RETROPERITONEAL
LIPOSARCOMA
IN
A CHILD
WILLIAM
J. PEEPLES,
M.D.
TAPAN HAZRA, M.D. From the Division of Radiotherapy, Baltimore, Maryland
ABSTRACT preuiously
Johns Hopkins
Hospital,
liposarcoma is a rare tumor in children and has been reported - Retroperitoneal on only three occasions. This is the fourth such case, presenting with a large mass on the left
side which displaced the sigmoid and ureters to the right. The patient was treated with surgery, radiotherapy, and chemotherapy. She is alive and well more than four years after therapy was instituted. A review of the pertinent literature cites the need for radio- and chemotherapy especially when surgical removal is incomplete.
Liposarcoma is a malignant tumor of adipose tissue derived from lipoblasts.’ Rarely is the tumor seen in children although it occurs frequently in adults and accounts for approximately 15 per cent of all soft tissue sarcomas2 Retroperitoneal tumors of fatty origin are even more uncommon in children, and liposarcoma has only been reported as arising in the retroperitoneal space on three occasions.3 We report the fourth such case.
except that the abdomen was rounded and protuberant with an ill-defined left flank mass extending from just above the iliac crest inferiorly to 4 cm. below the costal margin superiorly and just across the midline on the right. The liver edge was palpable 2 cm. below the right costal margin, There was no evidence of ascites or abnormal tenderness. Genitalia were normal. On rectal examination, a mass was palpable on the left which was firm and fixed. Lower extremities were normal and without swelling or limitation of motion. Neurologic examination was within normal limits. Hemoglobin was 10.2 Gm., hematocrit 35, and white blood cell count 7,600 with normal differential. Results of urinalysis and vanilmandelic acid spot test were negative. Twenty-four-hour urine specimen for catecholamine was also negative. Excretory urography showed bilateral hydronephrosis with obstruction in the midportion of both ureters from the mass in the left retroperitoneal space. Results of barium enema showed displacement of the colon to the right. Chest roentgenogram and metastatic bone survey were normal. The initial studies indicated that the mass was probably retroperitoneal in origin and was displacing the ureters and colon both to the right and anteriorly (Fig. 1). At laparotomy, an extensive
Case Report A fourteen-month-old black female was first noted to have a mass in the left lower quadrant of the abdomen on routine examination in January, 1971. Since the baby was somewhat constipated the mass was not thought to be significant. At a subsequent visit in late April, 1971, the mass was still present and had grown. The patient was referred to The Johns Hopkins Hospital on May 3, 1971, the only symptom being constipation for the past four to five months, probably due to the tumor. Family and social history were noncontributory. There was no other sign of intestinal obstruction and no urinary dimculty. Physical examination on May 3, 1971, showed vital signs to be normal. The head circumference was 47.4 cm., height 79 cm., and weight 9,580 Gm. Physical examination was essentially normal
UROLOGY
/ JANUARY 1976
/ VOLUME
VII,
NUMBER
1
89
FIGURE 1. (A) Intravenous pyelogram, May, 1971, note bilateral hydronephrosis and displacement to right of both ureters, plus concavity of bladder (residual barium). (B) Barium enema May, 1971, shows marked displacement of sigmoid colon and rectum to right.
retroperitoneal mass could be resected only partially because of involvement of the inferior vena cava, right iliac vessels, and both ureters. During the surgical procedure, the inferior vena cava was entered, and the patient went into shock from blood loss. She was given whole blood. Postoperatively, pulmonary edema developed and the patient was put in a respirator for twenty-four hours. Roentgenogram of the chest showed collapse of the right upper lobe. She was treated with antibiotics and postural drainage. The chest roentgenogram was completely normal ten days after surgery. The excised tumor was found to be irregular, lobulated, and hemorrhagic, with a gelatinous consistency. Approximately 100 Gm. of soft tissue were removed, mostly in fragments about one half of which appeared to be hemorrhagic; the rest was gelatinous tan-white tissue. Sections were diagnosed as liposarcoma with myxomatous change and a sheet of poorly differentiated cells (Fig. 2). Fat stain showed evidence of lipomatous tissue.
