Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia.

We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment. Lymphoscintigraphy is safe and useful in the diagnosis of lymphatic dysplasia in the newborn and children. Moreover, it is well tolerated by patients and well accepted by their parents.

Diagnosis and whole body screening using blood pool scintigraphy for evaluating congenital vascular malformations.

BACKGROUND: Because magnetic resonance imaging and angiography are inappropriate for whole-body screening because of high cost or invasiveness, we investigated the potential of whole-body blood pool scintigraphy (WBBPS) as a screening and diagnostic tool for congenital vascular malformations (CVMs). METHODS: The subjects of the study were 137 patients (mean age: 20 ± 16 years; range: 0.3-68 years) with suspected CVM. Whole-body anterior and posterior images were acquired twenty minutes after injection of 760 MBq (99m)Tc-labeled red blood cells (pediatric dose: 13 MBq/kg). The final diagnosis was determined by clinical findings, magnetic resonance imaging, angiography, Doppler sonography, and lymphoscintigraphy. RESULTS: Of these patients, 124 had venous malformations, and 13 had lymphatic malformations. WBBPS successfully detected abnormal blood pooling lesions in 96.8% (120/124) of the patients with venous malformations. None of the patients with lymphatic malformation showed abnormal uptake on WBBPS. In addition, WBBPS detected 41 additional abnormal vascular lesions that were not found during initial clinical evaluation in 16.9% (21/124) of the patients with venous malformations. CONCLUSION: WBBPS is a valuable diagnostic and screening modality for the initial evaluation of CVM because of its high characterizing accuracy of 97.1% and the ability to image the whole body.

Trypanosoma cruzi connatal transmission in dogs with Chagas disease: experimental case report.

Trypanosoma cruzi connatal transmission was studied in male and female mongrel dogs. Both dogs were experimentally infected, after which on the 20(th) day, lymphoadenomegaly and fever were found. Four months postinfection, they mated. At this time, Chagas disease was confirmed by two different diagnostic tests. The electrocardiogram and echocardiogram taken at the eight postinoculation month showed data consistent with ischemia, local conduction abnormalities and hypertrophy, as well as a diminished ejection fraction and left ventricular dilation, respectively. Four puppies were born and after weaning had weakness, progressive weight loss, and chronic diarrhea. Necropsy of all four showed digestive alterations and cardiac dilation. Serology in the offspring was positive for Chagas disease. The histopathological study demonstrated a cardiac chronic inflammatory process, although no parasites were found. Clinical data and serological determinations are consistent with death from advanced Chagas disease.

Aberrant lymphatic development in euploid fetuses with increased nuchal translucency including Noonan syndrome.

OBJECTIVE: Increased nuchal translucency in the human fetus is associated with aneuploidy, structural malformations and several syndromes such as Noonan syndrome. In 60­70% of the Noonan syndrome cases, a gene mutation can be demonstrated. Previous research showed that aneuploid fetuses with increased nuchal translucency (NT) demonstrate an aberrant lymphatic endothelial differentiation. METHOD: Fetuses with increased NT and normal karyotype (n = 7) were compared with euploid controls having normal NT (n = 5). A Noonan syndrome gene mutation was found in three out of seven fetuses with increased NT. Endothelial differentiation was evaluated by immunohistochemistry using lymphatic markers (PROX-1, Podoplanin, LYVE-1) and blood vessel markers vascular endothelial growth factor-A (VEGF-A), Neuropilin-1 (NP-1), Sonic hedgehog, von Willebrand factor, and the smooth muscle cell marker, smooth muscle actin. RESULTS: Nuchal edema and enlarged jugular lymphatic sacs (JLSs) were observed in fetuses with increased NT, together with abnormal lymphatic endothelial differentiation i.e. the presence of blood vessel characteristics, including high levels of VEGF-A and NP-1 expression. The enlarged JLSs contained erythrocytes and were surrounded by smooth muscle cells. CONCLUSION: This study shows an aberrant lymphatic endothelial differentiation in fetuses with increased NT and a normal karyotype (including Noonan syndrome fetuses), as was previously reported before in aneuploid fetuses.

