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Recurrent t(12;19)(q13;q13.3) in intracranial and extracranial hemangiopericytoma
Recurrent t(12;19)(q13;q13.3) in Intracranial and Extracranial Hemangiopericytoma Wolfram Helm, Bernd Wullich, Monika Th6nnes, Wolf-Ingo Steudel, Wolfgang Feiden, and Klaus D. Zang ABSTRACT: We rep•rt •n a recurrent intracrania• hemangi•pericyt•ma
cyi•genetica••y
studied after sh•rt-
term culture. The tumor had a uniform karyotype 47,XX, add(7)(q21),t(12;19)(q13;q13.3),del(13)(q14q22), + 21. Remarkably, one case with an identical reciprocal (12;19) translocation has been previously reported as the sole cytogenetic change in a recurrent retroperitoneal hemangiopericytoma. This nonrandom structural change may characterize a subentity of hemangiopericytoma and might be of diagnostic value.
INTRODUCTION Hemangiopericytomas are rare mesenchymal tumors of borderline malignancy which can arise at various sites of the body [1]. Hemangiopericytomas of the brain coverings have long been histologically classified as a subtype of meningioma [2] but are characterized by a significantly higher recurrence rate than genuine meningiomas. Cytogenetic studies on meningeal hemangiopericytomas have revealed the absence of monosomy 22 typical for meningiomas [3]; instead, hemangiopericytomas showed a variety of clonal chromosome rearrangements but no recurrent aberration so far [4, 5]. We report on an intracranial hemangiopericytoma with a reciprocal translocation t(12 ;19) apparently identical to that reported before from a retroperitoneal hemangiopericytoma [6].
lar coagulation. After surgery, the patient showed rapid recovery. MATERIALS AND METHODS A tissue specimen from the last tumor resection was obtained immediately after surgery and processed according to previously described procedures [7]. The cell culture was grown in Dulbecco's modified Eagle's minimal essential medium supplemented with 10% fetal calf serum and antibiotics. Chromosomes of tumor cells were harvested in the primary culture after 4 days and in the first in vitro passage. The patient's constitutional karyotype was established from a particle culture of a scalp biopsy taken at the operation site. Chromosome preparation and GTG-banding followed standard procedures [8]. The karyotype was defined according to the International System for Cytogenetic Nomenclature [9].
CASE REPORT The 64-year-old female patient was first operated in 1988 for a cerebellopontine angle tumor on her left side. Attacks of dizziness, headache and vomiting had increased over a couple of weeks. The tumor involving the posterior petrous ridge was removed subtotally with tentorial splitting. A local recurrent tumor was removed in 1989. The patient was free of symptoms until 1991 when headache and vomiting occurred again. The third operation followed in May 1992. Again the tumor arose from the posterior surface of the petrous ridge adjacent to the porous acousticus in the cerebellopontine angle. The site of dural attachment was cauterized with bipo-
From the Institute of Human Genetics (W. H., B. ILK.,M. T., K. D. Z.) and the Departments ofNeurosurgery (W.-I. S.), and Neuropathology (W. E ), University of the Saar, Homburg/Saar, Germany. Address reprint requests to: WolframHenn, M.D., Institute of Human Genetics, University of the Saar, University Bldg. 68, D-6650 Homburg/Saar, Germany. Received March 30, 1993; accepted July 16, 1993.
RESULTS
Histology Paraffin sections of all three resection specimens showed tumor tissue which consisted of tightly packed cells with moderate amounts of cytoplasm and ill-defined cytoplasm borders. The cells were arranged in solid areas and around thin-walled blood vessels some of which showed "staghorn" configuration (Fig. la). The solid areas did not show any special structure, i.e., fascicular or whorled structures, and looked yet chaotic (Fig. lc). Gomori's stain revealed a dense reticulin meshwork surrounding vessels and tumor cells. The tumor cell nuclei were oval and plump, somehow pleomorphic (Fig. lb). Mitotic figures were encountered in moderate numbers. Partly, nuclei resembled those of meningioma cells in that they were centrally pale (Fig. lc).
