Developmental Disorders of the Lymphatics

Understanding the Lymph System

2009-10-28T08:18:00.000-07:00

Understanding the Lymph System

I thought it would be helpful for readers to understand the lymph system, the anatomy, what it does, and how it helps with immunity.

Listed below are information pages that should be quite helpful and each page has many additional links for more a more in depth study.

Anatomy of the Lymph System

Lymphatic System Functions

Lymphatic System and Immunity

Pathology of the Lymph Nodes and Lymphoma

Lymph Nodes

Lymph Fluid

Pancreatic cystic lymphangioma: report of a case.

2009-10-17T05:15:00.000-07:00

Pancreatic cystic lymphangioma: report of a case.

Turk J Gastroenterol. 2009 Sep

Yüceyar S, Kapan M, Ozben V, Ertürk S, Aydin I, Kepil N.

Departments of Surgery, Istanbul University, CerrahpaSa School of Medicine, Istanbul. seryuce@istanbul.edu.tr

We herein present a patient referred to our clinic with the complaints of flatulence and left upper quadrant abdominal pain who was diagnosed to have pancreatic cystic neoplasia radiologically. The septated cyst was defined to be 9x12 cm in diameter by abdominal computed tomography and by ultrasonography originated from the tail of the pancreas. Distal pancreatectomy procedure with complete resection of the cystic lesion was performed in this patient. Pathologic examination revealed pancreatic cystic lymphangioma (PCL). Although PCL is very rare in adult patients, it can cause confusion due to the presence of other cystic pathologies of the pancreas. Complete excision of the cyst is mandatory to prevent recurrences. In our case, no recurrence was detected after a two-year follow-up.

Introduction

Lymphangiomas are rare congenital benign tumors arising from the lymphatic system (1), and are mostly encountered in the neck and axillary regions of pediatric patients (95%) (2). Lymphangioma cases have also been reported in other organs, such as the liver, spleen, lungs, mediastinum, colon, retroperitoneum, pancreas, omentum, pericardium, pleura, kidneys, ureters, bone, scrotum, penis, and cervix, etc. (2). Intraabdominal lymphangiomas are extremely rare, with a reported incidence of less than 1 in 20,000 to 1 in 250,000 hospital admissions (3). Pancreatic cystic lymphangioma (PCL) is mostly seen in female adults and particularly represents an exceptional report (3, 4). Since its first description by Koch in 1913, a literature review revealed only 64 PCL cases (4).

Lymphangiomas are classified into three groups as cystic, capillary and cavernous (2). Although rare, the diagnosis of PCL is not easy (3) and should be taken into account with other cystic neoplasms of the pancreas.

Case Presentation

A 50-year-old female patient was referred to our clinic with the complaints of flatulence and left upper quadrant abdominal pain. On physical examination, a palpable mass without clear borders was detected on the left subchondral region. All laboratory values, tumor markers and serologic tests were within normal limits.

Hemagglutination test for hydatid disease was negative. Abdominal computed tomography (CT) scan revealed a lobulated hypodense cystic mass 9x12 cm in diameter, originating from the tail of the pancreas (Figure 1). In ultrasonography (USG), the mass was defined to be a septated fluid-containing cyst. Upper gastrointestinal endoscopy revealed nothing but the erosive gastritis and there was no external compression to the stomach. Fine needle aspiration biopsy (FNAB) of the pancreas was performed, and lymphoid cell components in a benign cystic lesion were reported in the histologic examination.

The patient was operated with the preoperative diagnosis of pancreatic cystic neoplasia. Following the left subcostal incision, abdominal exploration was performed and a lobulated cystic lesion 10 cm in diameter originating from the tail of the pancreas and extending into the transverse mesocolon was detected. There was no invasion of the cyst into other organs or vascular structures. Distal pancreatectomy including the cyst and the distal onethird of the pancreas was performed. A clear liquid was aspirated from the cyst. The pancreas was closed with U-suture.

Macroscopic examination revealed a septated cystic lesion measuring 10x3x2 cm extending into the peripancreatic tissue; histopathology reported the cyst as peripancreatic lymphangioma with ectasia of the lymphatic vessels. Mature lymphocytes and rare macrophages were detected in the aspirated fluid (Figure 2). There was no postoperative complication.

Discussion

Lymphangiomas are endothelium-lined benign tumors that arise from the lymphatic system owing to congenital malformations. These malformations result in blockage of the lymphatic flow; thus, cystic dilatation of lymphatic channels occurs (5). Another theory is an inflammation leading to obstruction in lymphatic channels (3).

Lymphangioma is mostly encountered in the pediatric age group. They are characterized by cystic and cavernous spaces and are mostly localized in the neck and axilla (95%), whereas abdominal involvement is seen in about 1% of all cases (3,4). PCLs, described for the first time by Koch in 1913, are extremely rare lesions (4), and fewer than 100 cases have been reviewed in the literature (6).

Macroscopically, cystic lymphangiomas are multiloculated soft cystic masses that contain either serous or serohemorrhagic or lymphatic fluid. Dilated lymphatic channels of varying size divided by thin septae are observed histologically. The cystic wall is lined by thin and flat endothelial cells. Islands of lymphocytes can be present in the lumen and/or neighboring tissue (4). In our case, the cyst was found to be septated and contained clear fluid macroscopically, and the diagnosis of PCL was made on histopathologic examination.

Abdominal lymphangiomas (ALs) account for less than 1% of all lymphangiomas and can be seen in any age group but are more frequent in female adults (1, 3). In a study by Igarashi et al. (2) that included 45 pancreatic lymphangioma cases, the female:male ratio was found to be 29:16. ALs generally present with vague abdominal symptoms such as chronic abdominal pain, nausea and vomiting, distension, and palpable abdominal mass. These symptoms may develop acutely in children, whereas in adults, months or even years may pass from the onset of the symptoms until the diagnosis. Furthermore, although rare, acute abdomen can occur due to the complications such as intestinal obstruction, rupture and/or hemorrhage (7).

If the lymphangioma arises within the pancreatic tissue substance or if it is attached to the pancreas with a pedicle, it is termed as pancreatic lymphangioma (4). In our case, lymphangioma arose from the tail of the pancreas. In Igarashi’s review study (2), it was observed that PCLs mostly derived from the body and tail of the pancreas.

Abdominal US, CT, magnetic resonance imaging (MRI), angiography and FNAB can be employed for the preoperative diagnosis of lymphangiomas. In USG, septated cysts can be visualized. Although CT provides additional information about the characteristics of the lesion, the diagnosis is often not direct. The capsule and the septations of the cyst and their thickness and the characteristics of the fluid within can be evaluated with CT. Preoperative FNAB is still controversial as it might cause hemorrhage, rupture or tumor implantation in malignant cases (4). MRI does not yield any further information (1). None of the examinations described above are pathognomonic. A preoperative diagnosis of PCL is difficult. Definitive diagnosis can only be made by histopathologic examination of the resected lesion (7), and the diagnosis is supported immunohistochemically by positive staining of factor VIII-R antigen, CD31, and CD34 markers (2).

Although clinical follow-up with periodic imaging of patients with PCL has been suggested (8), surgery is the current treatment of choice (3, 4). Laparotomy is generally preferred; however, laparoscopic resection can also be performed in suitable cases. Total resection of the lesion is mandatory. In our case, we needed to perform distal pancreatectomy for the total removal of the lesion, and no recurrence has been observed after a two-year follow- up. We noted that in a review study by Igarashi (2) including 45 PCLs, six distal pancreatectomies were performed, and distal pancreatectomy procedure was also preferred in two cases by Casadei (4).

In summary, PCLs are very rare tumors and carry a potential risk of local invasion. Definitive diagnosis can only be made by histopathologic examination of the excised lesion. Total resection of the tumor is mandatory in case of recurrence. Therefore, as in our case, partial pancreatectomy may be needed in some patients.

Turkish Journal of Gastroenterology

Successful treatment of intraorbital lymphangioma with tissue fibrin glue.

2009-10-17T05:10:00.000-07:00

Successful treatment of intraorbital lymphangioma with tissue fibrin glue.

Surg Neurol. 2009 Oct 12

Hayasaki A, Nakamura H, Hamasaki T, Makino K, Yano S, Morioka M, Kuratsu JI.

Department of Neurosurgery, Kumamoto University Medical School, Kumamoto 860-8556, Japan.

BACKGROUND:

Although surgical resection is the first treatment choice in patients with cystic lymphangioma, the complete resection of orbital lymphangioma is often difficult. After partial resection of the cyst wall, some cystic lymphangiomas recur. The injection of tissue fibrin glue may prevent the recurrence of orbital lymphangioma.

CASE DESCRIPTION:

We present a 2-year-old girl with left progressive exophthalmos. Magnetic resonance imaging revealed a cystic mass lesion behind the left eyeball. At the first operation, the cyst wall was partially resected, and all cyst fluid was totally removed by suction. One week after the first operation, the cyst showed regrowth. At a second procedure, we injected tissue fibrin glue into the cyst. The cyst was completely sealed, and there was no recurrence.

CONCLUSION:

Tissue fibrin glue is adhesive and hemostatic and highly useful in the treatment of orbital cystic lymphangioma.

Elsevier

The Unique biology of lymphatic edema

2009-09-29T01:19:00.000-07:00

The Unique biology of lymphatic edema

Lymphat Res Biol. 2009

Rockson SG.

Stanford Center for Lymphatic and Venous Disorders, Stanford University School of Medicine, Stanford, California 94305, USA. srockson@cvmed.stanford.edu

Sadly, the subject of lymphatic vascular insufficiency continues to engender relative neglect by health care professionals, which represents a source of frustration and fear among patients. A re-consideration of the unique, complex biology of lymphatic vascular disorders has the capacity both to reinvigorate interest and facilitate the implementation of the correct, existing treatment interventions for individuals affected by these disease states. While most of this complex lymphatic biology remains somewhat elusive, growing insights into the molecular mechanisms of lymphatic development and repair have been instructive. Present and future considerations in lymphedema diagnosis and management must acknowledge the unique tissue biology of this disorder. Many changes are unique to the lymphatic mechanisms of chronic edema. The profound stimulus to collagen deposition in the integument seems to be unique to chronic lymphatic edema, although this biology remains largely unexplicated. Several lines of evidence also suggest that lymphatic function has a unique and important influence upon adipose biology. Molecular investigation of murine models of human acquired lymphedema are beginning to shed light on these processes. Such focused mechanistic, approaches to the study of lymphedema and other lymphatic diseases are vital, as we attempt to expand our insights into the complex biology of lymphedema and its potential responsiveness to pharmacologic control and molecular intervention, prevention, and reversal.

MaryAnnLiebert

Contractile Physiology of Lymphatics

2009-09-29T01:13:00.000-07:00

Contractile Physiology of Lymphatics

Lymphat Res Biol. 2009

Zawieja DC.

Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, Temple, Texas 77843-1114, USA.

The lymphatic system has important roles in body fluid regulation, macromolecular homeostasis, lipid absorption, and immune function. To accomplish these roles, lymphatics must move fluid and its other contents (macromolecules, lipids/chylomicra, immune cells) from the interstitium through the lymphatics, across the nodes, and into the great veins. Thus, the principal task of the lymphatic vascular system is transport.

The body must impart energy to the lymph via pumping mechanisms to propel it along the lymphatic network and use pumps and valves to generate lymph flow and prevent its backflow. The lymphatic system utilizes both extrinsic pumps, which rely on the cyclical compression and expansion of lymphatics by surrounding tissue forces, and intrinsic pumps, which rely on the intrinsic rapid/phasic contractions of lymphatic muscle.

The intrinsic lymph pump function can be modulated by neural, humoral, and physical factors. Generally, increased lymph pressure/stretch of the muscular lymphatics activates the intrinsic lymph pump, while increased lymph flow/shear in the muscular lymphatics can either activate or inhibit the intrinsic lymph pump depending on the pattern and magnitude of the flow. To regulate lymph transport, lymphatic pumping and resistance must be controlled.

A better understanding of these mechanisms could provide the basis for the development of better diagnostic and treatment modalities for lymphatic dysfunction.

MaryAnnLiebert

Vascular Malformations: an update

2009-09-29T01:09:00.000-07:00

Vascular Malformations: an update

Perspect Vasc Surg Endovasc Ther. 2009 Jun

Gloviczki P, Duncan A, Kalra M, Oderich G, Ricotta J, Bower T, McKusick M, Bjarnason H,Driscoll D.

