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Low-Grade Endometrial Stromal Sarcoma with Cardiovascular Involvement—A Report of Three Cases
Gynecologic Oncology 75, 495– 498 (1999) Article ID gyno.1999.5598, available online at http://www.idealibrary.com on
CASE REPORT Low-Grade Endometrial Stromal Sarcoma with Cardiovascular Involvement—A Report of Three Cases Tsutomu Tabata, M.D., Nobuhiro Takeshima, M.D., Yasuo Hirai, M.D., and Katsuhiko Hasumi, M.D. Department of Gynecology, Cancer Institute Hospital, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan Received May 20, 1999
CASE REPORTS
Background. In low-grade endometrial stromal sarcoma, it has been reported that vascular space involvement in surgical specimens is found in over 50% of patients. However, in contrast to intravenous leiomyomatosis, it has been thought that further tumor extension to large vessels is rarely observed. Cases. We present three cases of low-grade endometrial stromal sarcoma with cardiovascular involvement by recurrent tumors observed on imaging studies. Two cases demonstrated tumor infiltration inside the inferior vena cava while the other case showed tumor growth in the left ventricle. Conclusion. This report suggests that attention should be paid to the possibility of cardiovascular invasion during the entire course of this disease. © 1999 Academic Press Key Words: endometrial stromal sarcoma; low-grade; recurrence.
Case 1
INTRODUCTION
The patient was a 30-year-old woman. She had undergone a myomectomy under clinical diagnosis of myoma of the uterus by her local gynecologist in October 1990. Pathological diagnosis of the uterine tumor was leiomyoma at that time. Five years later, in 1995, a hysterectomy was performed at the same hospital due to reenlargement of the uterus. The tumor that protruded into the uterine cavity was approximately 5 cm in diameter. Pathological examination of the hysterectomy specimens revealed the presence of low-grade ESS. The diagnosis of low-grade ESS was made according to criteria proposed by Norris and Taylor [2]. Subsequently, she was treated with four cycles of adjuvant chemotherapy consisting of cisplatin and Adriamycin. In November 1996, computed tomography (CT) scan showed a large recurrent mass in the pelvis. At our hospital, the patient underwent a total pelvic exenteration because of the severe tumor invasion to the bladder and rectum. Pathological diagnosis of the recurrent tumor was low-grade ESS. Reevaluation of pathologic slides of surgical specimens at the initial myomectomy also confirmed the presence of low-grade ESS. After surgery, she received three cycles of chemotherapy, consisting of cisplatin, Adriamycin, and ifosfamide. Five months later, in April 1997, on CT scan examination, the presence of a tumor thrombus within the inferior vena cava was suggested. Angiography confirmed a large flow defect from the right external iliac veins extending to the inferior vena cava (Fig. 1). At surgery for the recurrent tumor, the tumor did not adhere to the intima of the inferior vena cava, allowing it to be extracted. Pathological diagnosis of the tumor inside the inferior vena cava was low-grade ESS. Although another recurrent tumor was noted on the surrounding of the external iliac artery, she remains alive with evidence of disease as of April 1999.
Endometrial stromal sarcoma (ESS) comprises approximately 10% of uterine sarcomas, and these account for 0.2% of all uterine malignancies, consisting of two-thirds with low-grade ESS and the remaining one-third with high-grade ESS [1]. The histological classification of tumor grade was based on mitotic activity: less than 10 mitotic figures per 10 high power fields (HPF) for low-grade ESS and more than 10 mitotic figures per 10 HPF for high-grade ESS [2]. In low-grade ESS, it has been reported that vascular space involvement in surgical specimens is found in over 50% of patients [3]. However, in contrast to intravenous leiomyomatosis, it has been thought that further tumor extension to large vessels is rarely observed [4]. We have recently encountered three cases with low-grade ESS in whom tumor invasion was noted in the major vascular channels. Two cases of inferior vena cava involvement and one case of cardiac involvement are reported. 495
0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
496
TABATA ET AL.
