BRIEF REPORT
Cytologic Findings of Gastric Schwannoma: A Case Report Erika Rodriguez, M.D., PhD,1 Steven Tellschow, M.D.,2 David M. Steinberg, M.D.,2 and Elizabeth Montgomery, M.D.1*
Spindle cell lesions of the stomach are rare. They usually affect the submucosa or muscularis propria and therefore can be sampled by endoscopic fine needle aspiration. The most common tumor in this category is gastrointestinal stromal tumor (GIST), followed by leiomyoma and gastric schwannoma. Gastric schwannoma is a benign tumor of neuroectodermal origin that has overlapping morphologic/cytologic features with GIST and leiomyoma. Gastric schwannomas differ from peripheral schwannomas by lacking a capsule, Verocay bodies, Antoni B areas, and thick-walled vessels. They are characterized morphologically by poorly defined borders, cuffs of lymphoid tissue and a haphazard spindle cell proliferation. We present here the cytologic and histopathologic features of a gastric schwannoma. The tumor was composed of spindle cells with delicate eosinophilic cytoplasm and wavy nuclei, with an associated conspicuous lymphoid backdrop. The latter feature raised the possibility of a lymphoid lesion, a problem cytopathologists should be aware of. Diagn. Cytopathol. 2012;00:000–000. ' 2012 Wiley Periodicals, Inc. Key Words: gastric schwannoma; gastrointestinal stromal tumor; GIST; spindle cell neoplasm
Mesenchymal tumors of the stomach encompass variable putative histogenesis. The most common tumor in this category is gastrointestinal stromal tumor (GIST), followed by leiomyoma and schwannoma.1,2 Gastric schwannoma represents an important subset of benign nerve sheath tumors of the gastrointestinal tract. This tumor is more common in females, can manifest over a broad age range (29–90 years of age), and the
1
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 2 Department of Pathology, St. Luke’s Hospital and Health Network, Bethlehem, Pennsylvania *Correspondence to: Elizabeth Montgomery, MD, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. E-mail: [email protected] Received 5 March 2012; Accepted 16 July 2012 DOI 10.1002/dc.22913 Published online in Wiley Online Library (wileyonlinelibrary.com). '
2012 WILEY PERIODICALS, INC.
patients are usually asymptomatic.1,3,4 Cytologic interpretation of spindle cell lesions of the stomach can be challenging. The morphologic features of these tumors have been well described in the literature. However, the cytologic features of gastric schwannomas in particular are incompletely described, which may lead to potential diagnostic pitfalls. Herein, we describe a case of gastric schwannoma with emphasis on cytologic features, and discuss the differential diagnosis.
Case Report Clinical History The patient was a 35-year-old previously asymptomatic female with an incidental gastric mass identified during evaluation following a motor vehicle accident. A partially exophytic hyperdense lesion in the gastric muscularis propria along the greater curvature was present on CT, measuring 3.6 3 2.5 cm. Multiple surrounding nodules, interpreted as lymph nodes, were also seen. The differential diagnosis included gastric hematoma or a neoplasm. Upper endoscopic ultrasound demonstrated a heterogeneous hypoechoic mass with small anechoic foci in the muscularis propria of the gastric body and greater curvature measuring 2.1 3 2.0 cm. A fine needle aspiration was performed using a 22-gauge Wilson Cook needle.
Pathologic Findings Cytology. The smears were variably cellular. On the Diff-Quick stain, they were composed predominantly of small reactive lymphocytes. Rare sparse aggregates of loosely cohesive spindle cells with variable infiltration by lymphocytes were present (Fig. 1). On Papanicolaou stain, the smears were paucicellular, composed predominantly of lymphocytes and rare groups of loosely cohesive spindle cells with delicate elongated cytoplasm. The nuclei were predominantly oval to elongated, with reticDiagnostic Cytopathology, Vol 00, No 00
1
Diagnostic Cytopathology DOI 10.1002/dc
RODRIGUEZ ET AL.
