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2484
Cytogenetic Findings in Liposarcoma
Correlate With Histopathologic Subtypes
Chandrika Sueekanfaiah, PhD,*ct Consfanf i n P. Karakousis, MD,S
Stanley P. L. Leong, MD,§(I and Avery A . Sandberg, MD, DSc*
The cytogenetic findings in 31 liposarcomas from 26 pa-
tients are reported. Four other tumors did not grow.
Three histologic types are represented in this analysis.
The well-differentiated liposarcomas were characterized
by telomeric associations, large marker chromosomes
and ring chromosomes, and in some cases, double min-
utes. The pleomorphic liposarcomas contained very high
clonal chromosomal numbers with near-tetraploid
modes and numerous variable, often unidentifiable, chro-
mosomal abnormalities. The myxoid liposarcomas were
characterized primarily by a t(12;16)(q13;pll)as the sole
abnormality or additional changes. These results indi-
cate that cytogenetic findings may provide a new crite-
rion, not only for establishing the diagnosis of liposar-
coma, but also for differentiating confusing histologic
types of liposarcoma and these lesions from other types
of sarcomas. Cancer 1992; 692484-2495.
Liposarcoma is one of the most common soft tissue sar-
comas, originating from primitive mesenchymal cells
rather than mature adipose tissue.' The tumor occurs
primarily in men and is situated most often in the ex-
tremities and retroperitoneum. It generally arises in
adults and is remarkable because of its frequent large
From *The Cancer Center of Southwest Biomedical Research
Institute and Genetrix, Inc., Scottsdale, Arizona; the $Department of
Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New
York; and the SDepartment of Surgery, Arizona Cancer Center, Col-
lege of Medicine, University of Arizona, Tucson, Arizona.
Supported in part by a grant (CA-41183) from the National
Cancer Institute.
11 Recipient of the American Cancer Society Clinical Oncology
Career Award 1987-1990.
t Current address: Lab of Genetics and Cancer Genetics, Memo-
rial Sloan-Kettering Institute, 1275 York Avenue, New York, NY
10021.
The authors thank Shirley Frazzini for secretarial assistance;
Robert Roeder, Debbie Griggs, and Fred Flohrschutz for photo-
graphic assistance; and Adam Wilson and Mary Powell for technical
assistance.
Address for reprints: Avery A. Sandberg, The Cancer Center of
Southwest Biomedical Research Institute and Genetrix, Inc., 6401
East Thomas Road, Scottsdale, AZ 85251.
Accepted for publication September 1, 1991.
size and variable histologic picture, which closely re-
flects its clinical behavior. Multiple classifications of li-
posarcomas have been proposed because of their het-
erogeneous histologic presentations. The Armed Forces
Institute of Pathology classification divides liposarco-
mas into four basic histologic categories: (1)myxoid, (2)
round cell, (3) well differentiated, and (4) pleomorphic.
The well-diff erentiated forms have low-grade malig-
nancy and rarely metastasize; the poorly differentiated
ones are often highly aggressive, tend to recur, and me-
tastasize in a high percentage of ~ a s e s . l - ~
We did a cytogenetic analysis of 31 liposarcomas
from 26 patients; four other tumors did not grow in
culture. The tumors successfully analyzed showed
clonal karyotypic abnormalities, which often were
found to correlate with histologic subtypes.
Materials and Method
Cytogenetic analyses of the tumors were done accord-
ing to previously described procedures.6 In brief, the
method involves overnight collagenase disaggregation
of the tumor; culturing in flasks and cover slips in
RPMI-1640 medium supplemented with fetal calf
serum l6%, antibiotics 2%, and glutamine 1%at 37°C
in 5% carbon dioxide; and harvesting usually after 4 to
5 days. G-banded karyotypes7 were expressed accord-
ing to the International System for Chromosome No-
menclature .'
Results
Clinical Findings
The available clinical and histopathologic information
on the 26 patients is summarized in Table 1. The age
distribution of the patients ranged from 37 to 92 years
(average, 62 years; median incidence, sixth decade).
There was an apparently even sex distribution. The tu-
mors were located primarily in the retroperitoneum and
lower extremities. All patients had definitive surgical
 10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Clinicopathologic and Cytogenetic Data of Liposarcomas
~~