Cytogenetics In both the primary culture (12 mitoses) and the first passage (20 mitoses), the hemangiopericytoma showed the uni151
© 1993 Elsevier Science P u b l i s h i n g Co., Inc. 655 A v e n u e of the Americas, N e w York, NY 10010
Cancer Genet Cylogenet 7 1 : 1 5 1 - 1 5 4 (1993) 0165-4608/93/$06.00
152
W. Henn et al.
Figure 1. Hemangiopericytoma. (a) Large gaping sinusoidal space in a tumor tissue of high cellularity. HE, × 90. (b) Capillary-sized vessel lined by a single layer of flattened endothelial cells. Pleomorphic tumor cell nuclei. HE, x 180. (c) Solid tumor area with centrally pale nuclei resembling meningioma. HE, x 180.
form karyotype 4ZXX,add(7)(q21),t(12;19)(q13;q13.3},del(13) (q14q22), + 21. The breakpoints of the reciprocal t(12;19) apparently are identical to those reported by Sreekantaiah et al. [6] from a recurrent retroperitoneal hemangiopericytoma. A representative karyogram in shown on Fig. 2. The patient's constitutional karyotype was 46,XX. DISCUSSION Several types of bone and soft tissue neoplasms are characterized by consistent tumor-specific reciprocal translocations
which are of diagnostic value, e.g., t(X;18) in synovial sarcoma [10] or t(11; 2 2} in Ewing's sarcoma [11]. In other mesenchymal tumors, specific structural aberrations only account for cytogenetic subtypes of less homogeneous entities, e.g., rearrangements of band 13q12 in lipoma [12, 13], t{12;14) in uterine leiomyoma [14], or a 19p + marker in malignant fibrous histiocytoma [15]. In the few cytogenetically studied cases of hemangiopericytoma, however, no recurrent chromosome aberration had been detected. The case presented here confirms a translocation t(12;19}{q13;q13.3) which had first been described by Sreekantaiah [6] as the sole cytogenetic
t(12;19) in H e m a n g i o p e r i c y t o m a
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ii
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7
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t! 2O F i g u r e 2.
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G-banded representative karyogmm; karyotype 47,XX,add(7)(q21),t(12;19)(q13;q13.3),del(13)(q14q22), + 21.
a n o m a l y in a retroperitoneal hemangiopericytoma. This translocation which, to the best of our knowledge, has not been found in any other type of t u m o r so far [16], may cytogenetically define a subtype of hemangiopericytoma. We suppose that trisomy 21, the interstitial del(13)(q21q31] and the not clearly assignable structural change of 7q are non-specific s e c o n d a r y c h r o m o s o m a l changes in this tumor as they have not been reported from other cases of hemangiopericytoma so far. However, cytogenetic data and their correlation to the clinical course of the disease are n e e d e d to outline the incidence of this (12;19) translocation and its possible clinical relevance. Remarkably, the breakpoints on chromosome 12 and 19, respectively, are involved in translocations with other chrom o s o m e s in several p u b l i s h e d hemangiopericytomas. Most striking is the involvement of b a n d 19q13.3 in four out of six clonally aberrant hemangiopericytomas described so far (three in the series of Sreekantaiah et al. [6], and our case). This observation points towards the localization of a yet unidentified gene at 19(t13.3, a rearrangement of w h i c h apparently is a crucial step in the tumorigenesis of hemangiopericytomas. Moreover, b a n d 12(t13 is a hot spot of chromosomal rearrangements in a variety of mesenchymal tumors such as l i p o m a [13], l i p o s a r c o m a [17], and uterine leiomyoma [14]. Several proliferation-associated genes have been m a p p e d to these b r e a k p o i n t regions [18], but their relevance for the pathogenesis of at least this cytogenetically defined subtype of h e m a n g i o p e r i c y t o m a still has to be elucidated by molecular analysis. This study was supported by the Hedwig-Stalter-Stiftung. REFERENCES
