Klippel-Trenaunay-Weber Syndrome

Klippel-Trenaunay-Weber Syndrome

Parkes Weber syndrome, PWS, Klippel-Trenaunay syndrome, KTS, Kasabach-Merritt syndrome, angioosteohypertrophy syndrome, cutaneous capillary malformation, congential vascular nevus, capillary hemangioma, port-wine stain, lymphedema

Synonyms

KTW syndrome, Klippel-Trenaunay syndrome, angio-osteohypertrophy syndrome, naevus vasculosus osteohypertrophicus; Parkes-Weber syndrome is a similar entity involving the presence of an arteriovenous malformation with high-flow vessel malformations and characteristic skin capillary changes, with associated skeletal or soft tissue hypertrophy (also known as haemangiectatic hypertrophy).

See also: Sturge-Weber syndrome

Clinical Features

First described by French physicians Klippel and Trenaunay in 1900, this syndrome is characterized by port-wine stain (capillary hemangioma), varicose veins and bony and soft tissue hypertrophy involving an extremity.

Other features involve lymphedema or lymphatic obstruction, cellulitis, chronic venous insufficiency, stasis dermatitis, poor wound healing, ulceration, thrombosis, and emboli.

Complications

Capillary hemangiomas (port-wine stain), stasis dermatitis, thrombophlebitis, cellulitis, limb disparity, and more serious sequelae such as thrombosis, coagulopathy, bleeding, pulmonary embolism, and congestive heart failure. (1), lymphedema is also a consistent complication.

Other indications may include asymmetric face, facial haemangiomas, advanced tooth eruption, macrocephaly, heterotopia, glaucoma, cutaneous pustules/ulcers

Etiology

Klippel Trenaunay appears to be a non-hereditary syndrome although there is still an ongoing discussion involving this.

Diagnosis

Simple diagnosis can be made by observation and examination. Venous and lymphatic complications are diagnosed using radiological tests such as lymphoscintigraphy, ultra-sounds, and MRI. Venograms, and arteriograms may also be used.

Treatment

Treatment is varied for the different symptoms present. Compression garments are used to control the lymphedema, prophylactic antibiotics are of course, used to treat the cellulitis and lymphangitis spells. Orthopedic procedures are available for the limb hypertrophy and wound treatment is sometimes necessary for ulcerations.

Other treatments for the symptoms or complications include lasers for the hemangiomas, and surgical intervention for the vascular anomalies may be called for.

For further information:  

Klippel-Trenaunay-Weber Syndrome

Nodular lymphoid hyperplasia - a rare case of lymphoproliferative disorder of the lungs.

2013

[Article in Polish]

Rogoziński P, Bruliński K, Malinowski E, Wandzel P, Kucharzewski M.

Abstract

Nodular lymphoid hyperplasia (NLH) belongs to a very rare, mild, lymphoproliferative disease of unestablished aetiology historically included in the group of pseudolymphomas. Its existence was controversial for many years, until modern techniques of pathomorphological diagnosis approved it as a separate entity of lung disease. It manifests in the form of well limited nodules localized in the lungs, which are mostly identified accidentally. Clinical symptoms are rare and nonspecific; the disease usually occupies only one lung. Pathomorphological diagnosis requires immunohistochemical designation of expressions of numerous antigens in order to exclude malignant lymphoma of the lungs. Surgical resection is used in cases of larger nodules; the smaller ones require periodic observation, and the prognosis is good. The authors describe the case of 65-year-old woman with pulmonary nodules which were detected accidentally in the right lung. The patient was qualified for right-sided videothoracoscopy and removal of the lung nodule. In classic HE staining of the histological material, the presence of lymphoid infiltration of the lungs was revealed, which formed lymph follicles with reactive germinal centres. In order to differentiate from the malignant lymphatic expansion, immunohistochemical designations were made, which showed positive expression of CD20 antigen in the B cell zone, positive expression of the CD3 antigen in the T cells zone, positive expression of CD23 antigen in the lymph follicles, negative expression of bcl-2 in the lymph follicles, and positive expression of MIB-1 in the germinal centres of lymph follicles. Such a histopathological and immunohistochemical picture provided the basis for diagnosis of nodular lymphoid hyperplasia of the lung.

PubMed

Nonimmune hydrops fetalis: two decades of experience in a university hospital

2012 

[Article in Portuguese]

Fritsch A, Müller AL, Sanseverino MT, Kessler RG, Barrios PM, Patusco LM, Magalhães JA.

Source

Centro Obstétrico, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil.

Abstract

PURPOSE:

To identify the etiology of nonimmune hydrops fetalis cases in pregnant women diagnosed and referred for prenatal care.