Clinical Last Culture

Age Primary tumor Histopathologic stage follow-up time
(yr) Sex site (date) type (grade) (date) (date) (days) Karyotype
62 F Retroperitoneum Well-differentiated 4-6 2: 46,XX
32: 42-44,XX,-1,-4,+6,del(ll)(q23),-11,
+der( 1l)t(1I:?)(p15;?),-12,+der( 12)
t( 12;?)(pl3;?),- 13,- 14,+der( 14)t(14;?)
(q32;?),-17,+?der(2O)t(ZO;?)(p13;?),-22
+O-3 mar,+r+2-4 large mars
58 F Left thigh (1983) Well-differentiated 8/88 4 13: 46,XX
17: 46-47,XX,+r
4: 90-96,+2r
5: 83-95,+r,+tas,+dmins
69 F Retroperitoneum Well-differentiated 5/90 8 12: 42-51,XX,t(3;4)(p13;p15.3),-5,-6,-9,
+der(9)?,t(5;9)(q15;q22),-12,+der(12),
t( 1;12) (q23; p13),- 15,-16,- 16,-19,
+4-6 mars,+2r
3: 84-89,+mars,+ 1-3r,
66 F Retroperi toneum Well-differentiated 1/90 5 3: 46,XX
3 1: 43-48,XX,+ 1-3r,+l-2 large mar(+RNSA
46 F Retroperitoneum Well-differentiated 10/89 4 17: 46,XY
(1981) 5: 49,XY,+3r (+RNSA)
47 F Retroperi toneum Well-differentiated 10/89 5 2: 46,XY
(1981) 25: 46-51,XY, I 2-3 mars,+2-4r,+tas
73 F Retroperitoneum Well-differentiated 5 6: 46,XX
25: 84-96,XXXX,-l 1,+der(l l)t(lI;?)(p15;?)
+2-4 mars,+2 large mars,+dmins
7: -180,+mars,+4 large mar
65 F Retroperitoneum Well-differentiated 10/89 5-1 1 1: 46,XX
(1975) 15: 45-47,XX,+ 1-2r,+tas
4: 46-47,XX,+1-2 large mars,+tas
16: 93+,+mars,+2-3 large mars,+tas
55 M Right thigh (8/89) Well-differentiated 8/89 2-10 18: 45-47,XY,de1(9)(pI2),+1-2r,(+RNSA)
6: very polyploid,+r,+large mars,+tas
63 M Left thigh Well-differentiated 8 9: 46,XY
9: 44-50,+r,+large mars,+tas,+dmins
4: polyploid,+r,+large mars,+tas,+dmins
63 M Left thigh Well-differentiated 4/90 4-10 46,XY
12: 42-47,+r,+large mars, +tas,+dmins
4: polyploid,+r,+large mars,+tas,dmins
63 M Retroperitoneum Pleomorphic (3) 10/88 8 4: 46,XY,inv(9)
(1984) 21: 106-112,XXXXYY,+1X3,+2,+2,+3,+de1(3
+deI(3)(~21),+4,+5,+der(5)t(5;?)(~15 l;?),
+6X3,+7X3,+8X3,+i(8q),+9X3,+inv(9)X3,+
+IO,+ll,+der(l l)t(11;?)(p15;?),+12,+i(
+13,+13,+14,+14,+15,+15,+16X3,+17,+17,+18
+18,+19X3,+20,+21X3,+6-8mars,+l-6
63 M Retroperitoneum Pleomorphic (3) 10/88 4 10: 46,XY,inv(9)
(1984) 23: 102-109 similar to 10a
Continued)
Clinical Last Culture
Age Primary tumor Histopathologic stage follow-up time
(yr) Sex site (date) type (grade) (date) (date) (days) -
Karyotype
72 F Right thigh (8/88) Pleomorphic P 7/89D 4 18: 46,XX
(high) 16: 74-77,XXXX,+del(l)(p22p36),+del(l),-2
+der(2)t(1;2)(p22;p11,2),-2,+der(2),+3,+
+5,+5,+der(6)t(6;?)(~23;?),+der(6),+7
+8,+8,+9,+9,-1 l,+der(l l)t(l1;18)(pll
qll.2),-1 l,+der( ll),del(l2)(pl1.2p13),
del( 12),t(13;?)(pl3;?),+15,+ 15,
t(19;?)(q13;?),t(19;?),+21,+21,+22,+22,
+6 rnars.fr
4: polyploid,+mars
63 M Retroperitoneum Pleomorphic/ R (12/88) 12/88 4-6 22: 40-47 count (poor morphology)
(1986) myxoid (2) 4 1,X, -X,de1(3)(q25q27), -5, +der(5)
t(5;?)(~15,1;?),-6,-6,+der(6)t(6;?)
(q25;?),de1(7)(q31),-8,-8,-9,-10,-11,
- 12,+der( 12)t(9;12)(q13;qZ1),-16,- 18,
-19,+der(19)t(8;19)(q21.2;q13.3),-21,
-22,+3 mars,+3 large mars
92 F Right leg (1987) Pleomorphic (3) R (1/89) 4/89 4 6: 46,XX
24: 41-45,X,-X,-l,del(l)(p13),-3,-3,+der(3
t(1;3)(p13;q13,1),-4,-5,-7,+der(7)t(7;
(p22;?),del(7)(p21),-9,-10,-11,-13,-15,
-21,-22,+9-10 mars,+l-3r
66 M Left thigh (1980) Pleomorphic (3) R (5/89) 1/90 3-4 10: 46,XY
6: 90-105,t(l;?)(q44;?)X2,t(l;?)(q23;?)x
deI(l)(q2l),der(3)X3,t(3;9)(q12;q13),
t(l1;13)(pll. 1;ql l),t(12;?)(q22;?),
t(19;?)(ql3.3;?),+22-30 mars (most mar
in duplicate),+dmins
10: 200-210 count with similar structural c
72 M Right thigh (5/89) Pleomorphic p (8/89) 9 27: 46,XY
(high) 3: polyploid, +multiple, complex
abnormalities, +tas
65 M Iliac fossa (2/90) Pleomorphic P 4/90 4-1 1 2: 46,XY
(high) 22: 130-136,+85 mars, identifiable markers
1 cell karyotyped included
t(2;?)(pl l;?),i(6p),t( 7; 15)(pl3;q13),
del( 1l)(q22),i(12q),t( 16;?)(q24;?),
t( 19;?)(q13.3;?),t(20;?)(q13.2;?)
60 M Right thigh Pleomorphic P 6-8 13: 46,XY
17: 63-67,XY,+der(l)(p13;?),+del(l)(qll),
del(2)(pl6),-3,+der(3)t(3;?)(ql l;?),
+de1(3)(q24),+?der(3),del(5)(pll),+ins
(5;?)(qll.l;?),del(6)(q22),+del(6)(ql5),
del(8)(pll.2),-9,-lO,del(l l ) ( p l 1),-12,
- 12,+der( 12)t(7;12)(pll.l;pll.l),-14,
-17,-18,- 19,+der( 19)t(19;?)(q13.3;?),
+der( 19)t(19;?)(pl3.3;?),-20,-2 1,-22,
+20-22 mars