1. Enzinger FM, Weiss SW (1988): Soft Tissue Tumors, Second Edition, The C.V. Mosby Company, Missouri.
2. D~,more ESG, Manivel JC, Sung JH (1990): Soft-tissue and meningeal hemangiopericytomas: An immunohistochemical and ultmstructural study. Hum Pathol 21:414-423. 3. Zang KD (1982): Cytological and cytogenetic studies on human meningioma. Cancer Genet Cytogenet 6:249-272. 4. Becher R, Wake N, Gibas Z, Ochi H, Sandberg AA (1984): Chromosome changes in soft tissue sarcomas. JNCI 72:823-831. 5. Limon J, Rao U, Dal Cin P, Gibas Z, Sandberg AA (1986): Tmnslocation (13;22) in a hemangiopericytoma. Cancer Genet Cytogenet 21:309-318. 6. Sreekantaiah C, Bridge J, Rao U, Neff JR, Sandberg AA (1991): Clonal chromosomal abnormalities in hemangiopericytoma. Cancer Genet Cytogenet 54:173-181. 7. Limon J, Dal Cin P, Sandberg AA (1986): Application of longterm collagenase disaggregation for the cytogenetic analysis of human solid tumors. Cancer Genet Cytogenet 23:305-313. 8. Seabright M (1971): A rapid banding technique for human chromosomes. Lancet 2:971-972. 9. ISCN (1985): An International System for Human Cytogenetic Nomenclature, Harnden DG, Klinger HP, eds. Karger, Basel. 10. Turc-Carel C, Dal Cin P, Limon J, Rao U, Li FP, Corson JM, Zimmerman R, Parry DM, Cowan JM, Sandberg AA (1987): Involvement of chromosome X in cytogenetic change in human neoplasia: Nonmndom tmnslocation in synovial sarcoma. Proc Natl Acad Sci USA 84:1981-1985. 11. Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM (1984): Chromosome study of Ewing's sarcoma (ES) cell lines: Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet Cytogenet 12:1-19. 12. Sreekantaiah C, Berger CS, Karakousis CP, Rao U, Leong SPL, Sandberg AA (1989): Cytogenetic subtype involving chromosome 13 in lipoma: report of 3 cases. Cancer Genet Cytogenet 39:281-288. 13. Sreekantaiah C, Leong SPL, Karakousis CP, McGee DL, Rappaport WD, Villar H, Neal D, Fleming S, Wankel A, Herrington PN, Carrnona R, Sandberg AA (1991): Cytogenetic profile of 109 lipomas. Cancer Genet Cytogenet 51:422-433. 14. Mark J, Havel G, Grepp C, Dahlenfors R, Wedell B (1990): Chromosomal patterns in human benign uterine leiomyomas. Cancer Genet Cytogenet 44:1-13.
154 15. Mandahl N, Heim S, Willen H, Rydholm A, Eneroth M, Nilbert M, Kreicbergs A, Mitelman F (1990): Characteristic karyotype anomalies identify subtypes of malignant fibrous histiocytoma. Genes Chrom Cancer 1:9-14. 16. Mitelman F (1988): Catalog of Chromosome Aberrations in Cancer, 3rd edition, Alan R. Liss, Inc., New York. 17. Eneroth M, Mandahl N, Heim S, Willen H, Rydholm A, Alberts
W. H e n n et al.
KA, Mitelman F (1990): Localization of the chromosomal breakpoints of the t(12;16) in liposarcoma to subbands 12q13.3 and 16p11.2. Cancer Genet Cytogenet 48:101-107. 18. Meltzer S, Jankowski SA, Dal Cin P, Sandberg AA, Paz IB, Coccia MA, Smith SH (1991): Identification and cloning of a novel amplified DNA sequence in human malignant fibrous histiocytoma derived from a region of chromosome 12 frequently rearranged in soft tissue tumors. Human Gene Mapping ll:A 27350.
