Technetium Tc 99M Labeled Red Blood Cells in the Preoperative

Home , Angiofibroma, Angioma, Hemangiopericytoma, Lymphangioma

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

Ennio Polito, MD; Luca Burroni, MD; Patrizia Pichierri, MD; Antonio Loffredo, MD; Angelo G. Vattimo, MD

Objectives: To evaluate technetium Tc 99m (99mTc) red lacrimal gland, 1 astrocytoma, 1 ophthalmic vein throm- blood cell scintigraphy as a diagnostic tool for orbital cav- bosis, and 1 orbital varix. ernous hemangioma and to differentiate between orbital masses on the basis of their vascularization. Conclusions: The confirmation of the preoperative diagnosis by 99mTc red blood cell scintigraphy shows that Methods: We performed 99mTc red blood cell scintig- this technique is a reliable tool for differentiating cav- raphy on 23 patients (8 female and 15 male; mean age, ernous hemangiomas from other orbital masses (sensi- 47 years) affected by an orbital mass previously re- tivity,100%; specificity,86%) when ultrasound, CT, and vealed with computed tomography (CT) and magnetic MRI are not diagnostic. Unfortunately, 99mTc red blood resonance imaging (MRI) and suggesting cavernous he- cell scintigraphy results were positive in 1 patient with mangioma. In our diagnosis, we considered the orbital hemangiopericytoma and 1 patient with lymphan- increase delayed uptake with the typical scintigraphic pat- gioma, which showed increased uptake in the lesion on tern known as perfusion blood pool mismatch. The patients underwent biopsy or surgical treatment with trans- SPET images because of the vascular nature of these tu- conjunctival cryosurgical extraction when possible. mors. Therefore, in these cases, the SPET images have to be integrated with data regarding clinical preopera- Results: Single-photon emission tomography (SPET) tive evaluation and CT scans or MRI studies. On the ba- showed intense focal uptake in the orbit corresponding sis of our study, a complete diagnostic picture, CT scans to radiologic findings in 11 patients who underwent sur- or MRI studies, and scintigraphic patterns can establish gical treatment and pathologic evaluation (9 cavernous the preoperative diagnosis of vascular orbital tumors such hemangiomas, 1 hemangiopericytoma, and 1 lymphan- as cavernous hemangioma, adult-type lymphangioma, and gioma). Clinical or histologic examination of the remain- hemangiopericytoma. ing 22 patients revealed the presence of 5 lymphoid pseudotumors, 2 lymphomas, 2 pleomorphic adenomas of the Arch Ophthalmol. 2005;123:1678-1683

HE CAVERNOUS HEMAN- papillary dysfunction can result from gioma is the most com- compression of the intraorbital contents mon benign orbital tumor by the hemangioma. The encapsulated na- in adults and accounts for ture of this tumor allows a progressive en- 3% to 7% of all orbital mass largement without invasion of nearby lesions.T1 It takes the form of a clearly structures or distant metastasis. Unfortu- delineated vascular mass that contains nately, the exact diagnosis is often estab- large blood-filled spaces, which are lined lished by the pathologist after the surgi- with flattened endothelial cells and sur- cal removal of the mass. rounded by a fibrous capsule. These spaces are apparently due to dilation and thick- For editorial comment ening of the walls of the capillary loops.2,3 see page 1739 These tumors may occur anywhere in the orbital cavity, but the typical localization The differential diagnosis of a unilateral is within the muscle cone, often lateral to orbital mass that causes proptosis can be the optic nerve. Usually this neoplasm oc- difficult; possibilities may include lymphoid curs in the third to the fifth decade of life, pseudotumor, orbital varices, malignant tu- Author Affiliations: and women are affected more commonly mor, lymphoma, schwannoma, menin- Departments of Ophthalmology 4 and Neurosurgery (Drs Polito, than men. No predilection exists for race gioma, hemangiopericytoma, ossifying he- Pichierri, and Loffredo) and or ethnicity. Its common manifestation is mangioma, adult-type lymphangioma, and 5 Nuclear Medicine (Drs Burroni a slowly progressive, painless, unilateral cavernoushemangioma. Computedtomog- and Vattimo), University of proptosis. Visual acuity or field compro- raphy (CT) and magnetic resonance imag- Siena, Siena, Italy. mise, diplopia, and extraocular muscle or ing (MRI) accurately illustrate the shape,

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Perfusion Images

B Early Blood Pool Images

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.