10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
 68 F Retroperitoneum Myxoid R (7/88) 2/89D 6 10: 80,XXX,-1,-2,+der(3)t(3;?)(q?;?) X2
(1980) +4,-5,+der(5)t(5;?)
(p15.1;?),+7,+7,+9,+9,+11,+16,+17,
+17,+20,+20,+21,+17 mars
(1 cell karyotyyed)
79 M Retroperi toneum Myxoid R (11/89) 11/89 2-4 30: 49-52,XY,+3,-5,+8,+1-4r
(1988) 5: polyploid,+4-6r,+large mar
79 M Retroperitoneum Myxoid (2) R (11/89) 11/89 2-4 24: 49-52,XY,+2,-5,+8,+1-5r
(1988) 7: polyploid,+4-8r,+large mars,+tas
51 F Right leg (1985) Myxoid (2) M (rib) (9/89) 8/89 5-7 25: 47,XX,t(3;15)(p23;q15),+5,t( 10;10)
(q26.1; q22),t(12;16)(q13;pll. 1)
41 F Shoulder (11/85) Myxoid (3) M (11/89) 11/89 4-5 14: 57-6O,XX,+X,+X,+l,+del(l)(q21),-4,
+5,+7,del(lO)(q24)X2,- 12,+i(12q),
13,- 14,+der(14)t( 14;?)(pll.1;?),
+
-16,+18,-20,+4 mars
48 F Right thigh (1979) Myxoid (2) R (thigh) (7/88) 4/90 4 24: 46,XX,t(l2; 16)(q13; p31)
(7/1 /88)
66 M Right groin (8/88) Myxoid p 4/90 2-3 12: 46,XY,t(12;16)(q13;pll)
21: 47,XX,+8,t(12;16)(ql3;pll)
41 F Right pelvis Myxoid R (abdomen) 5/90 4 17: 48,XX,+8,t(ll;l7)(q13;q21),
(1985) (10/31/88) (10/88) t( 12;16)(q13;pl1),+19
65 M Left thigh (1984) Myxoid (2) R (thigh) (2/89) 4/90 4-9 24: 47,XY,+8,t(12;16)(ql3;pll)
(2/9/89) 16: 94,XXYY,+8,+8,t(l2;16)(q13;pll),
t(12;16)(q13;pll)
37 M Left thigh (1984) Myxoid (2) R (thigh) (2/89) 5/90 4: 46,XY
(7/28/89) 31: 46,XY,t(12;16)(q13;p11)
37 M Left thigh Myxoid (2) R (thigh) (2/89) 5/90 4-6 6: 46,XY
(11/17/89) 14: 48,XY,-9,+10,-ll,
(p15;?),t(12;16)(q13;pll),-17,
fl-3mar
R: recurrence; M: metastases; D: deceased.
described cases.9