Fig. 1. Cytologic features of gastric schwannoma. A: Pap stain 203 showing clusters of spindle cells with intermixed lymphocytes in a myxoid background. B: Pap stain 603. The spindle cells are homogeneous, have delicate elongated cytoplasm, oval nuclei with reticular chromatin, inconspicuous nucleoli, and smooth nuclear membranes. C: Touch prep of resection 1003 showing spindle cells with delicate eosinophilic cytoplasm and ovoid elongated nuclei with reticular chromatin mixed with lymphocytes. D: Diff quick 6003 showing a mixed spindle cell population and smaller lymphocytes. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
ular chromatin, inconspicuous nucleoli, and smooth nuclear membranes. No necrosis or mitoses were identified (Fig. 1). The cell block showed aggregates of lymphocytes and a haphazard proliferation of spindle cells with eosinophilic cytoplasm, indistinct cell borders, and oval to spindle nuclei (Fig. 2). Immunohistochemistry performed on the cell block, showed a mixture of small CD3 and CD20 positive lymphocytes. The spindle cells were negative for cytokeratin AE1/AE3, CD117, SMA, and CD34. The tumor was diagnosed as a spindle cell neoplasm. Resection. The patient was subjected to a partial gastric resection. A 3.5 3 3.0 3 3.0 cm mass involving the muscularis propria was identified. The touch preparation showed a proliferation of spindle cells with delicate long cytoplasm and oval to round nuclei with reticular chromatin, all admixed with lymphocytes (Fig. 2). Histologic sections at low power demonstrated an unencapsulated, poorly circumscribed mass in the muscularis propria with a prominent lymphoid cuff with hyperplastic follicles (Fig. 2). No Verocay bodies, Antoni B areas, thick walled vessels, necrosis, or mitoses were identified. The 2
Diagnostic Cytopathology, Vol 00, No 00
gastric mucosa was unremarkable. By immunohistochemistry, the neoplastic cells were strongly and diffusely positive for S-100 and negative for CD117, DOG1, and CD-34 (Fig. 2). The diagnosis of gastric schwannoma was rendered.
Discussion Gastric tumors with a submucosal or mural location are usually not accessible by endoscopy, and FNA of these lesions is a useful method of sampling them.5 In this report, we describe the cytologic findings of a gastric schwannoma, an important spindle cell lesion presenting as a gastric wall mass. By endosonographic studies (EUS), the tumor generally demonstrates extremely low echogenicity when compared with surrounding tissues and a smooth surface. An important diagnostic feature is the marginal hypoechoic halo. This finding seems to correlate with the lymphoid cuff nearly always encountered on histologic sections. However, imaging studies are not completely specific, since other mesenchymal tumors such as GIST may share the same features including hypoechogenicity and marginal halos.6–8
Diagnostic Cytopathology DOI 10.1002/dc
CYTOLOGIC FINDINGS OF GASTRIC SCHWANNOMA
Fig. 2. Histologic features of gastric schwannoma. A: Cell Block 103 showing a prominent lymphoid cuff and spindle cell proliferation with collagenous stroma. B: The spindle cells are positive for S100 (resection) and negative for CD117 (cell block, inset). C: Low power view of the resection showing a mass centered in the muscularis propria, with a prominent lymphoid cuff. D: Resection 1003 showing bland spindle cells with round to ovoid nuclear reticular chromatin, eosinophilic cytoplasm, and scattered lymphocytes and plasma cells. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Grossly gastric schwannomas are well-circumscribed, ovoid, or round mural masses of variable size, most commonly located in the muscularis propria. On histologic sections, gastric schwannoma is an unencapsulated infiltrative lesion of moderate cellularity, composed of interlacing bundles of spindle cells with minimal palisading and abundant wavy collagen fibers that infiltrate mural smooth muscle. Of interest, areas of Antoni B are usually absent and, in contrast to schwannomas of the somatic soft tissues and the nervous system, these tumors lack NF2 mutations.9 By immunohistochemistry, gastric schwannoma is positive for S-100 and GFAP; the majority of the tumors are negative for CD34 and CD117.2,4 Cytologic findings of classic schwannomas in soft tissue are well-documented in the literature; however gastric schwannomas lack some of the most characteristic features, including Verocay bodies and thick-walled vessels. As expected, these features are also absent on cytologic smears. A characteristic finding is the presence of wavy nuclei,10,11 although it is nonspecific. We believe that one of the most helpful cytologic/morphologic features is the presence of lymphoid cells admixed with nests of spindle
