Role of light chain clearance in the recovery of renal function in multiple myeloma: another point of view.

Background: Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). Methods: This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. Results: A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). Conclusion: Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery.

Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids.

Melatonin is a molecule with different antitumor actions in breast cancer and has been described as an inhibitor of vascular endothelial growth factor (VEGF). Despite the recognition of the key role exerted by VEGF in tumor angiogenesis, limitations arise when developing models to test new antiangiogenic molecules. Thus, the aim of this study was to develop rapid, economic, high capacity and easy handling angiogenesis assays to test the antiangiogenic effects of melatonin and demonstrate its most effective dose to neutralize and interfere with the angiogenic sprouting effect induced by VEGF and MCF-7. To perform this, 3D endothelial cell (HUVEC) spheroids and a chicken embryo chorioallantoic membrane (CAM) assay were used. The results showed that VEGF and MCF-7 were able to stimulate the sprouting of the new vessels in 3D endothelial spheroids and the CAM assay, and that melatonin had an inhibitory effect on angiogenesis. Specifically, as the 1 mM pharmacological dose was the only effective dose able to inhibit the formation of ramifications around the alginate in the CAM assay model, this inhibition was shown to occur in a dose-dependent manner. Taken together, these techniques represent novel tools for the development of antiangiogenic molecules such as melatonin, with possible implications for the therapy of breast cancer.

Prevalencia de trastornos respiratorios del sueño en adolescentes y su relación con la presencia de obesidad e hipertensión arterial / Prevalence of sleep-disordered breathing among adolescents and its association with the presence of obesity and hypertension

Introducción: El aumento de prevalencia de trastornos respiratorios del sueño (TRS) y su relación con obesidad e hipertensión arterial (HTA) ha sido poco explorado en adolescentes. El objetivo de este estudio fue investigar la prevalencia de TRS y ronquido en esta población y analizar su asociación con obesidad e HTA. Población y métodos: Se realizó un estudio descriptivo de corte transversal en una muestra de adolescentes. Se realizaron mediciones de peso, talla, perímetro de cintura y cuello, tensión arterial, y el Cuestionario de Sueño Pediátrico (PSQ, por su sigla en inglés). Resultados: Participaron 826 adolescentes, 58 (7 %) presentaron TRS (varones: 5,8 %; mujeres: 8 %) y 80 (9,7 %) se consideraron roncadores (varones: 10,4 %; mujeres: 9,1 %). Se detectaron sobrepeso y obesidad en 216 (26,2 %) y 149 (18 %) sujetos, respectivamente. Una mayor proporción de sujetos con obesidad presentaron TRS con respecto a quienes no tenían obesidad (12,8 % versus 5,8 %; p = 0,004). La misma asociación fue encontrada para el ronquido (18,2 % versus 7,8 %; <0,001). El 24,6 % dormía menos de 8 horas por día. El 12,6 % presentó valores compatibles con HTA, con una asociación significativa con obesidad y horas de sueño. Conclusión: Se observó una prevalencia elevada de TRS y ronquido en adolescentes y una asociación entre obesidad e HTA, que pone de manifiesto la importancia de abordar esta problemática de manera temprana a fin de evitar complicaciones

ntroduction: The increased prevalence of sleep-disordered breathing (SDB) and its association with obesity and hypertension (HTN) have not been thoroughly explored in adolescents. The objective of this study was to investigate the prevalence of SDB and snoring in this population and analyze its association with obesity and HTN. Population and methods: This was a descriptive, cross-sectional study in a sample of adolescents. Weight, height, waist and neck circumference, and blood pressure were measured, and the Pediatric Sleep Questionnaire (PSQ) was administered. Results: A total of 826 adolescents participated, 58 (7 %) had SDB (males: 5.8 %; females: 8 %), and 80 (9.7 %) were considered snorers (males: 10.4 %; females: 9.1 %). Overweight and obesity were detected in 216 (26.2 %) and 149 (18 %) participants, respectively. A higher proportion of subjects with obesity had SDB compared to those who were not obese (12.8 % versus 5.8 %; p = 0.004). The same association was observed with snoring (18.2 % versus 7.8 %; p < 0.001). Also, 24.6 % slept less than 8 hours a day and 12.6 % had values compatible with HTN, with a significant association with obesity and sleep hours. Conclusion: A high prevalence of SDB and snoring was observed in adolescents, together with an association with obesity and HTN, which highlights the relevance of addressing this problem in an early manner in order to prevent complications

A primary inflammatory myofibroblastic tumor of the scapula in a child: imaging findings.

