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Figure 1.
Technetium Tc 99m–labeled red blood cell scintigraphy showing a typical perfusion blood pool mismatch (A). Radionuclide angiography and early blood pool studies (B) demonstrate uptake in the normal anatomical structures. Characteristic delayed blood pool slices (C) demonstrate an intense uptake of the tracer in the left orbit. SPET indicates single-photon emission tomography.

Technetium Tc 99m–labeled red blood cell scintigraphy showing a typical perfusion blood pool mismatch (A). Radionuclide angiography and early blood pool studies (B) demonstrate uptake in the normal anatomical structures. Characteristic delayed blood pool slices (C) demonstrate an intense uptake of the tracer in the left orbit. SPET indicates single-photon emission tomography.

Figure 2.
Two representative axial slices of orbit (A) and sagittal sinus (B) planes for the calculation of the asymmetry index.

Two representative axial slices of orbit (A) and sagittal sinus (B) planes for the calculation of the asymmetry index.

Figure 3.
Comparison of a characteristic magnetic resonance imaging axial slice (A) and delayed single-photon emission tomogram (B) in a patient with a cavernous hemangioma of the left orbit (asymmetry index = 10.71). Numbers in the lower right corners indicate the transverse, coronal, and sagittal planes.

Comparison of a characteristic magnetic resonance imaging axial slice (A) and delayed single-photon emission tomogram (B) in a patient with a cavernous hemangioma of the left orbit (asymmetry index = 10.71). Numbers in the lower right corners indicate the transverse, coronal, and sagittal planes.

Figure 4.
Normal scintigraphic patterns in 2 patients with left orbital masses revealed by radiologic findings. A, Astrocytoma (asymmetry index = 1.93); B, ophthalmic vein thrombosis (asymmetry index = 1.38). Numbers in the lower right corners indicate the transverse, coronal, and sagittal planes.

Normal scintigraphic patterns in 2 patients with left orbital masses revealed by radiologic findings. A, Astrocytoma (asymmetry index = 1.93); B, ophthalmic vein thrombosis (asymmetry index = 1.38). Numbers in the lower right corners indicate the transverse, coronal, and sagittal planes.

Table 1. 
Clinical Findings
Clinical Findings
Table 2. 
Histologic Features and Asymmetry Index Values
Histologic Features and Asymmetry Index Values
1.
Shields  JABakewell  BAugsburger  JJFlanagan  JC Classification and incidence of space-occupying lesions of the orbit: a survey of 645 biopsies. Arch Ophthalmol 1984;1021606- 1611
PubMedArticle
2.
Jones  ISJakobiec  FA Vascular tumors, malformations, and degeneration. Jones  ISJakobiec  FAed.Diseases of the Orbit. Hagerstown, Md Harper & Row1979;269- 283
3.
Duke-Elder  S The orbit. System of Ophthalmology. Vol 13 St Louis, Mo CV Mosby Co1974;1086- 1096
4.
Brackup  AHHaller  MLDanber  MM Hemangioma of the bony orbit. Am J Ophthalmol 1980;90258- 261
PubMed
5.
Reese  AB Orbital neoplasms and lesions simulating them. Tumors of the Eye 2nd ed. New York, NY Harper & Row1963;529- 580
6.
Fries  PDChar  DHNorman  D MR imaging of orbital cavernous hemangioma. J Comput Assist Tomogr 1987;11418- 421
PubMedArticle
7.
Wilms  GRaat  HDom  R  et al.  Orbital cavernous hemangioma: findings on sequential Gd-enhanced MRI. J Comput Assist Tomogr 1995;19548- 551
PubMedArticle
8.
Polito  ELeccisotti  AFrezzotti  R A re-evaluation of the transconjunctival approach to orbital tumors. Orbit 1994;1317- 24Article
9.
Gdal-On  MGelfand  YA Surgical outcome of transconjunctival cryosurgical extraction of orbital cavernous hemangioma. Ophthalmic Surg Lasers 1998;29969- 973
PubMed
10.
Groshar  DBen-Haim  SGips  S  et al.  Spectrum of scintigraphic appearance of liver hemangiomas. Clin Nucl Med 1992;17294- 299
PubMedArticle
11.
Malik  MH Blood pool SPECT and planar imaging in hepatic hemangioma. Clin Nucl Med 1987;12543- 547
PubMedArticle
12.
Brodsky  RIFriedman  ACMaurer  AH  et al.  Hepatic cavernous hemangioma: diagnosis with 99mTc-labeled red cells and single-photon emission CT. AJR Am J Roentgenol 1987;148125- 129
PubMedArticle
13.
Front  DIsrael  OKleinhaus  UGdal-On  M Tc-99m-labeled red blood cells in the evaluation of hemangiomas of the skull and orbit: concise communication. J Nucl Med 1982;231080- 1084
PubMed
14.
Ki  WWShin  JWWon  KS  et al.  Diagnosis of orbital cavernous hemangioma with Tc-99m RBC SPECT. Clin Nucl Med 1997;22546- 549
PubMedArticle
15.
Murata  YYamada  IUmehara  I  et al.  Perfusion and blood-pool scintigraphy in the evaluation of head and neck hemangiomas. J Nucl Med 1997;38882- 885
PubMed
16.
Sayit  EDurak  ICapakaya  G  et al.  The role of Tc-99m RBC scintigraphy in the differential diagnosis of orbital cavernous hemangioma. Ann Nucl Med 2001;15149- 151
PubMedArticle
17.
Burroni  LPolito  ETasciotti  A  et al.  The Tc99m-RBC SPET in the diagnosis of orbital cavernous hemangioma. Q J Nucl Med 2000;4470
18.
Gdal-On  MGelfand  YAIsrael  O Tc-99m labeled red blood cells scintigraphy: a diagnostic method for orbital cavernous hemangioma. Eur J Ophthalmol 1999;9125- 129
PubMed
Clinical Sciences
December 01, 2005