cells. A cell block for immunohistochemistry is helpful in confirming that the spindle cells are positive for S-100 protein, and therefore Schwannian. A limited battery of stains is recommended, and includes CD117, SMA, and CD34 when material is available.12 Spindle cell cytology in schwannomas of the GI tract immediately raises the important differential diagnosis of various mesenchymal lesions, in particular GIST. GIST is the main gastric submucosal and mural tumor. Suspicious findings for malignancy on EUS include larger size and irregular borders.5 On cytologic evaluation, GISTs are usually highly cellular, and composed of spindle cells distributed in tight and loose aggregates with irregular outlines.13 At high magnification, the neoplastic cells demonstrate scant light eosinophilic cytoplasm and tapered oval nuclei with low nuclear to cytoplasmic ratios. The nucleus has a smooth membrane, fine chromatin and inconspicuous nucleoli. The smear background is usually clean.14,15 Some features can be used to classify further GISTs on cytology samples, although it is difficult to assess malignant potential based on them. Features suggestive of malignant GIST include highly cellular smears, loosely coheDiagnostic Cytopathology, Vol 00, No 00
3
Diagnostic Cytopathology DOI 10.1002/dc
RODRIGUEZ ET AL.
sive groups with single cells in the background, as well as coarse granular, or clumped chromatin. The background has a dirty appearance, with many naked nuclei associated with hemorrhagic/necrotic debris. Nuclear features of malignancy such as nuclear pleomorphism, hyperchromasia, irregular membranes, and increased nuclear/ cytoplasmatic ratio can be present, but were not seen in the majority of the cases reported by Li et al. in a series of GISTs.16 In this series, cytoplasm was scant in malignant spindle cell GISTs, with occasional vacuoles and indistinct cell boundaries. However, in epithelioid GIST abundant eosinophilic cytoplasm and multiple small cytoplasmatic vacuoles were present. Another important differential diagnosis of schwannomas of the gastrointestinal tract is smooth muscle tumors. Leiomyoma is morphologically similar to GIST; however, when the smears are compared, the overall cellularity of leiomyoma is lower. The cells are spindled with fine delicate eosinophilic cytoplasm. The nucleus is round to oval with fine vesicular chromatin. An inflammatory background is absent on cell blocks.15 Smears of leiomyosarcoma are highly cellular, with the cells distributed in large three-dimensional arrangements with abundant crush artifact. The neoplastic cells are embedded in a wiry stroma. Marked cellular pleomorphism is common. The nuclei are spindle-shaped or blunt-ended, but wavy nuclei can also be encountered. Mitoses and necrosis can be present, but the majority of tumors lack that features.17 Given the nearly invariable lymphoid component of gastric schwannomas, the possibility of lymphoma may also be entertained. Immunohistochemical stains and/or flow cytometry can be used to exclude lymphoma and was performed in our case. However, it must be mentioned that cases of gastrointestinal spindle cell neoplasm coexisting with lymphomas have been documented.2 In summary, we report the cytologic findings of a case of gastric schwannoma. These neoplasms can be challenging on cytologic preparations but their characteristic lymphoid background is a clue. Other more common mesenchymal tumors (e.g., GIST, smooth muscle tumors) represent the main differential diagnosis and must be excluded with ancillary techniques. Pathologists who study these specimens must be aware of the key diagnostic features, which allow an accurate diagnosis and optimal patient management.
