Journal of Surgical Oncology 26:260-267 (1984)

Six Recent Liposarcomas Including Largest to Date

HlROSHl TAKAGI, MD, KlMlYUKl KATO, MD, ElKlCHl YAMADA, MD,AND

TAlZAN SUCHI, MD

From the Department of Surgery and Clinical Pathology, Aichi Cancer Center Hospital, Nagoya, lapan

This report describes six cases of liposarcoma. The primary sites were the retroperitoneum in three cases, the lower extremity in two cases and the jejunal mesenterium in one case. One retroperitoneum case had the heav- iest liposarcoma (40 kg) that has been reported in the literature. One patient with thigh liposarcoma who developed three recurrences and underwent hemipelvectomy has been free from the disease for the past 6 1 /2 years. Histologically, all three retroperitoneum cases showed well- differentiated liposarcoma and two lower extremity cases had myxoid type liposarcoma.

KEY WORDS: liposarcoma, hemipelvectomy, retroperitoneal tumor, mesenterial tumor

INTRODUCTION Liposarcoma, the malignant tumor of adipose tissue, is

an uncommon lesion. It is indeed rare in comparison with the ubiquitous benign fatty tumors, which are sometimes not easy to differentiate from liposarcoma.

The practicing physician still faces many clinical prob- lems in the various treatment modalities of liposarcoma because of its protean and unpredictable course [I]. The present study reports our experience with six cases of liposarcoma.

SUBJECTS AND METHODS In the 19 years from December 1964 to November

1983, six patients with liposarcoma were encountered at the Aichi Cancer Center Hospital (ACCH). They were three men and three women ages 29-65 years. The pri- mary sites were the retroperitoneum in three cases, the lower extremity in two cases and the jejunal mesenterium in one case (Table I).

CASE REPORTS Case 1

A 29-year-old woman was seen at ACCH in December 1964 because of distension of the abdomen. Five years prior to this visit the patient noticed persistent distension of the abdomen after delivery of her first baby. She was

admitted at another institution where a right retroperito- neal tumor (3 kg, 35 x 25 x 5 cm) was excised by one of the authors (E.Y.). The pathologic diagnosis was li- posarcoma, and mitomycin was given postoperatively. Two years later, however, a liposarcoma recurring in the same area (2.8 kg, 21 X 14 x 14 cm) was excised at the same institution and adjuvant chemotherapy with sarco- mycin and merphylin was administered. Ten months later the patient again showed distension of the abdomen, and a partial excision of the tumor was carried out due to infiltration to the adjacent organs. In October of 1962, 8 months later, the patient noticed redistension of the ab- domen, which was observed without treatment.

In the examination at ACCH this poorly nourished patient with an enlarged abdominal tumor with multiple nodules tolerated a regular diet well without any demon- strable metastasis. In December of 1966 the patient no- ticed a swelling over the bilateral lower extremities and was admitted to ACCH (Fig. 1) where a course of com- bination chemotherapy METT (mitomycin, cytoxan, tes- pamin and toyomycin) was administered without any

Accepted for publication December 13, 1983. Address reprint requests to Hiroshi Takagi, MD, Senior Staff Sur- geon, Department of Surgery, Aichi Cancer Center Hospital, Chi- kusa-ku, Nagoya 464, Japan.

0 1984 Alan R. Liss, Inc.

Liposarcoma of Six Cases 261

Fig. 1. Case 1 photo taken in February of 1967 (two months before death). Remarkable distension of the abdomen with nodularly lobu-

lated tumor in right lower area and congestive swelling of bilateral lower extremities.

TABLE I. Clinical Data on Six Liposarcoma Patients?

Case Age at No. of

1 25 F Rt. Retroperitoneum 2 - Surgery DWD at 7 years

2 39 F Rt. Retroperitoneum - - Surgery ANED at 15 years 3 62 M Rt. Leg I Liver Surgery DNED at 6 years

4 52 M Rt. Thigh 3 - Surgery ANED at 13 years

ANED at 9 years 5 38 F Lt. Retroperitoneum 6 54 M Mesenterium - - Surgery ANED at 3 years

+DWD, dead with disease; ANED, alive with no evidence of disease; DNED, dead with no evidence of disease; C.T., chemotherapy; R.T., radiotherapy.

