Malignant Solitary Fibrous Tumor of the Pancreas Jeannelyn S. Estrella, MD,* Huamin Wang, MD, PhD,* Priya R. Bhosale, MD,† Harry L. Evans, MD,* and Susan C. Abraham, MD* Abstract: Solitary fibrous tumor (SFT) arising in the pancreas is exceedingly rare, with only 11 cases reported in the English literature. All cases described thus far have exhibited benign histology. We report the first case of malignant SFT of the pancreas. The patient was a 52-year-old woman who presented with obstructive jaundice and a 15-cm pancreatic head mass. The mass showed areas with typical histologic features for SFT including small fibroblastlike cells arranged in the well-characterized “patternless pattern” of architecture, hemangiopericytomalike vessels, areas with dense collagen and infrequent mitoses (0–2 per 10 high-power fields [HPFs]). In addition, multiple areas with an overtly sarcomatous morphology were present, containing large spindle and epithelioid cells with nuclear pleomorphism, marked cellularity, up to17 mitoses per 10 HPFs, and necrosis. Immunohistochemical stains were positive for CD34 and B-cell CLL/lymphoma 2 (Bcl-2) in both benign and malignant components and showed strong, diffuse p53 and p16 staining in the malignant component. At last follow-up (40 months), the patient was alive and well without evidence of disease. However, given that the presence of a malignant component in extrapancreatic SFT has been associated with recurrence/ metastasis and death, complete surgical resection and close long-term follow-up is required. Key Words: solitary fibrous tumor, pancreas, malignant (Pancreas 2015;44: 988–994)


olitary fibrous tumor (SFT) was first described in the pleura as a spindle cell neoplasm considered to represent a form of localized or benign mesothelioma based on its cell culture characteristics and its typical occurrence along serosal surfaces.1 However, more recent studies using immunohistochemistry and electron microscopy have shown that SFT is a mesenchymal neoplasm composed of multipotential or undifferentiated perivascular cells, fibroblasts, myofibroblasts, and pericytes.2,3 The frequency of extrapleural SFTs is now reported to approach4 or even exceed pleural-based lesions.5 Extrapleural SFTs most commonly arise in the head and neck region, extremities, and retroperitoneum6 but have been described in almost every anatomic location between the toe7 and the temple.8 Solitary fibrous tumors arising in the pancreas are very rare. Pancreatic SFT was first reported in 1999 by Lüttges et al 9 in a 50-year-old woman of whom a 5.5-cm tumor was an incidental finding on abdominal ultrasound. Since then, there have been only 10 subsequent cases of pancreatic SFT reported in the English literature.10–19 Highlighting the rarity of this condition, only 2 patients with SFT of the pancreas were treated at Memorial Sloan-Kettering Cancer Center over an 18-year period, representing 2.5% of all 79 patients with SFTs and less than 0.001% of 4329 patients with soft tissue sarcomas treated at that institution during the same time frame.4 To date, all reported From the Departments of *Pathology, and †Diagnostic Radiology, University of Texas M. D. Anderson Cancer Center, Houston, TX. Received for publication May 30, 2014; accepted January 12, 2015. Reprints: Jeannelyn S. Estrella, MD, Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Unit 085, 1515 Holcombe Blvd, Houston, TX 77030 (e‐mail: [email protected]). The authors declare no conflict of interest. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


pancreatic SFTs have demonstrated benign histologic features and unremarkable clinical follow-up, with the exception of a single patient who died in the immediate postoperative period from hemorrhagic complications.20 Although most pleural and extrapleural SFTs behave in a benign fashion, a small proportion (5%–15%)21–23 can recur locally or metastasize. Histologic features associated with aggressive behavior include tumor necrosis; size, more than 5 cm; mitotic rate, more than 4 per 10 high-power fields; marked hypercellularity; nuclear pleomorphism; positive margins; and the presence of an overtly malignant-appearing component in the tumor.4,22–24 Recently, Mosquera and Fletcher25 reported a series of 8 tumors— 2 intrathoracic and 6 extrathoracic—which contained discrete anaplastic areas within otherwise benign SFTs, a phenomenon that the authors likened to dedifferentiation in low- to intermediategrade soft tissue tumors. Four of these patients developed recurrence and metastases, with death from disease occurring in 3 patients at 1, 8, and 34 months after initial presentation. Most of these “dedifferentiated SFTs” also had corresponding immunohistochemical abnormalities including loss of CD34 expression and/or gain of p53 or p16 staining in the anaplastic foci.25 We recently encountered an SFT of the pancreas leading to an unusual clinical presentation of obstructive jaundice due to infiltration of the distal common bile duct. Histologically, the tumor demonstrated areas of overtly sarcomatous, anaplastic malignancy within a background of typical SFT. We present the pathologic features and immunohistochemical characterization of this first reported case of malignant SFT to arise in the pancreas.

