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Cytogenetic findings in leiomyosarcoma of the small bowel
Cytogenetic Findings in Leiomyosarcoma of the Small Bowel Paola Dal Cin, Leslie Boghosian, and Avery A. Sandberg
ABSTRACT: A cytogenetic studv of a leiomyosarcoma of the small bowel revealed numerical and structural chromosome changes. Several of these changes, in particular the loss of one chromosome #14. #15, #18, and #22. and del(ll(p12p131 have been rel)orted previously m an unrelated leionLvosarcoma of th('. small bowel. We suggest that these or part of these findings could l)e characteristic of leiomyosarcoma of the small bowel.
INTRODUCTION
To date. the cytogenetic findings in only five leiomyosarcomas have been reported [1-5]. A normal female karyotype (46.XX) was reported in one [5], in all others clmlal chromosome changes were observed. A consistent involvement of chromnsam(; #1 was found in three of the four abnornlal leiomyosarcomas. We report the cytugenetic findings in a h;iomyosarcoma of the small bowel, which are similar to those described by Mark [1] in an identical type of tumor. CASE REPORT
In December 1985, a 56-year-old male u n d e r w e n t laparotolny for abdominal pain. A tumor of the small bowel was found, which was adherent to the sigmoid, and had resulted in perforation of the signloid colon with localized pelvic abscesses. The tumor was resected along with the adjacent small bowel. The pathologic diagnosis was leiomyosarcoma of the small intestine. Following surgery, the patient was giwm six courses of vincristine, adriamycin, and cyclophospharnide. I te was reexplored surgically in May and August, 1986. All macroscopic tumor was removed, i n c l u d i n g serosal implants in the pelvic peritoneum, ileum, and jejunum. There was iio liver ilwulvement. The patient was placed on DTIC and adriamycin therapy. Recently, the patient was readmitted for a "look-laparotomy" to reevaluate the progression of the disease. He was found to have multiple tumor implants in the pelvis (i.e., in the mesentery of the small bowel and colon), as well as multiple implants over the jejunum, ileum, and from the angle of Treitz to the sacrum. Again, the liver was not involved. All macroscopic tumor was removed at this laparotomy, and a pie(:e was examined cytogenetically. Multiple sections showed soft
From tile Rosv,,el]Park MenlorialInstitute. Buffal(). NY, Address requests for reprints to Dr. Avery A. Sandberg, The Cancer Center, Southwest Biomedical Research Institute, 6401 1,:. Thomas ltd.. Scottsdale. AZ 85251. l|eceived July 20. 1987: a(:t:epted September 4. 1987.
285 .~:.1988 ElsevierScit~n(:ePublishingCo.. lnc. 52 Vanderhilt Ave.. New York. NY 10017
Cancer (,(;]let Cytogenet 30:2,~5-288[1988) 0165-4608/88/$(13.50
P. Dal Cin, L. Boghosian,
286 tissue infiltration by with pink cytoplasm, ular chromatin. The erately differentiated CYTOGENETIC
and A. A. Sandberg
a spindle cell tumor. The cells were plump spindle shaped the nuclei were elongated with blunt corners and finely grancells were arranged in intervening fasicles. A recurrent modleiomyosarcoma was diagnosed.
ANALYSIS
Chromosomal analysis of tumor cells from one of the mesenteric implants was performed on a 4-day-old culture from a collangenase disaggregated specimen of the surgically excised tumor, according to procedures previously described [6]. Sixteen of the 27 metaphases analyzed exhibited a normal male karyotype (46,XY). Numerical and structural chromosome abnormalities were present in the 11 remaining mitoses (Table 1). The karyotype of the stem line was 42,XY,del(l)(pl2pl3), de1(4)(q31.1),-9,+der(9)t(9;?)(q34;?),-14,-15,-18,de1(21)(q22.1),-22 (Fig. 1). DISCUSSION Leiomyosarcomas are malignant neoplasms that arise from smooth muscle. They are principally tumors of adult life, more common in women than in men, and in rare cases may be radiation-induced [7]. They can occur anywhere in the body; Figure 1 Karyotype of a stem line cell. Arrows point to the monosomy of the chromosomes #14, #l.!i, #18, and #22.
