A 27-year-old man presented at the orthopedic department with a 3-year history of severe limitation on his locomotor capacity and persistent pain at the anteromedial side of the right thigh. These symptoms had been diagnosed and treated as a psychosomatic disorder because of his known mental illness

Antonicoli, M

Dragoni, M

Ippolito, E

Llubani, R

Manenti, G

Simonetti, G

Squillaci, E

Cineca Institutional Research Information System

Epithelioid hemangioendothelioma of the femur

MANENTI, GUGLIELMO

SQUILLACI, ETTORE

SIMONETTI, GIOVANNI MARIA EGISTO

Case 9298 Epithelioid hemangioendothelioma of the femurManenti G, Antonicoli M, Llubani R, Squillaci E, Dragoni M, Ippolito E, Simonetti G  Musculoskeletal System Section: 2011, May. 11 Published: 27 year(s), malePatient:Clinical HistoryA 27-year-old man presented at the orthopedic department with a 3-year history of severe limitationon his locomotor capacity and persistent pain at the anteromedial side of the right thigh. Thesesymptoms had been diagnosed and treated as a psychosomatic disorder because of his knownmental illness.Imaging FindingsDigital radiography revealed the presence of a large endosteal bone neoformation. The patientunderwent radiological investigations such as CT that confirmed the presence of a gross neoplasticlesion involving the middle third of the right femur proximal diaphysis, expanding the cortical bonethat appears discontinuous in several places, associated with periosteal reaction, most evident at thefront side. This lesion measured approximately 177x73x69 mm and showed an inhomogeneousenhancement after contrast injection. The angio-CT documented bilateral patency of leg arteries.Subsequently T1, T2-weighted MRI and fat-suppressing sequences were performed for furthercharacterization of the lesion, which confirmed the morpho-structural alteration of the proximalright femoral diaphysis caused by the lesion apparently constituted of a productive hypocellulartissue. At PET scan the neoplasm demonstrated a high captation of FDG. At last bone biopsy wasperformed for histological characterization.DiscussionVascular bone tumours represent less than 1% of all bone tumours and their classification seems tobe still evolving [1]. It was first described by Weiss and Enzinger in 1982 and often mistaken for ahigh grade malignant tumour. Considering their histological appearance and their biologicalbehaviour these tumours are classified as intermediate between benign haemangiomas andmalignant angiosarcomas and as proposed by Wanger and Wald they constitute their own subgroupbetween low grade and high grade bone vascular malignancies [2, 3]. So the term epithelioidhaemangioendothelioma was suggested to be used to designate these biologically borderline"neoplasms. EHE occurs in the calvarium, spine, femur, tibia and feet of adults during the second orthird decade. Chromosome analysis and molecular cytogenetic investigations showed that EHE ischaracterised by complex genetic rearrangements of 11q and 12q [4].Usually, epithelioid haemangioendotheliomas present with pain and swelling and if present in thespine, they can cause radicular symptoms or paraplegia. Radiographically the majority of EHEshow lytic bone destruction with associated alteration of matrix mineralisation, endosteal erosionand cortical thinning [5]. The contrast enhancement is easily evidenced by the ComputedTomography which can be applied for further characterisation of the neoplasm such as local andsystemic extension and for vascular supply assessment of the tumour. At MRI the EHE usuallypresents with intermediate signal intensity on T1-weighted images, high signal on T2-weighted andhomogeneous contrast enhancement without the detection of the typically serpentine vascularstructures that would help in the differential diagnosis. FDG PET scanning in EHE, shows bonemarrow involvement and determines the extent of the disease [6]. Although, the information gainedthrough the imaging techniques are useful to identify and to stage the lesion, they are not