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Tumor karyotype differentiates lipoblastoma from liposarcoma
Tumor Karyotype By Grant
Differentiates
G. Miller,
Natalie
Lipoblastoma
L. Yanchar,
Vancouver,
J. Fergal
Magee,
From Liposarcoma and
Geoffrey
K. Blair
Canada
Lipobiastoma is a rare benign pediatric soft tissue tumor that may be difficult to distinguish from a myxoid liposarcoma clinically or histologically. The authors present a case of a progressively growing, locally invasive soft tissue tumor in a child. Tissue culture for cytogenetic study showed a breakpoint in the long arm of chromosome 8. A review of the literature showed seven case reports of lipoblastoma karyotype, six of which had a similar breakpoint in chromosome 8. This distinguishes it from the histologically alike myxoid liposarcoma, the karyotype of which typically contains the clonal anomaly t(12;16)(q13:pll). The authors recommend
that when performing a biopsy of a childhood adipose tumor with unusual features, such as progressive or invasive growth, that fresh tissue be submitted for cell culture. The tumor karyotype will, in most cases, aid in differentiating lipoblastoma from myxoid liposarcoma. J Pediatr Surg 32:1771-1772. Copyright o 7997 by W.B. Saunders Company.
T
chromosome 8 with or without additional unidentified chromosome material. A small marker chromosome with the morphology of a ring was also present. The full karyotype was 47,XY,der(S)?t@q;?),+mar. The pathology and cytogenetic findings were consistent with a lipoblastoma, diffuse type.
HE MAJORITY of soft tissuetumors in children are benign and of vascular or fibroblastic origin. Adipose tumors are relatively rare, comprising about 6% of soft tissueneoplasmsthat develop in the first two decades of life. Approximately two thirds of these are simple lipomas or variants and up to 30% are lipoblastomas.’ Although benign in nature, lipoblastoma tends to recur and bears a striking histological similarity to myxoid liposarcoma, a low-grade sarcoma that is rare in childhood. Cytogenetic study findings have showncharacteristic clonal chromosomeabnormalitiesfor liposarcomaand lipoblastoma that are useful as tumor-specific markers.2-s We presenta caseof an adiposetumor with clinical and histological featuresnot unlike a myxoid liposarcomabut with a clonal chromosome8 breakpoint that is characteristic of lipoblastoma. CASE
REPORT
A healthy 17-month-old boy presented with a 3-month history of an asymptomatic progressively enlarging soft tissue mass in the right buttock, just adjacent to the natal cleft. Ultrasound scan and magnetic resonance imaging demonstrated a 5 X 4 X 4 cm soft tissue adipose tumor. At the time of resection, the tumor was mainly in the subcutaneous adipose tissue with ill-defined borders and invasion into the underlying fascia in the perirectal region. Fresh tissue was submitted for cell culture because of the poorly defined edges and invasive features of the tumor. Grossly, the tumor was fatty, homogenous, and tan-cream colored with a thin capsule. Its dimensions were 7.5 X 5 X 3.5 cm with a weight of 48 g. There were no areas of hemorrhage or necrosis. On cut surface there was a nodular pattern defined by fine septae. Microscopy findings displayed lobules of fat cells, most of which appeared mature, separated by bands of fibroconnective tissue and small focal collections of spindle-shaped cells and cells with vacuolated cytoplasm or central nuclei. Surrounding some lipoblastomas was mutinous-appearing material. There were no features of cellular atypia. Tumor was invading the fascial tissue and was present at the resection margins. The tumor cytogenetic analysis showed a clonal abnormality with a structural rearrangement of chromosome 8 and a deletion of the long arm of JournaloffediatricSurgery,
Vol32,
No 12 (December),
1997:
pp 1771-1772
INDEX WORDS: Lipoblastoma, cytogenetics, karyotype.
