Inguinal lymph nodes agenesia in a patient with Schimmelpenning-Feuerstein-Mims syndrome with proven somatic KRAS mutation.

Schimmelpenning-Feuerstein-Mims (SFM) syndrome is a neurocutaneous disorder that can affect many body systems. The principal and most characteristic anomalies are craniofacial naevus sebaceous in association with neurological, ocular and skeletal findings. The presence of vascular malformations in this condition is unusual; nevertheless, vascular malformations have been suggested by many authors to be part of the spectrum of the same disease. Few cases have been published on the association of SFM with lymphatic malformations. This syndrome is categorized as a mosaic RASopathy due to postzygotic mutations in the HRAS, KRAS or NRAS genes. These genes are involved in the RAF-MEK-ERK signalling pathway, which is activated by mutant cells, increasing cellular proliferation. These mutations have been found only in naevus sebaceous cells, and may be also the explanation for many of the associated pathologies. We report a case of an 18-year-old boy diagnosed with SFM syndrome associated with lymphatic malformation in the legs and agenesia of the inguinal lymph nodes. The lymphatic alterations were diagnosed by gammography of the legs. The genetic diagnosis was confirmed by the presence of a KRAS postzygotic mutation in naevus sebaceous cells of a skin specimen. Genetically confirmed cases of mosaic RASopathies should be used to more accurately characterize phenotypic presentations of this syndrome and develop a future therapeutic strategy, such as molecular targeted therapy.

Tularemia: A rare cause of pediatric lymph nodes adenitis.

Adenopathy in pediatrics can have many different causes: infectious, tumoral, and inflammatory. We report the case of an 8-year-old patient with a febrile popliteal ulceration associated with an inflammatory satellite inguinal lymph node adenitis. Serological tests and polymerase chain reaction analyses confirmed the diagnosis of ulceroglandular tularemia. An appropriate antimicrobial therapy led to a full recovery. This case reminds us to consider tularemia as a potential emergent disease in children presenting with subacute to chronic lymphadenopathy and thereby to choose the correct diagnostic tool and appropriate antimicrobial therapy.

MRI for Response Assessment of Extensive Lymphatic Malformations in Children Treated With Sirolimus.

BACKGROUND. Extensive lymphatic malformations (LMs) may cause substantial morbidity. The mammalian target of rapamycin (mTOR) inhibitor sirolimus shows promise for treating vascular anomalies, although response assessment is not standardized. OBJECTIVE. The purpose of this study was to retrospectively characterize changes seen on MRI of children with extensive LMs treated with sirolimus. METHODS. Twenty-five children treated with sirolimus for extensive LMs were included. Baseline MRI was defined as the MRI examination performed closest to therapy initiation; follow-up MRI was defined as the most recent MRI examination performed while the patient was receiving therapy. Two pediatric radiologists independently determined MRI lesion volume by tracing lesion contours on all slices (normalized to patient body surface area expressed in square meters) and determined signal by placing an ROI on the dominant portion of the lesions (normalized to CSF signal) on baseline and follow-up T2-weighted MRI sequences. Interreader agreement was determined, and values were averaged for further analysis. Volume and signal changes were compared with patient, lesion, and treatment characteristics. RESULTS. The mean (± SD) interval between initiation of sirolimus treatment and follow-up MRI was 22.1 ± 13.8 months. The mean lesion volume index on baseline and follow-up MRI was 728 ± 970 and 345 ± 501 mL/m2, respectively (p < .001). Ninety-two percent of children showed a decrease in lesion volume index that was greater than 10% (mean volume change, -46.4% ± 28.2%). Volume change was inversely correlated with age (r = -0.466; p = .02). The mean volume change was -64.7% ± 25.4% in children younger than 2 years old versus -32.0% ± 21.6% in children 2 years old or older (p = .008). The mean volume change was -58.1% ± 24.0% for craniocervical lesions versus -35.5% ± 28.2% for lesions involving the trunk and/or extremities (p = .03). Mean lesion signal ratio on baseline and follow-up MRI was 0.81 ± 0.29 and 0.59 ± 0.26, respectively (p < .001). Mean signal ratio change was -23.8% ± 22.7%. Volume and signal changes were moderately correlated (r = 0.469; p = .02). Volume and signal changes were not associated with sex, lesion subtype, serum concentration of sirolimus, or the interval between sirolimus initiation and follow-up MRI (p > .05). Interreader agreement for volume index change was excellent (intraclass correlation coefficient, 0.983), and that for signal ratio change was moderate to good (intraclass correlation coefficient, 0.764). CONCLUSION. Sirolimus treatment of extensive LMs in children is associated with significant reductions in volume and signal on T2-weighted MRI. The decrease in volume is greater in younger children and craniocervical lesions. CLINICAL IMPACT. The results may facilitate development of standardized MRI-based criteria for assessing the response of vascular malformations to pharmacotherapy.

