Retroperitoneal Liposarcoma SHELDON C. BINDER, M.D., F.A.C.S., BERTRAM KATZ, M.D., F.A.C.S., M.F. BARRY SHERIDAN, M.D., F.D.R.T.
A group of patients with retroperitoneal liposarcoma is presented and general guidelines of management reviewed. It is suggested that aggressive, radical total surgical excision followed by adjuvant postoperative irradiation be used as the treatment of choice. Although the management of recurrent disease may be discouraging in terms of ultimate cure, reasonable palliation and prolonged survival may result from aggressive therapy.
T IPOSARCOMAS COMPRISE between 7.5-25% of soft
L tissue sarcomas, which in themselves comprise one per cent of all cancers.2 4"0'14'16'19'21'22'25 They may occur wherever fat is present, especially within the deeper soft tissues, especially in the extremities, and with a predilection for the thighs. Between 12% and 40% occur in the retroperitoneum,4.8.10,12,16-18'21-24 were about 35% originate in the perirenal fat.3'8 Although the most common retroperitoneal soft tissues sarcoma, liposarcoma in this location comprises maximally only about 0.1% of all cancers. Since a general surgeon will only rarely encounter such a cancer, the experience at the Youngstown Hospital Association is reported and general guidelines in the management of this malignancy are presented.
Clinical Data Case 1. B.S. #857240. A 72-year-old Caucasian man with a ten year history of intermittent cramping lower abdominal pain after exertion developed more severe and persistent pain and discovered an abdominal mass two months prior to admission. On examination, he had a firm, nontender, mobile mass in the left lower quadrant of the abdomen. Chest x-ray and upper gastrointestinal barium contrast studies were normal. Intravenous pyelogram revealed a mass at the level of the left iliac crest which deviated the ureter medially. Barium enema revealed medial displacement of the left colon by an extrinsic mass. At operation on 2/10/70, he was found to have multi-
Reprint requests: Sheldon C. Binder, M.D., F.A.C.S., Professor and Chief of Surgery, The Youngstown Hospital Association, 345 Oak Hill Avenue, Youngstown, Ohio 44501. Submitted for publication: July 14, 1977. 0003-4932-78-0300-0257-0075
From the Departments of Surgery and Radiology, Northeastern Ohio Universities College of Medicine and the Youngstown Hospital Association, Youngstown, Ohio
nodular retroperitoneal tumor extending from the lower pole of the left kidney to the pelvic brim. It displaced the left ureter medially and bulged into the sigmoid mesentery but did not invade either structure. Total resection was effected without sacrificing any organs. Pathology revealed a grossly encapsulated well differentiated myxoid liposarcoma weighing 930 grams with one major nodule measuring 15.5 x 10 x 8.5 cm and another 12.5 x 10 x 5 cm. Two years later, he was readmitted with a recurrent painful mass in the left lower quadrant of the abdomen. At operation on 2/7/72, recurrent, still localized tumor was found lateral to the sigmoid colon and extending along the spermatic cord through the external inguinal ring. Complete excision was performed. Pathology revealed a 14 x 5 x 3.5 cm more poorly differentiated recurrent liposarcoma. Postoperatively, he received a tumor dose of irradiation of 4000 rads in 27 treatments via a 4 MEV linear accelerator to a field encompassing both operative areas. Two years later, he developed a recurrent painful mass in the left anterior flank with extension to the left hypochondrium. Upper gastrointestinal series revealed an extrinsic mass effect on the greater curvature of the stomach. Intravenous pyelogram and retroperitoneal ultrasonography revealed inferior and posterior displacement of the left kidney by the mass. Chest x-ray, liver scan, and barium enema were normal. At operation, he had recurrent retroperitoneal liposarcoma with invasion of the mesentery of the left colon, the spleen and tail of the pancreas, and the left diaphragm. A separate mass involved the mesentery of the transverse colon. Total resection was performed, with splenectomy, distal pancreatectomy, left hemicolectomy, and partial resection of the diaphragm. Gerota's fascia was excised, but the uninvolved left kidney was not resected. Pathology revealed a poorly differentiated liposarcoma invading the colonic mesentery and the spleen, and metastatic to lymph nodes in the splenic hilum. Postoperatively, a tumor dose of 4205 rads in 20 treatments via a 4 MEV linear accelerator was administered to the field of the most recent surgery. One month after completion of irradiation, he was found to have a right lower quadrant mass. Operation on 2/4/77, revealed generalized peritoneal carcinomatosis of anaplastic liposarcoma. Biopsy only was performed. He was readmitted one month later with multiple abdominal masses and died on 3/9/77, seven years after his original © J. B. Lippincott Company
257
258
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operation. Postmortem examination was not performed. At no time in his clinical course had he demonstrated evidence of metastatic disease to the liver or outside the abdomen. Case 2. F.G. #814310. A 55-year-old Caucasian man was discovered on routine examination to have a right lower quadrant abdominal mass. Intravenous pyelogram and chest x-ray were normal. Upper gastrointestinal series and barium enema revealed a mass displacing the right colon and ileum medially. At operation on 8/4/70, he was found to have a lipomatous tumor arising from the retroperitoneum posterior to the right colon and other separate tumor masses extending up the right retroperitoneum and in the right mesocolon. All tumors were individually excised. Pathology revealed eight grossly encapsulated well differentiated myxoid liposarcomas ranging in size from 14 x 8.5 x 5 cm to 5 x 4 x 1.7 cm and with an aggregate weight of 960 g. One year later,, he was found to have a recurrent right lower abdominal mass. Intravenous pyelogram revealed medial displacement of the right ureter; barium enema revealed superior displacement of the cecum and right colon. Operation on 8/15/71, revealed recurrent retroperitoneal tumor with invasion of the mesentery of the