Division of Vascular and Endovascular Surgery and Vascular Malformation Clinic, Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA. gloviczki.peter@mayo.edu , Division of Vascular and Interventional Radiology, Mayo Clinic, Rochester, MN, USA, Vascular Malformation Clinic, Gonda Vascular Center, mayo Clinic, Rochester, MN, USA, Division of Vascular and Endovascular Surgery, Gonda Vascular Center, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Vascular malformations occur as a result of an arrest in the development of the vascular system. The modified Hamburg classification distinguishes arterial, venous, arteriovenous, capillary, lymphatic, and mixed vascular malformations. Each malformation is further subdivided based on anatomy and on the time when arrest in development of the embryogenesis occurred; malformations can be truncular or extratruncular. Progress in the last decade in management has been significant because of improvements in open surgical procedures and perfection of percutaneous and hybrid endovascular interventions and devices, such as balloons, stents, and stent-grafts. There has been increasing use of embolization for the treatment of malformations with coils, other particles, glue, or with endovascular placement of occlusive plugs. Absolute alcohol, detergent liquids, or foam have been used for sclerotherapy with improved efficacy. The agents are delivered percutaneously or through a catheter placed either into the feeding arteries or the draining veins. This review aims to aid vascular and endovascular specialists in staying familiar with vascular malformations. These specialists need to be able to evaluate the patients, perform treatment if appropriate, or refer complex cases to multidisciplinary vascular malformation clinics and vascular centers.

Sage Publications

SoxF genes: Key players in the development of the cardio-vascular system.

2009-09-29T01:04:00.000-07:00

SoxF genes: Key players in the development of the cardio-vascular system

Francois M, Koopman P, Beltrame M.

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld 4072, Australia.

SoxF genes (Sox7, Sox17 and Sox18) encode a group of transcription factors that have a pivotal role in cardio-vascular development. SOXF factors orchestrate endothelial cell fate or direct cell differentiation in developing heart, blood vessels and lymphatic vessels. Their roles are highly conserved throughout animal evolution. SOXF activity is finely tuned with a variety of cell type-specific co-factors and partner proteins to effect transcription of genes critical for endothelial cell phenotype and function. Because SOXF factors play a central role in cardiogenesis, vasculogenesis and lymphangiogenesis, SOXF gene mutations figure prominently in the aetiology of human vascular disease.

Wiley InterScience

Lymphatic Development

2009-09-29T00:53:00.000-07:00

Lymphatic Development

Birth Defects Res C Embryo Today. 2009 Sep 11

Butler MG, Isogai S, Weinstein BM.

Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

email: Brant M. Weinstein (bw96w@nih.gov)

The lymphatic system is essential for fluid homeostasis, immune responses, and fat absorption, and is involved in many pathological processes, including tumor metastasis and lymphedema. Despite its importance, progress in understanding the origins and early development of this system has been hampered by lack of defining molecular markers and difficulties in observing lymphatic cells in vivo and performing genetic and experimental manipulation of the lymphatic system. Recent identification of new molecular markers, new genes with important functional roles in lymphatic development, and new experimental models for studying lymphangiogenesis has begun to yield important insights into the emergence and assembly of this important tissue. This review focuses on the mechanisms regulating development of the lymphatic vasculature during embryogenesis. Birth Defects Research (Part C)

Wiley InterScience

Intrauterine Treatment of Large Fetal Neck Lymphangioma with OK-432.

2009-09-20T12:37:00.000-07:00

Intrauterine Treatment of Large Fetal Neck Lymphangioma with OK-432.

Fetal Diagn Ther. 2009 Sep 11

Mikovic Z, Simic R, Egic A, Stosic Opincal T, Koprivsek K, Stanojevic D, Bogavac M, Popovac M, Mandic V.
Department of High-Risk Pregnancies, University Clinic of Gynaecology and Obstetrics 'Narodni Front', Belgrade, Serbia.

Lymphangiomas are benign vascular malformations of the lymphatic system and most commonly present in the neck area. Large lymphangiomas may compress and/or displace the larynx, trachea and esophagus and cause serious respiratory and feeding problems in neonates. Prenatal therapy could eliminate the risks of the mentioned complications. Prenatal therapy may include the EXIT (ex utero intrapartum treatment) procedure. As this procedure has certain risks for both the neonate and mother, the introduction of a safer method is justified. The use of OK-432, as a sclerosing agent, has shown positive results in several published cases of cystic hygroma, but there is no study about the prenatal use of this agent in the treatment of lymphangioma. The aim of this study was to present our experience with intrauterine intralesional injection of OK-432 in the treatment of neck lymphangiomas. Two cases of large multicystic neck lymphangiomas that were closely situated to the fetal airway were treated by single intralesional injection of OK-432. We noticed a progressive decrease in tumor volume throughout gestation. We did not experience any complications and there were no respiratory or feeding problems in the neonates. The esthetical appearance was satisfactory and both children were normal at the age of 2 years and 6 months, respectively. This report suggests that prenatal intralesional injection of OK-432 might be a safe and effective treatment in selected cases with large fetal neck lymphangiomas.

Fetal Diagnosis and Therapy

Case report of fetal axillo-thoraco-abdominal cystic hygroma.

2009-09-17T12:15:00.000-07:00

Case report of fetal axillo-thoraco-abdominal cystic hygroma.

Arch Gynecol Obstet. 2009 Apr 10

Masood SN, Masood MF.
Dow University of Health Sciences, Karachi, Pakistan, sh_naz@yahoo.com.

Cystic hygroma (moist tumor) was first described in 1828 by Redenbacher. The cyst usually results owing to an absence or an inefficient connection between the lymphatic and venous systems. Of this type of malformation 75% cases are localized in the nuchal region; however, only 20% are found in the axilla while 5% of these hygromas are in other locations. Prognosis depends on associated fetal co-morbidities. There are many case reports on cystic hygroma but only a few on the axillo-thoraco-abdominal variant. This is a case report of a huge late-onset fetal axillo-thoraco-abdominal cystic hygroma, which was diagnosed at term followed by a difficult vaginal delivery in a 38-year-old woman. The baby did not have any congenital anomaly other than cystic hygroma with no evidence of intrathoracic or intra-abdominal extension of mass and a pelvic kidney reported on neonatal ultrasound and CT scan. The surgical excision of the cyst was done on the fourth day following birth and the histopathology report confirmed the diagnosis. Management of fetal cystic hygroma with the use of a sclerosing agent is a new modality being explored. Risk of recurrence in subsequent pregnancies for aneuploidy is not increased. The baby has been followed up to 5 months of birth and is thriving well. Karyotype shows an XX pattern.

SpringerLink

Abdominal lymphangioma in children: Report of three cases.

2009-06-08T06:35:00.000-07:00

Abdominal lymphangioma in children: Report of three cases.
Surg Today. 2009
Muramori K, Zaizen Y, Noguchi S.
Department of Pediatric Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan.

Most cases of abdominal lymphangioma are asymptomatic. However, patients may occasionally present with acute abdomen because of an intestinal obstruction or peritonitis caused by infected cysts, hemorrhaging, and/or torsion. These conditions may differ based on the location of the lymphangioma and do not always require emergency surgery. This report presents two cases of abdominal lymphangioma derived from the omentum, which required emergency surgery because of severe abdominal distension and peritonitis caused by torsion, respectively. In contrast, another case of retroperitoneal lymphangioma presented with acute abdomen and underwent elective surgery after conservative therapy for peritonitis. Elective surgery is acceptable if the symptoms are controllable under conservative therapy. However, it is important not to overlook the possible lethal complications such as intestinal and/or urological obstruction, aggressive peritonitis, and torsion of the cyst, which require emergency surgery.

SpringerLink

Cystic lymphangiomatous hamartoma masquerading as massive ascites.

2009-06-08T06:31:00.000-07:00

Cystic lymphangiomatous hamartoma masquerading as massive ascites.
Indian J Pediatr. 2009 May

Parakh A, Dubey AP, Garg A, Khurana N, Aggarwal SK.
Department of Pediatric, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India, ankitparakh102@rediffmail.com.

We report a 4-year-old boy presenting with a tense massive ascites and large hydrocele. History and physical examination were unremarkable. Routine laboratory studies were normal. Abdominal ultrasonography revealed massive ascites. Contrast CT was suggestive of a large cyst covering the entire peritoneal cavity. At laparotomy, a large cystic tumor was found extending into the scrotum through the left inguinal ring. Histopathologic examination diagnosed the tumor as a cystic lymphangiomatous hemartoma. Although abdominal lymphangiomas are seen in children, but presenting as massive ascites with hydrocele is very rare.

SpringerLink

Congenital Lymphangioma Circumscriptum of the Vulva.

2009-06-08T06:27:00.000-07:00

Congenital Lymphangioma Circumscriptum of the Vulva

Indian Pediatr. 2009 May

Aggarwal K, Gupta S, Jain VK, Marwah N.
Department of Dermatology, Venereology and Leprology and Department of Pathology, Post Graduate Institute of Medical Sciences and Research, Rohtak, India; and Department of Dermatology, Venereology and Leprology, MM Institute of Medical Sciences and Research, Mullana, Ambala, India. Correspondence to: Dr Sanjeev Gupta, HNo B2, Near Shiv Mandir, MM Medical College Residential Campus, Mullana, District Ambala, Haryana 133 203. India. sanjeevguptadr@yahoo.com.

Lymphangioma circumscriptum of the vulva is a disorder of lymphatic channels involving deep dermal tissues. Most of these cases are confused with genital warts leading to improper diagnosis and treatment. We present a three years young female child who had multiple skin colored papular lesions over the genitals. Skin biopsy revealed features of lymphangioma circumscriptum.

IndianPediatrics.net (Full Text Article PDF)

Molecular targets for therapeutic lymphangiogenesis in lymphatic dysfunction and disease.

2008-12-30T06:20:00.000-08:00

Molecular targets for therapeutic lymphangiogenesis in lymphatic dysfunction and disease.
Lymphat Res Biol. 2008
Nakamura K, Rockson SG.

Stanford Center for Lymphatic and Venous Disorders, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California.

Abstract

The convergence of multiple disciplines upon the study of the lymphatic vasculature has invigorated a renaissance of research, using powerful investigative tools and an exponential growth of interest in this historically underappreciated system. Fundamental discoveries in lymphatic development have yielded relevant animal models for vexing clinical diseases that suffer from nonexistent of minimally effective treatments. Inherited and acquired lymphedema represent the current crux of research efforts to identify potential molecular therapies born from these early discoveries. The importance of the lymphatic system is, however, not limited to lymphedema but encompasses a diverse spectrum of human disease including inflammation and cancer metastasis. As the lymphatic vasculature continues to benefit from fruits of biomedical investigation, translation of mechanistic insights into targeted, rationally-conceived therapeutics will be become a reality.

Mary Ann Liebert Publications

The lymphatic system in health and disease.

2008-12-30T06:16:00.000-08:00

The lymphatic system in health and disease.
Cueni LN, Detmar M.
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.

Abstract

The lymphatic vascular system has an important role in the regulation of tissue pressure, immune surveillance and the absorption of dietary fat in the intestine. There is growing evidence that the lymphatic system also contributes to a number of diseases, such as lymphedema, cancer metastasis and different inflammatory disorders. The discovery of various molecular markers allowing the distinction of blood and lymphatic vessels, together with the availability of a increasing number of in vitro and in vivo models to study various aspects of lymphatic biology, has enabled tremendous progress in research into the development and function of the lymphatic system. This review discusses recent advances in our understanding of the embryonic development of the lymphatic vasculature, the molecular mechanisms mediating lymphangiogenesis in the adult, the role of lymphangiogenesis in chronic inflammation and lymphatic cancer metastasis, and the emerging importance of the lymphatic vasculature as a therapeutic target.

Mary Ann Liebert Publcations

Interstitial magnetic resonance lymphography: the clinical effectiveness of a new method.

2008-11-24T05:03:00.000-08:00

Interstitial magnetic resonance lymphography: the clinical effectiveness of a new method.
Lymphology. 2008 Sep

Dimakakos E, Koureas A, Koutoulidis V, Skiadas V, Katsenis K, Arkadopoulos N, Gouliamos A, Vlachos L.
Vascular Unit of 2nd Surgical Clinic, University of Athens, Greece. edimakakos@yahoo.gr

The aim of this study is to evaluate effectiveness of interstitial magnetic resonance lymphography as an examination for the depiction of the lymphatic system in humans by comparison with direct x-ray lymphography. We studied 14 subjects (two volunteers and 12 patients with clinical suspicion of lymphedema of the lower extremities). We first administered subcutaneous gadobutrol between the toes and performed MR lymphography. After seven days, we injected lipiodol into the lymph vessels of 8 patients and performed x-ray direct lymphography to compare findings of two methods. We identified the normal lymphatic system (lymph vessels and inguinal lymph nodes) of volunteers. In seven subjects, we were able to image an abnormal lymphatic system with decreased number of lymph vessels, lymphoceles, and ectatic lymph vessels. In three subjects we identified both an abnormal lymphatic and venous system and in two patients only the venous system. In all cases x-ray direct lymphography confirmed the findings of the MR lymphography. No side effects were observed from either contrast agent. We expect that in the future, interstitial MR lymphography will be improved and evolve into a valuable diagnostic tool for the evaluation of lymphatic diseases particularly those who present with primarily lymphedema in the lower limbs or second, in regions other than extremities.

