ANGIOSARCOMA AND HEMANGIOENDOTHELIOMA€¦ · ANGIOSARCOMA AND HEMANGIOENDOTHELIOMA Claudia Mª Valverde Vall d´Hebrón University Hospital. VASCULAR TUMORS BENIGN-> ... - Hemangioendothelioma

ANGIOSARCOMA AND ANGIOSARCOMA AND HEMANGIOENDOTHELIOMA

Claudia Mª ValverdeVall d´Hebrón University Hospital

VASCULAR TUMORS

BENIGN-> - Hemangioma

BORDERLINEBORDERLINE- Hemangioendothelioma

MALIGN-> A i- Angiosarcoma

- Kaposip

VASCULAR TUMORS

BENIGN-> - Hemangioma

BORDERLINEBORDERLINE- Hemangioendothelioma

MALIGN-> A i- Angiosarcoma

- Kaposip

HEMANGIOENDOTHELIOMA( HE)

Vascular tumors with a biologic behaviour intermediate between hemangioma and angiosarcoma: Ability tobetween hemangioma and angiosarcoma: Ability to recur locally and some to metastatize but at a far reduced rate compared with angiosarcomap g

Subtypes:- Epithelioid HE- Epithelioid HE- Kaposiform HE

Hobnail HE- Hobnail HE- Epithelioid sarcoma-like HE

EPITHELIOID EH

Clinical features:- Rare in childhood- Both sexes equally- Usually solitary, slightly

painful massSOFT TISSUE BONE LIVER

Weiss et al Kleer et al Makhlouf et alLocal recurrence 13%Metastasis 31% 31% 61%Mortality 13% 31% 43%

Weiss et al. Semin diagn pathol 1986.

Kleer et al. Am J Surg Pathol 1996.

Makhlouf et al . Cancer 1999.

EPITHELIOID EH

• Pathological features- Angiocentric- Angiocentric- Vascular differentiation more

primitive- Short strands or solid nests

of rounded/slightly spindled endothelial cells.endothelial cells.

- Form small intracellular lumens –”vacuoles”

- Atypia, >1mit/10HPF, spindling or necrosis-> more agressive

Weiss et al. Semin diagn pathol 1986

KAPOSIFORM HE

Clinical Features:Childh d- Childhood

- Trunk, retoperitoneum.- Kasabach-Merritt phenomenon- ill defined violaceus plaquep q- No tendency to regress- 10% mortality- 10% mortality- Virtually no metastatic.

KAPOSIFORM HE

• Pathological features:• Small CD31+ vessels

surrounded by actin-positive pericytes-> glomeruloid

• IHQ: vascular ( CD31, CD34, FLI1) and , )lympatic components (D2-40)( )

HOBNAIL HE

• Dabska tumor • Retiform HE- Children- Distal Extremities- Intraluminal growth of papillary

- Adults- Distal Extremities- Local recurrence >Intraluminal growth of papillary

endothelial structures- IHQ: CD31, CD34, vWF, VEGF3

Local recurrence >. - Virtually no metastatic like

Dabska. <10% N1

EPITHELIOID SARCOMA-LIKE HE

• Superficial or deep soft tissues of extremitiestissues of extremities

• Nodules of eosinophilic, cytokeratin + cellscytokeratin + cells

• Atypia mild-moderate with low mitotic activitywith low mitotic activity

• No multicellular vascular channels

• IHQ: CD31, FLI1 +, CD34-

Billings et al. Am J Surg Pathol 2003

ANGIOSARCOMA

• Malignant tumors that resemble many of the

Location N %skin 121 33resemble many of the

functional and morphological features of normal epithelium

skin 121 33soft tissue 89 24Breast 30 8

epithelium.• Wide morphologic spectrum.• <1% sarcomas

Liver 31 8Bone 20 6Spleen 16 4

• Predilection for skin and superficial soft tissueA di i 128 (79 5%)

Heart &GV 10 3Other 49 14All 366 100

• At diagnosis, 128 (79.5%) patients had localized disease, whereas 31 (19%)

Data from AFIP 1966-76. Adapted from Enzinger &Weiss

had metastases.Fayette J et al. Ann Oncol. 2007;18(12):2030-6.

