大韓放射線醫쩡왕註‘ 第 24 卷 第 5 ytt pp. 911 - 919, 1988 Journal of Korean Radiological Society, 24(5) 911-919, 1988

X @ His ti ocytosis 뼈 of Bone Scintigraphy 빼 Lu

Seoung Oh Yang, M.D. , Eun Mi Koh, M.D. , Myung Chu\ Lee, M.D. , Chang-Soon Koh, M.D. , In One Kim, M.D:, Kyung Mo Yeon, M.D: Department of Nuclear Medicine and Pediatric Radiology: Seoul Na tional University Hospital

〈국문초록〉

원인 불명성 조직구 증식증의 콜스캔 소견과 방사선학적 소견의 비교

서 울대학교 영원 핵의학파

앙승오 · 고은 미 · 이 명 철 · 고창순

서울대 학교 소아뱅원 방사선과 김 인 원 · 연 7~= 모

골 스캔파 방사선학석 검사를 함께 얻 을 수 있었띤 30예의 원인 불영성 조직구 증식증 환자에서 종래 에 보고된 바 있는 골 스캔의 비교적 낮은진단적 정확도 (50% 내외 ) 의 진위와 이 질환에서의 골 영밴의 양상파 분포를 알기 위 하여 후향적 분석 을 시 도하였 다. 대상으로 한 30 예의 연령분포는 1 47>> 월에서 45 세 였고 ， 펑균 9 . 3세， 20 대 이상의 4 예 를 제외하연 26예 가 14세 이하였마. 단일 골 영변이 1 5 예， 마말성 골 병변이 12 예， 정상이 3예이었고， 41 개 해부학석 영 역과 90 개 이상의산술적 영소를 판찰하였￡며， 이들의 분포양상은 두개골 ( 11/4 1)， 대퇴골 (7/4 1)， 척추골 (6/ 4 1)， 늑골， 하악골 등의 순서 를 냐타내였마. 땅사선학석 소견과 비교한 골 스캔의 예인도는 85% 로서 과거의 보고와는 상당한 차이가 있었고 골 스캔으로 경과 추적을 시행한 7 여)에서는 2 내지 20 개월에 치료에 짜른 골 맹소의 정상화를 볼 수 있었다. 골스캔은감마차메라의 해상력과땅사성 표지 화합물의 효율이 향상되고 ， 판성 부위에 대한확대 영 상 둥을 이용함에 짜라서 원인 불명성 조직쿠 증식증의 진단과 경파추석에 제한된 부위의 방사선학적 검사와 더불어 유용한 검사라고 할 수 있 다 .

A retrospective anal ysis of concurrent bone scintigraphs and rad iographs of 30 patients with histologically confirmed histiocytosis X was carri ed out to assess the pattern and distri bution of bone les ion and the sens itivity 。 f bone scintigraphy with reference to skeletal radiography. Totals of 41 regional and over 90 numeric bone lesions were found in all patients. Singl e bone lesions were seen in 15 patients and multiple lesions in 12 patients Three patients had not revealed bone lesion. Distribution of lesions was skull, vertebrae, fem ur, ribs, mandibl e and the like, in the o rder of decreasing frequency. Unlike previo us citations, th e sensitivity of bone scan was

relatively as high as over 85% and it showed two lesions of sk 비 I and cl avicle whi ch escaped from rad iologic detection. lmprovement of mechanical resolution and bone-seeking radiopharmaceuticals made it possible to detect bone lesions in histiocytosis X more accurately than previous decade. Bone scintigrap hy could be the

이 논운은 1 988 년 8 월 31 일에 접수하여 1 988 년 9월 8 일 에 채택되었음 Received August 31 , Accepted September 8, 1988 - 911 - 大韓放射線醫學會誌 : 第 24 卷 第 5 號 1988 -

effective, helpful diagnostic procedure in the initial diagnosis as well as convenient follow-up method in histiocytosis X.