cyi•genetica••y
studied after sh•rt-
term culture. The tumor had a uniform karyotype 47,XX, add(7)(q21),t(12;19)(q13;q13.3),del(13)(q14q22), + 21. Remarkably, one case with an identical reciprocal (12;19) translocation has been previously reported as the sole cytogenetic change in a recurrent retroperitoneal hemangiopericytoma. This nonrandom structural change may characterize a subentity of hemangiopericytoma and might be of diagnostic value.
INTRODUCTION Hemangiopericytomas are rare mesenchymal tumors of borderline malignancy which can arise at various sites of the body [1]. Hemangiopericytomas of the brain coverings have long been histologically classified as a subtype of meningioma [2] but are characterized by a significantly higher recurrence rate than genuine meningiomas. Cytogenetic studies on meningeal hemangiopericytomas have revealed the absence of monosomy 22 typical for meningiomas [3]; instead, hemangiopericytomas showed a variety of clonal chromosome rearrangements but no recurrent aberration so far [4, 5]. We report on an intracranial hemangiopericytoma with a reciprocal translocation t(12 ;19) apparently identical to that reported before from a retroperitoneal hemangiopericytoma [6].
lar coagulation. After surgery, the patient showed rapid recovery. MATERIALS AND METHODS A tissue specimen from the last tumor resection was obtained immediately after surgery and processed according to previously described procedures [7]. The cell culture was grown in Dulbecco's modified Eagle's minimal essential medium supplemented with 10% fetal calf serum and antibiotics. Chromosomes of tumor cells were harvested in the primary culture after 4 days and in the first in vitro passage. The patient's constitutional karyotype was established from a particle culture of a scalp biopsy taken at the operation site. Chromosome preparation and GTG-banding followed standard procedures [8]. The karyotype was defined according to the International System for Cytogenetic Nomenclature [9].
CASE REPORT The 64-year-old female patient was first operated in 1988 for a cerebellopontine angle tumor on her left side. Attacks of dizziness, headache and vomiting had increased over a couple of weeks. The tumor involving the posterior petrous ridge was removed subtotally with tentorial splitting. A local recurrent tumor was removed in 1989. The patient was free of symptoms until 1991 when headache and vomiting occurred again. The third operation followed in May 1992. Again the tumor arose from the posterior surface of the petrous ridge adjacent to the porous acousticus in the cerebellopontine angle. The site of dural attachment was cauterized with bipo-
From the Institute of Human Genetics (W. H., B. ILK.,M. T., K. D. Z.) and the Departments ofNeurosurgery (W.-I. S.), and Neuropathology (W. E ), University of the Saar, Homburg/Saar, Germany. Address reprint requests to: WolframHenn, M.D., Institute of Human Genetics, University of the Saar, University Bldg. 68, D-6650 Homburg/Saar, Germany. Received March 30, 1993; accepted July 16, 1993.
RESULTS
Histology Paraffin sections of all three resection specimens showed tumor tissue which consisted of tightly packed cells with moderate amounts of cytoplasm and ill-defined cytoplasm borders. The cells were arranged in solid areas and around thin-walled blood vessels some of which showed "staghorn" configuration (Fig. la). The solid areas did not show any special structure, i.e., fascicular or whorled structures, and looked yet chaotic (Fig. lc). Gomori's stain revealed a dense reticulin meshwork surrounding vessels and tumor cells. The tumor cell nuclei were oval and plump, somehow pleomorphic (Fig. lb). Mitotic figures were encountered in moderate numbers. Partly, nuclei resembled those of meningioma cells in that they were centrally pale (Fig. lc).