liposarcoma,
adipose
tumor,
DISCUSSION
Lipoblastoma and lipoblastomatosisare mesenchymal tumors of fat, reported as occurring primarily in infants and young children, usually lessthan 8 years of age, and most often before the age of 3.’ Some series’ report a male predominance,whereasothers find no sex predilection. Although clinically benign, recurrence occurs in 13% to 20% of cases,usually associatedwith incomplete excision.9 These tumors occur most commonly in the subcutaneoustissues of the limbs or trunk as well as various other locations. There are two clinicopathologic types of lipoblastoma. The most common type appears circumscribedor encapsulatedand is usually superficially located, mimicking a lipoma. The more diffuse type is deeper. It has an infiltrative growth pattern into the surrounding tissuesincluding muscle, and has a greater tendency to recur when incompletely excised. Although often seenin different age groups, clinically, lipoblastoma can mimic myxoid liposarcoma. Both tumors typically are nontender with slow but steady invasive growth and have the propensity to recur locally.
Franz the Depannzents of Surgery and Pathology, Universiry of British Columbia, British Columbia’s Children’s Hospital, Vancouver: Canada. Address reprint requests to Grant G. Miller, MD, University of Chicago, Section of Pediatric Surgery, 5841 S. Ma$and Ave, MC 4062, Chicago, IL 60637. Copyright 0 1997 by WB. Saunders Company 0022.3468/97/3212-0030$03.00/O 1771
1772
MILLER
Presumably, the natural history of an unresected lipoblastoma is to mature into a lipoma. Liposarcoma, in contrast, has the potential to metastasize. Microscopically, lipoblastoma is virtually indistinguishable from myxoid liposarcoma.1° Features suggesting malignancy include a poorly defined lobulation with larger lobules, the presence of mutinous pools or lakes, and/or cytological atypia such as nuclear pleqmorphism, hyperchromasia, or atypical mitoses. Pathologists are unable to reliably distinguish between lipoblastoma and myxoid liposarcoma purely on histological features and require the patient’s age to substantiate the diagnosis. The identification of a cytogenetic or molecular marker capable of predicting behavior provides a significant improvement in diagnostic accuracy. Advances in molecular biology and cytogenetics have helped investigators to discover specific markers in adipose tumors. The specific clonal chromosomal anomaly, t(12;16)(q13:pll), is characteristic of myxoid liposarcoma.2 Lipomas as well may have a breakpoint in chromosome 12 associated with a variable translocation. However, this break typically is distal to q13 (i.e., q15).3 A breakpoint in chromosome 8 was first reported in lipoblastoma in 1986.6 There have been seven additional
Table CESe NO.
Study Sandberg Ohjimi Fletcher
1. Lipoblastoma
et al4 et al5 et al6
ET AL
Karyotypes
KW-VP~
1
49,XY,t(7;8)(7qter-7p22::8ql2-8qter)
2 3
46,XY,t(3;8)(ql2;qll.2) 46,XY,der(l)t(l;8)(p13;q22)t(7;8)(p22;q24.1~
Fletcher
et al6
4
der(7)t(7;8)(p22;q13)t(1;8)(p13; q22),del(8)(q13q24.1) 46,XY,dir ins(6;8)(p25;ql3q24.1)
Fletcher
et al6
5
46,Xx
Sawyer et al7 Dal Cin et al8 Present case
6 7 8
46,XY,der(l4)t(8;14)(ql1.2;q24) 46,XY,t(8;9)(qll-12;p22) 46,XYder(S)?t(8q;?),+mar
cases of lipoblastoma karyotypes reported, six with a breakpoint in chromosome 8 (Table 1).5-8 There are no reports of lipomas or liposarcomas wi$ this rearrangement of chromosome 8. Likewise there have been no reports of lipoblastoma with a 12q13.3 or 12q15 breakpoint. Therefore, a child who has an unusual tumor of adipose tissue (ie, invading fascia or not well localized) should have a fresh specimen of representative tissue submitted for tissue culture and evaluation of tumor biology. The tumor karyotype will, in most cases, clearly distinguish lipoblastoma from myxoid liposarcoma.
