There continuous to be widespread misuse of nomenclature used to described vascular anomalies, This is even more pronounced in the case of intra-osseous lesions. Bone involvement is more common with vascular malformations and extremely rare in haemangiomas. An accurate diagnosis is mandatory for tailored management and often based on a thorough history, clinical examination, and cross-sectional imaging. Surgery remains the main stay for the management of symptomatic venous malformations. Embolisation with or without surgery is the main stay for arteriovenous malformations. Virtual surgical planning, with surgical guides and patient specific implants help achieve predictably excellent results.
Key points
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Specific imaging features can help characterize the individual vascular lesions.
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Multidisciplinary management will enable best outcomes for this patient group.
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Virtual surgical planning, with surgical guides and patient-specific implants, is helpful in obtaining consistently excellent results.
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Eventual form and function (eg, binocular vision and dental rehabilitation) will have to be taken into account in managing periorbital and midface lesions.
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Embolization has a crucial role to play in the management of high-flow arteriovenous malformations.
Vascular anomalies have been historically poorly understood and the terminology used to describe them confusing and ambiguous. The descriptive terminology used in the past (port-wine stain, strawberry hemangioma, salmon patch) conjure up visual approximations to the lesions but have no correlation with the biological behavior or natural history of the lesions. Since the seminal work of Mulliken and Glowacki, vascular lesions have been principally categorized as hemangiomas and vascular malformations. Flow characteristics have further helped in categorizing the vascular lesions into high-flow and low-flow lesions. The International Society for the Study of Vascular Anomalies (ISSVA) published a unified classification system for vascular anomalies in 1996, which were updated in 2007 and 2014, with the most recent update in 2018. This classification system divides these lesions into vascular tumors and malformations. This classification is meant to represent the “state of art” in vascular anomalies classification, acknowledging that it will require modifications as new scientific information becomes available. The ISSVA classification does not include a separate category for intraosseous lesions, but Nair and colleagues classified vascular lesions according to their location and depth and included a separate category for intraosseous lesions.
Although a widely accepted classification system for vascular lesions has existed for more than 30 years, there still continues to be widespread misuse of nomenclature and terminologies in the literature. , Hassanein and colleagues evaluated the literature with the search word “haemangioma” and found that 71% (228 of 320) had misused this terminology; of the patients who were mislabeled, 21% received improper management. All the patients who were accurately diagnosed received appropriate management. It is vitally important that precise terminology is used to enable appropriate treatment.
Vascular anomalies mainly affect soft tissues and primary intraosseous vascular lesions affecting the craniofacial region are uncommon and account for less than 1% of osseous tumors. Bony changes in hemangiomas were reported in only 1% of cases and were related to bony distortions such as depression of the outer cortex, nasal deviation, or orbital enlargement in the proliferative phase of hemangiomas. , Bony changes can however be present in up to 34% of vascular malformations. These changes in bone development were classified according to size, shape, and density changes. Hypertrophy and distortion were typical of lymphatic malformations. Hypoplasia and demineralization were characteristic finding in extremity venous malformations. Destructive and intraosseous changes were more commonly noted in arterial or high-flow lesions. Possible mechanisms of altered skeletal growth were postulated to include mechanical, physiologic, and developmental processes.
The use of inaccurate nomenclature is even more pronounced in the case of intraosseous vascular/venous malformations. Srinivasan and colleagues , found that all their patients found to have intraosseous venous malformation (IOVM) were all initially reported as “haemangiomas.” Liberale and colleagues reviewed the literature concerning vascular malformations of the bone, which had been reported as angioma, hemangioma, or hemangioendothelioma, published between January 2013 and October 2018. Clinical features, imaging, and histologic reports contained in the papers were reviewed and the diagnosis reclassified according to the 2018 ISSVA classification. Almost all the vascular anomalies presented in the reviewed papers as angiomas, hemangiomas, or hemangioendotheliomas were venous (mostly) or arteriovenous malformations. Only 8 out of 58 papers (14.7%) had an accurate diagnosis. Interestingly, all the papers reporting cavernous or capillary hemangiomas were actually venous malformations. In this article, the lesions will be described as per the recent ISSVA classifications, but the literature review will be presented with the terminology used in the relevant publications.