FIG. 1. Case 1: Angiography demonstrated a large flow defect from the right external iliac veins extending to the inferior vena cava.
Case 2
Case 3
The patient was a 43-year-old female who had undergone a hysterectomy under clinical diagnosis of myoma of the uterus at a previous hospital in 1976. The tumor in the uterus was approximately 4 cm in diameter. The pathological diagnosis of the uterine tumor was leiomyoma at that time. Five years later, in 1981, she was found to have a polyp on the vaginal vault. Pathological examination revealed that the polyp was low-grade ESS. After admission to our hospital, the hysterectomy specimens from the initial surgery were reviewed, and a diagnosis of low-grade ESS was made. CT scan showed a large pelvic mass involving the bladder and rectum, and chest X ray revealed multiple pulmonary metastases. She was treated with whole pelvic radiotherapy combined with chemotherapy consisting of dacarbazine, Adriamycin, and cyclophosphamide. Although a partial response was obtained several times and she remained alive with disease for more than 13 years, the recurrent tumors finally increased. One month before death, cardiac ultrasonography revealed a large mass in the left ventricle (Fig. 2). She died of heart failure in 1995. At autopsy, the pathological diagnosis of the mass in the left ventricle was low-grade ESS.
The patient was a 49-year-old woman who had undergone a hysterectomy under a diagnosis of myoma of the uterus at a previous hospital in March 1997. The tumor in the uterus was approximately 7 cm in diameter. Pathological diagnosis of the uterine tumor was low-grade ESS. Two months later, she was admitted to our hospital for adjuvant therapy. Magnetic resonance imaging performed in our hospital revealed that she already had a long irregular plug within the vessel from the right ovarian vein up to the inferior vena cava (Fig. 3). A recurrent tumor in the pelvis that involved the bladder was also noted. She was treated with four cycles chemotherapy consisting of cisplatin, Adriamycin, and ifosfamide, and partial tumor regression was achieved. Subsequently, resection of the recurrent tumor and retroperitoneal lymphadenectomy were performed. Since the tumor protruding into the inferior vena cava disappeared after chemotherapy, only resection of the right ovarian vein was performed to remove the residual tumor in the vascular channels. Pathological examination of the surgical specimen confirmed the presence of low-grade ESS, and several lymph node metastases were also recognized. After surgery, she received three more cycles of chemotherapy with the same regimen and has remained clinically free of disease for more than 16 months after the second surgery.
CASE REPORT
497
FIG. 2. Case 2: On short-axis view of cardiac ultrasonograpy, a large tumor filling the left ventricle was noted.
DISCUSSION Most patients with low-grade ESS have clinical symptoms similar to those in patients with leiomyoma of the uterus. The difficulty in early diagnosis of this disease has been reported. Accurate diagnosis of low-grade ESS is made preoperatively in only 10% of patients with this disease and is sometimes made when a recurrent tumor is found [3]. Indeed, all three cases in this series received hysterectomy under a preoperative diagnosis of leiomyoma at their initial treatment. Moreover, in two of the three cases presented, the wrong pathological diagnosis had been made. Although more than 80% of patients with low-grade ESS are in clinical stage I at the time of diagnosis [3, 5], a high incidence of recurrence has been reported. Piver et al. found that 56% of the patients with surgical stage I disease developed recurrence [5]. Despite the high relapse rate, the 5- or 10-year survival rates of stage I disease have been reported to be more than 80% [3, 5, 6]. This trend, i.e., long-term survival with evidence of disease, is also recognized in the current series. Because low-grade ESS is a slow-growing tumor, recurrences or metastases are often detected many years later after initial treatment. The mean time to recurrence has been reported to be 34 months for surgical stage I, but recurrences may occur as late as 20 years or more after surgery [5].