90
On May 19, 1971, this patient was given 5 mCi. of coloidal P-32 chromic phosphate into the abdominal cavity with 40 cc. of diluent. There were no complications. The patient was discharged on May 20, 1971, to be given radiotherapy on an outpatient basis. Radiotherapy with cobalt 60 was started on May 24, 1971. The patient received 50 rads to the abdomen for five days. Dosage was increased to 150 rads and finally to 180 rads daily through 10 by IO-cm. portals; 3,750 rads were given to the lower abdomen. On May 28, 1971, the portals were reduced, and an additional 1,000 rads were given to the principal area involved with tumor. The patient had no untoward symptoms during the course of treatment. Leukocyte count was 10,300 at the outset of treatment and varied between 4,000 and 6,300 during therapy. The patient had mild diarrhea which was relieved with antidiarrheal (Kaopectate) and paregoric. On the last day of therapy the white cell count was 5,200; hematocrit was 34.
UROLOGY
/ JANUARY 1976 / VOLUME
VII,
NUMBER
1
Chemotherapy was given on an outpatient basis and consisted of 12 courses of vincristine 0.45 mg., 0.55 mg. given intravenously at weekly intervals from June to September, 1971. Actinomycin D was given for one week, 200 pg. per day for five days at three monthly intervals, June, 1971 to July, 1972. In addition cyclophosphamide (Cytoxan) 25 mg. orally each day was given for approximately fourteen months from September, 1971 to November, 1972. The patient’s hematocrit and leukocyte counts remained stable during this period, and there were no severe complications. Cellulitis developed in one arm due to escape of actinomycin D. Vincristine appeared responsible for clonic inactivity. The patient was seen in the Pediatric Oncology Clinic regularly during the next three years. On her most recent visit, October 10, 1974, she was seen to be well. Findings on chest roentgenogram were negative; hematocrit was 37 and leukocyte count 5,000. The child shows normal growth patterns and has no sign of recurrence of the tumor. Comment FIGURE 2. Photomicrograph of liposarcoma. Upper half shows closely packed cells somewhat better differentiated while lower half is composed of poorly differentiated liposarcoma, positive for fat stain.
Retroperitoneal liposarcoma is a rare tumor in children. Even though lipomas are more common, malignant transformation is an infrequent occurrence. Liposarcomas arise de novo and not from preexisting lipomas. 2 Virchow4 described the first liposarcoma in 1854, and the following year Senftlaben5 reported another case which occurred in the cheek of an eight-year-old child. Retroperitoneal liposarwere reported by comas Harrington, Kretschmer3 and Pinto and co-workers.6 The latter 2 patients were two years of age or less. In the case by Pinto et al. the child was one and one half years old w h en the tumor was discovered, but it was not removed until age seven by which time the tumor had grown to huge proportions. In children, the infancy and adolescent periods are the two age peaks of incidence for liposarcoma.7 The most common location is the intermuscular fascial planes of the thigh, but tumors arise wherever there is adipose tissue.* Other sites are the neck, shoulder, chest wall, back, leg, and foot.g Mediastinal liposarcomas have been described. g*lo Liposarcomas in infants are less likely to metastasize than similar tumors in adults and usually show better differentiation.7 Older children have a higher percentage of poorly differentiated liposarcomas. Retroperitoneal tumors are less likely to be well differentiated and the survival
UROLOGY
/ JANUARY 1976 / VOLUME
VII, NUMBER
rate is closely associated with mitotic activity. More than five mitotic figures seen per highpower field is associated with a mortality rate of 90 per cent. Lowest survival rates occur in the poorly differentiated myxoid mixed and nonmyxoid types as described by Stout’ and Enterline et al. 8 Thirty-one per cent of the cases reported by Enterline et al.’ had metastasis, with the lung being the most common site, followed by the liver, brain, skeleton, lymph nodes, and peritoneum. Generalized metastases are less frequent in the pediatric age group, but local recurrences are common. Surgery plays a major role in the treatment of liposarcoma, and excision should be radical with margin allowance as large as possible.” Radiotherapy has been more recently described in the management of this tumor, however, the literature on this subject is scanty. Del Regato” described a highly radiosensitive embryonal liposarcoma. Edland13 has also reported on radiosensitivity. Spittle14 noted that the local recurrence rate was 20 per cent in an irradiated group as compared with 73 per cent in