PubMed

Langerhans cell histiocytosis in children under one year

2008-11-12T05:39:00.000-08:00

Langerhans cell histiocytosis in children under one year

Arch Argent Pediatr. 2008 Jun

Larralde M, Abad ME, Gomar B.
Hospital Alemán, Buenos Aires, Argentina.

Correspondencia: Dra. Begoña Gomar, begogomar@gmail.com

INTRODUCTION: Langerhans cell histiocytosis is characterized by a clonal proliferation of activated Langerhans cells that infiltrate various organs of the body. Occurs at any age, from newborn until adulthood, with an incidence peak at 1-4 years.

OBJECTIVE: To describe the morphologyc characteristics of skin lesions and clinical course of 15 patients with Langerhans cell histiocytosis.

METHODS: A retrospective review of the medical records of patients with Langerhans cell histiocytosis from Ramos Mejia Hospital and Aleman Hospital, between 1999-2007.

RESULTS: Review of medical records from 15 patients, 6 females and 9 males. Skin lesions were congenital in 8 cases and appeared between 2-12 months of age in 7 cases. The patients with congenital presentation only had a cutaneous manifestation; one patient who developed a systemic compromise (lung, liver and spleen) is currently under treatment. Three patients with presentation after birth only had cutaneous lesions, the others had a systemic disease. One of this patients died during treatment. Histopathology showed a histiocytic infiltrate in the papillary dermis with epidermotrophism; inmunomarking with S100 and CD1a was positive.

CONCLUSION: Both clinical manifestation (congenital and after birth) represent different ends of a spectrum of the same condition, with the potencial to develop into disseminated Langerhans cell histiocytosis.

SciELO

Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome.

2008-11-04T05:35:00.000-08:00

Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome.
J Pediatr Hematol Oncol. 2008 Aug
Laux D, Kratz C, Sauerbrey A.
Pediatric Hematology and Oncology Unit, Department of Pediatrics, HELIOS Klinikum Erfurt, Erfurt, Germany. danilaux@yahoo.de

Germline mutations in PTPN11 gene cause Noonan syndrome and the clinically similar LEOPARD syndrome (LS). LS is a rare congenital developmental disorder characterized by multiple lentigines, cardiac abnormalities, facial dysmorphism, retardation of growth, and deafness. Mutations in exons 7 and 12 of the PTPN11 gene can be identified in nearly 90% of patients with LS. PTPN11 gene encodes for an ubiquitously expressed protein tyrosine phosphatase SHP-2 involved in a variety of intracellular signaling processes in development and hematopoiesis. Somatic PTPN11 mutations contribute to leukemogenesis in children with hematologic malignancies including juvenile myelomonocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplasia. Two cases of leukemia (acute myeloid leukemia) have been reported in children with LS. The authors describe for the first time a girl with genetically confirmed LEOPARD syndrome presenting with common acute lymphoblastic leukemia.

PMID: 18799937 [PubMed - indexed for MEDLINE]

B lymphocytes: how they develop and function

2008-11-04T05:31:00.000-08:00

B lymphocytes: how they develop and function
Blood. 2008 Sep

LeBien TW, Tedder TF.
Department of Laboratory Medicine/Pathology, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. lebie001@umn.edu

The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated that B and T lymphocytes were responsible primarily for the basic functions of antibody production and cell-mediated immune responses, respectively. The decades that followed have witnessed a continuum of unfolding complexities in B-cell development, subsets, and function that could not have been predicted. Some of the landmark discoveries that led to our current understanding of B lymphocytes as the source of protective innate and adaptive antibodies are highlighted in this essay. The phenotypic and functional diversity of B lymphocytes, their regulatory roles independent of antibody production, and the molecular events that make this lineage unique are also considered. Finally, perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B-cell development and selection. Despite the significant advances that have been made at the cellular and molecular levels, there is much more to learn, and cross-disciplinary studies in hematology and immunology will continue to pave the way for new discoveries.

Blood Full Text Article

Developmental and pathological lymphangiogenesis: from models to human disease

2008-10-26T09:54:00.000-07:00

Developmental and pathological lymphangiogenesis: from models to human disease

Histochem Cell Biol. 2008 Oct 23

Maby-El Hajjami H, Petrova TV.
Division of Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV and University of Lausanne, Ch. des Boveresses 155, 1066, Epalinges, Switzerland.

The lymphatic vascular system, the body's second vascular system present in vertebrates, has emerged in recent years as a crucial player in normal and pathological processes. It participates in the maintenance of normal tissue fluid balance, the immune functions of cellular and antigen trafficking and absorption of fatty acids and lipid-soluble vitamins in the gut. Recent scientific discoveries have highlighted the role of lymphatic system in a number of pathologic conditions, including lymphedema, inflammatory diseases, and tumor metastasis. Development of genetically modified animal models, identification of lymphatic endothelial specific markers and regulators coupled with technological advances such as high-resolution imaging and genome-wide approaches have been instrumental in understanding the major steps controling growth and remodeling of lymphatic vessels. This review highlights the recent insights and developments in the field of lymphatic vascular biology.

Springer

Successful Bilateral Lung Transplantation for Lymphangiomatosis.

2008-08-15T03:28:00.000-07:00

Successful Bilateral Lung Transplantation for Lymphangiomatosis.
Am J Transplant. 2008 Jul 28

Kinnier CV, Eu JP, Davis RD, Howell DN, Sheets J, Palmer SM.
Division of Pulmonary Medicine, Duke University Medical Center, Durham, NC, USA.

Lymphangiomatosis is a rare disease of lymphatic proliferation for which no adequate treatment is known. We report the first successful case of bilateral lung transplantation for the treatment of end-stage pulmonary lymphangiomatosis. A successful outcome was achieved with continued survival beyond 4 years posttransplant and stable lung function. The primary obstacles to significant gains in pulmonary function were thoracic, skeletal and abdominal lymphangiomatosis, which led to pulmonary restriction. Our report demonstrates that pulmonary lymphangiomatosis should be included among those diseases for which lung transplantation is considered potentially beneficial treatment but also emphasizes the importance of screening patients carefully for chest wall and abdominal lymphangiomas that may impede recovery.

PMID: 18671675 [PubMed - as supplied by publisher]

Lymphangiomatosis: a differential diagnosis of lytic lesions of the temporal bone.

2008-08-15T03:25:00.000-07:00

Lymphangiomatosis: a differential diagnosis of lytic lesions of the temporal bone.
J Laryngol Otol. 2008 Jul
Naguib MB, Al-Jazan N, Hashem T.
Department of Otolaryngology, King Faisal University, Al-Khobar, Saudi Arabia.

Objective: We report a histologically proved case of lymphangiomatosis of the skull, involving the temporal bone and presenting as multiple lytic bone lesions.Method:A case report and a review of the literature concerning lymphangiomatosis are presented.

Results: Lymphangiomatosis affecting bones is a rare disorder caused by a congenital malformation of the lymphatic system, resulting in diffuse proliferation of the lymphatic channels and involving bones, parenchymal organs and soft tissue. Involved bones show massive osteolysis and progressive, localised bone resorption.

Conclusion: Lymphangiomatosis should be kept in mind in the differential diagnosis of lytic lesions of the skull.

PMID: 18667106 [PubMed - as supplied by publisher]

Organization and developmental aspects of lymphatic vessels

2008-08-04T01:33:00.000-07:00

Organization and developmental aspects of lymphatic vessels

Arch Histol Cytol. 2008 Mar
Ohtani O, Ohtani Y.
Department of Anatomy, Faculty of Medicine and Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.

The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils.

Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.

Archives of Histology and Cytology

Growth Hormone Promotes Lymphangiogenesis.

2008-07-13T03:54:00.000-07:00

Growth Hormone Promotes Lymphangiogenesis.
Am J Pathol. 2008 Jun 26.

Banziger-Tobler NE, Halin C, Kajiya K, Detmar M.
From the Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.

The lymphatic system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined using comparative transcriptional profiling studies of cultured lymphatic endothelial cells versus blood vascular endothelial cells, growth hormone receptor was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Growth hormone induced in vitro proliferation, sprouting, tube formation, and migration of lymphatic endothelial cells, and the mitogenic effect was independent of vascular endothelial growth factor receptor-2 or -3 activation. Growth hormone also inhibited serum starvation-induced lymphatic endothelial cell apoptosis. No major alterations of lymphatic vessels were detected in the normal skin of bovine growth hormone-transgenic mice. However, transgenic delivery of growth hormone accelerated lymphatic vessel ingrowth into the granulation tissue of full-thickness skin wounds, and intradermal delivery of growth hormone resulted in enlargement and enhanced proliferation of cutaneous lymphatic vessels in wild-type mice. These results identify growth hormone as a novel lymphangiogenic factor.

Journal of Pathology

Prenatal ultrasonographic diagnosis of abdominal cystic lymphangioma: A case report.

2008-07-13T03:52:00.000-07:00

Prenatal ultrasonographic diagnosis of abdominal cystic lymphangioma: A case report.
J Matern Fetal Neonatal Med. 2008 Jun

Santo S, Marques JP, Veca P, Melo A, da Graca LM.
Ultrasound Unit of the Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Santa Maria, Lisbon, Portugal.

Abdominal lymphangioma is a rare tumor of the lymphatic vessels. A case of an abdominal cystic lymphangioma identified at 22 weeks of gestation is reported. Ultrasonographic monitoring showed a progressive increase of mass size during the gestation. Pregnancy was terminated at 38 weeks and the newborn was submitted to a laparotomy with resection of all cystic structures. At the present time the infant is three years old and is doing well.

InformaWorld

Senile changes in human lymph nodes.

2008-06-29T06:03:00.000-07:00

Senile changes in human lymph nodes.

Lymphat Res Biol. 2008
Pan WR, Suami H, Taylor GI.
The Jack Brockhoff Reconstructive Plastic Surgery Research Unit, Royal Melbourne Hospital, Department of Anatomy and Cell Biology, University of Melbourne, Australia.

Abstract Background:

The degenerative process of lymph nodes is poorly documented.

Methods:

161 lymph nodes of seven fresh and one embalmed human cadavers in the head and neck were studied. We used 6% hydrogen peroxide, lead oxide injectant, and radiographs to demonstrate lymphatic vessels, and found both solidified and transparent lymph nodes. They were removed, fixed in 10% formalin and sent for histopathology cross section.

Results:

Thirty-eight solidified and 123 transparent lymph nodes were found. A series of histopathological sections show the degenerative process is variable and continuous. Senile involution affects all elements of the lymph node including the cortex, the medulla, and the architecture.

Conclusion:

This study provides actual anatomical and histopathological images of lymph nodes in different degenerative stages in the head and neck region. It may help explain some clinical conditions in the elderly, especially their diminished immunological response to infection and cancer metastasis.

Mary Ann Liebert

Observations on the prenatal development of human lymphatic vessels with focus on basic structural elements of lymph flow.

2008-06-29T05:50:00.000-07:00

Observations on the prenatal development of human lymphatic vessels with focus on basic structural elements of lymph flow.

Lymphat Res Biol. 2008

Petrenko VM, Gashev AA.
Department of Human Anatomy, St. Petersburg State Medical Academy, St. Petersburg, Russia.

Abstract Background:

The prenatal development of human lymphatic systems has not attracted enough attention by lymphatic researchers in the past. Yet clearly these critical, early events determine the fate and function of the human lymphatic system.

Methods and Results:

The main focus of these studies was to investigate the embryonic development of human lymphangions including lymphatic valves and muscle cells, to better understand the prenatal formation of basic structural elements of lymph flow. This review in most of its parts is a short summary of the findings. It provides important information necessary for understanding the development and functioning of the human lymphatic system.

Conclusions:

The structural basis of the active lymph transport system-the lymphatic muscle cells and lymphatic valves-which is absolutely necessary for all functions of lymphatic system, is already formed during the first half of the prenatal development in humans. During the second half of this development maturation of this system is already underway. The enlargement of lymphatic muscle cells together with increases in their quantity leads to formation of the multi-layered lymphatic vessel wall, able to develop contractions strong enough to propel lymph downstream of the lymphatic channels against gravity in bipedal humans. The development of the competent valves in lymphatic vessels occurs at the same time creating the ground for effective net, unidirectional lymph flow. The data summarized here represents some of the first systematic studies of the prenatal development of lymphatic muscle cells and valves in humans.

Mary Ann Liebert

Neostatin-7 regulates bFGF-induced corneal lymphangiogenesis.

2008-06-27T03:19:00.000-07:00

Neostatin-7 regulates bFGF-induced corneal lymphangiogenesis.
FEBS Lett. 2008 Jun 18

Kojima T, Azar DT, Chang JH.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612, USA.

