CASE REPORTS IN GI ONCOLOGY
Benign Schwannoma Masquerading as a Malignant Metastatic Lesion in a Patient With Renal Cell Carcinoma Santhosh Sadashiv,1 Georgios Deftereos,2 Eli Pakravan,3 Jan F. Silverman,2 Shifeng Mao1 Division of Hematology Oncology 2 Department of Pathology 3 Department of Radiology Allegheny General Hospital Allegheny Health Network Pittsburgh, PA
1
© 2014 by International Society of Gastrointestinal Oncology
CASE REPORT A 51-year-old Caucasian male with no significant past medical history presented with complaints of dull abdominal pain in the right upper quadrant of approximately 3 months’ duration. A liver function test was normal. An ultrasound of the abdomen revealed a 4.0-cm hypoechoeic mass between the gall bladder neck and the main portal vein and an additional finding of a 5.4-cm echogenic irregular mass in the lower pole of the left kidney. Follow-up computerized tomography (CT) (Figure 1a) confirmed the presence of a hetergenous mass in the porta hepatis and a 5.2 cm ⫻ 5 cm ⫻ 4.9 cm enhancing left renal mass suspicious for renal cell carcinoma with no evidence of renal vein or inferior vena cava extension. His lab parameters, namely, comprehensive metabolic panel, complete blood count, and urine analysis, were normal. The patient then underwent a successful radical nephrectomy of the left kidney. Pathology revealed papillary carcinoma type 1, nuclear grade 2, without vascular invasion and negative margins. To investigate his porta hepatis mass he underwent magnetic resonance imaging (MRI) and a positron emission tomography (PET) scan. MRI (Figure 1b) of the abdomen demonstrated a 3.9 cm ⫻ 1.9 cm mass in the porta hepatis encasing the cystic duct and the common bile duct with minimal biliary dilatation, which suggested malignant lymphadenopathy. A PET scan (Figure 1c) showed a hypermetabolic mass in the porta hepatis region with a standardized uptake value (SUV) of 8.5 units, suggestive of metastatic disease. There was no additional finding suggestive of metastatic disease elsewhere. To further investigate the porta hepatic mass, the patient underwent an endoscopic retrograde cholangiopancreatography with endoscopic ultrasound (EUS). No intraductal lesion in the biliary, cystic, or hepatic ducts was identified. A tissue sample from an EUS-guided biopsy of the mass was deemed inadequate by pathology for a definitive diagnosis. As he had no other sites suspicious for metastatic disease on clinical and radiological exams, surgical resection of the porta hepatic mass was recommended after discussion in a multidisciplinary liver conference. Intraoperatively, a rubbery mass was identified posterior to the gall bladder without involving the liver parenchyma. After manually separating the mass from the hepatic artery and portal vein, it was resected and removed enbloc along with gall bladder. Pathological examination of the mass described a spindle cell neoplasm with elongated and compact cells (Antoni A) alternating with loosely May–August 2014
disposed round cells (Antoni B) (Figure 2a). Immunohistochemical (IHC) staining was strongly positive for S-100 and negative for CD34, CD 117, and DOG-1(Figure 2b, 2c). The MIB-1 stain was low at 10%. Final pathological diagnosis was schwannoma. The patient’s postoperative recovery was uneventful. He remains free of tumor recurrence with more than two years of follow-up.
