Technetium-99m-Labeled Red Blood Cells in the Evaluation of Hemangiomas of the Liver in Infants and Children

John H. Miller Division of Nuclear Radiology, Department of Radiology, Childrens Hospital of Los Angeles, and University of Southern California, School of Medicine, Los Angeles, California

The vascular origin lesions of the liver (capillary hemangioma/infantile hemangioendothelioma) that present in infancy or early childhood often have a typical clinical picture of hepatomegaly and congestive heart failure. These lesions rarely present as asymptomatic hepatomegaly, simulating a primary hepatic malignancy. These lesions may also simulate a primary or secondary hepatic malignancy on cross-sectional imaging or angiography. Scintigraphic evaluations with technetium-99m-labeled red blood cells offers an accurate method of identification of these lesions, and allows differentiation from other common primary or secondary hepatic masses in infancy or childhood. This scintigraphic method may also be used to follow these patients after medical, radiation, or embolization therapy. Experience with seven patients with these tumors is reported and compared with eight children with other primary or secondary liver tumors also evaluated by this method.

J NucíMed 28:1412-1418,1987

H. i.emangiomatous lesions of the liver occurring in hood. The utilization of [99mTc]RBCalso allows a rel infancy and childhood include capillary hemangioma atively noninvasive method of sequential monitoring and infantile hemangioendothelioma (1-3). These tu of these patients during courses of therapy including mors are histologically benign, but may cause intracta therapeutic embolization of these lesions (12). ble high output cardiac failure because of marked vas cular shunting through the lesion (4). These lesions MATERIALS AND METHODS may be solitary or multiple throughout the entire liver (3,5). They may occasionally be mistaken for primary Fifteen children (nine males and six females) aged 2 days or secondary malignant involvement of the liver (3,6, to 8 yr presenting with hepatomegaly were evaluated with 9). This is particularly true of those solitary mass lesions [99mTc]RBCs.Seven children had vascular origin lesions of that present without an associated congestive heart the liver, including three with multiple (infantile hemangioen failure (3). It is of paramount importance to correctly dothelioma) and four with solitary (capillary hemangioma) identify these hemangiomatous lesions of the liver, as lesions. The three patients with multiple or multicentric le open or closed biopsy of these lesions may lead to sions all presented with congestive heart failure and palpable uncontrolled hemorrhage and has been reported to be hepatomegaly while the solitary lesions all presented as asymp fatal (10,11). Evaluation of these patients with techne- tomatic palpable abdominal masses or hepatomegaly. The tium-99m- (99mTc)labeled red blood cells (RBC) allows other lesions evaluated by this method include nodular hyper- plasia of the liver (four children), hepatoblastoma (one child), correct identification and accurate differentiation from metastatic neuroblastoma (two children), and mesenchymal other benign or malignant lesions of the liver in child- hamartoma (one child). All the nonhemangiomatous lesions were proven by biopsy or surgical removal. The vascular origin lesions were confirmed clinically. Twenty-six [99mTc]RBC Received Aug. 22, 1986; revision accepted Mar. 25, 1987 studies were conducted on this group of patients. In addition, For reprints contact: John H. Miller, MD, Head, Div. of there were 45 ultrasound (US) evaluations, 30 [99mTc]sulfur Nuclear Radiology, Childrens Hospital of Los Angeles, 4650 colloid (SC) hepatic-splenic scintigraphic examinations, five Sunset Blvd., Los Angeles, CA 90027. hepatobiliary studies utilizing [99mTc]iminodiacetic (IDA) Presented in part at the 9th Annual Western Regional Scientific Program of the Society of Nuclear Medicine Meeting, Monterey, derivatives, three isotopie skeletal examinations, ten com CA October 11-14, 1984. puted tomographic (CT) examinations with contrast enhance-

