Loss of Y Chromosome in the Malignant Peripheral Nerve Sheet Tumor of a Patient with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. In order to determine whether genomic alterations and/or chromosomal aberrations involved in the malignant progression of NF1 were present in a Korean patient with NF1, molecular and cytogenetic analyses were performed on the pathologically normal, benign, and malignant tissues and primary cells cultured from those tissues of the patient. The comparative genomic hybridization (CGH) array revealed a Y chromosome loss in the malignant peripheral nerve sheet tumor (MPNST) tissue. G-banding analysis of 50 metaphase cells showed normal chromosomal patterns in the histopathologically normal and benign cultured cells, but a mosaic Y chromosome loss in the malignant cells. The final karyotype for the malignant cells from MPNST tissue was 45,X,-Y[28]/46,XY[22]. The data suggest that the somatic Y chromosome loss may be involved in the transformation of benign tumors to MPNSTs.

Tumor de vaina nerviosa periférica maligno asociado a neurofibromatosis tipo 1: informe de dos casos / Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: report of two clinical cases

Introducción: El tumor de vaina nerviosa periférica maligno (TVNPM) es un sarcoma de alto grado de malignidad, originado de componentes de las vainas nerviosas, fibroblastos, células perineurales y células de Schwann, que se asocia a neurofibromatosis tipo 1 con un riesgo de 10 a 13 %. Casos clínicos: Se presentan dos casos de TVNPM asociado a neurofibromatosis tipo 1. El primero presentó dolor moderado sin causa aparente, además de lesión intrarraquídea en resonancia magnética nuclear, manejada quirúrgicamente en dos ocasiones. Histológicamente correspondió a lesión neurofibromatosa en transición con neoplasia maligna. El segundo se manifestó con cifoescoliosis torácica, dolor y aumento de volumen. Asociado a la deformidad, la resonancia magnética mostró tumor en la región torácica posterior (T1 a T8), que fue resecado; se identificó neoplasia sarcomatosa infiltrante, muy celular, con inmunopositividad para proteína S100 y vimentina. Conclusiones: Los TNVPM son sarcomas con alto índice de recurrencia, capaces de producir metástasis a distancia desde etapas tempranas. A pesar de la resección amplia, los pacientes descritos no sobrevivieron dado el avance y tamaño de las lesiones. Por el crecimiento progresivo de los TNVPM y la dificultad anatómica para su abordaje, deberá tenerse un control estrecho de los pacientes con neurofibromatosis tipo 1 a fin de identificar tempranamente la transformación maligna de las lesiones.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a sarcoma with a high grade of malignancy originating in the nerve sheath components, fibroblasts, perineural cells, and Schwann cells. It is associated with neurofibromatosis type 1 (NF-1) with a risk of 10-13%. CLINICAL CASES: We present two cases of NF-1-associated MPNST. The first patient presented moderate pain with no apparent cause, in addition to the presence of intraspinal lesion demonstrated by nuclear magnetic resonance imaging (NMRI), which was managed surgically on two occasions. Histologically, it corresponded to a neurofibromatosis lesion in transition with malignant neoplasm. The second case manifested with thoracic kyphoscoliosis, pain, and an increase in volume. Associated with the deformity, MRI showed a withering tumor in the posterior thoracic region (T1-T8), observing an infiltrating, cellular sarcomatous neoplasm with immunopositivity for S-100 protein and vimentin. CONCLUSIONS: MPNSTs are sarcomas with a high index of recurrence with the ability to produce distant metastasis during early stages. Despite wide resection, patients did not survive due to the advancement and size of the lesions (determining factors in the prognosis). Due to the progressive growth of MPNST and the anatomic difficulty for its approach, there should be strict surveillance of patients with NF-1 for early detection of malignant transformation in these lesions.