Malformaciones linfáticas complejas: implicaciones diagnósticas y terapéuticas / Complex lymphatic malformations: diagnostic and therapeutical implications

Introducción. Las malformaciones linfáticas complejas (MLC) son alteraciones del desarrollo del sistema linfático, en la mayoría de los casos de origen genético, con afectación mixta del sistema vascular: linfático, venoso y capilar. Se caracterizan por afectar de forma extensa la superficie corporal del niño o por asociarse a otros síndromes o enfermedades sistémicas. Material y métodos. Revisamos los 21 pacientes con MLC tratados en nuestro centro en los últimos 15 años. Utilizamos el anticuerpo monoclonal D2-40 (inmunohistoquímica) para evaluar el grado de afectación linfática (como marcador de la afectación linfática). Así mismo analizamos las implicaciones quirúrgicas en este tipo de pacientes. Resultados. Doce niños tenían afectación linfática exclusivamente y nueve linfático-capilar o linfático-venosa. Dos fallecieron por insuficiencia respiratoria (período neonatal) e hipoproteinemia refractaria (a los 8 años de edad). La piel estaba afectada entre el 10 y 35% de la superficie corporal. En tres casos había afectación visceral (pulmonar y mediastínica) y en 18 musculoesquelética. La sintomatología más frecuente fue la deformidad severa (20), seguida de linforragia (15), linfangitis de repetición (7) y dolor crónico (5). La intensidad de la inmunorreacción con el anticuerpo monoclonal D2- 40 se correlacionó con la severidad de la afectación local y sistémica así como con la existencia de malformaciones asociadas. Quince de los pacientes fueron sometidos a tratamiento quirúrgico secuencial, siete recibieron esclerosis seriadas con OK-432 y cuatro vaporización con láser de CO2. La linforragia residual de los pacientes en los que se pudo extirpar completamente la malformación cedió tras punciones evacuadoras repetidas considerándose la curación de la enfermedad. Conclusiones: 1. El anticuerpo monoclonal D2-40 es un marcador de mal pronóstico en las MLC. 2. La extirpación radical de la malformación consigue la curación y la linforragia asociada no debe considerarse una recidiva, cediendo en todos los casos tras punciones evacuadoras. 3. Las MLC requieren protocolos de tratamiento por un equipo multidisciplinario para paliar las secuelas postoperatorias y a largo plazo (AU)

BACKGROUND: Complex lymphatic malformations (CLM) consist of disturbances of lymphatic system development, most often with a genetic origin and with mixed vascular system involvement: lymphatic, venous and capillary. They affect a large corporal area or are associated to other syndromes or systemic diseases. METHODS: We reviewed 21 patients with CLM treated in our hospital during the last 15 years. We used D2-40 monoclonal antibody (by immunohistochemistry) as lymphatic marker to evaluate the level of lymphatic involvement. Furthermore we analysed surgical implications in this group of patients. RESULTS: Twelve children had only lymphatic involvement and nine mixed lymphatic-capillary or lymphatic-venous one. Two died of: respiratory insufficiency (in the neonatal period) and refractory hypoproteinemia (at 8 years of age). The skin was affected between 10 and 35% of total body surface. Three patients suffered from visceral involvement (lungs and mediastinum) and eighteen musculoskeletal. Severe deformity (20), lymphorhagia (15), repeated lymphangitis and chronic pain (5) were the most common symptoms reported. The immunoreaction intensity with monoclonal antibody D2-40 was related to the severity of the local and systemic involvement as well as to the presence of associated malformations. Fifteen cases underwent sequential surgical treatment, seven were treated with sclerotherapy (OK-432) and four with CO2 laser vaporization. Residual lymphorhagia in patients with total extirpation of the lymphatic malformation stopped after repeated evacuator punctures and healing took place. CONCLUSIONS: (1) D2-40 monoclonal antibody is a marker of bad prognosis in CLM. (2) The complete excision of the lymphatic malformation lead to healing and the associated lymphorragia should not be considered as a recurrence, which will stop with evacuator punctures in all cases. (3) A multidisciplinary team approach is essential for the proper care of CLM in order to minimize postoperative sequelae and late complications (AU)

Current concepts in lymphatic malformation.