In view of tumor invasion to the major cardiovascular channels in our series, clinical behaviors of low-grade ESS are similar to those of intravenous leiomyomatosis, a very rare smooth muscle tumor. Intravenous leiomyomatosis is characterized by worm-like extensions into the uterine veins in the broad ligament or into other pelvic veins [7]. Tumor growth involving the inferior vena cava is noted in more than 10% of patients with intravenous leiomyomatosis, and even cardiac involvement is occasionally seen [4]. Our three cases may resemble intravenous leiomyomatosis in the tumor spread pattern. Whitlatch and Meyer reported a case of recurrent lowgrade ESS tumor in which tumor invasion to the inferior vena cava was observed [8]. That patient was treated with radiotherapy and chemotherapy, but died of cardiovascular failure caused by intravascular tumor growth. Importantly, they reported that the metastatic site histologically resembled intravenous leiomyomatosis. In our series, however, such a trend was not observed. The histological diagnosis of low-grade ESS was confirmed both in primary tumors and in metastatic sites in all cases. In addition, tumor infiltrations to adjacent organs were observed in our series, while such an invasion is seldom seen in intravenous leiomyomatosis. Several cases of possible low-grade ESS with cardiovascular involvement have been reported in the literature [8 –10]. In
498
TABATA ET AL.
FIG. 3. Case 3: Magnetic resonance imaging demonstrated a long irregular plug consisting of sarcoma cells from the right ovarian vein extending to the inferior vena cava.
most cases, resection of the tumors in the cardiovascular channels was performed successfully. Although the long-term survival of these cases is unclear, it is likely that surgical treatment of this condition prevents fatal cardiac complications and has a significant impact at least on short-term survival. We report three cases of low-grade ESS in whom cardiovascular invasion was noted in their clinical courses. This study indicates that the possibility of intravascular tumor invasion should always be considered in the management of this disease. Intensive search for tumor involvement of the vascular system using imaging techniques at the time of diagnosis and follow-up would be useful for detecting metastatic or recurrent tumors. REFERENCES 1. Koss LG, Spiro RH, Brunschwig A: Endometrial stromal sarcoma. Surg Gynecol Obstet 121:531–537, 1965 2. Norris HJ, Taylor HB: Mesenchymal tumors of the uterus. A clinical and pathological study of 53 endometrial stromal tumors. Cancer 19:755–766, 1966
3. Chang KL, Crabtree GS, Lim-Tan SK, Kempson RL, Hendrickson MR: Primary uterine endometrial stromal neoplasms: a clinicopathologic study of 177 cases. Am J Surg Pathol 14: 415– 438, 1990 4. Clement PB: Intravenous leiomyomatosis of the uterus. Pathol Annu 23 (Pt 2): 153–183, 1988 5. Piver MS, Rutledge FN, Copeland L, Webster K, Blumenson L, Suh O: Uterine endolymphatic stromal myosis: a collaborative study. Obstet Gynecol 64:173–178, 1984 6. Gadducci A, Sartori E, Landoni F, Zola P, Maggino T, Urgesi A, Lissoni A, Losa G, Fanucchi A : Endometrial stromal sarcoma: analysis of treatment failures and survival. Gynecol Oncol 63: 247–253,1996 7. Norris HJ, Parmley T: Mesenchymal tumors of the uterus. V. Intravenous leiomyomatosis: a clinical and pathologic study of 14 cases. Cancer 36:2164 –2178, 1975 8. Whitlatch SP, Meyer RL: Recurrent endometrial sarcoma resembling intravenous leiomyomatosis. Gynecol Oncol 28:121–128, 1987 9. Debing E, Van Der Niepen P, Goossens A, Van den Brande P: Intracaval extension of a recurrent low-grade endometrial stromal sarcoma. Acta Chir Belg 98:264 –266, 1998 10. Vargas-Barron J, Keirns C, Barragan-Garcia R, Beltan-Ortega A, Rotberg T, Santana-Gonzalez A, Salazar-Davila E: Intracardiac extension of malignant uterine tumors. J Thorac Cardiovasc Surg 99:1099 –1103, 1990