Pathogenesis
A detailed description of the pathogenesis and genetic basis of the disease is beyond the scope of this article. In brief, the identification of gene mutation(s) in each disease through the widespread use of next-generation sequencers is a clue to the understanding of the 2018 ISSVA classification. Causative genes for vascular anomalies are often found on molecules on the rat sarcoma (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) pathway and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)/ak strain transforming (Akt)/mamilian target of rapamycin (mTOR) pathway.
The RAS/MEK/ERK pathway, as the so-called “RASopathy,” mainly causes high-flow vascular malformations, including arteriovenous malformations and vascular tumors. On the other hand, the PIK3CA/Akt/mTOR pathway, as “PIKopathy,” induces slow-flow vascular malformations, such as venous or lymphatic malformations.
Diagnosis
Diagnosis can often be established with a thorough history, clinical examination, and appropriate imaging.
Bone involvement can be isolated or form part of a more extensive soft tissue lesion. Most patients present with an enlarging hard lump with some reporting associated discomfort. Discoloration of the overlying skin and mucosa, pulsation, bruit, and compressibility can be present, especially when the bone involvement is associated with adjacent soft tissue involvement. Facial asymmetry, malocclusion, tooth displacement and mobility, and bleeding, including catastrophic bleeding following tooth extractions have all been reported at presentation. , , , The history of trauma was reported in up to 50% of patients. These lesions were more common in females with a male-to-female ratio of 1:3. The age range at presentation for venous malformations was 15 to 74 years, though most presented in the fourth to sixth decades. This differed from the high-flow arteriovenous malformations which presented earlier; most frequently in the third decade. The duration the lesions had been present varied from 2 months to 6 years.
Imaging
Intraosseous Venous Malformations
These demonstrate low-to-intermediate signal intensity on T1; there may be areas of sporadic internal T1-shortening at sites of hemorrhage or thrombosis. , On T2 they will demonstrate heterogeneous, high signal intensity. There is heterogenous, avid contrast enhancement, which may be delayed. Internal areas of signal void may be visible, often in a spiculated “sunburst” pattern, representing the characteristic radiating internal bony trabeculae. The sunburst pattern results from bony displacement by a network of vascular spaces, with reactive new bone formation resulting in thickened trabeculae. When these trabeculae are viewed in cross section, a “honeycomb” or “soap bubble” appearance is described. On CT, this trabecular pattern will be highlighted against a background of an expansile lucent osseous lesion, with intact cortical margins (Patients 1, 2). Phleboliths, appearing as rounded areas of signal void on MR imaging and calcification on CT, are occasionally identified, though they are considerably less frequent in IOVMs compared with their soft tissue counterparts.
Arteriovenous Malformations
CT with early arterial enhancement (CT angiography) and three-dimensional reconstruction images are quite helpful for diagnosis, follow-up, and planning of treatment. Current technique with three-dimensional reconstruction provides information about extension of the soft-tissue arteriovenous malformation (AVM) lesion, feeding artery, exact shunting points, draining vein, and involvement of the bone. Typical CT finding of intraosseous AVMs is contrast-enhancing multiple small osteolytic lesions or a single large cavitary lesion in the medulla with or without cortical destruction (Patients 4, 5). For evaluation of the cortical changes by AVMs, CT is better than MRI.
MRI can determine and distinguish between high-flow and low-flow malformations. Further, various imaging sequences make it easy to determine relationships to adjacent anatomic structures such as organs, muscles, nerves, and so on. The high temporal resolution of time-resolved MR angiography enables arterial, venous, and nidus localization. Intraosseous AVMs typically demonstrate signal voids in the cortex or medulla on most sequences. These flow voids are felt to be predominantly due to time-of-flight phenomena with turbulence-related rephasing also contributing to signal loss. An additional feature to differentiate high-flow lesions from low-flow lesions is the presence of enlarged feeding arteries and dilated draining veins. Gradient echo sequences show AVMs as bright, signal, serpiginous, and vascular structures (Patients 4, 5).