ANGIOSARCOMA

Etiology/associations:h i l h d- Chronic lymphedema

- Radiotherapy- A-V fistulas- Foreign materialg- Carcinogens: Thorotrast, AsO3 insecticides, Vinyl

ChlorideC o de- Other disseases: NF, bilateral Rb, XP

ANGIOSARCOMA

*Poor prognosis:- Delayed diagnosis- Margins and multifocal- Size-> <5 cm 32% 5y OS

> 5 cm 13% 5y OS- Localized/ metastatic disease. M1 lung, liver, nodes.- Primary tumor: visceral/bone vs soft tissue

ECOG- ECOG

Fayette J et al. Ann Oncol. 2007;18(12):2030-6.

ANGIOSARCOMA ( AS)

Clinical types:- Cutaneous AS not associated with

lymphedema- Cutaneous AS associated with lymphedema- Breast AS- Breast AS- Soft tissue AS- Radiation induced AS

CUTANEUS AS NOT ASSOCIATED WITH LYMPHEDEMAWITH LYMPHEDEMA

- The most common AS

- Elderly patientsElderly patients- Men>Women- H&N (scalp).

Margins difficult- Margins difficult - Often multifocal

CUTANEU A NOT A OCIATED CUTANEUS AS NOT ASSOCIATED WITH LYMPHEDEMA

• Larger chromatic l inuclei

• Papillations• Irregular vascular

channels infiltrating th d ithe dermis

• IHQ-> vWF, CD34, CD31CD31.

• Citogenetics-> gains 5 8 20 d lcrom 5,8,20 and losses

4,7,22,Y. Schuborg C et al. Cancer Genet Cytogenet 1998g

CUTANEUS AS ASSOCIATED WITH LYMPHEDEMALYMPHEDEMA

• Steward-Treves Synd.Ob i !• Obesity!

• 90% after mastectomy (0 45% i )(0.45% mastectomies).

• Latency 10-15yS ll il i d l• 7º decade. (Congenital

younger).- Small capilary-sized vessels

- Association with lymphangiomatosis

• OS 31m• M1 lung, pleural and Sordillo EM et al. J Dermatol Surg Oncol 1981

Woodward AH et al Cancer 1972g p

chest wallWoodward AH et al. Cancer 1972

Shon W et al. J Cutan Pathol. 2011

BREAST AS

• Affects breast parenchymaparenchyma

• Rapidly growing without classic signswithout classic signs of carcinoma

• 3 4º decade• 3-4º decade• Early metastasis: lung,

skin & boneskin & bone• mOS 3-5 y

Vorburger et al. Cancer 2005

Nascimento AF et al. Am J Surg Pathol. 2008

Kikawa Y et al. Breast Cancer. 2006;13(4):369-73.

BREAST AS

• Ill- defined• Cellular areas with• Cellular areas with

atypia, mitotic activity and necrosis

SOFT TISSUE/ AS

- All ages- Extremities or abdominal cavity

AP > More epithelioid- AP-> More epithelioid- IHQ-> vWF, CD31 and some cytoketatin +.- 1/3 associated to other diseases: NF

50% M1 l N1 b & ft ti- 50% M1: lung, N1, bone & soft tissue.

Fury MG et al. Cancer J 2005; 11: 241–247.

RADIOTHERAPY INDUCED AS

• 5-10 years latency• Median 50Gy• Ecchymosed or thickenning of the skin• Ecchymosed or thickenning of the skin• Multifocal• 50% recur and 40% M1


TREATMENT


Angiosarcoma after breast conserving therapy: long term outcomesAngiosarcoma after breast-conserving therapy: long-term outcomes with hyperfractionated radiotherapy.

Progression-free survival rates for the 14 patients at 2 years and 5 years were 71% and 64%, respectively.

The overall and cause-specific survival rates were both 86% at 2 years and 5 years.

Palta M et al. Cancer 2010 15;116(8):1872-8

TREATMENT: HEIFN α-2B-> There are several case reports of patients with EHE

achieving partial or more complete remission after treatmentachieving partial or more complete remission after treatment with interferon α-2B .

Two of these patients had pulmonary involvement as part of more id d diwidespread disease.

