ORIGINAL ARTICLES

Fine-Needle Aspiration Cytology of Malignant Nerve Sheath Tumors R. Vendraminelli, M.D., A.O. Cavazzana, A. Galligioni, M.D., and N. Pennelli, M.D.

M.D.,

A. Poletti,

Precise preoperative diagnosis of three malignant nerve sheath tumors (MNST) was based on their remarkably uniform and highly characteristic cytologic appearance. The differential diagnosis with benign nerve sheath tumors and other spindle cell sarcomas is addressed, and the possibility of achieving confident diagnosis on cytologic material from at least some soft-tissue sarcomas is confirmed. Diagn Cytopathol 1992;8:559-562. 1992 Wiley-Liss, Inc.

Key Words: Soft tissue sarcomas; Histology

Fine-needle aspiration (FNA) biopsy has gained wide acceptance among pathologists during the past few years as a useful technique in the evaluation of primary and metastatic lesions. This method has been successfully employed in recognizing the benign or malignant nature of most epithelial lesions for which well established cytological criteria are currently available. The cytologic diagnosis of soft-tissue tumors still represents a challenge, due to both the relative rarity of these lesions and the few large series reported in literature.’-’ Indeed, FNA was found be highly effective in distinguishing malignant from benign lesions, 2,6 but it often did not allow a correct classification of sarcomas, and an error rate of about 30% was reported. We describe cytological findings in three cases of malignant nerve sheath tumors (MNSTs) with special attention to the cytomorphological differential diagnosis with other spindle-cell tumors.



Materials and Methods Material was obtained with a fine needle (25- to 27-gauge) attached to a 10-ml plastic syringe, as previously described. Some smears were air-dried and then stained by



Received August 24, 1991. Accepted January 8, 1992. From the Ospedale Civile di Pordenone, ULSS 11; Istituto di Anatomia Patologica, Universita di Padova, Istituto di Anatomia ed Istologia Patologica, I1 Universita di Roma “Tor Vergata,” Rome, Italy. Address reprint requests to Dr. Andrea 0 Cavazzana, Institute of Anatomic Pathology, I1 University of Rome “Tor Vergata,” Via Carnevale, 8, 00173 Rome, Italy.

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the May-Grunwald-Giemsa (MGG) method, while others were alcohol-fixed and stained according to the Papanicolaou method. Surgical specimens were routinely formalinfixed and paraffin-embedded; 5-p-thick sections were then processed for staining with H&E, PAS, and reticulin stains. Immunocytochemical analysis of paraffin-embedded sections was performed according to the avidin-biotincomplex (ABC) technique as previously described, * and the following antibodies were used to confirm the microscopic diagnosis: anti-cytokeratin (monoclonal, AE- 1, Dako, 1:40), anti-desmin (monoclonal, Dako, 1:loo), antiNSE (monoclonal, Dako, 1:200), anti-muscle-specific actin (monoclonal, Lipshaw), and anti-S- 100 protein (polyclonal, Dako, 1:600).

Case 1 A 70-yr-old woman with a persistent lumbago of 4 months duration referred to the left flank, was admitted in April 1988. Physical examination disclosed an ill-defined mass in the left lumbar-dorsal region. A CT scan revealed a retroperitoneal mass of about 8 cm in diameter extending from the left psoas muscle to the subcutaneous planes. FNA was then performed, and a diagnosis of malignant soft-tissue tumor compatible with MNST was formulated.

Case 2 A 49-yr-old woman with a 5 x 3-cm right lateral neck mass was seen at the outpatient clinic in June 1987. At physical examination, it was seen that the patient had numerous caf6-au-lait spots, and many scattered cutaneous sessile fibrous lesions. The FNA smears were interpreted as a malignant soft-tissue tumor, compatible with MNST.

Case 3 A 68-yr-old woman with recurrent abdominal pain following a car accident 2 mo earlier was admitted for evaluation in May 1989. CT scan of the abdomen showed a large retroperitoneal mass of 8 x 7 X 7 cm adjacent to

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the left psoas muscle. The cytological findings were consistent with a malignant soft-tissue tumor, compatible with MNST.

Results CytologicaI Findings The aspirated material in all three cases was highly cellular, and its cytological appearance was quite similar. Smears showed compact clusters of spindle or oval cells with indistinct cellular borders and little interspersed ground substance. Within the clusters, cells were arranged in a storiform pattern and occasionally displayed evident nuclear palisading (Fig. 1). Numerous loosely distributed cells with distinctive cytonuclear characteristics were scattered among the clusters. The basophilic cytoplasm was at times finely vacuolated and, in most cases, polarized at one side of the cell with a typical comma-shaped morphology (Fig. 2); occasionally, the cells were arranged in a circular fashion with a rosettoid or pseudoglandular configuration (Fig. 3). Nuclei were spindle-shaped and hyperchromatic with evident nucleoli; occasional larger, bizarre nuclei were also ob-

Fig. 1. Case 1. Short nuclear palisades are a common finding in MNST. Cells are tightly cohesive with very little interspersed extracellular matrix (MGG, X 100).