CASE REPORT Low-Grade Endometrial Stromal Sarcoma with Cardiovascular Involvement—A Report of Three Cases Tsutomu Tabata, M.D., Nobuhiro Takeshima, M.D., Yasuo Hirai, M.D., and Katsuhiko Hasumi, M.D. Department of Gynecology, Cancer Institute Hospital, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan Received May 20, 1999
CASE REPORTS
Background. In low-grade endometrial stromal sarcoma, it has been reported that vascular space involvement in surgical specimens is found in over 50% of patients. However, in contrast to intravenous leiomyomatosis, it has been thought that further tumor extension to large vessels is rarely observed. Cases. We present three cases of low-grade endometrial stromal sarcoma with cardiovascular involvement by recurrent tumors observed on imaging studies. Two cases demonstrated tumor infiltration inside the inferior vena cava while the other case showed tumor growth in the left ventricle. Conclusion. This report suggests that attention should be paid to the possibility of cardiovascular invasion during the entire course of this disease. © 1999 Academic Press Key Words: endometrial stromal sarcoma; low-grade; recurrence.
Case 1
INTRODUCTION
The patient was a 30-year-old woman. She had undergone a myomectomy under clinical diagnosis of myoma of the uterus by her local gynecologist in October 1990. Pathological diagnosis of the uterine tumor was leiomyoma at that time. Five years later, in 1995, a hysterectomy was performed at the same hospital due to reenlargement of the uterus. The tumor that protruded into the uterine cavity was approximately 5 cm in diameter. Pathological examination of the hysterectomy specimens revealed the presence of low-grade ESS. The diagnosis of low-grade ESS was made according to criteria proposed by Norris and Taylor [2]. Subsequently, she was treated with four cycles of adjuvant chemotherapy consisting of cisplatin and Adriamycin. In November 1996, computed tomography (CT) scan showed a large recurrent mass in the pelvis. At our hospital, the patient underwent a total pelvic exenteration because of the severe tumor invasion to the bladder and rectum. Pathological diagnosis of the recurrent tumor was low-grade ESS. Reevaluation of pathologic slides of surgical specimens at the initial myomectomy also confirmed the presence of low-grade ESS. After surgery, she received three cycles of chemotherapy, consisting of cisplatin, Adriamycin, and ifosfamide. Five months later, in April 1997, on CT scan examination, the presence of a tumor thrombus within the inferior vena cava was suggested. Angiography confirmed a large flow defect from the right external iliac veins extending to the inferior vena cava (Fig. 1). At surgery for the recurrent tumor, the tumor did not adhere to the intima of the inferior vena cava, allowing it to be extracted. Pathological diagnosis of the tumor inside the inferior vena cava was low-grade ESS. Although another recurrent tumor was noted on the surrounding of the external iliac artery, she remains alive with evidence of disease as of April 1999.
Endometrial stromal sarcoma (ESS) comprises approximately 10% of uterine sarcomas, and these account for 0.2% of all uterine malignancies, consisting of two-thirds with low-grade ESS and the remaining one-third with high-grade ESS [1]. The histological classification of tumor grade was based on mitotic activity: less than 10 mitotic figures per 10 high power fields (HPF) for low-grade ESS and more than 10 mitotic figures per 10 HPF for high-grade ESS [2]. In low-grade ESS, it has been reported that vascular space involvement in surgical specimens is found in over 50% of patients [3]. However, in contrast to intravenous leiomyomatosis, it has been thought that further tumor extension to large vessels is rarely observed [4]. We have recently encountered three cases with low-grade ESS in whom tumor invasion was noted in the major vascular channels. Two cases of inferior vena cava involvement and one case of cardiac involvement are reported. 495
0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
496
TABATA ET AL.