4
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References 1. Bosman F, Carneiro F, Hruban R, Theise N.WHO Classification of Tumours of the Digestive System. World Health Organization Classification of Tumours. Lyon: International Agency for Research on Cancer: International Agency for Research on Cancer; 2010. 2. Agaimy A, Markl B, Kitz J, et al. Peripheral nerve sheath tumors of the gastrointestinal tract: A multicenter study of 58 patients including NF1-associated gastric schwannoma and unusual morphologic variants. Virchows Archiv 2010;456:411–422. 3. Daimaru Y, Kido H, Hashimoto H, Enjoji M. Benign schwannoma of the gastrointestinal tract: A clinicopathologic and immunohistochemical study. Hum Pathol 1988;19:257–264. 4. Voltaggio L, Murray R, Lasota J, Miettinen M. Gastric schwannoma: A clinicopathologic study of 51 cases and critical review of the literature. Hum Pathol 2012;43:650–659. 5. Hoda KM, Rodriguez SA, Faigel DO. EUS-guided sampling of suspected GI stromal tumors. Gastrointest Endosc 2009;69:1218–1223. 6. Hong HS, Ha HK, Won HJ, et al. Gastric schwannomas: Radiological features with endoscopic and pathological correlation. Clin Radiol 2008;63:536–542. 7. Jung MK, Jeon SW, Cho CM, et al. Gastric schwannomas: Endosonographic characteristics. Abdom Imaging 2008;33:388–390. 8. Kang JH, Lim JS, Kim JH, et al. Role of EUS and MDCT in the diagnosis of gastric submucosal tumors according to the revised pathologic concept of gastrointestinal stromal tumors. Eur Radiol 2009;19:924–934. 9. Lasota J, Wasag B, Dansonka-Mieszkowska A, et al. Evaluation of NF2 and NF1 tumor suppressor genes in distinctive gastrointestinal nerve sheath tumors traditionally diagnosed as benign schwannomas: s study of 20 cases. Lab Invest 2003;83:1361–1371. 10. Mooney EE, Layfield LJ, Dodd LG. Fine-needle aspiration of neural lesions. Diagn Cytopathol 1999;20:1–5. 11. Stelow EB, Lai R, Bardales RH, Linzie BM, Mallery S, Stanley MW. Endoscopic ultrasound-guided fine-needle aspiration cytology of peripheral nerve-sheath tumors. Diagn Cytopathol 2004;30: 172–177. 12. Stelow EB, Murad FM, Debol SM, et al. A limited immunocytochemical panel for the distinction of subepithelial gastrointestinal mesenchymal neoplasms sampled by endoscopic ultrasound-guided fine-needle aspiration. Am J Clin Pathol 2008;129:219–225. 13. Gu M, Ghafari S, Nguyen PT, Lin F. Cytologic diagnosis of gastrointestinal stromal tumors of the stomach by endoscopic ultrasoundguided fine-needle aspiration biopsy: Cytomorphologic and immunohistochemical study of 12 cases. Diagn Cytopathol 2001;25: 343–350. 14. Rader AE, Avery A, Wait CL, McGreevey LS, Faigel D, Heinrich MC. Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit. Cancer 2001;93:269–275. 15. Stelow EB, Stanley MW, Mallery S, Lai R, Linzie BM, Bardales RH. Endoscopic ultrasound-guided fine-needle aspiration findings of gastrointestinal leiomyomas and gastrointestinal stromal tumors. Am J Clin Pathol 2003;119:703–708. 16. Li SQ, O’Leary TJ, Buchner SB, et al. Fine needle aspiration of gastrointestinal stromal tumors. Acta Cytol 2001;45:9–17. 17. Wieczorek TJ, Faquin WC, Rubin BP, Cibas ES. Cytologic diagnosis of gastrointestinal stromal tumor with emphasis on the differential diagnosis with leiomyosarcoma. Cancer 2001;93: 276–287.
