Introduction

Leiomyosarcomas are malignant tumors of smooth cell origin [1]. They can thus arise from any organ with mesenchymal component especially the gastrointestinal, female genital tract, and soft tissues of the extremities. Leiomyosarcomas of gastrointestinal origin maybe more commonly found in the stomach, small intestine, and retroperitoneum [2]. Though rarely seen, leiomyosarcomas maybe of primary pancreatic origin (0.1–0.6% of pancreatic tumors). It occurs more commonly in the fifth decade and males are affected almost twice compared to females [3]. They are highly malignant with extreme metastatic potential [3]. Immunohistochemistry is required to demonstrate smooth muscle markers actin and desmin for diagnosis to be confirmed [1]. Prognosis is generally bad as most tumors are diagnosed when disease is metastatic. Tumors found early and which are amendable to surgery have had a better prognosis [3]. Metastatic disease presents 40–80% of the time and is heralded by short survival due to the aggressive nature of disease [4].

Only 37 cases excluding this one have been reported since 1951 with very few literature reviews. It is seldom mentioned in the oncology textbooks especially in regards to management.

We present the 38th case of primary leiomyosarcoma of the pancreas presenting with liver metastases who is alive 24 months postpancreatic surgery. Patient signed for consent for the case to be published in a medical journal for educative purposes.

Case Report

A 59-year-old man presented to the surgical department with a history of epigastric mass, weight loss, and anorexia in April 2009. He has no history of alcohol ingestion but a positive history of second-hand smoking from his father who died from cancer of the lung. He has had bilateral inguinal hernia repaired, but no significant previous medical history.

Investigative findings including chest X-ray was normal. Computed tomography (CT) scan of the abdomen with contrast showed a huge pancreatic tumor involving the head and tail of the pancreas and also bilateral liver lesions highly suggestive of metastases. Surgery done on 20 May 2009 revealed a pancreatic tumor of 240 × 170 × 190 mm involving the tail of the pancreas and firmly adherent to the transverse colon. Also found were multiple liver metastases. There was no lymph node involvement or ascites. The tumor was excised through a distal pancreatectomy with resection of attached transverse colon. Histopathology revealed macroscopically a large lobulated mass of above measure with a portion of bowel measuring 210 mm stretched over its surface. The cut surface showed a large cream-colored solid and focally cystic tumor. The mass appeared to infiltrate the wall of the bowel with overlying attenuated mucosal tissue. The second portion of the tissue also showed firm cream-colored solid and partially cystic tumor tissue.

Microscopically examination of multiple sections from tumor showed spindle cell tumor composed of cells showing moderate cellular pleomorphism arranged in interwoven fascicles. Nuclei are open, vesicular, and with small nucleoli. Frequent mitotic activity was seen with up to five mitosis per single high-power field (HPF). There are areas of degenerative and focal necrosis within the lesion which shows widespread infiltration into the bowel wall.

Morphologic features are those of malignant spindle cell tumor, most likely leiomyosarcoma.

Immunoperoxidase stains for CD117 showed negative reaction within tumor but smooth muscle actin and desmin show strong positivity within tumor cells. A diagnosis of high-grade leiomyosarcoma of the pancreas was made.

Postsurgery, the patient was referred to the radiotherapy department of the hospital where he received five cycles of capecitabine chemotherapy at 800 mg/m2 on account of liver metastasis without much response. Tumor markers were normal.

Chemotherapy was stopped and he has been seen in the clinic for supportive care since.

He then presented with cough, easy fatigability, and 3 kg weight loss over 1 month, 18 months after surgery. His performance status was ECOG 3. Chest X-ray done showed bilateral lung metastases. He was started on Adriamycin at 70 mg/m2 when his performance status improved to 2. He developed intractable hiccups after the third cycle of chemotherapy and a CT scan was ordered on suspicion of para-aortic involvement. The CT scan in December 2010, however, showed multiple bone metastases and no para-aortic lymph node involvement. It also showed partial regression of liver metastases. We therefore started him on biphosphonate therapy and continued Adriamycin chemotherapy. He received a total of eight cycles of chemotherapy and has stable weight and is presently asymptomatic. He is still alive and is the third known case of pancreatic leiomyosarcoma presenting with liver metastases alive for 2 years.