Key Words: Histiocytosis X, bone scintigraphy, radiography.

u Histiocytosis X was introduced by Lichtenstein l R ·께 ” ·- ” nM ·빼 • l ’ ” ” 매미“ 매 씨“ u 때t , nu u” ‘“ “” 삐 ” •• in 1953 to describe a clinical-radiologic-pathologic a complex, which includes a spectrum of conditions 80 that range from the benign eosinophilic granuloma through more disseminated chronic Hand-Schu­ ller-Christian disease to the acute fulminating type 1 of Letterer-Siwe disease •2l . Radionuclide studies using bone-seeking radiopharmaceutical agents are an important and accepted method for documenting the presence and extent of skeletal involvement in a variety of disease processes. But 10 20 30 40 50 bone scintigraphy had proved to be less sensitive ACE IYEARS I than radiography in the detection of osseous le­ Fig. 1. Age and sex distribution. Mean age among the 0-10 children is 4.3 years 01 age sions in histiocytosis X with disappointing 3 7 results - ). However, with recent mechanical and gamma cameras(Picker Dyna 415, ON 410 and radiopharmaceutical refinements, its sensitivity of Siemens Rota/ZLC 75). Liver scans with 99m detecting bone lesions in histiocytosis X has in­ Technetium-sulfur colloid were done in 4 patients creased to over 80% with additional usefulness in and follow-up bone scintigraphy after therapy in 7 the follow-up of the therapeutic response of the patlents. disease8•9) . Only 3 of the 30 patients had radiographic In this analysis, we collected pathologically-pro­ skeletal surveys, others had radiographs of clinical­ ven patients whose bone scintigraphs and radio­ ly or scintigraphically abnormal areas. Computed graphs were available from 1981 to June 1988 at tomography(CT) of head was done in 6 patients the Seoul National University Hospital and Chil­ and magnetic resonance imaging(MRI) in 2 pa­ dren’s Hospital. The purpose of this report is to tients to find intracerebral lesion. In one patient assess the distribution and pattem of bone lesions with irregular skull defect with mass formation, and the relative sensitivity and role of bone scin­ carotid angiography was performed to know the tigraphy and radiologic methods. vascularity. The clinical symptoms and signs at the initial Materials and Methods admission are shown in Figure 2. Overall regional and cumulative counting of bone lesions was done Thirty patients with an age range from 14 according to the results of bone scintigraphs and months to 45 years had been studied by bone radiographs. scintigraphy and radiography before pathologic di­ agnosis was made(Fig. 1). Results All had a 99m Technetium-Methylenedipho­ nate(MDP) bone scintigraphy using scintillation Twenty-seven patients had bone involvement,

- 912- - Seoung Oh Yang, et al Hi stiocytosis X: Comparison of Bone Scintigraphy and Rad iog raph y fifteen of which had single bone lesion, while 12 single lesions was missed on bone scintigraph and had multiple lesions. Table 1 and Figure 3 show radiograph. Of 26 multiple anatomic lesions, 5 the distribution of the bone lesions in single and lesions were missed on bone scintigraphs and one multiple involvement as well as regional and clavicular lesion was positive on bone scintigraph numeric distribution. A total of 91 bone lesions before radiograph became abnormal. Two patients (mean: 3) was found with the 41 regional distribu­ with multiple small punched--{)ut skull defects and tion(mean: 1.4 anatomic region). Each four pa­ no evidence of marginal sclerosis or beveled edge tients over 20 years of age had single bone lesion showed no scintigraphic abnormality of skull(Table at ribs in 2, skull and scapula in 1. One out of 15 2).