6
7
20
4 de14
3
2
1 del 1
8
9 dsr 9
10
21 del23
11
22
5
12*
XV
287
I , e i o m y o s a r c o m a of t h e S m a l l B o w e l
Table 1
Chromosome abnormalities Chromosome deviations
KaryotYt}C, number
Chromosome number
1
4
9
14
15
18
21
22
N
q+
-14 -14 -14 -14 -14 -14 -14 -14 N N N
-15 -15 -15 -15 -15 -15 -15 -15 N N N
-18 - 18 - 18 --18 -18 - 18 -18 - 18 N N N
qqIx,' N q(1qqN N N
22 -22 -22 -22 -22 -22 -22 -22 N -22 N
1
42
p-
2 3 4 5 6 7 8 9 10 11
42 40 42 42 42 42 42 46 42 45
pp p ppppN qp-
N N N qqqqqN N
qq+ q~ q-~ q ¢ q-¢ q*N q4 q ¢-
N. Presence of two normal chromosomes.
h o w e v e r , t h e y are h i s t o l o g i c a l l y s i m i l a r , t t a l f of all l e i o m y o s a r c o m a s o c c u r in t h e r e t r o p e r i t o n e u m , w h e r e t h e y are h i g h l y a g g r e s s i v e m a k i n g total r e s e c t i o n u s u a l l y impossible. O n l y four c y t o g e n e t i c a l l y a b n o r m a l ] e i o m y o s a r c o m a s h a v e b e e n d e s c r i b e d so far [1-4], t w o r e m o v e d f r o m t h e p r o s t a t e a n d t w o from t h e s m a l l b o w e l . I n v o l v e m e n t of t h e p a r m of c h r o m o s o m e # 1 was r e p o r t e d in t h r e e of t h e four cases. A t(1;22)(p32;q22) w a s f o u n d by B e c h e r et al. [2] as t h e o n l y c h a n g e in t w o of t h e 50 m e t a p h a s e s in a l e i o m y o s a r c o m a of t h e s m a l l b o w e l . A d e l ( 1 ) ( p 1 2 p 1 3 ) w a s des c r i b e d by Mark, in a l e i o m y o s a r c o m a of t h e s m a l l b o w e l [1] a n d in o n e of t h e p r o s t a t e (case 5 in ref. [3] b y A t k i n et al.). O u r case s h o w e d d e l ( 1 ) ( p 1 2 p 1 3 ) , del(4)(q31.1], der(9), del(21)(q22.1), a n d m o n o s o m y of c h r o m o s o m e s # 1 4 , # 1 5 , #18, and #22. It is i n t e r e s t i n g that in t h e case r e p o r t e d by Mark. t h o u g h del(111(q13-14) a n d t r i s o m y 7 w e r e p r e s e n t , d e l ( 1 ) ( p 1 2 - 1 3 ) a n d m o n o s o m y of c h r o m o s o m e s # 1 4 , # 1 5 , # 1 8 , a n d # 2 2 , as o b s e r v e d in o u r case, w e r e also c o n s i s t e n t f i n d i n g s . T h e r e f o r e , d e l ( 1 ) ( p 1 2 - 1 3 ) a n d m o n o s o m y 14, 15, 18, a n d 22 or a n y p a r t s of t h e s e c h a n g e s f o u n d in t w o u n r e l a t e d l e i o m y o s a r c o m a s of t h e s m a l l b o w e l , c o u l d c h a r a ( : t e r i z e a s u b g r o u p of r e t r o p e r i t o n e a l l e i o m y o s a r c o m a . Supported in part by Grant CA-14555 from the National Cancer Institute. The authors thank Dr. C. Karakousis for supplying the tumor sample, Joyce Romano for her technical assistance, and Sharon Zolnowski for clerical aspects of the paper.
REFERENCES
1. Mark J (1976}: G-band analyses of a human intestinal leiomyosarcoma. Acta Pathol Microbin[ Scand Sect A 84:538-540. 2. Becher R, Wake N, Gibas Z, Ochi H, Sandberg AA (1{.t84): Chromosome changes in soft tissue sarcomas. J Natl Cancer Inst 72:823-831. 3. Atkin NB, Baker MC (1985): Chromosome studies of five cancers of the prostate. Hum Genet 70:359--364. 4. Limon J, Dal Cin P, Sandberg AA (1986): Cytogenetic findings in a primary leiomyosarcmna of the prostate. Cancer Genet Cytogenet 22:159-167. 5. Wake N, Slocum IIK, Rustum YM, Matsui S, Sandberg AA (1981): Chromosomes and cau-
288
P. Dal Cin, L. Boghosian, and A. A. Sandberg
sation of humal~ cancer and leukemia. XI.,IV. A method fcJr chronloson~e analysis of solid tumors. Cancer Genet Cytoge, net 3:1-10. ~5. l,imon I, Dal Cin P, Sandberg AA (198fi): Application of long term collagenase disaggregation for the cytogenetic analysis of human solid tumors. Cancer Genet Cytogenet 23:3115317. 7. Enzinger FM, We,iss SW {1983): Soft Tissue 'l'umors. CV Mosby, St. Louis, Mo, pp. 298315.