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 10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2488 CANCER May 15,1992, Volume 69, No. 10

resection of the tumor and received adjuvant chemo-

therapy and/or radiation therapy. Three histologic
subtypes of the tumor were represented in our study:
well differentiated (Fig. l), pleomorphic (Fig. 2), and
myxoid (Fig. 3).

Cytogenetic Findings

The cytogenetic data on the tumors analyzed success-

fully are given in Table 1.Five cases have been reported
earlier.’ Four tumors, two of which were recurrences of
previously analyzed tumors, did not grow in culture. In
specimens from Patients 9 and 19, different areas of the
same tumor were received simultaneously for analysis,
and in Patients 5,10, and 26, two recurrences each were
examined. Of the 31 liposarcomas from 26 patients
with cytogenetic results, 11 were well-differentiated, 9
were pleomorphic, and 11 were myxoid neoplasms.

Figure 2. A pleomorphic liposarcoma (Patient 10) containing

spindle-shaped cells with elongated hyperchromatic nuclei, with
other nuclei being more oval or triangular, occasional Iipoblasts,
and markedly pleomorphic multinucleated cells (H & E, original
magnification X 150).

Clonal chromosomal aberrations were present in all tu-

mors (Figs. 4 to 11). Karyotypically normal cells were
present in addition to the abnormal clones in a high
proportion of the tumors.

Figure 1. A well-differentiated liposarcoma (Patient 1) consisting of
cells of variable size and shape with atypical hyperchromatic nuclei
and aggregates of multivacuolated lipoblasts. This tumor is called
an atypical lipoma by some (H & E, original magnification X150).
Well-Differentiated Liposarcomas
Eleven tumors from nine patients were analyzed, in-
cluding a subsequent recurrence from Patient 5. The
tumors had primarily near-diploid modes with chro-
mosome counts ranging from 42 to 5 1. Only one tumor
(6) had a near-tetraploid mode, although clones with
similar counts also were present in other tumors (Table
1).In the latter, the clones appeared to have originated
by a doubling of the near-diploid complement. No
common characteristic cytogenetic abnormality, either
structural or numerical, was seen. The most striking cy-

