated to be a marker of stemness and is considered as a putative marker of cancer stem cells (CSCs). We designed a study to describe the expression pattern of CD133 in normal skin and in epithelial cutaneous neoplasms. METHODS: The CD133 immunohistochemical expression of forty-three eccrine and apocrine tumors was compared to that observed in other epithelial tumors of the skin. In addition, flow cytometry was used to detect the CD133 expression of four epithelial skin neoplasms, including one porocarcinoma. RESULTS: CD133 immunoreactivity at the apical or at the apicolateral surface of cells forming glandular structures was observed. Cells from solid areas of benign or malignant tumors were not stained. The porocarcinoma derived culture cells showed a 22% of CD133 positive cells using flow cytometry, while squamous cell carcinoma cultures contained less than 0.1%. CONCLUSIONS: These observations indicate that CD133 is a specific marker of glandular differentiation that could be included in the diagnostic panel of cutaneous tumors with possible eccrine or apocrine differentiation. However, the use of CD133 expression as a marker of CSCs should be interpreted with caution in experiments of skin.

On-chip CMOS-compatible all-optical integrator.

All-optical circuits for computing and information processing could overcome the speed limitations intrinsic to electronics. However, in photonics, very few fundamental 'building blocks' equivalent to those used in multi-functional electronic circuits exist. In this study, we report the first all-optical temporal integrator in a monolithic, integrated platform. Our device--a lightwave 'capacitor-like' element based on a passive micro-ring resonator--performs the time integral of the complex field of an arbitrary optical waveform with a time resolution of a few picoseconds, corresponding to a processing speed of ∼200 GHz, and a 'hold' time approaching a nanosecond. This device, compatible with electronic technology (complementary metal-oxide semiconductor), will be one of the building blocks of next-generation ultrafast data-processing technology, enabling optical memories and real-time differential equation computing units.

Long-period-fiber-grating-based filter configuration enabling arbitrary linear filtering characteristics.

The filtering scheme proposed here is based on transmission through a dual long-period-fiber-grating (LPFG) configuration and enables implementation of arbitrary spectral transfer functions using available inverse-scattering design algorithms, such as those widely used for fiber Bragg gratings (FBGs) operating in reflection. Besides the important technical advantage of operation in transmission, the proposed device can reach large spectral bandwidths that would be extremely challenging to reach by, e.g., FBG devices. The proposed concept is demonstrated by designing and fabricating a LPFG-based filter for synthesis of transform-limited 1.5-ps-long square-like pulses.

Ultrafast all-optical first- and higher-order differentiators based on interferometers.

We demonstrate that a conventional two-arm interferometer can implement first-order temporal differentiation of ultrafast arbitrary optical waveforms. Straightforward extension of this technique to nth-order optical differentiation is also suggested. This approach is experimentally demonstrated by an efficient and accurate first- and second-order temporal differentiation of (sub-)picosecond Gaussian optical pulses.

Reconstructing arbitrary strain distributions within fiber gratings by time-frequency signal analysis.

We apply time-frequency signal-analysis techniques to recover arbitrary distributions of axial strain along a fiber grating from its reflection spectral response. The proposed method permits accurate strain reconstruction with no restrictions on the applied strain profile or on the grating length. We demonstrate the validity and accuracy of the technique by reconstructing the strain field in a fiber grating with a nonmonotonic strain profile, which includes all the following: a constant strain section, high gradient variations, and strain discontinuities.

Reconstruction of fiber grating period profiles by use of Wigner-Ville distributions and spectrograms.

The grating-period profile and length of an arbitrary fiber Bragg grating structure can be reconstructed from the structure's reflection response by use of a time-frequency signal representation based on the well-known Wigner-Ville distribution and spectrogram. We present a detailed description of this synthesis technique. By means of numerical simulations, the technique is tested with several fiber grating structures. In general, our results show good agreement between exact and reconstructed functions. The technique's advantages and limitations are discussed. We propose and demonstrate the application of the proposed synthesis technique to distributed mechanical strain or temperature sensing.

Technique for multiplying the repetition rates of periodic trains of pulses by means of a temporal self-imaging effect in chirped fiber gratings.

We show that a temporal effect that is equivalent to the spatial self-imaging (Talbot) effect applies to the reflection of periodic signals from linearly chirped fiber gratings. The effect can be used for multiplying the repetition frequency of a given periodic pulse train without distorting the individual pulse characteristics. The practical limit on the frequency-multiplication factor depends only on the temporal width of the individual pulse. Thus we demonstrate that a suitable combination of well-known techniques for short-pulse generation, such as pulse mode locking, and the technique proposed here allows us to obtain short-pulse trains with ultrahigh repetition rates (in the terahertz regime). Results from simulations show good agreement with those predicted by theory.