Lymphedema and Lymphovenous Bypass: Perioperative Nursing Implications.

Lymphedema-the accumulation of fluid in tissues, usually in the upper and lower extremities-often results from lymph node dissection or radiation and can cause painful and debilitating swelling that may interfere with a patient's daily living activities and quality of life. The goal of treatment for lymphedema is to reduce the volume of fluid in the affected area. Lymphedema is staged according to presenting characteristics, and interventions may be surgical or nonsurgical, such as complex decongestive therapy. Lymphovenous bypass is a surgical procedure performed for the management of lymphedema and involves rerouting microvascular channels to allow for the drainage of fluid that has accumulated in the lymphatic tissue of the upper or lower extremities. It requires supermicrosurgery techniques because of the small size of the vessels being anastomosed. Perioperative nursing implications for lymphovenous bypass include OR preparation and providing emotional support for patients living with lymphedema.

Metastatic Lymph Node Ratio (mLNR) is a Useful Parameter in the Prognosis of Colorectal Cancer; A Meta-Analysis for the Prognostic Role of mLNR.

Background and objectives: The presenting study aimed to elucidate the prognostic role of the metastatic lymph node ratio (mLNR) in patients with colorectal cancer (CRC), using a meta-analysis. Materials and Methods: Using data from 90,274 patients from 14 eligible studies, we performed a meta-analysis for the correlation between mLNR and survival rate. Besides, subgroup analyses were performed, based on tumor stage, tumor location, and mLNR. Results: A high mLNR showed significant correlation with worse overall survival and disease-free survival rates in CRC patients (hazard ratio (HR), 1.617, 95% confidence interval (CI) 1.393-1.877, and HR 2.345, 95% CI 1.879-2.926, respectively). In patients with stage III, who had regional LN metastasis, the HRs were 1.730 (95% CI 1.266-2.362) and 2.451 (95% CI 1.719-3.494) for overall and disease-free survival, respectively. According to tumor location, rectal cancer showed a worse survival rate when compared to colon cancer. In the analysis for overall survival, when mLNR was 0.2, HR was the highest across the different subgroups (HR 5.040, 95% CI 1.780-14.270). However, in the analysis for disease-free survival, the subgroup with an mLNR < 0.2 had a higher HR than the other subgroups (HR 2.878, 95% CI 1.401-5.912). Conclusions: The mLNR may be a useful prognostic factor for patients with CRC, regardless of the tumor stage or tumor location. Further studies are necessary for the detailed criteria of mLNR before its application in daily practice.

The prolactin inducible protein/gross cystic disease fluid protein-15 deficient mice develop anomalies in lymphoid organs.

The Prolactin Inducible Protein (PIP) is a 15 kDa protein secreted by normal apocrine glands, including salivary, lacrimal and sweat glands. PIP levels are normally low in the mammary glands of healthy individuals, but high levels have been observed in pathological conditions of the breast such as benign breast cystic disease and breast cancer. While the function of PIP is not well elucidated, accumulating evidence strongly point to a role in both innate and adaptive immunity. Using PIP deficient mice (Pip-/- mice) our laboratory demonstrated that loss of PIP function led to impaired T helper type 1 response and cell mediated immunity. In the present study we provide additional supporting evidence showing abnormal lymphocytic distribution in primary and secondary lymphoid organs of Pip-/- mice. Significant morphological changes in the Eustachian tube, an immune-protected site where PIP is normally found, were also associated with the absence of PIP. Collectively, these results further support an immuno-regulatory role for PIP and have implications for a spectrum of immune-related illnesses including otitis media and hearing loss as well as breast cancer.

