Upsala J Med Sci 93: 53-56, 1988 Familial Ovarian Dermoid Cysts Karl-Henrik Gustavson' and Curt Rune' 'Department of Clinical Genetics, University Hospital and 'Department of Gynecology, Samariterhemmet Hospital, Uppsala, Sweden ABSTRACT A f a m i l y c o n s i s t i n g showed an i n c r e a s e d chromosomal i n s t a b i o f a mother and h e r two daughters w i t h o v a r i a n dermoid c y s t s frequency o f aneuploidy and chromosomal breakage i n d i c a t i n g i t y . INTRODUCTION There a r e s e v e r a l r e p o r t s on f a m i l i a l occurrence o f dermoid c y s t s o f t h e ovary: (2,3,4,5,8,10,11). These r e p o r t s p l u s o t h e r c h a r a c t e r i s t i c s o f dermoids, such as h i g h percentage o f b i l a t e r a l i t y and low age o f occurrence, p o i n t t o g e n e t i c a l causes i n some o f t h e cases o f t h e disease. No c y t o g e n e t i c s t u d i e s o f f a m i l i a l cases seem t o have been done. T h i s r e p o r t d e s c r i b e s a f a m i l y c o n s i s t i n g o f a mother and two daughters w i t h o v a r i a n dermoid c y s t s who were s u b j e c t e d t o chro- mosomal i n v e s t i g a t i o n s . The mother and one daugther showed s i g n s o f chromosomal i n s t a b i l i t y . CASE REPORTS P a t i e n t 1: ( 1 : l i n t h e p e d i g r e e ) , i s a 54-year-old, 2-gravidae woman. She was operated on f o r a p e r f o r a t e d a p p e n d i c i t i s a t 26 years o f age, as n u l l i - g r a v i d a e woman because o f i n t e r m i t t e n t abdominal p a i n . A t o p e r a t i o n , an ovary t h e s i z e o f a s m a l l orange p a r t l y embedded i n adhesions was found. An ophorectomy was p e r - formed. The l e f t ovary was normal and h i s t o l o g i c a l examination o f t h e r i g h t ovary r e v e a l e d a corpus luteum c y s t i n a d d i t i o n t o a plum-sized dermoid c y s t t h a t was w i t h o u t h i s t o l o g i c a l s i g n s o f malignancy. P a t i e n t 2: ( I I : 2 i n t h e p e d i g r e e ) , a 24-year-old n u l l i g r a v i d a e woman p r e v i o u s l y h e a l t h y , who had been t a k i n g c o n t r a c e p t i v e p i l l s d u r i n g t h e 18 months preceeding t h e o p e r a t i o n . A r i g h t - s i d e d o v a r i a n lump had been found on r o u t i n e examination. A t o p e r a t i o n a dermoid c y s t t h e s i z e o f a s m a l l orange i n v o l v i n g t h e r i g h t ovary was found and removed. The l e f t ovary was normal. H i s t o l o g i c a l examination r e - vealed a dermoid c y s t w i t h o u t s i g n s o f malignancy. P a t i e n t 3: ( I I : 3 i n t h e p e d i g r e e ) , a 22-year-old n u l l i g r a v i d a e woman p r e v i o u s l y h e a l t h y , who had been t a k i n g c o n t r a c e p t i v e p i l l s d u r i n g t h e 24 months preceeding t h e o p e r a t i o n . On r o u t i n e examination a l e f t - s i d e d o v a r i a n lump had been found. A t o p e r a t i o n , a dermoid t h e s i z e o f a s m a l l orange i n v o l v i n g t h e l e f t ovary was found and removed. The r i g h t ovary was normal. H i s t o l o g i c a l examination r e v e a l e d a dermoid c y s t w i t h o u t s i g n s o f malignancy. METHODS On each o f t h e t h r e e p a t i e n t s b l o o d samples were taken on two separate occasions f o r c y t o g e n e t i c a l i n v e s t i g a t i o n s . A f t e r c o n v e n t i o n a l c e l l c u l t u r e procedure and 53 v2 I Pedigree of the affected family. 0 Normal 0 Ovarian dermoid cyst Giemsa-banding, 100 metaphases were analysed from each p a t i e n t . Chromosome breakage a n a l y s i s was performed on 100 metaphases o f Giemsa-stained a i r - d r i e d s l i d e s from each p a t i e n t . A n a l y s i s o f s i s t e r - c h r o m a t i d exchanges a f t e r BrdU- l a b e l l i n g were performed on c u l t u r e d lymphocytes from t h e p a t i e n t s , as d e s c r i b e d by A l v e s t & Jonasson ( 1 ) . RESULTS The r e s u l t s o f t h e chromosomal i n v e s t i g a t i o n s a r e shown i n Table 1. The t h r e e p a t i e n t s a l l had a normal female chromosomal c o n s t i t u t i o n . There was an i n c r e a s