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Volume 28 •Number 9 •September 1987 1413 ment and 11 angiograms, performed. Two patients with he- or CT) procedures, were compared to both the heart blood mangiomatous liver lesions were evaluated with [""TcJRBCs pool and the surrounding uninvolved hepatic parenchyma to prior to and following angiographie embolization therapy. assess relative vascularity. Lesions were then identified as The patient's RBCs were labeled utilizing either an in vivo being equal to the heart blood pool, equal to the liver, or or a modified in vitro method (13J4). A bolus of [""Te] greater than liver but less than the heart blood pool. Only RBCs was administered with a dose of 0.280 mCi/kg to a those lesions that had ["TcJRBC activity equal to that of the maximum of 18.0 mCi. A three-phase technique was utilized heart blood pool were considered to be hemangiomatous with 3-sec dynamic scintigraphy immediately followed by a lesions of the liver. postinjection 300,000-count static scintiphoto to assess early labeled blood-pool activity within the lesion. After allowing a period of 10 to 20 min for equilibration, static 300,000-count RESULTS scintiphotos of the liver were then acquired in various views. The results of the initial evaluation of the 15children In every patient with a hemangioma, scintiphotos of the head, are given in Table 1. In all children with multiple thorax, abdomen, and proximal extremities were obtained. In all patients an anterior scintiphoto of the chest and upper vascular lesions (infantile hemangioendothelioma), per abdomen was obtained in order to allow a direct comparison fusion of the lesions was identified on dynamic scintig between the [""Te] RBC within the cardiac chambers (heart raphy. On the immediate postinjection static blood- blood pool) and the hepatic lesions. The hepatic lesions, pool scintiphoto, activity persisted within the lesion and localized by reference to antecedent imaging ["TcJSC, US, was present on delayed static scintiphotos (Fig. 1) as

B

FIGURE 1 Infantile hemangioendothelioma (Pa tient 2). Transverse anterior US (A) of the liver reveals multiple hypo- echoic masses (arrows) distributed throughout both lobes of the liver. Anterior [""TcJSC static scintiphoto (B) reveals multiple focal voids throughout both lobes of the liver. Immediate anterior ["mTc]RBC post- injection scintiphoto of the torso (C) reveals abnormally increased inho- mogeneous activity throughout the liver; heart (H), renal activity (R). Sub sequent anterior static [""TcJRBCs scintiphoto (D) reveals multiple focal areas equal in intensity to the heart blood pool (H). Correlation with the ["TcjSC scintiphoto reveals that areas devoid of activity (arrowheads) are now seen to have increased ac tivity (arrowheads).

1414 Miller The Journal of Nuclear Medicine ''*

*

B C FIGURE 2 Capillary hemangioma (Patient 6). Transverse US (A) reveals a solid mass arising from the left lobe of the liver (arrows) which is of less echogenicity than the immediately adjacent uninvolved hepatic parenchyma. Anterior ["mTc]RBC perfusion scintiphoto (B) reveals the presence of a hypervascular mass (arrows) in the left abdomen. Anterior ["Te] RBC static scintiphoto (C) reveals a large vascular lesion (arrows) arising from the left lobe of the liver (L), with activity equal to the heart (H). well. In all individuals with large solitary vascular le was seen. In one patient, a large homogeneous lesion sions (capillary hemangioma) increased perfusion was immediately developed a large central photopenic de seen on dynamic scintigraphy. In all but one patient, fect (Fig. 3) that subsequently underwent involution activity was equal to the heart blood pool on the im following the embolization therapy. mediate postinjection static scintiphoto (Fig. 2). All In this group of patients with hemangiomas of the these individuals had activity equal to the heart blood liver, there were no false-negative examinations nor pool on delayed static scintiphotos. were there any false-positive examinations. In other In two patients with hemangiomas who were evalu words, no patients were encountered who had lesions ated with [99mTc]RBCs prior to and following angio with activity equal to that of the heart blood pool on graphie embolization therapy, diminution of lesion size delayed static scintiphotos who did not have heman-

FIGURE 3 Capillary hemangioma treated by an giographie embolization therapy (Pa tient 5). Anterior [TcJRBC scinti photo (A) reveals a vascular lesion (arrows) arising in the left lobe of the liver. Anterior [""TcJRBC scintiphoto (B) following arterial embolization now reveals a large central photo penic defect (arrow) in the lesion. Subsequent examinations revealed B complete absence of this lesion.