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served. The nuclei, showed a distinct groove and were often twisted or had a typical pear-shaped appearance (Fig. 4). An intranuclear pseudoinclusion was also frequently observed (Fig. 4) as well as numerous naked nuclei.

His topath o logic Fin dings The tumors were composed of sweeping fascicles of elongated spindle cells, occasionally in a vorticoid arrangement reminiscent of so-called tactoid bodies. Higher magnification disclosed the same cytonuclear characteristics present in the cytologic smears, such as comma-shaped nuclei and intranuclear pseudoinclusions. Positive reactions to S-100 protein and neuron-specific enolase antibodies were demonstrated in all three cases, whereas all the other markers were negative.

Discussion MNSTs are relatively rare lesions that constitute about 10% of all soft-tissue sarcomas, often associated with Von Recklinghausen’s disease. l o According to their presumed origin from cells covering the peripheral nervous

Fig. 2. Case 1. The characteristic cytonuclear morphology is depicted in this field. Cells have short asymmetric cytoplasms with spindle-shaped nuclei displaying a twisted appearance (MGG, x 100).

FNA CYTOLOGY OF MALIGNANT NERVE SHEATH TUMORS

Fig. 3. Case 2. A pseudoglandular arrangement is occasionally observed in small clusters (MGG, x 100).

Fig. 4. Case 3. Naked nuclei with a peculiar pear-shaped morphology are commonly observed in MNST. A distinct nuclear pseudoinclusion is seldom encountered (inset) (MGG, X 100).

trunks, they may arise anywhere in the body, but the retroperitoneum, and the extremities are the most commonly involved regions. Unlike their benign counterpart, MNSTs may cause difficulties in the differential diagnosis with other spindlecell sarcomas, particularly fibrosarcoma and leiomyosarcoma. Moreover, reports of cytological findings in MNSTs are scarce, and to our knowledge the literature counts only nine cases. 6,11-15 It has been stressed that the histomorphological diagnosis of MNST may be extremely difficult in the absence of a clear relationship with a major nervous trunk or a clinical history of multiple neurofibromatosis. l 6 In fact, MNSTs share many histologic aspects with other spindle cell sarcomas; the storiform pattern and the regular alignment of nuclei into palisades are frequently encountered in smooth-muscle tumors. Furthermore, MNST often lack distinctive histomorphologic traits of neural differentiation, such as tactoid and/or Verocay bodies. Cytonuclear features are often obscured in histologic sections, but in the present study, the single most reliable morphological marker of nerve sheath differentiation was

observed in cytological smears. Indeed, in every case, it was possible to recognize typical comma-shaped cells, occasionally arranged in palisades, in conjunction with highly characteristic twisted nuclei. The differential diagnosis mainly include benign forms of nerve sheath tumors and other spindle-cell sarcomas, principally leiomyosarcoma and fibrosarcoma. Benign nerve sheath lesions are easily recognized as cytological and histological findings are similar. These tumors, in fact, give rise to hypocellular smears that show loose tissue fragments with a fibrillar ground substance and more cellular clusters of spindle cells forming Verocay bodies, l’ in correspondence to the mixture of Antoni A and B areas observed on histology. On rare occasions, these lesions may be mistaken for sarcomas, mostly due to the occasional nuclear polymorphism and hyperchromasia that characterizes the “ancient” form of schwannomas. l 8 Despite the similar cytonuclear morphology, however, MNSTs show a higher cellularity than their benign counterpart and a more evident and diffuse nuclear pleomorphism and hyperchromasia. Leiomyomatous tumors may show tissue fragments Diagnostic Cytopathology, Vol 8, No 6

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with a fascicular or storiform pattern and/or a rhythmic arrangement of nuclei closely resembling nerve sheath tumor palisades. Nevertheless, the cytonuclear morphology of MNST strongly differs from that of smooth muscle tumors, in which the fibrillar eosinophilic cytoplasm is symmetrically arranged around blunt-ended nuclei (Fig. 5). The absence of nuclear palisading Verocay bodies and the more pointed nuclei helps distinguish fibrosarcoma from MNST. The presence of intranuclear pseudoinclusions deserves special mention, since this finding may be observed in other soft-tissue tumors, such as lipomatous tumors l 9 and paraganglioma, 2o as well as many epithelial lesions. 21,22 Therefore, although it has been previously reported to occur in schwannomas,23 it should not be considered a diagnostic sign of a nerve-sheath tumor. FNA thus not only may provide useful information in discriminating benign from malignant MNST, but may also enable a precise preoperative diagnosis of MNST on the basis of distinctive, and highly characteristic cytonuclear findings. These results encourage further studies

Fig. 5. The presence of spindle-shaped nuclei with smooth borders and a distinctly fibrillar cytoplasm distinguishes smooth muscle from nerve sheath tumors (cf. Fig. 2) (PAP, x 100).

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with the FNA technique in the preoperative diagnosis of soft-tissue lesions.

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Fine-needle aspiration cytology of malignant nerve sheath tumors.

Precise preoperative diagnosis of three malignant nerve sheath tumors (MNST) was based on their remarkably uniform and highly characteristic cytologic...
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