Cystic schwannoma of the pancreas

RADIOLOGIC-PATHOLOGIC CORRELATIONS

Cystic Schwannoma of the Pancreas Guangming Tan, MD, Kenneth Vitellas, MD, Carl Morrison, MD, and Wendy L. Frankel, MD Intrapancreatic schwannoma is a rare neoplasm. We report a case of a 46-year-old man with a cystic schwannoma in the head of the pancreas. This tumor, based on clinical manifestations and radiologic features, was initially suspected to be a cystic mucinous tumor of the pancreas or a pseudocyst. Histologically, the tumor was a typical schwannoma with cyst formation caused by degenerative changes. Immunostaining showed the tumor cells to be strongly and diffusely positive for S-100 protein, vimentin, and CD56, and negative for cytokeratin AE1/AE3, desmin, smooth muscle myosin specific, CD34, and CD117, which support the diagnosis of schwannoma. Cystic schwannoma is a rare neoplasm occurring in the pancreas and should be considered in the differential diagnoses for patients presenting with pancreatic cystic lesions. Ann Diagn Pathol 7: 285-291, 2003. © 2003 Elsevier Inc. All rights reserved. Index Words: Schwannoma, pancreas, pancreatic cystic tumor

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CHWANNOMA of the pancreas is an extremely rare lesion and only 20 cases have been previously described in the English literature.1-16 Intrapancreatic schwannomas have been reported to show degenerative changes, including cyst formation, calcification, hemorrhage, hyalinization, and xanthomatous infiltration.1 Based only on clinical manifestations and radiologic features, a preoperative diagnosis of schwannoma in the pancreatic area is difficult. A wide range of diagnostic possibilities exists for cystic lesions in this location including pseudocyst, cystadenoma and cystadenocarcinoma, lymphangiomas, or other pancreatic cystic tumors.2,3 The present case of an intrapancreatic schwannoma mimicking a pancreatic cystic tumor highlights the importance of considering this entity in the differential diagnosis of cystic lesions of the pancreas.

From the Departments of Pathology and Radiology, The Ohio State University Medical Center, Columbus, OH. This work was completed while Dr G. Tan was a Visiting International Fellow in Surgical Pathology at the Ohio State University Medical Center. Address reprint requests to Wendy L. Frankel, MD, Department of Surgical Pathology, The Ohio State University Medical Center, 401E Doan Hall, 410 W 10th Ave, Columbus OH 43210. © 2003 Elsevier Inc. All rights reserved. 1092-9134/03/0705-0004$30.00/0 doi:10.1053/S1092-9134(03)00082-0

Case Report A 46-year-old man was admitted to the hospital with a 1-year history of right upper quadrant pain and discomfort that was becoming progressively worse. He did not complain of weight loss, decreased appetite, or abdominal trauma. His past medical history, physical examination, and laboratory values were unremarkable. Radiologic Findings He underwent an abdominal computed tomography and was found to have a low-density lesion in the head of the pancreas measuring 3.3 ⫻ 3.7 cm in diameter. The mass had mixed cystic and solid components (Fig 1). There was no dilatation of the common bile duct or the pancreatic duct. The mass was well-delineated and did not appear to involve any of the vasculature including the portal vein and superior mesenteric vessels. Possible cholelithiasis was identified. The liver, spleen, adrenal glands, and left kidney were all unremarkable in appearance. There were a few less than 1-centimeter cortical cysts in the right kidney. The gastrointestinal tract was partially opacified with enteric contrast and was normal in caliber without evidence of obstruction or inflammatory lesions. It was felt that the neoplasm was a resectable pancreatic tumor and was most likely a mucinous cystadenoma or mucinous cystadenocarcinoma. The differential diagnosis also included chronic pseudocyst.

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Figure 1. Contrast-enhanced computed tomography shows a large, heterogeneous cystic mass of the pancreatic head (arrow).