Symptoms and Signs

Growth retadolioo Skin rosh ~ Hepolosplencmegoly SINCLE Arl emio Fever MULTlPLE Ddletes Ì1 sipidus 훌훌훌훌- Tooth k::ss N 。 RMAl Otameo Ex∞hthctn ∞ SpÎ1e defamily Lmping f.'oss Pa Î1

o 2 4 6 8 10

CA또 t'U.ffR

Fig.2. Symptoms and signs of hi stiocytosis X according to the pattern 01 bone lesion.(s ingle: 15, multiple: 12 , normal: 3)

Table 1. Regional and Cumulative Numeric Distribution of Bone Lesions

Single Multiple (N= 12) Regional Num eric (N=15) Regional Num eri c Total Total 4 ?‘ 갱 --41 % S kull 1 「 U 6 U Vertebrae hu 4 。 4 7 8 Femur J 2 ηJ 5 5 7 Ribs o nJ 6 3 6 Mandible o nJ 3 3 3 Clavicle l 1i 1 2 2 Pelvic bone 1 nu o 14 1 Scapula 1 nu o 1 1 Humeru s 4 1 nu o 1 l Metacarpal bone i 0 1i 1 - l Tibia

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Table 2. False Negative Bone Scans and Radiographs

Single Bone Lesion(15) Multiple Bone Lesion(l2) Location Bone Scan Radiograph Bone Scan Radiograph

Skull 2 0 Femur 0 0 0 Clavicle 0 0 Tibia 0 0 0

Numerical discrepancies were encountered important complementary role to delineate the ex­ mainly at calvarium with multiple small lytic le­ tent of soft tissue invasion(Fig. 5). Blood flow sions without sclerotic rim on radiographs, but study with radioisotope was done in one case of there were some evidence of cold defects or sur­ skull defect which showed hyperemia at blood rounding rim of increased uptake(Fig. 4) . On CT, pool phase and cold lesion surrounded by rim of low density lytic lesion was seen in the diploic increased activity at delayed image(Fig. 6). Vari­ space of the skull with rather smooth margin. In ous locations of bone involvements were demons­ one case of right retrobulbar lesion, CT was of trated in Figure 7. With the exception of sk 비 I and mandible, pattern of bone scintigraphic uptake was usually augmented. Seven patients had foll­ RaalonoJ. ~rlc ow-up bone scintigraphy, and all abnormal uptake "".“‘、-’“‘)

11(26.8) >‘’(53.8) lesions became normalized in 2-20 months after therapy. Two patients had evidence of hepatosple­ 3(7.3) 6 “-‘) nomegaly on liver scan. In one patient with symp­ 3(7.3) 3(3.3) 1< 2.‘ 1(‘ .1) tom of central diabetes insipidus, MRI detected 5(12.2) 7(7. 7) suprasellar infiltrative lesion with good anatomic 1(2.‘) “‘-‘) depiction but no specific diagnosis of histiocytosis 6(1 •. 6) 12(13.2) X was made preoperatively(Fig. 8).

2(‘-’ 2(2.2) Discussion

1(2.‘1(1.1)

The lesions grouped collectively as histiocytosis

7 (17. 1) 8(8.8) X are usually discovered by radiological investi­ gation of a mass or painf비 area within bone. In the presence of destructive bone lesions on radiographs, it is relatively characteristic if not

1(2.‘ i ‘(‘.1) pathognomic of histiocytosis X to appear on bone scintigraphy as areas of decreased or incre­ ased uptake 1,2,6). Large lesions in particular will appear as cold area. Some will present as pho­ Fig. 3. Anatomic di stribution of histiocytosis X clas. ton deficient areas, sometimes with a rim of in­ 9 sified into regional and numerical number creased activity around them ). In this series,

- 914- - Seoung Oh Yang, et al. : Histiocytosis X: Comparison 01 Bone Scintigraphy and Radiography -

AI-“ - “ * ‘ :;; #~ζ셔앙치1ν· ‘ B

、‘

..,.,...