ABSTRACT: A cytogenetic studv of a leiomyosarcoma of the small bowel revealed numerical and structural chromosome changes. Several of these changes, in particular the loss of one chromosome #14. #15, #18, and #22. and del(ll(p12p131 have been rel)orted previously m an unrelated leionLvosarcoma of th('. small bowel. We suggest that these or part of these findings could l)e characteristic of leiomyosarcoma of the small bowel.
INTRODUCTION
To date. the cytogenetic findings in only five leiomyosarcomas have been reported [1-5]. A normal female karyotype (46.XX) was reported in one [5], in all others clmlal chromosome changes were observed. A consistent involvement of chromnsam(; #1 was found in three of the four abnornlal leiomyosarcomas. We report the cytugenetic findings in a h;iomyosarcoma of the small bowel, which are similar to those described by Mark [1] in an identical type of tumor. CASE REPORT
In December 1985, a 56-year-old male u n d e r w e n t laparotolny for abdominal pain. A tumor of the small bowel was found, which was adherent to the sigmoid, and had resulted in perforation of the signloid colon with localized pelvic abscesses. The tumor was resected along with the adjacent small bowel. The pathologic diagnosis was leiomyosarcoma of the small intestine. Following surgery, the patient was giwm six courses of vincristine, adriamycin, and cyclophospharnide. I te was reexplored surgically in May and August, 1986. All macroscopic tumor was removed, i n c l u d i n g serosal implants in the pelvic peritoneum, ileum, and jejunum. There was iio liver ilwulvement. The patient was placed on DTIC and adriamycin therapy. Recently, the patient was readmitted for a "look-laparotomy" to reevaluate the progression of the disease. He was found to have multiple tumor implants in the pelvis (i.e., in the mesentery of the small bowel and colon), as well as multiple implants over the jejunum, ileum, and from the angle of Treitz to the sacrum. Again, the liver was not involved. All macroscopic tumor was removed at this laparotomy, and a pie(:e was examined cytogenetically. Multiple sections showed soft
From tile Rosv,,el]Park MenlorialInstitute. Buffal(). NY, Address requests for reprints to Dr. Avery A. Sandberg, The Cancer Center, Southwest Biomedical Research Institute, 6401 1,:. Thomas ltd.. Scottsdale. AZ 85251. l|eceived July 20. 1987: a(:t:epted September 4. 1987.
285 .~:.1988 ElsevierScit~n(:ePublishingCo.. lnc. 52 Vanderhilt Ave.. New York. NY 10017
Cancer (,(;]let Cytogenet 30:2,~5-288[1988) 0165-4608/88/$(13.50
P. Dal Cin, L. Boghosian,
286 tissue infiltration by with pink cytoplasm, ular chromatin. The erately differentiated CYTOGENETIC
and A. A. Sandberg
a spindle cell tumor. The cells were plump spindle shaped the nuclei were elongated with blunt corners and finely grancells were arranged in intervening fasicles. A recurrent modleiomyosarcoma was diagnosed.
ANALYSIS
Chromosomal analysis of tumor cells from one of the mesenteric implants was performed on a 4-day-old culture from a collangenase disaggregated specimen of the surgically excised tumor, according to procedures previously described [6]. Sixteen of the 27 metaphases analyzed exhibited a normal male karyotype (46,XY). Numerical and structural chromosome abnormalities were present in the 11 remaining mitoses (Table 1). The karyotype of the stem line was 42,XY,del(l)(pl2pl3), de1(4)(q31.1),-9,+der(9)t(9;?)(q34;?),-14,-15,-18,de1(21)(q22.1),-22 (Fig. 1). DISCUSSION Leiomyosarcomas are malignant neoplasms that arise from smooth muscle. They are principally tumors of adult life, more common in women than in men, and in rare cases may be radiation-induced [7]. They can occur anywhere in the body; Figure 1 Karyotype of a stem line cell. Arrows point to the monosomy of the chromosomes #14, #l.!i, #18, and #22.
