ClinicalRadiology (1992) 45, 206-207
Case Report: Liver Adenomatosis Presenting as Multiple Calcified Masses S_ S. K H A N ,
M . F I N K * a n d S. K I N G
Departments of Radiology, King's College Hospital, London, and *Addenbrookes Hospital, Cambridge Liver adenomatosis is a rare condition with only 14 cases reported. It is considered to be a distinct entity from liver adenoma. This is the first case in which calcification has been described. The differential diagnosis of multiple calcified lesions in the liver is discussed, and other features of liver adenomatosis. K h a n , S.S., F i n k , M . & K i n g , S. (1992). Clinical Radiology 45, 206 207. C a s e R e p o r t : L i v e r A d e n o m a t o s i s P r e s e n t i n g as M u l t i p l e C a l c i f i e d M a s s e s
CASE REPORT A 30-year-old caucasian male presented with severe right upper quadrant pain. The patient had been previously fit and well, except for a right subdiaphragmatic post-infective fluid collection that had been aspirated 7 years previously, when sulphur colloid nuclear medicine scan, US examination and liver function tests (LFT) had all been normal. He was on no medication and had never been on steroids or hormone therapy. On examination, the patient had a rigid abdomen with a pulse rate of 90/min and BP of 110/70 mmHg. Investigations revealed a normal full blood count, urea, electrolytes and bilirubin. The aspartate transaminase (AST) was elevated at 74 U/litre (normal, 0-40) and alkaline phosphatase at 396 U/litre (normal, 85-240). A gamma glutamyl transferase (GGT) level was not performed, A provisional diagnosis of a perforated duodenal ulcer was made and at laparotomy a large amount of blood was noted in the peritoneal cavity. A 'large turnout of the left lobe of the liver" was seen with no abnormality of the right lobe noted. A left lobectomy was performed and histology of the resected liver revealed two large masses within the left lobe, measuring 10.0 cm and 5.0 cm in diameter. The appearances were those of adenornata but the rest of the liver was normal. The patient made an uneventful recovery. Nine months later the patient had further vague upper abdominal pain. US scan showed multiple calcified lesions in the right lobe of the liver, measuring up to 5.0 cm in diameter (Fig, 1). CT scans confirmed the presence of multiple solid lesions in the remaining right lobe of the liver, with some calcification. A selective hepatic angiogram showed the lesions were avaseular. A repeat computed tomographic (CT) scan of the liver after 3 months showed no significant change (Fig. 2). There was no enhancement post-intravenous contrast. Tru-cut biopsies of two separate lesions were performed under CT guidance. Histology revealed adenoma with normal surrounding liver and no evidence of malignancy. A diagnosis of liver adenomatosis was made. Follow-up US scans over a 3 year period have shown no change in the lesions and the patient has remained asymptomatlc.
DISCUSSION L i v e r a d e n o m a t o s i s is a r a r e c o n d i t i o n w i t h o n l y 14 p r e v i o u s l y r e p o r t e d cases ( S i n k a a n d P r a s a d , 1982; F l e j o u et al., 1985). T h i s is the first case in w h i c h c a l c i f i c a t i o n has b e e n d e s c r i b e d . A d e n o m a t o s i s is d i a g n o s e d if m o r e t h a n 10 a d e n o m a s are present. M u l t i p l e lesions in liver aden o m a a r e u n u s u a l . O n l y 21% o f p a t i e n t s h a v e m o r e t h a n o n e a d e n o m a ( L u i et al., 1980) a n d o n l y e x t r e m e l y rarely h a v e t h e r e b e e n three o r m o r e a d e n o m a s . A d e n o m a t o s i s o c c u r s in p a t i e n t s w i t h o t h e r w i s e n o r m a l livers ( B r o p h y et al., 1979; C o i r e et al., 1985). T h e r e is n o sex difference, and no known association with oral contraceptives or r a i s e d a n d r o g e n i c h o r m o n e levels. U n l i k e liver a d e n o m a , Correspondence to: Dr S. S. Khan, Department of Radiology, King's College Hospital, Denmark Hill, Camberwell, London SE5 9RS.
