European Journal of Obstetrics & Gynecology and Reproductive Biology 100 (2001) 96±99
Case report
A huge abdominal mass mimicking ovarian cancer: p53-negative but aneuploid myxoid leiomyosarcoma of the uterus Semih Kalelia,*, Zerrin Calayb, Nuri Ceydelia, KyÂlyÂcË AydyÂnlyÂa, Derin KoÈsebaya Department of Obstetrics and Gynecology, Cerrahpaa Medical School, YÂstanbul University, P.O. Box 11, Cerrahpapa, Fatih, YÂstanbul, Turkey b Department of Obstetrics and Pathology, Cerrahpaa Medical School, YÂstanbul University, Cerrahpapa, Fatih, YÂstanbul, Turkey
a
Received 15 September 2000; accepted 1 June 2001
Abstract Objective: Less than 20 myxoid leiomyosarcoma cases were reported in literature. Since, these tumors are very rare and may exhibit highly malignant behavior despite their low mitotic index, clinical course and optimum type of therapy of myxoid variant of leiomyosarcoma were not well understood. The goal of this report is to contribute the better understanding of this rare type of tumor. Methods: A 39-year-old woman presented with a huge abdominal cystic mass. Laparotomy was performed and frozen section diagnosis was low-grade uterine leiomyosarcoma. TAH-BSO, omentectomy, pelvic lymph node and peritoneal samplings were carried out. No chemotherapy was performed after surgical therapy. Results: Final histopathological diagnosis was uterine myxoid leiomyosarcoma. The tumor was p53-negative and had aneuploid DNA content. The patient tolerated well the operation and she is alive and free of disease after 24 months of primary surgical treatment. Conclusion: Uterine myxoid leiomyosarcoma may present a huge abdominal cystic mass and can be treated successfully with surgery alone. # 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Uterus; Sarcoma; Myxoid; Abdominal mass; p53; DNA content; Flow cytometry
1. Introduction
2. Case report
Leiomyosarcoma of the uterus is a rare malignant neoplasm and account for approximately 45% of non-epithelial uterine cancers. It primarily involves the myometrium and forms a ¯eshy, poorly circumscribed mass, often with necrosis and hemorrhage. Myxoid leiomyosarcoma is rare variant of leiomyosarcoma which is accepted a subgroup of uterine smooth muscle tumors according to the ``classi®cation of mesenchymal and related tumors of the uterus'' done by the World Health Organization. These tumors have a striking myxoid appearance and exhibit highly malignant behavior despite their low mitotic index [1]. This type of tumor has only been recognized recently which was different from myxoid degeneration in benign leiomyomas. Only 19 cases have been reported in international literature over 17 years since it has been recognized ®rst [2±13]. We present an additional case in this article.
A 39-year-old woman, gravida three, abortus two, had an abdominal pain and progressive abdominal distention for 3 months. She underwent appendectomy 19 years ago and cholecystectomy 9 years ago. On physical examination, she was otherwise healthy except a huge abdominal distention. Abdomen was excessively tender and it was hard to palpate a mass. Vagina was normal but the cervix displaced downward to the introitus. Chest X-ray and routine blood chemistry were found to be normal. Ultrasonographical examination of the abdomen has revealed an enormous cystic mass that laid between deep in pelvis and diaphragma. The mass had multiple septations and hyperechoic areas mimicking stage III ovarian cancer. Abdominopelvic-computerized tomography, starting from renal hilus to the pelvis, has revealed the presence of a multiloculated and irregular-shaped cystic mass. An exploratory laparotomy was performed; entering the abdomen a 40 cm 45 cm, huge multicystic mass ®lling almost entire abdominal cavity was observed, both ovary were normal. After removing 2 l of ascites, total hysterectomy and bilateral salpingooophorectomy with ascite cytology were performed. On macroscopic examination, a
*
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[email protected] (S. Kaleli).