Discussion

Pancreatic mesenchymal tumors form about 1–2% of pancreatic tumors. They are rare and are classified based on their histological origin. They may arise from connective, lymphatic, vascular, and neuronal tissues in the pancreas. They include leiomyosarcomas, histiocytomas, shwannomas, liposarcomas rhabdomyosarcomas, lymphangiomas, and hemangiopericytomas [1]. Most have been reported as small series or single case studies without definitive electromagnetic cell differentiation or immunohistochemistry [2]. Pancreatic leiomyosarcoma does not have any specific look on radiological imaging, it may mimic pancreatic pseudocyst and therefore should be considered to have a differential diagnosis [5]. In this case, the cystic component was found in pathological specimen. On histopathathological examination, it may be epitheloid or spindle cell and may have cystic changes with areas of necrosis and hemorrhage especially in large tumors [6]. It stains positive for smooth muscle actin and desmin and negative for CD117 or C-KIT [7].

Leiomyosarcomas involving the pancreas may be of pancreatic origin or may be pancreatic extensions of sarcomas arising from gastrointestinal sarcomas; mainly gastric or duodenal or the retroperitoneum. Those of primary origin are the rarest sarcoma accounting for 0.1% of pancreatic tumors [3] and most likely arising from the pancreatic duct or blood vessel. The first recorded case in 1951 was an autopsy diagnosis [8]. Leiomyosarcomas have been described as being hypervascularised which makes it easily metastatic especially to the liver. In fact, 80% out of the recorded 33 were diagnosed in the metastatic stage and survival has been low with overall 1-year survival being 19% and 5-year survival being 4% [3, 4]. Left untreated, prognosis is much poorer. The best form of treatment from literature is total tumor resection for localized disease. Patients with early disease postsurgery have survived many years.

So far, from PubMed research, only 37 cases to our knowledge have been reported. In the search data, only two cases have been reported with liver metastases at presentation living at least 18 months.

We report the 38th case of pancreatic leiomyosarcoma in a 59-year-old male presenting with liver metastases 24 months ago. He had total excision of the pancreas without hepatic resection. A previous case report from France with similar presentation had in addition to pancreatic surgery, resection of liver metastases [9]. He developed local recurrence of the liver masses as well as other areas of involvement after 18 months. He did not receive any chemotherapy. A second case with similarity to ours, reported from Japan, presented with liver metastases and did not have surgery but rather received several cycles of chemotherapy and died after 33 months [10]. Our patient did not receive any active chemotherapy till the patient became symptomatic 18 months postpancreatic resection from bone and lung metastases and has remained stable in the past 6 months on bisphophonates and Adriamycin chemotherapy. In general, it is stated that this tumor is not chemosensitive except in the palliative setting. It could be worthwhile to investigate the role of newer agents including targeted therapies, especially in the palliative setting. In spite of the large size at presentation (24 cm), he has survived this long; this is in line with previous reviews indicating that size is not predictive of outcome [11]. His low mitotic count of five HPF could also be a reason for his slower-than-expected progression of disease as patients with higher mitotic counts have aggressive disease [12]. Other prognostic markers could be investigated.

From previous case presentations and our single case experience, we suggest that patients with liver metastases with good performance status may be evaluated for surgical resection if feasible followed by chemotherapy (sarcoma protocols)

Conclusion

Patients with metastatic leiomyosarcoma of the pancreas to the liver may have pancreatic tumor resected if feasible and consideration should be given to single-agent chemotherapy in addition to supportive care. So far, three cases presenting with liver metastases have survived more than 18 months with surgery and/or chemotherapy. Long-term survival is also achievable in the metastatic setting.