ileum and right colon. The kidney and ureter were not involved. Total resection was performed along with three feet of ileum and the right colon. Pathology revealed well differentiated recurrent liposarcoma in an aggregate mass of 20 x 12 x 5.5 cm. Four years later, he was found to have a recurrent mass in the right flank and a mass in the right spermatic cord. At operation on 3/13/75, he had a tumor mass overlying the promontary of the sacrum with compression but no invasion of the right iliac vessels and displacement but no invasion of the right ureter. The tumor was totally resected from the retroperitoneum and two separate tumor masses were resected from the right spermatic cord. Pathology revealed a 9 x 7 x 5 cm recurrent well differentiated liposarcoma of the retroperitoneum and a 5.5 x 4 x 1.5 cm and a 7 x 5 x 3 cm well differentiated liposarcoma of the spermatic cord. Foci of pleomorphic tumor cells, not seen in the previous specimens, were present histologically. Postoperatively, he received a tumor dose of 4,420 rads in 26 treatments to the lower abdomen via a 4 MEV linear accelerator. The patient has since been clinically free of recurrent disease 2-½ years after his latest resection and seven years after his original
operation. Case 3. C.B. #569089. A 45-year-old Caucasian
woman with a history of lumbar backache developed diffuse abdominal colic and noted an abdominal mass three weeks prior to admission. She had undergone hysterectomy and appendectomy for fibroid uterus 18 years before. On examination, she was found to have a nontender right abdominal mass extending from inferior to the liver to the iliac crest. Gastrointestinal x-ray studies revealed superior displacement of the gallbladder, medial displacement of the descending portion of the duodenum, and inferior displacement of the hepatic flexure of the colon by a radiolucent right retroperitoneal mass. Intravenous pyelogram revealed anteromedial displacement of the inferior pole of the right kidney and medial displacement of the ureter. At operation on 4/2/73, a large retroperitoneal mass adherent to the kidney was found to extend from above the kidney to the pelvic brim, with medial displacement but no invasion of the root of the mesentery and its viscera. The mass was totally excised outside its gross capsule with right nephrectomy and resection of Gerota's fascia. Pathology revealed a 20 x 18 x 6 cm lobulated well differentiated myxoid liposarcoma which, excluding the kidney, weighed 900 g and was adherent to but did not invade the kidney. Postoperatively, she received a tumor dose of 4,140 rads irradiation in 23 treatments to the right retroperitoneum via a 4 MEV linear accelerator. She has since been well and free of evidence of recurrent disease 4-½
one year
years
later.
Ann.
Surg. * March 1978
Case 4. G.M. #327133. A 73-year-old Caucasian woman was admitted to hospital with a one month history of weakness, dyspnea on exertion, melena, and anemia. On examination, she was found to have an ill-defined mass extending from above the umbilicus to the pelvic brim. Chest x-ray, barium enema, and upper gastrointestinal series were normal. Intravenous pyelogram revealed partial obstruction of the lower portion of the right ureter. At operation on 4/5/73, she was found to have a tumor mass filling the entire retroperitoneal space from diaphragm to the pelvic inlet and with invasion of the root of the mesentery. The tumor was considered technically nonresectable and was biopsied only. Pathology revealed well differentiated myxoid liposarcoma. Postoperatively, she received a tumor dose of 3,720 rads in 22 treatments via a 4 MEV linear accelerator. She did poorly thereafter and expired at home seven months after
operation. Case 5. #756776. A 48-year-old Caucasian woman with a four month history of left lower abdominal pain was found to have a left lower quadrant abdominal mass. At operation on 10/11/66, two separate lipomatous tumor masses were resected from the sigmoid and descending mesocolons. Pathology was reported as benign lipomyxofibroma. Postoperatively, she developed severe hypertension. Intravenous pyelogram revealed poor function in a hydronephrotic left kidney. At operation on 3/15/67, she was found to have extensive scarring about the left kidney, which was markedly hydronephrotic and had a thin renal cortex. The left ureter was bound down in dense fibrotic tissue. With an operative diagnosis of renal destruction secondary to operative injury, urinary extravasation, and fibrosis in Gerota's fascia, left nephroureterectomy was performed. No attempt was made to remove the mass of fibrotic tissue which was densely adherent to the retroperitoneum and periaortic tissues. Pathology revealed well differentiated myxoid liposarcoma obstructing the left ureter and causing severe renal destruction. Review of pathology from the original operation revealed well differentiated liposarcoma. Her hypertension remitted. Postoperatively, she received 4,500 rads tumor dose in 30 treatments via a Cofi apparatus. Seven years later, she developed epigastric pain, postprandial bloating, anorexia, and weight loss. Upper gastrointestinal series revealed anteriomedial displacement of the stomach by an extrinsic mass. Intravenous pyelogram and barium enema were unremarkable except for absence of the left kidney. Selective arteriography revealed a vascular tumor mass supplied by lumbar and left adrenal arteries which displaced the spleen and body of the pancreas anteriorly. At operation on 10/17/74, she had tumor filling the left retroperitoneum with direct invasion of the spleen and tail and body of the pancreas. The tumor was totally resected, with sacrifice of the spleen, body and tail of the pancreas, and left adrenal gland. The tumor was densely adherent to the aorta but could be resected by skeletonizing the left anterolateral surface of the aorta and the celiac axis and origin of the superior mesenteric artery. Postoperatively, the patient developed profound metabolic acidosis and signs of hepatic failure and expired 36 hours postoperatively. Postmortem examination revealed hepatic artery and superior mesenteric artery thrombosis with hepatic and mesenteric infarction. No residual or metastatic liposarcoma was discovered. The resected specimen revealed recurrent well differentiated liposarcoma with invasion of the pancreas and the capsules of spleen and adrenal gland.
