14 Vascular Tumors Kaan Gündüz and Zeynel A. Karcioglu ascular tumors and malformations of the orbit VIII related antigen (v,w,f), CV141 (endothelium, comprise an important group of orbital space- mesothelium, and squamous cells), and VEGFR-3 Voccupying lesions. Reviews indicate that vas- (channels, neovascular endothelium). None of the cell cular lesions account for 6.2 to 12.0% of all histopatho- markers is absolutely specific in its application; a com- logically documented orbital space-occupying lesions bination is recommended in difficult cases. CD31 is (Table 14.1).1–5 There is ultrastructural and immuno- the most often used endothelial cell marker, with pos- histochemical evidence that capillary and cavernous itive membrane staining pattern in over 90% of cap- hemangiomas, lymphangioma, and other vascular le- illary hemangiomas, cavernous hemangiomas, and an- sions are of different nosologic origins, yet in many giosarcomas; CD34 is expressed only in about 50% of patients these entities coexist. Hence, some prefer to endothelial cell tumors. Lymphangioma pattern, on use a single umbrella term, “vascular hamartomatous the other hand, is negative with CD31 and CD34, lesions” to identify these masses, with the qualifica- but, it is positive with VEGFR-3. VEGFR-3 expression tion that, in a given case, one tissue element may pre- is also seen in Kaposi sarcoma and in neovascular dominate.6 For example, an “infantile hemangioma” endothelium. In hemangiopericytomas, the tumor may contain a few caverns or intertwined abnormal cells are typically positive for vimentin and CD34 and blood vessels, but its predominating component is negative for markers of endothelia (factor VIII, CD31, usually capillary hemangioma. This nomenclature etc.) does not cover all bases either; it should be noted that Another focus of debate is whether lymphangioma although many vascular lesions are made of multiple and varix are related lesions. It has been suggested that histopathologic types, all are not. For instance, al- orbital venous anomaly be used for both types of le- though caverns lined by endothelial cells are seen in sion.7 However, most orbitologists still use lymphan- many vascular lesions, no other tissue element is gioma and varix separately. Angiolymphoid hyperpla- encountered with the classic intraconal “cavernous sia with eosinophilia and Kimura disease were once hemangioma.” In this chapter, the time-honored ter- thought to represent the same entity, although differ- minology is used to review cavernous hemangioma, ences between the conditions do exist. They no longer capillary hemangioma, lymphangioma, orbital varix, are considered to be the same disease.8 hemangiopericytoma, angiosarcoma, intravascular pap- illary endothelial hyperplasia, arteriovenous fistulas, vascular leiomyoma, angiolymphoid hyperplasia with CAVERNOUS HEMANGIOMA eosinophilia, and Kimura disease. From the standpoint of treatment and predicting Cavernous hemangioma is the most common benign prognosis, it is important to determine the predomi- orbital tumor in adults. It comprised 3.1 to 9.0% of nating tissue element: if a lesion predominantly con- all histopathologically proven orbital tumors in five tains capillary hemangioma, for example, it may scle- series (Table 14.1).1–5 It most frequently occurs in pa- rose significantly as the patient ages, and, if treated, tients 40 to 60 years old.3 Rarely, cavernous heman- it may respond well to steroid injections. On the other gioma can occur in children. Unlike capillary heman- hand, lesions with predominantly cavernous histology gioma, it is not associated with the presence of and/or large blood vessel malformations do not regress hemangiomas elsewhere in the body. over the years and do not respond to intralesional ste- roid injections, even though both these pathologies Clinical Features may be identified as “vascular hamartomatous le- sions.” In some cases, light-microscopic examination Orbital cavernous hemangioma can occupy an intra- with routine stains may not be sufficient to determine conal or extraconal position in the orbit (Figures 14.1 an answer; in these instances immunohistochemistry and 14.2). When the cavernous hemangioma is located may help. A number of cellular antigens identify the intraconally, it leads to a slowly progressive axial prop- endothelial cell. These include CD31, CD34, factor tosis (Figure 14.1). When it is located extraconally in 141 142 PART THREE: PRIMARY TUMORS OF THE ORBIT TABLE 14.1. Frequency of Various Vascular Tumors of the Orbit. No. of Cavernous Capillary Author cases hemangioma hemangioma Lymphangioma Varices Hemangiopericytoma Shields et al.1 645 20 (3.1%) 7 (1.1%) 4 (0.6%) 2 (0.3%) 5 (0.8%) Sen5 266 16 (6.0%) 5 (1.9%) 4 (1.5%) — 1 (0.3%) Günalp and Gündüz3 