Neostatin-7, with an anti-angiogenic potential, is generated from the proteolytic action of matrix metalloproteinase-7 on collagen XVIII. We previously reported that neostatin-7 inhibited angiogenesis in vitro and in vivo. Here we demonstrate that neostatin-7/collagen XVIII may possess anti-lymphangiogenic activities by: (1) corneal micropellet implantation of neostatin-7 reduced bFGF-induced corneal lymphangiogenesis; (2) neostatin-7 bound to VEGF receptor-3 in vitro; and (3) enhanced corneal lymphangiogenesis and VEGF-C expression in collagen XVIII knockout mice in a corneal wounding model. Understanding the mechanism of neostatin-7/collagen XVIII on corneal lymphangiogenesis may provide therapeutic interventions to treat lymphangiogenesis-related disorders, such as lymphedema, transplantation rejection and cancers.

Elsevier ScienceDirect

Lymphatic involvement in lymphangioleiomyomatosis.

2008-06-10T08:05:00.000-07:00

Lymphatic involvement in lymphangioleiomyomatosis.

Ann N Y Acad Sci. 2008 May
Glasgow CG, Taveira-Dasilva AM, Darling TN, Moss J.
PhD., Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10, Rm. 6D03 MSC 1590, Bethesda, MD 20892-1590. mossj@nhlbi.nih.gov.

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease affecting primarily premenopausal women. The disease is characterized by cystic lung disease, at times leading to respiratory compromise, abdominal tumors (in particular, renal angiomyolipomas), and involvement of the axial lymphatics (e.g., adenopathy, lymphangioleiomyomas).

Disease results from the proliferation of neoplastic cells (LAM cells), which, in many cases, have a smooth muscle cell phenotype, express melanoma antigens, and have mutations in one of the tuberous sclerosis complex genes (TSC1 or TSC2). In the lung, LAM cells found in the vicinity of cysts are, at times, localized in nodules and may be responsible for cyst formation through the production of proteases.

Lymphatic channels, expressing characteristic lymphatic endothelial cell markers, are found within the LAM lung nodules. LAM cells may also be localized within the walls of the axial lymphatics, and, in some cases, penetrate the wall and proliferate in the surrounding adipose tissue. Consistent with extensive lymphatic involvement in LAM, the serum concentration of VEGF-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers.

Annals of the New York Academy of Sciences

Bilateral renal lymphangiomatosis: Sonographic findings

2008-05-14T05:41:00.000-07:00

Bilateral renal lymphangiomatosis: Sonographic findings

J Clin Ultrasound. 2008 May

Bagheri MH, Zare Z, Sefidbakht S, Nabavizadeh SA, Meshksar A, Roozbeh J, Salehipour M.
Department of Radiology, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran.

*Correspondence to Seyed Ali Nabavizadeh, Department of Radiology, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran

Renal lymphangiomatosis is an exceedingly rare disorder characterized by developmental malformation of the lymphatic system surrounding the kidneys. We report a case of bilateral renal lymphangiomatosis in a 21-year-old man who underwent abdominal sonographic examination that revealed numerous cystic areas of varyious sizes around both kidneys with extension along the renal hilum. Subsequent abdominal CT examination demonstrated bilateral, multilocular, fluid-filled cystic masses with thin walls in the perirenal and peripelvic region. MRI of the patient revealed bilaterally enlarged kidneys with multiple hyperintense lesions in both perirenal spaces and the peripelvic area on T2-weighted images. These cystic spaces appeared hypointense on T1-weighted images with no enhancement in postcontrast images. The diagnosis of renal lymphangiomatosis was made based on typical imaging findings. (c) 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008.

Wiley InterScience

Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature

2008-04-22T07:53:00.000-07:00

Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature
Mol Cell Biol. 2008 Apr 14

Danussi C, Spessotto P, Petrucco A, Wassermann B, Sabatelli P, Montesi M, Doliana R, Bressan GM, Colombatti A.
Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, Aviano, Pordenone, Italy; IGM-CNR, Unit of Bologna c/o IOR, Bologna, Italy; Mouse Genetics Laboratory, Department of Histology Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy; Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy; and MATI Center of Excellence, University of Udine, Udine, Italy.

Lymphatic vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have been poorly taken into consideration when studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril associated protein, is highly expressed by LECs in vitro and co-localizes with lymphatic vessels in several mouse tissues. A comparative study between wild-type and Emilin1(-/-) mice highlighted that Emilin1 deficiency in both CD1 and C57BL/6 background results in hyperplasia, enlargement and frequently irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. Emilin1-deficient mice also develop larger lymphangiomas than wild-type mice. Lymphatic vascular morphological alterations are accompanied by functional defects such as mild lymphedema, highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for an efficient function. The phenotype displayed by Emilin1(-/-) mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis.

Molecular and Cellular Biology

Cervical lymph nodes

2008-03-14T04:50:00.000-07:00

Cervical lymph nodes

Eur J Radiol. 2008 Mar 10

Mack MG, Rieger J, Baghi M, Bisdas S, Vogl TJ.
Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.

The lymph node staging is a very important prognostic parameter for patients with presenting with head neck cancer and is influencing the selection of the different therapeutic strategies including surgery, chemotherapy, radiotherapy or a combination of them. The accuracy of imaging techniques, such as US, MR imaging, and CT, depends on the appropriateness of radiological criteria used for diagnosing lymph node metastases. Size of nodes and evidence of necrosis are still the most important radiological criteria. However, the size shows great variability. A spherical lymph node larger than 10mm is an indicator for a malignant node, whereas an oval shape and/or a fatty hilus are more benign signs. But there are many limitations and different cut offs published in the literature, indicating that the size of a lymph node is not a reliable criteria for the assessment of lymph nodes in the head and neck region. Today new high-resolution MRI sequences and the development of specific contrast agents are offering new possibilities in the diagnostic work-up of head and neck lymph nodes. Ultrasmall superparamagnetic iron oxide particles (USPIO's) are resulting after intravenous application in a reduction of the T2 relaxation time. This is causing a signal decrease on T2-weighted MR images in benign lymph nodes after administration of USPIO's, whereas malignant lymph nodes do not show a significant signal decrease. Some clinical studies presented already very promising results. Based on the fact, that the size evaluation of lymph nodes in the head and neck has not changed during the last decade, this paper will mainly focus on MRI with new contrast agents and new techniques as diffusion weighted imaging (DWI).

PMID: 18337039 [PubMed - as supplied by publisher]

Lymphangiogenesis in development and disease

2008-03-01T20:08:00.000-08:00

Lymphangiogenesis in development and disease

Thrombosis and Haemostasis 2007

Ruediger Liersch1, Michael Detmar2
1Department of Medicine, Hematology and Oncology, University Hospital Muenster, Muenster, Germany; 2Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland

Summary

The lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells.The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutation- al inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease.

Keywords
Lymphatic endothelium, lymphangiogenesis, lymphedema, inflammation, cancer metastasis

Schattauer

Overexpression of VEGF-C causes transient lymphatic hyperplasia but not increased lymphangiogenesis in regenerating skin

2008-02-26T19:25:00.000-08:00

Overexpression of VEGF-C causes transient lymphatic hyperplasia (lymphedema) but not increased lymphangiogenesis in regenerating skin.

Goldman J, Le TX, Skobe M, Swartz MA. Biomedical Engineering Department, Northwestern University, Evanston, Ill, USA.

Correspondence to Dr Melody A. Swartz, Assistant Professor, Institute for Biological Engineering and Biotechnology, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. E-mail melody.swartz@epfl.ch

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis and holds potential for lymphangiogenic therapy in diseases lacking adequate lymphatic drainage. However, the ability of VEGF-C to enhance sustainable, functional lymphatic growth in adult tissues remains unclear. To address this, we evaluated VEGF-C overexpression in adult lymphangiogenesis in regenerating skin. We used a model of mouse tail skin regeneration incorporating a suspension of either VEGF-C overexpressing tumor cells, which provide a continuous supplement of excess VEGF-C to the natural regenerating environment for more than 25 days, or otherwise identical control- transfected tumor cells. We found that excess VEGF-C did not enhance the rate of lymphatic endothelial cell (LEC) migration, the density of lymphatic vessels, or the rate of functionality -- even though lymphatic hyperplasia was present early on. Furthermore, the hyperplasia disappeared when VEGF-C levels diminished, which occurred after 25 days, rendering the lymphatics indistinguishable from those in control groups. In vitro, we showed that whereas cell-derived VEGF- C could induce chemoattraction of LECs across a membrane (which involves amoeboid-like transmigration), it did not increase LEC chemoinvasion within a 3-dimensional fibrin matrix (which requires proteolytic migration). These results suggest that whereas excess VEGF- C may enhance early LEC proliferation and cause lymphatic vessel hyperplasia, it does not augment the physiological rate of migration or functionality, and by itself cannot sustain any lasting effects on lymphatic size, density, or organization in regenerating adult skin.

AHA Journals

Definitive percutaneous treatment of lymphatic malformations of the trunk and extremities

2008-02-23T03:37:00.000-08:00

Definitive percutaneous treatment of lymphatic malformations of the trunk and extremities

J Pediatr Surg. 2008 Jan

Shiels WE 2nd, Kenney BD, Caniano DA, Besner GE.
Department of Radiology, Nationwide Children's Hospital, The Ohio State University Medical Center, Columbus, OH 43205, USA. william.shiels@nationwidechildrens.org

PURPOSE: The aim of this study is to investigate a new treatment regimen for macrocystic and microcystic lymphatic malformations (LMs) of the trunk and extremities.

METHODS: Sixteen patients (aged 2 months-22 years) underwent percutaneous treatment for LM of the trunk and extremities from 2002 to 2007. The LM involved the arm, leg, axilla, chest, abdomen, scrotum, and penis. Eleven patients underwent primary treatment of LM; 5 were treated for recurrence after prior operative resection. Macrocysts (>or=1 cm) were treated with dual-drug chemoablation (sequential intracystic sodium tetradecyl sulfate and ethanol); doxycycline was used for microcysts. Macrocysts and microcysts were treated after complete cyst aspiration using sonographic guidance. Twenty-four macrocysts and 103 microcysts were treated. The goal of treatment was complete cyst ablation documented by sonography or magnetic resonance imaging.

RESULTS: The mean number of treatments was 1.7 per patient; the mean number of treatments for macrocysts was 1.3 and for microcysts was 1.7. Ablation efficacy was 100% (127/127 cysts). Treatments included massive intraperitoneal cysts and cysts surrounding the adventitia of the brachial artery and brachial nerve. Infection occurred in 2 (13%) of 16 patients. No patient experienced postprocedural pain, skin necrosis, neuropathy, bowel obstruction, skin retraction, or myoglobinuria.

CONCLUSIONS: Percutaneous sclerotherapy provides effective treatment for macrocystic and microcystic LM as primary treatment or for recurrence after surgical resection.

Elsevier

Congenital vascular malformations: general diagnostic principles.

2008-02-18T17:17:00.000-08:00

Congenital vascular malformations: general diagnostic principles.
Phlebology. 2007

Lee BB, Laredo J, Lee SJ, Huh SH, Joe JH, Neville R.
Department of Surgery, Georgetown University, Washington, DC, USA. bblee38@comcast.net

Venous malformation (VM) is the most common congenital vascular malformation (CVM), which usually presents as a single lesion in the majority of cases. It also presents as a mixed lesion combined with other CVMs (e.g. lymphatic malformation and arteriovenous malformation [AVM]). Therefore, the diagnosis of VM should include an appropriate work-up, to not only confirm and characterize the VM as either extratruncular or truncular but also to diagnose or exclude the presence of other CVMs. The diagnosis of VM can be made safely using non-invasive to minimally invasive studies, which can also distinguish VM from infantile haemangioma. Invasive studies, such as venography and arteriography, are generally reserved for therapeutic planning and diagnosis of more virulent CVMs (e.g. AVM). The work-up of VM should include a complete assessment of the extent and severity of the primary VM lesion. In addition, its embryologic origin, as well as its haemodynamic characteristics and secondary effects should also be determined.

PMID: 18274332 [PubMed - in process]

Laser excision of multiple esophageal lymphangiomas: A case report and review of the literature.

2008-02-16T06:13:00.000-08:00

Laser excision of multiple esophageal lymphangiomas: A case report and review of the literature.
Auris Nasus Larynx. 2008 Feb 1

Best SR, Coelho DH, Ahrens WA, Atez G, Sasaki CT.
Yale University School of Medicine Division of Otolaryngology, Head & Neck Surgery, New Haven, CT, USA.

Lymphangiomas of the gastrointestinal tract are rare and benign submucosal tumors. We present the first case of multiple lymphangiomas in the cervical esophagus and only the 15th case of an esophageal lymphangioma. A 63-year-old male presented to our clinic with two years of dysphagia and an esophageal mass noted on MRI. A barium swallow confirmed a polypoid mass of the upper esophagus with operative findings of two smooth pedunculated lymphangiomas occupying the entire lumen of the esophagus. Previous reports have documented successful surgical intervention through open or endoscopic techniques, whereas the favorable location of the tumors in this case allowed for the first successful excision utilizing a CO(2) laser. We demonstrate here that esophageal laser surgery can provide an accurate, complete, and minimally invasive excision technique for lymphangiomas of the upper digestive tract with minimal morbidity for the patient. A complete review of all published cases is presented, with a focus on the clinical presentation and surgical treatment of this disease.