Cytogenetics In both the primary culture (12 mitoses) and the first passage (20 mitoses), the hemangiopericytoma showed the uni151
© 1993 Elsevier Science P u b l i s h i n g Co., Inc. 655 A v e n u e of the Americas, N e w York, NY 10010
Cancer Genet Cylogenet 7 1 : 1 5 1 - 1 5 4 (1993) 0165-4608/93/$06.00
152
W. Henn et al.
Figure 1. Hemangiopericytoma. (a) Large gaping sinusoidal space in a tumor tissue of high cellularity. HE, × 90. (b) Capillary-sized vessel lined by a single layer of flattened endothelial cells. Pleomorphic tumor cell nuclei. HE, x 180. (c) Solid tumor area with centrally pale nuclei resembling meningioma. HE, x 180.
form karyotype 4ZXX,add(7)(q21),t(12;19)(q13;q13.3},del(13) (q14q22), + 21. The breakpoints of the reciprocal t(12;19) apparently are identical to those reported by Sreekantaiah et al. [6] from a recurrent retroperitoneal hemangiopericytoma. A representative karyogram in shown on Fig. 2. The patient's constitutional karyotype was 46,XX. DISCUSSION Several types of bone and soft tissue neoplasms are characterized by consistent tumor-specific reciprocal translocations
which are of diagnostic value, e.g., t(X;18) in synovial sarcoma [10] or t(11; 2 2} in Ewing's sarcoma [11]. In other mesenchymal tumors, specific structural aberrations only account for cytogenetic subtypes of less homogeneous entities, e.g., rearrangements of band 13q12 in lipoma [12, 13], t{12;14) in uterine leiomyoma [14], or a 19p + marker in malignant fibrous histiocytoma [15]. In the few cytogenetically studied cases of hemangiopericytoma, however, no recurrent chromosome aberration had been detected. The case presented here confirms a translocation t(12;19}{q13;q13.3) which had first been described by Sreekantaiah [6] as the sole cytogenetic
t(12;19) in H e m a n g i o p e r i c y t o m a
153
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G-banded representative karyogmm; karyotype 47,XX,add(7)(q21),t(12;19)(q13;q13.3),del(13)(q14q22), + 21.
a n o m a l y in a retroperitoneal hemangiopericytoma. This translocation which, to the best of our knowledge, has not been found in any other type of t u m o r so far [16], may cytogenetically define a subtype of hemangiopericytoma. We suppose that trisomy 21, the interstitial del(13)(q21q31] and the not clearly assignable structural change of 7q are non-specific s e c o n d a r y c h r o m o s o m a l changes in this tumor as they have not been reported from other cases of hemangiopericytoma so far. However, cytogenetic data and their correlation to the clinical course of the disease are n e e d e d to outline the incidence of this (12;19) translocation and its possible clinical relevance. Remarkably, the breakpoints on chromosome 12 and 19, respectively, are involved in translocations with other chrom o s o m e s in several p u b l i s h e d hemangiopericytomas. Most striking is the involvement of b a n d 19q13.3 in four out of six clonally aberrant hemangiopericytomas described so far (three in the series of Sreekantaiah et al. [6], and our case). This observation points towards the localization of a yet unidentified gene at 19(t13.3, a rearrangement of w h i c h apparently is a crucial step in the tumorigenesis of hemangiopericytomas. Moreover, b a n d 12(t13 is a hot spot of chromosomal rearrangements in a variety of mesenchymal tumors such as l i p o m a [13], l i p o s a r c o m a [17], and uterine leiomyoma [14]. Several proliferation-associated genes have been m a p p e d to these b r e a k p o i n t regions [18], but their relevance for the pathogenesis of at least this cytogenetically defined subtype of h e m a n g i o p e r i c y t o m a still has to be elucidated by molecular analysis. This study was supported by the Hedwig-Stalter-Stiftung. REFERENCES
