Malignant rhabdoid tumor. A study with two established cell lines

Abstract

Background. Malignant rhabdoid tumor (MRT), originally described as a rare renal sarcoma in childhood, has been known to express phenotypic diversity. In this study, unique characteristics of the MRT cells were investigated by using established cell lines. Methods. Immunocytochemical, ultrastructural, cytogenetic, and molecular (by polymerase chain reaction, PCR) analyses were done for two MRT cell lines, one of renal and one of extrarenal origin, before and after differentiation‐induction with either 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA) or transretinoic acid (RA). Results. The proliferating cells in the original tumor tissues as well as in the established cell lines demonstrated neural, epithelial, and mesenchymal markers morphologically. Both cell lines had karyotypic abnormalities including chromosome 22q11.2. The cell line from the extrarenal MRT, Tm87–16, demonstrated distinct morphologic changes with neuroblastic differentiation and produced numerous neuritic processes after treatment with either TPA or RA. The cell line from the renal MRT, STM91‐01, suggested schwannian differentiation but did not change morphologically after chemical induction. Both cell lines expressed c‐myc, but did not express N‐myc, MyoD1, tyrosine hydroxylase, or neural cell adhesion molecule (N‐CAM). With PCR and immunocytochemical study, a high level of chromogranin expression was detected by the cells of Tm87–16 only after TPA induced differentiation. Conclusions. MRT cells demonstrated diverse phenotype of neuro‐ecto‐mesenchymal differentiation. The results of this study suggest that MRT may be derived from a primitive pluripotential cell, such as neural crest or equivalent. MRT, therefore, might be categorized as one of the subsets of primitive neuroectodermal tumor.

Expression of neural stem cell markers in malignant rhabdoid tumor cell lines

“…Previous studies have shown that NSC acting as CSC is recognized in CNS (24)(25)(26)(27)(28)(29). In the present study, we examined the expression of NSC markers such as CD133, nestin and Msi-1 before and after 4-HPR induced differentiation in MRT cell lines to elucidate the cytological characteristics of MRT cells that are considered to derive from neuroectodermal origin (8,9,12).…”

“…Primary MRT also has been described in the central nervous system (CNS), paravertebral regions, pelvis, liver, orbit and ovary as well as the kidney (2)(3)(4)(5)(6)(7). A characteristic feature of MRT cells is the presence of large cytoplasmic eosinophilic inclusions (8,9). In the brain, the tumors may present as a mixture of rhabdoid, primitive neuroectodermal, mesenchymal and/or epithelial elements, an entity referred to as atypical teratoid/rhabdoid tumors (10,11).…”

“…Various cellular origins of MRT, such as neuroectodermal (8,9,12), neural (13)(14)(15), epithelial (16), histiocytic (17) or myogenic (18), have been proposed. Despite the variability observed in tumor location and histology, most rhabdoid tumors share a similar genetic origin and are characterized by the presence of mutations in the hSNF5/INI1 gene on chromosome band 22q11.2 (19)(20)(21).…”

Malignant Rhabdoid Tumor of the Floor of Mouth: First Reported Case in the Oral Cavity of an Adult

“…The tumors are composed of large polygonal cells with eccentrically placed nuclei, and demonstrate an intracytoplasmic paranuclear eosinophilic condensation which compresses the nucleus [2]. Electron microscopy and immunohistochemical analysis has confirmed that these eosinophilic paranuclear condensations are composed of intermediate filaments [3]. Uncondensed chromatin and prominent nucleoli can often be found within the nuclei of the tumor cells [2,3].…”

“…The intracytoplasmic paranuclear condensations present in the rhabdoid cells are composed of intermediate filaments [3]. Most commonly, these are keratin filaments and can be highlighted by low and high molecular weight keratin immunohistochemical stains [24,25].…”