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Cytogenetic analysis of a plexiform fibrohistiocytic tumor
Cytogenetic Analysis of a Plexiform Fibrohistiocytic Tumor S. Smith, C. D. M. Fletcher, M. A. Smith, and B. A. Gusterson
abstract: A plexiform fibrohistiucytic tu mot was analyzed cytogenetically after short-term in vitro culture. The stemline karyotype of this tumor was interpreted as 46,XY,-6,-8,del(4)(q25q31), del(20)(ql 1.2), + der(8)t(8;?)(p22;?), + mar. We beliew', this to be the first report of chromosome findings in this recently described histological entity.
INTRODUCTION Plexiform fibrohistiocytic tumor is a very recently recognized soft tissue neoplasm. Histologically, it consists of fibroblasts, histiocytelike cells, and osteoclastlike giant cells and is distinguished from other fibrohistiocytic lesions by the characteristic plexiform arrangement of the fibroblastic and histiocytic components. Clinically, it presents as a dermal or subcutaneous mass, most commonly in the upper limb and appears to affect p r e d o m i n a n t l y children and young adults, has a tendency to recur locally after excision, and in rare instances to metastasize nonfatally to l y m p h nodes
[~.]. The recognition of this tumor as a clinically and histologically distinct entity extends established classifications, [e.g., 2], of fibrohistiocytic tumors. Because cytogenetic data have provided supportive evidence for histological grouping within some of the more extensively studied solid tumors [see ref. 3 for review], we undertook a cytogenetic analysis of a plexiform fibrohistiocytic tumor and compared our findings in this case with published information on the cytogenetics of other fibrohistiocytic tumors. CASE REPORT
At the age of 13 months a male white infant had an ill-defined soft tissue swelling on the dorsum of the left foot. This tissue was excised and diagnosed as an u n u s u a l fibromatosis. At the age of 4 years he had extensive local recurrence that extended between the metatarsal bones to the sole of the foot. Wide reexcision necessitating amputation of the fifth ray was performed in May 1989. Histologically, both excision specimens were similar and showed the typical features of a plexiform fibrohistiocytic From the Sectionof Pathology,Instituteof CancerResearch, SurreySM2 5NG,UK (S. S., B. A. G.) and the Departments of Histopathology (C. D. M. F.) and Orthopaedics (M. A. S.), St. Thomas's Hospital, London, England. Address reprint requests to: Dr. S. Smith, Section of Pathology, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey SM2 5NG, England. Received September 28, 1989; accepted October 31, 1989.
31 © 1990 ElsevierSciencePublishingCo., Inc. 655 Avenue of the Americas,New York, NY 10010
Cancer Genet Cytogenet48:31 34 (1990) 0165-4608/90/$03.50
32
s. Smith et al.
Figure 1 Histological section showing the characteristic appearances of a plexiform fihrohistiocytic tumor as described by Enzinger and Zhang [1] (H&E x 630).
tumor [1]. The lesion, w h i c h involved dermis, subcutis, periosteum, and skeletal muscle, consisted of well-defined nodules of p l u m p histiocytic cells and osteoclastlike giant cells associated with infiltrative fascicles of bland s p i n d l e cells showing no apparent mitotic activity (Fig. 1).
