Developmental Disorders of the Lymphatics

An information blog for disorders of the lymphatics. For all articles, please click on "Archives" - Due to spammers, I will no longer allow comments, sorry.

Friday, November 30, 2007

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

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,

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

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Thursday, November 22, 2007

Bilateral renal lymphangiomatosis: conservative management

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.

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]


Friday, November 16, 2007

Lymphatics and bone

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


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


Thursday, November 15, 2007

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

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.

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.



Saturday, November 10, 2007

Unilateral Lower Limb Swelling Secondary to Cavernous Lymphangioma.

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.


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


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.


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.


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Saturday, November 03, 2007

Research clarifies origin of mammalian network of lymphatic vessels

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

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