1
91
1. STOUT, A. P.: Liposarcoma - the malignant tumor of lipoblasts, Ann. Surg. 119:86 (1944).
2. PACK, G. T., and PEARSON, J. C.: Liposarcoma: a study of 105 cases, Surgery 36: 687 (1954). 3. HARVARD,B. M, : Retroperitoneal lipoma in children. Report of case and review of literature, J. Urol. 70: 159 (1953). 4. VIRCHOW, R.: Einfall von Bosartigen zum Thiel in der Form des Neuroms aufretenden Feltgeschwulstein, Virchows Arch. 11: 281 (1857). 5. SENFTLEBEN, H.: Zur Casinstik Seltenerer Geschwiilste, 1. Myxoma Lipomatodes. 2. Cancroides hoden cystoid mit verscheidenartigen Gewelistypen, ibid. 15: 336 (1858). 6. PINTO, V. C., et al. : Retroperitoneal myxolipoma report of a case in a child 7 years of age, Pediatrics 14: 11 (1954). 7. KAUFFMAN, S. L., and STOUT, A. P.: Lipoblastic tumors in children, Cancer 12: 912 (1959). 8. ENTERLINE, H. T., CULBERSON, J. D., ROCHLIN, D. B., and BRADY, L. W.: Liposarcoma, ibid. 13: 932 (1960). 10. CAPUTO, N. T., and SPALDING, E. D.: Mediastinal liposarcoma, Harper Hosp. Bull. 11: 122 (1968). 11. SUTOW, W. W., VIETTI, T. J., and FERNBACK, D. J. : Clinical Pediatric Urology, St. Louis, C. V. Mosby, 1973, pp. 465-467. 12. DEL REGATO, J. A.: Liposarcoma of thigh, Cancer Semin. 1: 12 (1950). 13. EDLAND, R. W.: Liposarcoma: a retrospective study of 15 cases, a review of the literature and discussion of radiosensitivity, Am. J. Roentgenol. 103: 778 (1965). 14. SPITTLE, M. F., NEWTON, K. A., and MACKENZIE, D. H.: Liposarcoma: a review of 60 cases, Br. J. Cancer, 24: 696 (1970). 15. MOLANDER, D. W. : Palliative treatment of the metastatic tumors of soft somatic tissue with irradiation and chemotherapy, Am. J. Roentgenol. 96: 150 (1966). 16. NEWTON, K. A.: Radiotherapy combined with chemotherapy in selected tumors, Br. J. Radiol. 40: 823 (1967). 17. JAMES, D. H., JOHNSON, W. W., and WRENN, E. . Effective chemotherapy of an abdominal liposarkma, J. Pediatr. 68: 311 (1966). 18. ENZINGER, F. M., and WINSLOW, D. J.: Liposarcoma: study of 103 cases, Virchows Arch. (Pathol. Anat.) 335: 367 (1962).
92
UROLOGY / JANUARY 1976 /
the nonirradiated group. Pack and Pearson2 cited regression when radiation therapy was given. Dactinomycin, vincristine, cyclophosphamide, and nitrogen mustard have been used. Molander15 and Newton16 have advocated combined radio- and chemotherapy and cite good palliative response. James17 reported a case of recurrent intra-abdominal liposarcoma treated with vincristine and cyclophosphamide after failure of radiotherapy to control the tumor. The patient had no evidence of disease eighteen months after treatment. Five-year survival rates in adults are between 36 to 64 per cent;8,12 70 per cent five-year survivals with well-differentiated sarcomas are reported by Enzinger and Winslow, l8 but only 18 per cent with undifferentiated tumors. In our case little morbidity occurred when 4,500 rads were administered to the abdomen. There were no untoward symptoms arising from abdominal administration of colloidal radioactive and for the most part intensive phosphorus, chemotherapy was well tolerated. This patient has now survived more than four with radiation years combined and chemotherapy. Radiation plus chemotherapy is advocated especially when surgical removal is incomplete. Baptist Hospital 1000 W. Moreno Street
Pensacola, Florida 32501 (DR. PEEPLES) References
VOLUME VII, NUMBER 1
LIPOSARCOMA
IN
A CHILD
WILLIAM
J. PEEPLES,
M.D.