Surgical Procedure At laparotomy, a mass was identified in the head of the pancreas without extrapancreatic extension or vascular involvement. The patient was also noted to have a total aberrant common hepatic artery with aberrant right and left hepatic branches. There was no lymphadenopathy in the base of the mesentery, no peritoneal studding, and no liver lesions. A pancreaticoduodenectomy and cholecystectomy were performed and the pancreas, duodenum, and gallbladder were submitted to pathology. Pathologic Findings The specimen consisted of gallbladder, a segment of duodenum, and the entire pancreas. The segment of duodenum measured 19 cm in length ⫻ 5 cm in maximum circumference. The mucosal surface was unremarkable except for a prominence of the ampulla of Vater, which appeared to be obstructed by the pancreatic mass. The attached segment of pancreas measured 5.5 ⫻ 4.5 ⫻ 3.0 cm and the outer surface was tan-pink and lobulated. In the head of the pancreas, a firm mass was easily palpable. Cut section revealed a 2.2 ⫻ 2.0 ⫻ 2.0 cm well-circumscribed, encapsulated cystic mass with focal areas of degenerative change that extended to within 1 mm of the near-

est soft tissue margin (Fig 2). The surrounding uninvolved pancreatic parenchyma was unremarkable. A few lymph nodes were identified in the surrounding soft tissue, the largest of which measured 2 cm in maximum dimension. The mucosal and serosa of gallbladder were unremarkable and no gallstones were identified. The cystic duct was patent. Microscopically, the tumor was surrounded by thick fibrous tissue and normal pancreatic parenchyma (Fig 3). The peripheral portion of the mass was partially solid and composed of sheets of spindle cells arranged in short bundles or fascicles. The cytoplasm was eosinophilic and fibrillar, and the nuclei were elongated and twisted with single, small, round nucleoli. Mitotic figures were absent. Interlacing fascicles of spindle cells showed foci of palisading arrangement of the nuclei (Verocay body) (Fig 4). The hypocellular areas of the tumor showed extensive degenerative changes including myxoid change, cyst formation, hemorrhage, and perivascular hyalinization (Fig 5). Immunohistochemical stains using labeled streptavidin biotin system for CD56 (1B6; Novocastra, Newcastle, UK: dilution, 1:50), S-100 (DAKO, Santa Barbara, CA: dilution, 1:3,000), and vimentin (V9; DAKO, Denmark: dilution, 1:50) were strongly and diffusely posi-

Radiologic-Pathologic Correlations

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Figure 2. Cut section of the pancreatic schwannoma shows a well-circumscribed encapsulated cystic mass with focal degenerative change.

tive (Fig 6), while stains for cytokeratin AE1/AE3 (AE1/AE3; DAKO, Carpinteria, CA: dilution, 1:100), desmin (DE-R-11; DAKO, Denmark: dilution, 1:15), smooth muscle myosin specific

(SMMS-1; DAKO, Carpinteria, CA: dilution, 1:300), CD34 (QBEND10; Immunotech, Marseille Cedex, France: dilution, 1:300), and CD117 (C-kit; DAKO, Kyoto, Japan: dilution, 1:300) were negative.

Figure 3. Thick fibrous tissue and normal pancreatic parenchyma are seen adjacent to the schwannoma (arrow). (Low power magnification.)

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Figure 4. Interlacing fascicles of spindle cells show foci of palisading arrangement of the nuclei. (Medium power magnification.)

The tumor was diagnosed as intrapancreatic schwannoma with cystic change. No evidence of carcinoma or mucinous cystic neoplasm was identified in the specimen.

Figure 5. Areas of the schwannoma show cyst formation. (Medium power magnification.)

Discussion Schwannomas are derived from Schwann’s cells, the lining cells of the nerve sheath. These tumors most commonly occur in the flexor surfaces of the

Radiologic-Pathologic Correlations

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Figure 6. The tumor cells are immunoreactive for S-100 protein. (High power magnification.)

extremities, neck, mediastinum, retroperitoneum, posterior spinal roots, and cerebellopontine angle.9 Rarely, schwannoma can involve the abdomen (eg, the stomach, small bowel, liver, appendix, large bowel, lesser sac, and fallopian tube).5 Pancreatic schwannomas are felt to arise from either autonomic sympathetic or parasympathetic fibers, both of which course through the pancreas via the vagus nerve.5 There have been only 20 cases of intrapancreatic schwannoma previously reported in the English literature.1-16 Schwannoma of the pancreas is, in general, a tumor of older adults with a nearly equal ratio of men to women.2 The tumors can vary considerably in size, from 1.5 to 20.0 cm in maximum diameter. The majority of tumors are located in the body and head of the pancreas, but a few have presented in the tail (Table 1).2 The computed tomography findings of nonpancreatic schwannomas have been well-described. These tumors are usually of low computed tomography attenuation (0 to 30 HU). The lower-density lesions may be homogeneous or mottled in appearance. These low-density areas result from a combination of factors, including low cellularity and cystic degeneration.5 The radiologic features of cystic intrapancreatic schwannoma correlate well with that of nonpancreatic schwannoma. However, cys-