As part of a more complex treatment strategy including transplantation or resectiontransplantation or resection

Kayler et al. Transplantation 2002;74,128-130Rosenthal et al. Skeletal Radiol 2001;30,219-222Vignon-Pennamen et al Ann Dermatol Venereol 1997;124 165-166Vignon Pennamen et al Ann Dermatol Venereol 1997;124,165 166Roudier-Pujol et al. Ann Dermatol Venereol 1994;121,898-904

TREATMENT: HE

* Complete response to six courses of* Complete response to six courses of carboplatin plus etoposide chemotherapy in

i i h l l EHE i l d ib da patient with pleural EHE is also described, with full remission at 18-month follow-up.

* Complete response after metronomic cyclofosfamide 100mg/12h + prednisonecyclofosfamide 100mg/12h + prednisone 20mg/d 1w on/1w off

Pinet, C et al. Aggressive form of pleural epithelioid haemangioendothelioma: complete response , gg p p g p pafter chemotherapy. Eur Respir J 1999;14,237-238Mir O et al.Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma.Eur J Cancer 2011 Mar;47(4):515-9.

Selective intra-arterial Y-90 microsphere therapy inSelective intra-arterial Y-90 microsphere therapy in hemangioendothelioma.

PFS 18mLaçin S et al. Turk J Gastroenterol. 2011 Feb;22(1):89-92

TREATMENT ANGIOSARCOMA

* CHEMO:- Anthracyclines+- Ifosfamide

Gemcitabine alone- Gemcitabine alone- Taxanes- Combinations* TARGETED THERAPIES* TARGETED THERAPIES

TREATMENT

SARCOMA CHEMO:- Anthracyclines+- Ifosfamide

Gemcitabine alone- Gemcitabine alone- Taxanes- Combinations

ANTHRACYCLINESRef N Treatment OutcomeHolloway et al 2005 1 LPD+RT (·30Gy) PR 4yEili t l 2002 1 LPD+RT CR 4Eiling et al 2002 1 LPD+RT CR 4mLankester et al. 1999 1 LPD+RT CR 15m

6 LPD 3PR 6,19,>20 m2 SD 7 11m

Skubitz KM et al 20052 SD 7,11m

1PDItaliano A et al 2011 42 Doxo 2 CR (6%)

8PR (23%)

• Respuestas no

( )10 SD (29.5

Respuestas no dependientes de localización

• PFS 3.7-5.4m


TREATMENT



GEMCITABINE

• Gem as a single agent (1000 mg/m(2) i.v. every week for 3 Ng ( ) yweeks every 4 weeks).

• 8/25 pts radiation induced sarcomas.

NTotal 25

CR 2PR 14PR 14SD 2PD 7

RR 68%

mPFS 7mmOS 17m

Stacchiotti S et al. Ann Oncol. 2011 Apr 4.

TREATMENT



Recent studies present paclitaxel as a single agent with substantial activity against angiosarcoma of the scalp or face, even in g p ,patients previously treated with chemotherapy or radiation therapychemotherapy or radiation therapy.

TAXANES• Case ReportsR f N T t t CR PR SDRef N Treatment CR PR SD

8 Paclitaxel w 2 3Vakkalanka B et al. 2010 1 Paclitaxel neo 1Nagano et al. 2007 9 Docetax 25mg/m2/w 2 4

Skubitz KM et al . 2005

• Clinical studies/larger seriesgRef N Treatment RR(CR+PR) mTTP mOSSchlemmer et al. 2008 32 Paclitaxel w 62% ( 78% scalp) 7.6m (9.6m scalp)Penel N et al. 2008. ANGIOTAX 30 Paclitaxel w 74% ( CR+PR+SD)a 2m 4m 8m

42% after 4m

• 40% 2-3rd line

Italiano A et al 2011 75 Paclitaxel w 53% 4.9 8.5

Penel N et al. Ann Oncol 2011

40% 2 3rd line• RR pretreated= naive• >RR in scalp• After adjustment to the performance status and compared with exclusive palliative j p p p

care, the following treatments significantly improve the outcome: doxorubicin-based regimen as first-line chemotherapy (HR = 0.38, P = 0.0165), weekly paclitaxel as first-line regimen (HR = 0.36, P = 0.0146) and metastasectomy (HR = 0.09, P = 0.0221).

