Primary leiomyosarcoma of the liver

Medical Intelligence PRIMARY LEIOMYOSARCOMA OF THE LIVER JULITA A. FONG, M.D.,* AND BORIS H. RUEBNER, M.D.t

Abstract

A 62 year old man developed an abdominal mass, which proved to be a hepatic leiomyosarcoma. During the subsequent two years he lost about 40 pounds. At autopsy the liver weighed 11,200 grams and was almost entirely replaced by tumor nodules. Small metastatic nodules were found in the lungs, pancreas, thyroid, adrenals, and kidneys. This appears to be the eighth case of p~qmaly smooth muscle tumor of the liver to have been reported. Primaly smooth muscle tumors of the lh~er progress relatively slowly, even if they are histologicaUy malignant.

Only 1 to 2 per cent o f the p r i m a r y malignant tumors o f the liver are sarcomas: the majority are carcinomas. A m o n g the sarcomas, primary leiomyosarcomas o f tile liver form a distinct subgroup. I f recognized earl}', they can be excised surgically because o f their slow growth and late metastasis. If untreated, however, they can attain an e n o r m o u s size and metastasize widely, as illustrated in the following case. CASE R E P O R T T h e patient, a 62 ) e a r old white male, first saw his private physician on October 12, 1966, because o f abdominal swelling o f one month's duration, which the patient thought was due to e n l a r g e m e n t o f his liver. During the preceding )'ear he had had some abdominal pain and a weight loss o f 20 pounds. Oil admission to a n o t h e r hospital, abdominal x-ray films showed a large mass or masses, probably the liver and spleen, occupying the major portion o f tile a b d o m e n and elevating the right henfidiaphragm. T h e chest was dear. *Associate Clinical Professor of l'athology, Uiiiversity of California, _Davis,_Schoolof Medicine. Pathologist, Sacramento Medical CenterTSacramento, California. -~Professor of Pathology, University of California, Davis, School of Medicine. Pathologist, Sacramento Medical Center, Sacramento, California.

A liver biopsy obtained oil October 24 consisted o f fragments of. t u m o r tissue without any liver parenchyma. T h e t u m o r was r e p o r t e d to consist o f elongated cells a r r a n g e d in bundles disposed in various directions. Tile cytoplasm was pink a n d tile nuclei were elongated with r o u n d e d ends. Some of the nuclei had a coarse chromatin pattern. Mitotic figures were present, averaging one per three o r f o u r high power fields. A diagnosis o f leiomyosarcoma was Inade. Liver scalming with 198Au showed a p p r o x i m a t e l y 60 p e r cent o f the liver to be replaced by nodules o f nonfimctioning tissue, which were scattered throughout tile viscus. T h e liver c o n t o u r was considerably enlarged and nodular. T h e patient was discharged from the hospital without specific therapy. He was admitted to tile Sacramento Medical Center for tile first time on August 8, 1967, becanse o f a severe nosebleed o f I0 to 12 hours' duration. Iris weight loss now a m o u n t e d to 40 potmds. He had been a restaurant worker who, for religious reasons, did not smoke o r drink. Physical examination revealed an emaciated male with a markedly protuberant abdomen. His pulse was 88 and the blood pressure, 110/60. T h e liver e x t e n d e d to the right iliac crest and across the midline to the left costal margin. Muhiple n o n t e n d e r nodules could be felt in the liver. Tile hemoglobin level was 12.3 gm. per 100 ml. and the white blood cell count was 10,500 p e r cu. ram. with a normal differential count. T h e p r o t h r o m b i n time was 15.9 seconds (control, 12.2 seconds). T h e nosebleed ceased with packing and he was discharged three days later. His second adlnission to the Sacralnent.o Medical Center occurred on March 26, 1968:; again because o f a nosebleed. At this time he also complained of shortness o f breath, as well as swelling of both his legs and the scrotum. Physical examination revealed m a r k e d venous distention over the feet, abdolnen, and anterior chest wall. T h e a b d o m e n was again markedly p r o t u b e r a n t with the m a r k e d enlargement o f the liver and nodules noted previously. In addition there was now ascites. Marked pitting e d e m a was noted to the midthigh level. T h e significant laboratory findings were the low serum sodium (130 milliequivalents per liter), chloride (92 milliequivalents p e r liter), and albumin (2.7 gm. per 100 nil.) levels as well as an elevated alkaline phosphatase o f 54 K.A. units (normal, 17). T h e

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Figure 1. Gross photograph of liver at autopsy, showing massive replacement by tumor nodules.

