SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Freiberger, Sandra N.; Brada, Muriel; Fritz, Christine; Höller, Sylvia; Vogetseder, Alexander; Horcic, Milo; Bihl, Michel; Michal, Michal; Lanzer, Martin; Wartenberg, Martin; Borner, Urs; Bode, P.; Broglie, Martina A.; Rordorf, Tamara; Morand, G; Rupp, Niels J.

doi:10.1016/j.neo.2021.03.008

Cited by 55 publications

(85 citation statements)

References 69 publications

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“…The molecular investigations are becoming helpful tools to help establish a correct diagnosis and provide prognostically important information, but they are expensive and less sensitive in some cases. However, recently described genomic alterations may help challenge cases and have future therapeutic implications [2], [3].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In recent years, several characteristic molecular alternations have been described in certain salivary gland neoplasms, resulting in abnormal fusion oncogenes [3]. Several techniques such as fluorescence in situ hybridization (FISH), polymerase chain reaction, and immunohistochemistry can detect these fusion oncogenes and their oncoprotein products [3]. Acinic cell carcinoma (AcCC) is a lowgrade malignant salivary gland neoplasm that comprises approximately 17% of primary salivary gland malignancies or about 6% of all salivary gland neoplasms.…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic Value of Nuclear Receptor Subfamily 4 Group A Member 3 in Salivary Gland Carcinomas

Algharyani

Maghrabi²,

Ezzat³

et al. 2022

Open Access Maced J Med Sci

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Salivary gland carcinomas are diagnostically challenging lesions in heterogeneous groups. However, recently described genomic alterations may be helpful and have future therapeutic implications. The molecular investigation is becoming useful tool to help diagnosis and provide prognostic information. Diagnosis of acinic cell carcinoma (AcCC) is challenging due to its rarity and similarity with other SGCs or normal acinar cells. Herein, the diagnostic performance of transcription factor nuclear receptor subfamily 4 group A member3 (NR4A3) was analysed immunohistochemically. This study was done on 68 cases of SCCs, including 32 of AcCC, 14 of adenoid cystic carcinoma (AdCC), 8 of mucoepidermoid carcinoma (MEC), 7 of epithelial myoepithelial carcinoma (EMC), 4 of salivary duct carcinoma (SDC), and only one case from each of carcinoma ex pleomorphic adenoma (CXPA), polymorphous adenocarcinoma (PAC) and secretory carcinoma (SC) for detecting NR4A3. All stained samples of AcCC (100%) responded positively to the NR4A3 antibody. However, only one case of AdCC and MEC demonstrated NR4A3 immunostaining in less than 10% of cells. On the other hand, the different types of SGCs, including EMC, SDC, CXPA, PAC, and SC, revealed negative expressions. Therefore, we can conclude that NR4A3 can be used as a potential marker for AcCC rather than other SGCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic Value of Nuclear Receptor Subfamily 4 Group A Member 3 in Salivary Gland Carcinomas

Algharyani

Maghrabi²,

Ezzat³

et al. 2022

Open Access Maced J Med Sci

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“…RNA was isolated from FFPE specimens using the Maxwell 16 LEV RNA FFPE Puri cation Kit (Promega, Madison, WI, USA). Library preparation for the custom Archer SalvGlandDx FusionPlex panel [13] was performed according to the manufacturer's protocol (ArcherDx; Boulder, CO, USA). Sequencing of the libraries was performed on an NextSeq550 Illumina machine and aTrusight Tumor 500 Illumina machine (Illumina).…”

Section: Methodsmentioning

confidence: 99%

Apocrine epithelial-myoepithelial carcinoma with phyllodes-like morphology of the parotid gland: A case report of an unusual histology with immunohistochemical and genetic analyses using next-generation sequencing