Cytologic Findings of Gastric Schwannoma: A Case Report Erika Rodriguez, M.D., PhD,1 Steven Tellschow, M.D.,2 David M. Steinberg, M.D.,2 and Elizabeth Montgomery, M.D.1*
Spindle cell lesions of the stomach are rare. They usually affect the submucosa or muscularis propria and therefore can be sampled by endoscopic fine needle aspiration. The most common tumor in this category is gastrointestinal stromal tumor (GIST), followed by leiomyoma and gastric schwannoma. Gastric schwannoma is a benign tumor of neuroectodermal origin that has overlapping morphologic/cytologic features with GIST and leiomyoma. Gastric schwannomas differ from peripheral schwannomas by lacking a capsule, Verocay bodies, Antoni B areas, and thick-walled vessels. They are characterized morphologically by poorly defined borders, cuffs of lymphoid tissue and a haphazard spindle cell proliferation. We present here the cytologic and histopathologic features of a gastric schwannoma. The tumor was composed of spindle cells with delicate eosinophilic cytoplasm and wavy nuclei, with an associated conspicuous lymphoid backdrop. The latter feature raised the possibility of a lymphoid lesion, a problem cytopathologists should be aware of. Diagn. Cytopathol. 2012;00:000–000. ' 2012 Wiley Periodicals, Inc. Key Words: gastric schwannoma; gastrointestinal stromal tumor; GIST; spindle cell neoplasm
Mesenchymal tumors of the stomach encompass variable putative histogenesis. The most common tumor in this category is gastrointestinal stromal tumor (GIST), followed by leiomyoma and schwannoma.1,2 Gastric schwannoma represents an important subset of benign nerve sheath tumors of the gastrointestinal tract. This tumor is more common in females, can manifest over a broad age range (29–90 years of age), and the
1
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 2 Department of Pathology, St. Luke’s Hospital and Health Network, Bethlehem, Pennsylvania *Correspondence to: Elizabeth Montgomery, MD, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. E-mail: [email protected] Received 5 March 2012; Accepted 16 July 2012 DOI 10.1002/dc.22913 Published online in Wiley Online Library (wileyonlinelibrary.com). '
2012 WILEY PERIODICALS, INC.
patients are usually asymptomatic.1,3,4 Cytologic interpretation of spindle cell lesions of the stomach can be challenging. The morphologic features of these tumors have been well described in the literature. However, the cytologic features of gastric schwannomas in particular are incompletely described, which may lead to potential diagnostic pitfalls. Herein, we describe a case of gastric schwannoma with emphasis on cytologic features, and discuss the differential diagnosis.
Case Report Clinical History The patient was a 35-year-old previously asymptomatic female with an incidental gastric mass identified during evaluation following a motor vehicle accident. A partially exophytic hyperdense lesion in the gastric muscularis propria along the greater curvature was present on CT, measuring 3.6 3 2.5 cm. Multiple surrounding nodules, interpreted as lymph nodes, were also seen. The differential diagnosis included gastric hematoma or a neoplasm. Upper endoscopic ultrasound demonstrated a heterogeneous hypoechoic mass with small anechoic foci in the muscularis propria of the gastric body and greater curvature measuring 2.1 3 2.0 cm. A fine needle aspiration was performed using a 22-gauge Wilson Cook needle.
Pathologic Findings Cytology. The smears were variably cellular. On the Diff-Quick stain, they were composed predominantly of small reactive lymphocytes. Rare sparse aggregates of loosely cohesive spindle cells with variable infiltration by lymphocytes were present (Fig. 1). On Papanicolaou stain, the smears were paucicellular, composed predominantly of lymphocytes and rare groups of loosely cohesive spindle cells with delicate elongated cytoplasm. The nuclei were predominantly oval to elongated, with reticDiagnostic Cytopathology, Vol 00, No 00
1
Diagnostic Cytopathology DOI 10.1002/dc
RODRIGUEZ ET AL.