DISCUSSSION Benign schwannomas are encapsulated nerve sheath tumors arising from Schwann cells. They are also known as neurilemomas, neurinomas, and perineural fibroblastomas. They are usually slow growing and may occur at any age, but reach a peak between the third and sixth decade and have no predilection to either sex or race.1 The vast majority of schwannomas tend to occur as a sporadic single lesion. Multiple schwannomas may occur as part of neurofibromatosis type 2, schwannomatosis, and Carney complex and as part of a syndrome with nevi and vaginal leiomyomas.2 Schwannomas do not occur in neurofibromatosis type 1. Schwannomas occur most frequently in the peripheral nerves of head, neck, and flexor surfaces of the extremities. Deep-seated tumors may occur in the mediastinum but are seldom seen in the retroperitoneum and extremely rare to occur in the mesentery and porta hepatis region.1,3 Our literature search resulted in only four reported cases of a benign schwannoma involving the porta hepatis.4–7 We believe ours is the first case where schwannnoma was identified concurrently with an active underlying malignancy. Signs and symptoms vary depending on the anatomic site and size of the neoplasm. Most schwannomas present as an asymptomatic or painless mass or as an incidental finding on a radiological examination.1 Malignant transformation can occur but is exceedingly uncommon.8 Histologically schwannomas exhibit biphasic architecture of Antoni A (dense) and Antoni B (loose) patterns, nuclear palisading (Verocay bodies) and a fibrous capsule containing the nerve.9 Neoplastic Schwann cells typically display spindle-shaped nuclei. Based on histology, four types of schwannomas have been observed:10 cellular, glandular, epitheloid, and ancient schwannomas. The cellular type contains predominantly Antoni A areas without verocay bodies. Epitheloid and glandular types are composed of cells corresponding to their names. Ancient schwanomas show bizarre hyperchromatic nuclei with degenerative changes such as www.myGCRonline.org
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Case Reports in GI Oncology
Figure 1. (a) CT of abdomen pelvis with contrast: heterogeneously enhancing mass in porta hepatis (red arrow). (b) MRI of abdomen, T2-weighted images: T2 intense mass at level of cystic duct and extending into porta hepatis encasing the cystic duct and common bile duct (red arrow). (c) PET with IV F-18 fluorodeoxyglucose: FDG uptake involving the porta hepatis, with maximum SUV of 8.5, corresponding to mass seen on CT and MRI (red arrow).
Figure 2. (a) Areas of elongated and compact cells (Antoni A, red arrow), alternating with areas composed of loosely disposed spindle cells (Antoni B, blue arrow). (b) Mass staining negative for CD117. (c) Mass staining strongly positive for S100 on IHC.
cyst formation, hemorrhage, calcification, and hyalinization. The presence of a capsule, two types of Antoni areas, and evenly intense immunostaining for S-100 protein differentiate schwannomas from neurofibromas. A schwannoma can also stain positive for glial fibrillary acidic protein and CD 57 (Leu 7) and negative for CD 34, DOG-1 and CD 117, distinguishing it from some gastrointestinal tumors that might sometime stain positive for S-100.11,12 The radiologic appearance of schwannoma may vary based on the distribution of the different histologies (Antoni A and Antoni B areas) and the presence or absence of underlying cystic degeneration, calcification, and hemorrhage. Most often, schwannomas appear as a well-defined mass with smooth margins and are relatively heterogeneous on CT and MR images.13,14 On MR imaging, they are usually hypointense on T1-weighted images and inhomogenously hyperintense on T2-weighted images corresponding to the alternating Antoni A and Antoni B areas. Cystic degeneration may appear as a central hyperintense signal on T2-weighted images. However, no specific MRI findings are characteristic of schwannomas.15 On PET scans, schwannomas show hypermetabolic uptake and hence may be mistaken for either primary malignant or metastatic lesions.16 Given its rarity, nonspecific radiological characteristics, and avid fluorodeoxyglucose (FDG) uptake on the PET scan, a preoperative diagnosis of schwannoma is hardly ever made. Most often surgical excision remains the mainstay in treatment. Disease recurrence is uncommon even after partial resection. Extended or incomplete excision can also be considered in cases where permanent nerve damage is likely to occur or when there are anatomical and technical challenges for a complete resection.1,17
CONCLUSION With advances in radiological modalities, oncologists frequently rely on radiological data not only to guide their diagnostic, staging, and management strategies, but also as a prognostic indicator. PET is currently considered as the most sensitive and specific tool in this regard.18 In addition to other described limitations, benign tumors
124
Gastrointestinal Cancer Research
on rare occasions have been misread as a malignant lesion, and this represents one of the pitfalls in the interpretation of PET.18 This can have a tremendous impact on both treatment recommendations and on patients’ emotional well-being. Our case report highlights these complexities and understanding that a benign tumor like a schwannoma can have increased FDG uptake and appear as a hyper-metabolic lesion on a PET scan. As rare as a schwannoma might be, it still needs to be considered in the differential diagnosis when performing PET during workup of a malignant neoplasm. This case report also illustrates the importance and advantages of a multidisciplinary team approach in cancer management.
