Primary Hepatic Leiomyosarcoma

GASTROENTEROLOGY 69:994- 997,

1975 Copyright© 1975 by The Williams & Wilkins Co.

Vol. 69, No.4 Printed in U.S.A .

PRIMARY HEPATIC LEIOMYOSARCOMA: A report of two cases HENRY MASUR, M.D., EDWARD B. SussMAN , M.D. , AND DAVID W. MoLANDER, M.D. Departments of Medicine and Pathology, M emorial Sloan Kettering Cancer Center, New York , New York

Two cases of primary hepatic leiomyosarcoma are reported. Review of the literature reveals only seven previous reports. Cases presented predominantly with either hepatomegaly or ascites. Neither history nor physical and laboratory examination distinguished these patients with primary leiomyosarcomas from those with other hepatic tumors. Analysis of the cases reviewed suggests that aggressive hepatic surgery may improve prognosis. Leiomyosarcoma is an uncommon malignant tumor which arises from a variety of sites including uterus, stomach, retroperitoneum, superficial soft tissues, bladder, kidney, and lung. The liver is a distinctly unusual locus for a primary leiomyosarcoma. This report describes the 8th and 9th cases recorded in the literature. 1-6 Case Reports M.F., a 62-year-old Caucasian woman, noted several weeks of progressive fatigue and right upper quadrant pain. Abdominal distention and an enlarged. nodular liver were noted 4 months antemortem at her local hospi· tal. Liver scanning with ••mTc showed an 18-cm liver with multiple filling defects. Chest X-ray, upper gastrointestinal series, small bowel series, anil barium enema were normal. Liver function tests were not done. Without tissue diagnosis the patient was treated with 5-fluorouracil, 250 mg thrice weekly for 4 months; subsequently thiotepa, 5 mg twice weekly for 6 weeks, and vincristine, 0.5 mg twice weekly, were added. The patient's symptoms persisted despite ther· apy. Ten days prior to her Memorial Hospital admission she noted increasing abdominal girth and symmetrical lower extremity swelling to midthigh. A paracentesis was done by her private physician and she was admitted to Memorial Hospital. Physical examination re· Case

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Received October 21, 1974. Accepted May 29, 1975. Address requests for reprints to: Dr. David W. Molander, 235 East 67th Street, New York , New York 10016 994

vealed a massively distended abdomen with multiple, nontender, 2· to 5-cm nodules adherent to the abdominal wall in all four quadrants, with a positive fluid wave. The liver was firm and nodular, 22 em in span, and nontender; no splenomegaly was noted. Superficial vasculature on the abdominal wall was prominent with apparent bidirectional flow'; pitting edema to the level of the umbilicus was found . Laboratory examination revealed that the bilirubin was 8.12 mg per 100 ml, the serum glutamic oxaloacetic transaminase was 145 U (normal 5 to 40 U), the alkaline phosphatase was 695 U (normal15 to 85 U) , the 5'-nucleotidase was 36 U (normal 3 to 15 U), the prothrombin time was 15.3 sec (control 12.0 sec), the blood urea nitrogen was 81 mg per 100 ml (normal 8 to 20), creatinine was 1.8 mg per 100 ml (normal 0.7 to 1.7). Chest X-ray showed bilateral lung nodules. Liver scanning with 99 mTc showed only a few patches of uptake but no definitely identifiable liver outline (fig. 1). An upper gastrointestinal series and barium enema were normal. While undergoing diagnostic work-up the patient went into hepatic failure, then renal failure, developed Escherichia coli sepsis, and died on day 11 after admission . At postmortem examination, the liver weighed 8700 g and was approximately 90 % replaced by confluent, fleshy, gray-white tumor nodules measuring up to 17 em in diameter with focal areas of hemorrhage, necrosis, and cystic degeneration. Pedunculated focally cystic tumor nodules up to 10 em in diameter bulged from the liver surface . The ligamentum teres

October 1975

CASE REPORTS

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distended abdomen with right upper quadrant tenderness and an ill -defined right upper quadrant mass. Laboratory examination revealed the total bilirubin was 0 .57 mg per 100 ml, the serum glutamic oxaloacetic transaminase was 17 U (normal 8 to 40 U), the alkaline phosphatase was 3.5 U (normal 3 to 15 U), the prothrombin time was 17.0 sec (control12.0 sec), and the bromosulfophthalein was 29 %. Chest X-ray, upper gastrointestinal series, and barium enema revealed no pertinent findings. A laporatomy was again performed. The right lobe of the liver was largely replaced by three gray-white tumor nodules, rubbery in consistency, well circumscribed, but nonencapsulated, with a scalloped border. The nodules were 13 em, 6 1!2 em, and 4 1/ 2 em in diameter. The right lobe of the liver, weighing 930 g, was excised. Histology was consistent with leiomyosarcoma (fig. 4) . The patient was lost to follow-up, but was known to have died 37 months later. Postmortem examination showed an enlarged left lobe of the liver with numerous white tumor nodules up

