Cytogenetics of Spindle Cell/Pleomorphic Lipomas: Karyotyping and FISH Analysis of 31 Tumors

Panagopoulos, Ioannis; Gorunova, Ludmila; Lund‐Iversen, Marius; Andersen, Kristin; Andersen, Hege Kilen; Lobmaier, Ingvild; Bjerkehagen, Bodil; Heim, Sverre

doi:10.21873/cgp.20077

Cited by 12 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar loss or deletion pattern has repeatedly been reported not only for spindle-cell/pleomorphic lipomas (19,24,25) but also other benign connective tissue tumors such as cellular angiofibroma (26,27), angiolipoma (28), and pseudoangiomatous pleomorphic/spindle-cell lipoma (29). Additionally, FISH studies have demonstrated heterozygous deletions/losses of the FOXO1/RB1 loci in cellular angiofibromas and extramammary and vaginal myofibroblastomas (13,(30)(31)(32)(33)(34).…”

Section: Discussionsupporting

confidence: 74%

“…The second clone showed monosomy 13 together with a structural rearrangement in which part of the q arm of chromosome 19 had been lost (q13-qter) while additional material of unknown origin was attached to chromosome band 19q13 (Figure 2A). This corresponded to the following karyotype: 45,XY,-13[3]/44~45,idem,add (19…”

Section: Resultsmentioning

confidence: 99%

“…Fresh tissue from a representative area of the resected tumor was used in further analyses. Cells were short-term cultured, harvested and processed for cytogenetic investigation, G-banded, and karyotyped as previously described (19). The methods for aCGH analysis have been described in detail elsewhere (20).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Monosomy 13 in Mammary Myofibroblastoma

et al. 2021

View full text Add to dashboard Cite

Background/Aim: Myofibroblastoma of the breast is a rare benign mesenchymal tumor whose morphology is similar to that of spindle-cell lipoma. The few hitherto genetically investigated mammary myofibroblastomas have been shown to have had loss of material from chromosome 13, changes that are also common in spindle-cell lipoma. Our aim was to add to the existing knowledge of genetic aberrations in mammary myofibroblastoma by investigating another such tumor. Materials and Methods: Cytogenetic and array comparative genome hybridization (aCGH) analyses were performed on a surgically removed mammary myofibroblastoma from a 76-year-old man. Results: Shortterm cultured cells from the tumor showed the karyotype 45, XY,idem,add(19)(q13)[cp2]. aCGH detected loss of one entire chromosome These findings add to the evidence that loss of 13q material is typical of mammary myofibroblastomas.Mammary myofibroblastoma is a rare benign mesenchymal tumor of the breast reported for the first time in 1987 in 11 male and 5 female adult patients as a lesion "largely composed of myofibroblasts arranged in fascicular clusters with interspersed bands of hyalinized collagen" (1). Until 2018, fewer than 90 tumors had been reported (2). In most of the publications (3-12), single cases were described adding to the evidence that these are rare tumors. Genetic information on mammary myofibroblastoma is available for 21 tumors: two were examined by G-banding and karyotyping (10); ten by fluorescence in situ hybridization (FISH) analysis using a probe specific for the forkhead box O1 (FOXO1) gene which maps to chromosome sub-band 13q14.11 (11,(13)(14)(15); eight using a FISH probe for the RB transcriptional corepressor 1 (RB1 located on 13q14.2) gene (16, 17); and one tumor was examined by OncoScan as part of a copy-number variant study of 11 benign mesenchymal tumors (18). Because of the rarity of the tumor and the limited genetic information, we present here another mammary myofibroblastoma examined by banding cytogenetics and array comparative genome hybridization (aCGH). Materials and MethodsEthics statement. The study was approved by the Regional Ethics Committee (Regional komité for medisinsk forskningsetikk Sør-Øst, Norge; http://helseforskning.etikkom.no; 2010/1389/REK sør-øst A). Written informed consent was obtained from the patient. The Ethics Committee's approval included a review of the consent procedure. All patient information has been de-identified. Case Report. A tumor was removed from the breast of a 76-year-old male patient. It measured 5×4×3 cm, had a solid consistency and was well demarcated from the surrounding adipose tissue (Figure 1A). Microscopically, the tumor was partly well demarcated from surrounding adipose tissue in some areas (Figure 1B) but in other areas less so (Figure 1C). The tumor cells were elongated and intermingled with hyaline fibers (Figure 1D). Loosely arranged spindle cells with indistinct cell borders were seen (Figure 1E). Mitotic figures were sparse. Necrosis was not present. No ductal structures w...

