Cytogenetics of Sacral Chordoma Joanne M. DeBoer, James R. Neff, and Julia A. Bridge
ABSTRACT: Only four cases of chordoma have been described cytogenetically. We report the cytogenetic findings of a fifth case. Chromosome analysis of a primary sacral chordoma from a 69-year-old man showed the following chromosome complement: 4 3 , X Y , - 2 , - 3 , d e l ( 4 ) ( q 3 2 ) , - 6 , + 7,-11, der(12)t(9;12)(q12;p11),add(16)(q23),-20,add(22)(q13),+mar.
INTRODUCTION Chordoma is a rare, malignant bone tumor believed to originate from the remnants of the fetal notochord [1]. Primary lesions occur most frequently in the sacrococcygeal region [2]. The literature regarding karyotypic anomalies of chordoma consists of two reports encompassing only four cases [3, 4]. We report a fifth case of chordoma and compare our findings with the findings of the previously described cases.
CASE HISTORY
The patient was a 69 year-old white man who was well until approximately 4 years before being evaluated medically for lower back and presacral pain. Radiographs of the sacrum showed a destructive process involving $2 and below. Histologic examination of the resulting biopsy showed cords and lobules of cells separated by mucoid intercellular substance. Many of the individual tumor cells were large, with vacuolated cytoplasms and prominent vesicular nuclei: "physaliferous cells" (Fig. 1). Clinical, radiographic, and pathologic findings were diagnostic of chordoma. After diagnosis, a radical sacral amputation was performed through the body of $1. A portion of the amputation specimen was submitted for cytogenetic analysis. The patient is clinically and radiographically free of disease.
MATERIALS AND METHODS
A 0.5-cm 3 sterile tumor sample removed at the time of sacral amputation was processed for cytogenetic studies by mechanical and enzymatic disaggregation before being
From the Department of Pediatrics (J. M. D., J. A. B.), Departments of Pathology and Microbiology (l. A. B.) and Orthopedics (J. R. N.), University of Nebraska Medical Center, Omaha, Nebraska. Address reprint requests to Dr. Julia A. Bridge, Departments of Pathology~Microbiology and Pediatrics, University of Nebraska Medical Center, 600 S. 42nd St., Omaha, NE 68198-5440. Received April 27, 1992; accepted July 1, 1992.
cultured. Six- to 16-day in situ and flask cultures produced metaphase cells by standard culture and harvest methods described previously [5]. The karyotypes were expressed according to the International System for H u m a n Cytogenetic Nomenclature 1991 [6]. RESULTS Twenty GTG-banded metaphase cells were analyzed. Eleven cells were karyotypically normal. The remaining nine cells showed the following abnormal clone: 43,XY, - 2, - 3 ,del(4)(q32), - 6, + 7, - 11 ,der(12)t(9 ;12)(ql 2 ;p 11), add(16)(q23),-20,add(22)(q13),+mar (Fig. 2). DISCUSSION
Chordoma, a rare malignant tumor of the axial skeleton, is characterized by repeated local recurrences and generally a fatal outcome. Microscopically, the tumor closely resembles normal notochord tissue in its different stages of development. Characteristic cells, k n o w n as physaliferous cells, are extremely large with a highly vacuolated cytoplasm. Cytogenetic reports of primary bone tumors are few. Chordoma is no exception. We describe only the fifth case to be characterized cytogenetically. Since our initial description of the cytogenetic findings in two sacral chordomas [3], two other cases have been reported [4]. In our first report, we described one case that exhibited a normal chromosome complement, with the exception of one randomly abnormal cell which was monosomic for chromosome 21. This monosomic cell was of interest because the second case studied demonstrated m o n o s o m y 21 as a clonal feature in one of two separate abnormal clones. Gibes et el. [4] also reported the potential significance of chromosome 21 in the development of chordoma; specifically, they noted chromosome band 21q22 as a translocation breakpoint in their two cases. In contrast, our present case did not show numerical or structural abnormalities of chromosome 21. Evaluation of the cytogenetic results of the five • chordoma cases studied thus far have not shown a characteristic chromosomal anomaly, although loss of certain 95
© 1992 Elsevier Science P u b l i s h i n g Co., Inc. 655 A v e n u e of the Americas, New York, NY 10010
Cancer Genet Cytogenet 6 4 : 9 5 - 9 6 (1992) 0165-4608/92/$05.00
96
J.M. DeBoer et el.