Inflammatory myofibroblastic tumor (IMT) is an uncommon tumor characterized by inflammatory cell infiltration and differentiated myofibroblastic spindle cells. IMT was first described in the lung and retroperitoneum. Occurrence in bone has been well described in the maxilla and occasionally in the long bones in the adult population. We present a unique case of IMT arising primarily from the scapula in an 8-year-old patient, not described previously in the pediatric or adult literature. Imaging demonstrated an ill-defined and aggressive osteolytic lesion with cortical bone destruction associated with an important soft tissue component that extended into the adjacent muscles. Histologically, the tumor was composed of spindle and polygonal cells distributed in an inflammatory background with different proportions of plasma cells, lymphocytes, eosinophils and neutrophils. The absence of cellular atypia helped to differentiate this entity from malignant spindle cell tumors, and imaging could differentiate the tumor from the nontumoral inflammatory reaction.

Angiographic characteristics of epileptogenic arteriovenous malformations and effectiveness in the seizure control after treatment with radiosurgery.

OBJETIVE: Define the angiographic characteristics of epileptogenic arteriovenous malformations (AVM) and assess symptom control of the seizure after treatment with radiosurgery. MATERIAL AND METHODS: Between 1996 and 2006, a total of 237 adults patients were diagnosed with AVM and were treated in our center by radiosurgery with linear accelerator. We analyzed demographics, clinicals, angiographics and radiosurgicals characteristics and the complications of the procedure in each of them. The first symptom was a seizure in 68 of them and the subsequent analysis of the treatment effectiveness for the seizure control was done, and the possible predictive factors of AVM nidus evolution were assessed. RESULT: The average volume of the epileptogenic AVMs was 7.17 cc, compared ot the non-epileptogenic AVM 5.06 cc (p<0.03). Other differentiating factors were surface blood supply (p<0.003), venous ectasia (p<0.064), angiogenesis (p<0.078), and the presence of unrelated aneurysms (p<0.08). For 68 patients (28.7%) with seizures a clinical control (Seizure Frequency Scoring System SFSS ≤2) was obtained in 70% of patients and there was an excellent control (SFSS ≤1) in 25% of them. The percent occlusion of their AVMs was 50%. There was statistical significance with SFSS ≤1 (p<0.01), but was not any significance with SFSS ≤2. Age (p<0.003) and diffuse nidus morphology (p<0.05) were predictors of good AVM nidus evolution. CONCLUSIONS: The stereotactic radiosurgery seems to be an effective method for control of symptomatic seizures for intracranial AVMs. Certain angiographic characteristics, such as the volume, surface blood supply, angiogenesis, venous ectasia, and unrelated aneurysms to the AVMs, seem to influence the appearance of epileptic seizures.

Generalized livedo reticularis induced by silicone implants for soft tissue augmentation.

Silicone is one of the most widely used filler for facial cosmetic correction and soft tissue augmentation. Although initially it was considered to be a biologically inert material, many local and generalized adverse effects have been reported after silicone usage for cosmetic purposes. We present a previously healthy woman who developed progressive and persistent generalized livedo reticularis after cosmetic surgery for volume augmentation of buttocks. Histopathologic study demonstrated dermal presence of interstitial vacuoles and cystic spaces of different sizes between the collagen bundles, which corresponded to the silicone particles implanted years ago. These vacuoles were clustered around vascular spaces and surrounded by a few foamy macrophages. General examination and laboratory investigations failed to show any evidence of connective tissue disease or other systemic disorder. Therefore, we believe that the silicone implanted may have induced some kind of blood dermal perturbation resulting in the characteristic violet reticular discoloration of livedo reticularis.

Diffuse lower limb lipoatrophy.