MATERIALS AND METHODS Case Presentation A 52-year-old white woman presented with a 3-week history of painless jaundice, dark urine, and acholic stools. She reported a decrease in appetite, but her weight had remained stable. Her medical history was significant only for hypothyroidism with multinodular goiter. There was no history of gastrointestinal, liver, or pancreatic disease. One year before presentation, she had undergone a total abdominal hysterectomy and bilateral salpingooophorectomy for endometriosis but had never had other abdominal surgeries, including cholecystectomy. On computed tomographic (CT) scan, there was a 12  7.7-cm mass that appeared to arise from the head of the pancreas, with mass effect on the duodenum and obstruction of the common bile duct in the region of the hepatoduodenal ligament (Fig. 1). The mass was noted to be heterogeneous, with a hypodense (necrotic) cranial component and a vascular caudal component after contrast injection, suggesting that it may represent a neuroendocrine tumor. Laboratory testing revealed direct hyperbilirubinemia with total bilirubin reaching a maximum of 6.7 mg/dL (reference range, ≤1.4 mg/dL), alkaline phosphatase of 530 U/L (reference range, 20–145 U/L), aspartate aminotransferase of 91 U/L (reference range, 3–70 U/L), and alanine aminotransferase of 224 U/L (reference range, 3–75 U/L). Serum tumor markers including alphafetoprotein, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and cancer antigen 125 (CA-125) Pancreas • Volume 44, Number 6, August 2015

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Pancreas • Volume 44, Number 6, August 2015

Malignant Pancreatic Solitary Fibrous Tumor

RESULTS Gross Appearance

FIGURE 1. Contrast-enhanced CT scan shows a large heterogeneous mass arising from the head of the pancreas (arrow). GB, gallbladder.

were within normal limits. Because of the radiographic suggestion of neuroendocrine tumor, serum levels of chromogranin A, gastrin, serotonin, and pancreatic polypeptide were obtained and were all within reference ranges. A pancreaticoduodenectomy and cholecystectomy was performed one month after onset of the patient's symptoms. At the time of surgery, a large mass abutted the superior mesenteric vein, portal vein, common hepatic artery, and gastroduodenal artery but did not directly invade any of these structures or the superior mesenteric artery. Clear tissue planes were established between the tumor and major vessels, allowing for a complete surgical resection. Results of intraoperative ultrasound of the liver and visual inspection of the abdomen were negative for metastatic disease.

Histology and Immunohistochemistry The resection specimen was examined in its fresh state, photographed, and then placed in 10% neutral buffered formalin for overnight fixation. Tissue sections were processed routinely, embedded in paraffin, and stained with hematoxylin-eosin. Select sections were subjected to immunohistochemistry for the following antigens: CD34 (clone My10, 1:40; BD Biosciences, San Jose, Calif ), CD99 (clone 12E7, 1:300; DAKO, Carpinteria, Calif ), B-cell CLL/lymphoma 2 (Bcl-2, clone 100, 1:200; Leica Microsystems, Buffalo Grove, Ill), CD117 (c-Kit, polyclonal, 1:100; DAKO), pankeratin (AE1/3, 1:50; DAKO; CAM5.2, 1:50; BD Biosciences; MNF116, 1:50, DAKO), synaptophysin (clone 27G12, 1:600, Novocastra, Newcastel Upon Tyne, UK), chromogranin A (LK2H10, 1:4,000; Chemicon, Temecula, Calif ), p53 protein (clone D0-7, 1:100, DAKO), and p16 (clone E6H4, 1:3 pre-dilute; Ventana, Tucson, AZ).

The surgical specimen comprised a 17  12  10-cm portion of pancreas, 5.5-cm length of stomach, 25-cm length of duodenum and jejunum, and a 6-cm long gallbladder. A pale firm to fleshy mass measuring 15  10  10 cm was present in the head of the pancreas, which displaced the adjoining normal-appearing pancreatic parenchyma (Fig. 2). The mass appeared grossly well circumscribed without apparent infiltration into the duodenum or common bile duct. Consistency was heterogeneous, with approximately one half described as firm in texture, whereas the remainder was soft and possibly necrotic. The gallbladder contained multiple green multifaceted stones up to 2.5 cm but was otherwise unremarkable. The stomach and duodenum were grossly normal.