Discussion
Pathology Liposarcomas occur at any age, but the majority occur in the 40-60 year age group, with an average of
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RETROPERITONEAL LIPOSARCOMA
about 53 years.24,8'9,12"3,17,18,2124 In most series, there is a distinct male predominance but no racial predominance. The neoplasms are malignant from their inception, with only rare cases originating from benign lipomas.2 8'12'24 Their growth rate varies greatly from case to case and even in the same individual. Usually, they grow slowly, sometimes rapidly; and occasionally they remain quiescent for months or even years and then develop an exaccerbation of growth rate.8'22 They may attain enormous size, especially when they originate in the clinically silent retroperitoneum.9'24 As in the case with soft tissue sarcomas generally, liposarcomas tend to have a deceptive gross apparent encapsulation. The "capsule," however, actually consists of tumor cells flattened and attenuated by continuing expansile growth of the cancer; and enucleation of the tumor invariably is followed by local recurrence, frequently multicentric in distribution, as the scattered retained remnants of the pseudocapsule continue to grow. 2,3,8,12,22 Primary liposarcomas tend to grow by local expansion without tendency to invasion of surrounding tissues and may grow along fascial tissue planes to present as apparently separate tumor masses at some distance from the primary tumor. This phenomenon was apparent in cases 1 and 2, in which the tumors extended along the spermatic cord and presented as separate masses distal to the external inguinal ring. It may also account for the multiple tumors found in case 2, though multicentricity or metastasis are equally likely. Recurrent tumors have a decided propensity for invasive and infiltrative growth, as was demonstrated in cases 1, 2, 4, and 5, a phenomenon which accounts in part for the tendency of recurrences to be more aggressively malignant in their clinical behavior than the primary tumor.2'8'9'13'19'21 Recurrences may kill the patient by invasion of vital structures even though the tumor may remain localized. Metastases from liposarcomas may occur anywhere in the body, but are most common in lung, liver, and lymph nodes. Distant metastases may occur despite local control of the primary neoplasm; but they are distinctly more common after local recurrence. Stout's system of histopathologic classification is most commonly used.24 Some investigators have attempted to correlate the histology of liposarcomas with their clinical behavior as follows:2'8'11'12'24 Stout's Type I: Well differentiated myxoid typethese rarely metastasize but recur locally after inadequate excision, and have a more favorable prognosis. Type II: Poorly differentiated myxoid type these are clinically more malignant, recur frequently, and may metasta-
259
size. Their prognosis is less favorable. Type III: Round cell or adenoid type these pursue an aggressive clinical course and frequently metastasize. Their prognosis is poor. Type IV: Mixed group these pursue an aggressive clinical course and frequently metastasize. Their prognosis is poor.
However, in most series, there is a wide variation in the histologic appearance in different areas within the same tumor; and most authorities agree that the biologic behavior is difficult to predict histologically.1'2'4'8'18'22 Recurrent liposarcomas tend to be more cellular and anaplastic than the primary tumor, a phenomenon demonstrated in cases 1 and 2 and which also accounts for the biologically more aggressive behavior of recurrent tumors. Diagnosis
Diagnosis of liposarcomas can be made only by biopsy and pathologic evaluation. If excision ofthe entire tumor is possible, this is the ideal way to treat the neoplasm.4'824 In larger tumors, however, this is not always possible; and wedge biopsy prior to definitive treatment may be more appropriate. In the retroperitoneum, neoplasms are so much more likely to be liposarcomas than benign lipomas that it is best to assume malignancy and proceed with total excision without preliminary biopsy.8'9 Rapid-section histopathology, as is the case with most soft tissue sarcomas, is difficult even for the experienced pathologist. Treatment It is generally agreed that aggressively radical excisional surgery based on anatomic location, size, and local spread is the treatment of choice of liposarcomas wherever they occur. As is universally accepted in the surgical treatment of soft tissue sarcomas in general, the sarcoma must be removed en bloc. The investiture of the neoplasm by healthy tissues and organs, including involved portions of the gastrointestinal tract if necessary and feasible, must remain inviolate; and the line of dissection must be well beyond the palpable or visible limits of the tumor and its pseudocapsule.2'4'8'12'13,17-19,21,2224 Recurrence is invariable after incomplete excision or enucleation of a pseudoencapsulated liposarcoma. In the retroperitoneum, the major dangers in resection are injury to mesenteric vessels, the aorta, the inferior vena cava, and the renal vessels.9'13 The mortality rate of resection of retroperitoneal liposarcomas
Ann. Surg. * March 1978 BINDER, KATZ AND SHERIDAN 260 ranges from 12% to 36%.9,18 The higher rates are usually series reporting the higher rates.8'9' 1'12'19-23'25 The incidence of recurrence depends on the adequacy of exencountered in resections of recurrent disease. Although response to irradiation may be variable and cision, with rates two to four times higher after local unpredictable,2'923 irradiation of retroperitoneal lipo- excision than after radical resection.5'6'19'21 In some sarcomas is of definite value in therapy. The dose given series, adjuvant radiation therapy is associated with for cure of extremity liposarcomas is 5000-6000 rads lower recurrence rates and prolonged free interval in in 41/2 to six weeks;10'23 but such dosage may be im- those patients who do develop recurrence.10'18 All possible to deliver safely to the retroperitoneum. The series report higher rates of recurrence after reresecslow-growing, well differentiated myxoid type of lipo- tion for recurrent disease than after primary radical sarcomas are relatively radiosensitive; while the rap- curative resections. Over half of the patients who develop local recuridly-growing, more anaplastic and highly malignant liposarcomas are relatively radioresistant.8"0"2 Recur- rence also develop concurrent distant metastases;5'6'18 rent liposarcomas are less radiosensitive than primary and local recurrence more than doubles the probability that a patient