I D

Fig. 4. Skull lesions of histiocytosis X A & B. Cold lesions with rim and correspond ­ ing osteolyti c les ions C & D. Decreased activity at mandible(arr­ ows) and frontal bone(open arrow) and cor­ responding lytic lesions. Some numeric di f­ ferences are shown C

pure cold defects on bone scintigraphy were Ii­ with limited radiographic survey of clinically sus­

mited at skull and mandibular large oste이 ytic le­ pected area. Active early lesions of histiocytosis X sion. It is known that bone scintigraphy is more can appear positive on bone scintigraphy while lO effective in localizing involvement of ribs, spine, radiographs are normal ). And this procedure can and pelvis. Bone scintigraphy is complemented tell us wheather the lesion is single or multiple and

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B

Fig. 5. Five-year-old girl with exophthalmos A. Coronal CT shows well-marginated right retrobulbar soft tissue density mass with benign nature B. Bone scintigraph shows increased activity around the right orbital region

?

A B C Fig. 6. Thirteen-year-old boy with toothache and fever A. Small ovoid low density lesion is seen in the diploic space of the right temporal bone B. Blood pool image shows hot up take at the same site C. Delayed image shows central cold defect with surround ing rim of increased activity the early response of the lesion after treatment tigraphic sensitivity in detecting histiocytosis X including surgery and che motheraphy. should be reconsidered in accordance with de­ Although bone scintigraphy is generally more velopment of mechanical devices and effective sensitive and become positive prior to radiographs radiopharmaceuticals. And it is still imperative in bone lesions, their use in histiocytosis X has that high resolution or magnification image of spe­ been in dispute3-7.11) Previous report of poor scin- cific sites should be obtained to improve diagnostic

- 916- - Seoung Oh Yang, et al.: Histiocytosis X: Co mparison 01 Bone Scintigraphy and Rad iography -

Fig. 7. Various locations of bone involvement A. A well-circum scribed osteolytic lesion at ilium with differential destruction and be­ veling of the medial margins B. Slightly extensive hot activity at the same lesion of A C. A 45-year-old man with C. c. of chest mass shows purely Iytic lesion and hot activity at left 1st rib D. A 2-year- old infant with hand swelling. Ex pansile lesion with inner sequestra at 3rd metacarpal bone E. A 2-year-old infant with spine deformity Characteristic shape of vertebra plana and increased uptake(arrows) of L1

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the equipment and technique used. The distribution of bone lesions in our series was not dissimilar to the literature in the order of skuIl, spine, femur, and ribs1,2,9,12). More single lesions were seen in our seires compared to the findings of Schaub et al. If one excludes the four adult patients of single bone lesion, the pattern would be similar to their children’s series. The ratio of male and female was 2:1 in our series same as Senac’s series. Liver scans can give information about hepatos­ plenic involvement and additional pulmonary up­ take of sulfur colloid by increased phagocytic func­ tion in the lungs. CT is preferred in the assess­ ment of CNS, orbital and mastoid lesions can be precisely distinguished from intracranial lesio- ns 13.14)-- '- ., The detailed information in the hypothalamic Fig. 8. Coronal and sagittal sections 01 T 1-weighted and sella region would be obtained much better by MR I 01 a 6-year-o ld male inlant show thick­ MRI, thus the application of MRI in histiocytosis ened suprasellar pituitary stalk with sli ghtly X will expand. low signal intensity(arrows). Preoperative di ­ ag nos ls was germl noma The indication for a diagnostic procedure to in­ dividual case is determined by the prognostic value accuracy. Table 3 lists the sensitivity of bone scin­ of the suspect pathologic findings and the c1inical tigraphy in comparison to radiography according necessities. Although recent studies stress the self to the Iiterature. As many bone lesions of histiocy­ Iimited course of the diseaseI5), an initial work-up tosis X are purely osteolytic without evident is done by bone scintigraphs and radiographs of osseous reaction, a certain percentage of cold and c1 inicaIly suspect areas to identify possible hidden false negative lesions has to be expected in bone orthopedic and neurologic sequelae in scintigraphy. False negative lesions on bone scin­ children 16,17). The follow-up of single lesions after tigraphy can be explained by their size and the surgery can be done by radiographs. However it absence or presence of normal bone. Other factors should be kept in mind that a patient presenting in f!uencing the sensitivity of bone scintigraphy are with single lesion initially, can develop other