CT and MR Angiograms and Catheter Angiograms
CT and MR angiograms are useful in the evaluation of flow and vascularity of the lesion and for initial decisions about the likelihood of potential embolization in its management. Digitally subtracted catheter angiography is principally used when embolization is considered for the management of the lesions, rather than for purely “diagnostic” purposes (Patients 4, 5).
Histopathology and immunohistochemistry
Histopathological analysis heamatoxylin and eosin (H&E) demonstrates thin-walled vascular channels lined by flattened endothelium with scant stroma and lacking a uniform muscular layer and can be useful in differentiating hemangiomas from vascular malformations. Vascular anomalies are notoriously difficult to diagnose and classify due to overlapping histologically features and until recently lack of specific markers to distinguish these lesions. Immunohistochemical analysis, especially glucose transporter 1 (GLUT 1) stains can provide additional certainty of diagnosis. North and colleagues initially reported the utility of GLUT 1 in differentiating hemangiomas and vascular malformations and demonstrated that 97% of hemangiomas expressed GLUT 1 staining (sensitivity 95%, Specificity 100%), but none of the vascular malformations expressed GLUT 1 staining (sensitivity and specificity 100%). Other investigators have subsequently confirmed the utility of GLUT 1 stains in differentiating between these two lesions, but principally for soft tissue lesions.
Srinivasan and colleagues , and Bruder and colleagues reported the use of GLUT 1 in diagnosing intraosseous venous/vascular malformations and highlighted the lack of staining, similar to that seen in the soft tissue lesions.
Management
Management of intraosseous vascular lesions is based on the specific diagnosis and influenced by the patients’ age and health, size, location, symptoms, elective/emergency presentation, team expertise, and resources.
Skull Vault Lesions
They present as a slowly enlarging mass, which can be symptomatic or picked up as an incidental finding during imaging for an unrelated problem. They account for about 0.2% of primary benign cranial tumors and 1.1% of the surgically treated cranial and spinal cavernous malformations. These lesions are most frequently found in the frontal, temporal, and parietal skull. , They were more common in women (M:F—1:1.6) and most frequently presented in the fourth decade.
IOVMs primarily occur within the diploic space with an expansile appearance and thinning of the overlying cortex. This appearance is best delineated with high-resolution CT imaging, which easily depicts the characteristic elements, variously described as stippled, spiculated, honeycomb, spoke wheel, or sunburst in appearance. The variable ossific density is thought reflective of osteoblastic activity from chronic and repeat hemorrhage. The imaging appearance of calvarial IOVMs with MR imaging is variable. IOVMs have strikingly hyperintense signal on T2-weighted imaging, reflecting slow-flowing blood or subacute thrombus. On T1-weighted imaging, some lesions have high signal from thrombus or fat, which may be differentiated with a fat-suppressed technique. Residual cortex has thin and hypointense signal on all MR pulse sequences, and the internal ossific spicules may be evident as internal areas of signal void. Extraosseous soft-tissue extension is possible and better discriminated on MR imaging, given its advantage in soft-tissue contrast resolution.
Heckel and colleagues reported expansion of the outer table with the inner table being intact in a majority of cases, with resorption of the inner table being found in larger lesions and lagging behind the changes in the outer table. Wang and colleagues reported that the inner table was invaded and destroyed in the majority of patients in their series and felt because the lesions were much larger are the only intact inner table was found in the patient whose tumor was the smallest in our series (1.0 cm).
Conservative management with clinical and imaging surveillance can be an option for asymptomatic vascular malformations away from esthetically critical areas.
Lesions that are symptomatic, enlarging, and present in locations that are esthetical critical are managed by surgery. Adjuvant interventions will depend on the specific diagnosis of the lesions.
Surgery remains the mainstay of treatment for these lesions. Curettage is generally not recommended due to the risk of bleeding and incomplete excision. Complete excision outside the perimeter of these lesions is recommended to reduce the risk of bleeding and recurrence. An accurate assessment of the clinical finding and cross-sectional imaging is mandatory to determine the margins of the lesions and plan the resection.
