Two novel translocations, t(2;4)(q35;q31) and t(X;12)(q22;q24), as the only karyotypic abnormalities in a malignant peripheral nerve sheath tumor of the skull base

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Abstract

Malignant peripheral nerve sheath tumor (MPNST) is a rare neoplasm that originates from Schwann cells and comprises 5%–10% of soft tissue sarcomas. Cytogenetic analysis of this tumor has shown a highly complex karyotype, and no single chromosomal aberration has been reported to date. We combined spectral karyotyping analysis and G-banding for cytogenetic characterization of this unique tumor, which originated in the anterior skull base. We report the simultaneous occurrence of a t(2;4)(q35;q31) and a t(X;12)(q22;q24) as the only chromosomal abnormalities in this tumor. To the best of our knowledge, apparently balanced translocations have not been identified previously in MPNST.

Introduction

Malignant peripheral nerve sheath tumor (MPNST), also known as neurofibrosarcoma, malignant Schwannoma, or neurogenic sarcoma, is a rare neoplasm of Schwann-cell origin. The tumor is relatively more common among adults between 20 and 50 years of age, and most frequently involves the limbs and trunk [1]. MPNST may be sporadic or associated with neurofibromatosis type 1 (NF-1), a hereditary autosomal dominant disorder known to predispose one to MPNST [2]. The NF1 gene is a tumor suppressor gene that was mapped to 17q11.2 [3], and frequent allelic losses of this gene are found in both sporadic and NF-1–associated MPNST [4], [5]. An MPNST may be highly aggressive, and the propensity for local recurrence of this tumor mandates complete radical excision.

The advance of novel molecular cytogenetic methods, among them spectral karyotyping (SKY), has opened new avenues for characterizing the chromosomal complexity of human malignancies [6], [7]. Cytogenetic characterization of human malignancies may serve as an adjunct to standard pathologic diagnostic tools and for assessment of prognosis [8].

Eighty-two cases of MPNST with chromosomal aberrations have been reported in the literature [9]. None of these cytogenetic studies reported specific karyotypic patterns for this tumor. MPNST frequently have a highly complex karyotype, and no simple balanced translocation has been reported to date. It was further suggested that the complex karyotypes with triploid or near-tetraploid clones might be associated with large-size, high-grade tumors, and may serve as discriminators between malignant and benign peripheral nerve tumors, which almost always display a near-diploid karyotype [10].

In the current study, we combined SKY analysis and a conventional G-banding technique for cytogenetic characterization of a highly aggressive MPNST of the skull base.

Section snippets

Clinical and pathologic parameters

An otherwise healthy 21-year-old man was referred for treatment of a mass that invaded the posterior nasal cavity, ethmoid sinuses, right posterior orbit, and anterior skull base. He complained of right nasal obstruction, intermittent nasal discharge, epiphora, and progressively expanding exophthalmus of his right eye over the past 18 months.

There was no family history of neurofibromatosis 1 or 2, and he had never received radiation or chemotherapy. Physical examination revealed no clinical

Results

A fresh sample of an MPNST of the skull base was excised from a patient with no previous history of radiation or chemotherapy. Ten metaphase cells from three primary cultures were studied using G-banding: they all suggested an abnormal karyotype with two apparently balanced translocations as the sole clonal aberrations (Fig. 2A).

To confirm the presence of an abnormal karyotype, we further analyzed an additional 10 cells using the SKY technique. Cytogenetic analysis of the tumor showed one clone

Discussion

Malignant peripheral nerve sheath tumor is a rare neoplasm, which infrequently involves the anterior skull base. In this study, we applied the G-banding and SKY techniques and found two novel translocations in this unusual tumor. We found that all the analyzed tumor cells had the simultaneous occurrence of apparently balanced t(2;4)(q35;q31) and t(X;12)(q22;q24) as the sole karyotypic abnormalities.

Twenty-one reports of 82 cytogenetically abnormal cases of MPNST have been described in the

Acknowledgements

Esther Eshkol is thanked for her editorial assistance.

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