6
7
20
4 de14
3
2
1 del 1
8
9 dsr 9
10
21 del23
11
22
5
12*
XV
287
I , e i o m y o s a r c o m a of t h e S m a l l B o w e l
Table 1
Chromosome abnormalities Chromosome deviations
KaryotYt}C, number
Chromosome number
1
4
9
14
15
18
21
22
N
q+
-14 -14 -14 -14 -14 -14 -14 -14 N N N
-15 -15 -15 -15 -15 -15 -15 -15 N N N
-18 - 18 - 18 --18 -18 - 18 -18 - 18 N N N
qqIx,' N q(1qqN N N
22 -22 -22 -22 -22 -22 -22 -22 N -22 N
1
42
p-
2 3 4 5 6 7 8 9 10 11
42 40 42 42 42 42 42 46 42 45
pp p ppppN qp-
N N N qqqqqN N
qq+ q~ q-~ q ¢ q-¢ q*N q4 q ¢-
N. Presence of two normal chromosomes.
h o w e v e r , t h e y are h i s t o l o g i c a l l y s i m i l a r , t t a l f of all l e i o m y o s a r c o m a s o c c u r in t h e r e t r o p e r i t o n e u m , w h e r e t h e y are h i g h l y a g g r e s s i v e m a k i n g total r e s e c t i o n u s u a l l y impossible. O n l y four c y t o g e n e t i c a l l y a b n o r m a l ] e i o m y o s a r c o m a s h a v e b e e n d e s c r i b e d so far [1-4], t w o r e m o v e d f r o m t h e p r o s t a t e a n d t w o from t h e s m a l l b o w e l . I n v o l v e m e n t of t h e p a r m of c h r o m o s o m e # 1 was r e p o r t e d in t h r e e of t h e four cases. A t(1;22)(p32;q22) w a s f o u n d by B e c h e r et al. [2] as t h e o n l y c h a n g e in t w o of t h e 50 m e t a p h a s e s in a l e i o m y o s a r c o m a of t h e s m a l l b o w e l . A d e l ( 1 ) ( p 1 2 p 1 3 ) w a s des c r i b e d by Mark, in a l e i o m y o s a r c o m a of t h e s m a l l b o w e l [1] a n d in o n e of t h e p r o s t a t e (case 5 in ref. [3] b y A t k i n et al.). O u r case s h o w e d d e l ( 1 ) ( p 1 2 p 1 3 ) , del(4)(q31.1], der(9), del(21)(q22.1), a n d m o n o s o m y of c h r o m o s o m e s # 1 4 , # 1 5 , #18, and #22. It is i n t e r e s t i n g that in t h e case r e p o r t e d by Mark. t h o u g h del(111(q13-14) a n d t r i s o m y 7 w e r e p r e s e n t , d e l ( 1 ) ( p 1 2 - 1 3 ) a n d m o n o s o m y of c h r o m o s o m e s # 1 4 , # 1 5 , # 1 8 , a n d # 2 2 , as o b s e r v e d in o u r case, w e r e also c o n s i s t e n t f i n d i n g s . T h e r e f o r e , d e l ( 1 ) ( p 1 2 - 1 3 ) a n d m o n o s o m y 14, 15, 18, a n d 22 or a n y p a r t s of t h e s e c h a n g e s f o u n d in t w o u n r e l a t e d l e i o m y o s a r c o m a s of t h e s m a l l b o w e l , c o u l d c h a r a ( : t e r i z e a s u b g r o u p of r e t r o p e r i t o n e a l l e i o m y o s a r c o m a . Supported in part by Grant CA-14555 from the National Cancer Institute. The authors thank Dr. C. Karakousis for supplying the tumor sample, Joyce Romano for her technical assistance, and Sharon Zolnowski for clerical aspects of the paper.
REFERENCES
1. Mark J (1976}: G-band analyses of a human intestinal leiomyosarcoma. Acta Pathol Microbin[ Scand Sect A 84:538-540. 2. Becher R, Wake N, Gibas Z, Ochi H, Sandberg AA (1{.t84): Chromosome changes in soft tissue sarcomas. J Natl Cancer Inst 72:823-831. 3. Atkin NB, Baker MC (1985): Chromosome studies of five cancers of the prostate. Hum Genet 70:359--364. 4. Limon J, Dal Cin P, Sandberg AA (1986): Cytogenetic findings in a primary leiomyosarcmna of the prostate. Cancer Genet Cytogenet 22:159-167. 5. Wake N, Slocum IIK, Rustum YM, Matsui S, Sandberg AA (1981): Chromosomes and cau-
288
P. Dal Cin, L. Boghosian, and A. A. Sandberg
sation of humal~ cancer and leukemia. XI.,IV. A method fcJr chronloson~e analysis of solid tumors. Cancer Genet Cytoge, net 3:1-10. ~5. l,imon I, Dal Cin P, Sandberg AA (198fi): Application of long term collagenase disaggregation for the cytogenetic analysis of human solid tumors. Cancer Genet Cytogenet 23:3115317. 7. Enzinger FM, We,iss SW {1983): Soft Tissue 'l'umors. CV Mosby, St. Louis, Mo, pp. 298315.