tic schwannoma of the pancreas is frequently mistaken for other cystic pancreatic lesions, such as cystadenoma, cystadenocarcinoma, intraductal papillary mucinous tumor, and pseudocyst complicating pancreatitis, most likely caused by the lack of awareness of intrapancreatic schwannoma. Other cystic pancreatic neoplasms that may be clinically confused with cystic pancreatic schwannoma include solid and pseudo-papillary tumor of the pancreas, neuroendocrine tumor, and lymphangiomas.5 Histologically, two different patterns, designated as Antoni A and B, can be found in varying proportions in schwannoma. Antoni A areas are cellular, composed of spindle cells often arranged in a palisading fashion or in an organoid arrangement (Verocay body). Mitotic figures are usually absent or extremely scant. Antoni B areas are relatively hypocellular and usually show degenerative changes such as myxoid change, cyst formation, stromal hemorrhage, and calcification. Most cells in a schwannoma express consistent and intense immunoreactivity for S-100 protein. These typical features of schwannoma have been documented in most of the reported cases of pancreatic schwannoma, and most have been reported to show little cellular pleomorphism or mitotic activity. On occasion, marked atypia can be seen in so-called ancient

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Table 1. Reported Cases of Schwannoma of the Pancreas

Case

1

19 20

Gender

Age (yrs)

Lee et al1

2001

F

63

Brown et al2 Brown et al2 Hsiao et al3 Feldman et al8 Feldman et al8 Todd et al9 Ferrozzi et al10 Ferrozzi et al10 Ferrozzi et al10 Sugiyama et al11 Steven et al12 Melato et al13 David et al14 Urban et al5 Burd et al7 Coombs RJ15 Walsh & Brandspigel16 Eggermont et al6 Moller Pederson et al4

1998 1998 1998 1997 1997 1997 1995 1995 1995 1995 1994 1993 1993 1992 1992 1990 1989

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

52 69 70 63 54 46 47 63 68 41 59 87 46 56 73 74 35

1987 1982

F M

40 60

* With von Recklinghausen’s neurofibromatosis. Abbreviations: A/W, alive and well; N/A, not available.

Size (cm)

10 5.5 6.0 17 2.5 2.0 12 3.5 N/A N/A 1.5 4 20 6⫻5 3⫻4 2 7 N/A 10 15-20

Location

Gross

Histology

Tail

Cystic

Benign

Body Head Body/tail Body Uncinate Head Body Body Body/head Uncinate Uncinate Body/tail Uncinate Body Body Head Head

Cystic Cystic Cystic Solid N/A Solid/cystic Inhomogeneous Cystic Cystic Cystic Solid Cystic Partially cystic Cystic Solid Necrotic center N/A

Head Body/head

Central necrosis Cystic

Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Benign Malignant Invading duodenum Malignant Malignant

Treatment

Follow-Up (mo)

Distal pancreatectomy with splenectomy Resection Whipple’s procedure Resection Resection (Enucleation) Resection (Enucleation) Excision Partial pancreatectomy Pancreatectomy N/A N/A Whipple Distal pancreatectomy Resection Distal pancreatectomy N/A Excision Whipple

A/W (6) N/A N/A A/W N/A A/W N/A A/W N/A A/W N/A A/W N/A N/A N/A N/A N/A A/W

Whipple Unresectable

A/W (9) A/W (4)

(24) (20) (48) (6) (10)

(2)