Table 3. Sensitivity 01 Bone Scan in Hi stiocytos is X acco rding to Literature

Lesions on Authors Patients X- ray sensitivity Bone Scan Sensitivity

Sidd iqui et al. (6) 21 95% 63% Kumar et al.(3) 7 92% 72% Schaub et al. (9)' 20 98% 84% Yang et al 30 95% 85% • Radiographs of clinical and/ or scintigraphi c suspect area

- 918- - Seoung Oh Yang , et al.: Hi stiocytosis X: Com pari son of Bone Scintigraphy and Rad iog raphy

9 bone lesions later ). In case of multiple lesions eosinophilic gran uloma. Ann Intern 1νed 89:289, follow-up bone scintigraphy will show the effects 1978 of the treatment as well as the appearance of new 8. Westra SJ , Van Woerden H, P os tm a A et al lesions. Bone scintigraphy proved of much benefit R adionuclide bone scintigraphy in patients with to the diagnosis of bone lesions in histiocytosis X histiocytosis X. EurJ Nucl M ed 8:303-306, 1983 along with appropriate radiologic examination. 9. Schaub T , Ash JM, Gilday DL: Radionuclide imag­ ing in histiocytosis X. P ediatr Radiol 17:397-404, 1987 REFERENCES 10. Freeman LM: Freeman and Johnson ’'s Clinical R adionuclide lmaging 3rd Ed Vol 1:349-350, l. Mirra JM: Bone Tum ors: Diagnosis and Treatment p.376'388, ].B. Lippincott Company, Philadelphia, Grun e & S tratton. New York. 1984 1980 1l. Gilday DL, Ash JM, Reilly B]: R adionuclide 2. Wilner D: Radiology of Bone Tumors and Allied sk eletal survey for pediatric neoplasms. Radiology Disorders. Vol 2.1329'141 8, W. B. S aunders, Ph" 123. 399-406. 1977 12. Senac MO, Isaacs H, Gw inn JL: P rimary lesions of ladelphia, 1982 3. Kumar R, Balachandran S: R elative roles of bone in the 1st decade of life: retrospective survey radionuclide scanning and ra diographic imaging in o f biopsy resu1ts. Radiology 160:4 91-495, 1986 eosinophilic granuloma. Clin Nucl Med 5:538'542, 13. Cunningham MJ , Curtin HD , Butkiewicz BL: His 1980 tiocytosis X of the temporal bone: CT findings. ] 4. Parker BR, P inckney L , Etcub anas E: R elative Comput Assist Tomogr 12:70-74, 1988 effi cacy of radiographic and radionuclide bone sur. 14. S mi th RJH , Evans JNG : Head and neck manifesta vey s in th e detection of th e sk eletal lesions of his tions of histiocytosis X. Laryngoscope 94:395-399, tiocytosis X. R adiology 134:377'380, 1980 1984 5. Antomattei S , Tetalman MR, Lloyd T V: The mul­ 15. Sartoris DJ , Parker BR: Histiocytosis X: rate and tiscan appearance of eosin ophilic granuloma. Clin pattern of resolution of osseous lesions. Radiology N ucl Med 4.'53-55. 1979 152.679-684, 1984 6. Siddiqui AR , T ashjian JH , Lazarus K et al: N uclear 16. Zinkh am WH : Multifocal eosinophilic granuloma, medicine studies in evalu ation of skeletallesions in natural history, etiology and management. Am ] children with histiocytosis X. R adiology M ed 60:45 7- 463, 1976 140:787-789, 1981 17. Lucaya ]: Histiocytosis X. Am ] Dis Child 7. Eil C, Adornato BT: Ca ution on bon e scans in 121289-295, 19 71

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