Angiosarcoma: a study of 98 cases with immunohistochemical evaluation of TLE3, a recently described marker of potentialevaluation of TLE3, a recently described marker of potential taxane responsiveness.

98 total cases; 37 cutaneous, 48 soft tissue/visceral and 13 post-i di tiirradiation

The median time to death was 2.1 years. TLE3 reactivity was observed in 0/37 (0%) cutaneous angiosarcomasTLE3 reactivity was observed in 0/37 (0%) cutaneous angiosarcomas, in 28/48 (58%) cases from soft tissue/viscera and in 4/13 (31%) post-irradiation angiosarcomas. (p = <0.0001). Improved 5 year survival was seen in vasoformative angiosarcomasImproved 5-year survival was seen in vasoformative angiosarcomas (p = 0.03). TLE3 expression was not associated with taxane response

Shon W et al. J Cutan Pathol 2011;38(12):961-6.

TREATMENT


Gemcitabine alone- Gemcitabine alone- Taxanes.- Combinations

.

Angiosarcoma of the scalp with complete response to a biweekly gemcitabine and docetaxel (GEMDOC) chemotherapy regimen.

Gemcitabine (1,500 mg/m²) and docetaxel (50 mg/m²) administered biweekly. The patient was free of disease at the 15-month follow-up..

A case of advanced scalp angiosarcoma successfully treated with combination chemotherapy of adriamycin, cisplatin and ifosfamide.

Adriamycin, cisplatin, ifosfamide and paclitaxel combination as front-line chemotherapy for locally advanced and metastatic angiosarcoma. Analysis of three case reports and review of the literature.

Adriamycin 40 mg/m2 day 1, ifosfamide 3 g/m2 day 1-2, cisplatin 35 mg/m2 day 1-2 and paclitaxel 175 mg/m2 day 3

Shkoukani MA et al. Ear Nose Throat J.2011

Kanat O et al. Clin Oncol (R Coll Radiol). 2006 Jun;18(5):426-7

Asmane I et aa. Anticancer Res. 2008 Sep-Oct;28(5B):3041-5.


* CHEMO:h li f f id- Anthracyclines+- Ifosfamide

- Gemcitabine alone- Taxanes.- Combinations • TARGETED THERAPIES:

Antiangiogenics- Antiangiogenics- Other

In an immunohistochemical study of 49 angiosarcomas, more than half of the tumors were positive for all three markers: D2 40 (53%) VEGFR3 (57%) andthree markers: D2-40 (53%), VEGFR3 (57%) and Prox-1 (76%)

Mankey et al. 2010

Sporadic cutaneous angiosarcomas generally lack hypoxia-inducibleSporadic cutaneous angiosarcomas generally lack hypoxia-inducible factor 1alpha: a histologic and immunohistochemical study of 45 cases.

Accordingly the hypoxic response pathway is not thought to be aAccordingly, the hypoxic response pathway is not thought to be a

documentable common mechanism of angiogenesis in this entity.

Abedalthagafi M et al. Ann Diagn Pathol.2010

Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypicalangiosarcoma but not in other radiation associated atypical vascular lesions

High-level MYC amplification was found in 100% of secondary AS, but in none of the AVL or other radiation-associated sarcomas.

Guo T et al. Genes Chromosomes Cancer. 2011

.

Koshiji M et al. The EMBO J. 2004

Coamplification of FLT4 (encoding VEGFR3) was identified in 25% of secondary AS, but not in other typesy yp

3/6 patients with both MYC and FLT4 amplification, were treated with sorafenib with complete response in one patient ( 26 m on treatment) and a partial response in the remaining two.

Guo T et al. Genes Chromosomes Cancer. 2011

KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors.

Expression profiling->AS up-regulation of vascular-specific receptor tyrosine kinases, including TIE1, KDR, SNRK, TEK, and FLT1.kinases, including TIE1, KDR, SNRK, TEK, and FLT1.

Full sequencing of these five candidate genes identified 10% of patients harboring KDR mutations.

A KDR-positive genotype was associated with strong KDR protein expression and was restricted to the breast anatomic site with or without prior exposure to radiation.