A B

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

size, and anatomical relationship of orbital masses but are images, the signal is hyperintense to fat. With gadolin- poor indicators of their vascular nature. Nevertheless, all ium, total homogeneous enhancement occurs, but be- cavernous hemangiomas share some common character- cause blood flow through the lesion is stagnant and inde- istics on CT scans, appearing as well-defined, oval to round, pendent from the orbital vascular system, a cavernous homogeneous, and encapsulated with a density somewhat hemangioma does not fill with contrast within the first 1 greater than that of muscle.5 Furthermore, CT scans are to 2 minutes.6,7 abletoshowmicrocalcifications,sometimespresentinlong- Surgical excision with transconjunctival cryosurgical ex- standing lesions. traction is the optimal procedure for removing an orbital On MRI studies (T1-weighted images), a cavernous he- cavernous hemangioma when not located in the posterior mangioma gives off a homogeneous signal, which is isoin- third of the orbital space.8 When the tumor is located in tense to muscle and hypointense to fat. On T2-weighted the posterior and lateral third of the orbital space, a lateral

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Patient No./ CT or MRI Histologic or Sex/Age, y (Diagnostic Hypothesis) Scintigraphic Pattern Clinical Diagnosis Size, cm 1/F/56 CT and MRI: cavernous hemangioma or meningioma Positive for angioma Cavernous hemangioma 1.6 ϫ 3 2/F/38 CT and MRI: cavernous hemangioma, hemangiopericytoma, Positive for angioma Cavernous hemangioma 1.1 ϫ 1.3 or meningioma 3/M/51 MRI: intraconal orbital mass Positive for angioma Cavernous hemangioma 2.5 ϫ 3.7 4/M/41 CT and MRI: cavernous hemangioma or angiofibroma Positive for angioma Cavernous hemangioma 1.6 ϫ 1.0 5/F/59 CT and MRI: pseudotumor or lymphoma Negative for angioma Lymphoma 6/M/32 CT and MRI: myositis Negative for angioma Lymphoid pseudotumor 7/M/35 MRI: pseudotumor Negative for angioma Lymphoid pseudotumor 8/M/45 CT and MRI: pleomorphic adenoma of lacrimal gland Negative for angioma Pleomorphic adenoma 9/M/86 CT: pseudotumor or lymphoma Negative for angioma Lymphoma 10/M/56 CT: orbital mass Positive for angioma Hemangiopericytoma 11/F/63 CT and MRI: ophthalmic vein thrombosis Negative for angioma Ophthalmic vein thrombosis 12/F/66 CT and MRI: orbital varix Negative for angioma Orbital varix 13/M/42 CT and MRI: cavernous hemangioma or angiofibroma Positive for angioma Cavernous hemangioma 2.0 ϫ 1.4 14/M/25 CT and MRI: glioma Negative for angioma Lymphoid pseudotumor 15/F/11 MRI: astrocytoma, meningioma, or hemangiopericytoma Negative for angioma Astrocytoma 16/M/46 MRI: orbital mass Positive for angioma Cavernous hemangioma 2.2 ϫ 1.2 17/F/44 CT: pseudotumor Negative for angioma Lymphoid pseudotumor 18/M/51 CT and MRI: pseudotumor Negative for angioma Lymphoid pseudotumor 19/M/43 CT and MRI: fibroangioma Positive for angioma Cavernous hemangioma 2.5 ϫ 3.0 20/M/26 MRI: cavernous hemangioma Negative for angioma Pleomorphic adenoma 21/F/76 CT: orbital mass Positive for angioma Cavernous hemangioma 2.2 ϫ 1.0 22/M/34 CT and MRI: cavernous hemangioma Positive for angioma Lymphangioma 3.0 ϫ 3.5 23/M/55 CT and MRI: orbital mass Positive for angioma Cavernous hemangioma 2.8 ϫ 2.4

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging.