will die of liposarcoma. Because pallative tumors.4'8'22 therapy yields dismal results, with only rare long-term Radiation therapy has generally been employed in most investigators advocate aggressive sursurvivors, the treatment of incompletely resected liposarcomas, or combined therapy in the radiotherapeutic, gical, recurrences at the primary site, inoperable primary disease. Although results of recurrent management tumors which can be biopsied only, and metastatic with the majority of pa1018.22'25 Even when the cancer is not comhave been poor, generally disease. with dead of disease within two years recurrence tients pletely eradicated locally, irradiation may provide good survivals have been long-term of initial diagnosis,6'15'25 palliation and prolong survival. Since irradiation is such an aggressive often to sufficiently justify reported most effective for microscopic, residual, or small tu1 2 in have achieved and our series Cases approach.18 mors but is generally ineffective in producing permasurvival after of comfortable nent ablation in gross recurrent, inoperable, or non- significant prolongation disease. Alfor recurrent such aggressive therapy resectable tumors, debulking of the tumor is indicated become most recurrences clinically evident though when technically feasible. Preoperative irradiation may make primary inopera- within two to five years of treatment, they may occur ble liposarcomas technically resectable.22 It is essen- much later, as was the situation in our case 5. Longtial, however, to perform the same wide en bloc re- term follow-up is, therefore, essential.3'6'8'9'15'18'25 Five year survival rates in various series of retrosection as would have been done without irradiation; since, in the majority of cases resected after irradiation, peritoneal liposarcomas have been reported from 0%1"3microscopic foci of residual sarcoma are found even 11,15,16 to 1 1%,7,9,11.12,25 with one report of 41%.18 Ten after seemingly favorable response to irradiation.2'8'22 year survival rates have been reported from 0%1.3.15.16.24 Radiosensitivity appears, therefore, greater than radio- to 7%,9.11.12 with one report of 12%.18 All investigators curability of liposarcomas. Because of the high inci- agree that the completeness of resection is the most dence of local recurrence after surgery, some investiga- important factor in effecting cure and that inadequacy tors recommend postoperative irradiation routinely, of the primary operation is the principle reason for even after grossly complete resection. 10"19'22 Our failure. Many investigators suggest that better results longest disease free survivor (case 3) had postoperative could be achieved by the routine use of irradiation irradiation after complete surgical excision. Even after radical excision. Kinne et al., who advocate an aggressive surgical therReferences apy, had their best results in terms of "cure" and disease free interval when irradiation was used postopera1. Atkinson, L., Garran, J. M. and Newton, M. C.: Behavior and tively. Perhaps our overall results would have imManagement of Soft Tissue Sarcomas. Cancer, 16:1552, 1%3. 2. Bowden, L.: Liposarcoma. In Pack, G. T. and Ariel, I. M., proved had we routinely used irradiation after primary (Eds.), Treatment of Cancer and Allied Diseases, 2nd Ed., resection, since in our cases local recurrence rather Volume VIII, The Soft Somatic Tissues and Bone. New York. than distant metastasis proved to be the important facHoeber, 1964. Chapter 8. pp. 120-129. 3. Braasch, J. W. and Mon, A. B.: Primary Retroperitoneal Tutor in ultimate result. Liposarcomas are nonresponsive mors. Surg. Clin. North Am., 47:663, 1967. to any reported conventional systemic chemother4. Brasfield, R. D. and DasGupta, T. K.: Liposarcoma. Cancer, 20:
apy.'8
Prognosis Retroperitoneal liposarcomas have a 20-85% rate of local recurrence after surgical resection, with most
3, 1970. 5. Brennhard, I. O.: The Treatment of Soft Tissue Sarcomas-A Plea for more Urgent and Aggressive Approach. Acta. Chir. Scand., 131:438, 1966. 6. Cantin, J., McNeer, G. P., Chu, F. C. and Booher, R. J.: The Problem of Local Recurrence After Treatment of Soft Tissue Sarcoma. Ann. Surg., 168:47, 1968.
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RETROPERITONEAL LIPOSARCOMA
7. Coran, A. G., Crocker, D. W. and Wilson, R. E.: A Twenty-Five Year Experience With Soft Tissue Sarcomas. Am. J. Surg., 119:288, 1970. 8. DasGupta, T. K.: Tumors and Tumor-like conditions of the Adipose Tissue. Curr. Prob. Surg. March, 1970, Chicago, Yearbook Medical Publishers. 9. DeWeerd, J. H. and Dockerty, M. B.: Lipomatous Retroperitoneal Tumors. Am. J. Surg., 84:397, 1952. 10. Edland, R. W.: Liposarcoma. A Retrospective Study of Fifteen Cases. A Review of the Literature, and a Discussion of Radiosensitivity. Am. J. Roentgenol., Radium Ther. Nucl. Med., 103:778, 1968. 11. Enzinger, F. M. and Winslow, D. J.: Liposarcoma. A Study of 103 cases. Virchows Arch. Pathol Anat., 335:367, 1962. 12. Enterline, H. T., Culberson, J. D., Rochlin, D. B. and Brady, L. W.: Liposarcoma. A Clinical and Pathological Study of 53 cases. Cancer, 13:932, 1960. 13. Farbman, A. A.: Retroperitoneal Fatty Tumors. Report of a Case and Collective Review of the Literature from 1937-1947. Arch. Surg., 60:343, 1950. 14. Ferrell, H. W. and Frable, W. J.: Soft Part Sarcomas Revisited. Cancer, 30:475, 1972. 15. Glen, F. and Watson, R. C.: Retroperitoneal Liposarcoma. N.Y. State J. Med., 72:2789, 1972.
261
16. Hare, H. F. and Cerny, M. J.: Soft Tissue Sarcoma. A Review of 200 Cases. Cancer, 16:1332, 1963. 17. Holtz, F.: Liposarcoma. Cancer, I11: 1103, 1958. 18. Kinne, D. W., CHU, F.C.H., Huvos, A. G., et al.: Treatment of Primary and Recurrent Retroperitoneal Liposarcoma. Cancer, 31:53, 1973. 19. Krementz, E. T. and Shaver, J. O.: Behavior and Treatment of Soft Tissue Sarcomas. Ann. Surg., 157:770, 1963. 20. Lieberman, E. and Ackerman, L. V.: Principles in the Management of Soft Tissue Sarcomas. A Clinical and Pathologic Review of 100 cases. Surgery, 35:350, 1954. 21. Martin, R. G., Butler, J. J. and Albores-Saavedra, J.: Soft Tissue Tumors: Surgical Treatment and Results. Tumors of Bone and Soft Tissue, Chicago, Yearbook Medical Publishers, 1965, pp. 333-347. 22. Pack, G. T. and Pierson, J. C.: Liposarcoma. A Study of 105 Cases. Surgery, 36:687-712, 1954. 23. Spittle, M. F., Newton, K. A. and Mackenzie, D. M.: Liposarcoma. A Review of 60 cases. Br. J. Cancer, 24:696, 1971. 24. Stout, A. P.: Liposarcoma-The Malignant Tumor of Lipoblasts. Ann. Surg., 119:86, 1944. 25. Thorbjarnarson, B.: Sarcomata at the New York Hospital. Arch. Surg., 82:489, 1961.