FIG. 1. Case 1: Angiography demonstrated a large flow defect from the right external iliac veins extending to the inferior vena cava.
Case 2
Case 3
The patient was a 43-year-old female who had undergone a hysterectomy under clinical diagnosis of myoma of the uterus at a previous hospital in 1976. The tumor in the uterus was approximately 4 cm in diameter. The pathological diagnosis of the uterine tumor was leiomyoma at that time. Five years later, in 1981, she was found to have a polyp on the vaginal vault. Pathological examination revealed that the polyp was low-grade ESS. After admission to our hospital, the hysterectomy specimens from the initial surgery were reviewed, and a diagnosis of low-grade ESS was made. CT scan showed a large pelvic mass involving the bladder and rectum, and chest X ray revealed multiple pulmonary metastases. She was treated with whole pelvic radiotherapy combined with chemotherapy consisting of dacarbazine, Adriamycin, and cyclophosphamide. Although a partial response was obtained several times and she remained alive with disease for more than 13 years, the recurrent tumors finally increased. One month before death, cardiac ultrasonography revealed a large mass in the left ventricle (Fig. 2). She died of heart failure in 1995. At autopsy, the pathological diagnosis of the mass in the left ventricle was low-grade ESS.
The patient was a 49-year-old woman who had undergone a hysterectomy under a diagnosis of myoma of the uterus at a previous hospital in March 1997. The tumor in the uterus was approximately 7 cm in diameter. Pathological diagnosis of the uterine tumor was low-grade ESS. Two months later, she was admitted to our hospital for adjuvant therapy. Magnetic resonance imaging performed in our hospital revealed that she already had a long irregular plug within the vessel from the right ovarian vein up to the inferior vena cava (Fig. 3). A recurrent tumor in the pelvis that involved the bladder was also noted. She was treated with four cycles chemotherapy consisting of cisplatin, Adriamycin, and ifosfamide, and partial tumor regression was achieved. Subsequently, resection of the recurrent tumor and retroperitoneal lymphadenectomy were performed. Since the tumor protruding into the inferior vena cava disappeared after chemotherapy, only resection of the right ovarian vein was performed to remove the residual tumor in the vascular channels. Pathological examination of the surgical specimen confirmed the presence of low-grade ESS, and several lymph node metastases were also recognized. After surgery, she received three more cycles of chemotherapy with the same regimen and has remained clinically free of disease for more than 16 months after the second surgery.
CASE REPORT
497
FIG. 2. Case 2: On short-axis view of cardiac ultrasonograpy, a large tumor filling the left ventricle was noted.
DISCUSSION Most patients with low-grade ESS have clinical symptoms similar to those in patients with leiomyoma of the uterus. The difficulty in early diagnosis of this disease has been reported. Accurate diagnosis of low-grade ESS is made preoperatively in only 10% of patients with this disease and is sometimes made when a recurrent tumor is found [3]. Indeed, all three cases in this series received hysterectomy under a preoperative diagnosis of leiomyoma at their initial treatment. Moreover, in two of the three cases presented, the wrong pathological diagnosis had been made. Although more than 80% of patients with low-grade ESS are in clinical stage I at the time of diagnosis [3, 5], a high incidence of recurrence has been reported. Piver et al. found that 56% of the patients with surgical stage I disease developed recurrence [5]. Despite the high relapse rate, the 5- or 10-year survival rates of stage I disease have been reported to be more than 80% [3, 5, 6]. This trend, i.e., long-term survival with evidence of disease, is also recognized in the current series. Because low-grade ESS is a slow-growing tumor, recurrences or metastases are often detected many years later after initial treatment. The mean time to recurrence has been reported to be 34 months for surgical stage I, but recurrences may occur as late as 20 years or more after surgery [5].