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Monosomy 13 in Mammary Myofibroblastoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Fresh tissue from a representative area of the tumors was analyzed cytogenetically as previously described (20).…”

Section: G-banding and Karyotypingmentioning

confidence: 99%

NDRG1-PLAG1 and TRPS1-PLAG1 Fusion Genes in Chondroid Syringoma

Panagopoulos

Gorunova

Andersen

et al. 2020

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: Chondroid syringoma is a rare benign tumor emanating from sweat glands. Although rearrangements of the pleomorphic adenoma gene 1 (PLAG1) have been reported in such tumors, information on PLAG1 fusion genes is very limited. Materials and Methods: Cytogenetic, fluorescence in situ hybridization, RNA sequencing, array comparative genomic hybridization, reverse transcription polymerase chain reaction, and Sanger sequencing analyses were performed on two chondroid syringoma cases. Results: Both tumors had structural rearrangements of chromosome 8. An NDRG1-PLAG1 transcript was found in the first tumor in which exon 3 of PLAG1 was fused with exon 1 of NDRG1. A TRPS1-PLAG1 chimeric transcript was detected in the second chondroid syringoma in which exon 2 or exon 3 of PLAG1 was fused with exon 1 of TRPS1. Conclusion: The NDRG1-PLAG1 and TRPS1-PLAG1 resemble other PLAG1 fusion genes inasmuch as the expression of PLAG1 comes under the control of the NDRG1 or TRPS1 promoter. Chondroid syringoma, also known as mixed tumor of the skin, is a rare benign tumor emanating from sweat glands and able to display a wide array of histological patterns (1-5). It may have histological similarities with another benign exocrine gland tumor, pleomorphic adenoma or mixed tumor of the salivary glands, something that may cause differential diagnostic difficulties (3, 5, 6). The name chondroid syringoma was coined by Hirsch and Helwing (3) because of the invariable presence in the tumor of sweat gland elements (syringoma) and because cartilage-like material (chondroid) was also present in most tumors they studied (3). Chondroid syringoma most commonly occurs in the headand-neck region of middle-aged males (3, 5, 7-9) but can also be found in the axilla and on the anterior chest, trunk, extremities, and scrotum (3, 7, 10-19). We studied genetically two chondroid syringomas finding fusion of the pleomorphic adenoma gene 1 (PLAG1) at 8q12.2 in one with the gene N-myc downstream regulated 1 (NDRG1), which maps to chromosome subband 8q24.22, and in the second with the gene transcriptional repressor GATA binding 1 (TRPS1), which maps to 8q23.3. Materials and Methods Ethics statement. The study was approved by the regional Ethics Committee (Regional komité for medisinsk forskningsetikk Sør-Øst, Norge, http://helseforskning.etikkom.no) and written informed consent was obtained from the patients. The ethics committee's approval included a review of the consent procedure. All patient information has been de-identified. Case description Case 1. A 60-year-old male without any relevant medical previous history was surgically treated for a tumor located at the left ankle. The tumor was found to be consistent with a chondroid syringoma. Surgical margins were doubtful. Six years later re-excision was performed. Macroscopically the tumor was lobulated, but well demarcated. The cut section was soft and gelatinous intermingled with harder areas. Microscopically the tumor was composed of small cystic spaces, areas with myxoid tissue and areas wit...

