cytologic findings of gastric schwannoma: a case report

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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 morpho- logically by poorly defined borders, cuffs of lymphoid tissue and a haphazard spindle cell proliferation. We present here the cyto- logic 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 tu- mor; 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), fol- lowed 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 patients are usually asymptomatic. 1,3,4 Cytologic interpre- tation of spindle cell lesions of the stomach can be chal- lenging. The morphologic features of these tumors have been well described in the literature. However, the cyto- logic features of gastric schwannomas in particular are incompletely described, which may lead to potential diag- nostic 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 differen- tial diagnosis included gastric hematoma or a neoplasm. Upper endoscopic ultrasound demonstrated a heteroge- neous hypoechoic mass with small anechoic foci in the muscularis propria of the gastric body and greater curva- ture 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 predomi- nantly of lymphocytes and rare groups of loosely cohe- sive spindle cells with delicate elongated cytoplasm. The nuclei were predominantly oval to elongated, with retic- 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 Pa- thology, 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. Diagnostic Cytopathology, Vol 00, No 00 1

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Page 1: Cytologic findings of gastric schwannoma: A case report

BRIEF REPORT

Cytologic Findings of GastricSchwannoma:A Case ReportErika 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 affectthe submucosa or muscularis propria and therefore can besampled by endoscopic fine needle aspiration. The most commontumor in this category is gastrointestinal stromal tumor (GIST),followed by leiomyoma and gastric schwannoma. Gastricschwannoma is a benign tumor of neuroectodermal origin thathas overlapping morphologic/cytologic features with GIST andleiomyoma. Gastric schwannomas differ from peripheralschwannomas by lacking a capsule, Verocay bodies, Antoni Bareas, and thick-walled vessels. They are characterized morpho-logically by poorly defined borders, cuffs of lymphoid tissue anda haphazard spindle cell proliferation. We present here the cyto-logic and histopathologic features of a gastric schwannoma. Thetumor was composed of spindle cells with delicate eosinophiliccytoplasm and wavy nuclei, with an associated conspicuouslymphoid backdrop. The latter feature raised the possibility of alymphoid lesion, a problem cytopathologists should be aware of.Diagn. Cytopathol. 2012;00:000–000. ' 2012 Wiley Periodicals, Inc.

Key Words: gastric schwannoma; gastrointestinal stromal tu-mor; 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), fol-

lowed 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

patients are usually asymptomatic.1,3,4 Cytologic interpre-

tation of spindle cell lesions of the stomach can be chal-

lenging. The morphologic features of these tumors have

been well described in the literature. However, the cyto-

logic features of gastric schwannomas in particular are

incompletely described, which may lead to potential diag-

nostic 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 differen-

tial diagnosis included gastric hematoma or a neoplasm.

Upper endoscopic ultrasound demonstrated a heteroge-

neous hypoechoic mass with small anechoic foci in the

muscularis propria of the gastric body and greater curva-

ture 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 predomi-

nantly of lymphocytes and rare groups of loosely cohe-

sive spindle cells with delicate elongated cytoplasm. The

nuclei were predominantly oval to elongated, with retic-

1Department of Pathology, The Johns Hopkins Medical Institutions,Baltimore, Maryland

2Department of Pathology, St. Luke’s Hospital and Health Network,Bethlehem, Pennsylvania

*Correspondence to: Elizabeth Montgomery, MD, Department of Pa-thology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.E-mail: [email protected]

Received 5 March 2012; Accepted 16 July 2012DOI 10.1002/dc.22913Published online in Wiley Online Library (wileyonlinelibrary.com).

' 2012 WILEY PERIODICALS, INC. Diagnostic Cytopathology, Vol 00, No 00 1

Page 2: Cytologic findings of gastric schwannoma: A case report

ular chromatin, inconspicuous nucleoli, and smooth nu-

clear membranes. No necrosis or mitoses were identified

(Fig. 1). The cell block showed aggregates of lympho-

cytes and a haphazard proliferation of spindle cells with

eosinophilic cytoplasm, indistinct cell borders, and oval

to spindle nuclei (Fig. 2). Immunohistochemistry per-

formed 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 gas-

tric 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 chro-

matin, 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 fol-

licles (Fig. 2). No Verocay bodies, Antoni B areas, thick

walled vessels, necrosis, or mitoses were identified. The

gastric mucosa was unremarkable. By immunohisto-

chemistry, the neoplastic cells were strongly and dif-

fusely positive for S-100 and negative for CD117, DOG-

1, and CD-34 (Fig. 2). The diagnosis of gastric schwan-

noma 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 his-

tologic sections. However, imaging studies are not com-

pletely specific, since other mesenchymal tumors such as

GIST may share the same features including hypoechoge-

nicity and marginal halos.6–8

Fig. 1. Cytologic features of gastric schwannoma. A: Pap stain 203 showing clusters of spindle cells with intermixed lymphocytes in a myxoid back-ground. B: Pap stain 603. The spindle cells are homogeneous, have delicate elongated cytoplasm, oval nuclei with reticular chromatin, inconspicuousnucleoli, and smooth nuclear membranes. C: Touch prep of resection 1003 showing spindle cells with delicate eosinophilic cytoplasm and ovoid elon-gated 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.]