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S. Kaleli et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 100 (2001) 96±99
multicystic mass with well-circumscribed borders which was full of translucent, green-colored gelatinous material was observed. On frozen section examination, multicut surfaces obtained from the mass have demonstrated myxomatous stroma and abundant spindle-shaped smooth muscle cells with low-mitotic activity (zero to two mitoses per 10 HPF). Intraoperative frozen section diagnosis was lowgrade uterine leimyosarcoma and the operation was completed performing infracolic omentectomy, pelvic lymph node sampling and multiple biopsies from abdominopelvic peritoneum and serosal surfaces. Peritoneal and serosal surfaces were normal in appearance and there was no residual mass left behind. Findings on ®nal histopathological examination was similar to those of frozen section. Spindle-shaped cells with mitotic counts ranging between zero to two per 10 HPF in abundant myxoid stroma was observed and the de®nitive diagnosis was myxoid leiomyosarcoma of the uterus (Fig. 1). 2.1. The p53 analysis Expression of p53 was evaluated according to previously published methods [14]. p53, D07 primary antibody was used at a dilution of 1:80 and 21N was used at a dilution of 1:150. After incubation with the primary antibodies at 188C for 30 min, incubation with a polyclonal biotinylated rabbit anti-mouse antibody (Dako Ltd., High Wycombe, UK) was performed for p53 staining. Incubation with an avidin±biotin complex conjugated to horseradish peroxidase followed by 3.3 diaminobenzidine as a chromogen was then performed for p53 immunostaining. Breast tumor of known p53
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Fig. 1. Myxoid leiomyosarcoma (H:E: 200). The smooth muscle cells are widely separated by myxoid material and there is low nuclear atypia.
expression was used as positive control. The p53 protein expression was indicated by nuclear staining of tumor cells. Lack of p53 protein expression was indicated by the absence of tumor cell nuclear staining with D07. A subjective assessment of p53 immunostaining was made. According to this method, tumor with less than 5% of tumor cell nuclei showing p53 staining was scored as p53-negative. Present case showed 2% positive staining. Because of the remaining below 5%, it is considered as negative. 2.2. DNA content analysis The principle DNA ¯ow cytometry has been used to the method of Hedley et al. [15]. Fifty micrometers sections
Fig. 2. Aneuploid (hypodiploid type) histogram obtained in flow cytometric DNA content analysis of tumor.
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S. Kaleli et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 100 (2001) 96±99
were cut from the embedded blocks. After con®rming the presence of tumor tissue under the light microscope, the cell suspension was prepared and stained with propidium iodide. DNA analysis was done using a Coulter pro®le ¯ow cytometry (Coulter Electronics, Hialeah, FL) equipped with a 5 W argon laser, wavelength of 488 nm. DNA histogram was evaluated by using Multicycle Software Program (Phoenix Flow Systems Inc., San Diego, CA). Aneuploidy was accepted as a discernible second peak in the histogram. Present case was found to have aneuploid DNA content of hypodiploid type (Fig. 2). Patient well tolerated the operation and received no adjuvant therapy. She was alive and tumor-free after 34 months of operation. 3. Discussion Myxoid leiomyosarcoma, although a rare variant of leiomyosarcoma, must be kept in mind in differential diagnosis of smooth muscle tumor with myxoid stroma. However, diagnosis of this histology is not easy at all. Because of its rarity, there is limited knowledge about this type of tumor. They are generally diagnosed as tumors with low mitotic activity, although the recurrence rate is high and prognosis is poor. More important, the tumor can be misdiagnosed as leiomyoma with myxoid degeneration. Myxoid degeneration is not rare in benign myomas that occurs in as many as 13% of cases, the diagnosis of myxoid leiomyosarcoma must be made tentatively [9]. Because of the absence of universally accepted pathologic criteria for diagnosis of this variant histology, we need criteria to be well de®ned. Criteria other than mitotic activity that should be paid attention to are likely the cellular atypia, involvement of vascular spaces, and in®ltration status of tumor margins microscopically; gross appearance, diameter and circumscription of tumor border macroscopically. Conventional pathologic diagnosis of sarcoma depends on mostly the number of mitoses per 10 HPF [1]. But, more than half of the reported cases including present case had less than ®ve mitoses per 10 HPF, although up to 30 mitoses has been reported [10]. Zero mitosis was demonstrated to be able to associate with abdominal recurrence provided with the other criteria should be met. In addition, despite the cellular atypia is absent, tumor may exhibit a malignant biologic behavior [4]. It has been suggested that the presence of myxoid ground substance could pause the mitotic activity even if the biologic behavior does not change. So, frozen section diagnosis may not be helpful to the surgeon, even it may cause faulty surgical approaches that can require re-laparotomy after ®nal histopathological diagnosis. In present case, frozen section diagnosis has failed to recognize myxoid variant of uterine leiomyosarcoma. The presence of myxomatous stroma at frozen section, even in the presence of low mitotic count, should warn the surgeon about the possibility of myxoid leiomyosarcoma with aggressive behavior.