entirelyspecific and the confirmation of the diagnosis is made possible only by biopsy and pathologicexamination. The epithelioid histological subtype of haemangioendothelioma has epithelial-likecells lining the vascular channels that are large and cuboidal and contain abundant eosinophyliccytoplasm. Immunohistochemical study is helpful in confirming the diagnosis by identifying themarkers for vascular endothelial cell. The clinical course and prognosis depend on uni ormultifocality, histological differentiation and cytologic atypia. The overall survival is 89% inunifocal disease and 50% in multifocal involvement [7]. Surgical excision is considered the besttreatment in addition or not with post-operatory chemotherapy or previous embolisation of thelesion [8].Final DiagnosisEpithelioid haemangioendotheliomaDifferential Diagnosis ListHaemangio-epithelioma , Haemangioma, Angiosarcoma, Chordoma, Chondrosarcoma,Adamantinoma of Long BonesFiguresFigure 1 Digital radiographyDigital radiography shows the presence of an extended endosteal bone neoformation in thecontext of a proximal diaphysis morphostructural alteration (cranio-caudal extension of 17cm and maximum transverse diameters of 73 x 73 mm) Area of Interest: Bones; Musculoskeletal bone; Musculoskeletal system;  Imaging Technique: Digital radiography; Figure 2 CT scanAxial CT scan reconstruction shows the presence of a gross expansive lesion involving theright femur proximal diaphysis, which appears to swell the cortical bone with discontinuitiesand periosteal reaction. Area of Interest: Bones; Extremities; Musculoskeletal bone; Coronal CT scan reconstruction shows the presence of a gross inhomogeneous expansivesolid lesion with calcifications involving the right femur proximal diaphysis with the corticalbone swelling and thick periosteal reaction. Area of Interest: Bones; Extremities; Musculoskeletal bone;  Imaging Technique: CT; MPVR CT reconstruction shows the presence of a gross expansive lesion involving the rightfemur proximal diaphysis. Area of Interest: Bones; Extremities; Musculoskeletal bone; Figure 3 MR imagesT1-weighted MR image with fat suppression after Gadolinium i.v. injection demonstrates alesion composed of juxtaposed hypocellular tissue, with mild-high contrast enhancement. Area of Interest: Bones;  Imaging Technique: MR; MRA MIP reconstruction coronal plane: vascular pedicles feeding the lesion from the rightfemoral artery. Area of Interest: Vascular;  Imaging Technique: MR-Angiography; MRA MIP reconstruction axial plane: vascular pedicles feeding the lesion from the rightfemoral artery. Area of Interest: Vascular;  Imaging Technique: MR-Angiography; Figure 4 Fusion PET-CT imagesFusion PET-CT axial image shows high and heterogeneous 18F-FDG uptake by theneoplastic mass (SUV max.3.5). Area of Interest: Bones; Oncology;  Imaging Technique: PET-CT; Fusion PET-CT coronal image shows an 18F-FDG avid neoplastic mass. Area of Interest: Bones;  Imaging Technique: PET-CT; Figure 5 Post-surgery digital radiographyPost-surgery digital radiography documents cadaveric femur transplantation and fibulaautologous graft with multiple bone screws at the diaphysis of the right femur. Area of Interest: Bones;  Imaging Technique: Digital radiography; Figure 6 Post-surgery DSA imagePost-surgery DSA image with superficial femoral and fibular pedicle arteries latero-lateralanastomosis. Area of Interest: Vascular; Figure 7 3D shaded-surface rendering CT reconstruction3D shaded-surface rendering CT reconstruction highlites anatomical proximity of screws(red) and grafts. Area of Interest: Bones;  Procedure: Computer Applications-3D; Figure 8 Lesion exposureLesion exposure during surgical excision. Area of Interest: Anatomy; Bones;  Procedure: Intraoperative; Removal; Surgery; Figure 9 Gross specimenGross specimen cut surfaces with solid inhomogeneous hypervascularised lesion.Poorly-defined intramedullary mass, extending through cortex with moth-eaten bonedestruction and aggressive periostal reaction. Area of Interest: Anatomy; Bones;  Procedure: