Cytogenetic analysis of a congenital fibrosarcoma

June 3, 2017 | Autor: A. Pearson | Categoria: Humans, Male, Karyotyping, Fibrosarcoma, Newborn Infant, Leg
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Cytogenetic Analysis of a Congenital Fibrosarcoma L. R. Adam, E. V. Davison, A. J. Malcolm, A. D. J. Pearson, and A. W. Craft

ABSTRACT: Congenital ( i n f a n t i l e ) f i b r o s a r c o m a is a rare soft tissue sarcoma occurring in children aged less than 5 years. We peffarmed crtogenetie analysis on such a tumor, w h i c h had an abn()rmal karyotype: 48,XY. + 11, -~ 20. Three other reports of k a r y o t r p e s in congenitol fibrosareoma describe similar cytogenetic changes, and a specific pattern of trisomies that m a y prove diagnostic for this tum()r is beginning to emerp, e.

INTRODUCTION

Histologically specific types of soft tissue sarcoma are now being associated with clonal cytogenetic abnormalities, e.g., t(X:18) in synovial sarcoma and t(2;13) in alveolar rhabdomyosarcoma [1-41. Among the soft tissue sarcomas, there is a wide spectrum of neoplasms of fibroblasts, including fibromatosis, infantile or congenital fibrosarcoma, and adult fibrosarcoma. Childhood fibromatosis (desmoid tumor) is relatively benign, being a locally infiltrative but very rarely metastatic proliferation of fibroblasts. Congenital fibrosarconms, on the other hand. are malignant, I)ut differ from adult fibrosar(:omas both bistoh)gically alld in their clinical behavior. Congenital fibrosarcomas ten(t to be more cellular an(l have a higher mitotic rate an(t less (:ollagen matrix. One third of infantile fibrosarcomas oc(:ur in the neonatal period, are rare o(:(:urring mostly in extremities, and grow rapidly. Although there is a high lo(:al re~:urre,n(:e rate (43%), metastatic spread is u n c o m m o n (less than 10('/,), and 5-year survival rates greater than 80% have been reporte(t 15 71. Adult fibrosar(:omas have a mm:h poorer prognosis and a higher metastati(: rate and tend to occur in the thigh, knee, ()r trunk. We describe the karyotype of a (:ongenital fibrosar(:oma.

CASE REPORT

A male infant was born at term by a normal delivery following an uneventh]l pregnancy. Family history was unremarkable. At birth, he had a 6 x 5-cm firm swelling on the anteromedial side of his right leg (Fig. 1). Otherwise the baby was well. Computed tomographic (CT) and ultrasound scans showed the lesion to be solid and

From the Cytogenetic:s Unit, Division ot ttuman (;eneti¢:s. University ot Newcaslle upon 'I'yne (L. R. A.), Departmelll ot Clinical Cytogenetics, Birmingham Maternity [tosl~ital. Birmingham (E. V. D,), and |)t!pai'tm(!nts of Pathoh)gy (A. ]. M.) and Child llealth (A. D. ]. P., A. W. C.]. University of Newc:asth? upon Tyne, England.

Address reprint requests to: L. F{. Adam, Cytogenetics Unit. Division of Human C,enetics, University of Newcastle upon Tyne. 19, Claremont Place, New, castle upon Tyne, NE2 4AA. Engbnd. Received May 29, 1990; accepted lane 21. 1990.

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Figure 1

Right lower leg at birth shows the presence of the tumor.

to arise from muscle. Radiologically, some reactive changes in the midshaft of the right tibia were detected. Chest roentgenogram and CT scan showed no evidence of p u l m o n a r y metastases. Bone scan showed some increased activity over the right tibia but no other skeletal abnormalities. When the infant was 24 hours old, the tumor was biopsied and a small sample was sent for cytogenetic analysis. Histological examination of the tumor showed a very vascular, round, and spindle-celled mesenchymal tumor. Soine of the cells were arranged in fascicles; elsewhere, the pattern was random. Nuclear pleomorphism was moderate, and mitoses were numerous {Fig. 2). These latter features, together with

Figure 2 Spindle-shaped cells with elongated nuclei show pleomorphism and mitoses supported by a delicate vascularity {Original magnification, hematoxylin and eosim × 4(}0, reduced by 33%).

(]ytogeneti(:s of Collgell ital Fibrosarcoma

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Karyotype,:48,XY, + 11, + 20.

the rich delicate vascularity exclude a diagnosis of fibromatosis amt confirm the diagnosis of congenital (infantile) fibrosarcoma. Surgical removal of the tuinor at this stage would have required an amputation because the tumor was so large. Because these tumors have been shown to be chemosensitive [8 10], the child received treatment with vincristine and actinomycin D to reduce the size of the tumor and permit less radical surgery. With this approach, the mass became smaller and was no longer palpable when the child was aged 3 months. In view of the very good response to treatment, surgical treatment was not believed to be indicated and the child is now event-free 16 months after diagnosis. MATERIALS A N D METHODS

Tile ttnnor biopsy was minced, and a single explant culture established in a c,ulture flask, in Chang tissue culture m e d i u m Isupplen~ented with penicillin, streptomycin, and glutamine]. The culture was grown in 5% CO~ in air with regular changes of medium and was subcultured after 10 days. Harvesting (on day 12) was done by trypsilfization of cells after exposure to 0.2/xg/ml Coh:emid for 4 tmurs. Hypotonic treatment with 0.(175 M KCI was followed by fixation with mettmnol :glacial acetic acid 3 : 1. Slide preparation was conventional, and G-banding was performed using trypsin, and Leishman's stain. RESULTS

Twenty-eight metaphases were analyzed: all cells showed an abnormal 48,XY, + 11, + 2(1 karyotype. No structural abnormalities were apparent (Fig. 3). DISCUSSION

Only a few reports of cytogenetic analyses of fibrosarcoma have been published. Of the four adult fibrosarcomas reported, one had a normal karyotype [11] and three had structural abnormalities [12-14]. No single specific structural or numerical abnormal-

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1~. R. A d a m et al.

ity e m e r g e s from these reports, and no fibrosarcoma s h o w e d gain of c l w o m o s o m e s 8, 11, 17, or 20.