Intraoperative macroscopic appearance of tumor may have some characteristics. The tumors were relatively large in reported cases including present case, despite the average diameter varies from 2 [8] up to 40 cm (present case). Patients at younger ages seem to have greater diameter of tumor [9]. At the time of surgery, the tumors were generally observed to be well circumscribed despite in®ltrative pattern could be observed microscopically [10]. In present case, smooth surface like a benign tumor facilitated the removal of the tumor. Gelatinous appearance of the ¯uid within the cystic dilatations was the most characteristic gross ®nding of the tumor as similar to other cases reported in the literature. Patient is alive and disease-free after 34 months of surgical therapy. According to our knowledge, appropriate therapy is surgical removal of tumor and adjuvant therapy is not preferred. Adjuvant therapy in myxoid variant of leiomyosarcoma is highly controversial. Kunzel et al. treated a patient with ifosfamide and mesna after complete surgical removal of tumor, however, adjuvant chemotherapy was ineffective and there was aggressive tumor growth while the patient was on this regimen [10]. The role of the myxoid stroma is, as yet, uncertain. However, one can speculate that the copious amount of acid mucopolysaccharide content in myxoid stroma may alter the effect of chemotherapy by preventing drug±cell interaction. In addition, in the management of uterine leiomyosarcoma, from analysis of small series using either historical controls or prospective, nonrandomized radiotherapy regimens, there is evidence that adjuvant whole-pelvic radiotherapy improves the rate of local control, but has little impact on overall survival [16], although some authors have been able to demonstrate a survival advantage [17]. The best results relating adjuvant chemotherapy are those of Peters et al. [18]. They reported 67% survival rate at a median follow-up of 34 months in 15 patients with no macroscopic residual disease following surgery who were treated with six cycles of adjuvant doxorubicin and cisplatin plus whole-pelvic external beam radiotherapy. References [1] Clement PB, Scully RE. Pathology of uterine sarcomas. In: Coppleson M, editor. Gynecologic oncology. 2nd ed. London: Churchill Livingstone, 1992. p. 803±25. [2] King ME, Dickerson GR, Scully RE. Myxoid leiomyosarcoma of the uterus. A report of six cases. Am J Surg Pathol 1982;6:589± 98. [3] Shroff CP, Deodhar KP, Bhagwat AG. Myxoid leiomyosarcoma of the uterus Ð a case report with light microscopic and ultrastructural appraisal. Tumori 1984;70:561±6. [4] Chen KT. Myxoid leiomyosarcoma of the uterus. Int J Gynecol Pathol 1984;3:389±92. [5] Pounder DJ, Iyer PV. Uterine leiomyosarcoma with myxoid stroma. Arch Pathol Lab Med 1985;109:762±4. [6] Delmonte V, Marino F. Myxoid leiomyosarcoma of the uterus. Rev Hosp Clin Fac Med Sao Paulo 1985;40:200±2. [7] Salm R, Evans DJ. Myxoid leiomyosarcoma. Histopathology 1985;9:159±69.
S. Kaleli et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 100 (2001) 96±99 [8] Aida Y, Tadokoro M. Myxoid variant of epitheloid leiomyosarcoma of the uterus. Acta Pathol Jpn 1991;41:778±83. [9] Peacock G, Archer S. Myxoid leiomyosarcoma of the uterus: case report and review of the literature. Am J Obstet Gynecol 1989; 160:1515±9. [10] Kunzel KE, Mills NZ, Muderspach LI, d'Ablaing G. Myxoid leiomyosarcoma of the uterus. Gynecol Oncol 1993;48:277±80. [11] Schneider D, Halperin R, Segal M, Maymon R, Bukovsky I. Myxoid leiomyosarcoma of the uterus with unusual malignant histologic pattern Ð case report. Gynecol Oncol 1995;59:156±8. [12] Sprogoe-Jacobsen S, Holund B. Immunohistochemistry (Ki-67 and p53) as a tool in determining malignancy in smooth muscle neoplasms (exemplified by a myxoid leiomyosarcoma of the uterus). APMIS 1996;104:705±8. [13] Chang E, Shim SI. Myxoid leiomyosarcoma of the uterus: a case report and review of the literature. J Kor Med Sci 1998;13:559±62.
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