In view of tumor invasion to the major cardiovascular channels in our series, clinical behaviors of low-grade ESS are similar to those of intravenous leiomyomatosis, a very rare smooth muscle tumor. Intravenous leiomyomatosis is characterized by worm-like extensions into the uterine veins in the broad ligament or into other pelvic veins [7]. Tumor growth involving the inferior vena cava is noted in more than 10% of patients with intravenous leiomyomatosis, and even cardiac involvement is occasionally seen [4]. Our three cases may resemble intravenous leiomyomatosis in the tumor spread pattern. Whitlatch and Meyer reported a case of recurrent lowgrade ESS tumor in which tumor invasion to the inferior vena cava was observed [8]. That patient was treated with radiotherapy and chemotherapy, but died of cardiovascular failure caused by intravascular tumor growth. Importantly, they reported that the metastatic site histologically resembled intravenous leiomyomatosis. In our series, however, such a trend was not observed. The histological diagnosis of low-grade ESS was confirmed both in primary tumors and in metastatic sites in all cases. In addition, tumor infiltrations to adjacent organs were observed in our series, while such an invasion is seldom seen in intravenous leiomyomatosis. Several cases of possible low-grade ESS with cardiovascular involvement have been reported in the literature [8 –10]. In
498
TABATA ET AL.
FIG. 3. Case 3: Magnetic resonance imaging demonstrated a long irregular plug consisting of sarcoma cells from the right ovarian vein extending to the inferior vena cava.
most cases, resection of the tumors in the cardiovascular channels was performed successfully. Although the long-term survival of these cases is unclear, it is likely that surgical treatment of this condition prevents fatal cardiac complications and has a significant impact at least on short-term survival. We report three cases of low-grade ESS in whom cardiovascular invasion was noted in their clinical courses. This study indicates that the possibility of intravascular tumor invasion should always be considered in the management of this disease. Intensive search for tumor involvement of the vascular system using imaging techniques at the time of diagnosis and follow-up would be useful for detecting metastatic or recurrent tumors. REFERENCES 1. Koss LG, Spiro RH, Brunschwig A: Endometrial stromal sarcoma. Surg Gynecol Obstet 121:531–537, 1965 2. Norris HJ, Taylor HB: Mesenchymal tumors of the uterus. A clinical and pathological study of 53 endometrial stromal tumors. Cancer 19:755–766, 1966
3. Chang KL, Crabtree GS, Lim-Tan SK, Kempson RL, Hendrickson MR: Primary uterine endometrial stromal neoplasms: a clinicopathologic study of 177 cases. Am J Surg Pathol 14: 415– 438, 1990 4. Clement PB: Intravenous leiomyomatosis of the uterus. Pathol Annu 23 (Pt 2): 153–183, 1988 5. Piver MS, Rutledge FN, Copeland L, Webster K, Blumenson L, Suh O: Uterine endolymphatic stromal myosis: a collaborative study. Obstet Gynecol 64:173–178, 1984 6. Gadducci A, Sartori E, Landoni F, Zola P, Maggino T, Urgesi A, Lissoni A, Losa G, Fanucchi A : Endometrial stromal sarcoma: analysis of treatment failures and survival. Gynecol Oncol 63: 247–253,1996 7. Norris HJ, Parmley T: Mesenchymal tumors of the uterus. V. Intravenous leiomyomatosis: a clinical and pathologic study of 14 cases. Cancer 36:2164 –2178, 1975 8. Whitlatch SP, Meyer RL: Recurrent endometrial sarcoma resembling intravenous leiomyomatosis. Gynecol Oncol 28:121–128, 1987 9. Debing E, Van Der Niepen P, Goossens A, Van den Brande P: Intracaval extension of a recurrent low-grade endometrial stromal sarcoma. Acta Chir Belg 98:264 –266, 1998 10. Vargas-Barron J, Keirns C, Barragan-Garcia R, Beltan-Ortega A, Rotberg T, Santana-Gonzalez A, Salazar-Davila E: Intracardiac extension of malignant uterine tumors. J Thorac Cardiovasc Surg 99:1099 –1103, 1990