Fig. 1 - Longitudinal section through the right lobe of the liver showing multiple low reflectivity lesions, one showing peripheral calcification. in w h i c h m a l i g n a n c y is a r a r e c o m p l i c a t i o n (especially in p a t i e n t s w i t h l a G l y c o g e n s t o r a g e disease ( L i m m e r et al., 1988)), t h e r e is n o r e p o r t e d case o f m a l i g n a n t c h a n g e in liver a d e n o m a t o s i s _ F i n a l l y , t h e r e m a y be raised G G T a n d a l k a l i n e p h o s p h a t a s e levels ( w i t h o u t e v i d e n c e o f b i l i a r y o b s t r u c t i o n ) , w h e r e a s liver f u n c t i o n tests are u s u a l l y n o r m a l in liver a d e n o m a . I n o u r case, b i o p s i e s o f the lesion h a v e c o n f i r m e d n o e v i d e n c e o f m a l i g n a n c y . A s w i t h liver a d e n o m a , p a t i e n t s f r e q u e n t l y p r e s e n t w i t h a c u t e a b d o m i n a l p a i n due to h a e m o r r h a g e i n t o t h e a d e n o m a _ C a l c i f i c a t i o n is likely to be s e c o n d a r y to p r e v i o u s h a e m o r r h a g e i n t o an a d e n o m a _ A s in this case, l a p a r o t o m y a n d liver r e s e c t i o n are o f t e n p e r f o r m e d d u r i n g a c u t e e p i s o d e s o f pain. U p to 9 0 % r e s e c t i o n o f the liver h a s b e e n p e r f o r m e d ( M o n a c o et al., 1964). A l t h o u g h the p a t i e n t has h a d f u r t h e r e p i s o d e s o f a b d o m i n a l p a i n , these h a v e b e e n m a n a g e d c o n s e r v a t i v e l y a n d he h a s n o t r e q u i r e d f u r t h e r surgery_ T h e r e are m a n y c a u s e s o f i n t r a h e p a t i c calcification. T h e s e i n c l u d e g r a n u l o m a s , in w h i c h the c a l c i f i c a t i o n is u s u a l l y m u l t i p l e a n d small, r i m c a l c i f i c a t i o n d u e to
LIVER ADENOMATOSIS
207
liver we r e c o m m e n d liver a d e n o m a t o s i s should be considered in the differential diagnosis. CalcificatiQn m a y or m a y not be present and the C T a p p e a r a n c e s m a y be identical to those f o u n d in p r i m a r y m a l i g n a n t or secondary liver tumours. H i s t o l o g i c a l e x a m i n a t i o n is essential and C T / U S - g u i d e d biopsies are r e c o m m e n d e d . A l t h o u g h there have been no r e p o r t e d cases o f m a l i g n a n t change, follow up is r e c o m m e n d e d due to the small n u m b e r o f r e p o r t e d cases.
Acknowledgements. The authors thank Mr J. Dawson for permission to report this case, and Dr P. Gishen for help with the manuscript.
REFERENCES
Fig. 2 CT of the liver showing multiple adenoma of low density with non-specific amorphous calcification.