Tan et al

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17* 18*

Year

Study

Radiologic-Pathologic Correlations

schwannoma and are of no clinical significance. In general, the diagnosis of intrapancreatic schwannoma is usually straightforward after routine histologic examination. Malignant transformation of schwannoma is an exceptionally rare event in contrast to neurofibroma. However, four malignant pancreatic schwannomas have been reported.4,6,15,16 Two malignant cases occurred in patients with von Recklinghausen’s neurofibromatosis.15,16Unlike neurofibromas, in which supervening malignancy resembles a spindle cell sarcoma, malignancy in schwannomas usually has an epithelioid appearance.18 This epithelioid appearance may suggest the possibility of a metastatic carcinoma. Cytokeratin positivity and S-100 negativity together with the lack of classic Antoni A or Antoni B features help to distinguish carcinoma from schwannoma. Cellular schwannoma are defined as highly cellular schwannomas that are exclusively composed of Antoni A areas without the presence of Verocay bodies.17 A cellular schwannoma may be difficult to distinguish from malignant schwannoma. However, cellular schwannoma usually lacks atypia in the mitotically active areas, may have small Antoni B areas, and has more consistent S-100 protein expression than malignant schwannoma.19 The distinction between malignant schwannoma and leiomyosarcoma may be difficult on hematoxylin-eosin–stained sections, especially when the leiomyosarcoma shows nuclear palisading. However, S-100 protein immunostaining is seldom observed in leiomyosarcoma. A Masson trichrome stain may be helpful in leiomyosarcoma to document the presence or absence of longitudinal striations.18 The differential diagnosis of pancreatic schwannoma also includes leiomyoma, gastrointestinal stromal tumor, and solitary fibrous tumor when the cellular area is predominant in the tumor. Immunohistochemical reactivity for S-100 protein and lack of staining for myogenic markers, CD117 (C-kit), and CD34 are helpful for confirming the diagnosis. In summary, based on clinical and radiologic features, the differential diagnosis of pancreatic cystic lesions is broad. Definitive diagnosis of cystic schwannoma of the pancreas can only be established by histopathologic examination. It is suggested that cystic schwannoma of the pancreas

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should be considered in patients presenting with pancreatic cystic lesions. Reference 1. Lee JS, Kim HS, Jung JJ, et al: Ancient schwannoma of the pancreas mimicking a cystic tumor. Virchows Arch 2001;439: 697-699 2. Brown SZ, Owen DA, O’Connell JX, et al: Schwannoma of the pancreas: A report of two cases and a review of the literature. Mod Pathol 1998;11:1178-1182 3. Hsiao WC, Lin PW, Chang KC: Benign retroperitoneal schwannoma mimicking a pancreatic cystic tumor: Case report and literature review. Hepatogastroenterology 1998;45:24182420 4. Moller Pedersen V, Hede A, Graem N: A solitary malignant schwannoma mimicking a pancreatic pseudocyst: A case report. Acta Chir Scand 1982;148:697-698 5. Urban BA, Fishman EK, Hruban RH, et al: CT findings in cystic schwannoma of the pancreas. J Comput Assist Tomogr 1992;16:492-493 6. Eggermont A, Vuzevski V, Huisman M, et al: Solitary malignant schwannoma of the pancreas: Report of a case and ultrastructural examination. J Surg Oncol 1987;36:21-25 7. Burd DA, Tyagi G, Bader DA: Benign schwannoma of the pancreas. AJR Am J Roentgenol 1992;159:675 8. Feldman L, Philpotts LE, Reinhold C, et al: Pancreatic schwannoma: Report of two cases and review of the literature. Pancreas 1997;15:99-105 9. Todd KE, Lewis MPN, Gloor B, et al: Management decisions for unusual periampullary tumors. Am Surg 1997;63:927-932 10. Ferrozzi F, Bova D, Garlaschi G: Pancreatic schwannoma: Report of three cases. Clin Radiol 1995;50:492-495 11. Sugiyama M, Kimura W, Kuroda A, et al: Schwannoma arising from peripancreatic nerve plexus. AJR Am J Roentgenol 1995;164:232 12. Steven K, Burcharth F, Holm N, et al: Single stage pancreaticoduodenectomy (Whipple’s procedure), radical cystectomy and bladder substitution with the urethral kock reservoir. Scand J Urol Nephrol 1994;28:199-200 13. Melato M, Bucconi S, Marus W, et al: The schwannoma: An uncommon type of cystic lesion of the pancreas. Ital J Gastroenterol 1993;25:385-387 14. David S, Barkin JS: Pancreatic schwannoma. Pancreas 1993;8:274-276 15. Coombs RJ: Case of the season. Semin Roentgenol 1990; 2:127-129 16. Walsh MM, Brandspigel K: Gastrointestinal bleeding duo to pancreatic schwannoma complicating von Recklinghausen’s disease. Gastroenterol 1989;97:1550-1551 17. Rosai J: Soft tissues, in Rosai J (ed): Ackerman’s Surgical Pathology (ed 8; vol 2). St Louis, MO, Mosby-Year Book, 1996, pp 2042-2049 18. Weiss SW, Goldblum JR: Benign tumors of peripheral nerves, in Weiss SW, Goldblum JR (eds): Enzinger and Weiss’s Soft Tissue Tumors (ed 4). St Louis, MO, Mosby, 2001, pp 1146-1167 19. Weiss LM: Soft tissues, in Weidner N, Cote RJ, Suster S, et al (eds): Modern Surgical Pathology (vol 2). Philadelphia, PA, Saunders, 2003, pp 1833-1836