A group of patients with retroperitoneal liposarcoma is presented and general guidelines of management reviewed. It is suggested that aggressive, radical total surgical excision followed by adjuvant postoperative irradiation be used as the treatment of choice. Although the management of recurrent disease may be discouraging in terms of ultimate cure, reasonable palliation and prolonged survival may result from aggressive therapy.
T IPOSARCOMAS COMPRISE between 7.5-25% of soft
L tissue sarcomas, which in themselves comprise one per cent of all cancers.2 4"0'14'16'19'21'22'25 They may occur wherever fat is present, especially within the deeper soft tissues, especially in the extremities, and with a predilection for the thighs. Between 12% and 40% occur in the retroperitoneum,4.8.10,12,16-18'21-24 were about 35% originate in the perirenal fat.3'8 Although the most common retroperitoneal soft tissues sarcoma, liposarcoma in this location comprises maximally only about 0.1% of all cancers. Since a general surgeon will only rarely encounter such a cancer, the experience at the Youngstown Hospital Association is reported and general guidelines in the management of this malignancy are presented.
Clinical Data Case 1. B.S. #857240. A 72-year-old Caucasian man with a ten year history of intermittent cramping lower abdominal pain after exertion developed more severe and persistent pain and discovered an abdominal mass two months prior to admission. On examination, he had a firm, nontender, mobile mass in the left lower quadrant of the abdomen. Chest x-ray and upper gastrointestinal barium contrast studies were normal. Intravenous pyelogram revealed a mass at the level of the left iliac crest which deviated the ureter medially. Barium enema revealed medial displacement of the left colon by an extrinsic mass. At operation on 2/10/70, he was found to have multi-
Reprint requests: Sheldon C. Binder, M.D., F.A.C.S., Professor and Chief of Surgery, The Youngstown Hospital Association, 345 Oak Hill Avenue, Youngstown, Ohio 44501. Submitted for publication: July 14, 1977. 0003-4932-78-0300-0257-0075
From the Departments of Surgery and Radiology, Northeastern Ohio Universities College of Medicine and the Youngstown Hospital Association, Youngstown, Ohio
nodular retroperitoneal tumor extending from the lower pole of the left kidney to the pelvic brim. It displaced the left ureter medially and bulged into the sigmoid mesentery but did not invade either structure. Total resection was effected without sacrificing any organs. Pathology revealed a grossly encapsulated well differentiated myxoid liposarcoma weighing 930 grams with one major nodule measuring 15.5 x 10 x 8.5 cm and another 12.5 x 10 x 5 cm. Two years later, he was readmitted with a recurrent painful mass in the left lower quadrant of the abdomen. At operation on 2/7/72, recurrent, still localized tumor was found lateral to the sigmoid colon and extending along the spermatic cord through the external inguinal ring. Complete excision was performed. Pathology revealed a 14 x 5 x 3.5 cm more poorly differentiated recurrent liposarcoma. Postoperatively, he received a tumor dose of irradiation of 4000 rads in 27 treatments via a 4 MEV linear accelerator to a field encompassing both operative areas. Two years later, he developed a recurrent painful mass in the left anterior flank with extension to the left hypochondrium. Upper gastrointestinal series revealed an extrinsic mass effect on the greater curvature of the stomach. Intravenous pyelogram and retroperitoneal ultrasonography revealed inferior and posterior displacement of the left kidney by the mass. Chest x-ray, liver scan, and barium enema were normal. At operation, he had recurrent retroperitoneal liposarcoma with invasion of the mesentery of the left colon, the spleen and tail of the pancreas, and the left diaphragm. A separate mass involved the mesentery of the transverse colon. Total resection was performed, with splenectomy, distal pancreatectomy, left hemicolectomy, and partial resection of the diaphragm. Gerota's fascia was excised, but the uninvolved left kidney was not resected. Pathology revealed a poorly differentiated liposarcoma invading the colonic mesentery and the spleen, and metastatic to lymph nodes in the splenic hilum. Postoperatively, a tumor dose of 4205 rads in 20 treatments via a 4 MEV linear accelerator was administered to the field of the most recent surgery. One month after completion of irradiation, he was found to have a right lower quadrant mass. Operation on 2/4/77, revealed generalized peritoneal carcinomatosis of anaplastic liposarcoma. Biopsy only was performed. He was readmitted one month later with multiple abdominal masses and died on 3/9/77, seven years after his original © J. B. Lippincott Company
257
258
BINDER, KATZ AND SHERIDAN
operation. Postmortem examination was not performed. At no time in his clinical course had he demonstrated evidence of metastatic disease to the liver or outside the abdomen. Case 2. F.G. #814310. A 55-year-old Caucasian man was discovered on routine examination to have a right lower quadrant abdominal mass. Intravenous pyelogram and chest x-ray were normal. Upper gastrointestinal series and barium enema revealed a mass displacing the right colon and ileum medially. At operation on 8/4/70, he was found to have a lipomatous tumor arising from the retroperitoneum posterior to the right colon and other separate tumor masses extending up the right retroperitoneum and in the right mesocolon. All tumors were individually excised. Pathology revealed eight grossly encapsulated well differentiated myxoid liposarcomas ranging in size from 14 x 8.5 x 5 cm to 5 x 4 x 1.7 cm and with an aggregate weight of 960 g. One year later,, he was found to have a recurrent right lower abdominal mass. Intravenous pyelogram revealed medial displacement of the right ureter; barium enema revealed superior displacement of the cecum and right colon. Operation on 8/15/71, revealed recurrent retroperitoneal tumor with invasion of the mesentery of the