hydatid disease, or calcification within a thick wall o f an a m o e b i c or other p y o g e n i c abscess. Old h a e m a t o m a s m a y calcify and calcification o f biliary calculi, gall-bladder or portal vein t h r o m b o s i s are usually easily recognized. Calcification o f t u m o u r s is unusual, but includes malignant n e o p l a s m s such as bile duct c a r c i n o m a , hepatocellular c a r c i n o m a (Teefey et al., 1987) and metastases, especially f r o m the gut but rarely f r o m the t h y r o i d or o s t e o s a r c o m a s (Bernardino, 1979). T h e p a t t e r n o f calcification in p r i m a r y or secondary m a l i g n a n c y often has no specific feature and m a y be identical to that f o u n d in this case. M u c i n o u s adenocarcin o m a m a y h o w e v e r have a m o r e distinctive pattern o f fine calcification. Benign t u m o u r s such as a d e n o m a s m a y also calcify, p r o b a b l y due to h a e m o r r h a g e within the t u m o u r . With m u l t i p l e low soft-tissue density lesions within the
Bernadino, ME (1979). Computed tomography of calcified liver metastases. Journal of" Computer Asszsted Tomography, 3, 32-35. Brophy, CM, Bock, JF, West AB & McKhann CF (1979). Liver cell adenoma: diagnosis and treatment of a rare hepatic neoplastic process. American Journal of Gastroenterology, 84, 429 432. Coire, CL, Qizilbash, AH & Castelli MF (1985). Hepatic adenomata in type 1a glycogen storage disease. Archives of Pathology and Laboratory Medicine, 111, 166 169. Flejou, JF, Barge, J, Menu, Y, Degott, C, Bismuth H, Potet F et al. (1985). Liver adenomatosis an entity distinct from liver adenoma? Gastroenterology, 89, 1132 1138. Limmer, J, Fleig, WE, Leupole, D, Bittner, R, Ditschuneit, H & Beget HG (1988). Hepato-cellular carcinoma in type 1 glycogen storage disease. Hepatology, 8, 531 537. Lui, AFK, Hiratzke, LF & Hirose, FM (1980). Multiple adenomas of the liver. Cancer, 45, 1001-1004. Monaco, AP, Hallgrimsson, J & McDermott, WV (1964). Multiple adenoma (harmartoma) of the liver treated by subtotal (90%) resection. Annals of Surgery, 159, 513 519. Sinha, MR & Prasad, SB (1982). Multiple adenomas of the liver. Journal of the Indian Medical Associatton, 79, 16 18. Teefey, SA, Stephens, DH & Weiland, LH (1987). Case report: calcification in hepatocellular carcinoma. American Journal of Roentgenology, 149, 1173 1174.
Case Report: Liver Adenomatosis Presenting as Multiple Calcified Masses S_ S. K H A N ,
M . F I N K * a n d S. K I N G
Departments of Radiology, King's College Hospital, London, and *Addenbrookes Hospital, Cambridge Liver adenomatosis is a rare condition with only 14 cases reported. It is considered to be a distinct entity from liver adenoma. This is the first case in which calcification has been described. The differential diagnosis of multiple calcified lesions in the liver is discussed, and other features of liver adenomatosis. K h a n , S.S., F i n k , M . & K i n g , S. (1992). Clinical Radiology 45, 206 207. C a s e R e p o r t : L i v e r A d e n o m a t o s i s P r e s e n t i n g as M u l t i p l e C a l c i f i e d M a s s e s
CASE REPORT A 30-year-old caucasian male presented with severe right upper quadrant pain. The patient had been previously fit and well, except for a right subdiaphragmatic post-infective fluid collection that had been aspirated 7 years previously, when sulphur colloid nuclear medicine scan, US examination and liver function tests (LFT) had all been normal. He was on no medication and had never been on steroids or hormone therapy. On examination, the patient had a rigid abdomen with a pulse rate of 90/min and BP of 110/70 mmHg. Investigations revealed a normal full blood count, urea, electrolytes and bilirubin. The aspartate transaminase (AST) was elevated at 74 U/litre (normal, 0-40) and alkaline phosphatase at 396 U/litre (normal, 85-240). A gamma glutamyl transferase (GGT) level was not performed, A provisional diagnosis of a perforated duodenal ulcer was made and at laparotomy a large amount of blood was noted in the peritoneal cavity. A 'large turnout of the left lobe of the liver" was seen with no abnormality of the right lobe noted. A left lobectomy was performed and histology of the resected liver revealed two large masses within the left lobe, measuring 10.0 cm and 5.0 cm in diameter. The appearances were those of adenornata but the rest of the liver was normal. The patient made an uneventful recovery. Nine months later the patient had further vague upper abdominal pain. US scan showed multiple calcified lesions in the right lobe of the liver, measuring up to 5.0 cm in diameter (Fig, 1). CT scans confirmed the presence of multiple solid lesions in the remaining right lobe of the liver, with some calcification. A selective hepatic angiogram showed the lesions were avaseular. A repeat computed tomographic (CT) scan of the liver after 3 months showed no significant change (Fig. 2). There was no enhancement post-intravenous contrast. Tru-cut biopsies of two separate lesions were performed under CT guidance. Histology revealed adenoma with normal surrounding liver and no evidence of malignancy. A diagnosis of liver adenomatosis was made. Follow-up US scans over a 3 year period have shown no change in the lesions and the patient has remained asymptomatlc.