A lymphatic malformation (LM) is the most common form of congenital vascular malformation (CVM). The new Hamburg classification of CVM distinguishes the truncular (T) form from the extratruncular (ET) form of LMs. Both are consequences of a developmental arrest at the different stages of lymphangiogenesis as a result of defective genes. The purpose of this review was to evaluate the current management results of both forms of LMs. A retrospective review of the clinical data of 315 patients with a diagnosis of LMs treated between September 1994 and December 2001 was performed. Lymphoscintigraphy was the most frequent diagnostic test. The patients with the ET form were treated with sclerotherapy with OK-432 and/or ethanol. Combinations of CDP (complex decongestive physiotherapy) and/or compressotherapy were used to treat all the T-form patients. In addition, surgery, either reconstructive or ablative, was offered to patients with the T form who failed to respond to the proper CDP. A multidisciplinary team performed the management of LM, and the results were evaluated every 6 months. Among 797 patients with CVM, 315 were confirmed to have LMs, either as the T form (226) or the ET form (89). Another 66 LMs were diagnosed with hemolymphatic malformations (HLM). Most of the ET forms (89/315) were the cystic type (70/89), while the T forms included aplasia and/or an obstruction (204/226). The ET form was most frequent in the head, neck, and thorax (69/89). The T form was located most frequently to the extremities (202/226), mostly to the lower limb (180/202). Two hundred and twenty-six T forms belonged to the various clinical stages: stages I-32, II-104, III-48, IV-18, and an unclear stage-24. The ET form was treated with sclerotherapy using OK-432 (108/120) and absolute ethanol (12/120). Among the 11 patients with the multiple ET form, 7 patients underwent perioperative sclerotherapy with OK-432 and a subsequent surgical excision. The clinical response of the T form at the extremity to CDP was excellent to good in a majority of clinical stages I to II (121/136) but decreased to a good to fair degree in stages III to IV (31/66). The additional surgical therapy, either reconstructive (10/19) or ablative (9/19), provided limited success in improving CDP efficacy, owing mainly to poor compliance. The long-term outcome of the initial success through self-motivated home-maintenance care during the follow-up period of up to 48 months was totally dependent on patient compliance. OK-432 sclerotherapy to 51 ET forms has shown excellent results on 88.9% of the cystic type (40/45) and 50% (3/6) of the cavernous type (minimum follow-up for 24 months). Seventeen ET forms in 7 patients were treated with a preoperative OK-432 sclerotherapy and a subsequent surgical excision, which provided good to excellent results in 14 for a minimum of 24 months. Primary lymphedema, which is the T form of LMs, can be managed safely by a combination of CDP with compressotherapy. Patients with good compliance can benefit from additional surgical therapy, either reconstructive or ablative. The ET form, particularly the cystic type, can be treated with various scleroagents that are preferably less toxic as the primary therapy. A surgical excision with or without perioperative sclerotherapy provides good results for patients with the localized cavernous type of the ET form. A multidisciplinary team approach is essential for the proper care of LM.

Sclerotherapy for congenital lesions in the head and neck.

OBJECTIVES: This study retrospectively reviews the results of sclerotherapy using several sclerosants for congenital lesions of the head and neck. METHODS AND PATIENTS: Between May 1990 and May 2002, patients with lymphatic malformations were treated by sclerotherapy; 10 with bleomycin, and 25 with OK-432. OK-432 sclerotherapy was also applied in 9 patients with plunging ranula and in 1 patient with branchial anomaly. Percutaneous sclerotherapy with ethanolamine oleate was used in 29 patients with venous malformations, and 28 patients with pyriform sinus fistula were treated by trichloroacetic acid chemocauterization. RESULTS: Overall, two thirds of patients with these lesions showed marked to complete response. One case of mortality occurred in the bleomycin sclerotherapy group. However, no major complications by other sclerosants were found. In lymphatic malformations, history of excision before sclerotherapy was a poor prognostic factor. CONCLUSION: Sclerotherapy using these sclerosants is a safe and effective primary treatment for congenital lesions in the head and neck.