PMID: 18243618 [PubMed - as supplied by publisher]

Increased risk of lymph node metastasis in multifocal hereditary and sporadic medullary thyroid cancer.

2008-02-03T06:59:00.000-08:00

Increased risk of lymph node metastasis in multifocal hereditary and sporadic medullary thyroid cancer.

World J Surg. 2007 Oct

Machens A, Hauptmann S, Dralle H.
Department of General, Visceral and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str 40, D-06097, Halle/Saale, Germany. AndreasMachens@aol.com

(1)
Department of General, Visceral and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097 Halle/Saale, Germany
(2)
Department of Pathology, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 14, D-06097 Halle/Saale, Germany

BACKGROUND: In sporadic and hereditary medullary thyroid cancer, tumor multifocality may constitute an independent risk factor of lymph node metastasis on top of primary tumor size when the diameter of the largest primary tumor is the same. METHODS: Included in this institutional cohort study were 232 consecutive patients operated on at our institution for hitherto untreated medullary thyroid cancer. Associations of clinicopathologic variables with lymph node metastasis were investigated simultaneously using multivariate Cox regression analysis.

RESULTS: On univariate analysis, multifocal cancers developed lymph node metastases significantly more often (p < or =" 0.005)" p =" 0.01)." or =" 3.1;">

CONCLUSION: The excess risk of lymph node metastasis of 34%-49% in multifocal medullary thyroid cancer seems to be caused by concurrent smaller thyroid cancers. A diagnosis of more than one medullary thyroid cancer signifies a higher risk of lymph node metastasis, warranting systematic lymph node dissection.

Springer Link

Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis.

2008-01-19T06:07:00.000-08:00

Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis.
Jan 2008

Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN.
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. john.bissler@cchmc.org

BACKGROUND: Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR). The drug sirolimus suppresses mTOR signaling.

METHODS: We conducted a 24-month, nonrandomized, open-label trial to determine whether sirolimus reduces the angiomyolipoma volume in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Sirolimus was administered for the first 12 months only. Serial magnetic resonance imaging of angiomyolipomas and brain lesions, computed tomography of lung cysts, and pulmonary-function tests were performed.

RESULTS: Of the 25 patients enrolled, 20 completed the 12-month evaluation, and 18 completed the 24-month evaluation. The mean (+/-SD) angiomyolipoma volume at 12 months was 53.2+/-26.6% of the baseline value (P<0.001) p="0.005)." p="0.06)," p="0.02),">

CONCLUSIONS: Angiomyolipomas regressed somewhat during sirolimus therapy but tended to increase in volume after the therapy was stopped. Some patients with lymphangioleiomyomatosis had improvement in spirometric measurements and gas trapping that persisted after treatment. Suppression of mTOR signaling might constitute an ameliorative treatment in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.

(ClinicalTrials.gov number, NCT00457808.) 2008 Massachusetts Medical Society

New England Journal of Medicine

Distributional characteristics of lymphatic vessels in normal human nasal mucosa and sinus mucosa.

2007-12-24T05:02:00.000-08:00

Distributional characteristics of lymphatic vessels in normal human nasal mucosa and sinus mucosa.

Cell Tissue Res. 2007

Kim TH, Lee SH, Moon JH, Lee HM, Lee SH, Jung HH.
Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, 126-1, 5 Ka, Anam-Dong, SungBuk-Ku, Seoul 136-705, South Korea.

An immunohistochemical staining technique with the D2-40 antibody was undertaken to examine the functional and morphological features of lymphatic networks in tissue sections and whole-mount preparations of normal nasal mucosa and ethmoid sinus mucosa. In normal nasal mucosa, most lymphatic vessels were found in the superficial mucosa beneath the epithelial layer. Some of these vessels were dilated, whereas others were compressed and had a slit-like lumen. Whole-mount preparations revealed the extent of lymphatic vessels in normal ethmoid sinus mucosa. A network of lymphatic vessels was mainly found in the subepithelial layer, where lymphatic vessels represented rich networks, possessing antler-like branches and typical blind ends. However, these lymphatic networks were not arranged in the form of lymphangion chains, with each lymphangion consisting of a contractile compartment and valve. Thus, recognition of the distinctive features of the lymphatic network in normal nasal and sinus mucosa might aid investigations of lymphatic involvement in sinonasal diseases, such as rhinitis, sinusitis, and malignancy.

Springer Link

The healing of tibial fracture and response of the local lymphatic system.

2007-12-21T02:00:00.000-08:00

The healing of tibial fracture and response of the local lymphatic system.
Szczesny G, Olszewski WL, Gewartowska M, Zaleska M, Górecki A.
Department of Surgical Research and Transplantology, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. g.szczesny@cmdik.pan.pl

BACKGROUND: Damage of tissues by mechanical injury and inflammation is followed by reaction of the regional lymphoid tissue, lymphatics, and lymph nodes. In our previous lymphoscintigraphic studies, we showed that closed fractures of a lower limb cause reaction of the local lymphoid tissue. There was dilation of lymphatics draining the site of the fracture and enlargement of inguinal lymph nodes. These changes persisted even after clinical healing of the fracture. In the long-lasting nonhealing fractures, the lymphoscintigraphic pictures were different. The draining lymphatics became obliterated, and the lymph nodes disappeared.

METHODS: In this study, we tried to correlate the lymphoscintigraphic images, reflecting the immune events at the fracture site, with the immunohistochemical observations of the biopsy specimens obtained during corrective operations from the healing and nonhealing fracture gaps. Thirty-eight patients with closed fracture of the tibia without traumatic skin changes were studied.

RESULTS: We confirmed that closed tibial fracture evokes response of the regional lymphatic system. Normal fracture healing with immune cell infiltrates and foci of ossification was accompanied by dilated lymphatics and enlarged lymph nodes. Prolonged nonhealing fracture with lack of cellular reaction in the gap proceeded with decreased mass of lymph nodes.

CONCLUSION: This study provides evidence for existence of a functional axis between wound of bone and surrounding soft tissue and the local lymphatic (immune) system. We hypothesize that the fast healing is regulated by influx into the wound of lymph node regulatory cells, whereas prolonged healing causes gradual exhaustion of the regional lymph node functional elements, and reciprocally impairment in sending regulatory cells to the fracture gap.

PMID: 18090016 [PubMed - in process]

Molecular Biology and Pathology of Lymphangiogenesis

2007-12-15T04:14:00.000-08:00

Molecular Biology and Pathology of Lymphangiogenesis

Karpanen T, Alitalo K.
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Haartman Institute, University of Helsinki and Helsinki University Central Hospital, FI-00014 Helsinki, Finland t.karpanen@niob.knaw.nl.

Abstract

The lymphatic vasculature is essential for the maintenance of tissue fluid balance, immune surveillance, and adsorption fatty acids in the gut. The lymphatic vessels are also crucially involved in the pathogenesis of diseases such as tumor metastasis, lymphedema, and various inflammatory conditions. Attempts to control or treat these diseases have drawn a lot of interest to lymphatic vascular research during the past few years. Recently, several markers specific for lymphatic endothelium and models for lymphatic vascular research have been characterized, enabling great technical progress in lymphatic vascular biology, and many critical regulators of lymphatic vessel growth have been identified. Despite these significant achievements, our understanding of the lymphatic vessel development and pathogenesis is still rather limited. Several key questions remain to be resolved, including the relative contributions of different pathways targeting lymphatic vasculature, the molecular and cellular processes of lymphatic maturation, and the detailed mechanisms of tumor metastasis via the lymphatic system. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 3 is January 24, 2008. Please see article for revised estimates.

PMID: 18039141 [PubMed - as supplied by publisher]

Lymphangiogenesis in Crohn's disease: an immunohistochemical study using monoclonal antibody D2-40.

2007-11-30T03:15:00.000-08:00

Lymphangiogenesis in Crohn's disease: an immunohistochemical study using monoclonal antibody D2-40.

Pedica F, Ligorio C, Tonelli P, Bartolini S, Baccarini P.
Section of Pathology, Bellaria Hospital, University of Bologna, Via Altura 3, 40139, Bologna, Italy, f.pedica@alice.it.

Crohn's disease (CD) is a chronic inflammatory bowel disorder of unknown etiology. An involvement of the intestinal lymphatic system has been suggested. Recently, monoclonal antibodies have become available to distinguish lymphatic vessels from blood vessels. The aim of the study was to examine the distribution of lymphatic vessels in ileal and colic walls of patients affected by CD and compare it with healthy controls and other inflammatory bowel diseases. Twenty-eight cases of CD, 13 cases of other inflammatory bowel diseases, and 10 normal ileal and colic walls were studied. Immunohistochemical staining was performed using the monoclonal antibody D2-40. Quantification of lymphatic vessels was performed by identifying four fields with high density of lymphatics and then counting the number of lymphatic vessels at high resolution. Lymphatic diameter was also evaluated by using an ocular micrometer. Lymphatic vessels showed the highest density in CD specimens. The median number of lymphatics was significantly higher both in ileal and colic samples of CD than the other inflammatory diseases as well as normal controls. Moreover, in patients with CD, diffuse lymphangiectasia was also observed. The present data suggest that lymphangiogenesis and lymphangiectasia probably play a role in the pathogenesis of CD.

Springer Link

Bilateral renal lymphangiomatosis: conservative management

2007-11-22T05:15:00.000-08:00

Bilateral renal lymphangiomatosis: conservative management

Arch Esp Urol. 2007 Sep

Tornero Ruiz JI, Ojados Castejón F, Nicolás Torralba J, Escudero Bregante F, Pérez Albacete M.
Servicio de Urología, Hospital Universitario Virgen de la Arrixaca, Murcia, España. ignaciotorne@hotmail.com

OBJECTIVE: Lymphangiomatosis is a benign disease of difficult diagnosis. The bilateral form is very rare, being in some cases an incidental finding.

METHODS: We report the case of a female patient with the incidental radiological diagnosis of bilateral lymphangiomatosis, who did not present symptoms in relation to the disease.

RESULTS: After a meticulous study with ultrasound, abdominal CT scan and the MRI the diagnosis was asymptomatic bilateral lymphangiomatosis and expectant management was decided with good outcome.

CONCLUSIONS: Most cases reported have been treated by nephrectomy for diagnosis, but in our case it was possible to do precise diagnosis adding the experience of the radiologist and the urologist and she had a good outcome with conservative management.

PMID: 17937345 [PubMed - in process]

Lymphatics and bone

2007-11-16T06:00:00.000-08:00

Lymphatics and bone

2007 Published by Elsevier Inc

James R. Edwards PhDa, Kelly Williams MSca, Lars G. Kindblom MD, PhDb, , Jeanne M. Meis-Kindblom MDb, Pancras C.W. Hogendoorn MD, PhDc, David Hughes MBb, Ramses G. Forsyth MDd, David Jackson PhDe and Nicholas A. Athanasou MD, PhDa

Summary

There is controversy regarding whether lymphatic vessels are present or absent in bone. Although lymphangiomas have been described in bone, lymphatic vessels have not been identified morphologically with certainty in any other benign or malignant bone tumors or in normal human bone.

In this study, we determined by immunohistochemistry, using 2 specific lymphatic endothelial cell markers, LYVE-1 and podoplanin, whether lymphatics are present in normal bone and a wide range of primary and secondary bone neoplasms. In normal bone, LYVE-1+/podoplanin+ lymphatic vessels were not identified in cortical or cancellous bone but were seen in connective tissue overlying the periosteum. With the exception of lymphangioma, Gorham-Stout disease, and hemangioendothelioma, primary benign and malignant bone tumors (as well as secondary carcinomas) that were confined to bone did not contain lymphatic vessels. Primary and secondary bone tumors that had extended through the bone cortex contained LYVE-1+/podoplanin+ lymphatic vessels that seemed to extend for a short distance from surrounding soft tissues into the tumor.

Three cases of osteosarcoma that had extended through the bone cortex and had lymph node metastases were all found to contain lymphatic vessels within the tumor.

These results indicate that the lymphatic circulation is unlikely to play a role in bone fluid transport in normal bone and that lymphatic vessels are absent from most primary and secondary tumors confined to bone.

These findings also suggest that lymphangiogenesis is not involved in the disease progression of most primary bone tumors and that carcinomatous metastasis to bone does not occur via lymphatics.

Keywords: Lymphatics; Bone tumors; Metastasis; Fluid transport

N. A. Athanasou, P. Hoogendorn, R. G. Forsyth, and L. G. Kindblom are partners in EuroBoNeT (European Network to promote research into uncommon cancers in adults and children: pathology, biology and genetics of bone tumors), which is funded by the European Union.

Science Direct

Diffuse large B-cell lymphoma with a novel translocation involving BCL6.