The Significance of Incidental Findings on Computed Tomography of the Chest.

BACKGROUND: Computed tomography (CT) of the chest has replaced lung scans and pulmonary angiography as the criterion standard for the diagnosis of pulmonary embolism (PE). Most of these examinations are negative for PE, but they frequently have incidental findings that may require further evaluation. OBJECTIVE: In order to examine common incidental findings and their possible clinical ramifications and required workup, we reviewed data from relevant studies in which chest CTs were performed and incidental findings discovered. DISCUSSION: The most common incidental findings on chest CT are pulmonary nodules and lymph nodes. Nodules are significantly more commonly found in smokers and are also more likely to be malignant in smokers. The recently updated 2017 Fleischner Society recommendations provide guidance to clinicians in deciding which nodules should be further evaluated. Enlarged lymph nodes similarly represent potential malignancy and most will need further evaluation with positron emission tomography scans or by transbronchial needle aspiration. CONCLUSIONS: Enlarged lymph nodes and pulmonary nodules are both common incidental findings on chest CT. Each represents the potential for malignancy, and under certain conditions requires additional workup and further evaluation. The majority will be benign, even in high-risk populations. However, because of the increasing prevalence of the chest CT and the frequency with which incidental findings will be seen, it is important that the emergency physician be aware of common features and recommended subsequent evaluation.

Lateral neck lumps: A systematic approach for the general paediatrician.

Lateral neck lumps are very common in children, and are largely benign in nature. The majority of lumps may be diagnosed on history and clinical examination alone, and further investigations are often not required. The most common pathologies in young children include reactive lymphadenopathy, lymphadenitis and atypical mycobacterial infections. A lateral neck lump is an uncommon presentation for malignancy and is largely restricted to older children and adolescents. The paediatric surgeon plays an important role in the assessment and management of lateral neck lumps, often in the form of reassurance to the patients and their carers.

Anatomic distribution of cervicofacial lymphatic malformations based on lymph node groups.

OBJECTIVES: To evaluate radiographic characteristics and to identify locations of cervicofacial lymphatic malformations in children based on known lymph node groupings. METHODS: Retrospective chart review of pediatric patients with cervicofacial lymphatic malformations who underwent imaging with magnetic resonance imaging (MRI), computed tomography (CT) or ultrasonography (US). Ninety charts were reviewed from November 2005 to June 2015. Demographic information and imaging characteristics were evaluated. RESULTS: Ninety children were included. The average age at presentation was 52 months (range, 1 day to 170 months). Imaging modalities were MRI in 73 (81%), CT in 7 (8%), US in 6 (7%), and multimodality imaging in 4 (4%) cases. Nearly half (49%) of lesions were found in the parotid and submandibular nodal group, 32% in the cervical group, and 19% in the midline face and oral cavity group. The lymphatic malformations were found on the left in 39 (43%) of cases, on the right in 30 (33%) of cases, and were bilateral in 21 (23%) cases. Nineteen (21%) lesions were macrocystic, twenty-two (24%) were microcystic, and forty-nine (49%) had mixed features. Mixed lesions were more likely to be extensive and involve multiple lymph node groups (P = 0.0005). Adjacent lymphadenopathy was present in 20 (22%) among all subjects, with an average size of 1.22 (± 1.92) cm in the short-axis. CONCLUSION: The results of this study demonstrate three lymph node groupings in which LM are commonly identified. The midline face and oral cavity lesions are predominantly microcystic, the parotid and submandibular lesions are predominately of mixed morphology, and the cervical lesions are predominately macrocystic and mixed. Further studies are needed to determine if such a classification system demonstrates clinically significant difference in disease progression and response to therapy.

Caso 24 / Case 24

Trata-se de apresentação da Análise da Imagem de lesões cutâneas e intracranianas reveladas pelo exame clínico direto e radiológico, em que características clínico-epidemiológicas e de exames complementares permitem a identificação de agente etiológico mais provável, e revela gravidade extrema de nosologia eminentemente brasileira, que requer alerta para seu diagnóstico precoce e tratamento adequado para impedir sequelas e morte precoce. (AU)

This is a presentation of the Image Analysis of cutaneous and intracranial lesions revealed by direct clinical and radiological examination, in which clinical-epidemiological and complementary features allow the identification of the most probable etiological agent, and reveals extreme severity of nosology in Brazil, which requires alertness for its early diagnosis and appropriate treatment to prevent sequelae and early death. (Au)

[Management for lymphatic malformation in infants: a single center experience].

