Elsevier

Human Pathology

Volume 35, Issue 11, November 2004, Pages 1404-1412
Human Pathology

Original contributions
Genetic instability in primary leiomyosarcoma of bone

https://doi.org/10.1016/j.humpath.2004.06.009Get rights and content

Abstract

Primary leiomyosarcoma (LMS) of bone is an exceedingly rare entity on which to date no molecular data have been reported. In a series of 6 tumors (5 grade IIB, 1 grade IIA), we assessed the prevailing genetic stability by microsatellite analysis at 7 loci. The IIB tumors demonstrated a rate of genomic loss as high as 90%, accompanied by an intratumoral heterogeneity in 30% of conspicuous markers. High microsatellite instability in the severe type was not observed, although hMLH1 immunostaining was consistently negative. We assume that intraosseous LMS pertains to “deletor phenotype” tumors. We did observe a locus-specific MSI in our marker linked with hMSH2. Immunostaining and allelotyping indicated a knock-out of pRb in all cases, confirming its major role in sarcomas. Only the stage IIB tumors (4 of 5) pointed to p53 inactivation. In addition, the human telomerase subunit-linked markers exhibited high rates of chromosomal loss. The stage IIA tumor still confined to the bone displayed no genetic instability. Moreover, the proliferation index made a clear distinction between the IIA and IIB tumors (5% vs 30%). We propose to further investigate the usefulness of loss of heterozygosity as a progression marker in this entity.

Section snippets

Tumor material

The study group comprised 6 patients (3 men and 3 women) with primary iLMS. The patients ranged in age from 30 to 54 years (mean, 40 years).

Imaging techniques

Preoperative 2-plane radiographs of all lesions were reviewed. Additional diagnostic methods (computed tomography [CT] and magnetic resonance imaging [MRI]) were used. These radiologic investigation techniques confirmed the tumor’s intraosseous nature (Fig 1).

Histomorphologic characterization

Specimens were fixed in formalin and embedded in paraffin immediately after resection.

Clinical and histopathologic features

Clinical data for the study group patients are summarized in Table 1. In all patients, the initial symptom was pain. After 2 to 12 months (mean, 5 months), the diagnosis was determined. The average follow-up time was 19 months (range, 6 to 31 months). Patient history was recorded. Tumor size ranged from 96 to 1764 cm3 (mean, 630 cm3). Two patients underwent adjuvant chemotherapy. Three patients are still alive, though 1 of them has developed pulmonary metastases. The tumors, just located in

Allelotyping

Soft tissue LMS is differentiated into 3 groups (LMS of uterine, gastrointestinal, and soft tissues). LMS of soft tissue is classified as LMS of deep soft tissue, cutaneous tissue, subcutaneous tissue, and, last but not least, vascular origin. By definition, soft tissue tumors arise in extraskeletal tissue; primary iLMS constitutes an entity by itself, though most probably arising from smooth muscle progenitor cells in microvessels.14 The existence of these subgroups of LMS has been validated

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