Biopsy; Removal; Surgery; Gross specimen cut surfaces with solid inhomogeneous hypervascularised lesion.Poorly-defined intramedullary mass, extending through cortex with moth-eaten bonedestruction and aggressive periostal reaction. Area of Interest: Anatomy; Bones;  Procedure: Biopsy; Removal; Surgery; Figure 10 Hematoxil-Eosin histopathologyLining cells of gland-like structure show irregular vesicular or optically clear nuclei withprominent basophilic nucleoli and occasional vacuolated cytoplasm. Epithelioidhaemangioendothelioma morphology characterised by epithelioid endothelial cells. Area of Interest: Musculoskeletal soft tissue; Figure 11 Hematoxil-Eosin histopathologyThe epithelioid histological subtype of haemangioendothelioma has epithelial-like cellslining the vascular channels that are large and cuboidal and contain abundant eosinophyliccytoplasm. Area of Interest: Musculoskeletal soft tissue; Figure 12 Hematoxil-Eosin histopathologyThe epithelioid histological subtype of haemangioendothelioma has epithelial-like cellslining the vascular channels that are large and cuboidal and contain abundant eosinophyliccytoplasm. Area of Interest: Musculoskeletal soft tissue; Figure 13 CD34 immunopathologyImmunohistochemical study is helpful in confirming the diagnosis by identifying themarkers for vascular endothelial cell (CD34+). Area of Interest: Musculoskeletal soft tissue; Figure 14 CD34Immunohistochemical study is helpful in confirming the diagnosis by identifying themarkers for vascular endothelial cell (CD34+). Area of Interest: Musculoskeletal soft tissue; MeSH [C04.557.645.375.370.380]Hemangioendothelioma, EpithelioidA tumor of medium-to-large veins, composed of plump-to-spindled endothelial cells that bulge intovascular spaces in a tombstone-like fashion. These tumors are thought to have "borderline"aggression, where one-third develop local recurrences, but only rarely metastasize. It is unclearwhether the epithelioid hemangioendothelioma is truly neoplastic or an exuberant tissue reaction,nor is it clear if this is equivalent to Kimura's disease (see ANGIOLYMPHOID HYPERPLASIAWITH EOSINOPHILIA). (Segen, Dictionary of Modern Medicine, 1992) [E04.035]Anastomosis, SurgicalSurgical union or shunt between ducts, tubes or vessels. It may be end-to-end, end-to-side,side-to-end, or side-to-side. [E01.370.350.500.500]Magnetic Resonance AngiographyNon-invasive method of vascular imaging and determination of internal anatomy without injectionof contrast media or radiation exposure. The technique is used especially in CEREBRALANGIOGRAPHY as well as for studies of other vascular structures.References[1] Weiss SW, Enzinger FM (1982) Epithelioid hemangioendothelioma: A vascular tumor oftenmistaken for a carcinoma Cancer 50:970-981[2] Wenger DE, Wold LE (2000) Malignant vascular lesions of bone: radiologic and phathologicfeatures Skeletal Radiol 29: 619-631[3] Zarine K. Shah, Wilfred C. G. Peh, Tony W. H. Shek, Jimmy W. K. Wong and Eric P. Chien(2005) Hemangioendothelioma with an epithelioid phenotype arising in hemangioma of the fibulaSkeletal Radiol 34:750-4[4] Tsarouha H, Kyriazoglou AI, Ribeiro FR. Teixeira MR (2006) Chromosome analysis andmolecular cytogenetic investigations of an epithelioid hemangioendothelioma Cancer GenetCytogenet 169: 164-8[5] Gupta A, Saifuddin A, Briggs, TWR (2006) Subperiosteal hemangioendothelioma of the femurSkeletal Radiology 35: 793-796[6] Rest CC, Botton E, Robinet G, Conan-Charlet V (2004) FDG PET in epithelioidhemangioendothelioma Clin Nucl Med 789-92[7] Deyrup AT, Tighiouart M, Montag AG, Weiss SW (2008) Epithelioid hemangioendotheliomaof soft tissue: a proposal for risk stratification based on 49 cases Am J Surg Pathol 24-7[8] Christodoulou A, Symeonidis PD, Kapoutsis D (2008) Primary epithelioidhemangioendothelioma of the lumbar spine Spine J 8:385-90CitationManenti G, Antonicoli M, Llubani R, Squillaci E, Dragoni M, Ippolito E, Simonetti G (2011, May.11)  Epithelioid hemangioendothelioma of the femur {Online}URL: http://www.eurorad.org/case.php?id=9298

