Thoracic lymphangiomatosis: report of 3 patients with different presentations.

Dec 2012

Liu Y, Sui X, Chen K, Li J, Yang F, Ho AK, Wang J.

Source

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Abstract

Lymphangiomatosis originates from congenital multiple malformations of the lymphatic vessel system. It is a benign lesion with malignant behavior. No radical treatment is indicated for this disease. The first patient presented initially with multiple bone cysts suggestive of multiple myeloma, the second with pleural effusion, and the third with mild shortness of breath. The lesions in these 3 patients were mainly located in the upper mediastinum, the parietal pleura, and the lung, respectively. Without any further treatment, their symptoms and radiographic images showed no progression of these conditions after a follow-up time of 7 to 42 months.

Science Direct

New advances in the diagnosis and treatment of autoimmune lymphoproliferative syndrome.

2012

Teachey DT.

Source

Division of Pediatric Hematology, Children's Hospital of Philadelphia, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA. teacheyd@E-Mail.chop.edu

Abstract

PURPOSE OF REVIEW:

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of disrupted lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. Clinical manifestations include lymphadenopathy, splenomegaly, and autoimmune cytopenias. A number of new insights have improved the understanding of the genetics and biology of ALPS. These will be discussed in this review.

RECENT FINDINGS:

A number of key observations have been made recently that better define the pathophysiology of ALPS, including the characterization of somatic FAS variant ALPS, the identification of haploinsufficiency as a mechanism of decreased Fas expression, and the description of multiple genetic hits in FAS in some families that may explain the variable penetrance of the disease. In addition, ALPS has been shown to be a more common condition, as patients diagnosed with other disorders, including Evans syndrome and common variable immune deficiency, have been found to have ALPS. Finally, the treatment of the disease has changed as splenectomy and rituximab have been shown to have unexpected ALPS-specific toxicities, and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease.

SUMMARY:

On the basis of novel advances, the diagnostic algorithm and recommended treatment for ALPS have changed significantly, improving quality of life for many patients.

Pediatrics

A Case of Hepatopulmonary Syndrome Solved by Mycophenolate Mofetil (An Inhibitor Of Angiogenesis and Nitric Oxid Production).

Oct 2012

Silva HM, Reis G, Guedes M, Cleto E, Vizcaíno JR, Kelly D, Gennery AR, Silva ES.

Source

Pediatric Gastroenterology Unit, Department of Child and Adolescent, Centro Hospitalar do Porto, Portugal.

Abstract

BACKGROUND:

The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multi-systemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation, andautoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multi-systemic cases; so far there is no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment.

CASE REPORT:

 A Teenage boy, diagnosed with ALPS at 4 years old (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13 years old when he developed insidiously hypoxemia (PaO2 = 46.7 mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intra-pulmonary shunt = 45%). He was treated with oxygen (maximum 6 liters/minute), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except the pulmonary symptoms, so, after evaluation in referral centers in England, OLT was proposed. Since he was to be submitted to major surgery, sirolimus, which has wound healing problems, was switched for mycophenolate mofetil (MMF). Following this change, we observed an enormous improvement of the pulmonary symptoms and reduction of oxygen needs. The intra-pulmonary shunt decreased from 45% to 0% in less than a year, and remains so until today (18 months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation.

CONCLUSION:

The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in the HPS pathogenesis). Therefore, we propose the conduct of clinical trials with MMF, and/or other angiogenesis and NO inhibitors, in a long-term treatment basis, to confirm their potential as a valid alternative for medical treatment of HPS.

Elsevier

Auto-immune lymphoproliferative disorder and other secondary immune thrombocytopenias in childhood.

Oct 2012

Price V.

Source

Division of Pediatric Hematology-Oncology, Department of Pediatrics, Dalhousie University, Halifax, Canada. Vicky.price@iwk.nshealth.ca.

Abstract

Primary immune thrombocytopenia (ITP) in childhood, typically presents as an acute self-limiting illness. However, secondary ITP is often a chronic disorder due to an underlying disease. Combined cytopenias in childhood, that is, secondary ITP occurring with auto-immune hemolytic anemia and/or auto-immune neutropenia, are often associated with disorders characterized by immune dysregulation. Such disorders include systemic lupus erythematosus, auto-immunelymphoproliferative syndrome, and common variable immune deficiency. Evans syndrome describes the combination of ITP,autoimmune hemolytic anemia, and/or autoimmune neutropenia. However, it is now clear that some patients with Evans syndrome have an underlying immunodeficiency. This report focuses on combined auto-immune cytopenias and highlights the challenges in their diagnosis and management.