DISCUSSION L i v e r a d e n o m a t o s i s is a r a r e c o n d i t i o n w i t h o n l y 14 p r e v i o u s l y r e p o r t e d cases ( S i n k a a n d P r a s a d , 1982; F l e j o u et al., 1985). T h i s is the first case in w h i c h c a l c i f i c a t i o n has b e e n d e s c r i b e d . A d e n o m a t o s i s is d i a g n o s e d if m o r e t h a n 10 a d e n o m a s are present. M u l t i p l e lesions in liver aden o m a a r e u n u s u a l . O n l y 21% o f p a t i e n t s h a v e m o r e t h a n o n e a d e n o m a ( L u i et al., 1980) a n d o n l y e x t r e m e l y rarely h a v e t h e r e b e e n three o r m o r e a d e n o m a s . A d e n o m a t o s i s o c c u r s in p a t i e n t s w i t h o t h e r w i s e n o r m a l livers ( B r o p h y et al., 1979; C o i r e et al., 1985). T h e r e is n o sex difference, and no known association with oral contraceptives or r a i s e d a n d r o g e n i c h o r m o n e levels. U n l i k e liver a d e n o m a , Correspondence to: Dr S. S. Khan, Department of Radiology, King's College Hospital, Denmark Hill, Camberwell, London SE5 9RS.
Fig. 1 - Longitudinal section through the right lobe of the liver showing multiple low reflectivity lesions, one showing peripheral calcification. in w h i c h m a l i g n a n c y is a r a r e c o m p l i c a t i o n (especially in p a t i e n t s w i t h l a G l y c o g e n s t o r a g e disease ( L i m m e r et al., 1988)), t h e r e is n o r e p o r t e d case o f m a l i g n a n t c h a n g e in liver a d e n o m a t o s i s _ F i n a l l y , t h e r e m a y be raised G G T a n d a l k a l i n e p h o s p h a t a s e levels ( w i t h o u t e v i d e n c e o f b i l i a r y o b s t r u c t i o n ) , w h e r e a s liver f u n c t i o n tests are u s u a l l y n o r m a l in liver a d e n o m a . I n o u r case, b i o p s i e s o f the lesion h a v e c o n f i r m e d n o e v i d e n c e o f m a l i g n a n c y . A s w i t h liver a d e n o m a , p a t i e n t s f r e q u e n t l y p r e s e n t w i t h a c u t e a b d o m i n a l p a i n due to h a e m o r r h a g e i n t o t h e a d e n o m a _ C a l c i f i c a t i o n is likely to be s e c o n d a r y to p r e v i o u s h a e m o r r h a g e i n t o an a d e n o m a _ A s in this case, l a p a r o t o m y a n d liver r e s e c t i o n are o f t e n p e r f o r m e d d u r i n g a c u t e e p i s o d e s o f pain. U p to 9 0 % r e s e c t i o n o f the liver h a s b e e n p e r f o r m e d ( M o n a c o et al., 1964). A l t h o u g h the p a t i e n t has h a d f u r t h e r e p i s o d e s o f a b d o m i n a l p a i n , these h a v e b e e n m a n a g e d c o n s e r v a t i v e l y a n d he h a s n o t r e q u i r e d f u r t h e r surgery_ T h e r e are m a n y c a u s e s o f i n t r a h e p a t i c calcification. T h e s e i n c l u d e g r a n u l o m a s , in w h i c h the c a l c i f i c a t i o n is u s u a l l y m u l t i p l e a n d small, r i m c a l c i f i c a t i o n d u e to
LIVER ADENOMATOSIS
207
liver we r e c o m m e n d liver a d e n o m a t o s i s should be considered in the differential diagnosis. CalcificatiQn m a y or m a y not be present and the C T a p p e a r a n c e s m a y be identical to those f o u n d in p r i m a r y m a l i g n a n t or secondary liver tumours. H i s t o l o g i c a l e x a m i n a t i o n is essential and C T / U S - g u i d e d biopsies are r e c o m m e n d e d . A l t h o u g h there have been no r e p o r t e d cases o f m a l i g n a n t change, follow up is r e c o m m e n d e d due to the small n u m b e r o f r e p o r t e d cases.