Successful management of congenital chyloperitoneum with fibrin glue.

Chylous ascites in children has been treated in a variety of ways, including a low-fat diet, medium chain triglycerides, diuretics, total parental nutrition, surgical exploration, and internal peritoneo-venous shunting. The authors describe a child with persistent congenital chyloperitoneum treated successfully with the application of fibrin glue and recommend this as an effective alternative to traditional approaches.

Absent or hypoplastic thymus on ultrasound: a marker for deletion 22q11.2 in fetal cardiac defects.

OBJECTIVE: Congenital heart defects (CHD), particularly conotruncal anomalies, may be associated with deletion of chromosome 22q11.2. Thymic aplasia or hypoplasia is known to be a typical feature in this condition. We aimed to establish (i) the prevalence of del22q11.2 in fetal CHD and (ii) whether ultrasound assessment of an absent or hypoplastic fetal thymus helps in preselection of a group who are at high risk for this deletion. STUDY DESIGN: In fetuses (> 16 weeks) with CHD, karyotyping and fluorescence in situ hybridization for 22q11.2 were offered and the fetal thymus was evaluated sonographically. RESULTS: One hundred and forty-nine fetuses with CHD and normal karyotype were analyzed. Seventy-six fetuses had conotruncal anomalies. 22q11.2 deletion was present in 10 cases (6.7%), all of which had conotruncal anomalies (13.1%). Thymic hypoplasia or absence was suspected in 11 cases with conotruncal anomaly. Nine of these 11 had the deletion; two cases were false positive. One fetus with a normal-sized thymus had deletion of 22q11.2 (sensitivity 90%, specificity 98.5%, positive predictive value 81.8%, and negative predictive value 99.2%). By subtype of cardiac anomaly, there was deletion in four of six fetuses with interruption of the aortic arch, two of four with absent pulmonary valve syndrome, three of nine with truncus arteriosus and one of 11 cases of tetralogy of Fallot. Pulmonary atresia with ventricular septal defect (n = 7), right-sided aortic arch (n = 4), transposition of the great arteries (n = 14), double outlet right ventricle (n = 13) and other complex malpositions of the great vessels (n = 8) were not associated with the deletion. CONCLUSION: Thymic hypoplasia or aplasia may reliably be diagnosed during fetal echocardiography. The technique allows identification of a group at high risk for 22q11.2 deletion and is more specific and sensitive than by subtype of cardiac anomaly alone.

Postmenarchal development of chylous ascites in acrocephalosyndactyly with congenital lymphatic dysplasia.

BACKGROUND: Acrocephalosyndactyly is a syndrome characterized by congenital malformation of the skull with craniosynostosis, midface hypoplasia, and symmetrical webbed fusion of the fingers and toes. We describe a possible pathophysiologic mechanism for chylous ascites that developed several months after menarche in a woman with acrocephalosyndactyly and congenital lymphatic dysplasia. CASE: A 25-year-old nulligravid woman with acrocephalosyndactyly, at 18 months after menarche, developed persistent abdominal distension at age 18 years. Laparoscopy at age 25 years revealed chylous ascites with marked chronic peritoneal inflammation, and lymphatic dysplasia with lymphocysts. With hormone manipulation, the chylous ascites fluctuated. CONCLUSION: After menarche in a woman with acrocephalosyndactyly, ovarian steroid hormones might have increased lymph production and hydrostatic pressure, causing rupture of congenitally dysplastic lymph vessels resulting in chylous ascites.

Therapeutic tactics and late results in predominant truncal congenital malformation.