Wiley OnLine

Lymphangioleiomyomatosis - a wolf in sheep's clothing.

Nov 2012

Henske EP, McCormack FX.

Abstract

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many forms of human cancer, including mutation, metabolic reprogramming, inappropriate growth and survival, metastasis via blood and lymphatic circulation, infiltration/invasion, sex steroid sensitivity, and local and remote tissue destruction. However, the smooth muscle cell that metastasizes, infiltrates, and destroys the lung in LAM arises from an unknown source and has an innocent histological appearance, with little evidence of proliferation. Thus, LAM is as an elegant, monogenic model of neoplasia, defying categorization as either benign or malignant.

Journal of Clinical Investigation

The role of vascular endothelial growth factor-D in diagnosis of lymphangioleiomyomatosis (LAM).

Nov 2012

Xu KF, Zhang P, Tian X, Ma A, Li X, Zhou J, Zeng N, Gui YS, Guo Z, Feng R, Zhang W, Sun W, Cai B.

Source

Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: kaifeng.xu@gmail.com.

Abstract

BACKGROUND:

Definite diagnosis of lymphangioleiomyomatosis (LAM) depends on either transbronchial lung biopsy or video-assisted thoracic surgery, unless there is a history of chylothorax, kidney angiomyolipoma (AML), or tuberous sclerosis complex (TSC). Vascular endothelial growth factor-D (VEGF-D) was recently considered as a novel diagnostic marker for LAM. Herein, we evaluated diagnostic value of serum VEGF-D in LAM patients.

METHODS:

Serum samples were obtained from 78 cases of LAM (50 definite and 28 probable LAM based on European Respiratory Society guidelines), and 40 healthy female volunteers. VEGF-D was measured using enzyme-linked immunosorbant assay according to product instruction (R&D).

RESULTS:

Serum VEGF-D was significantly increased in definite LAM group, compared with that of health control (median: 3841.9 pg/mL vs 405.5 pg/mL respectively, p < 0.001). The optimal cut-off point for definite LAM diagnosis was 850.7 pg/mL. In probable LAM group, the majority of patients (92.9%) had serum VEGF-D level over 850.7 pg/mL. The serum levels of VEGF-D in LAM patients with pulmonary cystic lesions only were lower than that in patients with any of evidences of AML, chylous effusions, adenopathy, lymphangioleiomyomas, or TSC, but higher than that in the health control. In addition, VEGF-D levels were correlated with disease severity measured as LAM CT grade, and presentations of chylous effusions and/or lymphatic involvement (p < 0.05).

CONCLUSION:

Serum VEGF-D should be added to the current diagnosis algorithm to enhance definitive diagnosis for LAM.

Elsevier

Fetal axillary cystic hygroma: A novel association with triple X syndrome.

Oct 2012

Iskender C, Tarım E, Cok T, Yalcinkaya C, Kalaycı H, Sahin F.

Source

Department of Obstetrics and Gynecology, Baskent University Faculty of Medicine, Seyhan, Adana, Turkey. c_iskender@yahoo.com.

Abstract

BACKGROUND:

Triple X syndrome is a relatively common sex chromosomal aneuploidy with an estimated incidence of one in every 1000 female births. There is considerable diversity in phenotypes among patients with triple X syndrome. Triple X syndrome has been shown to have associated abnormalities, with genitourinary malformations being the most consistent. Cystic hygroma (CH) is a lymphatic malformation that occurs because of the lack of development of communication between the lymphatic and the venous systems. CH has an incidence of 1 in every 6000-10,000 live births. CH is associated with a variety of conditions, including chromosomal aneuploidies and fetal malformations.

CASE:

We report a case of prenatally detected triple X syndrome with axillary CH as an isolated finding. The patient was referred because of a fetal cystic mass at the right axillary region. Amniocentesis revealed 47,XXX karyotype, and no additional abnormalities were detected prenatally or after abortion.

CONCLUSION:

This is a novel description of axillary CH associated with triple X syndrome. 

Wiley Online Library

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis.

Sept 2012

Glasgow CG, El-Chemaly S, Moss J.

