Abstract
Uterine leiomyosarcoma is a rare and aggressive malignancy with poor overall prognosis. There have been few reports of metastatic leiomyosarcoma in the gallbladder. We report a case of a 41-year-old female who underwent total abdominal hysterectomy due to presumed uterine fibroids. The postoperative pathology revealed high-grade pleomorphic leiomyosarcoma, with involvement of the uterine serosal surface. She subsequently underwent exploratory laparotomy, followed by pelvic radiation and chemotherapy. Since initial management she has developed metastatic disease and has been under treatment and surveillance for 11 years. She has undergone multiple surgical procedures and numerous lines of systemic therapy for metastatic leiomyosarcoma, including cholecystectomy for a metastatic lesion in the gallbladder. There have been no previous reports of metastatic leiomyosarcoma in the gallbladder. Despite extensive metastatic disease this patient has had prolonged survival with multi-modality management.
Introduction
Uterine leiomyosarcoma is a rare, aggressive smooth muscle malignancy, comprising 12% of uterine malignancies. 1 It is often diagnosed incidentally after hysterectomy or myomectomy for a presumed benign leiomyoma or other benign lesions. The prognosis of uterine leiomyosarcoma is very poor due to high rate of recurrence and metastasis. 2 Despite optimal local management, many patients die of distant metastatic disease. Metastatic sites often include the lungs, liver, brain and bone. 3 Other rare metastatic sites have been reported, such as breast, bile duct, bowel, pancreas, skull, adrenal gland and heart.4–12 However, to our knowledge there are no published reports of metastatic leiomyosarcoma of the gallbladder. Here, we present an extremely rare case of uterine leiomyosarcoma, with gallbladder metastasis along with lung, chest wall and thigh metastasis.
Case Report
A 41-year-old woman presented with vaginal bleeding and was found to have uterine fibroids on ultrasound. She underwent total abdominal hysterectomy at another center, and the pathology was reported as high-grade uterine leiomyosarcoma measuring 9 cm. She was then referred to our institution and underwent an exploratory laparotomy, extensive lysis of adhesions and left radical parametrectomy and omentectomy. She subsequently received 6 cycles of adjuvant gemcitabine and docetaxel followed by adjuvant radiation. Two years after the completion of adjuvant chemotherapy a surveillance scan detected lung metastases (Figure 1) and she subsequently underwent a left thoracoscopic wedge resection followed by 6 cycles of doxorubicin. Six months later a restaging computed tomography (CT) demonstrated increasing metastatic disease in the lungs and she was treated with 6 cycles of temozolamide. A CT scan following 6 cycles showed stable disease. She then underwent a right thoracoscopic wedge resection and was treated with 4 cycles of liposomal doxorubicin. A repeat CT showed stable lung nodules. Four cycles of trabectedin were then administered but she tolerated these poorly with grade 3 fatigue. She received 5 cycles of temozolamide with disease progression. She then underwent a left video-assisted thoracoscopic surgery resection and right thoracotomy wedge resection and was subsequently commenced on gemcitabine and docetaxel with bevacizumab. Following 6 cycles of gemcitabine and doceatexl she continued on single agent bevacizumab, with durable stable disease.
Pathology of lung metastasis, showing the tumor involving the lung parenchyma. A) 4×; B) 20×.
Three months following discontinuation of bevacizumab repeat imaging demonstrated a mass in the gall bladder, measuring 2.8×2.2×1.8 cm (Figure 2A). The patient had no obvious symptoms. Six months later, followup CT demonstrated increased size of the mass, measuring 5.0×4.2×2.5 cm (Figure 2B). She then underwent cholecystectomy. Pathology confirmed metastatic leiomyosarcoma in the gallbladder (6.5 cm), with tumor involving the wall of the gallbladder with extension into mucosa but not beyond the serosa and not involving perigallbladder fat (Figure 3). Immunochemistry showed the tumor cells to be strongly positive for smooth muscle actin (Figure 4).
Abdomen computed tomography demonstrated gallbladder lesion. A) Initial lesion size; B) lesion size after 6 months.
Pathology of gallbladder metastatic leiomyosarcoma. A) 4×; B) 20×.
Immunohistochemistry for alpha-smooth muscle actin (1A4) antibody.
Repeat imaging also demonstrated a right chest wall mass and a right posterior thigh mass. She underwent resection of all those lesions. Most recently, imaging showed multiple pancreatic nodules, Fine needle aspiration biopsy confirmed metastatic disease. She underwent standard pancreaticoduodenectomy. The pathology from all surgical specimens demonstrated morphological and imaging features consistent with metastatic leiomyosarcoma. As she had persistent lung metastases she commenced gemcitabine and navelbine with a partial response. She had 8 cycles of this schedule. She then went on to surveillance and most recently has been on pazopanib with stable disease. With multi-modality therapy she has lived for over 10 years with metastatic uterine leiomyosarcoma.
Discussion
The common metastatic sites of uterine leiomyosarcoma include lung, liver, brain, and bone. 3 Other rare metastatic sites have been reported including pancreas, skull, adrenal gland and heart, bile duct, bowel, breast, orbital and gingival.4–14 To the best of our knowledge, we are unaware of any other published reports of uterine leiomyosarcoma with gall bladder metastasis.
Uterine leiomysarcoma generally disseminates via the blood stream, with the lungs being a common site of metastatic spread. However, the gallbladder does not have a rich blood supply, and it is a rare site for metastatic disease. 15 Our patient had lived for many years with metastatic leiomyosarcoma prior to the identification of a metastasis in the gall bladder. Several cases of primary leiomyosarcoma of the gallbladder have been reported although this is not a common primary site.15–17
The prolonged survival of our patient with multimodality management, including systemic therapy, surgery and radiation, highlights the importance of managing patients with these rare tumors within a multi-disciplinary team. The median overall survival of patients with metastatic soft tissue sarcoma is in the region of 12-16 months. However, it is clear that in some patients prolonged survival can be achieved with aggressive management and access to novel treatment approaches. 18 Our case also highlights the importance of unusual patterns of metastatic spread in patients with leiomyosarcoma. Physicians need to be aware of such potential metastatic sites so that appropriate management can be initiated.
Conclusions
In conclusion, to our knowledge this is the first report of leiomyosarcoma uterine with metastatic disease in the gall bladder. This case also illustrates the importance of physicians being aware of unusual locations of metastasis and the applicability of multimodality therapy in patients with metastatic soft tissue sarcoma.