FIG. 1. Liver scan (••mTc), with the costal margins and the inferior border of palpable liver drawn in, shows a massively enlarged liver which has been extensively replaced by tumor. No definite liver outline is seen: a large, comma-shaped area of uptake is noted in the left lobe of the liver (LLL) . A posterior scan showed an enlarged spleen displaced posteriorly.

was surrounded by extrinsic tumor. The intrahepatic portion of the inferior vena cava was occluded by a recent tumor thrombus. There was no cirrhosis, Microscopically, the tumor was a leiomyosarcoma consisting predominantly of long spindle-shaped cells arranged in interlacing fascicles (figs. 2 and 3). Tumor cells stained red with Masson's trichrome and the cytoplasm contained myofibrils. Pleomorphic tumor giant cells were present focally. Mitotic figures average 17 per 10 high power fields. Case 2. E.W ., a 66-year-old Caucasian female, was well until 16 days prior to admission when she noted moderately severe right upper quadrant pain associated with anorexia but no nausea and vomiting. She noted a 20-lb weight loss during this period, and 5 days prior to admission she was admitted to her local hospital where an abdominal mass was noted . At laparotomy a large hepatic mass was noted and biopsied. The patient was then referred to Memorial HospitaL Past medical history was pertinent only for a partial gastrectomy 6 years previously for peptic ulcer disease; there was no significant drug or alcohol history . Physical examination was remarkable for a

FIG. 2. Case 1: hepatic leiomyosarcoma with interlacing fascicles of spindle-shaped tumor cells (hematoxylin and eosin, x 100).

FIG. 3. Case 1: elongated leiomyosarcoma cells with blunt-ended hyperchromatic nuclei (hematoxylin and eosin, x 4:10).

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CASE REPORTS

Vol. 69, No . 4

to 6 em in diameter throughout. Hepatic veins and inferior vena cava were free of tumor thrombus. There was no cirrhosis. Tumor was noted to involve the peritoneum, retroperitoneum, and right renal hilum grossly, and both lung bases microscopically. Microscopically the tumor consisted of interlacing spindle-shaped cells, consistent with leiomyosarcoma.

arise from hepatic veins or bile ducts. Discovery of this hepatic tumor requires careful search to ascertain that it neither arises in an adjacent structure nor is metastatic from another primary. There are numerous reports of primary leiomyosarcomas of the stomach and inferior vena cava, and isolated reports of the primary arising in diaDiscussion phragm, ligamentum teres, and gallbladder. Review of 310 primary hepatic malignan- There are several reports of leiomyosarcies seen at Memorial Hospital from 1947 coma metastatic to the liver. Evaluation of to 1973 revealed no other leiomyosarcoma. malignancy is based primarily on the numThe rarity of primary leiomyosarcoma at ber of mitoses per high power field, but Memorial Hospital is consistent with Ack- correlation with the clinical course is not erman's cumulative experience, which in- absolute. There has been one report of a primary hepatic leiomyoma. 8 cluded only "several" such tumors. 7 Data from 7 previously reported cases Hepatic smooth muscle tumors probably and the 2 patients reported here are summarized in table 1. The patients ranged in age from 32 to 63 years and included 6 females and 3 males. When initially seen 7 of 9 patients complained primarily of right upper quadrant pain, 1 noted pedal edema, and 1 had constitutional complaints, the duration of symptoms varying between 3 days and 1 year. On physical examination 7 presented with hepatomegaly, 1 with a normal sized liver but impressive ascites, and 1 with jaundice, hepatosplenomegaly, and skin nodules. Liver function tests showed no clear pattern, but only 1 patient FIG . 4. Case 2: interlacing fascicles of spindlepresented with all normal values. Liver shaped tumor cells, with hepatocytes present on the right side (hematoxylin and eosin, x 100). scan was done in 3 cases: each showed TABLE 1

Reference

Presenting Sign

Therapy

Survival

-· Extent of disease at postmortem

Fong and Ruebner'

Hepatomegaly

Conservative

20 months

Wilson et al. 2 Wilson et al. 2 MacMahon and Ball 3 Yamaguchi et al.

