Pancreatic Schwannoma: Literature Review

CASE REPORTS

Pancreatic Schwannoma: Literature Review Aditya Gupta, MD, Gokulakkrishna Subhas, MD, Vijay K. Mittal, MD, and Michael J. Jacobs, MD Department of General Surgery, Providence Hospital and Medical Centers, Southfield, Michigan Pancreatic schwannoma is a rare neoplasm. Accurate preoperative diagnosis remains difficult, but computed tomography (CT) scanning and magnetic resonance imaging (MRI) help to establish the diagnosis, and definitive diagnosis requires immunohistochemical examination. Cystic pancreatic schwannomas should be considered in the differential diagnosis of cystic neoplasms and pseudocysts. Simple enucleation may be adequate for pancreatic schwannoma. In this report, we examine a case of benign pancreatic schwannoma in a 56-year-old woman. She was being evaluated for an ovarian teratoma, and an 8-cm cystic mass was incidentally found in the head of the pancreas. She underwent a pylorus preserving Whipple procedure with bilateral oopherectomy. Only 37 cases have been reported in the English literature. We present a thorough review with an emphasis on the clinical presentation, diagnostic modalities, and treatment options in the management of this rare clinical entity. (J Surg 66:168-173. © 2009 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) KEY WORDS: endoscopic ultrasound, enucleation, pancreatic mass, pancreatic neoplasm, schwannoma, Whipple’s procedure COMPETENCY: Patient Care, Medical Knowledge

INTRODUCTION Pancreatic schwannoma is a rare neoplasm that originates from the Schwann cell. The Schwann cells line the nerve sheath and can generate either schwannoma or neurofibroma.1 The common sites for schwannoma are the extremities, neck, mediastinum, retroperitoneum, and posterior spinal roots.2 These tumors vary considerably in size and approximately two thirds are reported to undergo degenerative changes, which include cyst formation, calcification, hemorrhage, hyalinization, and xanthomatous infiltration.3 Accurate preoperative diagnosis remains difficult. Computed tomography (CT) scans and magnetic resonance imaging (MRI) help establish the diagnosis, and definitive diagnosis requires immunohistochemical examination. Immunohistochemically schwannomas are strongly positive for S-100.4 Correspondence: Inquiries to Gokulakkrishna Subhas, MD, Providence Hospital and Medical Centers, 16001 W. Nine Mile Road, Southfield, Michigan 48075; fax: (248) 8495380; e-mail: [email protected]

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The occurrence of schwannoma in the pancreas is rare, and only 37 cases have been reported in the English literature. In this report, we present a case of pancreatic schwannoma and provide a pertinent review of literature with emphasis on clinical presentation, diagnostic modalities, and treatment options.

CASE REPORT A 56-year-old woman was examined by her gynecologist because of pelvic pain and an intermittent reddish-brown discharge from the vagina for the last 2.5 years. She was morbidly obese with a body mass index of 43. A pelvic ultrasound showed an enlarged uterus with a fibroid that measured 2.5 cm and an 8-cm cyst superior to the uterus with nonvisualized ovaries. She had a CT scan of the abdomen and pelvis (Figs. 1 and 2), which revealed a cystic mass with a calcified peripheral rim that was inseparable from the posterior inferior base of the pancreas (7.9 cm in anteroposterior dimension and 8.3 cm laterally). The pelvic cyst noted in ultrasound was observed as a 7.3 ⫻ 8.9-cm cyst that developed on the left ovary. Blood test results for tumor markers CEA, CA 19-9, and CA-125 were all within normal limits. During the operation, a midline laparotomy was performed followed by a bilateral salpingo-oopherectomy. The pancreatic mass was found to be hard and cystic with dense adhesions adjacent to it. A wedge of the cyst wall was sent for frozen section, which was reported as benign, but it had some spindle cells. Mucinous-type debris was observed within the central aspect of the cyst. A pylorus preserving Whipple was performed based on the embedded nature of the cystic mass of spindle cells. The patient tolerated the procedure well and was discharged home 9 days later. The final pathologic diagnosis was benign serous cystadenofibroma, mature cystic teratoma (dermoid cyst) of the ovaries, and ancient/cellular schwannoma with cystic degeneration of the head of pancreas (Fig. 3). There was moderate-to-marked cellularity with very low mitotic activity (less than 1 mitoses/10 high-power field). Areas of Antoni A and Antoni B were also noted. Focally, there was continuity with peripheral nerves. The lesion was entirely capsulated and abutted the duodenum but was easily separable from the muscularis propria. Immunohistochemical staining for S-100 was positive (Fig. 4). Immunostains for CD117, CD34, HMB-45, smooth-muscle actin, and desmin were negative.