REFERENCES 1. Enzinger FM, Weiss SW: Benign tumors of peripheral nerves. In: Soft tissue tumors (3rd ed). St. Louis, MO: Mosby, 829 – 842, 1995 2. MacCollin M, Chiocca EA, Evans DG, et al: Diagnostic criteria for schwannomatosis. Neurology 64:1838 –1845, 2005 3. Ogose A, Hotta T, Morita T, et al: Tumors of peripheral nerves: correlation of symptoms, clinical signs, imaging features, and histologic diagnosis. Skeletal Radiol 28:183–188, 1999 4. Park MK, Lee KT, Choi YS, et al: A case of benign schwannoma in the porta hepats. Korean J Gastroenterol 47:164 –167, 2006 5. Panait L, Learn P, Dimaio C, et al: Resection of perihilar biliary schwannoma. Surg Oncol 20:e157–159, 2011 6. Kulkarni N, Andrews SJ, Rao V, et al: Case report: benign porta helatic schwannoma. Indian J Radiol Imaging 19:213–215, 2009 7. Choi H, Whitman G, Ro J, et al: Benign schwannoma in the porta hepatic. Am J Roentgenol 177:213– 652, 2001 8. Das Gupta TK, Brasfield RD: Solitary malignant schwannoma (neurilemmoma). Cancer 24:213–355, 1964 9. Skovronsky DM, Oberholtzer JC: Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am 15:213–157, 2004 10. Rosai J, editor. Ackerman’s surgical pathology (8th ed). St. Louis, MO: Mosby, 1995 11. Daimaru Y, Kido H, Hashimoto H, et al: Benign schwannomas of the gastrointestinal tract; a clinicopathologic and immunohistochemical study. Hum Pathol 19:257–264, 1988 12. Miettinen M, Lasota J: Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis and differential diagnosis. Arch Pathol Lab Med 130:1466 –1478, 2006
Volume 7 • Issue 3– 4
Case Reports in GI Oncology
13. Cohen LM, Schwartz AN, Rockoff SD: Benign schwannomas: pathologic basis for CT inhomogeneities. Am J Roentgenol 147:141–143, 1986
18. Cook GJ: Pitfalls in PET/CT interpretation. Q J Nucl Med Mol Imag 51:235– 243, 2007
14. Varma DGK, Moulopoulos A, Sara AS, et al: MR imaging of extracranial nerve sheath tumors. J Comput Assist Tomogr 16:448 – 453, 1992 15. Hayasaka K, Tanaka Y, Hupper S, et al: MR findings in primary retroperitoneal schwannoma. Acta Radiol 40:78 – 82, 1999 16. Beaulieu S, Rubin B, Djang D, et al: Positron emission tomography of schwannomas: emphasizing its potential in preoperative planning. Am J Roentgenol 182:971–974, 2004 17. Kim DH, Murovic JA, Tiel RL, et al: Operative outcomes of 546 Louisiana State University Health Sciences Center peripheral nerve tumors. Neurosurg Clin N Am 15:971–177, 2004
May–August 2014
Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Address correspondence to: Santhosh Sadashiv, MD, Division of Hematology Oncology, Allegheny Health Network, 320 E North Ave, Pittsburgh, PA 15212. Phone: 412-359-8353; Fax: 412-359-2198; E-mail: SSADASHI@ wpahs.org or Shifeng Mao, MD; E-mail: [email protected]
www.myGCRonline.org
125
Benign Schwannoma Masquerading as a Malignant Metastatic Lesion in a Patient With Renal Cell Carcinoma Santhosh Sadashiv,1 Georgios Deftereos,2 Eli Pakravan,3 Jan F. Silverman,2 Shifeng Mao1 Division of Hematology Oncology 2 Department of Pathology 3 Department of Radiology Allegheny General Hospital Allegheny Health Network Pittsburgh, PA
