Lipoblastoma with aberration in the long arm of chromosome 8

Lipoblastoma with aberration in the long arm of chromosome 8

J Orthop Sci (2000) 5:407–410 Lipoblastoma with aberration in the long arm of chromosome 8 Hiroshi Orui1, Akira Ishikawa1, Chikako Kanazawa2, Michihi...

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J Orthop Sci (2000) 5:407–410

Lipoblastoma with aberration in the long arm of chromosome 8 Hiroshi Orui1, Akira Ishikawa1, Chikako Kanazawa2, Michihiko Katsuura2, and Toshihiko Ogino1 1 2

Department of Orthopaedic Surgery, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan

Abstract We report a case of lipoblastoma in a 6-month-old girl with a new chromosomal aberration, 46, XX, der (2) add (2) (p23) del (2) (q33), add (8) (q1?). In addition to the patient’s age and pathological features, aberration of long arm of chromosome 8 in lipoblastoma can assist the differential diagnosis from myxoid or well differentiated liposarcoma. Key words Lipoblastoma · Shoulder · Cytogenetics · Liposarcoma

Introduction Lipoblastoma is a rare, benign, adipose tissue tumor usually seen in infants and young children. In some patients, its radiological and histological findings mimic those of myxoid or well differentiated liposarcomas.7 Chromosomal analysis has been introduced to differentiate these kinds of confusing cases.5 This method may have some usefulness in differentiating lipoblastoma from lipomatous sarcoma.

Case report A 6-month-old Japanese girl presented with a softtissue mass in her right shoulder girdle in June, 1996. Physical examination on presentation revealed an elastic soft, non-tender mass 4 cm in diameter in the anterior side of the left shoulder girdle. Neither lymph node enlargement nor hepatosplenomegaly was noted. Results of laboratory tests were within normal limits. A computed tomographic scan demonstrated a well demarcated, fat-density mass with a soft-tissue density

Offprint requests to: H. Orui Received: September 16, 1999 / Accepted: December 17, 1999

in the central area, which was enhanced with contrast material, in the anterior part of the left shoulder girdle. Magnetic resonance imaging revealed a well demarcated mass, which compressed the pectoralis major and deltoid muscles and protruded into the subcutaneous fatty tissue (Fig. 1). The mass showed the same signal intensity as fat tissue on T1- and T2-weighted images, except for the central area (Fig. 1a,c). The central area showed the same signal intensity as muscle on the T1weighted image and a higher signal intensity than fat tissue on the T2-weighted image (Fig. 1a,c). The central part of the tumor was enhanced with gadoliniumdiethylenetriamine pentaacetic acid on fat-suppression T1-weighted images (Fig. 1b). An open biopsy was performed in July, 1996, and a pathological diagnosis of lipoblastoma was made. Part of the specimen was submitted to chromosomal studies. Resection was performed, with a marginal procedure, in September, 1996. On gross examination, the specimen was a 4 3 4 3 3 cm, encapsulated, yellowish-white, solid mass with an uneven, gyrus-like appearance (Fig. 2a). The cut surface showed yellowish-white, multilobulated fatty tissue surrounding a gelatinous stroma-rich central area (Fig. 2b) corresponding to the area enhanced with gadolinium on magnetic resonance imaging. Microscopically, the fatty tissue was encapsulated with thin fibrous tissue and separated by fibrous septa (Fig. 3a). Myxoid stroma was occasionally found, only in the fibrous tissue of the central area. Vascular proliferation was often evident in the fatty tissue. Multivacuolated lipoblasts were occasionally detected (Fig. 3b). Neither hyperchromatic nuclei nor atypical mitoses were found, and no invasion into the surrounding muscles was evident. Chromosomal analysis was performed. Tissue obtained from the tumor was minced and treated with 0.8% collagenase II (Worthington Biochemicals, Freehold, NJ, USA) for 3 h. The cells were suspended in RPMI 1640 medium supplemented with 20% fetal calf