1092 35 (3.2%) 15 (1.3%) 3 (0.3%) 3 (0.3%) 1 (0.1%) Henderson et al.2 1376 60 (4.4%) 30 (2.2%) 18 (1.3%) 4 (0.3%) 16 (1.2%) Seregard and Sahlin4 300 27 (9%) 2 (0.7%) 2 (0.7%) 4 (1.3%) 1 (0.3%) Vascular Arteriovenous Author leiomyoma Angiosarcoma fistula Aneurysm Hamartoma Shields et al.1 2 (0.3%) — — — — Sen5 —— ——— Günalp and Gündüz3 — 3 (0.3%) 3 (0.3%) — — Henderson et al.2 1 (0.1%) — 5 (0.4%) 2 (0.1%) 1 (0.1%) Seregard and Sahlin4 —— ——— the orbit, the displacement of the globe is opposite the ally good unless the cavernous hemangioma com- position of the tumor. Rarely, a cavernous hemangi- presses the optic nerve. When the tumor is located in oma presents as a lacrimal gland mass9 or as an in- the vicinity of the globe, it may induce hyperopia and traosseous tumor.10,11 choroidal folds. It is interesting that the hyperopia and A palpable mass is rarely present. There are usu- choroidal folds may persist even after complete re- ally no significant inflammatory signs such as eyelid moval of the cavernous hemangioma (Figure 14.1).12 edema or conjunctival injection. Visual acuity is usu- Ocular motility may be slightly limited. Amaurosis FIGURE 14.1. (A–C) Typical cavernous hemangioma presentation with slowly progres- sive unilateral proptosis due to an intraconal lesion. (B,C) Axial T1-weighted MR images with and without contrast reveal a well- encapsulated, oval lesion within the cone. (D) Histopathologically, the specimen consists of multiple cavernous spaces separated by fibrous septae; most of the caverns are filled with blood. (E) The gross specimen after surgical excision shows a reddish blue encapsulated lesion. (F) Fundus photograph shows the choroidal folds (arrow) secondary to the compression of the lesion. CHAPTER 14: VASCULAR TUMORS 143 FIGURE 14.2. Axial CTs from three different cavernous hemangiomas. (A) A long-standing, large cavernous hemangioma within and outside of the cone of the right orbit. Note the bony invasion of this lesion into the cranium (white arrow). Inset: the cavernous hemangioma (c) invading the bone (b). (B) Large but well-delineated cavernous hemangioma of the orbit causing massive proptosis and compression of the globe. Note that the lesion is larger than the one shown in (A) but is much better circumscribed, without any bony invasion. (C,D) A multilobulated cavernous hemangioma of the left orbit. fugax, in extreme positions of gaze, is probably related On MRI, which details internal tissue features well, cav- to ischemia of the optic nerve as it is compressed by ernous hemangioma has a heterogeneous structure. The the retrobulbar mass.13 The rare occurrence of cav- tumor is isointense to the cerebral gray matter and ex- ernous hemangioma in a patient with hyperthy- traocular muscles on T1-weighted images and hyperin- roidism has been described.14 tense on T2-weighted images. On contrast injection, the Ophthalmoscopic findings include choroidal folds, cavernous hemangioma shows progressive filling and en- optic disk edema, and optic atrophy.15 The develop- hancement. The initial patchy enhancement increases ment of optic atrophy is related to the presence of a gradually and becomes homogeneous. This pattern is long-standing tumor. These tumors have been misdi- consistent with the pooling of the contrast medium in agnosed in the past as optic neuropathy. Such errors are the caverns within the lesion and is considered to be rare now, since the advent of neuroimaging studies. characteristic of cavernous hemangioma. Other orbital Cavernous hemangioma is typically a solitary uni- tumors may display similar characteristics. lateral tumor. However, rarely bilateral and multiple The differential diagnosis of well-circumscribed hemangiomas have been reported in the same patient orbital lesions on CT and MRI include cavernous hem- (Figure 14.2).16 Multiple orbital cavernous hemangi- angioma, schwannoma, fibrous histiocytoma, heman- omas may occur as a sporadic lesion or in association giopericytoma, and certain metastatic lesions. How- with Maffucci syndrome (multiple enchondromas, ever, cavernous hemangioma is the most frequently soft tissue hemangiomas, and a generalized tendency encountered well-circumscribed orbital lesion. to neoplasia) and blue rubber bleb nevus syndrome (bluish cutaneous and mucosal hemangiomas, soft tis- Morphologic Features sue hemangiomas, enteric hemangiomas with gas- trointestinal bleeding) (see Chapter 16).17 Grossly, the orbital cavernous hemangioma is an en- capsulated mass. The lesion is purple and has a spongelike consistency. On a cut surface, it displays Radiologic Features numerous ectatic vascular spaces (Figure 14.1). A-mode ultrasonography demonstrates medium to high Histopathologically, it consists of large, congested internal reflectivity.