Cytogenetics of Liposarcomas/Sreekantaiah et al.
Figure 3. A myxoid liposarcoma (Patient 20) consisting of lipoblasts
in varying stages of differentiation and many with multivacuolated
cytoplasm, vascular patterns, and abundant myxoid material
between vessels and tumor cells (H & E, original magnification
X150).
togenetic feature of this group of tumors, however, was
the presence of ring chromosomes, large marker chro-
mosomes, and/or telomeric associations (Figs, 4 to 6).
The telomeric associations were random, and in some
instances, the ends of the chromosomes appeared to be
fused. No preferential combination of chromosomes
was observed, and different telomeres were involved in
associations with different frequencies. Some of the
large marker chromosomes were apparently the result
of telomeric associations between different chromo-
somes (Figs. 4 to 6), normal or rearranged, and some
appeared to contain homogeneously staining regions or
abnormally banded regions, the origins of which could
not be determined in all instances. The origin of the ring
chromosomes could not be identified. In Patient 2, a
ring chromosome was the only cytogenetic anomaly in
10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2489
an otherwise normal karyotype. Double minute chro-
matin bodies (DM) were present in two specimens.
Structural rearrangements, other than those involved in
the makeup of the giant markers and ring chromo-
somes, were relatively uncommon.
Pleomorphic Liposarcomas
Nine pleomorphic liposarcomas, including a recurrence
in Patient 10, were analyzed. Six tumors had very high
chromosome counts ranging from 74 to over 200. They
were characterized by multiple and complex structural
chromosomal abnormalities and translocated material,
which, on most chromosomes, could not be identified
(Figs. 7 and 8). Two tumors (Patients 12 and 13) with
near-diploid modes also showed multiple and complex
aberrations. Ring chromosomes were present in two tu-
mors (Patients 11 and 13) and large marker chromo-
somes'in one (Patient 12).One to sixDh were observed
in two specimens (Patients 10 and 14).
Myxoid Liposarcomas
Eleven tumors from nine patients had a iistopathologic
diagnosis of myxoid liposarcoma. Six of these tumors
(Patients 22 to 26) with a t(12;16)(q13;p11) as the sole
change or with additional abnormalities have been re-
ported earlier.' Of the five tumors from four patients
reported here, only one (Patient 20), a metastatic lesion,
showed the t(12;16) (Fig. 9). The two tumors from Pa-
tient 19 had a cytogenetic pattern resembling that of a
well-diff erentiated liposarcoma with telomeric associa-
tions, large markers, and ring chromosomes although
the histologic diagnosis was myxoid (Fig. 10). Speci-
mens from Patients 18 and 21, also myxoid tumors, had
cytogenetic findings similar to those observed in the
pleomorphic liposarcomas: high chromosome counts
and multiple abnormalities (Fig. 11).
Discussion
Soft tissue tumors are a highly heterogeneous group of
tumors that are classified on a histologic basis according
to the adult tissue they resemble. Although specific
karyotypic abnormalities have been described in
various tumor types, the chromosomal pattern in others
remains to be established."
Liposarcomas are the second most common soft tis-
sue tumor next to malignant fibrous histiocytoma
(MFH). They show a wide variation in histologic, clini-
cal, and prognostic features. The histologic subtypes
 10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Figure 4. Representative G-
banded karyotype from Patient 1
with a well-differentiated
liposarcoma showing large and
other marker chromosomes
X (arrowheads) and numeric
changes.

differ from each other with respect to the age of the and progression of cancer. The end-to-end fusions and
patient, growth potential, tendency to recur and metas- ring chromosomes we observed may be caused by telo-
tasize, and prognosis. Retroperitoneal liposarcomas of- meric loss, resulting from the increased cell division as-
ten attain a large size and have a less favorable progno- sociated with tumorigenesis.20,21
sis than liposarcomas of the e~tremities.'-~ Histologic Giant tumor markers, ring chromosomes, and telo-
type has been shown to be significant in predicting the meric associations also have been observed nonran-
outcome of the disease in some ~ e r i e salthough
,~ others domly in benign tumors. A lipoma with atypia in cer-
have questioned the value of such correlations.",12 The
well-diff erentiated liposarcomas have a tendency to re-
cur locally with no distant metastases or deaths occur-
ring over a 10-year period. Myxoid liposarcomas have a
low rate of local recurrence and distant metastases,
whereas pleomorphic tumors have a high metastatic
rate and poor 5-year and 10-year survival rates.5
We found clonal chromosomal abnormalities in all
3 1 tumors we examined and correlated cytogenetic find-
ings with the histologic types in most instances. Lipo-
sarcomas, which were well differentiated, were charac-
terized by telomeric associations, ring chromosomes,
and giant marker chromosomes. Telomeric associations
have been reported rarely in human neoplasms.
Currently, they have been observed in le~kemia,'~.'~
cardiac myxoma,15 renal tumor,16 MFH,17 well-differ-
entiated liposarcoma,18 and squamous cell carcinoma
cell lines.'' The possible mechanisms underlying this
phenomenon have been discussed extensively in pre-
vious reports.13-19A recent study,20however, showed
that there was a reduction in the length of telomeric
Figure 5. G-banded hyperdiploid metaphases from Patient 7 with a
repeat arrays in cancer caused by increased cell division
well-differentiated liposarcoma showing ring chromosomes, large
and inactivity of telomerase in somatic tissues. Telo- markers, telomeric associations, and acrocentric associations
meric changes therefore may play a role in the initiation (arrowheads).