Technetium Tc 99m–Labeled Red Blood Cells in the Preoperative Diagnosis of Cavernous Hemangioma and Other Vascular Orbital Tumors

Author Affiliations

Author Affiliations: Departments of Ophthalmology and Neurosurgery (Drs Polito, Pichierri, and Loffredo) and Nuclear Medicine (Drs Burroni and Vattimo), University of Siena, Siena, Italy.

Arch Ophthalmol. 2005;123(12):1678-1683. doi:10.1001/archopht.123.12.1678
Abstract

Objectives  To evaluate technetium Tc 99m (99mTc) red blood cell scintigraphy as a diagnostic tool for orbital cavernous hemangioma and to differentiate between orbital masses on the basis of their vascularization.

Methods  We performed 99mTc red blood cell scintigraphy on 23 patients (8 female and 15 male; mean age, 47 years) affected by an orbital mass previously revealed with computed tomography (CT) and magnetic resonance imaging (MRI) and suggesting cavernous hemangioma. In our diagnosis, we considered the orbital increase delayed uptake with the typical scintigraphic pattern known as perfusion blood pool mismatch. The patients underwent biopsy or surgical treatment with transconjunctival cryosurgical extraction when possible.

Results  Single-photon emission tomography (SPET) showed intense focal uptake in the orbit corresponding to radiologic findings in 11 patients who underwent surgical treatment and pathologic evaluation (9 cavernous hemangiomas, 1 hemangiopericytoma, and 1 lymphangioma). Clinical or histologic examination of the remaining 22 patients revealed the presence of 5 lymphoid pseudotumors, 2 lymphomas, 2 pleomorphic adenomas of the lacrimal gland, 1 astrocytoma, 1 ophthalmic vein thrombosis, and 1 orbital varix.

Conclusions  The confirmation of the preoperative diagnosis by 99mTc red blood cell scintigraphy shows that this technique is a reliable tool for differentiating cavernous hemangiomas from other orbital masses (sensitivity, 100%; specificity, 86%) when ultrasound, CT, and MRI are not diagnostic. Unfortunately, 99mTc red blood cell scintigraphy results were positive in 1 patient with hemangiopericytoma and 1 patient with lymphangioma, which showed increased uptake in the lesion on SPET images because of the vascular nature of these tumors. Therefore, in these cases, the SPET images have to be integrated with data regarding clinical preoperative evaluation and CT scans or MRI studies. On the basis of our study, a complete diagnostic picture, CT scans or MRI studies, and scintigraphic patterns can establish the preoperative diagnosis of vascular orbital tumors such as cavernous hemangioma, adult-type lymphangioma, and hemangiopericytoma.

The cavernous hemangioma is the most common benign orbital tumor in adults and accounts for 3% to 7% of all orbital mass lesions.1 It takes the form of a clearly delineated vascular mass that contains large blood-filled spaces, which are lined with flattened endothelial cells and surrounded by a fibrous capsule. These spaces are apparently due to dilation and thickening of the walls of the capillary loops.2,3 These tumors may occur anywhere in the orbital cavity, but the typical localization is within the muscle cone, often lateral to the optic nerve. Usually this neoplasm occurs in the third to the fifth decade of life, and women are affected more commonly than men.4 No predilection exists for race or ethnicity. Its common manifestation is a slowly progressive, painless, unilateral proptosis. Visual acuity or field compromise, diplopia, and extraocular muscle or papillary dysfunction can result from compression of the intraorbital contents by the hemangioma. The encapsulated nature of this tumor allows a progressive enlargement without invasion of nearby structures or distant metastasis. Unfortunately, the exact diagnosis is often established by the pathologist after the surgical removal of the mass.