ileum and right colon. The kidney and ureter were not involved. Total resection was performed along with three feet of ileum and the right colon. Pathology revealed well differentiated recurrent liposarcoma in an aggregate mass of 20 x 12 x 5.5 cm. Four years later, he was found to have a recurrent mass in the right flank and a mass in the right spermatic cord. At operation on 3/13/75, he had a tumor mass overlying the promontary of the sacrum with compression but no invasion of the right iliac vessels and displacement but no invasion of the right ureter. The tumor was totally resected from the retroperitoneum and two separate tumor masses were resected from the right spermatic cord. Pathology revealed a 9 x 7 x 5 cm recurrent well differentiated liposarcoma of the retroperitoneum and a 5.5 x 4 x 1.5 cm and a 7 x 5 x 3 cm well differentiated liposarcoma of the spermatic cord. Foci of pleomorphic tumor cells, not seen in the previous specimens, were present histologically. Postoperatively, he received a tumor dose of 4,420 rads in 26 treatments to the lower abdomen via a 4 MEV linear accelerator. The patient has since been clinically free of recurrent disease 2-½ years after his latest resection and seven years after his original
operation. Case 3. C.B. #569089. A 45-year-old Caucasian
woman with a history of lumbar backache developed diffuse abdominal colic and noted an abdominal mass three weeks prior to admission. She had undergone hysterectomy and appendectomy for fibroid uterus 18 years before. On examination, she was found to have a nontender right abdominal mass extending from inferior to the liver to the iliac crest. Gastrointestinal x-ray studies revealed superior displacement of the gallbladder, medial displacement of the descending portion of the duodenum, and inferior displacement of the hepatic flexure of the colon by a radiolucent right retroperitoneal mass. Intravenous pyelogram revealed anteromedial displacement of the inferior pole of the right kidney and medial displacement of the ureter. At operation on 4/2/73, a large retroperitoneal mass adherent to the kidney was found to extend from above the kidney to the pelvic brim, with medial displacement but no invasion of the root of the mesentery and its viscera. The mass was totally excised outside its gross capsule with right nephrectomy and resection of Gerota's fascia. Pathology revealed a 20 x 18 x 6 cm lobulated well differentiated myxoid liposarcoma which, excluding the kidney, weighed 900 g and was adherent to but did not invade the kidney. Postoperatively, she received a tumor dose of 4,140 rads irradiation in 23 treatments to the right retroperitoneum via a 4 MEV linear accelerator. She has since been well and free of evidence of recurrent disease 4-½
one year
years
later.
Ann.
Surg. * March 1978
Case 4. G.M. #327133. A 73-year-old Caucasian woman was admitted to hospital with a one month history of weakness, dyspnea on exertion, melena, and anemia. On examination, she was found to have an ill-defined mass extending from above the umbilicus to the pelvic brim. Chest x-ray, barium enema, and upper gastrointestinal series were normal. Intravenous pyelogram revealed partial obstruction of the lower portion of the right ureter. At operation on 4/5/73, she was found to have a tumor mass filling the entire retroperitoneal space from diaphragm to the pelvic inlet and with invasion of the root of the mesentery. The tumor was considered technically nonresectable and was biopsied only. Pathology revealed well differentiated myxoid liposarcoma. Postoperatively, she received a tumor dose of 3,720 rads in 22 treatments via a 4 MEV linear accelerator. She did poorly thereafter and expired at home seven months after
operation. Case 5. #756776. A 48-year-old Caucasian woman with a four month history of left lower abdominal pain was found to have a left lower quadrant abdominal mass. At operation on 10/11/66, two separate lipomatous tumor masses were resected from the sigmoid and descending mesocolons. Pathology was reported as benign lipomyxofibroma. Postoperatively, she developed severe hypertension. Intravenous pyelogram revealed poor function in a hydronephrotic left kidney. At operation on 3/15/67, she was found to have extensive scarring about the left kidney, which was markedly hydronephrotic and had a thin renal cortex. The left ureter was bound down in dense fibrotic tissue. With an operative diagnosis of renal destruction secondary to operative injury, urinary extravasation, and fibrosis in Gerota's fascia, left nephroureterectomy was performed. No attempt was made to remove the mass of fibrotic tissue which was densely adherent to the retroperitoneum and periaortic tissues. Pathology revealed well differentiated myxoid liposarcoma obstructing the left ureter and causing severe renal destruction. Review of pathology from the original operation revealed well differentiated liposarcoma. Her hypertension remitted. Postoperatively, she received 4,500 rads tumor dose in 30 treatments via a Cofi apparatus. Seven years later, she developed epigastric pain, postprandial bloating, anorexia, and weight loss. Upper gastrointestinal series revealed anteriomedial displacement of the stomach by an extrinsic mass. Intravenous pyelogram and barium enema were unremarkable except for absence of the left kidney. Selective arteriography revealed a vascular tumor mass supplied by lumbar and left adrenal arteries which displaced the spleen and body of the pancreas anteriorly. At operation on 10/17/74, she had tumor filling the left retroperitoneum with direct invasion of the spleen and tail and body of the pancreas. The tumor was totally resected, with sacrifice of the spleen, body and tail of the pancreas, and left adrenal gland. The tumor was densely adherent to the aorta but could be resected by skeletonizing the left anterolateral surface of the aorta and the celiac axis and origin of the superior mesenteric artery. Postoperatively, the patient developed profound metabolic acidosis and signs of hepatic failure and expired 36 hours postoperatively. Postmortem examination revealed hepatic artery and superior mesenteric artery thrombosis with hepatic and mesenteric infarction. No residual or metastatic liposarcoma was discovered. The resected specimen revealed recurrent well differentiated liposarcoma with invasion of the pancreas and the capsules of spleen and adrenal gland.