2007-11-15T16:08:00.000-08:00

Diffuse large B-cell lymphoma with a novel translocation involving BCL6.
Cancer Genet Cytogenet. 2007 Oct

Iqbal J, Gupta S, Chen QH, Brody JP, Koduru P.
Department of Pathology, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA. jabel.iqbal@roswellpark.org

Translocation of the BCL6 gene is one of the most common chromosomal changes seen in diffuse large B-cell lymphoma, primarily affecting the 5' regulatory region which is usually replaced with the sequences of the translocation partner. This translocation involves both immunoglobulin and nonimmunoglobulin gene partners, the former being the more common. Here we report a case of diffuse large B-cell lymphoma with immunophenotypic features of a germinal center type, involving translocation of BCL6 to chromosome 11 and partnering with one or more nonimmunoglobulin genes. To our knowledge this novel translocation in the context of an activated B-cell type diffuse large B-cell lymphoma has not been previously described in the literature. We speculate about the putative partner gene involved in the translocation and the pathophysiological significance of the translocation.

Elsevier

Unilateral Lower Limb Swelling Secondary to Cavernous Lymphangioma.

2007-11-10T03:59:00.000-08:00

Unilateral Lower Limb Swelling Secondary to Cavernous Lymphangioma.
Eur J Vasc Endovasc Surg. 2007 Oct 25

Bains SK, London NJ.
Department of Vascular and Endovascular Surgery, Leicester Royal Infirmary, Leicester LE1 5WW, UK.

INTRODUCTION:

We report an unusual case of unilateral leg swelling secondary to cavernous lymphangioma (cystic hygroma), which normally affects the head and neck regions.

CASE REPORT:

A 25 year gentleman presented to our department with a 13-year history of gradually increasing unilateral leg swelling and recurrent infections. Investigations showed appearances consistent with cavernous lymphangioma, and partial excision of the lesion led to resolution of symptoms.

DISCUSSION:

The most common sites for cystic hygroma are the head and neck areas, but the extremities can be affected as demonstrated. Complete surgical excision is often difficult, and there is a tendency for recurrence. This case acts as an illustration of an uncommon yet important cause for unilateral leg swelling.

Elsevier

Research clarifies origin of mammalian network of lymphatic vessels

2007-11-03T09:43:00.000-07:00

Research clarifies origin of mammalian network of lymphatic vessels
Medical Research News
Published: Tuesday, 30-Oct-2007

Investigators at St. Jude Children's Research Hospital settled a century-old debate on the origin of the mammalian lymphatic vasculature - the network of vessels and capillaries critical to various essential housekeeping functions in the body.

The finding holds the promise for the development of new therapies for lymphatic system disorders, the researchers said.

The St. Jude team used various mouse models to demonstrate that the lymphatic vasculature arises in the embryo from veins by means of continuous release from the veins of cells that multiply and then migrate to different parts of the body.

Conclusively determining how the lymphatic vasculature develops in the embryo is an important step in fully understanding the mechanisms that form this vital network of vessels, according to Guillermo Oliver, Ph.D., a member of the St. Jude Department of Genetics and Tumor Cell Biology.

"This work is a major contribution in the long-term strategy of promoting the growth of new lymphatic vessels in people suffering from different forms of lymphatic disease that are either inherited or acquired after birth," Oliver said. "The detailed characterization of the formation of a normal, healthy lymphatic vasculature is central to our efforts to prevent, diagnose and cure lymphatic vasculature disorders." Oliver is senior author of a report on this work that appears in the October 1 issue of Genes & Development . His laboratory previously discovered that the gene Prox1 plays a critical role in development of the lymphatic vasculature.The lymphatic vasculature drains fluids that normally escape through the thin walls of the tiny blood vessels called capillaries, which provide nutrients for the cells forming the body's tissues and organs. The lymphatic vasculature reabsorbs much of this fluid, called lymph, from the spaces surrounding the cells. Failure of lymph transport promotes lymphoedema, a disfiguring, disabling and occasionally life-threatening disorder with limited treatment options. A defective lymphatic vasculature could also promote obesity, according to a previous finding by Oliver's team.

The lymphatic system is essential for the immune response to infectious agents; for example, during inflammation, immune system cells travel to sites of inflammation by way of lymphatic vessels.

The St. Jude team studied the origin of the mammalian lymphatic vasculature using a powerful technique called Cre/loxP-based lineage-tracing. This technique enables researchers to label specific progenitor cells in the embryo and follow them as they reach their final destinations in the developing body. Progenitor cells are parent cells that multiply and give rise to distinct populations of cells with different, specific functions in the body.

The researchers suspected, based on previous work done at St. Jude and elsewhere, that the entire mammalian lymphatic system arises from cells called lymphatic endothelial (LEC) progenitors located in the embryonic veins and that express (activate) the Prox1 gene. These LEC progenitor cells were thought to form lymph sacs-structures from which the entire lymphatic vasculature is derived. However, there was no proof of this; competing theories held that other cells, such as hematopoietic (blood-forming) cells contribute to formation of the lymphatic vasculature.

To conclusively address this question, the researchers did lineage tracing to follow the labeled LECs as they left the veins, formed the lymph sacs and spread through the entire mouse embryo. Using additional animal models, the investigators also determined that the loss of hematopoietic cells did not interfere with the early critical phase-formation of the lymph sacs-of lymphatic development. This finding indicated that hematopoietic-derived cells were not a main contributor to development of the mammalian lymphatic vasculature, according to Oliver.

"We showed that venous-derived LECs sprout from the lymph sacs, multiply and then migrate to their ultimate destination to give rise to the entire lymphatic vasculature; and that hematopoietic cells do not contribute significantly to this process," said R. Sathish Srinivasan, Ph.D. "Therefore, we concluded that in mammals, such as mice and humans, the lymphatic vasculature arises directly and solely from the embryonic veins." Srinivasan is a postdoctoral fellow in Oliver's laboratory and did most of the work on this project.

"This finding supports the original theory presented in the early 20th century by the eminent researcher Florence Sabin, who proposed that the origin of the mammalian lymphatic vasculature is the venous system," Oliver said. "She didn't have the technology to prove her idea back then. We did it for her 100 years later." Other authors of this study include Miriam Dillard and Oleg Lagutin (St. Jude); Fu-Jung Lin, Sophia Tsai and Ming-Jer Tsai (Baylor College of Medicine, Houston) and Igor Samokhvalov (Center for Developmental Biology, Kobe, Japan).

This work was supported in part by the National Heart, Lung, and Blood Institute, a Cancer Center support grant and ALSAC. Srinivasan is a recipient of a Lymphatic Research Foundation postdoctoral fellowship.

St. Judes

Lymphangiomatosis Gorham's Vanishing Bone Disease Alliance

2007-10-27T08:34:00.000-07:00

Lymphangiomatosis - Gorham's Vanishing Bone Disease

New Resource:

Lymphangiomatosis & Gorham's Vanishing Bone Disease Alliance

The LGD Alliance is a nonprofit foundation dedicated to patient support, advocacy, and effective treatments and cures for those affected by the rare lymphatic malformations known as lymphangiomatosis and Gorham's disease.

Thank you for visiting our website. Our goal is to provide relevant and useful information to help you become more knowledgeable about these diseases.

Please visit the website at:

Lymphangiomatosis & Gorham's Vanishing Bone Disease Alliance

If there is a particular subject you are trying to find information about, and you cannot find it, please send us an email and we will do our best to help. Our email address is info@lgdalliance.org .

Discussion forums are going to be added as well.

---------

I wanted to share this important new resource and wish the Alliance the utmost success in their endeavors

Pat

Antioxidants Suppress Lymphoma and Increase Longevity in Atm-Deficient Mice

2007-10-22T10:24:00.000-07:00

Antioxidants Suppress Lymphoma and Increase Longevity in Atm-Deficient Mice

2007 The American Society for Nutrition J. Nutr. 137:229S-232S, January 2007

Ramune Reliene and Robert H. Schiestl*
Departments of Pathology, Environmental Health and Radiation Oncology, Geffen School of Medicine and School of Public Health, University of California, Los Angeles, CA 90095
* To whom correspondence should be addressed. E-mail: rschiestl@mednet.ucla.edu

Ataxia telangiectasia (AT), a human hereditary disorder resulting from mutations in the ATM gene, is characterized by a high incidence of lymphoid malignancies, neurodegeneration, immunodeficiency, premature aging, elevated radiosensitivity, and genomic instability. Evidence has been accumulating that ATM-deficient cells are in a continuous state of oxidative stress. A variety of markers of oxidative stress were detected in AT patients as well as Atm-deficient mice, used as an animal model of AT. Since then, it has been proposed that oxidative stress contributes to the clinical phenotype of AT, especially carcinogenesis and neurodegeneration, and several animal studies were conducted to determine whether exogenous antioxidants mitigate the symptoms of AT. Tempol, EUK-189, and N-acetyl cysteine have been tested as chemopreventive antioxidants in Atm-deficient mice. We review these findings, mainly focusing on the effect of N-acetyl cysteine, which is known as a safe and efficient drug and nutritional supplement.

Journal of Nutrition

Complex lymphatic malformations: diagnostic and therapeutical implications

2007-09-26T05:51:00.000-07:00

Complex lymphatic malformations: diagnostic and therapeutical implications
Cir Pediatr. 2007 Apr
Luis AL, López JC, Encinas JL, Suárez O, Burgos L, Diaz M, Soto C, Ros Z.
Hospital Universitario La Paz, Departamento de Cirugía Pediátrica, Madrid. anacp5555@hotmail.com

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.

PMID: 17650723 [PubMed - in process]

Radiotherapy in congenital vulvar lymphangioma circumscriptum.

2007-09-12T18:56:00.000-07:00

Radiotherapy in congenital vulvar lymphangioma circumscriptum.

Int J Gynecol Cancer. 2007 Aug

Yildiz F, Atahan IL, Ozyar E, Karcaaltincaba M, Cengiz M, Ozyigit G, Aydin A, Usubütün A, Ayhan A.

Ferah Yildiz, MD, Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey. Email: fyildiz@hacettepe.edu.tr

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Congenital lymphangioma circumscriptum (LC) of the vulva is a rare disorder with unknown etiology. Treatment options include ablative approaches such as laser therapy, sclerotherapy, and surgery. Radiotherapy has been shown to be effective in the management of congenital lymphangioma especially in the thoracic and abdominal lesions. In this report, we describe a patient with persistent vulvar LC despite sclerosing therapy and several surgical excisions. She was treated with a course of external radiotherapy and showed a dramatic objective response with relief of all symptoms.

Blackwell Synergy

Plasticity and heterogeneity of lymphoid organs What are the criteria to call a lymphoid organ primary, secondary or tertiary?

2007-08-20T10:15:00.000-07:00

Plasticity and heterogeneity of lymphoid organs What are the criteria to call a lymphoid organ primary, secondary or tertiary?

Immunol Lett. 2007 Jul 24

Pabst R.
Department of Functional and Applied Anatomy, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

Lymphoid organs are generally classified in a hierarchy with primary lymphoid organs such as the thymus and bone marrow for the production of receptor specific T and B lymphocytes, respectively, independent of antigens.

In secondary lymphoid organs such as lymph nodes, spleen, and tonsils, the lymphocytes are expanded due to antigen exposure, producing memory T cells and effector B cells, resulting in plasma cells. Tertiary lymphoid tissues are often defined as aggregations of lymphoid cells in autoimmune diseases. It will be outlined that all these organs have a high plasticity and also the thymic medulla is included in the route of migrating mature T cells and the bone marrow, not only in the traffic of CD4(+) but also of CD8(+) lymphocytes.

The mucosa-associated lymphoid organs depend to a much larger extent on microbial antigen and are much more diverse than often described. The role of structural elements as well as blood and lymphatic vessels as an entry and exit site of lymphocytes will be outlined. Using a precise terminology, taking account of the plasticity of these organs at different ages and considering species differences will reduce misunderstandings among immunologists.

PMID: 17698207 [PubMed - as supplied by publisher]

Imaging of the lymphatic system: new horizons

2007-08-03T08:38:00.000-07:00

Imaging of the lymphatic system: new horizons

Contrast Media Mol Imaging.

Barrett T, Choyke PL, Kobayashi H.
Molecular Imaging Program, National Cancer Institute, Building 10, Room 1B40, Bethesda, MD 20892-1088, USA.

Keywords:
Lymphatic imaging • sentinel node imaging • lymphangiography • contrast agent • lymphoscintigraphy

The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra-lymphatic imaging methods have been developed. Direct lymphangiography is an all-but-extinct method of visualizing the lymphatic drainage from an extremity using oil-based iodine contrast agents. More recently, interstitially injected intra-lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi-modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy.

Wiley InterScience

Lymph node imaging: basic principles
Eur J Radiol.

