Potentially actionable FGFR2 high-level amplification in thymic sebaceous carcinoma. 2020

Stefan Porubsky, and Peter Jessup, and Damien Kee, and Rajiv Sharma, and Ayame Ochi, and Huiling Xu, and Jens J Froelich, and Louise Nott, and Clare Scott, and Raef Awad, and Cristina Moldovan, and Ashutosh A Hardikar, and Hanibal Bohnenberger, and Stefan Küffer, and Philipp Ströbel, and Alexander Marx
Institute of Pathology, University Medical Centre Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. Stefan.porubsky@umm.de.

Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (AR). One primary thymic carcinoma showed morphology of sebaceous carcinomas (keratinizing and foam cells, calcifications, giant cells), a strong expression of adipophilin and AR together with squamous markers. NGS revealed high-level amplification of fibroblast growth factor receptor 2 (FGFR2). In thymuses and thymomas, no cells with sebaceous morphology were present. Occasionally, macrophages or epithelial cells showed adipophilin-positivity, however, without co-expression of AR. Thymic sebaceous carcinoma should be considered if a thymic carcinoma shows clear or foamy features. Testing for FGFR2 amplification might be warranted when searching for actionable genomic alterations in sebaceous carcinomas in the mediastinum and in other locations.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002280 Carcinoma, Basal Cell A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471) Carcinoma, Basal Cell, Pigmented,Epithelioma, Basal Cell,Rodent Ulcer,Ulcer, Rodent,Basal Cell Carcinoma,Basal Cell Carcinomas,Basal Cell Epithelioma,Basal Cell Epitheliomas,Carcinomas, Basal Cell,Epitheliomas, Basal Cell,Rodent Ulcers,Ulcers, Rodent
D005784 Gene Amplification A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. Amplification, Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012626 Sebaceous Gland Neoplasms New abnormal growth of tissue in the SEBACEOUS GLANDS. Neoplasms, Sebaceous Gland,Neoplasm, Sebaceous Gland,Sebaceous Gland Neoplasm
D012878 Skin Neoplasms Tumors or cancer of the SKIN. Cancer of Skin,Skin Cancer,Cancer of the Skin,Neoplasms, Skin,Cancer, Skin,Cancers, Skin,Neoplasm, Skin,Skin Cancers,Skin Neoplasm
D013945 Thymoma A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed) Carcinoma, Thymic,Carcinomas, Thymic,Thymic Carcinoma,Thymic Carcinomas,Thymomas
D013953 Thymus Neoplasms Tumors or cancer of the THYMUS GLAND. Cancer of Thymus,Thymus Cancer,Thymus Tumors,Cancer of the Thymus,Neoplasms, Thymic,Neoplasms, Thymus,Thymic Cancer,Thymic Neoplasms,Thymic Tumors,Cancer, Thymic,Cancer, Thymus,Cancers, Thymic,Cancers, Thymus,Neoplasm, Thymic,Neoplasm, Thymus,Thymic Cancers,Thymic Neoplasm,Thymic Tumor,Thymus Cancers,Thymus Neoplasm,Thymus Tumor,Tumor, Thymic,Tumor, Thymus,Tumors, Thymic,Tumors, Thymus
D014408 Biomarkers, Tumor Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or BODY FLUIDS. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including HORMONES; ANTIGENS; amino and NUCLEIC ACIDS; ENZYMES; POLYAMINES; and specific CELL MEMBRANE PROTEINS and LIPIDS. Biochemical Tumor Marker,Cancer Biomarker,Carcinogen Markers,Markers, Tumor,Metabolite Markers, Neoplasm,Tumor Biomarker,Tumor Marker,Tumor Markers, Biochemical,Tumor Markers, Biological,Biochemical Tumor Markers,Biological Tumor Marker,Biological Tumor Markers,Biomarkers, Cancer,Marker, Biochemical Tumor,Marker, Biologic Tumor,Marker, Biological Tumor,Marker, Neoplasm Metabolite,Marker, Tumor Metabolite,Markers, Biochemical Tumor,Markers, Biological Tumor,Markers, Neoplasm Metabolite,Markers, Tumor Metabolite,Metabolite Markers, Tumor,Neoplasm Metabolite Markers,Tumor Markers, Biologic,Tumor Metabolite Marker,Biologic Tumor Marker,Biologic Tumor Markers,Biomarker, Cancer,Biomarker, Tumor,Cancer Biomarkers,Marker, Tumor,Markers, Biologic Tumor,Markers, Carcinogen,Metabolite Marker, Neoplasm,Metabolite Marker, Tumor,Neoplasm Metabolite Marker,Tumor Biomarkers,Tumor Marker, Biochemical,Tumor Marker, Biologic,Tumor Marker, Biological,Tumor Markers,Tumor Metabolite Markers

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