ORIGINAL ARTICLES

Fine-Needle Aspiration Cytologyof Malignant Peripheral NerveSheath TumorsKirti Gupta, M.D.,1 Pranab Dey, M.D., M.I.A.C.,2*and Rakesh Vashisht, M.D., M.R.C.Path.

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The histopathologic features of malignant peripheral nerve sheathtumors (MPNSTs) have been well described. There have beenlimited studies on the cytologic features of MPNST. In this presentstudy, we have retrospectively reviewed eight histopathology con-firmed cases of MPNST over a 5-year period. Detailed cytomor-phlogical analysis of these cases was carried out individually bytwo observers. On cytology, these cases were diagnosed as benignspindle-cell tumor (two), spindle-cell tumor possibly benign (one),spindle-cell tumor possibly malignant (one), malignant spindle-cell tumor (two), spindle-cell tumor, and neural origin (two). Thecardinal cytomorphologic features were loosely cohesive clustersand fascicular arrangement of spindle cells with rounded ends.The kinking of nuclei was not a conspicuous finding. Fibrillarybackground was noted in two of the cases. Nuclear pleomorphismwas ranged from mild to moderate degree. One case exhibitedextensive intranuclear pseudoinclusions. Mitotic figures (includingatypical forms) were present in almost all the cases. Possibly aconstellation of cytologic features such as clusters of short andlong fascicles of cells admixed with dissociated spindle cells ofround-ended nuclei and prominent nucleoli on myxoid or fibrillarybackground and frequent mitosis may be helpful in diagnosis ofMPNSTs. The cytomorphologic features along with clinical cor-relation are necessary to increase the diagnostic accuracy ofMPNST on aspiration cytology. Diagn. Cytopathol. 2004;31:1–4. © 2004 Wiley-Liss, Inc.

Key Words: cytology; spindle-cell tumor; malignant peripheralnerve sheath tumors

Soft-tissue tumors constitute a large and heterogeneousgroup of neoplasms. Traditionally, soft-tissue sarcomashave been classified according to a histogenetic concept.

However, due to limited material availability in the needleaspirates, it is not always possible to classify soft-tissuesarcomas on a histogenetic basis. Frequently, the soft-tissuesarcomas are categorized morphologically into three maingroups, namely, spindle-cell tumors, pleomorphic-cell tu-mors, and round-cell tumors.1 Malignant peripheral nervesheath tumors (MPNSTs) form an important subgroup ofthese spindle-cell sarcomas. MPNST encompasses the olderdesignations of neurofibrosarcoma and malignant schwan-noma. It implies that tumors arising from peripheral nerveor showing nerve sheath differentiation may recapitulateany or all elements of the nerve sheath, including schwanncells, perineural fibroblasts, or fibroblasts.2,3 Although therole of fine-needle aspiration cytology is well established asa diagnostic modality at many sites,4 its role in the evalua-tion of mesenchymal lesions is limited.5 This is partly due tothe paucity of number of soft-tissue lesions evaluated bycytopathologist and mainly due to the overlapping spectrumof cytomorphologic features exhibited by these neoplasms.In the present retrospective study, we evaluated the cyto-morphologic features of eight hitopathologically confirmedcases of MPNST and present the characteristic diagnosticcytomorphological features.

Materials and MethodsThis is a retrospective study of eight histopathologicallyconfirmed cases of MPNST selected from the archival ma-terial of cytopathology department over a 5-year period. Thelesions were aspirated using 22 gauge needle and the smearswere air-dried and fixed in alcohol for May-Grunwald-Giemsa (MGG) and hematoxylin-eosin (H&E) staining, re-spectively. All the fine-needle aspiration cytology (FNAC)smears were thoroughly studied by two cytologists (P.D.and K.G.) independently. The histopathology sections cutfrom the paraffin blocks were immunostained for S-100protein by indirect immunoperoxidase method. The corre-sponding histopathology sections were studied along withcytology smears.

1Department of Pathology, Post Graduate Institute of Medical Educationand Research, Chandigarh, India

2Department of Cytology, Post Graduate Institute of Medical Educationand Research, Chandigarh, India

3Department of Histopathology, Post Graduate Institute of MedicalEducation and Research, Chandigarh, India

*Correspondence to: Pranab Dey, M.D., M.I.A.C., Histopathology Lab-oratory, Kuwait Cancer Controlling Center, Post Box 42262, 70653 Shu-waikh, Kuwait. E-mail: deypranab@hotmail.com

Received 18 July 2003; Accepted 21 January 2004DOI 10.1002/dc.20079Published online in Wiley InterScience (www.interscience.wiley.com).