show abstract

“…Fresh tissue from a representative area of the tumor was short-term cultured and analyzed cytogenetically as previously described (19).…”

Section: G-banding and Karyotypingmentioning

confidence: 99%

Fusion of the Genes PHF1 and TFE3 in Malignant Chondroid Syringoma

Panagopoulos

Gorunova

Lund‐Iversen

et al. 2019

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: Malignant chondroid syringoma is a rare tumor of unknown pathogenesis. Materials and Methods: Genetic analyses were performed on a malignant chondroid syringoma. Results: G-banding analysis of shortterm cultured tumor cells yielded the karyotype 46,Y,t(X;6)(p11;p21)[15]/46,XY[2]. RNA sequencing detected an in-frame fusion of PHF1 from 6p21 with TFE3 from Xp11, verified by RT-PCR and Sanger sequencing. Genomic PCR showed that the PHF1-TFE3 junction was identical to the fusion found by RNA sequencing and RT-PCR. Conclusion: Malignant chondroid syringoma is genetically related to tumors with PHF1 rearrangements such as low-grade endometrial sarcoma and ossifying fibromyxoid tumor, but also with tumors having TFE3 rearrangements such as renal cell carcinoma, alveolar soft part sarcoma, PEComa, and epithelioid hemangioendothelioma. Further investigations on malignant chondroid syringomas are needed in order to determine whether genetic heterogeneity exists among them and the clinical impact of the PHF1-TFE3 fusion. Malignant chondroid syringoma, also known as malignant mixed tumor of the skin, is a very rare tumor with less than 50 cases being described in the relevant literature. It is considered to be the malignant counterpart of benign chondroid syringoma (benign mixed tumor) (1, 2). Malignant chondroid syringomas are twice as common in women as in men and show predilection for the trunk and extremities (1-3). The clinical course is unpredictable (4). Half of the reported cases had local recurrences whereas nodal and distant metastases were observed in 39% and 36% of the cases, respectively. The most common sites for distant metastases are the lungs, bone, and brain (4). Malignant chondroid syringoma is composed of both epithelial and mesenchymal tissue. The epithelial component consists of neoplastic cells with hyperchromatic nuclei and abundant mitotic figures, with occasional areas of necrosis. The mesenchymal component may show myxoid, chondroid, osteoid, adipose or fibrous features enclosing clusters of epithelial cells (1-3). Malignant and benign chondroid syringomas are cutaneous myoepithelial neoplasms (5-9). Genetic studies of both cutaneous and soft tissue myoepithelial neoplasms have demonstrated considerable genetic heterogeneity (10-14). In some of these tumors, EWSR1-ZNF444, EWSR1-PBX1, EWSR1-PBX3 or EWSR1-POU5F1 fusion genes have been found (10, 12, 13, 15) whereas others had rearrangements of PLAG1 (11, 14). The differential diagnosis for myoepithelial tumor is extremely broad and may include ossifying fibromyxoid tumors (7, 16). In the latter, the PHD finger protein 1 gene (PHF1) is recurrently rearranged (17) with an EP400-PHF1 fusion being detected in some tumors (17, 18). Herein, we present a malignant chondroid syringoma which had a t(X;6)(p11;p21) as the sole karyotypic aberration. Using RNA sequencing and molecular methodologies, we demonstrated that the molecular consequence of the translocation was the fusion of the PHF1 gene from 6p21 with the transcription factor binding t...

show abstract

Cytogenetics of Spindle Cell/Pleomorphic Lipomas: Karyotyping and FISH Analysis of 31 Tumors

Cited by 12 publications

References 32 publications

Monosomy 13 in Mammary Myofibroblastoma

Monosomy 13 in Mammary Myofibroblastoma

NDRG1-PLAG1 and TRPS1-PLAG1 Fusion Genes in Chondroid Syringoma

Fusion of the Genes PHF1 and TFE3 in Malignant Chondroid Syringoma

Contact Info

Product

Resources

About