Fig. 1. Cytologic features of gastric schwannoma. A: Pap stain 203 showing clusters of spindle cells with intermixed lymphocytes in a myxoid background. B: Pap stain 603. The spindle cells are homogeneous, have delicate elongated cytoplasm, oval nuclei with reticular chromatin, inconspicuous nucleoli, and smooth nuclear membranes. C: Touch prep of resection 1003 showing spindle cells with delicate eosinophilic cytoplasm and ovoid elongated nuclei with reticular chromatin mixed with lymphocytes. D: Diff quick 6003 showing a mixed spindle cell population and smaller lymphocytes. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
ular chromatin, inconspicuous nucleoli, and smooth nuclear membranes. No necrosis or mitoses were identified (Fig. 1). The cell block showed aggregates of lymphocytes and a haphazard proliferation of spindle cells with eosinophilic cytoplasm, indistinct cell borders, and oval to spindle nuclei (Fig. 2). Immunohistochemistry performed on the cell block, showed a mixture of small CD3 and CD20 positive lymphocytes. The spindle cells were negative for cytokeratin AE1/AE3, CD117, SMA, and CD34. The tumor was diagnosed as a spindle cell neoplasm. Resection. The patient was subjected to a partial gastric resection. A 3.5 3 3.0 3 3.0 cm mass involving the muscularis propria was identified. The touch preparation showed a proliferation of spindle cells with delicate long cytoplasm and oval to round nuclei with reticular chromatin, all admixed with lymphocytes (Fig. 2). Histologic sections at low power demonstrated an unencapsulated, poorly circumscribed mass in the muscularis propria with a prominent lymphoid cuff with hyperplastic follicles (Fig. 2). No Verocay bodies, Antoni B areas, thick walled vessels, necrosis, or mitoses were identified. The 2
Diagnostic Cytopathology, Vol 00, No 00
gastric mucosa was unremarkable. By immunohistochemistry, the neoplastic cells were strongly and diffusely positive for S-100 and negative for CD117, DOG1, and CD-34 (Fig. 2). The diagnosis of gastric schwannoma was rendered.
Discussion Gastric tumors with a submucosal or mural location are usually not accessible by endoscopy, and FNA of these lesions is a useful method of sampling them.5 In this report, we describe the cytologic findings of a gastric schwannoma, an important spindle cell lesion presenting as a gastric wall mass. By endosonographic studies (EUS), the tumor generally demonstrates extremely low echogenicity when compared with surrounding tissues and a smooth surface. An important diagnostic feature is the marginal hypoechoic halo. This finding seems to correlate with the lymphoid cuff nearly always encountered on histologic sections. However, imaging studies are not completely specific, since other mesenchymal tumors such as GIST may share the same features including hypoechogenicity and marginal halos.6–8
Diagnostic Cytopathology DOI 10.1002/dc
CYTOLOGIC FINDINGS OF GASTRIC SCHWANNOMA
Fig. 2. Histologic features of gastric schwannoma. A: Cell Block 103 showing a prominent lymphoid cuff and spindle cell proliferation with collagenous stroma. B: The spindle cells are positive for S100 (resection) and negative for CD117 (cell block, inset). C: Low power view of the resection showing a mass centered in the muscularis propria, with a prominent lymphoid cuff. D: Resection 1003 showing bland spindle cells with round to ovoid nuclear reticular chromatin, eosinophilic cytoplasm, and scattered lymphocytes and plasma cells. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Grossly gastric schwannomas are well-circumscribed, ovoid, or round mural masses of variable size, most commonly located in the muscularis propria. On histologic sections, gastric schwannoma is an unencapsulated infiltrative lesion of moderate cellularity, composed of interlacing bundles of spindle cells with minimal palisading and abundant wavy collagen fibers that infiltrate mural smooth muscle. Of interest, areas of Antoni B are usually absent and, in contrast to schwannomas of the somatic soft tissues and the nervous system, these tumors lack NF2 mutations.9 By immunohistochemistry, gastric schwannoma is positive for S-100 and GFAP; the majority of the tumors are negative for CD34 and CD117.2,4 Cytologic findings of classic schwannomas in soft tissue are well-documented in the literature; however gastric schwannomas lack some of the most characteristic features, including Verocay bodies and thick-walled vessels. As expected, these features are also absent on cytologic smears. A characteristic finding is the presence of wavy nuclei,10,11 although it is nonspecific. We believe that one of the most helpful cytologic/morphologic features is the presence of lymphoid cells admixed with nests of spindle
