Phenotypical and molecular distinctness of sinonasal haemangiopericytoma compared to solitary fibrous tumour of the sinonasal tract

Agaimy, Abbas; Barthelmeß, Sarah; Geddert, Helene; Boltze, Carsten; Moskalev, Evgeny A.; Koch, Michael; Wiemann, Stefan; Hartmann, Arndt; Haller, Florian

doi:10.1111/his.12452

Cited by 40 publications

(49 citation statements)

References 21 publications

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“…24,25 In this study, all glomangiopericytomas were immunohistochemically negative for STAT6 similar to the results recently reported in another study cohort, where all glomangiopericytomas were also negative for NAB2-STAT6 fusion gene transcripts. 26 Therefore, STAT6 expression is also discriminatory between these entities.…”

Section: Discussionmentioning

confidence: 99%

Nuclear expression and gain-of-function β-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker

et al. 2015

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Glomangiopericytoma (sinonasal-type hemangiopericytoma) is a rare mesenchymal neoplasm with myoid phenotype (smooth muscle actin-positive), which distinguishes this tumor from soft tissue hemangiopericytoma/solitary fibrous tumor. Molecular genetic changes underlying the pathogenesis of glomangiopericytoma are not known. In this study, 13 well-characterized glomangiopericytomas were immunohistochemically evaluated for b-catenin expression. All analyzed tumors showed strong expression and nuclear accumulation of b-catenin. Following this observation, b-catenin glycogen serine kinase-3 beta phosphorylation region, encoded by exon 3, was PCR amplified in all cases and evaluated for mutations using Sanger sequencing. Heterozygous mutations were identified in 12 of 13 tumors. All mutations consisted of single-nucleotide substitutions: three in codon 32 (c.94G4C (n ¼ 2) and c.95A4T), four in codon 33 (two each c.98C4G and c.98C4T), two in codon 37 (c.109T4G), one in codon 41 (c.121A4G), and two in codon 45 (c.133T4C). At the protein level, these substitutions would lead to p.D32H, p.D32V, p.S33C, p.S33F, p.S37A, p.T41A, and p.S45L mutations, respectively. Previously, similar mutations have been reported in different types of cancers and shown to trigger activation of b-catenin signaling. All analyzed glomangiopericytomas showed prominent nuclear expression of cyclin D1, as previously shown for tumors with nuclear expression of b-catenin as a sign of oncogenic activation. These results demonstrate that mutational activation of b-catenin and associated cyclin D1 overexpression may be central events in the pathogenesis of glomangiopericytoma. In additon, nuclear accumulation of b-catenin is a diagnostic marker for glomangiopericytoma. Modern Pathology (2015) 28, 715-720; doi:10.1038/modpathol.2014.161; published online 28 November 2014Glomangiopericytoma (sinonasal-type hemangiopericytoma) is a rare mesenchymal neoplasm of the nasal cavity and sinuses of low biologic potential. [1][2][3][4] It shows a myoid phenotype with consistent expression of smooth muscle actin. 3 b-Catenin, a cadherin-associated membrane protein, participates in the regulation of cell-to-cell adhesion and in some circumstances, also gene transcription as a nuclear protein, a terminal component of the canonical Wnt-signaling pathway. Aberrant expression of b-catenin encoded by CTNNB1 gene is a well-known event in tumorigenesis and tumor progression. 5,6 Among soft tissue tumors, somatic mutations in CTNNB1 are well known in the pathogenesis of sporadic desmoid-type fibromatosis. 7,8 These mutations cluster in CTNNB1 glycogen serine kinase-3 beta (GSK3b) phosphorylation region and constitutionally activate b-catenin signal by upholding cellular b-catenin levels. This happens via interference of ubiquitin-mediated proteolytic degradation by elimination of the phosphorylation sites necessary for ubiquitin action. 7,8 Accumulation of b-catenin in turn results in nuclear translocation, which is a telltale sign of a mutation, typically seen in sporadic de...