BACKGROUND: Congenital vascular malformations are rare vascular lesions of unknown etiology, non-degenerative or of inflammatory nature, which begin during embryological development; they are characterized by anomalies of the vascular system, apparently due to hemodynamic and metabolic disturbances. METHODS: Our diagnostic and therapeutic management in addition to the late results in 60, mainly truncal cases, out of 265 congenital vascular malformations, are analyzed in the present study. In a 20-year period 25,000 vascular examinations were carried out, among which 265 (1.06%) congenital vascular malformations (CVMs) were discovered, that is 77% (205/265) extra-truncal venous angiomata and 22.7% (60/265) truncal diffuse or localized types. The distribution of the above types was: 22 (36.6%) arteriovenous, 30 (50%) venous and 8 (13.4%) lymphatic. RESULTS: Surgery was carried out in 48.3% (29/60) of the truncal types of which 37.9% of the cases, on average, recurred 8 years later. Of the 22 arteriovenous malformations 20 patients were operated on (90%), of whom 35% (7/20) had a recurrence; of the 30 venous defects 30% (9/30) were operated on and 44.5% (4/9) of these had a recurrence. The recurrence rate rose to 50% (5/10) in cases of operative therapy of arteriovenous defects and to 20% (2/10) with combined surgical and non surgical methods. The recurrence incidence of venous defects with surgical treatment and sclerotherapy was 54.1% (6/11). CONCLUSIONS: Timely diagnosis, microsurgical techniques and highly specialized surgical and interventional experience are expected to improve these results significantly.

Congenital thymic aplasia in a Holstein-Israeli female calf.

An unusual case of congenital thymic aplasia in a Holstein-Israeli female calf is described. The most prominent clinical findings were diarrhoea and weakness. At necropsy, the only significant pathological finding was the marked decrease in thymus size. Histologically, this organ was composed of loose connective tissue in which a few lymphocytes were scattered randomly.

Histiocitosis de células de Langerhans solitaria congénita autoinvolutiva / Solitary congenital self-healing Langerhans cells histiocytosis

Se presentan dos casos de recién nacidos con una lesión solitaria (en ingle y hombro), respectivamente, de histiocitosis de células de Langerhans (HCL) que se resolvieron espontáneamente. Hasta la fecha, los pacientes no han presentado afectación orgánica por HCL. Esta forma de presentación es infrecuente y parece ser una variante de la reticulohistiocitosis congénita autoinvolutiva (AU)

Association of reticular dysgenesis (thymic alymphoplasia and congenital aleukocytosis) with bilateral sensorineural deafness.

Reticular dysgenesis is a rare congenital disorder characterized by severe combined immunodeficiency and profound neutropenia, curable to date, only by bone marrow transplantation. This report describes the association of bilateral sensorineural deafness with this disease.

Lymphatic dysplasia in paediatrics. A new classification.

A classification of dysplasias of the lymphatic system is proposed on the basis of the anatomical structures involved: lymph vessel-angiodysplasia, lymphadeno(nodal)-dysplasia and the summary of both lymphangio-adeno(nodal)dysplasias. The suggested terminology is: LAD I (Lymphangiodysplasias), LAD II (Lymphadeno(nodal)dysplasia) and LAAD (lymphadeno(nodal)-dysplasia). With this classification we may coherently group the malformations we already know, relate them to the big syndromes and to all the other angiodysplasias and also create the reference background for another chapter of lymphology: primary or idiopathic lymphedema.

[Hashimoto-Pritzker self-healing reticulohistiocytosis and congenital histiocytosis]. / Réticulohistiocytose auto-involutive de Hashimoto-Pritzker et les histiocytoses congénitales.

BACKGROUND: Congenital histiocytosis is divided into four entities differing in their clinical and histological features and prognosis. Early, accurate diagnosis is essential for treatment. CASE REPORT: Seven cutaneous nodules were seen in a male neonate. One of these nodules was biopsied on the 7th day of life; it showed the typical findings of Hashimoto-Pritzker reticulohistiocytosis by optical and electron microscopy using immunological markers. The nodules spontaneously disappeared after a few months. CONCLUSIONS: Congenital forms of histiocytosis must be accurately characterized. Hashimoto-Pritzker reticulohistiocytosis is a benign and self-healing disease restricted to the skin, while the Letterer-Siwe disease has a completely different course and treatment.