1
© 2014 by International Society of Gastrointestinal Oncology
CASE REPORT A 51-year-old Caucasian male with no significant past medical history presented with complaints of dull abdominal pain in the right upper quadrant of approximately 3 months’ duration. A liver function test was normal. An ultrasound of the abdomen revealed a 4.0-cm hypoechoeic mass between the gall bladder neck and the main portal vein and an additional finding of a 5.4-cm echogenic irregular mass in the lower pole of the left kidney. Follow-up computerized tomography (CT) (Figure 1a) confirmed the presence of a hetergenous mass in the porta hepatis and a 5.2 cm ⫻ 5 cm ⫻ 4.9 cm enhancing left renal mass suspicious for renal cell carcinoma with no evidence of renal vein or inferior vena cava extension. His lab parameters, namely, comprehensive metabolic panel, complete blood count, and urine analysis, were normal. The patient then underwent a successful radical nephrectomy of the left kidney. Pathology revealed papillary carcinoma type 1, nuclear grade 2, without vascular invasion and negative margins. To investigate his porta hepatis mass he underwent magnetic resonance imaging (MRI) and a positron emission tomography (PET) scan. MRI (Figure 1b) of the abdomen demonstrated a 3.9 cm ⫻ 1.9 cm mass in the porta hepatis encasing the cystic duct and the common bile duct with minimal biliary dilatation, which suggested malignant lymphadenopathy. A PET scan (Figure 1c) showed a hypermetabolic mass in the porta hepatis region with a standardized uptake value (SUV) of 8.5 units, suggestive of metastatic disease. There was no additional finding suggestive of metastatic disease elsewhere. To further investigate the porta hepatic mass, the patient underwent an endoscopic retrograde cholangiopancreatography with endoscopic ultrasound (EUS). No intraductal lesion in the biliary, cystic, or hepatic ducts was identified. A tissue sample from an EUS-guided biopsy of the mass was deemed inadequate by pathology for a definitive diagnosis. As he had no other sites suspicious for metastatic disease on clinical and radiological exams, surgical resection of the porta hepatic mass was recommended after discussion in a multidisciplinary liver conference. Intraoperatively, a rubbery mass was identified posterior to the gall bladder without involving the liver parenchyma. After manually separating the mass from the hepatic artery and portal vein, it was resected and removed enbloc along with gall bladder. Pathological examination of the mass described a spindle cell neoplasm with elongated and compact cells (Antoni A) alternating with loosely May–August 2014
disposed round cells (Antoni B) (Figure 2a). Immunohistochemical (IHC) staining was strongly positive for S-100 and negative for CD34, CD 117, and DOG-1(Figure 2b, 2c). The MIB-1 stain was low at 10%. Final pathological diagnosis was schwannoma. The patient’s postoperative recovery was uneventful. He remains free of tumor recurrence with more than two years of follow-up.