Cytogenetic Analysis Fresh tissue obtained from the May 1989 recurrence was digested overnight in 2 rag/ ml (wt/vol) collagenase (Sigma Chemical, St. Louis, MO), and a monolayer culture was established in Ham's F12 tissue culture m e d i u m s u p p l e m e n t e d with 20% fetal calf serum. Cells were harvested for cytogenetic analysis after 7 days in vitro, and Gb a n d e d c h r o m o s o m e preparations were obtained using standard procedures. Of the 38 metaphases analysed, 12 had either a normal male karyotype or showed only r a n d o m c h r o m o s o m e loss. Clonal chromosomal abnormalities were present in the remaining 26 metaphases. These were identified as loss of a chromosome 6, an interstitial deletion w i t h i n the long arm of chromosome 4, a metacentric marker resulting from the translocation of chromosome material onto the short arm of chromosome 8 (although not identified with certainty, this translocated portion may derive from c h r o m o s o m e 6q), an apparently terminal deletion of part of the long arm of c h r o m o s o m e 20, and an unidentified marker chromosome. The stemline karyotype of this tumor was interpreted as 4 6 , X Y , - 6 , - 8 , d e l ( 4 ) (q25q31),del(20)(q11.2),+der(8)t(8;?)(p22;?),+mar. A cell with this karyotype is
33
Plexiform Fibrohistiocytic Tumor
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F i g u r e 2 G-bandedkaryotype of a cell from a plexiform fibrohistiocytic tumor. Abnormal or missing chromosomes are indicated. Insets: Marker chromosomes together with their normal homologues (G-banded partial karyotypes selected from different metaphases). Breakpoints (arrowhead).
shown in Figure 2. Partial karyotypes from additional cells to illustrate the origin of clonal rearrangements are shown in the insets to Figure 2. DISCUSSION
We believe this to be the first report of chromosome findings in a plexiform fibrohistiocytic tumor, which in addition to establishing the presence of clonal chromosomal abnormalities in a tumor entity considered to be of borderline malignant potential [1] contributes to the limited information available on fibrohistiocytic tumors in general. To date, such information appears to be confined to the various subtypes of malignant fibrous histiocytoma (MFH). Chromosomal abnormalities have been described in 14 tumors after short-term culture [4-7] and in one cell line [8]. As yet, no consistent specific chromosome change has been found to characterize this group of tumors, although identification of common abnormalities is complicated by the presence of tumor karyotypes with multiple numerical and structural abnormalities and unidentified marker chromosomes. However, of those MFHs with relatively simple karyotypes, two storiform-pleomorphic tumors analyzed by Bridge et al. [4] showed trisomy for chromosome 7 as a clonal change. In terms of gross karyotypic features, the frequent occurrence of telomeric associations, dicentrics, and ring chromosomes in pleomorphic MFH has been noted [5]. Ring chromosomes were also found in two myxoid
34
s. Smith et al.
MFHs in this series and in an MFH of unspecified subtype studied by Molenaar et al. [7]. An examination of published karyotype descriptions of MFH did not show any marked similarity to the findiflgs in our own example of plexiform fibrous histiocytoma. Such data are limited in number, however, and further reports of c h r o m o s o m e findings in defined tumor entities will be necessary to establish karyotypic and histological correlations within the fibrohistiocytic tumors.
REFERENCES 1. Enzinger FM, Zhang, R (1988): Plexiform fibrohistiocytic tumor presenting in children and young adults. An analysis of 65 cases. Am I Surg Patbol 12:818-826. 2. Enzinger FM, Weiss SW (1988): Soft Tissue Tumors, 2nd ed. St. Louis, C. V. Mosby. 3. Sandberg AA, Turc-Carel C (1987): The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer 59:387-395. 4. Bridge JA, Sanger WG, Shaffer B, Neff JR (1987): Cytogenetic findings in malignant fibrous histiocytoma. Cancer Genet Cytogenet 29:97-102. 5. Mandahl N, Heim S, Arheden K, Rydholm A, Will~n H, Mitelman F (1988): Rings, dicentrics and telomeric association in histiocytomas. Cancer Genet Cytogenet 30:23-33. 6. 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 primary cytogenetic change in human neoplasia. Nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci USA 84:1981-1985. 7. Molenaar WM, DeJong B, Buist J, Idenburg vJS, S~ruca R, Vos AM, Hoekstra HJ (1989): Chromosomal analysis and the classification of soft tissue sarcomas. Lab Invest 60:266-274. 8. Hecht F, Berger C, Kaiser-McCaw Hecht B, Speiser BL (1983): Fibrous histiocytoma cell line. Chromosome studies of mouse and man. Cancer Genet Cytogenet 8:359-362.
abstract: A plexiform fibrohistiucytic tu mot was analyzed cytogenetically after short-term in vitro culture. The stemline karyotype of this tumor was interpreted as 46,XY,-6,-8,del(4)(q25q31), del(20)(ql 1.2), + der(8)t(8;?)(p22;?), + mar. We beliew', this to be the first report of chromosome findings in this recently described histological entity.