Hepatomegaly Hepatomega ly Ascites Pedal edema Hepatomegaly with mass Abdominal mass

Right lobectomy Wedge resection Exploratory la parotomy Conservative

Well at 8 months 18 months 6 weeks 9 months

" Widespread" Liver, inferior vena cava Liver, peritoneum

Left lobectomy

24 months

Unknown

Melnikov and Sukharov ' Demel•

Wedge resection

No follow-up

Masur

Hepatomegaly with mass Hepatomegaly

Right lobectomy

49 months

Masur

Hepatomegaly

Chemotherapy

6 mont hs

Liver, lung, pancreas, thyroid, adrenal, kidney

Liver, lungs, renal hilum , peritoneu m Liver, lungs, porta hepatis

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CASE REPORTS

large or multiple defects. Only 1 patient was documented to have metastatic disease on initial presentation. 4 With regard to therapy, 2 patients underwent right hepatic lobectomy in which all apparent tumor was removed: 1 survived 49 months after initial presentation to her physician before expiring, with autopsy showing involvement of liver, lungs, renal hilum, and peritoneum; the other patient was alive and clinically free of disease at 8 months postsurgery. Two patients underwent wedge resection of the tumor, 1 surviving 18 months, autopsy showing "widespread" tumor; no follow-up was available on the second. Two patients received only supportive therapy: 1 survived 20 months, autopsy showing disease in liver, lungs, pancreas, peritoneum, adrenal, kidney, and thyroid; the other died at 9 months with postmortem evidence of liver and peritoneal involvement. One patient died after exploratory laparotomy of Budd-Chiari syndrome, and patient M.F. reported here survived 6 months on combination chemotherapy before succumbing to sepsis. Of note, no association with cirrhosis was apparent from autopsy or surgical examination. Thus, evaluation of these 9 patients reveals that there is little evidence from history on physical or on laboratory examination to suggest leiomyosarcoma. Once the tissue diagnosis is established, a decision with regard to mode of therapy must be made. While assessment of malignancy by histological criteria is of some help in determining degree of aggressiveness of the tumor, assumption that a leiomyosarcoma arising in the liver will behave similarly to one with identical histology arising elsewhere is probably unwarranted. 9 It should be noted, however, that morbidity in the 6 cases reviewed here was related primarily either to massive replacement of hepatic parenchyma or to compression of, or extension into local vessels, not to metastases. Except for the postsurgical death, survival, regardless of therapy, ranged from

997

6 to 49 months from initial diagnosis. This suggests that with this slow growing tumor, excision of the bulk primary tumor may be appropriate even in the face of metastatic disease. This situation is in sharp contrast to the experience with primary hepatocellular carcinoma, in which average survival from time of diagnosis is 2 to 5 months, survival for more than 12 months is unusual, and the presence of metastases is generally considered to be a contraindication to surgery. 10 • 11 Thus, consideration of the possibility of primary hepatic leiomyosarcoma is important because, even in the presence of distant metastases, prognosis may not be as limited as with the more common maligr1ancies, and, despite the significant risks of hepatic lobectomy, prognosis may be improved by aggressive surgery. REFERENCES 1. Fang JA, Ruebner BH: Primary leiomyosarcoma of the liver. Hum Pathol 5:115-119, 1974 2. Wilson WE, Braisted H, Plested WG, et al: Primary leiomyosarcoma of the liver. Ann Surg 174:232-237, 1971 3. MacMahon HE, Ball HG: Leiomyosarcoma of hepatic vein and the Budd-Chiari syndrome. Gastroenterology 61:239-243, 1!J71 4. Yamaguchi T, Yanagisawa M, Ootori M, ct al: Case of primary leiomyosarcoma of the liver. Naika 22:1495, 1968 5. Melnikov RA, Sukharov VF: Leiomyosarcoma of the liver. Boprosi Onkologii IG:7:l, 1970 6. Demel P: Ein operierter fall von Ieber myom. Virchous Arch 281:881, 1926 7. Ackerman LV: Sur{.lical PatholoJ;y. Fourth edition St. Louis, CV Mosby Co, 1968, p 4GB 8. Rios-Dalenz ,JL : Leiomyoma of the liver. Arch Pathol 79:54-56, 1965 9. Stout AP, Lattes R: Tumors of the soft tissues. In Atlas of Tumor Pathology. Second series, Fascicle 1, Washington DC , Armed Forces Institutes of Pathology, 1967, p 132 10. Foster ,JH: Survival after liver resection for cancer. Cancer 26:493-502, 1970 11. EI-Domeiri AA, Huvos AG , Goldsmith HS, eta!: Primary malignant tumors of the liver. Cancer 27:7-11, 1971