Volume 28 •Number 9 •September 1987 1415 giomatous lesions of the liver. In addition, no patients equal to that of the heart blood pool. However, several with lesions who had activity less than that of the heart individuals with lesions other than a hemangioma (Pa blood pool were subsequently shown to have heman- tients 8, 14, 15) did have lesions with increased [99mTc] giomas of the liver by other imaging modalities, surgical RBC activity as compared with the surrounding liver specimen, or autopsy. Evaluation of the patients with parenchyma, but none were equal to the heart blood vascular lesions by CT (Patients 5 and 7) was less pool in activity. In every instance, these liver lesions valuable as tumor could not be excluded on the basis were clearly differentiated from those of hemangioma of the CT findings. In the nonhemangioma group of tous origin. This method allowed the accurate differ patients, especially those with malignant disease, CT entiation of capillary hemangioma/infantile heman- was valuable in both identifying nature and extent of gioendothelioma from those lesions that are the major the liver lesion. differential concern in infants and children: hepatoblas- toma, metastatic neuroblastoma, nodular hyperplasia (Fig. 4), and fibrovascular hamartoma. However, as DISCUSSION biopsy of the hemangiomatous lesions is contraindi- Previously, the diagnosis of a hemangioma of the cated, the distinction between the vascular origin lesions liver in an infant or child was based on a combination is based on clinical presentation and imaging studies: of imaging findings (6), especially scintiangiography multiple liver lesions associated with heart failure in performed at the time of administration of [WmTc]SC infantile hemangioendothelioma and a solitary liver (4,6J5). The characteristic findings were that of in lesion causing hepatomegaly in capillary hemangioma. creased flow on dynamic scintigraphy and photopenic Based on this experience with hemangiomatous le areas or voids within the liver parenchyma on delayed sions of the liver in infants and children, it appears that static scintiphotos. However, there was potential for these lesions have significantly different characteristics overlap of these scintigraphic findings with other lesions from those previously reported in adult patients (18, that have pronounced tumor vascularity and focal de 21). The reported experience in adult patients is one of fects on the delayed [99mTc]SC scintiphotos (15,16). a predominantly hypovascular process being seen on Often, angiography was necessary for confirmation of dynamic scintigraphy with only minimal to no activity the presence of a hemangiomatous lesion ( 74, / 7). How being identified on the immediate postinjection static ever, there could be overlap of the angiographie ap scintiphoto but with appearance of considerable activity pearance of these lesions with primary hepatic malig in the lesion within several hours. This delayed appear nancies (17). Several patients (Patients 8, 11, 14, and ance in these lesions has been likened to the same 15) who did not have hemangiomatous liver tumors phenomenon which may be observed on contrast en and were evaluated by [WmTc]RBC had lesions which hanced CT in adult patients (22-25). A qualitative were seen to have increased perfusion on dynamic difference between vascular origin tumors in infants scintigraphy (Table 1). In none of these individuals, and children and those seen in adult patients is that of however, was activity seen in the lesion on either im clinical presentation. Adult lesions are never implicated mediate postinjection or delayed static scintiphotos as a cause of congestive heart failure and are often

FIGURE 4 Nodular hyperplasia (Patient 13). An terior [99mTc]SC perfusion scinti photo (A) reveals increased perfusion to a focal lesion (arrows) in the mid- portion of the liver. Anterior ["mTc] RBC static scintiphoto (B) reveals an area (arrows) of increased activity as compared with the remainder of the liver. Activity in this region is greater than that of the surrounding liver but is not equal to that of the heart blood pool. B