© 2004 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 31, No 1 1

ResultsThe age range of the patients was from 22 years to 60 years,with male:female ratio of 1:3. The site of involvement ofMPNST was soft-tissue extremity (five), vertebral column(one), soft-tissue neck (one), and retroperitoneum (one).Out of eight patients, two cases were known cases of VonRecklinghausen’s disease with soft-tissue swelling at mul-tiple sites (Table I). All these cases were primarily diag-nosed as spindle-cell tumor on aspiration cytology. Thecytological diagnosis of MPNST included benign spindle-cell tumor (two), spindle-cell tumor possibly benign (one),spindle-cell tumor possibly malignant (one), malignantspindle-cell tumor (two), and spindle-cell tumor of neuralorigin (two).

Table II shows detailed cytologic features of MPNST.There were low (three) to moderate (two) to high (three)cellularity on cytology smears. The arrangement of cells

predominantly was in long and short fascicles and in smallclusters. One case showed parallel arrangements of cells inaddition to long and short fascicles. Seven out of the eightcases showed predominant spindle-cell pattern with roundnuclear ends (Fig. 1). Only one case showed predominantround to oval cells with less number of spindle cells. Kink-ing of nuclei was rarely noted (1/8). Most cells had prom-inent nucleoli. One case revealed extensive intranuclearpseudoinclusions. Pleomorphism was marked in three caseswith many mitotic figures (including atypical forms). Thecytoplasm of the cells often showed vacuolation with ill-defined borders. There was dense admixture with inflam-matory cells (lymphocytes, polymorphs) in one case. Mildto extensive myxoid background (Fig. 2 and Fig. 3) in fourcases and fibrillary background in two cases were noted.

All the eight cases revealed classic features of malignantnerve sheath tumors on histopathological examination. Three

Table I. Clinical Findings of Eight Cases

Cytology diagnosisAge

(years) Sex Site Clinical diagnosis

Spindle-cell tumor, possibly benign 42 F Soft-tissue thigh MPNST ?Spindle-cell tumor, neural origin 60 M Soft-tissue elbow known case of von Recklinghausen’s disease,

MPNST?Spindle-cell tumor, neural origin 44 M Soft-tissue foot Neurofibroma?Spindle-cell tumor, malignant 40 F Soft-tissue thigh Neurofibroma?Spindle-cell tumor, benign 32 F Soft-tissue thigh Neurofibroma?Spindle-cell tumor, possibly malignant 45 F Soft-tissue vertebral column MPNST? known case of von Recklinghausen’s

diseaseSpindle-cell tumor, malignant 22 F Subcutaneous tissue neck Neurofibroma?Spindle-cell tumor, benign 35 F Retroperitoneum Sarcoma

Table II. Detailed Cytomorphological Features of Eight Histopathologically Confirmed Cases of MPNST

Cellularity ArrangementCellular

morphology

Nuclear-cytoplasmic

ratio PleomorphismCytoplasmicvacuolation

Nucleolarprominence

Nakednuclei

Stromalbackground

Mitoticfigure

Inflammatorycells

High Clusters; long andshort fascicles;parallelarrangement

Spindle cellswith fusiformnuclei;kinkingpresent

High Moderate Oftenvacuolated

Inconspicuous Frequent Myxoid Occasional Mild

Moderate Discrete; looselycohesive clusters

Spindle cell withfusiformnuclei withround ends

Low Mild Moderate withill-definedborders

Prominent;multiple

Few Abundant;fibrillary

Few Absent

Moderate Clusters; shortfascicle

Spindle cellswith roundends, ovalcells

High Mild Nonvacuolated Inconspicuous Few Myxoid;fibrillary

Absent Absent

High Long and shortfascicle; parallelarrangement

Spindle cellswith roundends

High Marked Nonvacuolated Prominent Few Extensive;myxoid

Frequent Moderate(lymphocyte,polymorphs)

Low Clusters; occasionalfascicle

Spindle cellswith pointedends

Variable Mild Vacuolated Prominent Occasional Less stroma Absent Absent

Low Discrete; occasionalclusters

Round to ovalcells,spindling less

High Marked;multinucleatedcells present

Nonvacuolated Prominent;multiple;Macronucleoli;intranuclearinclusions

Occasional Extensive;myxoid

Few Absent

High Clusters; long andshort fascicle

Spindle cellswith roundends

High Marked;multinucleatedcells present

Nonvacuolated Prominent;multiple

Occasional Less Frequent Absent

Low Cluster; shortfascicle

Spindle cellswith roundends

Low Mild Vacuolated Conspicuous Occasional Less Absent Absent

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cases revealed extensive fibrosis and hyalinization. All eightcases revealed strong nuclear positivity for S-100 protein.