A B

Transverse 66 67 68

Coronal 54 55 56

Sagittal 55 56 57

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.

surgical approach is performed. When this surgical ap- accurate preoperative diagnosis of a cavernous heman- proach proves impossible, the patient is monitored via se- gioma or other vascular orbital tumor. rial radiographic studies approximately every 3 months.9 Tothisend,wehaveadoptedtechnetiumTc99m(99mTc)– Moreover, early and complete surgical excision of the labeled red blood cell scintigraphy as a diagnostic tool when mass is necessary in the management of a malignant vas- the diagnosis of an orbital vascular tumor (particularly a cular tumor (ie, hemangiopericytoma) even when lo- cavernous hemangioma) is suggested on CT scans or MRI cated in the orbital apex. In fact, complete excision of studies. This technique is a recognized tool in the evalu- the tumor seems to avoid or reduce the risk of recur- ation of hepatic hemangiomas.10 In fact, the procedure is rence and metastasis. This explains the importance of an considered 100% specific and 94% sensitive for the diag-

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Transverse 55 56 57

Coronal 44 45 46 2 cm

Sagittal 57 58 59

Transverse 63 64 65

Coronal 53 54 55

Sagittal 70 71 72

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.

nosis of liver hemangiomas.11,12 The aims of our study are pertechnetate–labeled red blood cells was prepared using a com- to evaluate 99mTc red blood cell scintigraphy as a diagnos- mercial kit suitable for routine clinical use (Eritrotec; Nycomed tic tool for orbital cavernous hemangiomas and to differ- Amersham,Sorin,Italy).Radionuclideangiographywasperformed entiate orbital masses on the basis of their vascularization. with 2-second images (60 images during 2 minutes in a 64ϫ64 matrix) obtained following a bolus injection of the radiopharma- ceutical using a 90°-oriented dual-headed camera in anterior and METHODS lesion-side lateral projections. The perfusion study was immedi- In this retrospective case series, we reviewed the medical re- ately followed by an early blood pool study conducted simulta- cords of 23 patients (8 female and 15 male; age range, 11-86 years; neously for the anterior and lesion-side lateral views. Finally, late mean age, 47 years) affected by an orbital mass suggestive of cav- blood pool single-photon emission tomography (SPET) was per- ernous hemangioma who were operated on in the Orbital Ser- formed 3 to 4 hours following injection. Transaxial, coronal, and vice at the University of Siena since 1990. Patients with exoph- sagittal slices were generated with iterative filtered reconstruction thalmos and retrobulbar lesions apparent on CT and MRI were (Figure 1). Two indicative slices at the orbital and sagittal sinus evaluated by 99mTc red blood cell scintigraphy. The study was levels were chosen. Three regions of interest were drawn over the approved by the local ethics committee, and all patients gave their slices, and mean counts were calculated. Then an asymmetry in- written informed consent before examination. dex (AI) was calculated using the following formula: AI=(lesion- A perfusion study and early and delayed blood pool studies sideorbitcounts/sagittalsinuscounts)/(normalorbitcounts/sagittal were performed: 15 to 20 mCi (555 to 740 MBq) of 99mTc sinus counts) (Figure 2). Diagnosis was based on orbital increase