1. Enzinger FM, Weiss SW (1988): Soft Tissue Tumors, Second Edition, The C.V. Mosby Company, Missouri.
2. D~,more ESG, Manivel JC, Sung JH (1990): Soft-tissue and meningeal hemangiopericytomas: An immunohistochemical and ultmstructural study. Hum Pathol 21:414-423. 3. Zang KD (1982): Cytological and cytogenetic studies on human meningioma. Cancer Genet Cytogenet 6:249-272. 4. Becher R, Wake N, Gibas Z, Ochi H, Sandberg AA (1984): Chromosome changes in soft tissue sarcomas. JNCI 72:823-831. 5. Limon J, Rao U, Dal Cin P, Gibas Z, Sandberg AA (1986): Tmnslocation (13;22) in a hemangiopericytoma. Cancer Genet Cytogenet 21:309-318. 6. Sreekantaiah C, Bridge J, Rao U, Neff JR, Sandberg AA (1991): Clonal chromosomal abnormalities in hemangiopericytoma. Cancer Genet Cytogenet 54:173-181. 7. Limon J, Dal Cin P, Sandberg AA (1986): Application of longterm collagenase disaggregation for the cytogenetic analysis of human solid tumors. Cancer Genet Cytogenet 23:305-313. 8. Seabright M (1971): A rapid banding technique for human chromosomes. Lancet 2:971-972. 9. ISCN (1985): An International System for Human Cytogenetic Nomenclature, Harnden DG, Klinger HP, eds. Karger, Basel. 10. Turc-Carel C, Dal Cin P, Limon J, Rao U, Li FP, Corson JM, Zimmerman R, Parry DM, Cowan JM, Sandberg AA (1987): Involvement of chromosome X in cytogenetic change in human neoplasia: Nonmndom tmnslocation in synovial sarcoma. Proc Natl Acad Sci USA 84:1981-1985. 11. Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM (1984): Chromosome study of Ewing's sarcoma (ES) cell lines: Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet Cytogenet 12:1-19. 12. Sreekantaiah C, Berger CS, Karakousis CP, Rao U, Leong SPL, Sandberg AA (1989): Cytogenetic subtype involving chromosome 13 in lipoma: report of 3 cases. Cancer Genet Cytogenet 39:281-288. 13. Sreekantaiah C, Leong SPL, Karakousis CP, McGee DL, Rappaport WD, Villar H, Neal D, Fleming S, Wankel A, Herrington PN, Carrnona R, Sandberg AA (1991): Cytogenetic profile of 109 lipomas. Cancer Genet Cytogenet 51:422-433. 14. Mark J, Havel G, Grepp C, Dahlenfors R, Wedell B (1990): Chromosomal patterns in human benign uterine leiomyomas. Cancer Genet Cytogenet 44:1-13.
154 15. Mandahl N, Heim S, Willen H, Rydholm A, Eneroth M, Nilbert M, Kreicbergs A, Mitelman F (1990): Characteristic karyotype anomalies identify subtypes of malignant fibrous histiocytoma. Genes Chrom Cancer 1:9-14. 16. Mitelman F (1988): Catalog of Chromosome Aberrations in Cancer, 3rd edition, Alan R. Liss, Inc., New York. 17. Eneroth M, Mandahl N, Heim S, Willen H, Rydholm A, Alberts
W. H e n n et al.
KA, Mitelman F (1990): Localization of the chromosomal breakpoints of the t(12;16) in liposarcoma to subbands 12q13.3 and 16p11.2. Cancer Genet Cytogenet 48:101-107. 18. Meltzer S, Jankowski SA, Dal Cin P, Sandberg AA, Paz IB, Coccia MA, Smith SH (1991): Identification and cloning of a novel amplified DNA sequence in human malignant fibrous histiocytoma derived from a region of chromosome 12 frequently rearranged in soft tissue tumors. Human Gene Mapping ll:A 27350.