Figure 1 Chordoma cells showing variation in size and marked cytoplasmic vacuolization. (Hematoxylin and eosin, × 300).
Figure 2 Representative karyotype of abnormal clone from primary chordoma: 43,XY,-2,-3,del(4)(q32),-6,+7,-11, der(12)t(9;12)(q12;p11),add(16)(q23),- 20,add(22)(q13),+mar. Monosomy for chromosomes 13 and 14 was observed only in this metaphase.
i~
~
~ i~
~!!
~
~ ~ ii~
5
11,I
chromosomes was noted. M o n o s o m y was most frequently observed for chromosomes 2, 3, and 21 (each involved in three of the four abnormal cases). Chromosomes 4, 11, 13, and 22 were each monosomic in two of the four abnormal cases. Cytogenetic analysis of five chordomas has s h o w n clonal chromosomal abnormalities in four of five neoplasms. Although specific chromosomes (#2, 3, 4, 11, 21, and 22) may be significant in the d e v e l o p m e n t of chordoma, a specific karyotypic abnormality has not yet been defined. Additional cytogenetic studies of this rare n e o p l a s m are necessary to determine the critical genetic events in this tumor. REFERENCES
9
m
11
. i._l,
t 13
10
15
14
16
12
t°
17
18
21
22
~
\ 19
20 mar
1. Healy JH, Lane JM (1989): Chordoma: A critical review of diagnosis and treatment. Orthop Clin North Am 2 0 : 4 1 7 - 4 2 6 . 2. Rich TA, Schiller A, Suit HD, Mankin HJ (1984): Clinical and pathologic review of 48 cases of chordoma. Cancer 56:182-187. 3. Persons DL, Bridge JA, Neff JR (1991): Cytogenetic analysis of two sacral chordomas. Cancer Genet Cytogenet 56:197-201. 4. Gibes Z, Miettinen M, Sandberg AA (1992): Chromosomal abnormalities in two chordomas. Cancer Genet Cytogenet 58:169-173. 5. Bridge JA, Neff JR, Mouron BJ (1992): Giant cell tumor of bone: Chromosomal analysis of 48 specimens and review of the literature. Cancer Genet Cytogenet 58:2-13. 6. ISCN (1991): Cancer Cytogenetics, Supplement to An International System for Human Cytogenetic Nomenclature. Mitelman F (ed.), published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1991).
ABSTRACT: Only four cases of chordoma have been described cytogenetically. We report the cytogenetic findings of a fifth case. Chromosome analysis of a primary sacral chordoma from a 69-year-old man showed the following chromosome complement: 4 3 , X Y , - 2 , - 3 , d e l ( 4 ) ( q 3 2 ) , - 6 , + 7,-11, der(12)t(9;12)(q12;p11),add(16)(q23),-20,add(22)(q13),+mar.
INTRODUCTION Chordoma is a rare, malignant bone tumor believed to originate from the remnants of the fetal notochord [1]. Primary lesions occur most frequently in the sacrococcygeal region [2]. The literature regarding karyotypic anomalies of chordoma consists of two reports encompassing only four cases [3, 4]. We report a fifth case of chordoma and compare our findings with the findings of the previously described cases.
CASE HISTORY
The patient was a 69 year-old white man who was well until approximately 4 years before being evaluated medically for lower back and presacral pain. Radiographs of the sacrum showed a destructive process involving $2 and below. Histologic examination of the resulting biopsy showed cords and lobules of cells separated by mucoid intercellular substance. Many of the individual tumor cells were large, with vacuolated cytoplasms and prominent vesicular nuclei: "physaliferous cells" (Fig. 1). Clinical, radiographic, and pathologic findings were diagnostic of chordoma. After diagnosis, a radical sacral amputation was performed through the body of $1. A portion of the amputation specimen was submitted for cytogenetic analysis. The patient is clinically and radiographically free of disease.