METHODS:

Retrospective analysis of cases with nonimmune hydrops fetalis that were monitored between March 1992 and December 2011. Diagnosis was confirmed by the presence of fetal subcutaneous edema (≥ 5 mm) with effusion in at least one serous cavity using obstetric ultrasound, and etiological investigation was conducted with cytogenetic (karyotype), infectious (syphilis, parvovirus B19, toxoplasmosis, rubella, cytomegalovirus, adenovirus and herpes simplex), hematologic and metabolic (inborn errors) analysis and fetal echocardiography. Twin pregnancies were excluded. Statistical analysis was performed using the χ² test for adhesion (software R 2.11.1).

RESULTS:

We included 116 patients with nonimmune hydrops fetalis; the etiology was elucidated in 91 cases (78.5%), while 25 cases (21.5%) were classified as idiopathic. Most cases had a chromosomal etiology, for a total of 26 cases (22.4%), followed by lymphatic etiology with 15 cases (12.9% with 11 cases of cystic hygroma), and cardiovascular and infectious etiology with 14 cases each (12.1%). In the remaining cases, the etiology was thoracic in 6.9% (eight cases), malformation syndromes in 4.3% (five cases), extrathoracic tumors in 3.4% (four cases), metabolic in 1.7% (two cases), and hematologic, gastrointestinal and genitourinary in 0.9% (one case each). During the postnatal period, 104 cases were followed up until the 40th day of life, and 12 cases had intrauterine fetal death. The survival rate of these 104 newborns was 23.1% (24 survived).

CONCLUSION:

An attempt should be made to clarify the etiology of hydrops diagnosed during pregnancy since the condition is associated with a wide spectrum of diseases. It is especially important to determine whether a potentially treatable condition is present and to identify disease at risk for recurrence in future pregnancies for adequate pre-conception counseling.

Scielo

The effect of lenalidomide on rare blood disorders: Langerhans cell histiocytosis, multicentric Castleman disease, POEMS syndrome, Erdheim-Chester disease and angiomatosis

Nov 2012

[Article in Czech]

Adam Z, Pour L, Krejčí M, Zahradová L, Szturz P, Koukalová R, Rehák Z, Nebeský T, Hájek R, Král Z, Mayer J.

Abstract

Lenalidomide has been licenced for the treatment of multiple myeloma and, in 2012, it is used as a standard treatment of relapses of the disease. Literature contains a number of publications on the effects of lenalidomide in myelodysplasticsyndrome, in malignant lymphomas and chronic B lymphocytic leukaemia. The effects of the drug in rare diseases, however, have not been investigated so far. In this paper, we summarize our experience with lenalidomide in rare blood disorders. We observed an excellent effect of lenalidomide in multifocal aggressive, repeatedly relapsing Langerhans cell histiocytosis where it led to complete remission. This patient was treated with 2-chlorodeoxyadenosine and with CHOEP (cyclophosphamide, etoposide, doxorubicin, vincristine and prednisone) chemotherapy and high dose BEAM chemotherapy with autologous transplantation of haematopoietic tissue for an early disease relapse. Following another early relapse, the patient was treated with lenalidomide (25 mg). Treatment with lenalidomide induced complete remission on PET-CT. The patient was consolidated during the remission with a reduced intensity conditioning regimen and allogeneic transplantation of haematopoietic tissue. Following allogeneic transplantation, the patient has been in full remission for 10 months. We further showed an excellent effect of lenalidomide in multicentric Castleman disease with generalized involvement of lymphaticnodes, B symptoms and vasculitis. The patient was first treated R-CHOP chemotherapy (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone). Due to a lack of efficacy, this was changed to the CVD combination (cyclophosphamide, thalidomide, dexamethazone). This treatment delivered complete remission but was complicated by thalidomide-associated neuropathy. Due to persistent neuropathy, thalidomide could not be used to manage further relapse and thus lenalidomide (25 mg, 11 cycles) was used. The patient has been in complete PET-CT remission for 7 months following this treatment. We observed partial efficacy in Erdheim-Chester disease. We used 2-chlorodeoxyadenosine as part of initial treatment that delivered partial regression of brain infiltrates only; fluorodeoxyglucose accumulation in the bones has not changed. Lenalidomide 25 mg was used as second line treatment. This led to complete regression of CNS infiltrates on MRI but fluorodeoxyglucose accumulation in bone lesions did not change. Regression of clinical signs and regression of fibrosis of retroperitoneum was achieved with an ongoing treatment with anakinra. A patient with multiple angiomatosis affecting the abdominal cavity, mediastinum and vertebrae and digestive tract had been stabilized with zoledronate (4 mg once every 2 months) and thalidomide (100 - 200 mg/den) for several years. However, several years of this treatment led to severe neuropathy. Consequently, we attempted to substitute thalidomide for lenalidomide. However, 10 mg of lenalidomide alone was not sufficiently effective and thus low dose of 50 mg of thalidomide was added. Combined treatment with zoledronate, lenalidomide 10 mg/day and thalidomide 50 mg/day stabilized the condition for 9 months. Due to relapsed gastrointestinal bleeding the treatment had to be changed after 9 months to thalidomide 100 mg/day and Sandostatin 0.1 mg twice daily s.c. A patient with osteosclerotic myeloma and POEMS syndrome was initially treated with CAD chemotherapy (cyclophosphamide, adriamycine and dexamethazone) that was followed by tandem high dose chemotherapy (melphalan 100 mg/m2) and autologous transplantation. Treatment with thalidomide was given due to insufficient efficacy but was not tolerated. Lenalidomide was administered as the fourth line treatment. Even though literature describes remission of POEMSsyndrome following lenalidomide, four cycles did not lead to remission in our patient. Conclusion: We showed an effect of lenalidomide in Langerhans cell histiocytosis and in Castleman disease. The treatment led to regression of brain infiltrates in a patient with Erdheim-Chester disease. A dose of 10 mg of lenalidomide daily in combination with 50 mg of thalidomide stabilized a course of angiomatosis. Lenalidomide did not deliver the required treatment response in a patient with POEMS syndrome and multiple previous therapies. 

