Nonkeratinizing Nasopharyngeal Carcinoma, Undifferentiated Type With Trisomy 2: A Case Report and Short Review of Cytogenetic and Molecular Literature.

Carcinoma originating from the surface epithelium of the nasopharynx is classified by the World Health Organization (WHO) as nasopharyngeal carcinoma (NPC) and has 3 main types: keratinizing squamous cell carcinoma (WHO type 1) and nonkeratinizing carcinoma, differentiated (WHO type II), and undifferentiated (WHO type III). Nonkeratinizing NPC is strongly associated with prior Epstein-Barr virus (EBV) infection. These tumors may be divided into differentiated and undifferentiated carcinoma. Histologically, the tumor is characterized by syncytia of large malignant cells with vesicular nuclei, conspicuous nucleoli, and easily observed mitotic figures. We report a case of a 14-year-old boy diagnosed with EBV and human papillomavirus (HPV)-positive NPC (WHO type 3) with cytogenetics showing the presence of mosaic trisomy 2. This case report brings to light a rare cytogenetic aberration to our knowledge only reported once before in the literature in a xenograft model.

Malignant glioma with primitive neuroectodermal tumor-like component (MG-PNET): novel microarray findings in a pediatric patient.

Central nervous system (CNS) tumors exhibiting dual features of malignant glioma (MG) and primitive neuroectodermal tumor (PNET) are rare and diagnostically challenging. Previous studies have shown that MG-PNET carry MYCN or MYC gene amplifications within the PNET component concomitant with glioma-associated alterations, most commonly 10q loss, in both components [9]. Here we confirm and extend the profile of molecular genetic findings in a MG-PNET involving the left frontal lobe of a 12-year-old male. Histologically, the PNET-like component showed morphological features akin to anaplastic medulloblastoma highlighted by widespread immunoreactivity for ßIII-tubulin (TUBB3) and nonphosphorylated neurofilament protein, and to a lesser degree, Neu-N, synaptophysin, and CD99, whereas the gliomatous component was demarcated by glial fibrillary acidic protein (GFAP) labeling. Immunohistochemical labeling with an anti-H3K27M mutant-specific antibody was not detectable in either gliomatous and/or PNET-like areas. Interphase fluorescent in situ hybridization (FISH) study on touch preparations from frozen tumor and formaldehyde-fixed, paraffin-embedded histological sections showed amplification of MYC in both PNET-like and gliomatous areas. Single nucleotide polymorphism (SNP) microarray analysis revealed that the tumor carried gains of multiple chromosomes and chromosome arms, losses of multiple chromosomes and chromosome arms, gains of multiple chromosomal segments (not limited to amplification of chromosomal segments 4q12 including PDGFRA, and 8q24.21 including MYC), and a hitherto unreported chromothripsis-like abnormality on chromosome 8. No mutations were identified for IDH1, IDH2, or BRAF genes by sequence analysis. The molecular genetic findings support the presence of a CNS-PNET as an integral part of the tumor coupled with overlapping genetic alterations found in both adult and pediatric high-grade gliomas/glioblastoma. Collectively, microarray data point to a complex underpinning of genetic alterations associated with the MG-PNET tumor phenotype.
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Unusual genetic aberrations including a deletion of KLF6 tumor suppressor gene revealed by integrated cytogenetic approaches in a pediatric ewing sarcoma.

Ewing sarcoma is the third most common sarcoma in children and young adults. Its characteristic chromosomal rearrangement results in a chimerical EWSR1-ETS transcription factor. Secondary genetic alterations are very common. Membranous expression of CD99 is seen in almost all tumors. We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6. The latter has not been described previously in pediatric neoplasms. Molecular pathways in tumorigenesis and genetic complexity in cancer are discussed.

Co-occurrence of non-mosaic trisomy 22 and inherited balanced t(4;6)(q33;q23.3) in a liveborn female: case report and review of the literature.

Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non-mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non-mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non-mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non-mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed.

Tetrasomy 13q32.2qter due to an apparent inverted duplicated neocentric marker chromosome in an infant with hemangiomas, failure to thrive, laryngomalacia, and tethered cord.

BACKGROUND: Approximately 100 small supernumerary marker chromosomes (sSMCs) with a non-α-satellite neocentromere structure have been reported in the literature. Of the few derived from chromosome 13, five have consisted of inverted duplicated segment 13q32qter. CASE REPORT: We herein describe the sixth case, characterized by genome wide SNP array, conventional cytogenetics and FISH studies. The de novo occurrence of the marker, the poor prognosis and the presence of hemangiomas are consistent with previous cases. CONCLUSION: We hereby expand the clinical spectrum of this rare cytogenetic disorder and suggest a possible mechanism for the pathogenesis of associated congenital vascular malformations.

FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma.

Rhabdomyosarcoma is the most common pediatric soft tissue malignancy. Two major subtypes, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma, constitute 20 and 60% of all cases, respectively. Approximately 80% of alveolar rhabdomyosarcoma carry two signature chromosomal translocations, t(2;13)(q35;q14) resulting in PAX3-FOXO1 fusion, and t(1;13)(p36;q14) resulting in PAX7-FOXO1 fusion. Whether the remaining cases are truly negative for gene fusion has been questioned. We are reporting the case of a 9-month-old girl with a metastatic neck mass diagnosed histologically as solid variant alveolar rhabdomyosarcoma. Chromosome analysis showed a t(8;13;9)(p11.2;q14;9q32) three-way translocation as the sole clonal aberration. Fluorescent in situ hybridization (FISH) demonstrated a rearrangement at the FOXO1 locus and an amplification of its centromeric region. Single-nucleotide polymorphism-based microarray analysis illustrated a co-amplification of the FOXO1 gene at 13q14 and the FGFR1 gene at 8p12p11.2, suggesting formation and amplification of a chimerical FOXO1-FGFR1 gene. This is the first report to identify a novel fusion partner FGFR1 for the known anchor gene FOXO1 in alveolar rhabdomyosarcoma.

Study of an ovarian sclerosing stromal tumor presenting as vaginal bleeding in a 7-month-old.

This communication describes the histological, immunohistochemical, ultrastructural, and cytogenetic study of an ovarian sclerosing stromal tumor resected from a 7-month-old girl who presented with vaginal bleeding. The tumor is very rare, its pathogenesis is not clear, and its hormonal activity has been subject to debate. In addition, it has been rarely seen in children and never in infants, with the youngest patient reported being 10 years of age. Histological study of the tumor showed a process of multinodular asynchronous growth followed by gradual loss of cells, hyalinization, and eventual transformation into corpora albicantia-like structures, thus indicating that the process may be more akin to an ovarian nodular follicular hyperplasia than to a classical neoplasm. The study also documented an elevated proliferative MIB-1 index in the process, which had not been investigated in earlier reports, and illustrated the immunohistochemical reactivity of some of its stromal cells to progesterone receptors.

Histological study of osteoid osteoma's blood supply.

The osteoid osteoma is a painful lesion with a special predilection for the femur and tibia of young patients. Although the lesion has been described as richly innervated, its vascular supply has not been critically appraised to date in the pathology literature. To this end, we have undertaken a morphological study of 16 archival cases of osteoid osteoma, focusing primarily on the patterns of vascularization, utilizing traditional histological and immunohistochemical approaches. The study demonstrated that a prominent arterial and arteriolar blood supply was a constant finding within the various zones of soft tissues, skeletal muscle, and bone surrounding the nidus. It also showed that the caliber of the vessels underwent gradual attenuation throughout their centripetal course toward the nidus, where the vessels lost their muscularis as they merged into the capillary network of the nidus. Immunostaining with antibodies to neurofilament and S100 proteins revealed a pattern of innervation that was overall less exuberant than that described in some reports and that was virtually absent from the nidus. Taken together with data reported in the radiological literature, our findings lead us to wonder whether the osteoid osteoma may represent a response to the local stimulation of bony tissue by a primarily aberrant vasculature, a hypothesis that warrants further elucidation using state-of-the-art imaging approaches.

Glioneuronal phenotype in a diencephalic pilomyxoid astrocytoma.

We report the presence of divergent populations of cells in a hypothalamic/chiasmatic pilomyxoid astrocytoma of an 11-month-old male, exhibiting differential immunohistochemical localizations for glial fibrillary acidic protein (GFAP) and synaptophysin. The tumor cells were negative for Neu-N and neurofilament protein. Ultrastructurally, the tumor comprised 2 cell types, one with features attributable to a neuronal phenotype alongside cells exhibiting an overt astroglial phenotype. This composite organization was confirmed by confocal microscopy, which revealed 2 distinct, albeit tightly interwoven, populations of GFAP and synaptophysin-labeled tumor cells. Our results indicate that a subset of the so-called pilomyxoid astrocytomas of the hypothalamic/chiasmatic region may represent phenotypically mixed glioneuronal neoplasms distinct from the pilocytic astrocytomas.