Objective: To assess the therapeutic effect of management for lymphatic malformation (LM) in infants. Methods: This retrospective study recruited clinical data of 996 patients with LM from June 2004 to July 2015 in our center. All patients were diagnosed as LM after ultrasound, CT or MR scan. All patients were divided into Group 1 (427 patients, treated by endoscopic LM partial resection combined with cautery and postoperative intratumoral negative pressure and absolute ethyl alcohol),Group 2 (239 patients, treated by combined pinyangmycin and dexamethasone injection),Group 3 (330 patients, treated by surgical resection only).The clinical effects were observed in three groups, and therapeutic effect differences in gender, age, maximum diameter, location, range, histological typing, lymph property and treatments were analysed in cervicofacial LM. Results: Group 1:333 patients were cured (78.0％),Group 2:165 patients were cured (69.0％),Group 3:238 patients were cured (72.1％).The difference in cure rate between Group 1 and Group 2 or between Group 1 and Group 3 was significant(P ＜0.05).The number of patients with ≥ 2 treatments in Group 3 was significantly less than that in other two groups. The cure rate of LM in cervicofacial area was significantly lower than that in other parts of body (P ＜ 0.05).In cervicofacial LM patients, the therapeutic effect differences in maximum diameter, range, histological typing, lymph property were statistically significant (P ＜ 0.05).At the multivariable logistic regression analysis, LM range as well as histological typing were independent factors influencing the therapeutic effect (P ＜ 0.05). Conclusions: Both treatment of endoscopic LM partial resection combined with cautery and postoperative intratumoral negative pressure and absolute ethyl alcohol, and surgical resection have good therapeutic effect on LM in infants. LM range as well as histological typing are important factors independently influencing the therapeutic effect of cervicofacial LM in infants.

Effects of Hospital Type and Distance on Lymph Node Assessment for Colon Cancer Among Metropolitan and Nonmetropolitan Patients in Appalachia.

We studied differences in access to large or accredited cancer programs as a possible explanation for geographic disparities in adherence to the national guideline on lymph node assessment for Stages I to III colon cancer. State cancer registries were linked with Medicare claims of patients diagnosed from 2006 to 2008 from Appalachian counties of four states. Metropolitan and nonmetropolitan patients differed on adherence, proximity to high-volume or accredited hospitals, and hospital type. We modeled effects of hospital type on adherence with ordinary least squares and instrumental variables (instrumenting for hospital type with relative distance). The evidence was strongest for improved adherence in high-volume hospitals for nonmetropolitan patients. We estimate that roughly 100 deaths might be prevented over 5 years among each year's incident cases if the nonmetropolitan disparity in hospital volume were eliminated nationally. We conclude that regionalization or targeting smaller hospitals would improve adherence in nonmetropolitan areas, but also argue for improving adherence generally.

[Venous aneurysms associated with lymphatic malformations]. / Aneurismas venosos asociados a malformaciones linfáticas.

OBJECTIVES: To analyze and describe the association between the development of venous aneurysms of the mayor vessels in patients with lymphatic malformations. MATERIAL AND METHODS: Retrospective review of patients diagnosed with both VA and LM from 1993 to 2014 and a descriptive analysis of clinical course was performed. RESULTS: We found 6 patients, 50% females, who had LM and VA confirmed with imaging techniques. All were diagnosed between 20 weeks- 12 years of age. LM were found within the thoracic cavity (n= 4), intrathoracical-cervical area (n= 1) and lower extremities (n= 1). In most cases the dilated veins were near the LM and thus, the mediastinal vessels were most commonly affected (superior vena cava-innominated (n= 1), venous jugulosubclavian confluence (n= 2), superior vena cava (n= 2) and popliteal vein (n= 1)). A total of 4 patients required surgical treatment of the LM with complete excision in 2 of the cases. Patients with a prenatal diagnosis of lymphatic malformation were most likely to present venous aneurysms at birth (n= 2), however the remaining patients (without prenatal diagnosis) developed them later on (average 6 years). Unlike lower extremity aneurysms, none of these aneurysms grew or required antiplatelet therapy; local thrombosis developed in one which resulted in pulmonary thromboembolism and one developed mitral valve insufficiency (regurgitation?) which required valve replacement. CONCLUSION: VA is extremely rare, and there is not therapeutic algorithm, therefore treatment should be individualized.