REFERENCES 1. Chung EB, Enzinger FM: Benign lipoblastomatosis. An analysis of 35 cases. Cancer 32:482-92, 1973 2. Rabbit& TH, Forster A, Larson R, et al: Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nature Genet 4: 175 180,1993 3. Mrozek K, Karakousis CP, Bloomfield CD: Chrosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: Localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3. Cancer Res .53:1670-1675,1993 4. Sandberg AA, Gibas Z, Saren E, et al: Chromosome abnormalities in two benign adipose tumors. Cancer Genet Cytogenet 22:55-61, 1986 5. Ohjimi Y, Iwasaki H, Kaneko Y, et al: A case of lipoblastoma with t(3;8)(q12;q11.2). Cancer Genet Cytogenet 62:103-105, 1992 6. Fletcher JA, Kozakewich HP, Schoenberg ML, et al: Cytogenetic
findings in pediatric adipose tumors: Consistent rearrangement of chromosome 8 in lipoblastoma. Genes Chromosomes Cancer 6:24-29, 1993 7. Sawyer JR, Parson EA, Crowson ML, et al: Potential diagnostic implications of breakpoints in the long arm of chromosome 8 in lipoblastoma. Cancer Genet Cytogenet 76:39-42, 1994 8. Dal Cin P, Sciot R, De Wever I, et al: New discriminative chromosomal marker in adipose tissue tumors. The chromosome 8qll-q13 region in lipoblastoma. Cancer Genet Cytogenet 78:232-235, 1994 9. Coffin CM, Dehner LP: Soft tjssue tumors in the first year of life: A report of 190 cases. Pediatr Path01 10:509-526, 1990 10. Allen PW: Myxoid tumors of soft @sues, in Sommers SC, Rosen PP (eds): Pathology Annual, Part I, New York, NY, Appleton-CenturyCrofts, 1980
Differentiates
G. Miller,
Natalie
Lipoblastoma
L. Yanchar,
Vancouver,
J. Fergal
Magee,
From Liposarcoma and
Geoffrey
K. Blair
Canada
Lipobiastoma is a rare benign pediatric soft tissue tumor that may be difficult to distinguish from a myxoid liposarcoma clinically or histologically. The authors present a case of a progressively growing, locally invasive soft tissue tumor in a child. Tissue culture for cytogenetic study showed a breakpoint in the long arm of chromosome 8. A review of the literature showed seven case reports of lipoblastoma karyotype, six of which had a similar breakpoint in chromosome 8. This distinguishes it from the histologically alike myxoid liposarcoma, the karyotype of which typically contains the clonal anomaly t(12;16)(q13:pll). The authors recommend
that when performing a biopsy of a childhood adipose tumor with unusual features, such as progressive or invasive growth, that fresh tissue be submitted for cell culture. The tumor karyotype will, in most cases, aid in differentiating lipoblastoma from myxoid liposarcoma. J Pediatr Surg 32:1771-1772. Copyright o 7997 by W.B. Saunders Company.
T
chromosome 8 with or without additional unidentified chromosome material. A small marker chromosome with the morphology of a ring was also present. The full karyotype was 47,XY,der(S)?t@q;?),+mar. The pathology and cytogenetic findings were consistent with a lipoblastoma, diffuse type.