English

Archivio della Ricerca - Università di Roma Tor vergata

Case 9298 
Epithelioid hemangioendothelioma of the femur
Manenti G, Antonicoli M, Llubani R, Squillaci E, Dragoni M, Ippolito E, Simonetti G 
 Musculoskeletal System Section:
 2011, May. 11 Published:
 27 year(s), malePatient:
Clinical History
A 27-year-old man presented at the orthopedic department with a 3-year history of severe limitation
on his locomotor capacity and persistent pain at the anteromedial side of the right thigh. These
symptoms had been diagnosed and treated as a psychosomatic disorder because of his known
mental illness.
Imaging Findings
Digital radiography revealed the presence of a large endosteal bone neoformation. The patient
underwent radiological investigations such as CT that confirmed the presence of a gross neoplastic
lesion involving the middle third of the right femur proximal diaphysis, expanding the cortical bone
that appears discontinuous in several places, associated with periosteal reaction, most evident at the
front side. This lesion measured approximately 177x73x69 mm and showed an inhomogeneous
enhancement after contrast injection. The angio-CT documented bilateral patency of leg arteries.
Subsequently T1, T2-weighted MRI and fat-suppressing sequences were performed for further
characterization of the lesion, which confirmed the morpho-structural alteration of the proximal
right femoral diaphysis caused by the lesion apparently constituted of a productive hypocellular
tissue. At PET scan the neoplasm demonstrated a high captation of FDG. At last bone biopsy was
performed for histological characterization.
Discussion
Vascular bone tumours represent less than 1% of all bone tumours and their classification seems to
be still evolving [1]. It was first described by Weiss and Enzinger in 1982 and often mistaken for a
high grade malignant tumour. Considering their histological appearance and their biological
behaviour these tumours are classified as intermediate between benign haemangiomas and
malignant angiosarcomas and as proposed by Wanger and Wald they constitute their own subgroup
between low grade and high grade bone vascular malignancies [2, 3]. So the term epithelioid
haemangioendothelioma was suggested to be used to designate these biologically borderline"
neoplasms. EHE occurs in the calvarium, spine, femur, tibia and feet of adults during the second or
third decade. Chromosome analysis and molecular cytogenetic investigations showed that EHE is
characterised by complex genetic rearrangements of 11q and 12q [4].
Usually, epithelioid haemangioendotheliomas present with pain and swelling and if present in the
spine, they can cause radicular symptoms or paraplegia. Radiographically the majority of EHE
show lytic bone destruction with associated alteration of matrix mineralisation, endosteal erosion
and cortical thinning [5]. The contrast enhancement is easily evidenced by the Computed
Tomography which can be applied for further characterisation of the neoplasm such as local and
systemic extension and for vascular supply assessment of the tumour. At MRI the EHE usually
presents with intermediate signal intensity on T1-weighted images, high signal on T2-weighted and
homogeneous contrast enhancement without the detection of the typically serpentine vascular
structures that would help in the differential diagnosis. FDG PET scanning in EHE, shows bone
marrow involvement and determines the extent of the disease [6]. Although, the information gained
through the imaging techniques are useful to identify and to stage the lesion, they are not entirely
specific and the confirmation of the diagnosis is made possible only by biopsy and pathologic
examination. The epithelioid histological subtype of haemangioendothelioma has epithelial-like
cells lining the vascular channels that are large and cuboidal and contain abundant eosinophylic
cytoplasm. Immunohistochemical study is helpful in confirming the diagnosis by identifying the