Source

Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA.

Abstract

The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM) and idiopathic pulmonary fibrosis (IPF). LAM, a disease primarily affecting females, involves the lung (cystic destruction), kidney (angiomyolipoma) and axial lymphatics (adenopathy and lymphangioleiomyoma). LAM occurs sporadically or in association with tuberous sclerosis complex (TSC). Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF) express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

European Respiratory

A fatal case of Kikuchi-Fujimoto disease.

Jan 2012

Dosi RV, Ambaliya A, Patel JS, Bhambhani YS, Patell RD.

Source

Department of Medicine, Medical College and SSG Hospital, Vadodara 390001.

Abstract

Kikuchi-Fujimoto disease is an extremely rare, benign, auto-immune, clinicopathological condition presenting with fever and lymphadenopathy. It has higher prevalance among Japanese and other Asiatic individuals. It is usually self-limiting with extremely rare mortality. A case of an adolescent girl who presented with fever and cervical lymphadenopathy, found to have Kikuchi's disease on histopathology of cervical lymph node is being reported. She eventually succumbed to the disease.

PubMed

see also:

Kikuchi-Fujimoto disease in an HIV carrier

Kikuchi disease with skin lesions mimicking lupus erythematosus.

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) after laparoscopic Roux-en-Y gastric bypass for morbid obesity: a case report.

Kikuchi-Fujimoto disease in fine needle aspiration smears: A clinico-cytologic study of 18 pediatric cases and correlation with 68 adult patients.

Kikuchi-Fujimoto disease with cutaneous presentation in a patient with subacute cutaneous lupus erythematosus.

Klippel-Trenaunay Syndrome Complicated by Ascites and Vaginal Lymphatic Drainage in Adolescence: A Case Report.

Oct 2012

Scribner DR Jr, Lara-Torre E, Heineck RJ, Weiss PM.

Source

Virginia Tech Carilion School of Medicine, Roanoke, VA.

Abstract

BACKGROUND:

 Klippel-Trenaunay syndrome is a rare disease characterized by capillary malformationsand soft tissue and bony hypertrophy and atypical varicosities. Management of this syndrome is focused primarily on treatment of the complications that arise from these malformations. Ascites and lymphedema are two of the more common complications in these patients.

CASE:

 A 15-year-old female with Klippel-Trenaunay syndrome presented with chylous ascites, vaginal drainage, and unilateral lower extremity lymphedema. Treatment included dilation, hysteroscopy and curettage, and laparoscopic evacuation of abdomino-pelvic ascites with resolution of symptoms for 32 months. Repeat laparoscopic drainage was successful and remains symptom free after 12 months.

CONCLUSION:

 Vaginal drainage of chylous ascites is a rare complication from Klippel-Trenaunay syndrome and can be successfully managed by techniques to remove abdomino-pelvic ascites.

Elsevier

Castleman disease.

Sept 2012

Saeed-Abdul-Rahman I, Al-Amri AM.

Source

Division of Nephrology, Department of Internal Medicine, King Fahd University Hospital, Dammam University, Al-Khobar, Saudi Arabia.

Abstract

Castleman and Towne described a disease presenting as a mediastinal mass resembling thymoma. It is also known as "giant lymph node hyperplasia", "lymph node hamartoma", "angiofollicular mediastinal lymph node hyperplasia", and "angiomatous lymphoid hyperplasia". The pathogenesis is unknown, but the bulk of evidence points toward faulty immune regulation, resulting in excessive B-lymphocyte and plasma-cell proliferation in lymphatic tissue. In addition to the mediastinal presentation, extrathoracic involvement in the neck, axilla, mesentery, pelvis, pancreas, adrenal gland, and retroperitoneum also have been described. There are 2 major pathologic variations of Castleman disease: (1) hyaline-vascular variant, the most frequent, characterized by small hyaline-vascular follicles and capillary proliferation; and (2) the plasma-cell variant, in which large lymphoid follicles are separated by sheets of plasma cells. The hyaline-vascular cases usually are largely asymptomatic, whereas the less common plasma-cell variant may present with fever, anemia, weight loss, and night sweats, along with polyclonal hypergamma-globulinemia. Castleman disease is a rare lymphoproliferative disorders. Few cases have been described world widely. In this article we reviewed the classification, pathogenesis, pathology, radiological features and up to date treatment with special emphasis on the role of viral stimulation, recent therapeutic modalities and the HIV-associated disease.