e d frequency o f aneuploidy (4-20:;) and chromosomal breakage i n patients 1 and 3 as compared w i t h c o n t r o l s . The frequency o f s i s t e r chromatid exchanges was n o t increased. D I S C U S S I O N Most o v a r i a n teratomas have a normal 46,XX karyotype, suggesting t h a t o v a r i a n teratomas a r i s e from germ c e l l s and most o f t e n through p a r t h o g e n e s i s ( 7 ) . The p r e s e n t study as w e l l as o t h e r i n v e s t i g a t i o n s (2,4,5,8,10,11) have c l e a r l y demonstrated t h e e x i s t e n c e o f f a m i l i a l forms o f o v a r i a n dermoid c y s t s . Our study demonstrated an i n c r e a s e i n t h e number o f a n e u p l o i d c e l l s and chromosomal breakage i n lymphocyte c u l t u r e s o f t h e mother and one o f h e r daughters. These f i n d i n g s support t h e t h e o r y t h a t g e n e t i c f a c t o r s a r e o f importance i n t h e de- velopment o f o v a r i a n dermoid c y s t s . The s i g n i f i c a n c e o f t h e a s s o c i a t i o n between t h e o v a r i a n teratomas, which a r e p r o b a b l y dominantly i n h e r i t e d , and t h e f o r e - mentioned c y t o g e n e t i c a l f i n d i n g s i n c u l t u r e d c e l l s i s u n c e r t a i n . I t i s p o s s i b l e , however, t h a t t h e i n c r e a s e d frequency o f aneuploidy and chromosomal breakage a r e s i g n s o f chromosomal i n s t a b i l i t y t y p i c a l l y seen i n some d i s t i n c t g e n e t i c d i s - o r d e r s w i t h a p r o p e n s i t y t o develop neoplasia, such as F a n c o n i ' s anemia, Bloom's syndrome, a t a x i a t e l a n g i e t a s i a , xeroderma pigmentosum and Gardner's syndrome, considered t o be expression o f t h e u n d e r l y i n g gene d e f e c t ( 9 ) , and t h a t t h e i n - creased frequency o f a n e u p l o i d c e l l s i n c u l t u r e d lymphocytes from our f a m i l i a l cases r e f l e c t s a d i s t u r b a n c e o f t h e m i t o t i c and m e i o t i c processes, which m i g h t be o f pathogenetic importance. Such a d i s t u r b a n c e o f t h e m i t o t i c and m e i o t i c process i n our f a m i l i a l cases c o u l d be r e l a t e d t o an u n d e r l y i n g gene d e f e c t or due t o m e t a b o l i c and/or hormonal i n f l u e n c e s . I t should be o f i n t e r e s t t o p e r f o r m f u r t h e r s t u d i e s and compare n o n - f a m i l i a l w i t h f a m i l i a l cases. We have t h u s s t a r t e d a p r o s p e c t i v e study o f c o n s e c u t i v e l y operated cases o f o v a r i a n teratomas i n t h e Uppsala H o s p i t a l Region, Sweden, i n c l u d i n g chromosomal analyses and DNA a n a l y t i c a l procedures o f b l o o d and dermoid t i s s u e . We have a l s o s t a r t e d a r e t r o - s p e c t i v e study i n o r d e r t o f i n d o u t t h e frequency o f f a m i l i a l cases o f t h e disease. 54 P at ie n t T ab le 1 . C yt oq en et ic f in di nq s in c u lt u re d l ym p h oc yt es f ro m t h e th re e re la ti ve s w it h o va ri an t er at om as K ar o t e & iis ) A be rr at io ns p e r ce ll S C E F ra gi le s it es (I n No . C h ro m at id a nd 1s - ga ps fr ag m en ts to ta l (m ea n p e r o f ce ll s of 1 0 0 ch ro m at id b re ak ag es ce ll ) ex am in ed c el ls ) P at ie n t 1 (k l) 1s t cu lt u re 2n d cu lt ur e P at ie n t 2 (1 1: l) 1s t cu lt ur e 2n d cu lt ur e P at ie n t 3 ( k 2 ) 1s t cu lt ur e 2n d cu lt ur e C on tr ol s 46 ,X X (1 7) 0. 15 0. 01 0. 03 0. 19 0 4 7 ,X X X (l ) 4 8 ,X X X X (l ) 4 5 ,X (1 ) 4 6 ,X X (4 0 ) 0. 08 47 ,X X ,+ 8( 1) 45 ,X (1 ) 45 ,X X ,- 4( 1) 45 ,X X -1 2( 1) 4 4 ,X X ,- l, -l (l ) 44 ,X ,- 3, -1 8( 1) 0. 03 0. 03 0. 14 8. 5 0 4 6 ,X X (1 9 ) 47 ,X X ,+ 21 (1 ) 46 ,X X (4 3) 47 ,X X ,+ 5( 1) 4 6 ,X X A ne up lo id y 4 % 0. 01 0. 03 0. 30 0. 04 0. 02 0 0 0. 01 7. 6 0 0 0. 03 0. 18 0. 08 0. 56 0 0. 04 0. 01 0. 09 5. 1 0. 05 0. 00 2 0. 01 2 11 .4 0 ACKNOWLEDGEMENT T h i s study was supported by a g r a n t from t h e Cancer Foundation o f t h e U n i v e r s i t y H o s p i t a l , Uppsala. REFERENCES 1. 2. 3 . 4 . 5 . 6 . 7 . 8. 9 . 10. 1 1 . 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