HE MAJORITY of soft tissuetumors in children are benign and of vascular or fibroblastic origin. Adipose tumors are relatively rare, comprising about 6% of soft tissueneoplasmsthat develop in the first two decades of life. Approximately two thirds of these are simple lipomas or variants and up to 30% are lipoblastomas.’ Although benign in nature, lipoblastoma tends to recur and bears a striking histological similarity to myxoid liposarcoma, a low-grade sarcoma that is rare in childhood. Cytogenetic study findings have showncharacteristic clonal chromosomeabnormalitiesfor liposarcomaand lipoblastoma that are useful as tumor-specific markers.2-s We presenta caseof an adiposetumor with clinical and histological featuresnot unlike a myxoid liposarcomabut with a clonal chromosome8 breakpoint that is characteristic of lipoblastoma. CASE
REPORT
A healthy 17-month-old boy presented with a 3-month history of an asymptomatic progressively enlarging soft tissue mass in the right buttock, just adjacent to the natal cleft. Ultrasound scan and magnetic resonance imaging demonstrated a 5 X 4 X 4 cm soft tissue adipose tumor. At the time of resection, the tumor was mainly in the subcutaneous adipose tissue with ill-defined borders and invasion into the underlying fascia in the perirectal region. Fresh tissue was submitted for cell culture because of the poorly defined edges and invasive features of the tumor. Grossly, the tumor was fatty, homogenous, and tan-cream colored with a thin capsule. Its dimensions were 7.5 X 5 X 3.5 cm with a weight of 48 g. There were no areas of hemorrhage or necrosis. On cut surface there was a nodular pattern defined by fine septae. Microscopy findings displayed lobules of fat cells, most of which appeared mature, separated by bands of fibroconnective tissue and small focal collections of spindle-shaped cells and cells with vacuolated cytoplasm or central nuclei. Surrounding some lipoblastomas was mutinous-appearing material. There were no features of cellular atypia. Tumor was invading the fascial tissue and was present at the resection margins. The tumor cytogenetic analysis showed a clonal abnormality with a structural rearrangement of chromosome 8 and a deletion of the long arm of JournaloffediatricSurgery,
Vol32,
No 12 (December),
1997:
pp 1771-1772
INDEX WORDS: Lipoblastoma, cytogenetics, karyotype.
liposarcoma,
adipose
tumor,
DISCUSSION
Lipoblastoma and lipoblastomatosisare mesenchymal tumors of fat, reported as occurring primarily in infants and young children, usually lessthan 8 years of age, and most often before the age of 3.’ Some series’ report a male predominance,whereasothers find no sex predilection. Although clinically benign, recurrence occurs in 13% to 20% of cases,usually associatedwith incomplete excision.9 These tumors occur most commonly in the subcutaneoustissues of the limbs or trunk as well as various other locations. There are two clinicopathologic types of lipoblastoma. The most common type appears circumscribedor encapsulatedand is usually superficially located, mimicking a lipoma. The more diffuse type is deeper. It has an infiltrative growth pattern into the surrounding tissuesincluding muscle, and has a greater tendency to recur when incompletely excised. Although often seenin different age groups, clinically, lipoblastoma can mimic myxoid liposarcoma. Both tumors typically are nontender with slow but steady invasive growth and have the propensity to recur locally.
Franz the Depannzents of Surgery and Pathology, Universiry of British Columbia, British Columbia’s Children’s Hospital, Vancouver: Canada. Address reprint requests to Grant G. Miller, MD, University of Chicago, Section of Pediatric Surgery, 5841 S. Ma$and Ave, MC 4062, Chicago, IL 60637. Copyright 0 1997 by WB. Saunders Company 0022.3468/97/3212-0030$03.00/O 1771
1772
MILLER
Presumably, the natural history of an unresected lipoblastoma is to mature into a lipoma. Liposarcoma, in contrast, has the potential to metastasize. Microscopically, lipoblastoma is virtually indistinguishable from myxoid liposarcoma.1° Features suggesting malignancy include a poorly defined lobulation with larger lobules, the presence of mutinous pools or lakes, and/or cytological atypia such as nuclear pleqmorphism, hyperchromasia, or atypical mitoses. Pathologists are unable to reliably distinguish between lipoblastoma and myxoid liposarcoma purely on histological features and require the patient’s age to substantiate the diagnosis. The identification of a cytogenetic or molecular marker capable of predicting behavior provides a significant improvement in diagnostic accuracy. Advances in molecular biology and cytogenetics have helped investigators to discover specific markers in adipose tumors. The specific clonal chromosomal anomaly, t(12;16)(q13:pll), is characteristic of myxoid liposarcoma.2 Lipomas as well may have a breakpoint in chromosome 12 associated with a variable translocation. However, this break typically is distal to q13 (i.e., q15).3 A breakpoint in chromosome 8 was first reported in lipoblastoma in 1986.6 There have been seven additional
Table CESe NO.
