Acta chir belg, 2007, 107, 468-471
Giant Liposarcoma of the Stomach Involving the Mediastinum A. Michiels, G. Hubens, M. Ruppert, L. Balliu, W. Vaneerdeweg Department of Abdominal Surgery, University Hospital Antwerp.
Key words. Liposarcoma ; stomach. Abstract. A case of a liposarcoma of the stomach in a 27-year old woman is described. Initially the patient consulted with epigastric pain. MRI showed a giant tumour of the stomach wall, invading the surrounding organs, as well as the mediastinal region. After surgical ‘en-bloc’ resection of the tumour, histopathologic examination yielded a diagnosis of pleiomorphic liposarcoma. Because of the bad prognosis of this histologic type, the patient received adjuvant chemotherapy : a combination of doxorubicin and ifosfamide (MAI). Nine months after surgery, she represented with a relapse of the tumour that had become inoperable. Palliative chemotherapy was started with the intent to prolong the young patient’s life. However 6 months later, the patient died of the recurrent disease. Although liposarcoma is a very common soft tissue sarcoma, it is rarely seen in the stomach. The standard therapy is surgical excision. Over the last years, adjuvant therapy became more accepted. Drugs of choice are doxorubicin and ifosfamide, although the benefits of this therapy are still largely unknown and doubtful.
Introduction Liposarcoma is one of the most common soft tissue sarcomas in adults and accounts for approximately 20% of all mesenchymal malignancies. It tends to occur in the limbs and the retroperitoneum (1). However it is rarely seen in the gastrointestinal tract, especially the stomach. Reviewing the literature, we could find only 11 cases (Table 1) (2-5). We report the case of a 27-year old woman with a pleiomorphic epigastric liposarcoma not only involving the abdomen, but also expanding to the mediastinum. We also discuss the use of adjuvant chemotherapy in this report. Case report A 27-year old Caucasian woman presented at the emergency room in January 2005 with epigastric pain. Clinical investigation revealed tenderness in the right and left hypochondrium with a positive Murphy test. Blood samples showed an anemia, an elevated CRP and disturbed livertests. Abdominal CT scan revealed a nodular lesion, partly necrotic, partly firm tissue. This mass originated from the ventral wall of the stomach. MRI confirmed this, showing a massive tumour (5 kg) originating from the anterior stomach wall, invading the diaphragm and pericardium with bilateral pleural fluid, pericardial effusion and hemorrhagic ascites (Fig. 1). Precardial lymph nodi were present, but no arguments for liver metastasis was seen. A sarcomatous tumour,
possibly leiomyosarcoma or gastrointestinal stromal tumour (GIST), was suspected. Her clinical status necessitated a pericardiocentesis before surgery could be performed. The tumour was resected through a left thoracophrenolaparotomy. Because of local invasion to surrounding organs, ‘en bloc’ excision was needed with a subtotal gastrectomy, segment II of the liver, a large part of the left diaphragm, the pancreas tail and the spleen. The diaphragm was reconstructed with a polypropylene mesh. Histopathologic examination demonstrated a high grade pleiomorphic liposarcoma (highly necrotic) T2bN0M0, grade 3, stage III. Postoperative course was uneventful. Because of the patients’ poor prognosis, four cycles adjuvant chemotherapy with the combination doxorubicin/ifosfamide (MAI) in a 3-weekly scheme were started. In the following months, the patient was admitted several times due to the side effects of the chemotherapy : gastrointestinal problems, neutropene fever, thrombocytopenia and the chemotherapy had to be stopped prematurely. Nine months after surgery she represented with dyspnea and retrosternal pain. CT thorax confirmed recurrence of the disease as an inhomogenous mass pre- and paracardial right and a supradiafragmatic mass on the left side. An attempt for resection or debulking through a clamshell-approach failed. The tumour had invaded the right ventricle, expanding from the atrioventricular groove to the pulmonary artery. Because of her young age and the reserved prognosis, it was decided to administer palliative chemotherapy by
Gastric Liposarcoma
469 Table 1 Review of literature
Authors (year)
Age (years)
Sex
Symptoms
Treatment
Site
Size (cm)
ABRAMS and TURBERVILLE (1) (1941)
52
M
Epigastrialgia, nausea, vomiting, epigastric mass
Laparotomic biopsy
Greater curvature and metastasis (liver and omentum)