TAPAN HAZRA, M.D. From the Division of Radiotherapy, Baltimore, Maryland
ABSTRACT preuiously
Johns Hopkins
Hospital,
liposarcoma is a rare tumor in children and has been reported - Retroperitoneal on only three occasions. This is the fourth such case, presenting with a large mass on the left
side which displaced the sigmoid and ureters to the right. The patient was treated with surgery, radiotherapy, and chemotherapy. She is alive and well more than four years after therapy was instituted. A review of the pertinent literature cites the need for radio- and chemotherapy especially when surgical removal is incomplete.
Liposarcoma is a malignant tumor of adipose tissue derived from lipoblasts.’ Rarely is the tumor seen in children although it occurs frequently in adults and accounts for approximately 15 per cent of all soft tissue sarcomas2 Retroperitoneal tumors of fatty origin are even more uncommon in children, and liposarcoma has only been reported as arising in the retroperitoneal space on three occasions.3 We report the fourth such case.
except that the abdomen was rounded and protuberant with an ill-defined left flank mass extending from just above the iliac crest inferiorly to 4 cm. below the costal margin superiorly and just across the midline on the right. The liver edge was palpable 2 cm. below the right costal margin, There was no evidence of ascites or abnormal tenderness. Genitalia were normal. On rectal examination, a mass was palpable on the left which was firm and fixed. Lower extremities were normal and without swelling or limitation of motion. Neurologic examination was within normal limits. Hemoglobin was 10.2 Gm., hematocrit 35, and white blood cell count 7,600 with normal differential. Results of urinalysis and vanilmandelic acid spot test were negative. Twenty-four-hour urine specimen for catecholamine was also negative. Excretory urography showed bilateral hydronephrosis with obstruction in the midportion of both ureters from the mass in the left retroperitoneal space. Results of barium enema showed displacement of the colon to the right. Chest roentgenogram and metastatic bone survey were normal. The initial studies indicated that the mass was probably retroperitoneal in origin and was displacing the ureters and colon both to the right and anteriorly (Fig. 1). At laparotomy, an extensive
Case Report A fourteen-month-old black female was first noted to have a mass in the left lower quadrant of the abdomen on routine examination in January, 1971. Since the baby was somewhat constipated the mass was not thought to be significant. At a subsequent visit in late April, 1971, the mass was still present and had grown. The patient was referred to The Johns Hopkins Hospital on May 3, 1971, the only symptom being constipation for the past four to five months, probably due to the tumor. Family and social history were noncontributory. There was no other sign of intestinal obstruction and no urinary dimculty. Physical examination on May 3, 1971, showed vital signs to be normal. The head circumference was 47.4 cm., height 79 cm., and weight 9,580 Gm. Physical examination was essentially normal
UROLOGY
/ JANUARY 1976
/ VOLUME
VII,
NUMBER
1
89
FIGURE 1. (A) Intravenous pyelogram, May, 1971, note bilateral hydronephrosis and displacement to right of both ureters, plus concavity of bladder (residual barium). (B) Barium enema May, 1971, shows marked displacement of sigmoid colon and rectum to right.
retroperitoneal mass could be resected only partially because of involvement of the inferior vena cava, right iliac vessels, and both ureters. During the surgical procedure, the inferior vena cava was entered, and the patient went into shock from blood loss. She was given whole blood. Postoperatively, pulmonary edema developed and the patient was put in a respirator for twenty-four hours. Roentgenogram of the chest showed collapse of the right upper lobe. She was treated with antibiotics and postural drainage. The chest roentgenogram was completely normal ten days after surgery. The excised tumor was found to be irregular, lobulated, and hemorrhagic, with a gelatinous consistency. Approximately 100 Gm. of soft tissue were removed, mostly in fragments about one half of which appeared to be hemorrhagic; the rest was gelatinous tan-white tissue. Sections were diagnosed as liposarcoma with myxomatous change and a sheet of poorly differentiated cells (Fig. 2). Fat stain showed evidence of lipomatous tissue.
