Lúcia Roque

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry.

Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.

Amplification of chromosome subregion 12p11.2-p12.1 in a metastasis of an I(12p)-negative seminoma: relationship to tumor progression?

Cytogenetic analysis of a metastasis of a human testicular germ cell tumor (seminoma) revealed multiple numerical and structural anomalies, including an abnormally banding region (ABR) present on the short arm of one of the chromosome 12 homologs. Fluorescence in situ- and comparative genomic hybridization experiments revealed that the ABR results from the amplification of 12p11.2-p12.1 derived sequences. We speculate that this particular region may harbor gene(s) relevant for testicular germ cell tumor progression.

Karyotypic characterization of papillary thyroid carcinomas

Cytogenetic studies performed in papillary thyroid carcinoma (PTC) identified chromosome 10q rearrangements with breakpoints at 10q11.2 as the most frequent aberrations in these tumors. In the current study, the authors aimed to identify other chromosomal abnormalities nonrandomly associated with papillary thyroid carcinomas.

Malignant salivary gland neoplasms: a cytogenetic study of 19 cases

A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, myoepithelial carcinoma, basal cell adenocarcinoma, carcinoma ex-pleomorphic adenoma, ductal carcinoma, adenocarcinoma not otherwise specified and undifferentiated carcinoma) were cytogenetically investigated. Previous karyotypic information revealed deletion of the long arm of chromosome 6, loss of chromosome Y and the gain of chromosome 8 as the most recurrent deviations found in these neoplasms. Clonal chromosome aberrations were detected in 11 cases of this series. In 7 of them there were only numerical deviations (gain of chromosomes 2, 7, 8, 10 and X and loss of chromosomes 18, 21 and Y) without concomitant structural anomalies. Structural rearrangements such as t(2;7), t(6;16), t(6;9) and t(1;1) translocations were found in two mucoepidermoid carcinomas, one adenoid cystic carcinoma and one ductal carcinoma, respectively. The wide spectrum of changes found in this group of neoplasms may reflect the diversity in their histogenesis and differentiation phenotypes.

Follicular thyroid carcinoma: Chromosome analysis of 19 cases

Short‐term cultures of 19 follicular thyroid carcinomas were examined cytogenetically. Clonal chromosomal changes were detected in 12 tumors. Two follicular carcinomas had only numerical alterations: one with a hyperdiploid karyotype with trisomies/polysomies of chromosomes 7 and 12, similar to the karyotypes previously identified in a sub‐group of benign thyroid lesions, and the other with monosomy 20. In the remaining ten cases several structural chromosome anomalies were found. Loss of the short arm of chromosome 3 was observed in one tumor. In two widely invasive and metastasizing follicular carcinomas there was a t(7;8)(p15;q24) as the sole abnormality in one case and a der(8)t(7;8)(p15;q24) together with other cytogenetic alterations in the other case. This finding suggests that t(7;8)(p15;q24) may be related to an aggressive behavior of follicular thyroid carcinomas. Genes Chromosomes Cancer 21:250–255, 1998.

Cytogenetic similarities between two types of salivary gland carcinomas: adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

Adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) are low-grade adenocarcinomas of salivary glands with a putative common histogenesis from the intercalated ducts but featuring distinct histological appearances. Hybrid tumors containing areas with histological patterns of both neoplasms have been reported but, to our knowledge, the question of their genotypic similarity has not yet been approached. As part of an ongoing study on cytogenetic characterization of salivary gland tumors, from a group of 24 malignant neoplasms, three out of five cases of ACC and three of four cases of PLGA were selected for their similar karyotypic changes. All of them displayed chromosome 12 abnormalities, affecting the 12q12-q13 region in four (all ACC cases and one PLGA case), 12q22 in one PLGA case, and 12p12.3 in the remaining. From this group of neoplasms, one PLGA and one ACC showed the same t(6;12)(p21;q13). Our findings favor the concept that tumors of salivary glands displaying epithelial and myoepithelial phenotypes share a common histogenesis.