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 may assert that 99mTc red blood cell scintigraphy is highly Table 2. Histologic Features and Asymmetry Index Values sensitive (sensitivity,100%) and specific (specificity,86%) in detecting cavernous hemangiomas, with a Patient Asymmetry Histologic negative predictive value of 100% and a positive predic- No. Index Features tive value of 82%. 1 23.34 Cavernous hemangioma 2 23.11 Cavernous hemangioma 3 18.23 Cavernous hemangioma COMMENT 4 12.88 Cavernous hemangioma 5 10.71 Cavernous hemangioma 6 5.67 Cavernous hemangioma Scintigraphy with 99mTc red blood cells is commonly used 7 5.15 Cavernous hemangioma in the evaluation of hepatic hemangiomas and may also 8 4.94 Hemangiopericytoma be used in the noninvasive evaluation of extrahepatic vas- 9 4.52 Cavernous hemangioma cular lesions such as vascular tumors of the orbit,13-18 as 10 3.68 Lymphangioma 11 3.17 Cavernous hemangioma well as in gastrointestinal bleeding imaging, cardiac- 12 1.93 Astrocytoma gated blood pool studies, and radionuclide venograms. 13 1.42 Lymphoid pseudotumor In all the patients with orbital cavernous heman- 14 1.38 Ophthalmic vein thrombosis gioma whom we treated, the preoperative diagnosis was 15 1.38 Orbital varix confirmed by the typical pattern of perfusion blood pool 16 1.18 Lymphoid pseudotumor mismatch on the 99mTc red blood cell scintigraphy. Be- 17 1.13 Pleomorphic adenoma cause all patients displayed negative images of perfu- 18 1.12 Lymphoid pseudotumor 19 1.05 Lymphoma sion, we suggest performing only the late study with SPET 20 1.03 Lymphoid pseudotumor at 3 to 4 hours after injection for diagnostic use. On the 21 1.02 Lymphoid pseudotumor basis of our study, we have found this procedure to be 22 0.98 Lymphoma 100% sensitive and 86% specific for the diagnosis of or- 23 0.96 Pleomorphic adenoma bital cavernous hemangioma. This shows that 99mTc- labeled red blood cell scintigraphy is a reliable tool for recognizing a cavernous hemangioma before surgical ex- delayed uptake with a typical scintigraphic pattern known as per- cision. In fact, orbital lesions that show the characteris- fusion blood pool mismatch, which is typical of cavernous hem- tic scintigraphic pattern can be diagnosed as cavernous angiomas because of their vascular structure (Figure 1). A statis- hemangioma with a high degree of certainty. This asser- tical comparison between the groups was also performed using tion is borne out by several studies reported in the lit- theMann-Whitneytest.Patientsunderwentbiopsyorsurgicaltreat- erature.13-17 Moreover, we may assert that patients with ment with transconjunctival cryosurgical extraction when pos- an AI greater than 5.0 are almost certainly affected by cav- sible. Histologic diagnosis was obtained for 19 patients, and clini- ernous hemangioma. Patients with an AI between 5.0 and cal diagnosis was obtained for only 4 patients. 2.0 are likely to be affected by a vascular tumor (hemangiopericytoma, lymphangioma, or cavernous heman- RESULTS gioma). Finally, patients with an AI less than 2.0 are most probably affected by nonvascular tumors. Data regarding the clinical manifestation, pathologic ocu- The 99mTc red blood cell scintigraphy results were posi- lar findings, CT scans and MRI studies, 99mTc red blood tive in all cases of cavernous hemangioma and unfortu- cell scintigraphy, operative reports, and pathologic re- nately also in 1 case of hemangiopericytoma and 1 case ports were collected and are summarized in Table 1. of lymphangioma. These 2 cases displayed increased up- All patients showed normal images for perfusion and early take within the lesion on SPET images (AI=4.94 and 3.68, blood pool studies. However, later SPET images showed respectively), which is probably due to the vascular na- intense focal uptake in the orbit corresponding to the ra- ture of these tumors.18 Therefore, in these cases the SPET diologic findings in 11 patients. Transconjunctival cryo- images need to be integrated with data regarding clini- surgical extraction of the lesion confirmed the presence cal preoperative evaluation (anamnestic evaluation of on- of cavernous hemangioma in 9 patients and hemangio- set and pain, careful palpation of the globe, and ocular pericytoma and adult-type lymphangioma in the remain- motility study) and CT scans or MRI studies. ing 2 patients. Clinical or histologic examination of the Hemangiopericytomas typically display slowly pro- remaining 12 patients revealed the presence of 5 lym- gressive, abaxial proptosis. In fact, they are often clini- phoid pseudotumors, 2 lymphomas, 2 pleomorphic ad- cally mistaken for a cavernous hemangioma. Instead, on enomas of the lacrimal gland, 1 astrocytoma, 1 ophthal- CT scans, this tumor appears as a solid, homogeneous, mic vein thrombosis, and 1 orbital varix (Figure 3 and rounded mass with parenchymal density, sometimes with Figure 4A and B) irregular borders. The MRI study shows a round to oval The SPET images delineated the location and size of tumor. On T1-weighted images, the signal is isointense the vascular benign tumors and clearly differentiated these to muscle and hypointense to fat. The T2-weighted im- from the normal vascularity of the other lesions. More- age is hyperintense to fat. Moderate enhancement is seen over, a significant statistical difference (PϽ.001) was found with gadolinium administration. between the group with cavernous hemangioma In the case of adult-type lymphangiomas, affected pa- (AI=11.86±8.01) and the others (AI=1.65±1.17) tients have progressive, painless proptosis. The CT scans (Table 2). On the basis of the results of our study, we reveal an irregular, heterogeneous, and poorly defined