90
On May 19, 1971, this patient was given 5 mCi. of coloidal P-32 chromic phosphate into the abdominal cavity with 40 cc. of diluent. There were no complications. The patient was discharged on May 20, 1971, to be given radiotherapy on an outpatient basis. Radiotherapy with cobalt 60 was started on May 24, 1971. The patient received 50 rads to the abdomen for five days. Dosage was increased to 150 rads and finally to 180 rads daily through 10 by IO-cm. portals; 3,750 rads were given to the lower abdomen. On May 28, 1971, the portals were reduced, and an additional 1,000 rads were given to the principal area involved with tumor. The patient had no untoward symptoms during the course of treatment. Leukocyte count was 10,300 at the outset of treatment and varied between 4,000 and 6,300 during therapy. The patient had mild diarrhea which was relieved with antidiarrheal (Kaopectate) and paregoric. On the last day of therapy the white cell count was 5,200; hematocrit was 34.
UROLOGY
/ JANUARY 1976 / VOLUME
VII,
NUMBER
1
Chemotherapy was given on an outpatient basis and consisted of 12 courses of vincristine 0.45 mg., 0.55 mg. given intravenously at weekly intervals from June to September, 1971. Actinomycin D was given for one week, 200 pg. per day for five days at three monthly intervals, June, 1971 to July, 1972. In addition cyclophosphamide (Cytoxan) 25 mg. orally each day was given for approximately fourteen months from September, 1971 to November, 1972. The patient’s hematocrit and leukocyte counts remained stable during this period, and there were no severe complications. Cellulitis developed in one arm due to escape of actinomycin D. Vincristine appeared responsible for clonic inactivity. The patient was seen in the Pediatric Oncology Clinic regularly during the next three years. On her most recent visit, October 10, 1974, she was seen to be well. Findings on chest roentgenogram were negative; hematocrit was 37 and leukocyte count 5,000. The child shows normal growth patterns and has no sign of recurrence of the tumor. Comment FIGURE 2. Photomicrograph of liposarcoma. Upper half shows closely packed cells somewhat better differentiated while lower half is composed of poorly differentiated liposarcoma, positive for fat stain.
Retroperitoneal liposarcoma is a rare tumor in children. Even though lipomas are more common, malignant transformation is an infrequent occurrence. Liposarcomas arise de novo and not from preexisting lipomas. 2 Virchow4 described the first liposarcoma in 1854, and the following year Senftlaben5 reported another case which occurred in the cheek of an eight-year-old child. Retroperitoneal liposarwere reported by comas Harrington, Kretschmer3 and Pinto and co-workers.6 The latter 2 patients were two years of age or less. In the case by Pinto et al. the child was one and one half years old w h en the tumor was discovered, but it was not removed until age seven by which time the tumor had grown to huge proportions. In children, the infancy and adolescent periods are the two age peaks of incidence for liposarcoma.7 The most common location is the intermuscular fascial planes of the thigh, but tumors arise wherever there is adipose tissue.* Other sites are the neck, shoulder, chest wall, back, leg, and foot.g Mediastinal liposarcomas have been described. g*lo Liposarcomas in infants are less likely to metastasize than similar tumors in adults and usually show better differentiation.7 Older children have a higher percentage of poorly differentiated liposarcomas. Retroperitoneal tumors are less likely to be well differentiated and the survival
UROLOGY
/ JANUARY 1976 / VOLUME
VII, NUMBER
rate is closely associated with mitotic activity. More than five mitotic figures seen per highpower field is associated with a mortality rate of 90 per cent. Lowest survival rates occur in the poorly differentiated myxoid mixed and nonmyxoid types as described by Stout’ and Enterline et al. 8 Thirty-one per cent of the cases reported by Enterline et al.’ had metastasis, with the lung being the most common site, followed by the liver, brain, skeleton, lymph nodes, and peritoneum. Generalized metastases are less frequent in the pediatric age group, but local recurrences are common. Surgery plays a major role in the treatment of liposarcoma, and excision should be radical with margin allowance as large as possible.” Radiotherapy has been more recently described in the management of this tumor, however, the literature on this subject is scanty. Del Regato” described a highly radiosensitive embryonal liposarcoma. Edland13 has also reported on radiosensitivity. Spittle14 noted that the local recurrence rate was 20 per cent in an irradiated group as compared with 73 per cent in