RODRIGUEZ ET AL.

2 Diagnostic Cytopathology, Vol 00, No 00

Diagnostic Cytopathology DOI 10.1002/dc

Page 3: Cytologic findings of gastric schwannoma: A case report

Grossly gastric schwannomas are well-circumscribed,

ovoid, or round mural masses of variable size, most com-

monly located in the muscularis propria. On histologic

sections, gastric schwannoma is an unencapsulated infil-

trative lesion of moderate cellularity, composed of inter-

lacing 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 major-

ity of the tumors are negative for CD34 and CD117.2,4

Cytologic findings of classic schwannomas in soft tis-

sue are well-documented in the literature; however gastric

schwannomas lack some of the most characteristic fea-

tures, 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 dis-

tributed in tight and loose aggregates with irregular out-

lines.13 At high magnification, the neoplastic cells demon-

strate scant light eosinophilic cytoplasm and tapered oval

nuclei with low nuclear to cytoplasmic ratios. The nucleus

has a smooth membrane, fine chromatin and inconspicu-

ous 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 malig-

nant potential based on them. Features suggestive of ma-

lignant GIST include highly cellular smears, loosely cohe-

Fig. 2. Histologic features of gastric schwannoma. A: Cell Block 103 showing a prominent lymphoid cuff and spindle cell proliferation with collage-nous stroma. B: The spindle cells are positive for S100 (resection) and negative for CD117 (cell block, inset). C: Low power view of the resectionshowing a mass centered in the muscularis propria, with a prominent lymphoid cuff. D: Resection 1003 showing bland spindle cells with round toovoid 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.]

CYTOLOGIC FINDINGS OF GASTRIC SCHWANNOMA

Diagnostic Cytopathology, Vol 00, No 00 3

Diagnostic Cytopathology DOI 10.1002/dc

Page 4: Cytologic findings of gastric schwannoma: A case report

sive groups with single cells in the background, as well

as coarse granular, or clumped chromatin. The back-

ground has a dirty appearance, with many naked nuclei

associated with hemorrhagic/necrotic debris. Nuclear fea-

tures of malignancy such as nuclear pleomorphism, hyper-

chromasia, 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 malig-

nant spindle cell GISTs, with occasional vacuoles and

indistinct cell boundaries. However, in epithelioid GIST

abundant eosinophilic cytoplasm and multiple small cyto-

plasmatic vacuoles were present.

Another important differential diagnosis of schwan-

nomas of the gastrointestinal tract is smooth muscle

tumors. Leiomyoma is morphologically similar to GIST;

however, when the smears are compared, the overall cel-

lularity of leiomyoma is lower. The cells are spindled

with fine delicate eosinophilic cytoplasm. The nucleus is

round to oval with fine vesicular chromatin. An inflamma-

tory background is absent on cell blocks.15 Smears of

leiomyosarcoma are highly cellular, with the cells distrib-

uted in large three-dimensional arrangements with abun-

dant 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 men-

tioned 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 challeng-

ing on cytologic preparations but their characteristic

lymphoid background is a clue. Other more common mes-

enchymal tumors (e.g., GIST, smooth muscle tumors) rep-

resent the main differential diagnosis and must be

excluded with ancillary techniques. Pathologists who

study these specimens must be aware of the key diagnos-

tic features, which allow an accurate diagnosis and opti-

mal patient management.

References

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Tumours of the Digestive System. World Health Organization Clas-sification of Tumours. Lyon: International Agency for Research onCancer: 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 includ-ing NF1-associated gastric schwannoma and unusual morphologicvariants. Virchows Archiv 2010;456:411–422.

3. Daimaru Y, Kido H, Hashimoto H, Enjoji M. Benign schwannoma

of the gastrointestinal tract: A clinicopathologic and immunohisto-chemical study. Hum Pathol 1988;19:257–264.

4. Voltaggio L, Murray R, Lasota J, Miettinen M. Gastric schwan-

noma: A clinicopathologic study of 51 cases and critical review ofthe literature. Hum Pathol 2012;43:650–659.

5. Hoda KM, Rodriguez SA, Faigel DO. EUS-guided sampling of sus-

pected GI stromal tumors. Gastrointest Endosc 2009;69:1218–1223.

6. Hong HS, Ha HK, Won HJ, et al. Gastric schwannomas: Radiologi-

cal features with endoscopic and pathological correlation. ClinRadiol 2008;63:536–542.

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nographic characteristics. Abdom Imaging 2008;33:388–390.

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sis of gastric submucosal tumors according to the revised pathologic con-cept 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 gastrointestinalnerve sheath tumors traditionally diagnosed as benign schwan-nomas: s study of 20 cases. Lab Invest 2003;83:1361–1371.

10. Mooney EE, Layfield LJ, Dodd LG. Fine-needle aspiration of neurallesions. 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 pe-ripheral nerve-sheath tumors. Diagn Cytopathol 2004;30: 172–177.

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14. Rader AE, Avery A, Wait CL, McGreevey LS, Faigel D, HeinrichMC. Fine-needle aspiration biopsy diagnosis of gastrointestinal stro-mal tumors using morphology, immunocytochemistry, and muta-tional analysis of c-kit. Cancer 2001;93:269–275.

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