Cytogenetics of Liposarcomas/Sreekantaiah et al.
Figure 6 . G-banded partial metaphase from Patient 8 with a well-
differentiated liposarcoma showing large markers and ring
chromosomes (arrowheads).
tain areas of the tumor had cytogenetic features"
similar to those described in well-diff erentiated liposar-
comas.18Ring chromosomes have been found in lipo-
mas with atypiaZ3and lei om yo ma^.^^,^^ Telomeric asso-
ciations commonly have been observed in desmoid tu-
mors.26 The pathogenetic significance of these
aberrations in benign neoplasms is not certain.
The pleomorphic liposarcomas showed a cytoge-
netic pattern different from that of the well-differen-
tiated tumors. The chromosome counts were higher,
and extensive numeric and structural rearrangements
(including numerous unidentifiable marker chromo-
somes) were present. In some markers, the chromo-
somes involved (but not the translocated material)
could be identified. In this group of tumors, no consis-
tent abnormalities specific to pleomorphic liposarcomas
were observed. Two had ring chromosomes, and in one
specimen, large markers were present. The cytogenetic
pattern may reflect the advanced or highly aggressive
nature of this malignant lesion.
10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2491
Most of the myxoid liposarcomas contained the
characteristic t(12; 16)(q13;pll). Six of these tumors
have been described earlier, and all contain trisomy 8 as
a nonrandom secondary change.' The specimen from
Patient 20 also had t(12;16) in addition to other
changes. The remaining tumors had cytogenetic abnor-
malities similar to those found in well-differentiated
(Patient 19) and pleomorphic liposarcomas (Patients 18
and 21). The t(12; 16) can be used to differentiate myx-
oid liposarcomas from other myxoid tumors when the
pathologic findings are confusing or the diagnosis is
uncertain. In addition, this approach has been used by
us on several occasions.
The similarities in the chromosomal abnormalities
in tumors with the same histologic diagnosis may repre-
sent a relationship between cytogenetic changes and
the histogenesis of the tumor. However, as seen in some
of our specimens, different chromosomal abnormalities
were found in tumors with the same histologic findings,
and tumors with different histologic findings showed
similar chromosomal changes. Liposarcomas usually
attain large size and are known to be of mixed histologic
types.'-5 Thus, the tumor sample received for cytoge-
netic analysis may contain an area different from that
examined histopathologically. Such a situation may
have occurred in the samples from Patients 19 to 21.
Several samples studied were recurrences of tumors ini-
tially excised 1 to 14 years earlier. Tumor progression
may have led to clonal evolution and given rise to addi-
tional changes in some instances. Progression of the
tumor also may have resulted in poorly differentiated
areas, similar to those observed in pleomorphic tumors.
The chromosomal picture therefore may reflect these
changes. Some of these patients had received prior che-
motherapy and/or radiation therapy. Although un-
likely, the type of change we observed might be related
to the treatment received.
It is also possible that, in some cases of liposarcoma,
the cytogenetic results more faithfully limn the nature
of the original tumor than do the histologic observa-
tions, with the chromosomal findings reflecting the
pristine cellular nature of a tumor that, during its histo-
logic progression, may undergo transformation into an-
other type, e g , from pleomorphic to myxoid and vice
versa.
Cytogenetic reports of liposarcomas are relatively
scarce. Only the myxoid subtype has been analyzed in
sufficient numbers and shown to contain a specific
translocation (12; 16)(q13;pl l).' Chromosomal data
from only 17 other liposarcomas of differing histologic
type are a ~ a i l a b l e . Those
' ~ ~ ~reported
~ ~ ~ ~ include eight
well-differentiated liposarcomas, three poorly diff eren-
tiated, three pleomorphic, two round cell, and two in
 10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2492 CANCER May 15, 1992, Volume 69, No. 10

Figure 7. G-banded
representative karyotype from
Patient 14 with pleomorphic
liposarcoma showing multiple
structural (arrowheads), numeric
abnormalities, and a large
number of unidentifiable
chromosomes (markers).

which the histologic type was not specified. Similar to
our findings, the well-diff erentiated liposarcomas were
characterized by ring chromosomes, giant markers, and
telomeric associations; the poorly differentiated and
pleomorphic tumors had many numeric changes and
numerous, mostly unidentifiable, marker chrorno-
somes.
The cytogenetic findings in lipomas, benign coun-
terparts of liposarcomas, are different.31Approximately
50% of the tumors analyzed have an apparently normal
karyotype. Most of the other 50'/0 have simple recipro-
cal translocations, usually involving chromosome 12.
Complex chromosomal abnormalities, often balanced
rearrangements, characterize a few t ~ m o r s . The~~,~~

Figure 8. G-banded
representative karyotype from
Patient 17 with pleomorphic
liposarcoma showing many
^. complex abnormalities
(arrowheads) and a large number
of markers of unidentifiable
MARKERS origin.
 10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Cytogenetics of Liposarcomas/Sreekantaiah et al. 2493