Cytogenetic characterisation of Warthin's tumour

Warthins tumour is a peculiar subtype of monomorphic adenomas of the salivary glands, frequently cystic, and that characteristically associates an epithelial glandular cell component to a dense lymphoid infiltrate. Short-term cultures from 12 Warthins tumours of salivary glands, including 5 previously reported cases were successfully karyotyped and clonal numerical and/or structural changes were detected in 7 of them (58%). 3 cases showed numerical abnormalities with loss of chromosomes Y (2 cases) and X (1 case). The remaining 4 abnormal cases presented the following structural changes: complex translocation t(11;19;16)(q21;p12;p13.3); reciprocal translocations t(6;8)(p23;q22) and t(6;15)(p21;q15) (2 cases); and 1p22, 3p26, 11p13 changes. In 1 case, clonal numerical deviations (+ 7 and -Y) were concurrent with the structural rearrangement t(6;8). Two of these aberrations are suggested to be Warthins tumour-associated: 11q;19p translocation has already been described in 3 cases, and structural rearrangements of 6p23 have also been reported in another case. Our study extends the cytogenetic information about Warthins tumour and identifies two recurrent abnormalities --6p rearrangements and t(11;19)--specific for this salivary neoplasm.

Cytogenetic and fluorescence in situ hybridization studies in a case of anaplastic thyroid carcinoma.

Cytogenetic analysis of a case of anaplastic thyroid carcinoma revealed multiple numerical and structural chromosomal changes, including a der(9) add(9)(p22)hsr(9)(p?). Fluorescence in situ hybridization (FISH) studies performed to identify the genetic nature of this derivative chromosome showed that both the additional material and the hsr region were composed of only chromosome 9 sequences and that the C-ABL oncogene was not one of the genes harbored at the hsr region. We suggest that amplification of gene(s) located at chromosome 9, other than the C-ABL, may play a significant role in anaplastic evolution of thyroid carcinomas.

Atypical teratoid/rhabdoid tumour following craniopharyngioma radiotherapy during childhood.

Dear Editor: This letter reports a rare clinical issue based on the onset of an atypical teratoid/rhabdoid tumour (AT/RT), consequently after radiotherapy. Besides being rare, this is a first report of this event after craniopharyngioma radiotherapy. Craniopharyngioma radiotherapy (RTh) is considered in situations of subtotal surgical excision, performed when there is a high risk of morbidity associated with total resection. Tumour development after RTh is well known and accepted. To the best of our knowledge, this is the third case of an AT/RT after RTh and the first after craniopharyngioma RTh. The case refers to a 22-year-old female patient submitted to 3D conformational RTh (34Gy) at the age of 12 years, after a subtotal surgical removal of a craniopharyngioma. During follow-up, the tumour residue remained stable. She was admitted to the hospital with a 2-days evolution of headaches, nausea and vomiting. Neurological findings showed somnolence with psychomotor slowing but reacting to verbal stimulus, without focal deficits. MRI showed a large sagittal frontal lesion with left frontal extension andmarkedmass effect with heterogeneous contrast enhancement (Fig. 1). Surgery was performed but the tumour was highly vascularized and only a partial removal was possible. At D2 post-operation, a clinical worsening was observed. CT scan showed a bilateral anterior cerebral artery ischemia with intra-tumour haemorrhage. The patient died 4 days after surgery. Neuropathology disclosed a malignant neoplastic tumour, with a high mitotic and proliferative index and areas of geographic necrosis. Immunohistochemical study showed extensive, immunoreactivity for vimentin and epithelial membrane antigen (EMA), polyfocal for neurofilaments, and only focal for glial fibrillary acidic protein (GFAP). INH1 was negative. A diagnosis of AT/RT was done. FISH analysis was performed with several probes for chromosome 22 targeting the SMARCB1/INI1 gene, the PDGFRβ gene, the EWS, HIRA and ARSA genes (Fig. 2). Chromosomal comparative genomic hybridization (CGH) was also performed, and abnormalities were detected by comparing the dynamic standard reference interval to the confidence interval of the mean ration profile of the test samples. CGH analysis revealed a relatively complex karyotype where the chromosomal alterations were observed, namely a deletion involving 22q. AT/RT affects more frequently children less than 3 years old, with only 42 adult cases published so far. Despite aggressive treatment protocols, it has a poor prognosis mainly in children with less than 1-year survival. Our case showed the histological hallmark of this entitywhich are rhabdoid cells with undifferentiated elements with areas of differentiated mesenchymal cells. In immunohistochemical * Edson Oliveira edsoliveira@gmail.com

Biphasic synovial sarcoma

© 2008 The Authors JEADV 2009, 23, 441–496 Journal compilation