A 40-year-old woman was seen by family physician with nocturnal lower back pain in April 1999. The pain was moderate to severe, and occasionally associated with nausea. Her family physician arranged an abdominal ultrasound. This study revealed a 9 × 10-cm cystic mass in the region of the body and tail of the pancreas. A solid, mural nodule was also evident, measuring 2.3 × 2.9 cm. The patient was referred to a general surgeon, who completed an endoscopic retrograde cholangiopancreatography in June 1999. The pancreatic duct was displaced superiorly, and a portion of the duct in the tail and body of the pancreas was not opacified with contrast. Extrinsic compression was favored as the cause of this filling defect. A correlative computed tomography scan of the abdomen was completed the following day (Fig. 1). A well-defined 10-cm cystic mass arising from the posterior aspect of the pancreatic tail was evident. An irregular solid lobulation at the lateral aspect of the cyst was also visible and measured 3 cm in maximum dimension. The cyst caused displacement of the splenic vein and pancreas. Local extension in adjacent organs was not seen.
On review of her computed tomography scan findings, the patient was admitted to the hospital. The likelihood of a malignant pancreatic neoplasm was discussed, and a laparotomy was performed 4 days later. Intraoperatively, a 15-cm mixed translucent/opaque neoplasm was identified. The pancreas was splayed over the top of and adherent to the lesion. The mass bulged through the transverse mesocolon and against the stomach. It was mobile on the retroperitoneum. Enlarged gastric vessels and mild splenic enlargement suggested splenic vein thrombosis and mild portal hypertension. Surprisingly, en bloc resection was successful without rupture of the cyst wall. Coincident splenectomy and a partial pancreatectomy were also completed. Sepsis and a small bowel obstruction from adhesions complicated her postoperative course. She had a second laparotomy 3 weeks after her initial surgery to relieve her bowel obstruction. She made a full recovery and was discharged from the hospital 3 weeks later.
Pathologic evaluation revealed a very unusual tumor (Fig. 2). The neoplasm had two distinct components—a mucinous, neoplastic epithelial cyst with nodular areas of multinucleated tumor giant cells. This unique combination of a mucinous neoplastic epithelium with foci of multinucleated tumor giant cells is pathognomonic of osteoclastic giant cell tumor of the pancreas. The patient remains free of recurrence 10 months after surgical excision. The significance of this entity is discussed.
This rare mixed neoplasm of the pancreas has been well described in a number of anecdotal reports. There have been at least 26 publications since 1977, representing more than 40 patients. 1–26 Alguacil-Garcia and Weiland 1 were first to describe a malignant giant-cell tumor of the pancreas with osteoclast-like giant cells. During the past 2 decades, reports have described this neoplasm fairly uniformly with respect to clinical and pathologic characteristics. Osteoclast-like giant-cell tumors have been noted to occur in the parotid gland, thyroid gland, skin, orbit, kidney, and breast. 27–32 However, the pancreas seems to have the highest predilection for this pathological lesion. Lesions that occur in the pancreas most commonly present as large cystic neoplasms, often greater than 5 cm to 10 cm in maximum diameter. 15 Focal hemorrhage or necrosis is not uncommon. Nodal or intraabdominal metastasis is the predominate mode of spread and is apparent in the majority of cases. 10,14,15,21
In this instance, the osteoclastic tumor giant cells appeared to arise on a background of a mucinous neoplastic epithelial component (Fig. 2). This occurrence has been reported in several instances. 14,15 Most pathologic evaluations have distinguished this neoplasm as comprising two cell types: a mononuclear population (mucinous adenocarcinoma in the present case) and osteoclastic tumor giant cells of uncertain lineage. 10,15,33 Immunohistochemical analysis by immunostaining for epithelial membrane antigen (EMA) and keratin demonstrates an epithelial origin for the mononuclear cell population in the majority of reports (Table 1). Conversely, osteoclastic giant cells rarely stain positive for epithelial markers and show staining consistent with a histiomonocytic origin (CD68+). Sun et al. 21 in 1998 report on a case of osteoclastic giant cell tumor of the pancreas with nodal metastasis. Light microscopy of the involved nodes revealed both cell populations present. The authors have proposed that the neoplastic component may produce chemotactic and growth factors that stimulate the proliferation and dedifferentiation of circulating precursors cells in osteoclastic giant cells. The question of whether the giant cell component is neoplastic or reactive is controversial and will require further pathologic investigation to answer.
Although some authors have reported a “ more favorable prognosis” than that for pancreatic adenocarcinoma of ductal origin, this observation does not hold true on review of published reports. 11 The exception, however, may be those patients with gross total, en bloc resection without adverse features such as nodal metastasis. Outcome after surgical resection is variable (Table 1). Appraisal of the literature where outcome is reported reveals the interval to death or disease progression varies from 4 months to 10 years. However, the majority of patients have survival of less than a year, median of 11 months. This is similar to outcome for common ductal pancreatic carcinoma. 34,35
Difficulties in making treatment decisions obviously arise from the rarity of this neoplasm. Large cystic tumors of the pancreas are often misdiagnosed as pseudocysts and may therefore delay initial pathologic diagnosis. Computed tomography imaging features of hemorrhage, mural nodules, or multiloculations should raise suspicion of a pancreatic neoplasm. Intraoperative management may be complicated by a tense, cystic structure, filling much of the upper abdomen. En bloc resection may not always be feasible and thus raises the risk of intraoperative tumor spill.
To date, there is no reported experience of radiotherapy or chemotherapy in the management in these unusual cases. Acknowledging the radiosensitivity of giant-cell tumor of the bone, one may extrapolate possible benefits of radiation in the adjuvant setting. 36,37 In this case, the multidisciplinary gastrointestinal oncology group considered the possibility of abdominal radiotherapy. However, with en bloc resection and the absence of nodal metastasis or tumor spill, a simple program of surveillance was recommended. Additionally, radiotherapy based on the presurgical tumor volume would have resulted in a large abdominal field with associated morbidity from small-bowel irradiation.
Given the epithelial origin of the mononuclear, neoplastic population of cells, it may be reasonable to consider agents such as gemcitabine for palliation of disease recurrence. 38 It is important and necessary that future reports detail treatment modalities, patterns of spread, and clinical outcome. To date, there is no evidence to suggest a management approach different from that for typical ductal pancreatic adenocarcinoma.
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