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H. Orui et al.: Lipoblastoma with chromosome 8 aberration

c

a,b Fig. 1a–c. Magnetic resonance imaging reveals the tumor as a a high-signal intensity mass (arrow) with a low-intensity central area (arrowhead) on axial T1-weighted images (TR 460 ms, TE 9 ms), and b a low-signal intensity mass with a gadolinium-enhanced central area on fat-suppression axial

a

a

serum, and distributed in collagen-coated dishes. After 15 days of culture, the cells were treated with 0.1% colcemid for 12 h, and slides were G-banded by trypsin pretreatment. The karyotypes were expressed according to the International System of Human

T1-weighted image (TR 460 ms, TE 9 ms). c The mass shows high-signal intensity with a higher-intensity central area on axial T2-weighted image (TR 4280 ms, TE 105 ms). p, Pectoralis major muscle; d, deltoid muscle

b

Fig. 2a,b. Macroscopic findings show a 4 3 4 3 3-cm, encapsulated, yellowishwhite, solid mass with uneven, gyruslike appearance. b The cut surface shows yellowish-white, multilobulated fat tissue separated by fibrous tissue (arrowheads) surrounding a gelatinous stroma-rich central area

b

Fig. 3a,b. Microscopic findings show a the fatty tissue separated by fibrous septae (arrow). Vascular proliferation was often found in the fatty tissue (asterisk). b Multivacuolated lipoblasts were occasionally detected (arrow)

Cytogenetic Nomenclature.11 Eighteen metaphase cells exhibited an identical abnormal karyotype: 46, XX, der (2) add (2) (p23) del (2) (q33), add (8) (q1?) (Fig. 4). The remaining 10 cells showed a normal female karyotype.

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Table 1. Cytogenetic data of lipoblastomas reported in the literature Age of patient (months) 24 48 16 36 24 17 8 14 13 6

Karyotype [no. of cells]

Reference number

46,XY,t(7;8) (p22;q12)[7]/49,idem,18,19,112 46,XY,t(3;8)(q12;q11.2)[5]/47,idem,1mar[14]/46,XY[10] 46,XX,der(1)t(1;8)(p13;q22)t(7;8)(p22;q24.1)der(7)t(7;8)(p22;q13) t(1;8) (p13;q22),del(8)(q13q24.1),inv(9)(p11q21.1)[15] 46,XY,dir ins(6;8)(p25;q13q24.1)[25]/46,XY[6] 46,XX[30] 46,XY,der(14)t(8;14)(q11.2;q24)[18]/46XY[3] 46,XY,t(8;9)(q11–12;p22)[20]/46,XY[10] 46,XX,ins(8;6)(q11.2;q13q27)[8]/46,XX[12] 46,XY,t(7;8)(q31;q13)[18]/46,XY[2] 46,XX,der(2)add(2)(p23)del(2)(q33),add(8)(q1?)[18]/46,XX[2]

15 12 6

Fig. 4. Representative G-band karyotype of tumor cell with 46, XX, der (2) add (2) (p23) del (2) (q33), add (8) (q1?). Arrows indicate rearranged chromosomes

Three years after the excision, the patient had no evidence of recurrence or metastasis.

Discussion Lipoblastoma is a rare, benign, adipose tissue tumor usually seen in infants and young children. Jaffe,8 for the first time, used the term “lipoblastoma” for a tumor composed of immature adipose tissue. After the description by Vellios et al.,21 lipoblastoma was widely accepted as a distinct entity. However, its radiological and histopathological findings mimic those of myxoid or well differentiated liposarcoma.4 For the differential diagnosis of lipoblastoma, one of the most important factors is thought to be patient age. Chung and Enzinger2 reported that lipoblastoma or lipoblastomatosis occurred almost exclusively in children, with 88% of all cases occurring before the age of 3 years. However, lipoblastoma occurring in adults was occasionally reported.1,20 Further, as reported by Shmookler and Enzinger,18 among more than 2500 cases