Discussion
Pathology Liposarcomas occur at any age, but the majority occur in the 40-60 year age group, with an average of
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about 53 years.24,8'9,12"3,17,18,2124 In most series, there is a distinct male predominance but no racial predominance. The neoplasms are malignant from their inception, with only rare cases originating from benign lipomas.2 8'12'24 Their growth rate varies greatly from case to case and even in the same individual. Usually, they grow slowly, sometimes rapidly; and occasionally they remain quiescent for months or even years and then develop an exaccerbation of growth rate.8'22 They may attain enormous size, especially when they originate in the clinically silent retroperitoneum.9'24 As in the case with soft tissue sarcomas generally, liposarcomas tend to have a deceptive gross apparent encapsulation. The "capsule," however, actually consists of tumor cells flattened and attenuated by continuing expansile growth of the cancer; and enucleation of the tumor invariably is followed by local recurrence, frequently multicentric in distribution, as the scattered retained remnants of the pseudocapsule continue to grow. 2,3,8,12,22 Primary liposarcomas tend to grow by local expansion without tendency to invasion of surrounding tissues and may grow along fascial tissue planes to present as apparently separate tumor masses at some distance from the primary tumor. This phenomenon was apparent in cases 1 and 2, in which the tumors extended along the spermatic cord and presented as separate masses distal to the external inguinal ring. It may also account for the multiple tumors found in case 2, though multicentricity or metastasis are equally likely. Recurrent tumors have a decided propensity for invasive and infiltrative growth, as was demonstrated in cases 1, 2, 4, and 5, a phenomenon which accounts in part for the tendency of recurrences to be more aggressively malignant in their clinical behavior than the primary tumor.2'8'9'13'19'21 Recurrences may kill the patient by invasion of vital structures even though the tumor may remain localized. Metastases from liposarcomas may occur anywhere in the body, but are most common in lung, liver, and lymph nodes. Distant metastases may occur despite local control of the primary neoplasm; but they are distinctly more common after local recurrence. Stout's system of histopathologic classification is most commonly used.24 Some investigators have attempted to correlate the histology of liposarcomas with their clinical behavior as follows:2'8'11'12'24 Stout's Type I: Well differentiated myxoid typethese rarely metastasize but recur locally after inadequate excision, and have a more favorable prognosis. Type II: Poorly differentiated myxoid type these are clinically more malignant, recur frequently, and may metasta-
259
size. Their prognosis is less favorable. Type III: Round cell or adenoid type these pursue an aggressive clinical course and frequently metastasize. Their prognosis is poor. Type IV: Mixed group these pursue an aggressive clinical course and frequently metastasize. Their prognosis is poor.
However, in most series, there is a wide variation in the histologic appearance in different areas within the same tumor; and most authorities agree that the biologic behavior is difficult to predict histologically.1'2'4'8'18'22 Recurrent liposarcomas tend to be more cellular and anaplastic than the primary tumor, a phenomenon demonstrated in cases 1 and 2 and which also accounts for the biologically more aggressive behavior of recurrent tumors. Diagnosis
Diagnosis of liposarcomas can be made only by biopsy and pathologic evaluation. If excision ofthe entire tumor is possible, this is the ideal way to treat the neoplasm.4'824 In larger tumors, however, this is not always possible; and wedge biopsy prior to definitive treatment may be more appropriate. In the retroperitoneum, neoplasms are so much more likely to be liposarcomas than benign lipomas that it is best to assume malignancy and proceed with total excision without preliminary biopsy.8'9 Rapid-section histopathology, as is the case with most soft tissue sarcomas, is difficult even for the experienced pathologist. Treatment It is generally agreed that aggressively radical excisional surgery based on anatomic location, size, and local spread is the treatment of choice of liposarcomas wherever they occur. As is universally accepted in the surgical treatment of soft tissue sarcomas in general, the sarcoma must be removed en bloc. The investiture of the neoplasm by healthy tissues and organs, including involved portions of the gastrointestinal tract if necessary and feasible, must remain inviolate; and the line of dissection must be well beyond the palpable or visible limits of the tumor and its pseudocapsule.2'4'8'12'13,17-19,21,2224 Recurrence is invariable after incomplete excision or enucleation of a pseudoencapsulated liposarcoma. In the retroperitoneum, the major dangers in resection are injury to mesenteric vessels, the aorta, the inferior vena cava, and the renal vessels.9'13 The mortality rate of resection of retroperitoneal liposarcomas
Ann. Surg. * March 1978 BINDER, KATZ AND SHERIDAN 260 ranges from 12% to 36%.9,18 The higher rates are usually series reporting the higher rates.8'9' 1'12'19-23'25 The incidence of recurrence depends on the adequacy of exencountered in resections of recurrent disease. Although response to irradiation may be variable and cision, with rates two to four times higher after local unpredictable,2'923 irradiation of retroperitoneal lipo- excision than after radical resection.5'6'19'21 In some sarcomas is of definite value in therapy. The dose given series, adjuvant radiation therapy is associated with for cure of extremity liposarcomas is 5000-6000 rads lower recurrence rates and prolonged free interval in in 41/2 to six weeks;10'23 but such dosage may be im- those patients who do develop recurrence.10'18 All possible to deliver safely to the retroperitoneum. The series report higher rates of recurrence after reresecslow-growing, well differentiated myxoid type of lipo- tion for recurrent disease than after primary radical sarcomas are relatively radiosensitive; while the rap- curative resections. Over half of the patients who develop local recuridly-growing, more anaplastic and highly malignant liposarcomas are relatively radioresistant.8"0"2 Recur- rence also develop concurrent distant metastases;5'6'18 rent liposarcomas are less radiosensitive than primary and local recurrence more than doubles the probability that a patient will die of liposarcoma. Because