No. Onset Sex Site Recurrences Metastasis Treatment Follow-up

C.T.

R.T.

R.T. - - Surgery

262 Takagi et a1

Fig. 2. staining, x 2M)). Well-differentiated liposarcoma.

Histological picture of autopsied specimen in case 1 (H.E.

remarkable effect. Another chemotherapic agent COPP (cobaltiprotoporphyrin) was tried but it was discontinued due to side effects.

The patient started to develop swelling of the upper extremities associated with dyspnea and palpitation and expired in April of 1967. The autopsy examination dis- closed a huge multilobulated abdominal mass weighing 40 kg (body weight 91 kg) without invading the adjacent organs. No distant metastases were demonstrated. The histopathology of the tumor is largely composed of highly differentiated adipose tissue that almost appears to be adult fat tissue, admixed with areas composed of slightly larger hyperchromatic nuclei, and faintly eosinophilic matrix lymphocytic infiltration is rather conspicuous throughout (Fig. 2).

This liposarcoma is larger than that reported by Wells (32 kg) [2]. To the authors’ knowledge, it is the largest reported to date. This case clearly illustrates Gideon Wells’s concept [2] that the fat in a lipoma is not available to the body economy, and while the normal body fat wastes away the lipogenic tumor actually increases in size.

The patient’s offspring reached the age of eight by the time of the mother’s death, and was apparently healthy.

Case 2 A 39-year-old woman was admitted to ACCH in Oc-

tober of 1968, because of increasing right hypochondria- cal distention for the previous 8 months. The examination revealed right retroperitoneal tumor, hypovascular and relatively radiolucent, that displaced the right kidney, the duodenum, the hepatic flexure of colon, and so on. A yellowish elastic, encapsulated tumor weighing 2.9 kg (35 X 24 x 9 cm) was excised. The histologic diagnosis was well-differentiated liposarcoma. Postoperatively, the displaced intraabdominal organs returned to the normal position. The patient is now well without any evidence of recurrence.

Case 3 Two and half years before referral, a 65-year-old man

underwent excision of a 5-cm tumor on the right leg at a local hospital. The histologic diagnosis was benign li- poma. Three months also before referral a recurrent

Liposarcoma of Six Cases 263

Fig. 3. The excised specimen of hepatic metastasis of case 3.

tumor weighing 150 gm, (12 x 5 X 5 cam) at the same site was again excised at the same hospital. Since the histologic diagnosis this time was liposarcoma, the pa- tient was referred to ACCH in August of 1970. Radiation therapy was started over the excised area.

An epigastric mass found on admission was diagnosed as a yellowish and hypovascular tumor in the left lobe of the liver by several examinations including angiography and peritoneoscopy. The tumor (13 X 12 X 10 cm) was duly excised (Fig. 3). The histologic examination showed myxoid type liposarcoma, the same picture with the tu- mor excised from the leg.

The patient had been well without any evidence of disease for 1 year before undergoing an emergency lap- arotomy at another local hospital because of intestinal obstruction. The patient died postoperatively, but an au- topsy was not permitted.

Case 4

A 54-year-old man was admitted to ACCH because of recurrent liposarcoma in the upper medial part of the right thigh in December of 1973. During World War 11,

the patient had a piece of bomb shrapnel removed from the same site. Then, in September of 1971, a 3-cm di- ameter tumor was excised at the same site in a local hospital. Because of a histological diagnosis of liposar- coma, the patient underwent re-excision of a wider area. However, he noticed a recurrent tumor at the same exci- sion site in October of 1973, which was excised. The histological diagnosis was again liposarcoma, so the man was referred to ACCH.

The patient was submitted to a radical excision of the upper-medial area of the thigh including the groin dissec- tion, using a skin graft for cover (Fig. 4). A meticulous examination of the excised specimen, however, failed to reveal any residual liposarcoma. In January of 1975 the patient noticed a nodule on the margin of the skin graft area, which was excised. The diagnosis was recurrent liposarcoma. Radiation therapy (5,000 rad by the beta- tron) was administered.