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Figure 2. High power light microscopic view of relatively well differentiated area of the tumor. The cells are elongated and arranged in bundles. (Hematoxylin and eosin stain, x 3.50.)

9MEDICAL I N T E L L I G E N C E

Figure 3. Light microscopic view of relatively poorly differentiated area of the tumor with a bizarre giant cell. (ttematoxylin and eosin stain, x 350.)

prothrombin time was 15.4 seconds on admission (control, 11 seconds). T h e bilirubin was normal and the S G O T was slightly elevated to 58 Karman traits (normal, 15 to 40); the urinalysis was normal. T r e a t m e n t was primarily with diuretics. He was discharged on April 4, 1968, slightly improved, with a hemoglobin of 14 gm. per 100 nil. a n d a prothrombin time of 13.9 seconds. He was readmitted for the third and final time on May 7, 1968, with increasing shortness of breath and increasing abdominal girth. Physical examination showed his abdominal girth to be 117 cm. (46 inches). T h e skin was taut and the liver again markedly enlarged. Ascites was present as well as scrotal and pedal edema. On this admission the hemoglobin level was 9.2 gtn. per 100 hal. with a hematocrit of 32 per cent. T h e serum albumin had fallen to 2.3 gin. per 100 nil. and the alkaline pltosphatase was 38 K.A. units. T h e S G O T was 47 Karnmn units. Chest and abdominal x-ray views continued to show distention of the abdomen, enlargement of the liver, and decreased lung volume. Attempts to relieve Iris edenm resulted initially in a loss of 20 pounds. However, he expired on J u n e 17, 1968, 20 tnonths after diagnosis of Iris tumor. At autopsy the body was that of an etnaciated male with a markedly protuberant abdomen. No icterus was noted. T h e r e was moder-

ate edema of the external genitalia and extremities. Tile liver was hard and nodular and occnpied most of the abdomen. T h e r e was approximately 5000 ec. of ascitic fluid. Small white hard t u m o r nodules were scattered on tile peritoneal and serosal surfaces. T h e mucosa of the bowel was nnremarkable. T h e liver weighed I 1,200 grams, 95 per cent of which was replaced b)" coalescing pale t u m o r nodules ranging in size ft'om 2 to 15 cm. (Fig. 1). T h e inferior vena eava was patent but its l u m e n was reduced by the nodules. Tire portal vein was patent. T h e thoracic cavities were markedly reduced in capacity by elevation of the dome of the diaphragm to the second intercostal space on the right side and the third intercostal space on the left. T h c plcural surface was smooth without evidence of tnetastasis. T h e lungs, however, ~,vele atelectatic and contained muhiple wlfite t u m o r nodules 5 to 15 ram. in diameter. Metastatic nodules were also found in the pancreas grossly. Microscopically, the t u m o r in the liver as well as in the metastatic foci showed many elongated spindle-slmped tumor cells forming interlacing bundles (Fig. 2). Most of the nuclei were elongated, although some had an oval or irregular, bizarre appearance. T h e chromatin pattern was variable. Some tumor cells had a tltin delicate nuclear m e m b r a n e with fine stippled chromatin, whereas in the more

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Figure 4. • 140.)