Histology Many sections of the mass showed typical histologic features for SFT (Fig. 3) including small fibroblastlike cells arranged in the well-characterized “patternless pattern” of architecture. More cellular areas had readily visible, thin, hemangiopericytomalike vessels with perivascular hyalinization. Less cellular areas were heavily collagenized. In these low-grade areas of typical SFT, nuclei were small and uniform with infrequent mitoses (0–2 per 10 high-power fields [HPFs]). In addition, multiple areas with an overtly sarcomatous morphology were also present (Fig. 3). These high-grade areas contained large spindled and epithelioid cells with a moderate to marked degree of nuclear pleomorphism. In these foci, the mitotic rate averaged 5 per 10 HPFs but reached up to 3 mitoses in a single HPF and up to 17 per 10 HPFs in the most active area. Atypical mitotic figures were readily apparent, including tripolar and tetrapolar mitoses. Some areas of the high-grade tumor were highly cellular and were indistinguishable from an unclassified spindle cell sarcoma or epithelioid sarcoma by hematoxylin-eosin staining. Other high-grade areas, however, partially retained their morphologic similarity to SFT. Broad fronts of tumor necrosis were present and comprised approximately 20% of the sampled tumor volume. Smaller foci of cystic degeneration were also evident in hypercellular areas. The mucosa and muscular wall of the distal common bile duct were microscopically infiltrated by low-grade SFT, which entrapped peribiliary glands. The adjacent pancreatic parenchyma lacked any evidence of obstructive pancreatitis and was essentially normal except for small foci of low-grade pancreatic intraepithelial

Review of Previous Pancreatectomy Specimens We conducted a review of the computerized diagnoses on all pancreatic resections performed at our institution over an 18-year period from January 1996 to January 2014. Cases of nontumoral pancreatic disease (eg, autoimmune pancreatitis) or secondary involvement of the pancreas by neoplastic disease from an adjacent organ (eg, ampullary carcinoma and retroperitoneal liposarcoma) were excluded. For any diagnosis of unclassified sarcoma, undifferentiated tumor, or unusual pancreatic primary (eg, gastrointestinal stromal tumor), we reviewed the original histologic sections and immunostained slides to exclude the possibility of solitary fibrous tumor. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

FIGURE 2. Resected SFT with adjoining pancreatic parenchyma (arrowheads). The tumor at right shows a typical white fibrous cut surface, whereas the tumor at left is fleshier and partially necrotic.

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Pancreas • Volume 44, Number 6, August 2015

Estrella et al

FIGURE 3. Histologic features in benign and malignant components of the solitary fibrous tumor. Bland fibroblastic cells with both hypocellular (A) and moderately cellular (B) areas. C, Abrupt transition between a hypocellular area with thick collagen bundles at upper right and a hypercellular focus with round cell morphology at left. D, Marked hypercellularity and rounding of tumor cells. Nuclear pleomorphism involving both less cellular (E) and hypercellular (F) foci. G, Mitoses numbered up to 17 per 10 HPFs; 2 mitotic figures (including a tripolar mitosis) are seen in close proximity in the center of the field. H, Tumor necrosis. (A–H, Hematoxylin and eosin preparations).

neoplasia (PanIN-1A). Twenty-four regional lymph nodes were identified and were free of tumor. All resection margins, including pancreatic, bile duct, retroperitoneal, gastric, and small intestinal margins, were free of tumor.

Immunohistochemistry The same panel of immunohistochemical stains was applied to representative areas of typical SFT and to the spindled and


epithelioid sarcomatous components (Table 1, Fig. 4). The typical SFT component demonstrated diffuse staining for Bcl-2, focal positivity for CD34, and negative staining for CD99. Negative staining for pankeratin, synaptophysin, chromogranin A, and CD117 excluded sarcomatoid carcinoma, neuroendocrine carcinoma, and extragastrointestinal stromal tumor. The malignant component exhibited diffuse staining for CD34, focal positivity for Bcl-2, and negative staining for CD99. Interestingly, there were rare pancytokeratin-positive cells in the malignant component. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

© 2015 Wolters Kluwer Health, Inc. All rights reserved.










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Kwon,11 2008

Chetty et al,10 2009

Sugawara et al,14 2010

Tasdemir et al,15 2012

van der Vorst et al,17 2012

Azadi et al,19 2012

Santos et al,18 2012

Chen et al,16 2013

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Obstructive jaundice

Abdominal distension and mild upper abdominal pain

Incidental finding on PET/CT Incidental finding on CT and MRI

Abdominal pain

Mild epigastric pain

Right upper abdominal pain Back pain, fatigue, weight loss Incidental finding on ultrasound Incidental finding on CT for hematuria Incidental finding on ultrasound

Incidental finding on abdominal ultrasound














Size (cm)


Suggestive of NET Benign (areas of ill-defined borders but no necrosis or mitoses) Suspect NET Benign (no atypia, necrosis, or mitoses) NET Benign (no atypia or necrosis;

Malignant Solitary Fibrous Tumor of the Pancreas.

Solitary fibrous tumor (SFT) arising in the pancreas is exceedingly rare, with only 11 cases reported in the English literature. All cases described t...
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