1
91
1. STOUT, A. P.: Liposarcoma - the malignant tumor of lipoblasts, Ann. Surg. 119:86 (1944).
2. PACK, G. T., and PEARSON, J. C.: Liposarcoma: a study of 105 cases, Surgery 36: 687 (1954). 3. HARVARD,B. M, : Retroperitoneal lipoma in children. Report of case and review of literature, J. Urol. 70: 159 (1953). 4. VIRCHOW, R.: Einfall von Bosartigen zum Thiel in der Form des Neuroms aufretenden Feltgeschwulstein, Virchows Arch. 11: 281 (1857). 5. SENFTLEBEN, H.: Zur Casinstik Seltenerer Geschwiilste, 1. Myxoma Lipomatodes. 2. Cancroides hoden cystoid mit verscheidenartigen Gewelistypen, ibid. 15: 336 (1858). 6. PINTO, V. C., et al. : Retroperitoneal myxolipoma report of a case in a child 7 years of age, Pediatrics 14: 11 (1954). 7. KAUFFMAN, S. L., and STOUT, A. P.: Lipoblastic tumors in children, Cancer 12: 912 (1959). 8. ENTERLINE, H. T., CULBERSON, J. D., ROCHLIN, D. B., and BRADY, L. W.: Liposarcoma, ibid. 13: 932 (1960). 10. CAPUTO, N. T., and SPALDING, E. D.: Mediastinal liposarcoma, Harper Hosp. Bull. 11: 122 (1968). 11. SUTOW, W. W., VIETTI, T. J., and FERNBACK, D. J. : Clinical Pediatric Urology, St. Louis, C. V. Mosby, 1973, pp. 465-467. 12. DEL REGATO, J. A.: Liposarcoma of thigh, Cancer Semin. 1: 12 (1950). 13. EDLAND, R. W.: Liposarcoma: a retrospective study of 15 cases, a review of the literature and discussion of radiosensitivity, Am. J. Roentgenol. 103: 778 (1965). 14. SPITTLE, M. F., NEWTON, K. A., and MACKENZIE, D. H.: Liposarcoma: a review of 60 cases, Br. J. Cancer, 24: 696 (1970). 15. MOLANDER, D. W. : Palliative treatment of the metastatic tumors of soft somatic tissue with irradiation and chemotherapy, Am. J. Roentgenol. 96: 150 (1966). 16. NEWTON, K. A.: Radiotherapy combined with chemotherapy in selected tumors, Br. J. Radiol. 40: 823 (1967). 17. JAMES, D. H., JOHNSON, W. W., and WRENN, E. . Effective chemotherapy of an abdominal liposarkma, J. Pediatr. 68: 311 (1966). 18. ENZINGER, F. M., and WINSLOW, D. J.: Liposarcoma: study of 103 cases, Virchows Arch. (Pathol. Anat.) 335: 367 (1962).
92
UROLOGY / JANUARY 1976 /
the nonirradiated group. Pack and Pearson2 cited regression when radiation therapy was given. Dactinomycin, vincristine, cyclophosphamide, and nitrogen mustard have been used. Molander15 and Newton16 have advocated combined radio- and chemotherapy and cite good palliative response. James17 reported a case of recurrent intra-abdominal liposarcoma treated with vincristine and cyclophosphamide after failure of radiotherapy to control the tumor. The patient had no evidence of disease eighteen months after treatment. Five-year survival rates in adults are between 36 to 64 per cent;8,12 70 per cent five-year survivals with well-differentiated sarcomas are reported by Enzinger and Winslow, l8 but only 18 per cent with undifferentiated tumors. In our case little morbidity occurred when 4,500 rads were administered to the abdomen. There were no untoward symptoms arising from abdominal administration of colloidal radioactive and for the most part intensive phosphorus, chemotherapy was well tolerated. This patient has now survived more than four with radiation years combined and chemotherapy. Radiation plus chemotherapy is advocated especially when surgical removal is incomplete. Baptist Hospital 1000 W. Moreno Street
Pensacola, Florida 32501 (DR. PEEPLES) References
VOLUME VII, NUMBER 1