Full Text Article

NIH/Korean Journal of Hematology

Treatment of lymphatic malformations: a more conservative approach.

Oct 2012

Gilony D, Schwartz M, Shpitzer T, Feinmesser R, Kornreich L, Raveh E.

Source

Department of Otolaryngology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: drorgil@zahav.net.il.

Abstract

BACKGROUND/PURPOSE:

Lymphatic malformation is a benign disfiguring lesion of the neck and face in children. This study investigated the application and outcome of different modes of treatment.

METHODS:

The medical files of all children with lymphatic malformation of the head and neck attending a tertiary medical center in 1999 to 2010 were reviewed. Findings were compared by treatment: surgery, OK-432 sclerotherapy, or observation.

RESULTS:

The study group included 46 patients, most (65%) with macrocystic disease. Twenty were treated by OK-432 sclerotherapy, and 15, by surgery; 11 (with minor disfigurement) were observed only. Mean follow-up time was 2.4 years. Complete removal or complete response to treatment was achieved in 67% of the surgery group and 45% of the OK-432 group; fair results (>50% reduction in swelling) were achieved in 20% and 50%, respectively. Sclerotherapy failure did not interfere with subsequent surgery. Complete spontaneous regression occurred in 5 patients under observation only.

CONCLUSIONS:

OK-432 sclerotherapy is associated with good aesthetic results in children with lymphatic malformation. Observation alone is sometimes sufficient. Surgery should be reserved for cases requiring a histologic diagnosis, microcysticdisease, patients with an urgent clinical problem (eg, airway obstruction), and sclerotherapy failures.

Elsevier

Lymphatics, lymph nodes and the immune system: barriers and gateways for cancer spread.

Oct 2012

Ferris RL, Lotze MT, Leong SP, Hoon DS, Morton DL.

Source

Hillman Cancer Center Research, Pavilion 5117 Centre Avenue, Room 2.26b, Pittsburgh, PA, 15213, USA, ferrisrl@upmc.edu.

Abstract

Metastasis to the regional lymph node is the most important prognostic indicator for the outcomes of patients with sold cancer. In general, it is well recognized that cancer development is genetically determined with progression from the microenvironment of the primary tumor site, oftentimes via the SLN gateway, to the distant sites. In about 20 % of the time, the cancer cells may spread directly through the blood vascular system to the distant sites. Thus, in general, cancer progression is consistent with Hellman's spectrum theory in that development of nodal and systemic metastasis from a localized cancer growth is a progressive process. 

Cancer proliferation within the tumor microenvironment may give rise to increased tumor heterogeneity, which is further complicated by its continuous change through its evolution within the host in a Darwinian sense. It is crucial to understand the molecular process of lymphangiogenesis and hemangiogenesis in the tumor microenvironment with respect to the initial steps of cancer cells entering into the lymphatic and vascular systems so that rational therapy can be developed to curb the process of specific routes of metastasis. This chapter elucidates the role of lymphatics, nodal metastasis and antitumor immunity. 

We present novel immune targets in nodal metastases, the importance of the lymph node as a pre-metastatic niche, and immune-related proteins as biomarkers of metastasis.

PubMed

Study of the primo-vascular system and location-dependent oxygen levels for a mouse embryo.

July 2012

Hong M, Park SS, Do H, Jhon GJ, Suh M, Lee Y.

Source

Department of Biological Sciences, Sungkyunkwan University, Suwon, Kyunggi-Do, 440-746, South Korea.

Abstract

The two major circulatory systems, the lymph system and the blood vessel system, play significant roles in controlling embryonic development. The primo-vascular system (PVS) was recently reported as an additional circulatory system in various animals. In this paper, the PVS in a mouse embryo was investigated. The structural characterization of the PVS in the mouse placenta and umbilical cord, which was visualized with the trypan blue staining technique, was focused on. The PVS was well_developed in the mouse placenta area. Using a nanopore-based amperometric oxygen sensor, the oxygen levels at four different areas of the embryonic brain, placenta, blood vessel, and primo-vessel of the PVS were measured. The relatively higher oxygen levels that were measured at the primo-vessels than at the brain and the placenta, while still lower than the oxygen level that was measured at the blood vessels, may suggest a role of PVS in oxygen transport.

PubMed