Lipoatrophic panniculitis is the term used to describe those panniculitides in which atrophy of the subcutaneous fat is the main residual lesion. They can be classified as primary or secondary. Primary lipoatrophic panniculitis is idiopathic, whereas secondary lipoatrophic panniculitides include those because of infection, malignancy, pancreatic disorders or connective tissue diseases. Usually, these entities are characterized by the appearance of tender, erythematous nodules or plaques that resolve leaving one or several localized areas with loss of subcutaneous fat. We report a 76-year-old female who developed diffuse and symmetric lipoatrophy of lower limbs after an extensive inflammatory process affecting both extremities from thighs to ankles. Histopathologic assessment revealed a lobular panniculitis with a lymphohistiocytic infiltrate, foamy macrophages and lipophagic granuloma formation. The most striking feature in our patient was the clinical presentation as a symmetrical diffuse inflammatory process resulting in lipoatrophy of the lower limbs.

Plaque-like osteoma cutis with transepidermal elimination.

Osteoma cutis is a rare lesion that consists of the presence of bone tissue within the dermis and/or hypodermis. It may be classified as primary osteoma cutis, when bone tissue develops in the skin without any pre-existing lesion and secondary osteoma cutis, which is more frequent and occurs when osseous tissue develops on a pre-existing lesion. We present a case of primary plaque-like osteoma cutis involving the scalp, left forehead and left cheek, which appeared in an adult male. Histopathological study showed several islands of mature osseous tissue involving the full thickness of the dermis. In some areas, there was also transepidermal elimination of bone spicules. We review the literature about previously reported similar cases.

Lipedematous alopecia: an uncommon clinicopathologic variant of nonscarring but permanent alopecia.

A 52-year-old black woman presented with a 5-year history of gradual swelling and slowed hair growth involving the vertex and both parietal regions of the scalp. Gradually, the swelling progressed to involve the entire scalp, only sparing a peripheral crown. She reported no history of trauma or medications. Slight pruritus of the involved area was the only accompanying symptom. There was no family history of a similar condition. Her past medical history included surgery for ovarian cysts, 10 years previously, and cholelithiasis. Physical examination revealed diffuse hair thinning and alopecia, more prominent along the vertex and parietal regions (Fig. 1a). There was no evidence of scalp inflammation, scaling, or increased hair fragility. The scalp was mildly tender on palpation and had a boggy, spongy consistency. The hairs which still remained in the involved areas were thin, short, and soft (Fig. 1b). The involved area was slightly hypopigmented when compared with adjacent noninvolved scalp. The rest of the physical examination was within normal limits. No abnormalities of the hair shaft were observed on microscopic examination of several plucked hairs. Laboratory investigations, including a complete blood cell count, blood chemistry, urinalysis, sedimentation rate, antinuclear antibodies, and serologic tests for syphilis, hepatitis B and C virus, and human immunodeficiency virus, were negative. A computed tomography scan of the skull demonstrated diffuse and regular thickening of subcutaneous fatty tissue of the scalp, disclosing a maximum scalp thickness of 15 mm at the vertex (Fig. 2). The biopsy from the vertex revealed a normal epidermis and dermis, with diffuse loss of hair follicles. The most striking feature consisted of a large increase in thickness of the subcutaneous fatty tissue (Fig. 3a). Pre-existing hair follicles were replaced by vertical fibrous tracts of lamellar fibroplasia with no inflammatory infiltrate (Fig. 3b). Adipocytes showed a normal size and shape, but the connective tissue septa, which are normally present separating the subcutaneous tissue into fat lobules, were lacking, and subcutaneous fatty tissue consisted of a continuous and diffuse sheet of mature adipocytes (Fig. 3c). Orcein stain revealed normal contents of elastic fibers with foci of condensation at the sites of disappeared pre-existing hair follicles (Fig. 3d). Colloidal iron and Alcian blue (pH 2.5) stains revealed no mucin deposits.

Leukemia cutis presenting as localized cutaneous hyperpigmentation.