Light microscopic view of a metastatic tumor nodule in the hmg. (Hematoxyliu and eosin stain.

bizarre pleomorpltic cells, the chromatin was dense and coarse (Fig. 3). Mitotic figures averaged one per two or three high power fields. Van Gieson staining o f the t u m o r sltowed the cells to stain a pale yellow, whereas Masson's trichrome stain showed the t u m o r cells to be r e d - b o t h characteristic for myofibrils. T h e r e was no cirrhosis. Microscopically, metastatic t u m o r nodules were found not only in the hmgs, pancreas, and peritoneal surfaces, as noted grossly, but also in the thyroid, adrenals, and kidneys (Fig. 4). T h e h m g metastases w e r e found a r o u n d stnall bronchi and bronchioles as well as within the alveoli. Hyperemia, atelectasis, terminal bronchopneumonia, and thickening o f the medium sized p u h n o n a r y arterial wails were also seen in the htngs. DISCUSSION

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B)" far the commonest site o f origin o f tntnors o f smooth mnscle is the uterus, followed b)' the gastrointestinal tract. An origin in these organs has to be exclnded before considering snch a tnmor to be primar)' in the liver. Review o f the literature shows tlmt tiffs condition has been largely fidfilled in seven previons cases. ~-6 In addition A c k e r m a n 7 mentions, without details, lmving seen several primar)- hepatic leiomyosarcomas. In the absence o f metastasis, leiomyosarcomas have to

be distinguished fi-om leiomyomas on the basis o f cytology. In tire uterus, mitotic counts have been found to be tile best criterion for distinguislting leiomyosarcomas from leiomyomas. In these tnmors five mitoses or m o r e p e r 10 high power fields have been suggested as the best criterion for a diagnosis o f leiomyosarcotna, s Prinmr)" smooth muscle tumors o f tile liver are thought to arise from hepatic vascular structures. All except two o f tltose pt-evionsly r e p o r t e d were considered to b e . malignant.l,s Because o f its capacity to metastasize, o n r patient's t n m o r clearly was a leiomyosarcoma r a t h e r titan a leiomyoma. T h e cellular pleomorphistn and freqttenc)" o f mitosis varied greatly in different areas o f tlte tnmor. T h e n u m b e r o f mitoses in o u r case was perhaps slightly less than that required for a diagnosis o f malignant change in a smooth mttscle tttmor o f the uterus. However, only a study of f n r t h e r cases will define more clearly the cytologic criteria o f tnalignant cltange in smootlt mnscle tumors o f the liver. Surgical excision was perfortned in four o f the previously r e p o r t e d cases?" s, 4 Although one of these tumors was histologically highl)" malignant (six to eight mitoses p e r high power field), the patient is known to have survived approximately two )'ears without clinically obvious metastasis, s Two o f the other patients were tumor-free at the time of publication ttp to eight months after snrger)', 1'4 and one died

MEDICAL INTELLIGENCE f r o m metastatic disease o n e and o n e - h a l f }ears a f t e r o p e r a t i o n ? As for the t u m o r s not treated surgically, o n e l)atient was k n o w n to have h a d the m i n o r for f o u r )'ears p r i o r to death. ~ In spite o f a clinical history o f only a few months, o u r patient's t u m o r was i n o p e r a b l e at tim t i m e o f diagnosis because o f massive hepatic dissentination. Nevertheless he st, rvived for almost two )'ears. P r i m a r y l e i o m y o s a r c o m a s have also b e e n r e p o r t e d in various sites in tim vicinity o f tim liver. A m o n g these is the l i g a m e n t u m t e r e s ? T h i s patient was k n o w n to h a v e lived for 20 }'ears with his t u m o r . L e i o m y o s a r c o m a s o f the gallbladder h a v e also b e e n r e p o r t e d . Leiom y o s a r c o m a s o f the hepatic vein t e n d to manifest themselves by the B u d d - C h i a r i s y n d r o m e . Leiontyosarcomas metastatic to the liver are also rare but p r o b a b l y are c o m m o n e r than prim a r y leiomyosarcomas, a T h e y a p p a r e n t l y s h a r e a relatively i n d o l e n t course with p r i m a r y hepatic leiomyosarcomas. B e n g m a r k et al? ~ r e c o m m e n d e d aggressive t r e a t m e n t o f malign a n t Itepatic t u m o r s , both p r i m a r y a n d metastatic. T h e i r r e g i n t e n consisted o f hepatic dearterialization a n d the infusion o f 5-fluorouracil