We currently use surgical guides and intraoperative navigation to enable safe and complete excision. There were no instances of increased intraoperative bleeding in our series. Tailored reconstruction of the resultant defect is necessary to achieve excellent functional and esthetic outcomes. Titanium mesh and bone grafts are among the most frequently used reconstructive methods described in the literature. Surgical guides and patient-specific implants were most frequently used in our practice.
Patient 1
A 76-year-old woman presented with a slowly enlarging swelling in the left forehead of a year’s duration ( Fig. 1 A). It had more recently been associated with discomfort and she denied any previous history of trauma. A CT scan demonstrated an expansile lesion with a narrow zone of transition and a sun burst pattern of trabecular thickening radiating from the center. The inner cortex was intact ( Fig. 1 B, C).
A hemicoronal flap within the hairline ( Fig. 1 D) was raised in the subgaleal plane and a separate pericranial flap created ( Fig. 1 E). The lesion was exposed ( Fig. 1 F) and a surgical guide was placed to facilitate the planned resection margins and reconstruction ( Fig. 1 G, H). A full-thickness excision of the calvarium was carried out ( Fig. 1 I). A PEEK patient-specific implant was used to reconstruct the defect and held in place with plates ( Fig. 1 J). A folded pericranial flap ( Fig. 1 K) was placed over the implant and the wound closed in layers ( Fig. 1 L).
Orbital rims and zygoma
Zygoma and the periorbital bone are the second most common sites of intraosseous vascular malformation in the facial skeleton, following the jaw bones. , There was a female predilection (F:M—3:1), and they most frequently presented in the fourth decade. A history of trauma was elicited in 14% of patients. The lesions were described as symptomatic (pain/discomfort) in 37% of patients and 14% demonstrated ophthalmologic changes. , In frontal lesions involving the orbital rim and walls and other periorbital intraosseous lesions including those arising from the zygoma, additional factors such as orbital dystopia, proptosis, diplopia, foraminal, and fissural compression would also have to be considered when determining the need for intervention. The risk of damage to the orbital structures, and extension of the resultant defect into the nasal cavity and adjacent air sinuses will have to be carefully assessed and is likely to influence the resection and the subsequent reconstruction.
Complete surgical excision was the most frequently carried out treatment and was reported in 86% of cases. Partial excision and curettage were reported in a smaller number of patients and can be associated with an increased risk of recurrence. , , The need to accurately recreate the premorbid orbital shape and volume in paramount to achieve excellent cosmesis and function. Intraoperative navigation will greatly help in confirming the location of the relevant and critical structures and achieving the preplanned resection of the lesion. Accurate reconstruction of the defect is best achieved with patient-specific implants and surgical guides. Contoured bone grafts have been the most frequently reported reconstructive method (split calvarium > iliac crest > rib) and were carried out primarily, but the need for an additional donor site (including split calvarial bone grafts), the unpredictable resorption in the postoperative period, and difficulty in recreating the complex three-dimensional anatomy of these sites consistently, makes it a less than ideal reconstructive option. Although “on table” contouring of a titanium mesh can be undertaken for more “straight forward” defects, a pre-contoured implant created on stereolithographic models or computerized planning is preferred for the more complex defects. The choice of the alloplastic material is varied and will be determined by the need for intraoperative adjustments, imaging surveillance, clinician experience/preference, and resources.
Patient 2
A 46-year-old woman presented with a right supraorbital swelling of 1-month duration. A CT and MRI scan were reported as keeping with an intraosseous (hemangioma) venous malformation. The patient initially elected to pursue a “conservative” course with clinical and imaging surveillance. The lesions had continued to grow and were becoming more noticeable and symptomatic and she elected for surgery 18 months after the initial presentation ( Fig. 2 A). A CT scan confirmed a lesion in the right supraorbital rim, exhibiting sun burst pattern of trabeculae radiating from the center and extending into the orbital roof ( Fig. 2 B, C). A virtual surgical plan was undertaken to determine the extent of resection and the resultant defect was “virtually reconstructed” by mirroring the contralateral side ( Fig. 2 D). A stereolithographic model was created with the “reconstructed” defect and used to prebend a patient-specific titanium mesh ( Fig. 2 E).