INTRODUCTION Plexiform fibrohistiocytic tumor is a very recently recognized soft tissue neoplasm. Histologically, it consists of fibroblasts, histiocytelike cells, and osteoclastlike giant cells and is distinguished from other fibrohistiocytic lesions by the characteristic plexiform arrangement of the fibroblastic and histiocytic components. Clinically, it presents as a dermal or subcutaneous mass, most commonly in the upper limb and appears to affect p r e d o m i n a n t l y children and young adults, has a tendency to recur locally after excision, and in rare instances to metastasize nonfatally to l y m p h nodes
[~.]. The recognition of this tumor as a clinically and histologically distinct entity extends established classifications, [e.g., 2], of fibrohistiocytic tumors. Because cytogenetic data have provided supportive evidence for histological grouping within some of the more extensively studied solid tumors [see ref. 3 for review], we undertook a cytogenetic analysis of a plexiform fibrohistiocytic tumor and compared our findings in this case with published information on the cytogenetics of other fibrohistiocytic tumors. CASE REPORT
At the age of 13 months a male white infant had an ill-defined soft tissue swelling on the dorsum of the left foot. This tissue was excised and diagnosed as an u n u s u a l fibromatosis. At the age of 4 years he had extensive local recurrence that extended between the metatarsal bones to the sole of the foot. Wide reexcision necessitating amputation of the fifth ray was performed in May 1989. Histologically, both excision specimens were similar and showed the typical features of a plexiform fibrohistiocytic From the Sectionof Pathology,Instituteof CancerResearch, SurreySM2 5NG,UK (S. S., B. A. G.) and the Departments of Histopathology (C. D. M. F.) and Orthopaedics (M. A. S.), St. Thomas's Hospital, London, England. Address reprint requests to: Dr. S. Smith, Section of Pathology, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey SM2 5NG, England. Received September 28, 1989; accepted October 31, 1989.
31 © 1990 ElsevierSciencePublishingCo., Inc. 655 Avenue of the Americas,New York, NY 10010
Cancer Genet Cytogenet48:31 34 (1990) 0165-4608/90/$03.50
32
s. Smith et al.
Figure 1 Histological section showing the characteristic appearances of a plexiform fihrohistiocytic tumor as described by Enzinger and Zhang [1] (H&E x 630).
tumor [1]. The lesion, w h i c h involved dermis, subcutis, periosteum, and skeletal muscle, consisted of well-defined nodules of p l u m p histiocytic cells and osteoclastlike giant cells associated with infiltrative fascicles of bland s p i n d l e cells showing no apparent mitotic activity (Fig. 1).
Cytogenetic Analysis Fresh tissue obtained from the May 1989 recurrence was digested overnight in 2 rag/ ml (wt/vol) collagenase (Sigma Chemical, St. Louis, MO), and a monolayer culture was established in Ham's F12 tissue culture m e d i u m s u p p l e m e n t e d with 20% fetal calf serum. Cells were harvested for cytogenetic analysis after 7 days in vitro, and Gb a n d e d c h r o m o s o m e preparations were obtained using standard procedures. Of the 38 metaphases analysed, 12 had either a normal male karyotype or showed only r a n d o m c h r o m o s o m e loss. Clonal chromosomal abnormalities were present in the remaining 26 metaphases. These were identified as loss of a chromosome 6, an interstitial deletion w i t h i n the long arm of chromosome 4, a metacentric marker resulting from the translocation of chromosome material onto the short arm of chromosome 8 (although not identified with certainty, this translocated portion may derive from c h r o m o s o m e 6q), an apparently terminal deletion of part of the long arm of c h r o m o s o m e 20, and an unidentified marker chromosome. The stemline karyotype of this tumor was interpreted as 4 6 , X Y , - 6 , - 8 , d e l ( 4 ) (q25q31),del(20)(q11.2),+der(8)t(8;?)(p22;?),+mar. A cell with this karyotype is
33
Plexiform Fibrohistiocytic Tumor
g,
/
!