Large NK Infiltrative mass occupied entire length of the stomach
HOHF et al. (2) (1955)
77
M
Epigastric mass
Subtotal gastrectomy, adjuvant radiotherapy
Anterior wall of antrum, between mucosa and subserosa
Pleiomorphic 15 8 6 (encapsula-ted) liposarcoma
HAWKINS and TERRELL (3) (1965)
86
M
Bloody diarrhea, hematemesis
75% subtotal gastrectomy
Posterior wall 10 10 of fundus, submucosa
ORITA et al. (4) (1968)
42
M
Epigastrialgia, Total abdominal fullness, gastrectomy diarrhea
Posterior wall of body, submucosa
SHOKOUH-AMIRI et al. (5) (1986)
15
M
Gastrialgia, anorex- Subtotal ia, nausea gastrectomy
Greater curva- 20 30 ture, exophytic (5 kg) growth (sharply demarcated)
LAKY and STOICA (6) (1986)
67
F
Dyspepsia, gastrialgia, hematemesis
Dorsal wall of 5 2 1,5 NK antrum, (relatively well submucosa demarcated)
NER 12 months PO
FERROZZI et al. (7) (1993)
58
M
Abdominal mass, Resection fullness, discomfort
Anterior wall of the antrum, exophytic growth
YAMAMOTO et al. (3) (1995)
58
M
NK
LOPEZ- NEGRETE et al. (4) (1997)
74
F
SEKI et al. (2) (1998)
68
PHILLIPPS et al. (5) (2000) Present case
Subtotal gastrectomy
Histologic subtype
Myxoid liposarcoma
1,2 1,0 1,0 NK (spherical in shape) Myxoid liposarcoma
Outcome
DOD 4 months after diagnosis
NER 8 months PO
NER 2 years PO
NER 60 months PO NER 8 months PO
25 20 8 (well demarcated)
Pleiomorphic liposarcoma
NK
Greater Endoscopic curvature resection, subtotal gastrectomy
1,3 0,5 (by endoscopic US)
Pleiomorphic and myxoid liposarcoma
NER 1 year PO
Solid food intolerance
Total gastrectomy
Curvatura minor, submucosal, exophytic growth
ca. 15
Well differenti- DOD 2 months ated and PO myxoid liposarcoma
F
Gastrialgia, hematemesis
Total gastrectomy
Posterior wall of body, submucosa
10,5 5,5 4 (well demarcated)
Well differenti- NER 13 months ated, PO sclerosing liposarcoma
74
F
Fullness, gastrialgia, dyspepsia, weight loss
Subtotal gastrectomy
Stomach wall of antrum, submucosal
3,4 1,3 0,5 Well differenti- NER 15 days PO ated and (well myxoid demarcated) liposarcoma
27
F
Gastrialgia
Subtotal gastrectomy, liver, diaphragm, pancreas, spleen, pericardium ; Adjuvant chemotherapy
Curvatura minor, exophytic growth
20 30 (5 kg)
NK : not known, NER : no evidence of reccurence, PO : postoperative, DOD : death of disease.
Pleiomorphic liposarcoma
DOD 16 months PO
470
A. Michiels et al.
Fig. 1 Liposarcoma of the stomach
decarbazine. After 2 cycles, side-effects necessitated ending of chemotherapy in March 2006. Patient died of her disease in April 2006. Discussion Only 11 cases (7 men and 4 women with a mean age of 58 years) of liposarcoma of the stomach have been reported in literature so far (2-5). Clinical data of these 11 cases, and our case (nr. 12), are summarized in Table 1. Our patient (27 years) was the youngest except for one patient of only 15 years old. Some clinical symptoms assumed an intra-abdominal space-occupying mass while others were only vague abdominal complaints. Four tumours arose in the gastric antrum, two in the body, one in the fundus and three tumours arose from the greater curvature while two from the minor curvature. Five tumours showed exophytic growth from the gastric wall and seven tumours were localised in the submucosa. Most of the masses were well circumscribed. In no case, development of metastases was mentioned. All cases were treated with surgical resection. The outcome of gastric liposarcoma is still questionable. Of the 11 described, 2 patients died of the disease, while the outcome of the other 9 patients is not known. Our patient died quickly despite extensive surgery and aggressive chemotherapy, her young age and no evi-
dence of metastatic disease. However large primary tumour and extensive recurrence could explain early death. The biggest tumours (20 30 cm) were seen in the two youngest patients of this series which suggests a possible relation in aggressiveness and young age. Clinically, the lack of specific gastrointestinal symptoms makes it difficult to acheave an early diagnosis. The principal prognostic factor of the primary tumour is the histologic type, combined with the extent and location of the tumour. Only 5% are located intraabdominal (1). Clinically, the typical abundant exophytic growth explains the lack of specific gastrointestinal symptoms and the delayed diagnosis (2). Pleiomorphic liposarcoma is an uncommon form of liposarcoma that has only recently been properly characterized. Other types of liposarcoma as differentiated, myxoid, round cell and dedifferentiated