cells. A cell block for immunohistochemistry is helpful in confirming that the spindle cells are positive for S-100 protein, and therefore Schwannian. A limited battery of stains is recommended, and includes CD117, SMA, and CD34 when material is available.12 Spindle cell cytology in schwannomas of the GI tract immediately raises the important differential diagnosis of various mesenchymal lesions, in particular GIST. GIST is the main gastric submucosal and mural tumor. Suspicious findings for malignancy on EUS include larger size and irregular borders.5 On cytologic evaluation, GISTs are usually highly cellular, and composed of spindle cells distributed in tight and loose aggregates with irregular outlines.13 At high magnification, the neoplastic cells demonstrate scant light eosinophilic cytoplasm and tapered oval nuclei with low nuclear to cytoplasmic ratios. The nucleus has a smooth membrane, fine chromatin and inconspicuous nucleoli. The smear background is usually clean.14,15 Some features can be used to classify further GISTs on cytology samples, although it is difficult to assess malignant potential based on them. Features suggestive of malignant GIST include highly cellular smears, loosely coheDiagnostic Cytopathology, Vol 00, No 00
3
Diagnostic Cytopathology DOI 10.1002/dc
RODRIGUEZ ET AL.
sive groups with single cells in the background, as well as coarse granular, or clumped chromatin. The background has a dirty appearance, with many naked nuclei associated with hemorrhagic/necrotic debris. Nuclear features of malignancy such as nuclear pleomorphism, hyperchromasia, irregular membranes, and increased nuclear/ cytoplasmatic ratio can be present, but were not seen in the majority of the cases reported by Li et al. in a series of GISTs.16 In this series, cytoplasm was scant in malignant spindle cell GISTs, with occasional vacuoles and indistinct cell boundaries. However, in epithelioid GIST abundant eosinophilic cytoplasm and multiple small cytoplasmatic vacuoles were present. Another important differential diagnosis of schwannomas of the gastrointestinal tract is smooth muscle tumors. Leiomyoma is morphologically similar to GIST; however, when the smears are compared, the overall cellularity of leiomyoma is lower. The cells are spindled with fine delicate eosinophilic cytoplasm. The nucleus is round to oval with fine vesicular chromatin. An inflammatory background is absent on cell blocks.15 Smears of leiomyosarcoma are highly cellular, with the cells distributed in large three-dimensional arrangements with abundant crush artifact. The neoplastic cells are embedded in a wiry stroma. Marked cellular pleomorphism is common. The nuclei are spindle-shaped or blunt-ended, but wavy nuclei can also be encountered. Mitoses and necrosis can be present, but the majority of tumors lack that features.17 Given the nearly invariable lymphoid component of gastric schwannomas, the possibility of lymphoma may also be entertained. Immunohistochemical stains and/or flow cytometry can be used to exclude lymphoma and was performed in our case. However, it must be mentioned that cases of gastrointestinal spindle cell neoplasm coexisting with lymphomas have been documented.2 In summary, we report the cytologic findings of a case of gastric schwannoma. These neoplasms can be challenging on cytologic preparations but their characteristic lymphoid background is a clue. Other more common mesenchymal tumors (e.g., GIST, smooth muscle tumors) represent the main differential diagnosis and must be excluded with ancillary techniques. Pathologists who study these specimens must be aware of the key diagnostic features, which allow an accurate diagnosis and optimal patient management.