2
5
4
3
/
/
'6
7
h
8
9
II
14
16
15
i 4del(4)
I
I
I
12
el
13
I
":I
'IY 10
I
17
18
8 der (8)
t
8 d.r(8)
I
/
I I
/ [ 20 del(20)l
19
20
21
22
X X Y
mar
F i g u r e 2 G-bandedkaryotype of a cell from a plexiform fibrohistiocytic tumor. Abnormal or missing chromosomes are indicated. Insets: Marker chromosomes together with their normal homologues (G-banded partial karyotypes selected from different metaphases). Breakpoints (arrowhead).
shown in Figure 2. Partial karyotypes from additional cells to illustrate the origin of clonal rearrangements are shown in the insets to Figure 2. DISCUSSION
We believe this to be the first report of chromosome findings in a plexiform fibrohistiocytic tumor, which in addition to establishing the presence of clonal chromosomal abnormalities in a tumor entity considered to be of borderline malignant potential [1] contributes to the limited information available on fibrohistiocytic tumors in general. To date, such information appears to be confined to the various subtypes of malignant fibrous histiocytoma (MFH). Chromosomal abnormalities have been described in 14 tumors after short-term culture [4-7] and in one cell line [8]. As yet, no consistent specific chromosome change has been found to characterize this group of tumors, although identification of common abnormalities is complicated by the presence of tumor karyotypes with multiple numerical and structural abnormalities and unidentified marker chromosomes. However, of those MFHs with relatively simple karyotypes, two storiform-pleomorphic tumors analyzed by Bridge et al. [4] showed trisomy for chromosome 7 as a clonal change. In terms of gross karyotypic features, the frequent occurrence of telomeric associations, dicentrics, and ring chromosomes in pleomorphic MFH has been noted [5]. Ring chromosomes were also found in two myxoid
34
s. Smith et al.
MFHs in this series and in an MFH of unspecified subtype studied by Molenaar et al. [7]. An examination of published karyotype descriptions of MFH did not show any marked similarity to the findiflgs in our own example of plexiform fibrous histiocytoma. Such data are limited in number, however, and further reports of c h r o m o s o m e findings in defined tumor entities will be necessary to establish karyotypic and histological correlations within the fibrohistiocytic tumors.
REFERENCES 1. Enzinger FM, Zhang, R (1988): Plexiform fibrohistiocytic tumor presenting in children and young adults. An analysis of 65 cases. Am I Surg Patbol 12:818-826. 2. Enzinger FM, Weiss SW (1988): Soft Tissue Tumors, 2nd ed. St. Louis, C. V. Mosby. 3. Sandberg AA, Turc-Carel C (1987): The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer 59:387-395. 4. Bridge JA, Sanger WG, Shaffer B, Neff JR (1987): Cytogenetic findings in malignant fibrous histiocytoma. Cancer Genet Cytogenet 29:97-102. 5. Mandahl N, Heim S, Arheden K, Rydholm A, Will~n H, Mitelman F (1988): Rings, dicentrics and telomeric association in histiocytomas. Cancer Genet Cytogenet 30:23-33. 6. 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 primary cytogenetic change in human neoplasia. Nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci USA 84:1981-1985. 7. Molenaar WM, DeJong B, Buist J, Idenburg vJS, S~ruca R, Vos AM, Hoekstra HJ (1989): Chromosomal analysis and the classification of soft tissue sarcomas. Lab Invest 60:266-274. 8. Hecht F, Berger C, Kaiser-McCaw Hecht B, Speiser BL (1983): Fibrous histiocytoma cell line. Chromosome studies of mouse and man. Cancer Genet Cytogenet 8:359-362.