type were already known. The pleiomorphic type accounts for approximately 5% of liposarcomas and is said to be a highly malignant lesion. This bad outcome of pleiomorphic type is only seen in our patient, but is not that clear in 3 other cases (Table 1), again taking into account the unknown outcome of patients. Standard treatment of liposarcoma still consists of wide surgical excision whenever possible (1) ; as seen in all 12 cases. If total resection is not feasible, surgical debulking can be beneficial in case of compressive symptoms. In our case, the spread to the right ventricle made debulking impossible. Given the high local recurrence rate of 70%-90% for high grade soft-tissue sarcomas (STS) that undergo local treatment by surgery alone, the need for adjuvant therapy arose (6). Research showed 3 drugs being active in adult soft tissue sarcoma : ifosfamide, doxo/epirubicin and decarbazine. The toxicities of these products are substantial and make treatment difficult : leukopenia, neutropenic fever, CNS toxicity, nausea & vomiting, hemorrhagic cystitis (now prevented by addition of mesna). The literature is scarse about the use of chemotherapy specifically for liposarcoma. Here, current use of adjuvant therapy for soft-tissue sarcoma in general is discussed. Currently ifosfamide and doxorubicin are administered for four cycles after surgery in those patients with large, high-grade sarcomas with good performance status (ECOG 0-1) and who did not receive neoadjuvant therapy. For older patients, or those with a worse postoperative performance status, single-agent doxorubicine therapy is opted, with the caveat that the benefits are still largely unknown (7). Other sarcoma centres would agree that patients with small (< 5 cm) and/or low-grade STS, with retroperitoneal tumours or patients older than 70 years should not receive adjuvant chemotherapy outside a trial setting (6).
Gastric Liposarcoma For patients presenting with large (> 5 cm), intermediate- or high-grade lesions, neoadjuvant therapy mostly with MAID regimen (doxorubicin, ifosfamide, decarbazine) in conjunction with radiotherapy is recommended (7). In our patient, diagnosis was just made after surgery so that neoadjuvant was not relevant. The administration of decarbazine as palliative therapy was an accepted second line product, after little results of adjuvant chemo with first line products as doxorubicin and ifosfamide. 10 of the 11 cases mentioned in literature were treated only surgically, of which 2 patients died of disease several time after surgery. Adjuvant radiotherapy was administered in just one patient in whom was no evidence of recurrence 8 months post-operative. Our patient was the only one who received adjuvant as well as palliative chemotherapy, with excessive sideeffects but without any major results ; she died 16 months after diagnosis was made and large surgical excision was performed. Although adjuvant chemotherapy is being suggested in extensive soft tissue sarcomas (STS), except for violent side-effects, no results at all – except from large side-effects – were seen in our patient. Perhaps chemotherapy failed in this case because of the extensiveness of the tumour. Conclusion Primary gastric pleomorphic liposarcomas are extremely rare tumours that are generally large and invade and compress adjacent structures. Reviewing the literature, preferred location of the neoplasm seems to be in the gastric antrum. The undifferentiated character of a pleiomorphic liposarcoma makes those tumours aggressive resulting in a bad prognosis. Despite their rarity in the stomach, liposarcomas should be included in the differential diagnosis of gastric tumours. The strongest predictors of survival of pleomorphic liposarcoma are the surgical resectability combined with the pathological
471 grade of the tumour. The extent, the intracardial spreading and the histologic type of the liposarcoma result in a bad prognosis for our reported case. Despite extensive postoperative chemotherapy, our patient had a very short survival. In contrary to classical retroperitoneal liposarcoma, where after surgical resection or debulking prolonged survival is possible, in general, survival of gastric liposarcoma in literature is very doubtfull and poor outcome is known.
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A. Michiels Department of Abdominal Surgery University Hospital Antwerp Wilrijkstraat 10 B-2650 Edegem, Belgium Tel. : 03 821 3148 Fax : 03 825 13 08 E-mail :
[email protected]