DiscussionSince FNA yields smaller tissue fragments than that ob-tained by incisional or excisional biopsy, many morpho-logic criteria used by histopathologists in the diagnosis ofsarcomas are not present or are obscured in the materialobtained by FNAC.6 Hence, other morphologic criteria areused in the cytologic assessment of these neoplasms. Suen7

has stressed the use of five broad cytologic criteria, whichform the basis of interpretation for FNA diagnosis. Theseare cellular morphology, cellular pattern, cellular composi-tion, smear cellularity, and background appearance. Thesecriteria have been extensively applied for diagnosis of soft-tissue sarcoma.8 Cytologic diagnosis of MPNST poses adiagnostic challenge to the cytopathologist partly due tooverlapping cytomorphological features and partly becauseof limited exposure to these lesions.

In this retrospective study of eight histopathologicallyconfirmed cases of MPNST, we have evaluated the cyto-morphological features extensively and have tried to eluci-date its characteristic diagnostic features. Limited studiesare available in the literature for this entity.9–13

Correlation with the clinical information is a helpfuladjunct to cytologic examination and often necessary foraccurate diagnostic interpretation. History of Von Reckling-hausen’s disease may be helpful to identify the lesion asneural origin.

In this study, the predominant pattern of arrangement wasfascicular (both long and short) with regimentation (parallelarrangement) reminiscent of Verocay body in two cases.Among the cytomorphological features, kinking of the nu-clei or the characteristic wavy pattern of cellular outline wasnot a conspicuous feature. The fibrillary background wasnot a common feature in this study as highlighted by pre-vious studies.9–12 The presence of intranuclear pseudoinclu-sion is a rare finding and cannot be relied on as a diagnostickey feature. The presence of mitotic figures, specifically, theatypical forms, is often a conspicuous finding in MPNSTs.Possibly a constellation of cytologic features such as clus-ters of short and long fascicles of cells admixed with dis-sociated spindle cells of round-ended nuclei and prominentnucleoli on myxoid or fibrillary background and frequentmitosis may be helpful in the diagnosis of MPNSTs onFNAC.

The diagnosis of benign spindle-cell tumor on FNAC inthree cases was because of poor yield and paucity of mitoticfigures. Histopathological examination in these cases re-vealed extensive fibrosis and hyalinization contributing tolow yield.

The differential diagnosis of MPNST is the other spindle-cell tumors such as fibrosarcoma, leiomyosarcoma, synovialsarcoma, and spindle-cell melanoma.14 The presence of

Fig. 1. Clusters of oval to spindle cells in a case of malignant nerve sheathtumor (MGG, �480).

Fig. 2. Moderately pleomorphic nuclei in a myxoid background (MGG,�240).

Fig. 3. Moderately pleomorphic cells in an extensive myxoid background(MGG, �240).

MALIGNANT PERIPHERAL NERVE SHEATH TUMORS

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gland-like structure along with keratin, vimentin, and car-cinoembryonic antigen positivity may be helpful to diag-nose synovial sarcoma. Perinuclear vacuoles and desminpositivity may be helpful to distinguish leiomyosarcomafrom MPNST. Cytology smears of spindle-cell melanomamay show melanin and the cells may be positive for S-100and HMB-45 immunostaining. Fibrosarcoma may be diffi-cult to distinguish from MPNST on cytology smears. Chro-mosomal alteration may be noted in fibrosarcoma cases.14

Since current management of soft-tissue tumors requirespositive identification of the benign or malignant nature ofa process and the degree of differentiation of sarcomas, atissue diagnosis is necessary.13 Diagnosis of MPNSTs onFNAC is difficult; however, constellation of cytologic fea-tures along with clinical information may be helpful inidentifying the tumor preoperatively.

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11. Vendraminelli R, Cavazzana AO, Poletti A, et al. Fine needle aspira-tion cytology of malignant nerve sheath tumors. Diagn Cytopathol1992;8:559–562.

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