Journal of Surgical Education • © 2009 Association of Program Directors in Surgery Published by Elsevier Inc. All rights reserved.

1931-7204/09/$30.00 doi:10.1016/j.jsurg.2008.12.001

FIGURE 1. CT scan showing cystic lesion in the head and body of the pancreas.

DISCUSSION Schwannoma, which are also known as neurinoma, perineural fibroblastoma, and neurilemmoma, are benign encapsulated neoplasms that develop from the Schwann cell of nerve sheaths. Schwannomas are sometimes solitary, but more frequently they are associated with von Recklinghausen disease.5 Schwannomas that occur in the pancreas are rare with only 37 cases reported in the English literature. Generally, pancreatic schwannomas have slow growth rates and usually originate from the peripheral epineurium of either autonomic sympathetic or parasympathetic fibers, which course embryologically through the pancreas via the vagus nerve.6,7 Malignant schwannomas are uncommon, and the malignant transformation of a benign schwannoma is very rare and is usually associated with Recklinghausen disease.1,8 Schwannoma commonly occurs in the extremities, trunk, head and neck, retroperitoneum, mediastinum, and pelvis.1,9 A review of the literature for pancreatic schwannoma shows an almost equal gender ratio at an male-to-female ratio of 19 to 18, and the patients’ ages ranged from 35 to 87 years with the average age of 59 years. In the pancreas, schwannomas are most commonly observed in the head (15/37), followed by body

FIGURE 2. CT scan showing cystic lesion that developed from the left ovary.

FIGURE 3. Hematoxylin and eosin staining of pancreatic mass demonstrating schwannoma.

(7/37), uncinate process (5/37), junction of head and body (4/37), junction of body and tail (4/37), and tail (2/37). The sizes of the tumors ranged from 1.0 cm to 20.0 cm in the maximum diameter; most (22/34) were less than 6 cm. Small tumors were generally solid, whereas the larger tumors underwent degenerative changes, which include cyst formation, calcification, hemorrhage, hyalinization, and xanthomatous infiltration.6,10 Vague abdominal pain was the most common symptom, but patients were often asymptomatic. Symptoms such as back pain, anorexia, vomiting, weight loss, jaundice, and gastrointestinal bleeding have also been reported.6,11-14 A clinical examination revealed tenderness in the upper abdomen and a mass in larger cysts.8 Transabdominal ultrasound examination is not very reliable, and it can miss small pancreatic lesions11 because of the overlaying bowel. A contrast-enhanced CT scan with fine slices is often the initial study of choice for a pancreatic lesion. Computed tomography findings are typically similar to nonpancreatic schwannomas, which demonstrate well-defined and hypodense tumors with encapsulation and cystic degeneration.15 The most characteristic CT findings of benign pancreatic schwannomas were well-defined round masses with multiple, lowattenuation cystic necrotic areas.8 Degenerative changes with cyst formation cause a diagnostic dilemma because of the difficulty in differentiating from the spectrum of cystic pancreatic

FIGURE 4. Positive S-100 immunostaining confirming schwannoma.