4
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References 1. Bosman F, Carneiro F, Hruban R, Theise N.WHO Classification of Tumours of the Digestive System. World Health Organization Classification of Tumours. Lyon: International Agency for Research on Cancer: International Agency for Research on Cancer; 2010. 2. Agaimy A, Markl B, Kitz J, et al. Peripheral nerve sheath tumors of the gastrointestinal tract: A multicenter study of 58 patients including NF1-associated gastric schwannoma and unusual morphologic variants. Virchows Archiv 2010;456:411–422. 3. Daimaru Y, Kido H, Hashimoto H, Enjoji M. Benign schwannoma of the gastrointestinal tract: A clinicopathologic and immunohistochemical study. Hum Pathol 1988;19:257–264. 4. Voltaggio L, Murray R, Lasota J, Miettinen M. Gastric schwannoma: A clinicopathologic study of 51 cases and critical review of the literature. Hum Pathol 2012;43:650–659. 5. Hoda KM, Rodriguez SA, Faigel DO. EUS-guided sampling of suspected GI stromal tumors. Gastrointest Endosc 2009;69:1218–1223. 6. Hong HS, Ha HK, Won HJ, et al. Gastric schwannomas: Radiological features with endoscopic and pathological correlation. Clin Radiol 2008;63:536–542. 7. Jung MK, Jeon SW, Cho CM, et al. Gastric schwannomas: Endosonographic characteristics. Abdom Imaging 2008;33:388–390. 8. Kang JH, Lim JS, Kim JH, et al. Role of EUS and MDCT in the diagnosis of gastric submucosal tumors according to the revised pathologic concept of gastrointestinal stromal tumors. Eur Radiol 2009;19:924–934. 9. Lasota J, Wasag B, Dansonka-Mieszkowska A, et al. Evaluation of NF2 and NF1 tumor suppressor genes in distinctive gastrointestinal nerve sheath tumors traditionally diagnosed as benign schwannomas: s study of 20 cases. Lab Invest 2003;83:1361–1371. 10. Mooney EE, Layfield LJ, Dodd LG. Fine-needle aspiration of neural lesions. Diagn Cytopathol 1999;20:1–5. 11. Stelow EB, Lai R, Bardales RH, Linzie BM, Mallery S, Stanley MW. Endoscopic ultrasound-guided fine-needle aspiration cytology of peripheral nerve-sheath tumors. Diagn Cytopathol 2004;30: 172–177. 12. Stelow EB, Murad FM, Debol SM, et al. A limited immunocytochemical panel for the distinction of subepithelial gastrointestinal mesenchymal neoplasms sampled by endoscopic ultrasound-guided fine-needle aspiration. Am J Clin Pathol 2008;129:219–225. 13. Gu M, Ghafari S, Nguyen PT, Lin F. Cytologic diagnosis of gastrointestinal stromal tumors of the stomach by endoscopic ultrasoundguided fine-needle aspiration biopsy: Cytomorphologic and immunohistochemical study of 12 cases. Diagn Cytopathol 2001;25: 343–350. 14. Rader AE, Avery A, Wait CL, McGreevey LS, Faigel D, Heinrich MC. Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit. Cancer 2001;93:269–275. 15. Stelow EB, Stanley MW, Mallery S, Lai R, Linzie BM, Bardales RH. Endoscopic ultrasound-guided fine-needle aspiration findings of gastrointestinal leiomyomas and gastrointestinal stromal tumors. Am J Clin Pathol 2003;119:703–708. 16. Li SQ, O’Leary TJ, Buchner SB, et al. Fine needle aspiration of gastrointestinal stromal tumors. Acta Cytol 2001;45:9–17. 17. Wieczorek TJ, Faquin WC, Rubin BP, Cibas ES. Cytologic diagnosis of gastrointestinal stromal tumor with emphasis on the differential diagnosis with leiomyosarcoma. Cancer 2001;93: 276–287.