Study Sandberg Ohjimi Fletcher
1. Lipoblastoma
et al4 et al5 et al6
ET AL
Karyotypes
KW-VP~
1
49,XY,t(7;8)(7qter-7p22::8ql2-8qter)
2 3
46,XY,t(3;8)(ql2;qll.2) 46,XY,der(l)t(l;8)(p13;q22)t(7;8)(p22;q24.1~
Fletcher
et al6
4
der(7)t(7;8)(p22;q13)t(1;8)(p13; q22),del(8)(q13q24.1) 46,XY,dir ins(6;8)(p25;ql3q24.1)
Fletcher
et al6
5
46,Xx
Sawyer et al7 Dal Cin et al8 Present case
6 7 8
46,XY,der(l4)t(8;14)(ql1.2;q24) 46,XY,t(8;9)(qll-12;p22) 46,XYder(S)?t(8q;?),+mar
cases of lipoblastoma karyotypes reported, six with a breakpoint in chromosome 8 (Table 1).5-8 There are no reports of lipomas or liposarcomas wi$ this rearrangement of chromosome 8. Likewise there have been no reports of lipoblastoma with a 12q13.3 or 12q15 breakpoint. Therefore, a child who has an unusual tumor of adipose tissue (ie, invading fascia or not well localized) should have a fresh specimen of representative tissue submitted for tissue culture and evaluation of tumor biology. The tumor karyotype will, in most cases, clearly distinguish lipoblastoma from myxoid liposarcoma.
REFERENCES 1. Chung EB, Enzinger FM: Benign lipoblastomatosis. An analysis of 35 cases. Cancer 32:482-92, 1973 2. Rabbit& TH, Forster A, Larson R, et al: Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nature Genet 4: 175 180,1993 3. Mrozek K, Karakousis CP, Bloomfield CD: Chrosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: Localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3. Cancer Res .53:1670-1675,1993 4. Sandberg AA, Gibas Z, Saren E, et al: Chromosome abnormalities in two benign adipose tumors. Cancer Genet Cytogenet 22:55-61, 1986 5. Ohjimi Y, Iwasaki H, Kaneko Y, et al: A case of lipoblastoma with t(3;8)(q12;q11.2). Cancer Genet Cytogenet 62:103-105, 1992 6. Fletcher JA, Kozakewich HP, Schoenberg ML, et al: Cytogenetic
findings in pediatric adipose tumors: Consistent rearrangement of chromosome 8 in lipoblastoma. Genes Chromosomes Cancer 6:24-29, 1993 7. Sawyer JR, Parson EA, Crowson ML, et al: Potential diagnostic implications of breakpoints in the long arm of chromosome 8 in lipoblastoma. Cancer Genet Cytogenet 76:39-42, 1994 8. Dal Cin P, Sciot R, De Wever I, et al: New discriminative chromosomal marker in adipose tissue tumors. The chromosome 8qll-q13 region in lipoblastoma. Cancer Genet Cytogenet 78:232-235, 1994 9. Coffin CM, Dehner LP: Soft tjssue tumors in the first year of life: A report of 190 cases. Pediatr Path01 10:509-526, 1990 10. Allen PW: Myxoid tumors of soft @sues, in Sommers SC, Rosen PP (eds): Pathology Annual, Part I, New York, NY, Appleton-CenturyCrofts, 1980