Only three (:ases ()f infantile fibr()sarcoma have been reported, all wilh c y t o g e n e t i c changes similar h) those ()f our patient. S p e h m m n et al. [151 des(:ribe(t n m n e r i c a l changes ill a re(:urrenl (:mlgenital fibrosar(:oma, with the mosai(: karyotype 4 9 , X Y . + 8, + 11.+ 20/47,XY. ~ 8/47,XY,+ 11. M a n d a h l et al. 1161 ret)orte(I a 5 - m o n t h - o l d bal)y w h o also ha(I a mosai(: karyotyl)e 4 9 . X Y , + 8 , ~ l I , + 2 0 / 50,XY, + 8.+ 11,+ 17,+ 20/46,XY, T h e third, analyze(t by I)al (;in (t)ersolml c o m m u n i cation), had a c o n g e n i t a l f i h r o s a r c o m a w i t h t h e k a r y o t y p e 4 9 , X , X.+11,+11,+17, + 20 (one cell had an a p p a r e n t l y normal 46,XX karyotype). T h e s e results, and the t)resent patient, suggest that infantile fibrosarcoma is characterized by n o n r a n d o m gains of (:hromosomes and, perhaps, that it is c y t o g e n e t i c a l l y distinct from adult fibrosarcoma, fihromatosis, and ()ther m e s e n c h y m a l tumors. Te, yssi~," an(I Ferre, [171 ret)()rte(t a case of benign mesoblasti(: n e p h r o m a with a karyotype identi(:al to that of our l)atieid, i.e., with t r i s o m v 11 and trisomv 20. K¢)va(:s el al. 1181 als() d e s c r i b e d a (:ase, ()[ c()ngenital mesoblastic: n e p h r o m a . Analysis s h o w e d a mosai{: karyotype: 46,XY/54,XX, + 7, + 8, + g, + 9. -- 1l, ~ 17, + 18, ~- 20. Th{,q'e were, n() structural rearrangements. The c y t o g e n e t i c observati(}ns in both these cases are similar to those (tescribcd ill the four cases of infantile fibr()sarcolna. Mesoblastic t m p h r o m a is a usually I)enign renal tmn()r ()f infancy. The t u m o r is (:omi)()sed m a i n l y of fihr()blastic tissue and al)l)ears to I)e histoh)gi(:ally related to W i l m s ' t m n o r I IGt, 2(11. The, similarity ~+f tile cyt()ger.,qic changes in these two) cases of mes()lflastic m+phroma to th(; c y t o g e n e t i c observati(ms in tim four cases tfl infantile t]l)r()sar(:oma may reflect the comm()n fihroblasti(: tmtm'e ol b()th these IleOl)laSlllS. In these four cases (d (:(n]genital fibrosarcoma, m) two sub(:h)nes share the s a m e karyotype, and no single (:hr()mosome gain is (:()mmon t() ,11 clones, w h i c h makes inte, rpretation of the results difficult. Sl)e, leman et a l. II 5] suggested that a (h)se effect of gem~,s lo(:ated on c h r o m o s o m e s 8, 11, 17, and 20 lllaV I)e i m p o r t a n h T r i s o m y 8 is a c o m m o n finding in l c u k e m i a s and solid tumors, usualh, in a(hlili(m to other m m l e r i cal and structural abnormalities. T r i s o m v 11 as the s()le change has been observed in a few (:ases of acute myeloi(I l e u k e m i a an(I is also observe(I as a se(:on(tary a l m o r m a l i t y in m a n y l e u k e m i a s and solid tmnors, a l t h o u g h less freqtmiHlythan t r i s o m v 8. T r i s o m y 17 an(l t r i s o m v 21) have, not been (:ited as spe(:ifi(: markers in malignancy, but both are observed as scx:on(larv changes in m a n y n e o p l a s m s IV l I. The pattern of c y t o g e n e t i c changes observed in the above cases does not i m p l y o n c o g e n e i n v o l v e m e n t , but the p r i m a r y event in t u m o r i g e n e s i s of c o n g e n i t a l fibrosarc o m a may be a s u b m i c r o s ( : o p i c rearrangement, e.g., a d e l e t i o n or t r a n s l o c a t i o n l e a d i n g to a c t i v a t i o n of an o n c o g e n e . T h e numeri(:al changes that follow are s e c o n d a r y and are probably i n v o l v e d in t u m o r progression. Further cytogeneti(: and m o l e c u l a r investigations of fibrosarcomas may help us u n d e r s t a n d the m e c h a n i s m s i n v o l v e d in the i n i t i a t i o n and progression of this rare c h i l d h o o d tumor. Clinically, s e p a r a t i o n of (:ongenital fibrosarcoma from c o n g e n i t a l fibromatosis can be a p r o b l e m , but the d i s t i n c t i o n is i m p o r t a n t because t r e a t m e n t differs for the two diseases. T h e p r e s e n c e of a clonal c h r o m o s o m e a b n o r m a l i t y w o u l d favor a fibrosarcoma, and the c o n s i s t e n t pattern of specific trisomies that is b e g i i m i n g to e m e r g e m a y prove to be d i a g n o s t i c for c o n g e n i t a l fibrosarcoina.

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C y t o g e n e t i c s of C o n g e n i t a l F i b r o s a r c o m a

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