Luciani A, Itti E, Rahmouni A, Meignan M, Clement O.
Service d'Imagerie Médicale, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil cedex, France. alain.luciani@hmn.ap-hop-paris.fr

Keywords: Lymph node, Sentinel node, Magnetic resonance (MR), Positron emission tomography (PET), Computed tomography (CT

Lymph nodes are involved in a wide variety of diseases, particularly in cancer. In the latter, precise nodal staging is essential to guide therapeutic options and to determine prognosis. For long, imaging of the lymphatic system has been limited to lymph vessel,especially via the exclusive use of conventional lymphography, at the expense of invasive procedures and patient's discomfort. Three main technical advances, however, have recently completed the clinical armamentarium for lymph node imaging: first, the refinement of cross sectional imaging, i.e. CT and MRI, combined or not with dedicated contrast agents, has progressively replaced conventional lymphography in oncology situations; second, the development of intra-operative sentinel node mapping has profoundly modified the diagnostic and therapeutic procedures in several cancer situations, mostly melanoma and breast cancer; finally, the increased availability of functional imaging, especially through the use of FDG-PET, has greatly contributed to the accuracy improvement of nodal metastases identification. The aim of this review will thus be to briefly review the anatomy and physiology of the lymphatic systems and to overview the basic principles of up-to-date lymph node imaging.

Elsevier

Cavernous lymphangioma of the breast

2007-07-15T04:16:00.000-07:00

Cavernous lymphangioma of the breast
2007 Ogun et al; licensee BioMed Central Ltd.

Gabriel O Ogun,1 O Oyetunde,1 and EffiongE Akang2
1Department of Pathology, University College Hospital, PMB 5116, Ibadan, Nigeria
2Department of Surgery, Jericho General Hospital, Ibadan, Nigeria
Corresponding author.
Gabriel O Ogun: olabiyiogun/at/yahoo.com; O Oyetunde: droyetunde2007/at/yahoo.com; EffiongE Akang: akangee/at/comui.edu.ng

Received March 19, 2007; Accepted June 20, 2007.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
Cavernous lymphangioma is a rare lesion in the breast of adults. Only a few cases have been documented in literature.

Case presentation
We describe a 38-year-old woman who presented with a palpable breast lump, which measured 5 × 4 cm. A local excision of the lump was performed and a diagnosis of cavernous lymphangioma was made. The patient is alive and well, after five years of follow-up, with no complaints or recurrence.

Conclusion
To the best of our knowledge, this is the first case to be documented in a black African woman. Complete surgical excision seems to be the best modality of treatment of this lesion.

Background
Lymphangioma in the breast is a rare entity, and only a few cases have been documented in the literature [1-9]. Lymphangiomas are composed of dilated lymphatic channels lined by endothelium. They occur predominantly in children, with up to 90% of cases presenting by the second year of life [10,11]. The cases that have been previously documented in literature ranged from three to 25 cm in diameter and were mainly located in the upper outer quadrant of the breast (Table 1). This anatomical pattern of distribution is related to the drainage pattern of the lymphatics in the breast, which is mainly towards the tail and the axilla [9]. We present a case of lymphangioma in the breast of a black African woman.

Case presentation
A 38-year-old black female presented with a two-month history of a painful left breast lump. The pain was relieved by simple analgesics. There was no associated nipple discharge. There were no other clinical symptoms. Her past medical and family history was not significant. Physical examination revealed a well circumscribed, slightly mobile, and tender soft lump measuring about 5 × 4 cm, located in the upper outer quadrant of the left breast. There was no axillary lymphadenopathy. Clinical examination did not reveal any other significant findings. A fine needle aspiration cytology specimen obtained from the breast lesion was reported as inflammatory. The patient subsequently had excisional biopsy of the lump.

Macroscopically, the lump measured 5 × 3 × 2.5 cm and weighed 30 gm. It was nodular, and soft in consistency. Serial sections of the lump revealed greyish white surfaces, with multifocal dark brown coloured areas. Microscopically, the tumour was composed of numerous cavernous and cystically dilated spaces lined by a single layer of flattened endothelial cells, and containing brightly eosinophilic lymphatic fluid. The distended lymphatic channels were supported by a prominent fibrocollagenous stroma. There was infiltration of the stroma by lymphocytes.

Islands of adipose tissue and normal breast lobules were observed around the dilated lymphatic channels (Figures 1 and 2). The margins of the resection were free of the lesion. The definitive histological diagnosis was cavernous lymphangioma. The patient was offered no other treatment. Five years later, the patient is alive and well without any complaint or recurrence.

Discussion
Lymphangiomas are relatively uncommon lesions, more so in the breast, where they are very rare. Some authorities regard lymphangiomas to be true neoplasms that are capable of local aggressive behaviour, but overall they are benign [11].

By contrast, others believe that lymphangiomas are hamartomatous malformations that result from the failure of the lymphatic system to communicate with the venous system. Another closely related view is that lymphangiomas represent sequestrated lymphatic tissue that fails to communicate normally with the lymphatic system. According to these latter two hypotheses, abnormal rests of lymphatic tissue possess some capacity to proliferate and accumulate vast quantities of fluid, accounting for their cystic appearance [11].

Lymphangiomas are classified as capillary, cavernous, and cystic forms. The distinction between cavernous and cystic lymphangioma is often arbitrary, since both components may occur in the same lesion, thus raising the possibility that the so-called cystic lymphangioma is merely a long-standing cavernous lymphangioma in which the cavernous spaces are very large sized [5,6,8].

Table 1 show the clinical features of cases already documented in literature along with our index case. The localization of most cases to the upper outer quadrant of the breast is probably related to the route of drainage of the lymphatic system of the breast [9].

Typically, lymphangiomas are described as fairly well circumscribed and soft, as was observed in our index case [1,6,11]. Imaging techniques such as ultrasonography, mammography, and magnetic resonance imaging may be used to assess, make a clinical diagnosis and for follow-up [1-3,5-9].

The final diagnosis is based on a combination of clinical, radiological, and histopathological findings [1,2,6,9].

Histologically, cavernous lymphangiomas show numerous narrow spaces containing amorphous eosinophilic fluid and few lymphocytes and lined by a monolayer of attenuated endothelial cells [6,11]. Some of the channels may contain blood because of secondary haemorrhage, resulting in misdiagnosis of this lesion as cavernous haemangioma. However, the presence of large collections of lymphoid cells in the stroma, sometimes with lymphoid follicle formation, and the relatively greater irregularity of the lumina of the cavernous spaces, tilt the diagnosis in favour of lymphangioma [11,12].

Vascular endothelial markers such as factor VIII- associated antigen and CD 31 may be positive in lymphatic endothelium and are therefore not reliable in distinguishing between haemangiomas and lymphangiomas [6,11]. Laminin may be expressed in the discontinuous basal lamina of lymph vessels [6,12]. It is best expressed in blood vessels than lymphatic channels, therefore making a sharp distinction between the two structures difficult.

A possible differential diagnosis is lymphangiomyomatosis, which exclusively occurs in women and is localised to the lymphatics of the mediastinum, retroperitoneum and the pulmonary parenchyma. Lymphangiomyomatosis is characterised by a distinctive and very prominent smooth muscle proliferation in the affected lymphatics and the smooth muscle cells co-express muscle and melanocytic markers [11,12]. Another differential diagnosis is acquired lymphangiectasis, which occurs in patients who have had surgery and radiation therapy for malignancy. Morbidly obese individuals may also develop lymphangiectasis, due to the weight of large dependent folds of fat causing lymphatic obstruction. This may be more pronounced with previous surgery interrupting the lymphatics [11].

Local surgical excision is the best modality of treatment of this benign breast disease, as is the practice for lymphangiomas in other parts of the body, and as illustrated by this case and previously reported cases. The probability of recurrence is low if completely excised.

Conclusion
To our knowledge, this is the first case to be documented in a black African woman. Complete surgical excision seems to be the best modality of treatment.
Competing Interests
The author(s) declare that they have no competing interests.
Author's contributions
OGO and AEE designed the study, performed the histological assessment and picture acquisition and drafted part of the manuscript. OO performed the surgery, carried out data acquisition and drafted part of the manuscript. All authors participated in the editing and have read and approved the final manuscript.
Acknowledgements

Written consent was obtained from the patient or their relative for publication of study.

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World Journal of Surgical Oncology

Lymphangioleiomyomatosis (LAM)--an uncommon cause of bilateral spontaneous pneumothorax

2007-07-08T10:47:00.000-07:00

Lymphangioleiomyomatosis (LAM)--an uncommon cause of bilateral spontaneous pneumothorax

Rev Med Chir Soc Med Nat Iasi. 2007

Grigorescu C, Bosânceanu M, Boişteanu D, Aldea A, Chiseliţă I, Cozma LG.
Clinica de Chirurgie Toracică, Facultatea de Medicină, Universitatea de Medicină si Farmacie "Gr. T. Popa", Iaşi.

LAM, a rare lung disease typically affecting women of reproductive age, is characterized by abnormal proliferation of smooth--muscle cells and progressive loss of pulmonary function due to destruction of lung parenchyma. Two cases of bilateral succesive recurrent spontaneous pneumothorax and haemoptysis are presented.

Repeated conventional and video-assisted surgery was required in both cases, for drainage of the recurrent pneumothorax and resection of subpleural bulae, with good immediate postoperative evolution. Immunohistochemical studies of resected specimens revealed LAM cells in the lung parenchyma with receptors for oestrogen and progesterone. HMB45 monoclonal antibodies in the LAM cells were identified in one case.

The follow-up of the patients revealed no signs of recurrence at 84 and 18 months respectively, although pulmonary transplantation should be considered in case of further deterioration of respiratory function.

PMID: 17595857 [PubMed - in process]

A case of lymphangioleiomyomatosis found due to chylous ascites, pleural effusion and pelvic lymphadenopathy

2007-06-30T23:14:00.000-07:00

A case of lymphangioleiomyomatosis found due to chylous ascites, pleural effusion and pelvic lymphadenopathy

Nihon Kokyuki Gakkai Zasshi. 2007

Yano T, Hasizume I, Kasamatsu N, Kato T, Shibata M, Ashinuma N, Kobayashi K, Yasuda T, Nakamura A.
Department of Respiratory Medicine, Hamamatsu Medical Center.

We report a case of lymphangioleiomyomatosis, complaining initially of abdominal distension due to massive chylous ascites. The patient was a 28-year-old woman in whom abdominal ultrasound had strongly suggested the existence of both pelvic lymphadenopathy and massive ascites, the latter subsequently turning out to be chylous. Pelvic lymph node biopsy yielded a diagnosis of lymphangioleiomyomatosis. High-resolution computed tomography (HRCT) of the chest showed no remarkable findings except for very few cystic changes in the lung parenchyma.

Pulmonary function had remained normal except for a temporary constrictive pattern when chylous pleural effusion developed. No airflow obstruction was detected on pulmonary function tests.

Although lymphangioleiomyomatosis is often associated with pulmonary symptoms, we should bear in mind the possibility of lymphangioleiomyomatosis even in the absence of such symptoms when facing any woman of child-bearing age with abdominal chylous ascites of unknown etiology.

PMID: 17554983 [PubMed - indexed for MEDLINE]

Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice.

2007-06-24T05:24:00.000-07:00

Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice.
J Nutr. 2007 Jan
Reliene R, Schiestl RH.
Department of Pathology, Geffen School of Medicine and School of Public Health, University of California, Los Angeles, CA 90095, USA.

* To whom correspondence should be addressed. E-mail: rschiestl@mednet.ucla.edu

Ataxia telangiectasia (AT), a human hereditary disorder resulting from mutations in the ATM gene, is characterized by a high incidence of lymphoid malignancies, neurodegeneration, immunodeficiency, premature aging, elevated radiosensitivity, and genomic instability. Evidence has been accumulating that ATM-deficient cells are in a continuous state of oxidative stress. A variety of markers of oxidative stress were detected in AT patients as well as Atm-deficient mice, used as an animal model of AT. Since then, it has been proposed that oxidative stress contributes to the clinical phenotype of AT, especially carcinogenesis and neurodegeneration, and several animal studies were conducted to determine whether exogenous antioxidants mitigate the symptoms of AT. Tempol, EUK-189, and N-acetyl cysteine have been tested as chemopreventive antioxidants in Atm-deficient mice. We review these findings, mainly focusing on the effect of N-acetyl cysteine, which is known as a safe and efficient drug and nutritional supplement.

Full Text Article:

Journal of Nutrition

Kawasaki disease: diagnosis, management and cardiac sequelae

2007-06-18T04:29:00.000-07:00

Kawasaki disease: diagnosis, management and cardiac sequelae

May 2007, Vol. 5, No. 3, Pages 553-561
(doi:10.1586/14779072.5.3.553)

Louise Wood and Robert Tulloh

† Author for correspondence

Kawasaki disease (KD) is an acute self-limiting systemic vasculitis of unknown etiology and the most common cause of acquired coronary disease in children aged 6 months to 5 years. The inflammatory process results in coronary arteritis, aneurysmal lesions, arterial thrombotic occlusion or even sudden death. The diagnostic tests are unknown but treatment with immunoglobulin and aspirin is effective at reducing cardiac complications from 25 to 4.7% in the UK. Myocardial, endocardial or pericardial inflammation may occur acutely or many years later and abnormalities of myocardial blood flow may require ongoing medication, interventional catheterization or even cardiac surgery. There are several new drugs that may have important roles to play in managing KD in children and young adults.