In April of 1977 the patient complained of an ill- defined tumor in the same site. An attempted excision was unsuccessful, because of extensive infiltration in the form of fatty nodules among the thigh muscles. After

264 Takagi et al

Fig. 4. Excised specimen with groin dissection of case 4. The center of the skin bore a scar from excision of the recurrent tumor. No residual liposarcoma was found in this specimen.

denying any distant metastasis, right hemipelvectomy [3,4] was carried out in June 1977. The patient has remained well without any evidence of disease (Fig. 5).

Three recurrent episodes occurred at intervals of 23 months, 15 months, and 27 months, respectively (aver- age: 22 months). Histologic pictures of each excised specimen were the same, ie, myxoid type liposarcoma without remarkable changes. The tumor showed fusiform and stellate, hyperchronatic nuclei in myxoid stroma ac- companied by networks of capillaries. Mitoses are rather infrequent (Fig. 6).

Case 5 A 38-year-old woman was admitted to ACCH in Janu-

ary of 1974 because of a large abdominal tumor in left upper quadrant associated with constipation. The exami- nations revealed a left retroperitoneal hypovascular and radiolucent tumor. A large multinodular elastic and li- pomatous tumor was excised en bloc with left ureter and kidney, and the splenic flexure of colon because the ureter was buried within the tumor. The excised tumor weighed 2,100 gm (Fig. 7). The histologic diagnosis of

the excised tumor was well-differentiated liposarcoma. The patient has fully recovered with no evidence of disease.

Case 6 A 54-year-old man was admitted to ACCH in October

of 1980 because of an abdominal tumor. The physical examination revealed a 10-cm diameter tumor in the left upper quadrant of the abdomen that was easily movable in all directions. Further studies showed that the hypo- vascular tumor was located in the mesenterium of the jejunum. The encapsulated lipomatous tumor (560 gm, 16.0 X 9.5 X 9 cm) was excised. The histologic diag- nosis of the specimen was well-differentiated liposar- coma of low-grade malignancy.

The patient has fully recovered with no evidence of any disease.

DISCUSSION Most simple lipomas are located in subcutaneous fat,

whereas liposarcomas develop deeply from within the interior intramuscular fatty tissue [5].

Lipsarcoma of Six Cases 265

Fig. 5 . Roentgenogram of the pelvis of case 6 after right hemipelvectomy .

Until Weiss and Enzinger [6] proposed a reliable but more all-embracing criterion for malignant fibrous histio- cytoma (MFH), liposarcoma was considered to be the most common malignant mesenchymal soft-tissue tumor occurring in adults. Recently, Evans [7] and Hashimoto and Enjoji [8] reassessed the classification of liposar- coma. There was a variation in the site of predilection of the cases: The great majority of myxoid type tumors occurred in the thigh, popliteal fossa, and buttock, while the majority of well-differentiated type tumors were seen in the retroperitoneum. The cases described in this report also support their findings.

Retroperitoneal liposarcoma [9] has presented a thera- peutic dilemma because of its tendency to attain enor- mous size due to early silent growth and the relative inaccessibility of tumors in the retroperitoneal space to wide en bloc excision. Liposarcomas in this region char- acteristically have had a less favorable prognosis than extremity lesions. For the management of retroperitoneal liposarcoma, complete excision of the tumor en bloc with adjacent involved organs should be performed whenever

feasible. In this sense, the procedure for case 5 in this report was only reasonable. For inoperable cases, those with residual disease or suspected residual disease fol- lowing surgery, intensive radiation therapy should be given in an attempt to cure or at least to prolong the disease-free interval. Case 1 in this report should have received radiation therapy postoperatively.

The literature suggests that, although there is a great deal of fat in the mesentery, both lipomas and Iiposar- coma are very rare. Some cases, however, give evidence that an incompletely removed liposarcoma can be termi- nal, but there is no proof that any mesenteric liposarcoma has metastasized by embolism [ 101.

Liposarcomas most commonly involved the lower ex- tremities, particularly the thigh, buttock, and popliteal fossa, composing 56% of all liposarcomas [8].

The role of trauma in the etiologic mechanism of lipo- sarcoma is admittedly controversial. This is especially true of tumors appearing in the extremities, since fre- quently the patient’s attention is drawn to these neo- plasma after an injury [5]. It is difficult to accept the

266 Takagi et al

Fig. 6. Histological picture of excised specimen of case 4 (H.E. staining, X200). Myxoid type liposarcoma with rich capillary network.

doctrine of traumatic etiology for sarcoma of soft somatic tissues, yet there may occasionally occur a case, as re- lated in case 4.