via the portal vein, followed by resection, if possible. Such m a n a g e m e n t would seem to be particularly indicated for leiomyosarcomas affecting the liver o r its adjacent structures. References I. Demel, 1'.: Ein Operierter Fall ~on I.ebermyom. Virch. Arch., 281:881, 1926. 2. Watanuki, K., and Kusama, K.:A case of leiom)osarcoma of the liver. Nippon Ika Daig. Z., 22:552, 1955. 3.'Melnikov, R. A., and Jukharov, V. F.: Leiomyosarcoma of the liver. Veprosi Onkologii., 16:73, 1970. 4. Wilson, S. E., Bratman, It., Hested, W. G., et al.: Primary leiomyosarcoma of the liver. Ann. Surg., 174:232, 1971. 5. Rios Dalenz, J. L.: I.eiomyoma of the liver. Arch. Path., 79:54, 1965. 6. Yamaguchi, T;, Yanagisawa, M., Ootori, M., et al.: Case of primary leiomyosarcoma of the liser. Naika, 22:1495, 1968. 7. Ackerman, L. V.: Surgical Pathology. Ed. 4. St. Louis, The C. V. Mosby Co., 1968, p. 468. 8. Christopherson, W. M., Williamson, E. D., and Gray, L. A.: keiomyosarcoma of the uterus. Cancer, 29: 1512, 1972. 9. Mital, R. N., and Bazaz-Mauk, G. I'.: I.eionDosarcoma of ligamentum teres of the liver. Am. J. Gastnmnt., 56:48, 1972. 10. Bengmark, S., Brix, M., Borjesson, B., et al.: Treatment of hepatic tumors. I)igestion, 3:309, 1970. l)epartnmnt of Pathology Sacramento Medical Center 2315 Stockton Boulevard Sacramento, California 95817 (Dr. Fong)

Editorial Tiffs first issue o f 1974 is a m a j o r nfilestone for Human Patholog% It was only f o u r }'ears ago that a small g r o u p o f patltologists, w o r k i n g with the W. B. S a u n d e r s C o m p a n y , c o n c e i v e d o f a j o u r n a l for all pathologists c o n c e r n e d with u n d e r s t a n d i n g h u m a n disease. Human Patholo/,9 9 was b o r n a n d g u i d e d in its earl}', f o r m a t i v e days by a d e d i c a t e d Editorial Board. T h e j o u r nal was to be published q u a r t e r l y a n d various issues were to be d e v o t e d to symposia on specific subjects. F r o m a m o d e s t trickle o f subntitted papers, the j o u r n a l has g r o w n rapidly, g a i n i n g wide acceptance. B e g i n n i n g with this issue, Human Patholog9" will be in yottr h a n d s e v e r y two months. I am p r o u d o f the loyal, c o m m i t t e d m e m b e r s o f the Editorial B o a r d w h o h a v e m a d e o u r success possible. As Editor, I c o n t i n u e to p l e d g e o u r full e n e r g i e s toward publication o f a m e a n i n f g u l j o u r n a l . We will

constantly be alert for new ideas and elt'ective p r o d u c t i o n techniques. In this r e g a r d , tile W. B. S a u n d e r s C o m p a n y has c o o p e r a t e d to tile fullest in h e l p i n g to p r o d u c e a visually excellent j o u r n a l . We look f o r w a r d to 1974 and b e y o n d in m a i n t a i n i n g the h i g h s t a n d a r d s set by the f o u n d e r s o f the j o u r n a l a n d in b r i n g i n g to the r e a d e r the kinds o f i n f o r m a t i o n useful in the daily practice o f pathology. With this issue we i n a u g u r a t e the section, "Progress in H u m a n Patlmlogy," u n d e r the editorial gtfidance o f Dr. William *1. T h u r l b e c k . Tltis section will be a regularly o c c u r r i n g feature o f the j o u r n a l , a n d it is to be h o p e d that you will give us }'our o p i n i o n as to how tim " l ' r o g r e s s " series reflects y o u r needs. BERNARD M. "~VAGNER

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