Antonescu CR et al. Cancer Res.2009

Transient transfection of KDR mutants into COS-7 cells showed ligand-independent activation of the kinaseg p


Which was inhibited by specific KDR inhibitors


These data provide a basis for the activity of vascular endothelial growth factor receptorvascular endothelial growth factor receptor-directed therapy in the treatment of primary and radiation-induced AS.

Angiosarcoma of the retroperitoneum: report on a patient treated with sunitinib.with sunitinib.

The hepatic mass tumors had VDT values of 16 days on paclitaxel, 66 days on doxorubicin and 145 days on sunitinibdays on doxorubicin, and 145 days on sunitinib.

Yoo C et al. Sarcoma. 2009

Scalp Angiosarcoma Remission with Bevacizumab and Radiotherapy without Surgery: A Case Report and ReviewRadiotherapy without Surgery: A Case Report and Review of the Literature.

Ref N Treatment Outcome

K t t l 2008 2 B RT 2 CR 8 5&26Koontz et al.2008 2 Bvz+RT 2 CR 8.5&26m

Gkalpakiotis et al.2008 1 RT 1CR 5y

De Yao et al.2011 1 Bvz+RT 1CR 7m

De Yao JT et al. Sarcoma. 2011

Antiangiogenetic therapy with pioglitazone rofecoxib andAntiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors.

Patients: 5 angiosarcomas and 1 hemangioendotheliomaTreatment: pioglitazone (45 mg per day orally) plus rofecoxib (25 mg per

d ll ) d ft 14 d t f f id (3 50 d ll )day orally) and, after 14 days, trofosfamide (3 x 50 mg per day orally). Outcome: 2 CR, 1 PR and 3 SD. PFS 7.7 months

Vogt T et al. Cancer. 2003

Ref Phase

Treatment N RR SD mPFS PFS 24w mOS

Maki RB et al II Sorafenib 400 bid 37(VS) 14% 21% 3.8m 14.3

George S et al II Sunitinib 37.5mg 2 0% 0% 0

Columna 1Columna 2Columna 3

Von Mehren M et al

II Sorafenib 400 bid 8/37 (VS) 0% 75% 5m 38% 23m

Sl ijf S t l II P ib 800 5 /44(VS) ? ? 3 10Sleijfer S et al II Pazopanib 800mg 5 /44(VS) ? ? 3m "others"

10m "others"

Agulnik M et al II Bevacizumab 15mg/kg/3w

26 12% 62% ?

Fila 1 Fila 2 Fila 3 Fila 415mg/kg/3w

Maki RB et aJ Clin Oncol 2009; 27: 3133–3140George S et al. J Clin Oncol 2009; 27:3154–3160Von Mehren M et al. Cancer. 2011.Sleijfer S et al . J Clin Oncol 2009 ;27:3126-3132.Agulnik M et al. J Clin Oncol 2009


* CHEMO:h li f f id- Anthracyclines+- Ifosfamide

- Gemcitabine alone- Taxanes.- Combinations • TARGETED THERAPIES:

Antiangiogenics- Antiangiogenics- Other

Clinicopathologic assessment of postradiation sarcomas: KIT as a potential treatment target.potential treatment target.

Fourteen of 16 tumor samples were KIT-positive (88%). p p ( )Five of 23 (22%) spontaneous soft tissue sarcomas of comparable

histological types, including 2 angiosarcomas, were KIT-positive.No mutations in exon 11 of the c-kit gene were found

Komdeur R et al.

Komdeur R et al.Clin Cancer Res. 2003 Aug 1;9(8):2926-32

Dramatic and durable efficacy of imatinib in an advanced angiosarcoma without detectable KIT and PDGFRA mutations.

Kiesel H et al.Cancer Biol Ther. 2009 Feb;8(4):319-21.

Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors.

A fully human monoclonal antibody to anti–αv integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical g g g pstudies

Of the six patients who received extended dosing, one patient (10.0 /k ) ith t i h d 9 th ti lmg/kg), with cutaneous angiosarcoma, had a 9-month partial response

Mullamitha SA et al. Clin Cancer Res. 2007 Apr 1;13(7):2128-35.