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 density mass that infiltrates normal orbital structures. On Jones IS, Jakobiec FA, ed. Diseases of the Orbit. Hagerstown, Md: Harper & Row; MRI studies, lymphangiomas reveal a diffuse, infiltra- 1979:269-283. 3. Duke-Elder S. The orbit. In: System of Ophthalmology. Vol 13. St Louis, Mo: CV tive mass that may have 1 or more distinct cystic cavi- Mosby Co; 1974:1086-1096. ties. A complete diagnostic picture therefore leads to an 4. Brackup AH, Haller ML, Danber MM. Hemangioma of the bony orbit. Am J accurate preoperative diagnosis. Ophthalmol. 1980;90:258-261. In conclusion, 99mTc red blood cell imaging is safe, rela- 5. Reese AB. Orbital neoplasms and lesions simulating them. In: Tumors of the Eye. 2nd ed. New York, NY: Harper & Row; 1963:529-580. tively inexpensive, easy to perform, and highly accu- 6. Fries PD, Char DH, Norman D. MR imaging of orbital cavernous hemangioma. rate. In particular, on the basis of the results of our study, J Comput Assist Tomogr. 1987;11:418-421. an overview of clinical evaluations, CT scans or MRI stud- 7. Wilms G, Raat H, Dom R, et al. Orbital cavernous hemangioma: findings on se- ies, and scintigraphic patterns can establish the preop- quential Gd-enhanced MRI. J Comput Assist Tomogr. 1995;19:548-551. 8. Polito E, Leccisotti A, Frezzotti R. A re-evaluation of the transconjunctival ap- erative diagnosis of some vascular tumors of the orbit, proach to orbital tumors. Orbit. 1994;13:17-24. such as cavernous hemangioma, adult-type lymphan- 9. Gdal-On M, Gelfand YA. Surgical outcome of transconjunctival cryosurgical ex- gioma, and hemangiopericytoma. Moreover, 99mTc red traction of orbital cavernous hemangioma. Ophthalmic Surg Lasers. 1998; blood cell scintigraphy is a useful diagnostic tool in ex- 29:969-973. cluding tumors with a nonvascular origin responsible for 10. Groshar D, Ben-Haim S, Gips S, et al. Spectrum of scintigraphic appearance of liver hemangiomas. Clin Nucl Med. 1992;17:294-299. unilateral painless proptosis. 11. Malik MH. Blood pool SPECT and planar imaging in hepatic hemangioma. Clin Nucl Med. 1987;12:543-547. Submitted for Publication: December 6, 2003; final revi- 12. Brodsky RI, Friedman AC, Maurer AH, et al. Hepatic cavernous hemangioma: di- sion received November 16, 2004; accepted March 14, 2005. agnosis with 99mTc-labeled red cells and single-photon emission CT. AJRAmJ Roentgenol. 1987;148:125-129. Correspondence: Ennio Polito, MD, via A. De Gasperi 13. Front D, Israel O, Kleinhaus U, Gdal-On M. Tc-99m-labeled red blood cells in the 3, 53100 Siena, Italy ([email protected]). evaluation of hemangiomas of the skull and orbit: concise communication. J Nucl Financial Disclosure: None. Med. 1982;23:1080-1084. Disclaimer: Dr Polito had full access to all the data in 14. Ki WW, Shin JW, Won KS, et al. Diagnosis of orbital cavernous hemangioma with Tc-99m RBC SPECT. Clin Nucl Med. 1997;22:546-549. the study and takes responsibility for the integrity of the 15. Murata Y, Yamada I, Umehara I, et al. Perfusion and blood-pool scintigraphy in data and the accuracy of the data analysis. the evaluation of head and neck hemangiomas. J Nucl Med. 1997;38:882-885. 16. Sayit E, Durak I, Capakaya G, et al. The role of Tc-99m RBC scintigraphy in the differential diagnosis of orbital cavernous hemangioma. Ann Nucl Med. 2001; REFERENCES 15:149-151. 17. Burroni L, Polito E, Tasciotti A, et al. The Tc99m-RBC SPET in the diagnosis of 1. Shields JA, Bakewell B, Augsburger JJ, Flanagan JC. Classification and inci- orbital cavernous hemangioma. Q J Nucl Med. 2000;44:70. dence of space-occupying lesions of the orbit: a survey of 645 biopsies. Arch 18. Gdal-On M, Gelfand YA, Israel O. Tc-99m labeled red blood cells scintigraphy: a Ophthalmol. 1984;102:1606-1611. diagnostic method for orbital cavernous hemangioma. Eur J Ophthalmol. 1999; 2. Jones IS, Jakobiec FA. Vascular tumors, malformations, and degeneration. In: 9:125-129.

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