1416 The Journal of Nuclear Medicine detected incidentally during the course of the evaluation tigation of hepatic tumors in childhood. Radiology of the liver for other reasons (11,18-25). Lesions in 1977; 124:451-458. 7. Kaude JV, Felman AH, Hawkins IF. Ultrasonography children also spontaneously regress and/or are respon in primary hepatic tumors in early childhood. Fed sive to steroid therapy in the majority of instances (4, Radial 1980; 9:77-83. 12,16). 8. Mac Pherson RI, Saldana JA, Cone RM, et al. Primary Evaluation of the liver utilizing [99mTc]RBChas a liver masses in infants. CañadAssoc Radial 1981; 32:81-87. number of advantages in the pediatrie patient. This 9. Abramson SJ, Lack EE, Teel RL. Benign vascular procedure is relatively noninvasive, there is virtually no tumors of the liver in infants: sonographic appearance. risk of an untoward reaction, and in the majority of Am J Roentgenol 1982; 138:629-632. instances no patient sedation is required. This proce 10. Kassner EG, Friedman AP. Liver masses. In: Haller dure has been well tolerated by patients and is well JO, Shkolnik A, eds. Clinics in diagnostic ultrasound: ultrasound in pediatrics. New York: Churchill Living accepted by parents, who are often concerned by the stone. 1981:80-97. technical aspects of angiographie evaluation of these 11. Kato M, Sugawara I, Okada A, et al. Hemangioma of lesions. This procedure can be performed on an out the liver: diagnosis with combined use of laparoscopy patient basis and is well suited to sequential utilization. and hepatic arteriography. Am J Surg 1975; 129:698- The total-body radiation dose is between 100 and 400 704. mrad (0.020 rad/mCi) (26-28). Often this technique 12. Stanley P, Grinnell VS. Stanton RE, et al. Therapeutic embolization of infantile hepatic hemangioma with has been performed on critically ill patients utilizing a polyvinyl alcohol. Am J Roentgenol 1983; 141:1047- portable gamma camera. Also in those patients with 1051. congestive heart failure, there is no risk of volume 13. Pavel DG, Zimmer AM, Patterson VN. In vitro label overload or contrast injury to hypoperfused kidneys ing of red blood cells with Tc-99m: a new approach to blood pool visualization. J NucíMed 1977; 18:305- from this procedure. 308. The initial evaluation of an infant or child presenting 14. Callahan RJ, Froelich JW, McKusick KA, et al. A with either clinical findings of a hemangiomatous liver modified method for the in vivo labeling of red blood lesion or asymptomatic hepatomegaly and/or a palpa cells with Tc-99m: concise communication. J Nucí ble upper abdominal mass should be with ultrasound Med 1982; 23:315-318. 15. Gates GF, Miller JH, Stanley P. Scintiangiography of (6,29). If the ultrasonographic appearance suggests that hepatic masses in childhood. JAMA 1978; 239:2667- of a hemangiomatous lesion (5), the next evaluation should be with [99mTc]RBCs.When increased perfusion 2670. 16. Sty JR, Starshak RJ, Miller JH. Gastrointestinal nu and activity equal to the heart blood pool is identified clear medicine. In: Sty JR, Starshak RJ, Miller JH. in a liver lesion in a child indicating a hemangioma, no Pediatrie nuclear medicine. Norwalk: Appleton-Cen- tury-Crofts, 1983: 53-82. further evaluation is indicated as no other liver lesion 17. Stanley P, Miller JH. Hepatic arteriography. In: Stan has this appearance. In the majority of patients, CT will ley P, Miller JH, eds. Pediatrie angiography. Balti not be utilized as the combination of US and [99mTc] more: Williams and Wilkins. 1982: 179-213. RBCs in the appropriate clinical setting will be diag 18. Good LI, Alavi A, Trotman BW, et al. Hepatic he nostic. mangiomas: pitfalls in scintigraphic detection. Gastro- enterology 1978; 74:752-758. 19. Engel MA, Marks DS, Sandier MA, et al. Differentia tion of focal intrahepatic lesions with Tc-99m-RBC imaging. Radiology 1983; 146:777-782. 20. Rabinowitz SA, McKusick KA, Strauss HW. Tc-99m REFERENCES red blood cell scintigraphy in evaluating focal liver 1. Landing BH. Tumors of the liver in childhood. In: lesions. Am J Roentgenol 1984; 143:63-68. Okuda K, Peter RL, eds. Hepatocellular carcinoma. 21. Front D, Israel O, Groshard D, et al. Technetium- New York: John Wiley and Sons, 1976: 205-206. 99m-labeled red blood cells imaging. Semin NucíMed 2. Witzlehen C. Liver. In: Rissane JM. Pathology of 1984; 14:226-250. infancy and childhood. St. Louis: C. V. Mosby, 1975: 22. Freeny PC, Vimont TR, Barnett DC. Cavernous he 267-308. mangioma of the liver: ultrasonography, arteriog 3. Dachman AH, Lichtenstein JE, Friedman AC, et al. raphy, and computed tomography. Radiology 1979; Infantile hemangioendothelioma of the liver: a radio- 132:143-148. logic-pathologic-clinical correlation. Am J Roentgenol 23. Itai Y, Furui S, Araki T, et al. Computed tomography 1983; 140:1091-1096. of cavernous hemangioma of the liver. Radiologv 4. 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Volume 28 •Number 9 •September 1987 1417 134:439-447. tion No. (FDA) 78-8044. 26. Loevinger R, Bennan M. MIRO Pamphlet 1(revised). 28. Srivastava SC, Chervu LR. Radionuclide labeled red A revised scheme for calculating the absorbed dose of blood cells: current status and future prospects. Semin biologically distributed radionuclides. New York: The NucíMed 1984; 14:68-82. Society of Nuclear Medicine, 1978. 29. Miller JH, Greenspan BS. Integrated imaging of he- 27. Kereiakes JG, Feller PA, Ascoli FI, et al. Pediatrie patic tumors in childhood, part I: malignant lesions radiopharmaceutical dosimetry, 1976, HEW Publica- (primary and metastatic). Radiology 1985; 154:83-90.

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