DISCUSSSION Benign schwannomas are encapsulated nerve sheath tumors arising from Schwann cells. They are also known as neurilemomas, neurinomas, and perineural fibroblastomas. They are usually slow growing and may occur at any age, but reach a peak between the third and sixth decade and have no predilection to either sex or race.1 The vast majority of schwannomas tend to occur as a sporadic single lesion. Multiple schwannomas may occur as part of neurofibromatosis type 2, schwannomatosis, and Carney complex and as part of a syndrome with nevi and vaginal leiomyomas.2 Schwannomas do not occur in neurofibromatosis type 1. Schwannomas occur most frequently in the peripheral nerves of head, neck, and flexor surfaces of the extremities. Deep-seated tumors may occur in the mediastinum but are seldom seen in the retroperitoneum and extremely rare to occur in the mesentery and porta hepatis region.1,3 Our literature search resulted in only four reported cases of a benign schwannoma involving the porta hepatis.4–7 We believe ours is the first case where schwannnoma was identified concurrently with an active underlying malignancy. Signs and symptoms vary depending on the anatomic site and size of the neoplasm. Most schwannomas present as an asymptomatic or painless mass or as an incidental finding on a radiological examination.1 Malignant transformation can occur but is exceedingly uncommon.8 Histologically schwannomas exhibit biphasic architecture of Antoni A (dense) and Antoni B (loose) patterns, nuclear palisading (Verocay bodies) and a fibrous capsule containing the nerve.9 Neoplastic Schwann cells typically display spindle-shaped nuclei. Based on histology, four types of schwannomas have been observed:10 cellular, glandular, epitheloid, and ancient schwannomas. The cellular type contains predominantly Antoni A areas without verocay bodies. Epitheloid and glandular types are composed of cells corresponding to their names. Ancient schwanomas show bizarre hyperchromatic nuclei with degenerative changes such as www.myGCRonline.org
123
Case Reports in GI Oncology
Figure 1. (a) CT of abdomen pelvis with contrast: heterogeneously enhancing mass in porta hepatis (red arrow). (b) MRI of abdomen, T2-weighted images: T2 intense mass at level of cystic duct and extending into porta hepatis encasing the cystic duct and common bile duct (red arrow). (c) PET with IV F-18 fluorodeoxyglucose: FDG uptake involving the porta hepatis, with maximum SUV of 8.5, corresponding to mass seen on CT and MRI (red arrow).
Figure 2. (a) Areas of elongated and compact cells (Antoni A, red arrow), alternating with areas composed of loosely disposed spindle cells (Antoni B, blue arrow). (b) Mass staining negative for CD117. (c) Mass staining strongly positive for S100 on IHC.
cyst formation, hemorrhage, calcification, and hyalinization. The presence of a capsule, two types of Antoni areas, and evenly intense immunostaining for S-100 protein differentiate schwannomas from neurofibromas. A schwannoma can also stain positive for glial fibrillary acidic protein and CD 57 (Leu 7) and negative for CD 34, DOG-1 and CD 117, distinguishing it from some gastrointestinal tumors that might sometime stain positive for S-100.11,12 The radiologic appearance of schwannoma may vary based on the distribution of the different histologies (Antoni A and Antoni B areas) and the presence or absence of underlying cystic degeneration, calcification, and hemorrhage. Most often, schwannomas appear as a well-defined mass with smooth margins and are relatively heterogeneous on CT and MR images.13,14 On MR imaging, they are usually hypointense on T1-weighted images and inhomogenously hyperintense on T2-weighted images corresponding to the alternating Antoni A and Antoni B areas. Cystic degeneration may appear as a central hyperintense signal on T2-weighted images. However, no specific MRI findings are characteristic of schwannomas.15 On PET scans, schwannomas show hypermetabolic uptake and hence may be mistaken for either primary malignant or metastatic lesions.16 Given its rarity, nonspecific radiological characteristics, and avid fluorodeoxyglucose (FDG) uptake on the PET scan, a preoperative diagnosis of schwannoma is hardly ever made. Most often surgical excision remains the mainstay in treatment. Disease recurrence is uncommon even after partial resection. Extended or incomplete excision can also be considered in cases where permanent nerve damage is likely to occur or when there are anatomical and technical challenges for a complete resection.1,17
CONCLUSION With advances in radiological modalities, oncologists frequently rely on radiological data not only to guide their diagnostic, staging, and management strategies, but also as a prognostic indicator. PET is currently considered as the most sensitive and specific tool in this regard.18 In addition to other described limitations, benign tumors
124
Gastrointestinal Cancer Research
on rare occasions have been misread as a malignant lesion, and this represents one of the pitfalls in the interpretation of PET.18 This can have a tremendous impact on both treatment recommendations and on patients’ emotional well-being. Our case report highlights these complexities and understanding that a benign tumor like a schwannoma can have increased FDG uptake and appear as a hyper-metabolic lesion on a PET scan. As rare as a schwannoma might be, it still needs to be considered in the differential diagnosis when performing PET during workup of a malignant neoplasm. This case report also illustrates the importance and advantages of a multidisciplinary team approach in cancer management.