The differential diagnosis of a unilateral orbital mass that causes proptosis can be difficult; possibilities may include lymphoid pseudotumor, orbital varices, malignant tumor, lymphoma, schwannoma, meningioma, hemangiopericytoma, ossifying hemangioma, adult-type lymphangioma, and cavernous hemangioma.5 Computed tomography (CT) and magnetic resonance imaging (MRI) accurately illustrate the shape, size, and anatomical relationship of orbital masses but are poor indicators of their vascular nature. Nevertheless, all cavernous hemangiomas share some common characteristics on CT scans, appearing as well-defined, oval to round, homogeneous, and encapsulated with a density somewhat greater than that of muscle.5 Furthermore, CT scans are able to show microcalcifications, sometimes present in long-standing lesions.

On MRI studies (T1-weighted images), a cavernous hemangioma gives off a homogeneous signal, which is isointense to muscle and hypointense to fat. On T2-weighted images, the signal is hyperintense to fat. With gadolinium, total homogeneous enhancement occurs, but because blood flow through the lesion is stagnant and independent from the orbital vascular system, a cavernous hemangioma does not fill with contrast within the first 1 to 2 minutes.6,7

Surgical excision with transconjunctival cryosurgical extraction is the optimal procedure for removing an orbital cavernous hemangioma when not located in the posterior third of the orbital space.8 When the tumor is located in the posterior and lateral third of the orbital space, a lateral surgical approach is performed. When this surgical approach proves impossible, the patient is monitored via serial radiographic studies approximately every 3 months.9

Moreover, early and complete surgical excision of the mass is necessary in the management of a malignant vascular tumor (ie, hemangiopericytoma) even when located in the orbital apex. In fact, complete excision of the tumor seems to avoid or reduce the risk of recurrence and metastasis. This explains the importance of an accurate preoperative diagnosis of a cavernous hemangioma or other vascular orbital tumor.

To this end, we have adopted technetium Tc 99m (99mTc)–labeled red blood cell scintigraphy as a diagnostic tool when the diagnosis of an orbital vascular tumor (particularly a cavernous hemangioma) is suggested on CT scans or MRI studies. This technique is a recognized tool in the evaluation of hepatic hemangiomas.10 In fact, the procedure is considered 100% specific and 94% sensitive for the diagnosis of liver hemangiomas.11,12 The aims of our study are to evaluate 99mTc red blood cell scintigraphy as a diagnostic tool for orbital cavernous hemangiomas and to differentiate orbital masses on the basis of their vascularization.

METHODS

In this retrospective case series, we reviewed the medical records of 23 patients (8 female and 15 male; age range, 11-86 years; mean age, 47 years) affected by an orbital mass suggestive of cavernous hemangioma who were operated on in the Orbital Service at the University of Siena since 1990. Patients with exophthalmos and retrobulbar lesions apparent on CT and MRI were evaluated by 99mTc red blood cell scintigraphy. The study was approved by the local ethics committee, and all patients gave their written informed consent before examination.

A perfusion study and early and delayed blood pool studies were performed: 15 to 20 mCi (555 to 740 MBq) of 99mTc pertechnetate–labeled red blood cells was prepared using a commercial kit suitable for routine clinical use (Eritrotec; Nycomed Amersham, Sorin, Italy). Radionuclide angiography was performed with 2-second images (60 images during 2 minutes in a 64 × 64 matrix) obtained following a bolus injection of the radiopharmaceutical using a 90°-oriented dual-headed camera in anterior and lesion-side lateral projections. The perfusion study was immediately followed by an early blood pool study conducted simultaneously for the anterior and lesion-side lateral views. Finally, late blood pool single-photon emission tomography (SPET) was performed 3 to 4 hours following injection. Transaxial, coronal, and sagittal slices were generated with iterative filtered reconstruction (Figure 1). Two indicative slices at the orbital and sagittal sinus levels were chosen. Three regions of interest were drawn over the slices, and mean counts were calculated. Then an asymmetry index (AI) was calculated using the following formula: AI = (lesion-side orbit counts/sagittal sinus counts)/(normal orbit counts/sagittal sinus counts) (Figure 2). Diagnosis was based on orbital increase delayed uptake with a typical scintigraphic pattern known as perfusion blood pool mismatch, which is typical of cavernous hemangiomas because of their vascular structure (Figure 1). A statistical comparison between the groups was also performed using the Mann-Whitney test. Patients underwent biopsy or surgical treatment with transconjunctival cryosurgical extraction when possible. Histologic diagnosis was obtained for 19 patients, and clinical diagnosis was obtained for only 4 patients.