Future Drugs

Generalized lymphangiomatosis presenting as cardiomegaly

2007-06-10T05:39:00.000-07:00

Generalized lymphangiomatosis presenting as cardiomegaly

J Formos Med Assoc. 2007 Mar
Chen YL, Lee CC, Yeh ML, Lee JS, Sung TC.
Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

Lymphangioma refers to the local proliferation of well-differentiated lymphatic tissue.

Generalized lymphangiomatosis is rare. We report a previously healthy 8-month-old infant who suffered from tachypnea with mild fever for 2 weeks. Imaging studies revealed a well-defined, large mass occupying the mediastinum, which presented as cardiomegaly. The disseminated mass extended to the thymus, lung, and spleen. Lymphangiomatosis was diagnosed by biopsy.

Drainage of the pericardial fluid and total parenteral nutrition did not result in improvement of chylopericardium.

Secondary hypogammaglobulinemia and septic shock developed sequentially. Surgical removal of the mediastinal mass and spleen were performed. Daily subcutaneous injection of interferon (IFN) alpha-2b was then given for 3 months. No recurrence was noted during 2 years of follow-up. IFN alpha-2b may be considered as an alternative for the treatment of generalized lymphangiomatosis.

Elsevier

New Treatment for Noonan Syndrome

2007-06-02T05:37:00.000-07:00

FDA OK's DRUG FOR NOONAN SYNDROME

June 1, 2007

WASHINGTON, June 1 (UPI) -- The U.S. Food and Drug Administration Friday approved Copenhagen-based Novo Nordisk's Norditropin for children with Noonan syndrome.

The genetic disorder is characterized by short stature, congenital heart defects and unique facial features, notably widely set eyes.

The use of Norditropin -- somatropin injection -- is aimed at treatment of short stature in these individuals.

Fewer than 200,000 people have the condition, prompting the FDA to give Norditropin an orphan drug designation. No other treatment for short stature in these patients is available.

The prevalence of Noonan syndrome has not been determined accurately to date, but most authors report 1 in 1,000 to 1 in 2,500 live births, affecting males and females equally. In addition to heart abnormalities and short stature -- affecting 80 percent of people with Noonan syndrome -- patients may also have visual and hearing deficits, bleeding abnormalities and lack muscle tone.

"Noonan syndrome is a heterogeneous genetic condition in which the clinical features are quite variable," said Alicia Romano, a pediatric endocrinologist at the New York Medical College, in a statement issued by Novo Nordisk.

"Short stature, which can be severe, is one of the most common characteristics. Treatment with Norditropin may help children with Noonan syndrome improve one of the most concerning physical features of the condition."

Norditropin is also approved for treatment of children with growth failure due to inadequate secretion of endogenous growth hormone and for replacement of endogenous growth hormone in adults with growth hormone deficiency.

United Press International

LIGHTHOUSE LYMPHEDEMA NETWORK LYMPHEDEMA EDUCATION & AWARENESS PROGRAM

2007-05-25T05:35:00.000-07:00

THE LIGHTHOUSE LYMPHEDEMA NETWORK

INVITES YOU TO OUR 10th ANNUAL

LYMPHEDEMA EDUCATION & AWARENESS PROGRAM:

“Lymphedema: Empowerment through Knowledge"

October 5-7, 2007
Renaissance Waverly Hotel
2450 Galleria Parkway
Atlanta GA 30339

The Lighthouse Lymphedema Network is pleased to invite you to an outstanding educational and awareness conference this fall! Continuing our annual efforts to increase awareness about lymphedema, we have assembled a terrific group of speakers to provide information on a wide variety of topics for patients, family, caregivers, and professionals. We will also have a large number of our excellent vendor associates present to demonstrate current products for lymphedema care and treatment.

Whether you are newly-diagnosed with lymphedema and eager to get more information about what it is and how it can be treated, or perhaps you are interested in learning what the latest research in this field promises, attendance at our program will definitely be beneficial. [Professionals, remember LLN offers CEUs for attendance.

Our program starts Friday afternoon, October 5, with a pre-conference tour of Sigvaris’ garment manufacturing plant here in Atlanta, and will be followed by a Kick-Off Party from 5:00-7:00 PM. Saturday and Sunday are full of plenary sessions open to everyone, with instructional sessions for both professionals and all other conference attendees.

Program Information Page

For further information, schedule and registration:

The Primary Valves in the Initial Lymphatics during Inflammation.

2007-05-19T19:48:00.000-07:00

The Primary Valves in the Initial Lymphatics during Inflammation.

Lymphat Res Biol. 2007
Lynch PM,
Delano FA,
Schmid-Schonbein GW.
Department of Bioengineering, University of California San Diego, La Jolla, California., Supported by United States Public Health Service Grant HL 10881.

Background: The primary valve system in the initial lymphatics prevents fluid transport from the initial lymphatics back into the interstitium. The authors hypothesize that since the primary valves are made up of an extraordinarily thin endothelium, they are readily compromised by mechanical or biochemical inflammatory stimuli. Thus, the opening dimension of the primary valves and their ability to prevent reflux into the interstitium during inflammation were investigated.

Methods and Results: Acute inflammation was generated in the intact rat spinotrapezius muscle by suffusion of f-Met-Leu-Phe and platelet-activating factor. Once inflamed, the effective opening dimensions of the primary valves and the transport back out of the initial lymphatics were determined by examining the transport of fluorescent tracers from the interstitium to the lymphatics. Quantum dots and fluorescently labeled albumin readily enter initial lymphatics from the interstitium. The maximum diameter of microspheres that enter the initial lymphatics is between 0.5 mum and 0.8 mum in both control and inflamed tissue. While under control conditions no quantum dots escaped from initial lymphatics back into the interstitium, during inflammation there was extensive escape of quantum dots.

Conclusions: These results suggest that, in acute inflammation, the function of the endothelial barriers in the initial lymphatics may be compromised.

A failure of the primary lymphatic valves has two consequences.

First, fluid clearance from the tissue is less efficient, which causes the level of edema to increase.

Second, the leaking initial lymphatics allow inflammatory mediators to accumulate in the tissue, therefore enhancing interstitial and lymphatic inflammatory reactions.

PMID: 17508898 [PubMed - in process]

Pr08 lymphatic malformations and the molecular basis of lymphangiogenesis. Options

2007-05-11T20:17:00.000-07:00

Pr08 lymphatic malformations and the molecular basis of lymphangiogenesis.

Options

ANZ J Surg. 2007 May

Ch'ng S, Tan ST. Wellington Regional Plastic Unit, Hutt Hospital, Wellington, New Zealand.
This paper reviews the clinical features of lymphatic malformations and the molecular basis of embryonic lymphangiogenesis.

Lymphatic malformations are classified as microcystic, macrocystic, or combined. Most commonly found in the axilla/chest and cervicofacial region, they can be localised or diffuse. The commonest complications are intralesional bleeding and infection. Other significant complications are due mainly to their mass effect on nearby anatomic structures including the airway and eyeball, and soft tissue and skeletal overgrowth including macrocheilia, macroglossia, macrotia, macromala and mandibular prognathism, resulting in functional problems in feeding, speech, occlusion, oral hygiene, and disfigurement.

The characteristic radiological finding of a LM on gadolinium-enhanced T1-weighted MRI is a low-density lesion with septation or rim enhancement. Histologically, LMs are cystic lesions that contain eosinophilic proteinaceous fluid whose walls are composed of smooth and skeletal muscle fibres, collagen and lymphocytes. Management options range from observation, comfort cares, empirical antibiotic treatment for LM cellulitis to sclerotherapy, surgical excision and Nd:YAG laser for selected cases.

Lymphangiogenesis is believed to occur in four sequential but overlapping stages: lymphatic endothelial cell competence, bias and specification, and finally lymphatic vessel terminal differentiation and maturation. Multiple genes are involved in this process including Lyve1, Nrp2, podoplanin, Prox1, VEGFR3, VEGFC and Ang2. Developmental defects during embryonic lymphangiogenesis result in lymphatic malformations.

PMID: 17490238 [PubMed - in process]

Molecular mechanisms of lymphatic vascular development.

2007-05-05T05:04:00.000-07:00

Molecular mechanisms of lymphatic vascular development.

Cell Mol Life Sci. 2007 Apr 27

Keywords: Lymphangiogenesis - vascular remodeling - PROX1 - VEGFR-3 -FOXC2 - Ephs/ephrins

Lymphatic vasculature has recently emerged as a prominent area in biomedical research because of its essential role in the maintenance of normal fluid homeostasis and the involvement in pathogenesis of several human diseases, such as solid tumor metastasis, inflammation and lymphedema. Identification of lymphatic endothelial specific markers and regulators, such as VEGFR-3, VEGF-C/D, PROX1, podoplanin, LYVE-1, ephrinB2 and FOXC2, and the development of mouse models have laid a foundation for our understanding of the major steps controlling growth and remodeling of lymphatic vessels.

In this review we summarize recent advances in the field and discuss how this knowledge as well as use of model organisms, such as zebrafish and Xenopus, should allow further in depth analysis of the lymphatic vascular system.

Springerlink

New Medicine for Lymph Node Cancer

2007-04-29T19:25:00.000-07:00

Quick cure for lymph node cancer‎

Sun, 29 Apr 2007 06:27:04

A new medicine against lymph node cancer is the latest invention of Czech scientists. The new drug has had very good effects in tests so far. Lab dogs with expanded tumors on their throat and stomachs were treated by the new medicine, after six days, no sign of cancer was discerned. The new medicine is unique in the way that it only affects cancerous cells without destroying healthy tissue of body. Hence, unlike chemotherapy which leaves drastic effects on immunity system, no side effects are caused by this new drug.

The U.S. Company Gilead has already started to test the substance, developed in Prague's Institute for Organic Chemistry and Biochemistry and designed to treat lymph node cancer on several thousands of patients in the U.S If the new medicine is approved it might be available on sale in about six years. The new medicine is effective in the case of lymph node cancer that makes up one-fourth of all cancerous diseases. It affects tumors in abdomen, chest, thymus and spleen, the paper wrote.

MMN/HAR

presstv

Czech scientists develop new anti-cancer medicine -- press

Prague- Czech scientists have developed a new medicine against cancer which has had very good effects in tests so far, the daily Mlada fronta Dnes (MfD) writes today, adding that malignant tumours on tested dogs' throats and stomachs disappeared after six days of treatment.

The U.S. company Gilead has started to test the substance, developed in Prague's Institute for Organic Chemistry and Biochemistry and designed to treat lymph node cancer, on several thousands of patients in the USA, MfD writes.

The researchers are now trying to detect possible side effects of the medicine that could be put on sale in about six years.

Three Czech companies have cooperated on its development, headed by Antonin Holy and Ivan Votruba from the above-mentioned institute and Berta Otova from Charles University's 1st medical faculty.

Holy's team previously won world appreciation for the developed substances against viral diseases and AIDS, MfD recalls.

It says the new medicine is unique as it affects only cancer-hit cells without destroying healthy tissue. Its application is thus not as drastic as, for example, chemotherapy, which destroys the whole immunity system.

"We don't know for the time being why our substance affects only the ill cells and leaves the healthy untouched," the institute director Zdenek Havlas told the daily.

The new medicine is effective in the case of lymph node cancer that makes up one-fourth of all cancerous diseases. It affects tumours in abdomen, chest, thymus and spleen, MfD writes.

Cesknoviny

Colorectal lymphangioma.

2007-04-26T13:26:00.000-07:00

Colorectal lymphangioma.
Am Surg. 2007 Apr

Huguet KL,
Metzger PP,
Menke DM.
Department of Surgery, Mayo Clinic, Jacksonville, Florida 32224, USA.

Lymphangiomas of the colon are historically rare benign tumors. Only 331 cases have been reported in the world medical literature between 1931 and 2004. With widespread use of colonoscopy, however, they are being found more frequently. We report the case of a 74-year-old woman in whom a colonoscopy revealed a 3 x 4-cm submucosal lesion in the cecum that was eventually diagnosed as a lymphangioma. A CT of the abdomen showed a soft-tissue mass in the cecum and a low-density hepatic lesion.

An endoscopic ultrasound of the colon showed a 3 x 4-cm hypoechoic lesion with internal septa arising from the submucosal layer of the cecum. This lesion resembled a vascular malformation; therefore a biopsy specimen was not taken. Pathologic findings of a specimen taken after a subsequent right hemicolectomy identified a submucosal lymphangioma. Published reports indicate that colonoscopy cures most lesions smaller than 2.5 cm in diameter. Resection should be reserved for larger lesions or those in patients exhibiting protein-losing enteropathy.

PMID: 17439042 [PubMed - in process]