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lesions, which include pancreatic pseudocysts, neuroendocrine tumors, cystadenoma, cystadenocarcinoma, intraductal papillary mucinous tumor, lymphangiomas, von Hipple-Lindau disease, and hydatid cysts.6,7,16,17 MRI in schwannomas shows typical encapsulation, hypointensity on T1-weighted images, and hyperintensity on T2weighted image, which helps in differentiating it from adenocarcinomas.6,11,15,18 Based on CT scan and MRI, it is difficult to distinguish benign from malignant lesions; however, faster growth, invasion of surrounding tissues, marked contrast enhancement, irregular contours, and vascular thrombosis are considered as indicators of malignancy.17 An endoscopic ultrasound (EUS) is helpful in the evaluation of pancreatic and peripancreatic masses found on CT scan, in terms of the involvement of surrounding structures and also in guiding for fine-needle aspiration cytology (FNAC).19 An accurate preoperative diagnosis of a pancreatic schwannoma is very difficult if patients have no history of Recklinghausen disease.8 A definitive diagnosis is typically made at the time of laparotomy after frozen section biopsy.6 Having a diagnosis preoperatively/intraoperatively has a big influence in planning the correct operative management. Fasanella et al20 reported a case in which a laparoscopic enucleation was planned after having a preoperative EUS-guided FNAC confirming benign schwannoma in a 4-cm cystic lesion in the uncinate process.20 EUS-guided or CT-guided FNAC can be obtained from the cyst preoperatively and FNAC under vision can also be performed intraoperatively.2,6 A new technique of EUS-guided fine-needle tissue aspiration (FNTA) using high negative suction pressure has been described, which helped in the diagnosis of gastric schwannoma that was missed on routine EUS-guided FNAC evaluation.21 Schwannomas are composed of Schwann cells with a variable amount of reticulin fibers, and they do not contain any nerve tissue or collagen.17 Histologically, a typical schwannoma is composed of 2 areas, namely the Antoni A and Antoni B areas. The Antoni A area is hypercellular and characterized by closely packed spindle cells with occasional nuclear palisading and Verocay bodies, whereas the Antoni B area is hypocellular with degenerative changes and is occupied by loosely arranged tumor cells, which are separated by abundant myxoid stroma. On CT scan, the schwannoma with a predominantly Antoni A pattern usually shows a solid enhancing mass, whereas one with a prevalence of the Antoni B pattern often shows a cystic appearance.11,17 Cytologically, a schwannoma is characteristically composed of spindle-shaped cells, which possess indistinct cytoplasmic borders and wavy nuclei embedded in a fibrillary and occasionally myxoid or collagenous matrix. An Antoni A area (cohesive cellular clusters) and an Antoni B area (loosely cohesive or poorly cellular sheets) are occasionally found. Immunohistochemical staining for S100 helps in confirmation of diagnosis.2,4,22 170

The cytologic features of other common cystic lesions of pancreas are as follows: 1. Mucinous cystic neoplasms are mucus-producing columnar cells arranged in sheets or a papillary structure within a prominent mucinous background.23 2. Serous cystic neoplasms include hypocellular materials with nonmucinous cuboidal cells that possess bland nuclei and pale cytoplasm.24 3. Pseudocysts contain little or no epithelial cells and a predominance of histiocytes and inflammatory cells.24 Immunohistochemically, schwannomas are strongly positive for S-100 protein and are also positive for vimentin and CD56. Leu-7 (CD57) and glial fibrillary acidic protein are occasionally expressed. Schwannomas are negative for other tumor markers, such as cytokeratin AE1/AE3, desmin, smooth-muscle myosin, CD34, and CD117.1,2,4,25 Neurofibromas that are also associated with von Recklinghausen disease can develop as a solid mass or a cystic lesion but histologically do not have the Antoni A and B architecture and have a less uniform staining for S-100.1 Although malignant pancreatic schwannoma have been described in literature in 3 cases,9,12-14 the accuracy of such diagnosis is doubted because of the absence of immunohistochemical confirmation. They could also represent misdiagnosed degenerated malignant neurofibromas.26 Walsh and Bradspigel12 described a case of pancreatic schwannoma eroding into the bowel wall and presenting with gastrointestinal bleed that mimicked a recurrently bleeding duodenal ulcer. Todd et al27 described a case in which a 12-cm solid/cystic mass was noted that developed from the head of the pancreas on CT scan, but on laparotomy, this mass was free from the pancreas, and histologically, it was a schwannoma. Schwannomas have been reported in the remnant choledochal cyst28 and in the lesser sac.29 A review of the treatment in 37 cases revealed that the most commonly performed operation was distal pancreatectomy (10/37) and Whipple procedure (9/37). These procedures were generally performed in larger tumors that involved the ampulla of Vater or tumors that were difficult to separate from the portal vein and superior mesenteric vessels. Because the malignant transformation of pancreatic schwannomas is uncommon and recurrence of pancreatic schwannoma is rare and has not been documented, simple enucleation is usually sufficient and ideal in smaller tumors. Six patients underwent enucleation, which included a tumor that measured 3.0 ⫻ 3.5 ⫻ 4.0 cm.20 No resection was performed in 3 patients, and the operative details for 9 patients were not available. The involvement of surrounding structures like splenic vein,1,6 portal vein,27,30 and superior mesenteric artery (SMA)6,27 has been reported. Because of the benign nature of the tumor and positive response of radiotherapy on schwannoma, radiotherapy was attempted in 1 case of pancreatic schwannoma in which the tumor was encasing the portal vein confluence and SMA. However, the role of radiation therapy in the management of pancreatic schwannomas is still unclear.6 Follow-up of 3– 48