REFERENCES 1. Enzinger FM, Weiss SW: Benign tumors of peripheral nerves. In: Soft tissue tumors (3rd ed). St. Louis, MO: Mosby, 829 – 842, 1995 2. MacCollin M, Chiocca EA, Evans DG, et al: Diagnostic criteria for schwannomatosis. Neurology 64:1838 –1845, 2005 3. Ogose A, Hotta T, Morita T, et al: Tumors of peripheral nerves: correlation of symptoms, clinical signs, imaging features, and histologic diagnosis. Skeletal Radiol 28:183–188, 1999 4. Park MK, Lee KT, Choi YS, et al: A case of benign schwannoma in the porta hepats. Korean J Gastroenterol 47:164 –167, 2006 5. Panait L, Learn P, Dimaio C, et al: Resection of perihilar biliary schwannoma. Surg Oncol 20:e157–159, 2011 6. Kulkarni N, Andrews SJ, Rao V, et al: Case report: benign porta helatic schwannoma. Indian J Radiol Imaging 19:213–215, 2009 7. Choi H, Whitman G, Ro J, et al: Benign schwannoma in the porta hepatic. Am J Roentgenol 177:213– 652, 2001 8. Das Gupta TK, Brasfield RD: Solitary malignant schwannoma (neurilemmoma). Cancer 24:213–355, 1964 9. Skovronsky DM, Oberholtzer JC: Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am 15:213–157, 2004 10. Rosai J, editor. Ackerman’s surgical pathology (8th ed). St. Louis, MO: Mosby, 1995 11. Daimaru Y, Kido H, Hashimoto H, et al: Benign schwannomas of the gastrointestinal tract; a clinicopathologic and immunohistochemical study. Hum Pathol 19:257–264, 1988 12. Miettinen M, Lasota J: Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis and differential diagnosis. Arch Pathol Lab Med 130:1466 –1478, 2006
Volume 7 • Issue 3– 4
Case Reports in GI Oncology
13. Cohen LM, Schwartz AN, Rockoff SD: Benign schwannomas: pathologic basis for CT inhomogeneities. Am J Roentgenol 147:141–143, 1986
18. Cook GJ: Pitfalls in PET/CT interpretation. Q J Nucl Med Mol Imag 51:235– 243, 2007
14. Varma DGK, Moulopoulos A, Sara AS, et al: MR imaging of extracranial nerve sheath tumors. J Comput Assist Tomogr 16:448 – 453, 1992 15. Hayasaka K, Tanaka Y, Hupper S, et al: MR findings in primary retroperitoneal schwannoma. Acta Radiol 40:78 – 82, 1999 16. Beaulieu S, Rubin B, Djang D, et al: Positron emission tomography of schwannomas: emphasizing its potential in preoperative planning. Am J Roentgenol 182:971–974, 2004 17. Kim DH, Murovic JA, Tiel RL, et al: Operative outcomes of 546 Louisiana State University Health Sciences Center peripheral nerve tumors. Neurosurg Clin N Am 15:971–177, 2004
May–August 2014
Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Address correspondence to: Santhosh Sadashiv, MD, Division of Hematology Oncology, Allegheny Health Network, 320 E North Ave, Pittsburgh, PA 15212. Phone: 412-359-8353; Fax: 412-359-2198; E-mail: SSADASHI@ wpahs.org or Shifeng Mao, MD; E-mail: [email protected]
www.myGCRonline.org
125