markers for vascular endothelial cell. The clinical course and prognosis depend on uni or
multifocality, histological differentiation and cytologic atypia. The overall survival is 89% in
unifocal disease and 50% in multifocal involvement [7]. Surgical excision is considered the best
treatment in addition or not with post-operatory chemotherapy or previous embolisation of the
lesion [8].
Final Diagnosis
Epithelioid haemangioendothelioma
Differential Diagnosis List
Haemangio-epithelioma , Haemangioma, Angiosarcoma, Chordoma, Chondrosarcoma,
Adamantinoma of Long Bones
Figures
Figure 1 Digital radiography
Digital radiography shows the presence of an extended endosteal bone neoformation in the
context of a proximal diaphysis morphostructural alteration (cranio-caudal extension of 17
cm and maximum transverse diameters of 73 x 73 mm)
 Area of Interest: Bones; Musculoskeletal bone; Musculoskeletal system; 
 Imaging Technique: Digital radiography; 
Figure 2 CT scan
Axial CT scan reconstruction shows the presence of a gross expansive lesion involving the
right femur proximal diaphysis, which appears to swell the cortical bone with discontinuities
and periosteal reaction.
 Area of Interest: Bones; Extremities; Musculoskeletal bone; 
Coronal CT scan reconstruction shows the presence of a gross inhomogeneous expansive
solid lesion with calcifications involving the right femur proximal diaphysis with the cortical
bone swelling and thick periosteal reaction.
 Area of Interest: Bones; Extremities; Musculoskeletal bone; 
 Imaging Technique: CT; 
MPVR CT reconstruction shows the presence of a gross expansive lesion involving the right
femur proximal diaphysis.
 Area of Interest: Bones; Extremities; Musculoskeletal bone; 
Figure 3 MR images
T1-weighted MR image with fat suppression after Gadolinium i.v. injection demonstrates a
lesion composed of juxtaposed hypocellular tissue, with mild-high contrast enhancement.
 Area of Interest: Bones; 
 Imaging Technique: MR; 
MRA MIP reconstruction coronal plane: vascular pedicles feeding the lesion from the right
femoral artery.
 Area of Interest: Vascular; 
 Imaging Technique: MR-Angiography; 
MRA MIP reconstruction axial plane: vascular pedicles feeding the lesion from the right
femoral artery.
 Area of Interest: Vascular; 
 Imaging Technique: MR-Angiography; 
Figure 4 Fusion PET-CT images
Fusion PET-CT axial image shows high and heterogeneous 18F-FDG uptake by the
neoplastic mass (SUV max.3.5).
 Area of Interest: Bones; Oncology; 
 Imaging Technique: PET-CT; 
Fusion PET-CT coronal image shows an 18F-FDG avid neoplastic mass.
 Area of Interest: Bones; 
 Imaging Technique: PET-CT; 
Figure 5 Post-surgery digital radiography
Post-surgery digital radiography documents cadaveric femur transplantation and fibula
autologous graft with multiple bone screws at the diaphysis of the right femur.
 Area of Interest: Bones; 
 Imaging Technique: Digital radiography; 
Figure 6 Post-surgery DSA image
Post-surgery DSA image with superficial femoral and fibular pedicle arteries latero-lateral
anastomosis.
 Area of Interest: Vascular; 
Figure 7 3D shaded-surface rendering CT reconstruction
3D shaded-surface rendering CT reconstruction highlites anatomical proximity of screws
(red) and grafts.
 Area of Interest: Bones; 
 Procedure: Computer Applications-3D; 
Figure 8 Lesion exposure
Lesion exposure during surgical excision.
 Area of Interest: Anatomy; Bones; 
 Procedure: Intraoperative; Removal; Surgery; 
Figure 9 Gross specimen
Gross specimen cut surfaces with solid inhomogeneous hypervascularised lesion.
Poorly-defined intramedullary mass, extending through cortex with moth-eaten bone
destruction and aggressive periostal reaction.
 Area of Interest: Anatomy; Bones; 
 Procedure: Biopsy; Removal; Surgery; 
Gross specimen cut surfaces with solid inhomogeneous hypervascularised lesion.
Poorly-defined intramedullary mass, extending through cortex with moth-eaten bone
destruction and aggressive periostal reaction.
 Area of Interest: Anatomy; Bones; 