Key words: lenalidomide - thalidomide - cladribin - anakinra - Langerhans cell histiocytosis - Erdheim-Chester disease - Castleman disease - POEMS syndrome - angiomatosis.

Propranolol as an alternative treatment option for pediatric lymphatic malformation.

2013

Ozeki M, Kanda K, Kawamoto N, Ohnishi H, Fujino A, Hirayama M, Kato Z, Azuma E, Fukao T, Kondo N.

Source

Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu University.

Abstract

Lymphatic malformation (LM), which was previously termed lymphangioma, is a rare congenital malformation of the lymphatic system and its treatment is still challenging. Propranolol (beta blocker) has been recently developed as a first-line treatment of infantile hemangioma. Our study aimed to assess the effect of propranolol on pediatric LM and the relationship between its effectiveness and vascular endothelial growth factor (VEGF) family members (VEGF-A, C and D). Six Japanese patients with LM (age range: 10 months-19 years old; 2 macrocystic, 2 microcystic and 2 combined type) were enrolled. Oral propranolol was administered at 2 mg/kg/day. The efficacy of propranolol for LM was evaluated by the rate of volume change as calculated from MRI imaging and by symptomatic improvement. In all patients, there were no significant side effects. Patients 3 and 5 were classified as objective responders with tumor volume reduction of 30.6% and 22.9%, respectively, at 24 weeks. Patient 1 showed 8% tumor volume reduction and patient 6 showed symptomatic improvement, hence, both were classified as minimal responders. The other two patients were classified as non-responders. Plasma VEGF-A, C, and D levels were significantly higher in the LM group than in the controls (all P < 0.01 by Mann-Whitney test). VEGF-A and D levels at 24 weeks were significantly lower than those at pre-treatment (P = 0.031, 0.047 by Wilcoxon matched pairs test). Though further trials with this treatment must be carried out, we propose that propranolol may be an alternative therapy option for intractable LM.

PubMed

Lymphatic System and immune system illustrated

Cancer Nirvana




LGDA

Hyaline vascular type of unicentric Castleman's disease with proliferation of glomerular endothelial cells.

Dec 2012

Wakabayashi K, Asanuma K, Takeda Y, Arakawa A, Osawa I, Horikoshi S, Yao T, Tomino Y.

Abstract

Castleman's disease (CD) is a lymphoproliferative disorder of uncertain etiology. It can be classified histopathologically as hyaline vascular (HV) or plasma cell (PC) type; and clinically as unicentric or multicentric. Multicentric CD mostly manifests as the PC type and is often associated with a variety of systemic complications, although renal complications are uncommon. We present here a case of HV type, unicentric CD with a variety of systemic and renal complications, including the proliferation of glomerular endothelial cells. Various cytokines are thought to be involved in the etiology of this disease, especially interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), which are the main cytokines inducing systemic complications. It has been reported that most PC types and/or multicentric types of CD show increasing levels of serum IL-6 and VEGF, as well as systemic symptoms. Although the current case showed high serum IL-6 and VEGF levels as well as systemic symptoms, the pathological and clinical type were of the HV type and unicentric type, respectively. After immunosuppressive therapy, the serum levels of IL-6 and VEGF returned to the normal range, and systemic complications, including renal involvement, also improved. We report the possibility of pathogenesis via the serum and the pathology of this rare case.

PubMed

Lymphatic vessels in health and disease.

Dec 2012

Kesler CT, Liao S, Munn LL, Padera TP.

Source

E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.

Abstract

The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism, and cancer metastasis. In adults, lymphatic vessel formation and remodeling occur primarily during inflammation, development of the corpus luteum, wound healing, and tumor growth. Unlike the blood circulation, where unidirectional flow is sustained by the pumping actions of the heart, pumping actions intrinsic to the lymphatic vessels themselves are important drivers of lymphatic flow. This review summarizes critical components that control lymphatic physiology. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1201 For further resources related to this article, please visit the WIREs website.

Wiley OnLine