Figure 9. G-banded
representative karyotype of
Patient 20 with myxoid
liposarcoma showing the
t(12;16)(q13;pll) typical of this
type of tumor and the presence
of other chromosomal
rearrangements.

consistent change common to lipomas and myxoid li-

Figure 10. G-banded metaphase from Patient 19 with myxoid
liposarcoma showing rings, a large marker chromosome, and
telomeric associations (arrowheads), changes more typical of well-
differentiated liposarcoma than of the myxoid type. ~
posarcomas, however, is involvement of band q13 on
chromosome 12. However, in a recent report,33 we
showed that myxoid liposarcomas have altered restric-
tion fragments detectable with GLI probes that were
highly specific and reproducible from case to case be-
cause of methylation differences that are unique to
myxoid liposarcoma. These changes were not seen in
lipomas with translocations involving 12q13 or 14.
Additional extensive studies correlating the cytoge-
netic results with histopathologic findings probably will
resolve whether these changes more closely reflect the
nature of the biologic and genetic processes involved in
lymphosarcoma and, thus, resolve their diagnostic and
prognostic aspects. This will be particularly important
in instances where the cytogenic and histopathologic
findings are discordant. Based on reports about leuke-
mias and other sarcomas (e.g., synovial sarcoma, Ew-
ing's sarcoma, rhabdomyosarcoma, and chondrosar-
coma)," it would appear that the cytogenetic findings
reflect the nature of the pristine cell involved and,
hence, the basic histogenetic origin of the leukemia or
tumor, whereas histopathologic findings describe the
microscopic appearance of the leukemia or tumor, in-
formation which may be valuable in treating the dis-
ease. For optimal benefit to the clinician, and hence the
patient! using both cytogenetic and histopathologic Ob-
servations would appear to be appropriate.

2494 CANCER May 15, 1992, Volume 69,No. 10
19 20 21
References
1. Enzinger FM, Weiss SW. Soft Tissue Tumors, ed. 2. St. Louis: CV
Mosby, 1988; 346-382.
2. Enterline HT, Culberson JD, Rochlin DB, Brady LW. Liposar-
coma: A clinical and pathological study of 53 cases. Cancer 1960;
13x932-950.
3. Kindblom L-G, Angevall L, Svendsen P. Liposarcoma: A clinico-
pathologic, radiographic and prognostic study. Ada Pathol Mi-
crobiol Scand (Suppl) 1975; 253:5-71.
4. Evans HL. Liposarcoma: A study of 55 cases with a reassess-
ment of its classification. A m ] Surg Pathol 1979; 3:507-523.
5. Chang HR, Hajdu SI, Collin C, Brennan MF. The prognostic
value of histologic subtypes in primary extremity liposarcoma.
Cancer 1989; 64:1514-1520.
6. Sreekantaiah C, Berger CS, Karakousis CP, Rao U, Leong SPL,
Sandberg AA. Cytogenetic subtype involving chromosome 13
in lipoma: Report of 3 cases. Cancer Genet Cytogenet 1989;
39:281-288.
7. Seabright M. Rapid banding technique for human chromo-
somes. Lancet 1971; 2:971-972.
8. Harnden DG, Klingerr HP, eds. ISCN: An International System
for Human Cytogenetic Nomenclature. Basel: Karger, 1985.
9. Sreekantaiah C, Karakousis CP, Leong SPL, Sandberg AA. Tri-
somy 8 as a nonrandom secondary change in myxoid liposar-
coma. Cancer Genet Cytogenet 1991; 51:195-205.
10. Sandberg AA. The Chromosomes in Human Cancer and Leuke-
mia, ed. 2. New York: Elsevier, North Holland, 1990; 756-757.
11. Evans RW. Tumors of adipose tissue. In: Histologic Appearance
of Tumors. Baltimore: Williams and Williams, 1978; 54-65.
12. DasGupta TK. Tumors and tumor-like conditions of adipose tis-
sue. Curr Probl Surg 1970; 7:l-60.
13. Fitzgerald PH, Morris CM. Telomeric association in B-cell lym-
phoid leukemia. H u m Genet 1984; 67:385-390.
10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Figure 11 G-banded
representative karyotype of
22
Patient 21 with myxoid
X liposarcoma with multiple and
complex abnormalities
I (arrowheads), changes more
typical of pleomorphic
liposarcoma than of myxoid
sarcoma
14. Morgan R, Jarzabek V, Jaffe JP, Hecht BK, Hecht F, Sandberg
4A. Telomeric fusion in pre-T-cell acute lymphoblastic Ieuke-
mia. H u m Genet 1986; 73:260-263.
15. Dewald GW, Dahl RJ, Spurbeck JL, Carney JA, Gordon H. Chro-
mosomally abnormal clones and nonrandom telomeric translo-
cations in cardiac myxomas. Mayo Clin Proc 1987; 62:558-567.
16. Kovacs G, Muller-Brechlin R, Szucs S. Telomeric association in
two human renal tumors. Cancer Genet Cytogenet 1987; 28:363-
366.
17. Mandahl N, Heim S, Arheden K, Rydholm A, Wil1i.n H, Mitel-
man F. Rings, dicentrics and telomeric association in histiocyto-
mas. Cancer Genet Cytogenet 1988; 30:23-33.
18. Karakousis CP, Dal Cin,'I Turc-Carel C, Linion J, Sandberg AA.
Chromosomal changes in soft-tissue sarcomas. Arch Surg 1987;
122x1257-1260.
19. Pathak S, Wang Z, Dhaliwal MK, Sacks PC. Telomeric associa-
tion: Another characteristic of cancer chromosomes? Cytogenet
Cell Genet 1988; 47:227-229.
20. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green
DK, Allshire RC. Telomere reduction in human colorectal carci-
noma and with ageing. Nature 1990; 346366-868.
21. Wilkie AOM, Lamb J, Harris PC, Finney RD, Higgs DR. A trun-
cated human chromosome 16 associated with thalassaemia is
stabilized by addition of telomeric repeat (TTAGGG). Nature
1990; 346:868-871.
22. Sreekantaiah C, Leong SPL, Davis JR, Sandberg AA. Intratu-
moral cytogenetic heterogeneity in a benign neoplasm. Cancer
1991; 67:3110-3116.
23. Mandahl N, Heim S, Arheden K, Rydholm A, Willhn H, Mitel-
man F. Three major cytogenetic subgroups can be identified
among chromosomally abnormal solitary lipomas. H u m Genet
1988; 791203-208.
24. Nilbert M, Heim S. Uterine leiomyoma cytogenetics. Genes,
Chrorn 0 Cancer 1990; 2:3-13.