RESULTS

Data regarding the clinical manifestation, pathologic ocular findings, CT scans and MRI studies, 99mTc red blood cell scintigraphy, operative reports, and pathologic reports were collected and are summarized in Table 1. All patients showed normal images for perfusion and early blood pool studies. However, later SPET images showed intense focal uptake in the orbit corresponding to the radiologic findings in 11 patients. Transconjunctival cryosurgical extraction of the lesion confirmed the presence of cavernous hemangioma in 9 patients and hemangiopericytoma and adult-type lymphangioma in the remaining 2 patients. Clinical or histologic examination of the remaining 12 patients revealed the presence of 5 lymphoid pseudotumors, 2 lymphomas, 2 pleomorphic adenomas of the lacrimal gland, 1 astrocytoma, 1 ophthalmic vein thrombosis, and 1 orbital varix (Figure 3 and Figure 4A and B)

The SPET images delineated the location and size of the vascular benign tumors and clearly differentiated these from the normal vascularity of the other lesions. Moreover, a significant statistical difference (P<.001) was found between the group with cavernous hemangioma (AI = 11.86 ± 8.01) and the others (AI = 1.65 ± 1.17) (Table 2). On the basis of the results of our study, we may assert that 99mTc red blood cell scintigraphy is highly sensitive (sensitivity, 100%) and specific (specificity, 86%) in detecting cavernous hemangiomas, with a negative predictive value of 100% and a positive predictive value of 82%.

COMMENT

Scintigraphy with 99mTc red blood cells is commonly used in the evaluation of hepatic hemangiomas and may also be used in the noninvasive evaluation of extrahepatic vascular lesions such as vascular tumors of the orbit,1318 as well as in gastrointestinal bleeding imaging, cardiac-gated blood pool studies, and radionuclide venograms.

In all the patients with orbital cavernous hemangioma whom we treated, the preoperative diagnosis was confirmed by the typical pattern of perfusion blood pool mismatch on the 99mTc red blood cell scintigraphy. Because all patients displayed negative images of perfusion, we suggest performing only the late study with SPET at 3 to 4 hours after injection for diagnostic use. On the basis of our study, we have found this procedure to be 100% sensitive and 86% specific for the diagnosis of orbital cavernous hemangioma. This shows that 99mTc-labeled red blood cell scintigraphy is a reliable tool for recognizing a cavernous hemangioma before surgical excision. In fact, orbital lesions that show the characteristic scintigraphic pattern can be diagnosed as cavernous hemangioma with a high degree of certainty. This assertion is borne out by several studies reported in the literature.1317 Moreover, we may assert that patients with an AI greater than 5.0 are almost certainly affected by cavernous hemangioma. Patients with an AI between 5.0 and 2.0 are likely to be affected by a vascular tumor (hemangiopericytoma, lymphangioma, or cavernous hemangioma). Finally, patients with an AI less than 2.0 are most probably affected by nonvascular tumors.

The 99mTc red blood cell scintigraphy results were positive in all cases of cavernous hemangioma and unfortunately also in 1 case of hemangiopericytoma and 1 case of lymphangioma. These 2 cases displayed increased uptake within the lesion on SPET images (AI = 4.94 and 3.68, respectively), which is probably due to the vascular nature of these tumors.18 Therefore, in these cases the SPET images need to be integrated with data regarding clinical preoperative evaluation (anamnestic evaluation of onset and pain, careful palpation of the globe, and ocular motility study) and CT scans or MRI studies.

Hemangiopericytomas typically display slowly progressive, abaxial proptosis. In fact, they are often clinically mistaken for a cavernous hemangioma. Instead, on CT scans, this tumor appears as a solid, homogeneous, rounded mass with parenchymal density, sometimes with irregular borders. The MRI study shows a round to oval tumor. On T1-weighted images, the signal is isointense to muscle and hypointense to fat. The T2-weighted image is hyperintense to fat. Moderate enhancement is seen with gadolinium administration.

In the case of adult-type lymphangiomas, affected patients have progressive, painless proptosis. The CT scans reveal an irregular, heterogeneous, and poorly defined density mass that infiltrates normal orbital structures. On MRI studies, lymphangiomas reveal a diffuse, infiltrative mass that may have 1 or more distinct cystic cavities. A complete diagnostic picture therefore leads to an accurate preoperative diagnosis.