MATERIALS AND METHODS
A 0.5-cm 3 sterile tumor sample removed at the time of sacral amputation was processed for cytogenetic studies by mechanical and enzymatic disaggregation before being
From the Department of Pediatrics (J. M. D., J. A. B.), Departments of Pathology and Microbiology (l. A. B.) and Orthopedics (J. R. N.), University of Nebraska Medical Center, Omaha, Nebraska. Address reprint requests to Dr. Julia A. Bridge, Departments of Pathology~Microbiology and Pediatrics, University of Nebraska Medical Center, 600 S. 42nd St., Omaha, NE 68198-5440. Received April 27, 1992; accepted July 1, 1992.
cultured. Six- to 16-day in situ and flask cultures produced metaphase cells by standard culture and harvest methods described previously [5]. The karyotypes were expressed according to the International System for H u m a n Cytogenetic Nomenclature 1991 [6]. RESULTS Twenty GTG-banded metaphase cells were analyzed. Eleven cells were karyotypically normal. The remaining nine cells showed the following abnormal clone: 43,XY, - 2, - 3 ,del(4)(q32), - 6, + 7, - 11 ,der(12)t(9 ;12)(ql 2 ;p 11), add(16)(q23),-20,add(22)(q13),+mar (Fig. 2). DISCUSSION
Chordoma, a rare malignant tumor of the axial skeleton, is characterized by repeated local recurrences and generally a fatal outcome. Microscopically, the tumor closely resembles normal notochord tissue in its different stages of development. Characteristic cells, k n o w n as physaliferous cells, are extremely large with a highly vacuolated cytoplasm. Cytogenetic reports of primary bone tumors are few. Chordoma is no exception. We describe only the fifth case to be characterized cytogenetically. Since our initial description of the cytogenetic findings in two sacral chordomas [3], two other cases have been reported [4]. In our first report, we described one case that exhibited a normal chromosome complement, with the exception of one randomly abnormal cell which was monosomic for chromosome 21. This monosomic cell was of interest because the second case studied demonstrated m o n o s o m y 21 as a clonal feature in one of two separate abnormal clones. Gibes et el. [4] also reported the potential significance of chromosome 21 in the development of chordoma; specifically, they noted chromosome band 21q22 as a translocation breakpoint in their two cases. In contrast, our present case did not show numerical or structural abnormalities of chromosome 21. Evaluation of the cytogenetic results of the five • chordoma cases studied thus far have not shown a characteristic chromosomal anomaly, although loss of certain 95
© 1992 Elsevier Science P u b l i s h i n g Co., Inc. 655 A v e n u e of the Americas, New York, NY 10010
Cancer Genet Cytogenet 6 4 : 9 5 - 9 6 (1992) 0165-4608/92/$05.00
96
J.M. DeBoer et el.
Figure 1 Chordoma cells showing variation in size and marked cytoplasmic vacuolization. (Hematoxylin and eosin, × 300).
Figure 2 Representative karyotype of abnormal clone from primary chordoma: 43,XY,-2,-3,del(4)(q32),-6,+7,-11, der(12)t(9;12)(q12;p11),add(16)(q23),- 20,add(22)(q13),+mar. Monosomy for chromosomes 13 and 14 was observed only in this metaphase.
i~
~
~ i~
~!!
~
~ ~ ii~
5
11,I
chromosomes was noted. M o n o s o m y was most frequently observed for chromosomes 2, 3, and 21 (each involved in three of the four abnormal cases). Chromosomes 4, 11, 13, and 22 were each monosomic in two of the four abnormal cases. Cytogenetic analysis of five chordomas has s h o w n clonal chromosomal abnormalities in four of five neoplasms. Although specific chromosomes (#2, 3, 4, 11, 21, and 22) may be significant in the d e v e l o p m e n t of chordoma, a specific karyotypic abnormality has not yet been defined. Additional cytogenetic studies of this rare n e o p l a s m are necessary to determine the critical genetic events in this tumor. REFERENCES
9
m
11
. i._l,
t 13
10
15
14
16
12
t°
17
18
21
22
~
\ 19
20 mar
1. Healy JH, Lane JM (1989): Chordoma: A critical review of diagnosis and treatment. Orthop Clin North Am 2 0 : 4 1 7 - 4 2 6 . 2. Rich TA, Schiller A, Suit HD, Mankin HJ (1984): Clinical and pathologic review of 48 cases of chordoma. Cancer 56:182-187. 3. Persons DL, Bridge JA, Neff JR (1991): Cytogenetic analysis of two sacral chordomas. Cancer Genet Cytogenet 56:197-201. 4. Gibes Z, Miettinen M, Sandberg AA (1992): Chromosomal abnormalities in two chordomas. Cancer Genet Cytogenet 58:169-173. 5. Bridge JA, Neff JR, Mouron BJ (1992): Giant cell tumor of bone: Chromosomal analysis of 48 specimens and review of the literature. Cancer Genet Cytogenet 58:2-13. 6. ISCN (1991): Cancer Cytogenetics, Supplement to An International System for Human Cytogenetic Nomenclature. Mitelman F (ed.), published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1991).