OBJETTIVOS: Analizar y describir la asociación entre el desarrollo de aneurismas venosos (AV) de grandes troncos en pacientes con malformaciones linfáticas (ML). MATERIAL Y METODOS: Estudio retrospectivo de los pacientes de nuestro centro entre 1993-2014, y análisis descriptivo de la asociación AV y ML. RESULTADOS: Se identificaron 6 pacientes, 50% mujeres, con una ML confirmada mediante prueba de imagen y una dilatación aneurismática de un tronco venoso. Los pacientes tenían edades entre 20 semanas-12 años y las ML se encontraban intratorácicas (n= 4), intratorácicas-cervical (n= 1) y en miembro inferior (n= 1); y las venas dilatadas en sus proximidades, siendo afectadas con mayor frecuencia los grandes vasos mediastínicos (vena cava superior- innominada (n= 1), confluencia venosa subclavioyugular (n= 2), vena cava superior (n= 2) y la vena poplítea (n= 1)). Se intervinieron n= 4, no pudiéndose extirpar completamente en 2 casos. Los niños que presentaron un diagnóstico prenatal de la malformación linfática presentaban una dilatación aneurismática de una gran vena en el control neonatal de la malformación (n= 2). En cambio, los pacientes con diagnóstico tardío de ML no presentaban dilatación vascular hasta pasados varios años (media 6 años). Ningún AV ha iniciado tratamiento antiagregante, y no han aumentado bruscamente su tamaño, uno desarrolló un trombo y posteriormente un tromboembolismo pulmonar, y otro debutó una insuficiencia mitral necesitando un recambio valvular mitral. CONCLUSION: El AV es una entidad poco común, y no existe algoritmo terapéutico, siendo una máxima el tratamiento individualizado de cada paciente.

ULTRASONOGRAPHIC FINDINGS IN 13 HORSES WITH LYMPHOMA.

Ultrasonography and radiography are commonly used for staging of lymphoma in horses, however there is little published information on imaging characteristics for horses with confirmed disease. The purpose of this retrospective, case series study was to describe ultrasonographic and radiographic findings for a group of horses with a confirmed diagnosis of lymphoma. A total of 13 horses were sampled. Lymphadenopathy (8/13), peritoneal effusion (6/13), splenic (6/13), and hepatic (5/13) lesions were the most frequently identified. The predominant splenic and hepatic ultrasonographic lesions were hypoechoic nodules, organomegaly, and changes in echogenicity. Digestive tract lesions were detected in three horses and these included focal thickening and decreased echogenicity of the small (2/13) and large intestinal (2/13) wall. Thoracic lesions were predominantly pleural effusion (4/13), lymphadenopathy (4/13), and lung parenchymal changes (3/13). Enlarged lymph nodes were detected radiographically (4/13) and/or ultrasonographically (2/13) in the thorax and ultrasonographically in the abdomen (7/13) and in the caudal cervical region (4/13). Findings supported the use of abdominal and thoracic ultrasonography for lymphoma staging in horses. Ultrasound landmarks for localizing cecal and caudal deep cervical lymph nodes were also provided.

Bacterial translocation in alymphoplasia (aly/aly) mice.

Bacterial translocation (BTL) is defined as the passage of viable bacteria from the gastrointestinal tract to the organs. This study was to elucidate the roles of Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) in BTL. Alymphoplastic mutant mice and phenotypically normal heterozygous micewere dominantly colonized with streptomycin-resistant Escherichia coli and BTL was examined. In PP- and MLN-competent mice, BTL to MLNs was detected in 100% of mice, but BTL to organs was rare (25%). On the other hand, in PP- and MLN-deficientmice, BTL to organs was detected in 91% of mice. The results clearly indicate that PPs are not the only site for bacterial entry.