In conclusion, 99mTc red blood cell imaging is safe, relatively inexpensive, easy to perform, and highly accurate. In particular, on the basis of the results of our study, an overview of clinical evaluations, CT scans or MRI studies, and scintigraphic patterns can establish the preoperative diagnosis of some vascular tumors of the orbit, such as cavernous hemangioma, adult-type lymphangioma, and hemangiopericytoma. Moreover, 99mTc red blood cell scintigraphy is a useful diagnostic tool in excluding tumors with a nonvascular origin responsible for unilateral painless proptosis.

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Article Information

Correspondence: Ennio Polito, MD, via A. De Gasperi 3, 53100 Siena, Italy (enniopolito@virgilio.it).

Submitted for Publication: December 6, 2003; final revision received November 16, 2004; accepted March 14, 2005.

Financial Disclosure: None.

Disclaimer: Dr Polito had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

References
1.
Shields  JABakewell  BAugsburger  JJFlanagan  JC Classification and incidence of space-occupying lesions of the orbit: a survey of 645 biopsies. Arch Ophthalmol 1984;1021606- 1611
PubMedArticle
2.
Jones  ISJakobiec  FA Vascular tumors, malformations, and degeneration. Jones  ISJakobiec  FAed.Diseases of the Orbit. Hagerstown, Md Harper & Row1979;269- 283
3.
Duke-Elder  S The orbit. System of Ophthalmology. Vol 13 St Louis, Mo CV Mosby Co1974;1086- 1096
4.
Brackup  AHHaller  MLDanber  MM Hemangioma of the bony orbit. Am J Ophthalmol 1980;90258- 261
PubMed
5.
Reese  AB Orbital neoplasms and lesions simulating them. Tumors of the Eye 2nd ed. New York, NY Harper & Row1963;529- 580
6.
Fries  PDChar  DHNorman  D MR imaging of orbital cavernous hemangioma. J Comput Assist Tomogr 1987;11418- 421
PubMedArticle
7.
Wilms  GRaat  HDom  R  et al.  Orbital cavernous hemangioma: findings on sequential Gd-enhanced MRI. J Comput Assist Tomogr 1995;19548- 551
PubMedArticle
8.
Polito  ELeccisotti  AFrezzotti  R A re-evaluation of the transconjunctival approach to orbital tumors. Orbit 1994;1317- 24Article
9.
Gdal-On  MGelfand  YA Surgical outcome of transconjunctival cryosurgical extraction of orbital cavernous hemangioma. Ophthalmic Surg Lasers 1998;29969- 973
PubMed
10.
Groshar  DBen-Haim  SGips  S  et al.  Spectrum of scintigraphic appearance of liver hemangiomas. Clin Nucl Med 1992;17294- 299
PubMedArticle
11.
Malik  MH Blood pool SPECT and planar imaging in hepatic hemangioma. Clin Nucl Med 1987;12543- 547
PubMedArticle
12.
Brodsky  RIFriedman  ACMaurer  AH  et al.  Hepatic cavernous hemangioma: diagnosis with 99mTc-labeled red cells and single-photon emission CT. AJR Am J Roentgenol 1987;148125- 129
PubMedArticle
13.
Front  DIsrael  OKleinhaus  UGdal-On  M Tc-99m-labeled red blood cells in the evaluation of hemangiomas of the skull and orbit: concise communication. J Nucl Med 1982;231080- 1084
PubMed
14.
Ki  WWShin  JWWon  KS  et al.  Diagnosis of orbital cavernous hemangioma with Tc-99m RBC SPECT. Clin Nucl Med 1997;22546- 549
PubMedArticle
15.
Murata  YYamada  IUmehara  I  et al.  Perfusion and blood-pool scintigraphy in the evaluation of head and neck hemangiomas. J Nucl Med 1997;38882- 885
PubMed
16.
Sayit  EDurak  ICapakaya  G  et al.  The role of Tc-99m RBC scintigraphy in the differential diagnosis of orbital cavernous hemangioma. Ann Nucl Med 2001;15149- 151
PubMedArticle
17.
Burroni  LPolito  ETasciotti  A  et al.  The Tc99m-RBC SPET in the diagnosis of orbital cavernous hemangioma. Q J Nucl Med 2000;4470
18.
Gdal-On  MGelfand  YAIsrael  O Tc-99m labeled red blood cells scintigraphy: a diagnostic method for orbital cavernous hemangioma. Eur J Ophthalmol 1999;9125- 129
PubMed
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