Acknowledgements. The authors thank Mr J. Dawson for permission to report this case, and Dr P. Gishen for help with the manuscript.
REFERENCES
Fig. 2 CT of the liver showing multiple adenoma of low density with non-specific amorphous calcification.
hydatid disease, or calcification within a thick wall o f an a m o e b i c or other p y o g e n i c abscess. Old h a e m a t o m a s m a y calcify and calcification o f biliary calculi, gall-bladder or portal vein t h r o m b o s i s are usually easily recognized. Calcification o f t u m o u r s is unusual, but includes malignant n e o p l a s m s such as bile duct c a r c i n o m a , hepatocellular c a r c i n o m a (Teefey et al., 1987) and metastases, especially f r o m the gut but rarely f r o m the t h y r o i d or o s t e o s a r c o m a s (Bernardino, 1979). T h e p a t t e r n o f calcification in p r i m a r y or secondary m a l i g n a n c y often has no specific feature and m a y be identical to that f o u n d in this case. M u c i n o u s adenocarcin o m a m a y h o w e v e r have a m o r e distinctive pattern o f fine calcification. Benign t u m o u r s such as a d e n o m a s m a y also calcify, p r o b a b l y due to h a e m o r r h a g e within the t u m o u r . With m u l t i p l e low soft-tissue density lesions within the
Bernadino, ME (1979). Computed tomography of calcified liver metastases. Journal of" Computer Asszsted Tomography, 3, 32-35. Brophy, CM, Bock, JF, West AB & McKhann CF (1979). Liver cell adenoma: diagnosis and treatment of a rare hepatic neoplastic process. American Journal of Gastroenterology, 84, 429 432. Coire, CL, Qizilbash, AH & Castelli MF (1985). Hepatic adenomata in type 1a glycogen storage disease. Archives of Pathology and Laboratory Medicine, 111, 166 169. Flejou, JF, Barge, J, Menu, Y, Degott, C, Bismuth H, Potet F et al. (1985). Liver adenomatosis an entity distinct from liver adenoma? Gastroenterology, 89, 1132 1138. Limmer, J, Fleig, WE, Leupole, D, Bittner, R, Ditschuneit, H & Beget HG (1988). Hepato-cellular carcinoma in type 1 glycogen storage disease. Hepatology, 8, 531 537. Lui, AFK, Hiratzke, LF & Hirose, FM (1980). Multiple adenomas of the liver. Cancer, 45, 1001-1004. Monaco, AP, Hallgrimsson, J & McDermott, WV (1964). Multiple adenoma (harmartoma) of the liver treated by subtotal (90%) resection. Annals of Surgery, 159, 513 519. Sinha, MR & Prasad, SB (1982). Multiple adenomas of the liver. Journal of the Indian Medical Associatton, 79, 16 18. Teefey, SA, Stephens, DH & Weiland, LH (1987). Case report: calcification in hepatocellular carcinoma. American Journal of Roentgenology, 149, 1173 1174.