Kusafuka

Rupp

Freiberger

et al. 2022

Preprint

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Background Phyllodes tumor (PT) is a relatively common tumor of the breast; however, it is known that it rarely occurs in other organs. We report a unique case of salivary PT-like carcinoma. Case presentation: A 79-year-old Japanese man noticed an elastic-hard mass in the right parotid region and consecutively underwent right superficial lobectomy. Histologically, the tumor was circumscribed with a fibrous capsule, and showed a cystic space and leaf-like architectures in the subcapsular area. The glandular epithelium showed fused glands with atypia and covered the spindle cell component with the leaf-like structures. Spindle cells harbored cellular atypia and overgrowth with a fascicular pattern. Immunohistochemically, the epithelial component was diffusely positive for cytokeratin (CK)7, androgen receptor, and gross cystic disease fluid protein-15, whereas the spindle cells were diffusely positive for vimentin, p63, SOX10, alpha-smooth muscle actin, and RAS Q61R. The latter was also partially positive for CK7 and CK14. The Ki-67 labeling index was 20.6%. Next-generation sequencing (NGS) indicated a missense mutation in HRAS (c.182A > G) and KRAS (c.35G > A,). Conclusions We diagnosed apocrine epithelial-myoepithelial carcinoma (EMC) with overgrowth of the myoepithelial carcinoma component and a PT-like morphology of the salivary gland. NGS is a very powerful tool for the diagnosis of unusual histology, like EMC.

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“…DNA and RNA were isolated using the Maxwell® 16 FFPE Tissue LEV DNA Purification Kit16 or LEV RNA FFPE Purification Kit, respectively (Promega, Madison, WI, USA). Library preparation for fusion analysis was performed using the Archer FusionPlex technology (ArcherDX, Boulder, CO, USA) and a custom primer set for salivary gland neoplasms (“SalvGlandDx panel,” described previously 16 ). Libraries were sequenced paired end on a NextSeq™550 (Illumina, San Diego, CA, USA) and data analysis was performed using the Archer analysis software (ArcherDX, Boulder, CO, USA).…”

Section: Methodsmentioning

confidence: 99%

Expanding the clinicopathological spectrum of TGFBR3‐PLAG1 rearranged salivary gland neoplasms with myoepithelial differentiation including evidence of high‐grade transformation

Rupp

Höller

Brada

et al. 2021

Genes Chromosomes & Cancer

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PLAG1 rearrangements have been described as a molecular hallmark of salivary gland pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), and myoepithelial carcinoma (MECA). Several fusion partners have been described, however, commonly no further assignment to the aforementioned entities or a morphological prediction can be made based on the knowledge of the fusion partner alone. In contrast, TGFBR3‐PLAG1 fusion has been specifically described and characterized as an oncogenic driver in MECA, and less common in MECA ex PA. Here, we describe the clinicopathological features of three TGFBR3‐PLAG1 fusion‐positive salivary gland neoplasms, all of which arose in the deep lobe of the parotid gland. Histopathology showed high morphological similarities, encompassing encapsulation, a polylobular growth pattern, bland basaloid and oncocytoid cells with myoepithelial differentiation, and a distinct sclerotic background. All cases showed at least limited, unusual foci of minimal invasion into adjacent salivary gland tissue, including one case with ERBB2 (Her2/neu) amplified, TP53 mutated high‐grade transformation, and lymph node metastases. Of note, all cases illustrated focal ductal differentiation. Classification remains difficult, as morphological overlaps between myoepithelial‐rich cellular PA, myoepithelioma, and MECA were observed. However, evidence of minimal invasion advocates classification as low‐grade MECA. This case series further characterizes the spectrum of uncommon cellular myoepithelial neoplasms harboring TGFBR3‐PLAG1 fusion, which show recurrent minimal invasion of the adjacent salivary gland tissue, a predilection to the deep lobe of the parotid gland, and potential high‐grade transformation.

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SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

Cited by 55 publications

References 69 publications

Diagnostic Value of Nuclear Receptor Subfamily 4 Group A Member 3 in Salivary Gland Carcinomas

Diagnostic Value of Nuclear Receptor Subfamily 4 Group A Member 3 in Salivary Gland Carcinomas

Apocrine epithelial-myoepithelial carcinoma with phyllodes-like morphology of the parotid gland: A case report of an unusual histology with immunohistochemical and genetic analyses using next-generation sequencing

Expanding the clinicopathological spectrum of TGFBR3‐PLAG1 rearranged salivary gland neoplasms with myoepithelial differentiation including evidence of high‐grade transformation

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