Seemingly, lipomas of adult form undergo malignant transformation into liposarcoma only with the greatest rarity [ll]. But this malignancy is reportedly not of “the greatest rarity” in the case of lipomatosis [l]. It is, however, much more important that occasionally, as il- lustrated in case 3 above, the differential diagnosis be- tween a lipoma and a liposarcoma may be mistaken by the pathologist, with fatal results.

The high recurrence rate is due to several factors such as pseudoencapsulation, the deep location adjacent to major blood vessels and nerves, the presence of lobula- tion, and the frequently large size of the neoplasm. Ac- tually, the pseudocapsule is connective tissue that is

compressed secondarily by the tumor’s expansile growth [5]. It is reported that the average time of appearance of recurrent lesions after local excision of the primary tu- mor was 15 months, the longest period being 5 years [5].

The variability of the histologic pattern in recurrent liposarcoma is another point of interest [ 121, although the recurrent lesions in this report failed to show any histo- logical changes.

It has been said that liposarcoma is radiosensitive [ 131, although the present case 4 does not fulfill this condition. But high radiation doses combined with hyperthermia should be tried [14].

Chemotherapy was not considered effective for the liposarcoma seen in above case 1. However, regional hyperthemic perfusion of anticancer drugs is reportedly effective in liposarcoma [ 15,161.

Liposarcoma of Six Cases 267

Fig. 7. The cut-surface of the excised specimen of case 5.

REFERENCES 1. Sawyer KC, Sawyer RB, Lubchenco AE, Bramley HF, Fenton

WC: The unpredictable fatty tumor. Arch Surg 96:773-785, 1968.

2. Wells HG: Adipose tissue, a neglected subject. JAMA 114:2177- 2183, 1940.

3. Phelan JT, Nadler SH: A technique of hemipelvectomy. Surg Gynecol Obstet 119:311-318, 1964.

4. Higinbotham NL, Marcove RC, Casson P: Hemipelvectomy: A clinical study of 100 cases with five year followup on 60 patients. Surgery 59:706-708, 1966.

5. Kimbrough RF, Soule EH: Liposarcoma of the extremities. Clin

6. Weiss SW, Enzinger FM: Malignant fibrous histiocytoma. An analysis of 200 cases. Cancer 41:2250-2266, 1978.

7. Evans HL: Liposarcoma. A study of 55 cases with a reassessment of its classification. Am J Surg Pathol3:507-523, 1979.

8. Hashimoto H, Enjoji M: Liposarcoma. A clinicopathoIogic sub- typing of 52 cases. Acta Pathol Jpn 32:933-948, 1982.

9. Kinne DW, Chu FCH, Havos AG, Yogoda A, Fortner JG: Treat- ment of primary and recurrent retroperitoneal liposarcoma.

Orthop 19:40-54, 1971.

Twenty-five-year experience at Memorial Hospital. Cancer

10. Yannopoulos K, Stout AP: Primary solid tumors of the mesen- tery. Cancer 16:914-927, 1963.

11. Stout AP: Liposarcoma-The malignant tumor of lipoblasts. Ann Surg 119:86-107, 1944.

12. Snover DC, Sumner HW, Dehner LP: Variability of histologic pattern in recurrent soft tissue sarcomas originally diagnosed as liposarcoma. Cancer 49: 1005-1015, 1982.

13. McNeer GP, Cantin J, Chu F, Nickson JJ: Effectiveness of radiation therapy in the management of sarcoma of the soft somatic tissues. Cancer 22:391-397, 1968.

14. Overgaard J: Influence of sequence and interval on the biological response to combined hyperthermia and radiation. Nat Cancer Inst Monogr 61:325-332, 1982.

15. Krementz ET, Carter RD, Sutherland CM: Chemotherapy of sarcomas of the limbs by regional perfusion. Ann Surg 185555- 564, 1977.

16. Eilber FR, Mirra JJ, Grant TT, Weisenburger T, Morton DL: Is amputation necessary for sarcomas? A seven-year experience with limb salvage. Ann Surg 192:431-438, 1980.

31:53-64, 1973.