Mullamitha SA et al. Clin Cancer Res. 2007 Apr 1;13(7):2128-35.

Cancer-specific mutations in PIK3CA are oncogenic in vivo.

They induce tumors in the chorioallantoic membrane of the chicken embryo and cause hemangiosarcomas in the animal. These tumors are marked by increased angiogenesis and an activation of the Akt pathwayp y

The H1047R induced tumors classify as hemangiosarcomas; tumors caused by the helical domain mutations E542K and E545K were di d ith h i h idiagnosed as either hemangiomas or hemangiosarcomas

Bader AG et al. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1475-9.

Inhibition of H1047R-induced tumor growth by RAD001 therapy g y py(10mg/kg/d)

Bader AG et al. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1475-9.

INMUNOTHERAPY:Complete remission in a patient with angiosarcoma by the

Recombinant human interleukin-2 (rhIL-2) has been used for the treatment of angiosarcoma because it has a direct effect on tumor cells

p p g ycombination of OK-432, rhIL-2, and radiotherapy.

treatment of angiosarcoma because it has a direct effect on tumor cells and also activates natural killer (NK) cells, and lymphokine-activated killer (LAK) cells

OK 432 i illi d h i i d l hili d d fOK-432, a penicillin- and heat-inactivated lyophilized powder of a Streptococcus pyogenes A3 sub strain. Toll-like receptor 4 (TLR4) on dendritic cells (DCs) recognize OK-432 polysaccharide antigen-> signaling pathway-> expression of inflammatory genes and stimulates dendritic cells.

OK 432 for 6 days followed by rhIL 2 for 30 days The levels of NK cellOK-432 for 6 days followed by rhIL-2 for 30 days. The levels of NK cell and LAK cell activity were up-regulated after combination therapy

Inaba T et al. Eur J Dermatol. 2005 Sep-Oct;15(5):411-3.

Liposome-encapsulated muramyl tripeptide

INMUNOTHERAPY:

Liposome encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy for splenic hemangiosarcoma in the dog: a randomized multi-institutional clinical trialinstitutional clinical trial.

Thirty-two dogs with HSA and without gross evidence of metastases were treatedThirty two dogs with HSA and without gross evidence of metastases were treated with splenectomy, stratified by clinical stage, and randomized to receive doxorubicin/cyclophosphamide chemotherapy and either L-MTP-PE immunotherapy or lipid equivalent (placebo liposomes). py p q (p p )

Dogs receiving L-MTP-PE had significantly prolonged disease-free survival (P = 0.037) and overall survival (P = 0.029) .

D i i L MTP PE h d i ifi l i fDogs receiving L-MTP-PE had significantly greater serum tumor necrosis factor-alpha (P < 0.001) and interleukin 6 (P = 0.007) activities.

Vail DM et al.Clin Cancer Res. 1995 Oct;1(10):1165-70

Galectin-3 as a potential therapeutic target in tumors arising from li t d th limalignant endothelia.

Galectin-3 (Gal-3) a beta-galactoside-binding lectin implicated in tumorGalectin-3 (Gal-3), a beta-galactoside-binding lectin implicated in tumor progression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neoplastic cell response to cytotoxic drugsdrugs

Johnson KD et al. Neoplasia. 2007 Aug;9(8):662-70

Johnson KD et al. Neoplasia. 2007 Aug;9(8):662-70

*

CONCLUSIONSRare: <1% sarcomas and heterogeneous group.* Poor prognosis* Surgery remains mainstay of theatment +/- RT as in other

sarcomas* Histotype tailored chemotherapy-> Taxanes & anthracyclines* Novel approaches:* Novel approaches:

- Antiangiogenics: TKIs, Mabs, ..- Inmunotherapy- Inmunotherapy- Others: PI3K , Gal3, integrins

Need for specific trials and international ll b ti !collaboration!

Thank you!Thank you!

Documents

ANGIOSARCOMA AND HEMANGIOENDOTHELIOMA€¦ · ANGIOSARCOMA AND HEMANGIOENDOTHELIOMA Claudia Mª Valverde Vall d´Hebrón University Hospital. VASCULAR TUMORS BENIGN-> ... - Hemangioendothelioma