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Section: Discussionmentioning

confidence: 99%

Nuclear expression and gain-of-function β-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker

et al. 2015

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“…Rare examples of glomangiopericytoma may contain mature adipose tissue (lipomatous GPC) or reveal extramedullary hematopoiesis [6,[20][21][22]. Concurrent, collision tumors may be found, with SFT noted as a distinctly separate and immunophenotypically different neoplasm [6,23,24]. Rarely, severe pleomorphism, necrosis and increased mitoses may be identified, with a malignant designation applied to these cases, which have a much higher chance of developing recurrence or rarely metastasis with death due to disease [6].…”

Section: Pathology Findingsmentioning

confidence: 99%

“…By immunohistochemistry, SFTs reveal diffuse reactivity with CD34, bcl-2, STAT6, and CD99, but are negative with actins and bcatenin [7,32,34], although a subset of SFT may express bcatenin [35]. SFT is further characterized by NAB2-STAT6 gene fusion and over expression of the fusion protein [36], a finding not found in GPC [8,23].…”

Section: Differential Diagnosismentioning

confidence: 99%

Update on Select Benign Mesenchymal and Meningothelial Sinonasal Tract Lesions

Thompson

Fanburg‐Smith

2016

Head and Neck Pathol

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“…The notion that the entities SFT and HPC are closely related, if not similar, is also endorsed in the current World Health Organization classification of softtissue and bone tumors [29,30]. It is thus widely accepted that distinguishing HPCs as a separate entity from SFTs is becoming obsolete [31].…”

Section: Histopathologymentioning

confidence: 99%

Head and neck solitary fibrous tumors: a rare and challenging entity

Künzel¹,

Hainz²,

Ziebart³

et al. 2015

Eur Arch Otorhinolaryngol

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The objective of this study is to analyze the outcome of treatment for solitary fibrous tumors (SFTs) in the head and neck area. SFTs present as slow-growing masses, often with local compressive symptoms that are difficult to distinguish from other soft-tissue tumors. SFTs are commonly treated using local excision without adjuvant therapy. To date, only heterogeneous small series have been published, documenting the treatment results and outcome with these tumors. Retrospective study of patients with histopathologically confirmed SFT treated at two tertiary referral hospitals between 2004 and 2014. Eight men and four women with histologically confirmed SFT were identified in the records. Their age range was 37-82 years (mean 57.8 years). The mean follow-up period for eight patients was 6.75 years (range 1-24 years). Four patients were lost to follow-up. Sublocalizations were neck (n = 3), orbit (n = 2), paranasal sinus (n = 2), cheek (n = 2), hard palate (n = 1), parotid gland (n = 1), and tongue (n = 1). The first-line treatment for all of the tumors identified was surgical excision. In four cases, the surgical margins were narrow or unclear due to piecemeal resection in the paranasal sinus and orbit (n = 3) or a tumor location deep in the parapharyngeal space (n = 1). Recurrences developed in two of these cases (in the orbit and parapharyngeal space), and the other two patients were lost to follow-up. Radiotherapy and chemotherapy were not administered as first-line treatments. Overall, the local recurrence rate (n = 2/8) was 25 %. The disease-specific survival rate was 100 %. These results are consistent with the literature data and show that safe surgical excision, without opening of the tumor capsule, reduces the risk of local recurrence and leads to a favorable outcome. Tumors in the head and neck often represent a surgical challenge, and wide surgical margins are rarely possible due to the complex three-dimensional anatomic compartments in the region. Head and neck surgeons should therefore be aware that there is an increased risk of recurrence in these patients; tightly scheduled follow-up visits are mandatory for at least 10 years, if not longer. Radiotherapy only appears to be an option in patients with unresectable tumors or when wide surgical excision would cause severe functional morbidity.

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Phenotypical and molecular distinctness of sinonasal haemangiopericytoma compared to solitary fibrous tumour of the sinonasal tract

Abstract: These findings confirm the molecular and phenotypical distinctness of these two entities. While SN-HPC is a site-specific sinonasal neoplasm of as yet unknown molecular pathogenesis, sinonasal SFTs show phenotypical and molecular identity to their pleural/extrapleural counterparts.

Cited by 40 publications

References 21 publications

Nuclear expression and gain-of-function β-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker

Nuclear expression and gain-of-function β-catenin mutation in glomangiopericytoma (sinonasal-type hemangiopericytoma): insight into pathogenesis and a diagnostic marker

Update on Select Benign Mesenchymal and Meningothelial Sinonasal Tract Lesions

Head and neck solitary fibrous tumors: a rare and challenging entity

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