 Procedure: Biopsy; Removal; Surgery; 
Figure 10 Hematoxil-Eosin histopathology
Lining cells of gland-like structure show irregular vesicular or optically clear nuclei with
prominent basophilic nucleoli and occasional vacuolated cytoplasm. Epithelioid
haemangioendothelioma morphology characterised by epithelioid endothelial cells.
 Area of Interest: Musculoskeletal soft tissue; 
Figure 11 Hematoxil-Eosin histopathology
The epithelioid histological subtype of haemangioendothelioma has epithelial-like cells
lining the vascular channels that are large and cuboidal and contain abundant eosinophylic
cytoplasm.
 Area of Interest: Musculoskeletal soft tissue; 
Figure 12 Hematoxil-Eosin histopathology
The epithelioid histological subtype of haemangioendothelioma has epithelial-like cells
lining the vascular channels that are large and cuboidal and contain abundant eosinophylic
cytoplasm.
 Area of Interest: Musculoskeletal soft tissue; 
Figure 13 CD34 immunopathology
Immunohistochemical study is helpful in confirming the diagnosis by identifying the
markers for vascular endothelial cell (CD34+).
 Area of Interest: Musculoskeletal soft tissue; 
Figure 14 CD34
Immunohistochemical study is helpful in confirming the diagnosis by identifying the
markers for vascular endothelial cell (CD34+).
 Area of Interest: Musculoskeletal soft tissue; 
MeSH
 [C04.557.645.375.370.380]Hemangioendothelioma, Epithelioid
A tumor of medium-to-large veins, composed of plump-to-spindled endothelial cells that bulge into
vascular spaces in a tombstone-like fashion. These tumors are thought to have "borderline"
aggression, where one-third develop local recurrences, but only rarely metastasize. It is unclear
whether the epithelioid hemangioendothelioma is truly neoplastic or an exuberant tissue reaction,
nor is it clear if this is equivalent to Kimura's disease (see ANGIOLYMPHOID HYPERPLASIA
WITH EOSINOPHILIA). (Segen, Dictionary of Modern Medicine, 1992)
 [E04.035]Anastomosis, Surgical
Surgical union or shunt between ducts, tubes or vessels. It may be end-to-end, end-to-side,
side-to-end, or side-to-side.
 [E01.370.350.500.500]Magnetic Resonance Angiography
Non-invasive method of vascular imaging and determination of internal anatomy without injection
of contrast media or radiation exposure. The technique is used especially in CEREBRAL
ANGIOGRAPHY as well as for studies of other vascular structures.
References
[1] Weiss SW, Enzinger FM (1982) Epithelioid hemangioendothelioma: A vascular tumor often
mistaken for a carcinoma Cancer 50:970-981
[2] Wenger DE, Wold LE (2000) Malignant vascular lesions of bone: radiologic and phathologic
features Skeletal Radiol 29: 619-631
[3] Zarine K. Shah, Wilfred C. G. Peh, Tony W. H. Shek, Jimmy W. K. Wong and Eric P. Chien
(2005) Hemangioendothelioma with an epithelioid phenotype arising in hemangioma of the fibula
Skeletal Radiol 34:750-4
[4] Tsarouha H, Kyriazoglou AI, Ribeiro FR. Teixeira MR (2006) Chromosome analysis and
molecular cytogenetic investigations of an epithelioid hemangioendothelioma Cancer Genet
Cytogenet 169: 164-8
[5] Gupta A, Saifuddin A, Briggs, TWR (2006) Subperiosteal hemangioendothelioma of the femur
Skeletal Radiology 35: 793-796
[6] Rest CC, Botton E, Robinet G, Conan-Charlet V (2004) FDG PET in epithelioid
hemangioendothelioma Clin Nucl Med 789-92
[7] Deyrup AT, Tighiouart M, Montag AG, Weiss SW (2008) Epithelioid hemangioendothelioma
of soft tissue: a proposal for risk stratification based on 49 cases Am J Surg Pathol 24-7
[8] Christodoulou A, Symeonidis PD, Kapoutsis D (2008) Primary epithelioid
hemangioendothelioma of the lumbar spine Spine J 8:385-90
Citation
Manenti G, Antonicoli M, Llubani R, Squillaci E, Dragoni M, Ippolito E, Simonetti G (2011, May.
11) 
 Epithelioid hemangioendothelioma of the femur {Online}
URL: http://www.eurorad.org/case.php?id=9298


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Epithelioid hemangioendothelioma of the femur

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