6 6 17 3 9 14 Present study

of liposarcoma in the files of the Armed Forces Institute of Pathology, 17 cases had occurred in children ranging in age from 8 months to 15 years, with the youngest patient with liposarcoma in their report being an 8month-old girl. These reports suggest that patient age is not a definitive factor that can be used to differentiate liposarcoma from lipoblastoma. Although MR imaging is useful for the differential diagnosis of soft-tissue tumors, it is difficult to distinguish lipoblastoma from myxoid or well differentiated liposarcoma on MR imaging7 and on CT.10 Furthermore, it is occasionally difficult to distinguish lipoblastoma from liposarcoma microscopically. Lipoblastoma is composed of adipocytes at various stages of differentiation, ranging from stellate or spindle-shaped mesenchymal cells to univacuolar signet ring-like mature fat cells.4 These adipocytes show no cellular atypia. On the other hand, liposarcoma contains multivacuolar spider-cell-like lipoblasts showing features of nuclear atypia such as chromatin condensation and atypical mitoses.4 However, the differentiation of lipoblastoma from liposarcoma is occasionally difficult, because lipoblastoma also contains multivacuolar lipoblasts, and cellular atypia is often mild in well differentiated liposarcoma. Chromosomal analysis of only nine patients with lipoblastoma has been published since the report of Sandberg et al.15 in 1986 (Table 1). One patient had a normal karyotype,6 and the other eight patients showed a common aberration in the long arm of chromosome 8. This included translocation of chromosome 8 in six patients3,6,12,14,15,17 and insertion from chromosome 8 in two.6,9 On the other hand, myxoid liposarcoma showed the characteristic translocation t(12;16)(q13;p11).13 Well differentiated liposarcoma often demonstrated ring chromosome 12, a large marker chromosome, or telomeric association.19 Furthermore, rearrangement of chromosome 8 is rarely found in liposarcomas16 and in ordinary lipomas.5 Accordingly, aberration of the long arm of chromosome 8 aids in the diagnosis. The present

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patient with lipoblastoma showed a previously undescribed aberration of chromosome 8 in the region 8q1. In addition to the patient’s age and pathological features, chomosomal analysis assisted in the diagnosis of lipoblastoma.

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H. Orui et al.: Lipoblastoma with chromosome 8 aberration 9. Kanazawa C, Mitsui T, Shimizu Y, et al. Chromosomal aberration in lipoblastoma: a case with 46, XX ins (8; 6) (q11.2; q13q27). Cancer Genet Cytogenet 95:163–5. 10. Kransdorf MJ, Moster RP, Meis JM, et al. Fat-containing softtissue masses of the extremities. Radiographics 1991;11:81–106. 11. Mitelman F, Klinger HP, Rowley JD, et al. Guidelines for cancer cytogenetics, supplement to an international system for human cytogenetic nomenclature. Basel; Karger; 1991. 12. Ohjimi Y, Iwasaki H, Kaneko Y, et al. A case of lipoblastoma with t (3; 8) (q12; q11.2). Cancer Genet Cytogenet 1992;62:103–5. 13. Örndal C, Mandahl N, Rydholm A, et al. Chromosomal evolution and tumor progression in a myxoid liposarcoma. Acta Orthop Scand 1990;61:99–105. 14. Panarello C, Rosanda C, Morerio C, et al. Lipoblastoma: a case with t (7; 8) (q31; q13). Cancer Genet Cytogenet 1998;102:12–4. 15. Sandberg AA, Gibas Z, Saren E, et al. Chromosome abnormalities in two benign adipose tumors. Cancer Genet Cytogenet 1986;22:55–61. 16. Sandberg AA, Bridge JA. The cytogenetics of bone and soft tissue tumors. Austin: Landes; 1994. p. 147–216. 17. Sawyer JR, Parsons EA, Crowson ML, et al. Potential diagnostic implications of breakpoints in the long arm of chromosome 8 in lipoblastoma. Cancer Genet Cytogenet 1994;76:39–42. 18. Shmookler BM, Enzinger FM. Liposarcoma occurring in children. An analysis of 17 cases and review of the literature. Cancer 1983;52:567–74. 19. Sreekantaiah C, Karakousis CP, Leong SPL, et al. Cytogenetic findings in liposarcoma correlate with histopathologic subtypes. Cancer 1992;69:2484–95. 20. Stout AP, Lattes R. Tumor of the soft tissue. In: Firminger HI, editor. Atlas of tumor pathology, second series. Fascicle 1. Washington DC: Armed Force Institute of Pathology; 1967. p. 52– 7. 21. Vellios F, Baez J, Shumacker HB. Lipoblastomatosis: a tumor of fetal fat different from hibernoma. Report of a case, with observations of the embryogenesis of human adipose tissue. Am J Pathol 1958;34:1149–59.