pallative tumors.4'8'22 therapy yields dismal results, with only rare long-term Radiation therapy has generally been employed in most investigators advocate aggressive sursurvivors, the treatment of incompletely resected liposarcomas, or combined therapy in the radiotherapeutic, gical, recurrences at the primary site, inoperable primary disease. Although results of recurrent management tumors which can be biopsied only, and metastatic with the majority of pa1018.22'25 Even when the cancer is not comhave been poor, generally disease. with dead of disease within two years recurrence tients pletely eradicated locally, irradiation may provide good survivals have been long-term of initial diagnosis,6'15'25 palliation and prolong survival. Since irradiation is such an aggressive often to sufficiently justify reported most effective for microscopic, residual, or small tu1 2 in have achieved and our series Cases approach.18 mors but is generally ineffective in producing permasurvival after of comfortable nent ablation in gross recurrent, inoperable, or non- significant prolongation disease. Alfor recurrent such aggressive therapy resectable tumors, debulking of the tumor is indicated become most recurrences clinically evident though when technically feasible. Preoperative irradiation may make primary inopera- within two to five years of treatment, they may occur ble liposarcomas technically resectable.22 It is essen- much later, as was the situation in our case 5. Longtial, however, to perform the same wide en bloc re- term follow-up is, therefore, essential.3'6'8'9'15'18'25 Five year survival rates in various series of retrosection as would have been done without irradiation; since, in the majority of cases resected after irradiation, peritoneal liposarcomas have been reported from 0%1"3microscopic foci of residual sarcoma are found even 11,15,16 to 1 1%,7,9,11.12,25 with one report of 41%.18 Ten after seemingly favorable response to irradiation.2'8'22 year survival rates have been reported from 0%1.3.15.16.24 Radiosensitivity appears, therefore, greater than radio- to 7%,9.11.12 with one report of 12%.18 All investigators curability of liposarcomas. Because of the high inci- agree that the completeness of resection is the most dence of local recurrence after surgery, some investiga- important factor in effecting cure and that inadequacy tors recommend postoperative irradiation routinely, of the primary operation is the principle reason for even after grossly complete resection. 10"19'22 Our failure. Many investigators suggest that better results longest disease free survivor (case 3) had postoperative could be achieved by the routine use of irradiation irradiation after complete surgical excision. Even after radical excision. Kinne et al., who advocate an aggressive surgical therReferences apy, had their best results in terms of "cure" and disease free interval when irradiation was used postopera1. Atkinson, L., Garran, J. M. and Newton, M. C.: Behavior and tively. Perhaps our overall results would have imManagement of Soft Tissue Sarcomas. Cancer, 16:1552, 1%3. 2. Bowden, L.: Liposarcoma. In Pack, G. T. and Ariel, I. M., proved had we routinely used irradiation after primary (Eds.), Treatment of Cancer and Allied Diseases, 2nd Ed., resection, since in our cases local recurrence rather Volume VIII, The Soft Somatic Tissues and Bone. New York. than distant metastasis proved to be the important facHoeber, 1964. Chapter 8. pp. 120-129. 3. Braasch, J. W. and Mon, A. B.: Primary Retroperitoneal Tutor in ultimate result. Liposarcomas are nonresponsive mors. Surg. Clin. North Am., 47:663, 1967. to any reported conventional systemic chemother4. Brasfield, R. D. and DasGupta, T. K.: Liposarcoma. Cancer, 20:
apy.'8
Prognosis Retroperitoneal liposarcomas have a 20-85% rate of local recurrence after surgical resection, with most
3, 1970. 5. Brennhard, I. O.: The Treatment of Soft Tissue Sarcomas-A Plea for more Urgent and Aggressive Approach. Acta. Chir. Scand., 131:438, 1966. 6. Cantin, J., McNeer, G. P., Chu, F. C. and Booher, R. J.: The Problem of Local Recurrence After Treatment of Soft Tissue Sarcoma. Ann. Surg., 168:47, 1968.
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7. Coran, A. G., Crocker, D. W. and Wilson, R. E.: A Twenty-Five Year Experience With Soft Tissue Sarcomas. Am. J. Surg., 119:288, 1970. 8. DasGupta, T. K.: Tumors and Tumor-like conditions of the Adipose Tissue. Curr. Prob. Surg. March, 1970, Chicago, Yearbook Medical Publishers. 9. DeWeerd, J. H. and Dockerty, M. B.: Lipomatous Retroperitoneal Tumors. Am. J. Surg., 84:397, 1952. 10. Edland, R. W.: Liposarcoma. A Retrospective Study of Fifteen Cases. A Review of the Literature, and a Discussion of Radiosensitivity. Am. J. Roentgenol., Radium Ther. Nucl. Med., 103:778, 1968. 11. Enzinger, F. M. and Winslow, D. J.: Liposarcoma. A Study of 103 cases. Virchows Arch. Pathol Anat., 335:367, 1962. 12. Enterline, H. T., Culberson, J. D., Rochlin, D. B. and Brady, L. W.: Liposarcoma. A Clinical and Pathological Study of 53 cases. Cancer, 13:932, 1960. 13. Farbman, A. A.: Retroperitoneal Fatty Tumors. Report of a Case and Collective Review of the Literature from 1937-1947. Arch. Surg., 60:343, 1950. 14. Ferrell, H. W. and Frable, W. J.: Soft Part Sarcomas Revisited. Cancer, 30:475, 1972. 15. Glen, F. and Watson, R. C.: Retroperitoneal Liposarcoma. N.Y. State J. Med., 72:2789, 1972.
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16. Hare, H. F. and Cerny, M. J.: Soft Tissue Sarcoma. A Review of 200 Cases. Cancer, 16:1332, 1963. 17. Holtz, F.: Liposarcoma. Cancer, I11: 1103, 1958. 18. Kinne, D. W., CHU, F.C.H., Huvos, A. G., et al.: Treatment of Primary and Recurrent Retroperitoneal Liposarcoma. Cancer, 31:53, 1973. 19. Krementz, E. T. and Shaver, J. O.: Behavior and Treatment of Soft Tissue Sarcomas. Ann. Surg., 157:770, 1963. 20. Lieberman, E. and Ackerman, L. V.: Principles in the Management of Soft Tissue Sarcomas. A Clinical and Pathologic Review of 100 cases. Surgery, 35:350, 1954. 21. Martin, R. G., Butler, J. J. and Albores-Saavedra, J.: Soft Tissue Tumors: Surgical Treatment and Results. Tumors of Bone and Soft Tissue, Chicago, Yearbook Medical Publishers, 1965, pp. 333-347. 22. Pack, G. T. and Pierson, J. C.: Liposarcoma. A Study of 105 Cases. Surgery, 36:687-712, 1954. 23. Spittle, M. F., Newton, K. A. and Mackenzie, D. M.: Liposarcoma. A Review of 60 cases. Br. J. Cancer, 24:696, 1971. 24. Stout, A. P.: Liposarcoma-The Malignant Tumor of Lipoblasts. Ann. Surg., 119:86, 1944. 25. Thorbjarnarson, B.: Sarcomata at the New York Hospital. Arch. Surg., 82:489, 1961.