The usual clinical presentations of leukemia cutis include solitary infiltrated erythematous or violaceous plaques or nodules and multiple localized or generalized papules. On the other hand, cutaneous hyperpigmentation is a frequent finding in patients with malignancies, most of the cases because of chemotherapy or other drugs that the patient is taking. We present a case of cutaneous hyperpigmentation as the presenting sign of leukemia cutis. A 61-year-old male presented with cutaneous hyperpigmentation, which had appeared during the last chemotherapy cycle for treatment for biphenotypic leukemia. Cutaneous lesions consisted of bluish to brownish irregular well-defined discoloration of the skin involving the upper part of the trunk and the temporal regions of the forehead. The patient was asymptomatic and the skin was not infiltrated at all. However, histopathologic study showed nodular infiltrates involving the full-thickness of the dermis and destroying pre-existing adnexa. This infiltrate was composed of atypical basophilic cells with large hyperchromatic nuclei and scant cytoplasm. Immunohistochemical studies showed intense immunoexpression for CD43, CD68, CD45RO and myeloperoxidase within these cells. A diagnosis of biphenotypic leukemia cutis was established. In our review of the literature we have not found any report of cutaneous hyperpigmentation as the presenting manifestation of leukemia cutis.

Facial granulomas secondary to Dermalive microimplants: Report of a case with histopathologic differential diagnosis among the granulomas secondary to different injectable permanent filler materials.

Wrinkle reduction and the correction of skin defects using injectable aesthetic microimplants are now widely performed by dermatologists and plastic surgeons. In recent years, dermal filler substances containing polymer particle suspensions such as Bioplastique, Artecoll, and Dermalive are the most commonly used materials. These microimplants are permanent, non-biodegradable, and generally well tolerated, although various adverse reactions are still possible. We describe here a patient with facial granulomas secondary to Dermalive injections for correction of naso-labial folds and wrinkles. The particular shape of the injected particles allows for correct identification of the implanted material. Therefore, histopathologic examination is the best means to obtain the correct diagnosis of foreign body granuloma and to identify the type of filler particles. We discuss the histopathologic differential diagnosis among the granulomas secondary to the most commonly used aesthetic permanent filler materials.

[Multiple linear spiradenoma with a linear distribution]. / Espiradenomas múltiples con distribución lineal.

We report the case of a 32-year old woman who presented with multiple nodules in the left arm and breast that had been present for 15 years. These nodules had a bluish colour and were occasionally painful. She had gone under excision of three other nodules on the left arm with the histopathological diagnosis of spiradenoma. All of the nodules were disposed in a linear arrangement and underneath a maculo-papular erythematous lesion which clinically seemed to be an epidermal nevus. The case described in the literature of multiple spiradenomas are very rare and multiple linear spiradenomas are even rarer.

[Mastocytosis in adults. Description of nine clinicopathological cases]. / Mastocitosis del adulto. Descripción de 9 casos clinicopatológicos.

INTRODUCTION: Mastocytosis is a hyperplastic process characterized by the infiltration of different organs and tissues by mature mastocytes. It is more frequent in childhood, although cases also occur in adults. There are significant differences between the ways mastocytosis presents in adults and children, as well as in its development and prognosis. MATERIAL AND METHODS: In this work, we describe the clinicopathological findings for 9 adult patients with mastocytosis. The clinical, evolutional and genetic characteristics of mastocytosis in adults are also compared to those of childhood mastocytosis. RESULTS: In contrast with childhood mastocytosis, the skin lesions of adult mastocytosis are very monomorphous, and consist of macules and papules of less than 1 cm in diameter, brownish-red in color. There are few symptoms, and there is usually discrete pruritus. Darier's sign is very often negative. Furthermore, the skin lesions do not tend to spontaneously regress, which is what usually occurs in children. Finally, systemic involvement in adults is practically a constant, with mastocyte infiltration of the bone marrow in over 90 % of cases, and bone involvement in over 50 % of cases, while systemic involvement is rarer in children. In any case, even if there is infiltration of systemic organs in adult mastocytosis, there are usually no accompanying clinical symptoms. The mutation of the c-kit proto-oncogene consists of the replacement of Asp with Val at codon 816, and this is nearly always found in adult mastocytosis. It is less frequent in childhood mastocytosis. CONCLUSIONS: All of these findings make it possible to classify adult mastocytosis as a separate clinicopathological entity from mastocytoses in children.

Localization of Sweet's syndrome in radiation-induced locus minoris resistentae.

Sweet's syndrome is a reactive dermatosis clinically characterized by fever, leukocytosis, and multiple, erythematous, painful plaques. Histopathologically, the lesions show edema of the papillary dermis and a dermal infiltrate mainly composed of neutrophils, without vasculitis. We describe a patient with breast carcinoma and Sweet's syndrome mostly involving previously irradiated skin.