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TABLE 1. Summary of Cases with Pancreatic Schwannoma

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

Year

Author

Sex

Age

Size (cm)

Location

Treatment

Follow-up (months)

2008 2008 2008 2008 2007 2007 2006 2005 2005 2005 2004 2004 2004 2004 2003 2001 2001 2001 1999 1998 1998 1998 1997 1997 1995 1995 1995 1995 1994 1993 1993 1992 1992 1990 1990 1989 1987 1982

Current case Tafe and Suriawinata31 Hirabayahsi et al2 Okuma et al32 Fasanella et al20 Di Benedetto et al1 Yu and Sun8 Novellas et al18 Wu et al11 Soumaoro et al33 Bui et al6 Von Dobschuetz et al30 Akiyoshi et al34 Paranjape et al26 Tan et al16 Almo and Traverso35 Almo and Traverso35 Lee et al3 Morita et al25 Brown et al36 Brown et al36 Hsiao et al37 Feldman et al15 Feldman et al15 Ferrozzi et al17 Ferrozzi et al17 Ferrozzi et al17 Sugiyama et al19 Steven et al38 Melato et al39 David and Barkin40 Urban et al7 Burd et al10 Liessi et al41 Coombs9 Walsh and Brandspigel12 Eggermont et al14 Móller Pederson et al13

F M M F M M M F M F F F F F M F M F F M M F M F M M F M M M M F M F F F F M

56 46 51 71 36 42 72 46 71 64 69 55 67 77 46 73 47 63 50 52 69 70 63 54 47 63 68 41 59 87 46 56 73 75 74 35 40 60

8.3 11.0 6.0 N/A 4.0 2.5 1.0 3.0 1.5 2.5 5.0 8.0 5.0 3.5 2.2 3.0 5.5 10 9.5 5.5 6.0 18.0 2.5 2.0 3.5 N/A N/A 1.5 4.0 20.0 6.0 4.0 2.0 7.0 7.0 N/A 10.0 20.0

Head/body Body/tail Tail Body Uncinate Body Head/body Head Head Head Head Head Head Head Head Head Head Tail Body Body Head Body/tail Body Uncinate Body Body Head/body Uncinate Uncinate Body/tail Uncinate Body Body/tail Head Head Head Head Head/body

Whipple DP DP DP Enucleation DP N/A Whipple Enucleation Enucleation Not resected Whipple Whipple Enucleation Whipple Whipple Whipple DP DP N/A Whipple N/A Enucleation Enucleation DP N/A N/A N/A DP N/A DP DP N/A Not resected N/A Whipple Whipple Not resected

— N/A N/A N/A N/A N/A N/A 24 10 24 N/A 10 43 3 N/A 17 14 6 N/A N/A N/A 24 N/A 20 48 N/A 6 NA 10 N/A N/A N/A N/A 7 N/A 24 9 4

DP, distal pancreatectomy; N/A, not available.

months has been documented in 18 patients, and the follow-up details in the remaining 19 patients were not mentioned. (See Table 1.31-41) In conclusion, we present a case of an 8-cm pancreatic schwannoma characterized by cystic degeneration, which was asymptomatic and was diagnosed incidentally while an examination was performed for an ovarian teratoma. Although pancreatic schwannoma is a rare benign disease, it should be included in the list of differential diagnoses of pancreatic mass with cystic changes. Attempts should be made to obtain preoperative diagnosis with EUS-guided FNAC. Improvement is needed in the techniques used to obtain FNAC/FNTA from the pancreas. Immunohistochemical staining should be performed on fine-needle aspirated samples when schwannoma is suspected. A simple enucleation is usually adequate and should be aimed for whenever possible. Results from longer follow-up studies are needed in pancreatic schwannoma.

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