Cytogenetics of LiposarcomaslSreekantaiah et al.
25. Kiechle-Schwarz M, Sreekantaiah C, Berger CS et al. Nonran-
dom cytogenetic changes in leiomyomas of the female genitouri-
nary tract: A report of 35 cases. Cancer Genet Cytogenet 1991;
53: 125-1 36.
26. Bridge JA, Sreekantaiah C, Mouron B et al. Clonal chromosomal
abnormalities in desmoid tumors: Implications for histopatho-
genesis. Cancer 1992; 69:430-436.
27. Sonta S, Oshimura M, Evans JT, Sandberg AA. Chromosomes
and causation of human cancer and leukemia: XX. Banding pat-
terns of primary tumors. ] Natl Cancer lnst 1977; 58:49-59.
28. Becher R, Wake N, Gibas Z, Ochi H, Sandberg AA. Chromo-
some changes in soft tissue sarcomas. Nail Cancer fnst 1981;
72:823-831.
29. Mertens F, Johansson B, Mandahl N et ul. Clonal chromosome
10970142, 1992, 10, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(19920515)69:10<2484::AID-CNCR2820691017>3.0.CO;2-2 by INASP/HINARI - INDONESIA, Wiley Online Library on [17/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2495
abnormalities in two liposarcomas. Cancer Genet Cytogenet 1987;
28337-144.
30. Molenaar WM, DeJong B, Buist J et al. Chromosomal analysis
and the classification of soft tissue sarcomas. Lab Invest 1989;
60:266-274.
31. Sreekantaiah C, Leong SPL, Karakousis CP et ul. Cytogenetic
profile of 109 lipomas. Cancer Res 1991; 51:422-433.
32. Sreekantaiah C, Leong SPL, Sandberg AA. Complex cytogenetic
changes in benign neoplasms: Report of six lipomas. Cancer
Genet Cytogenet 1990; 47113-130.
33. Paulien S, Turc-Care1 C, Dal Cin P et al. Myxoid liposarcoma
with t(12; 16)(q13; 11) contains site-specific differences in meth-
ylation patterns surrounding a zinc-finger gene mapped to the
breakpoint region on chromosome 12. Cancer Res 1990;
50:7902-7907.