Malignant prediction in paragangliomas: analysis for clinical risk factors

Torres-Costa, Miquel; Flores, Benito; Torregrosa, Nuria; González, Maraelys Morales; Ríos, Antonio; Febrero, Beatríz; Flores, Diego; Rodríguez, Pablo Fernández; Carbonell, Pablo; Ortuño, María Isabel; Rodrı́guez, José Manuel

doi:10.1007/s00423-021-02222-9

Cited by 4 publications

(5 citation statements)

References 32 publications

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“…Pertinent to this case is the presence of de novo atypical features at the time of original resection including confluent growth pattern, coagulative necrosis and angiolymphatic tumor emboli. The significance of this finding viz‐a‐viz the development of metastasis is not clear, consistent with precedent literature 32,33 …”

Section: Discussionsupporting

confidence: 72%

“…The significance of this finding viz-a-viz the development of metastasis is not clear, consistent with precedent literature. 32,33 The clinical course of paraganglioma is unpredictable and some cases show aggressive disease potential. [2][3][4] While a significant portion of these aggressive tumors are associated with germline cancer inheritable genes and well characterized, little is known of the sporadic cases.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of this finding viz‐a‐viz the development of metastasis is not clear, consistent with precedent literature. 32 , 33 …”

Section: Discussionmentioning

confidence: 99%

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Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

Javaid

Patton

Tinoco

et al. 2022

Genes Chromosomes & Cancer

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Chromosomal translocations with gene fusions are uniquely rare events in paraganglioma, mostly involving UBTF::MAML3 gene fusion. Precedent literature suggests that tumors involving MAML3 gene fusion correlate with poor clinical outcomes. Herein, we report a case of metastatic sporadic paraganglioma harboring EWSR1::CREM gene fusion in a 36‐year‐old male, that has not been previously described. The patient presented with large paraspinal mass that was resected the same year. Tumor recurred 3‐years later and on further work‐up, patient was found to have metastases involving both lungs. Histopathologic evaluation of the original primary tumor showed tightly packed irregular nests and cords of cells containing palely eosinophilic cytoplasm. Features considered atypical included: areas of solid growth pattern, coagulative tumor necrosis, focal cellular atypia and angiolymphatic invasion were also identified. By immunohistochemistry, the tumor cells were positive for synaptophysin and chromogranin and negative for keratin. The S100 stain highlights the sustentacular cells and the Ki‐67 proliferation index of 15%. The recurrence specimen was similar but showed increased cellularity, atypia, necrosis, and proliferative activity (Ki‐67 proliferation index of 35%). CT guided biopsy of the right lung lesion was consistent with metastasis. Next generation sequencing identified EWSR1::CREM fusion. The breakpoints were found in chromosome 22: 29683123 for EWSR1 exon 7 (NM_005243.3) and at chromosome 10:35495823 for CREM exon 6 (NM_001267562.1). Fluorescence in situ hybridization for EWSR1 gene rearrangement was positive. In summary, we report a case of metastatic paraganglioma with EWSR1::CREM gene fusion, not previously described in this entity, and expands on the phenotypic diversity within the genetic landscape of EWSR1::CREM gene fusion positive tumors.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

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Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

Javaid

Patton

Tinoco

et al. 2022

Genes Chromosomes & Cancer

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“…Identifying such metastatic potential would prompt more aggressive treatment of the paraganglioma, with potentially better outcomes 14. There are no reliable features on histology that would be diagnostic of a paraganglioma with metastatic potential, so it is recommended that all patients with paragangliomas are routinely screened for metastatic disease 15. The size of the tumour (if more than 5 cm) might be a characteristic suggesting the potential for metastatic spread,16 as well as, thoracoabdominal sympathetic paragangliomas 8.…”

Section: Discussionmentioning

confidence: 99%

Metastatic paraganglioma

et al. 2023

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A man in his 70s, with a history of a glomus jugulare paraganglioma diagnosed 18 years ago, presented with an unprovoked deep vein thrombosis (DVT). The paraganglioma had been treated by radiotherapy, and yearly scans had not shown any progression since treatment. A sclerotic focus in L4 vertebral body was reported on a CT scan of the neck and trunk which was done to exclude a neoplastic process being the precipitating factor for the DVT. Nuclear imaging showed multiple areas of bony uptake, suggestive of metastases. A bone biopsy of the left femur resulted positive for metastatic paraganglioma. A monthly intramuscular injection of octreotide 30 mg was prescribed.

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“…These cells, which in many aspects resemble normal cells, may not readily respond to cytotoxic treatment but gradually accumulate new mutations leading to increased malignancy and subsequently manifest as late metastases. Tumors belonging to the phaeochromocytoma/paraganglioma group show histology close to normal, making it impossible to predict malignancy ( 28 ). In fact, only metastases that may occur decades after initial diagnosis ( 29 ) can definitively determine whether these tumors were benign or malignant.…”

Section: Cell Of Origin: Differentiated Versus Stem Cellsmentioning

confidence: 99%

Correctly identifying the cells of origin is essential for tailoring treatment and understanding the emergence of cancer stem cells and late metastases

Waldum,

Slupphaug

2024

Front. Oncol.

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Malignancy manifests itself by deregulated growth and the ability to invade surrounding tissues or metastasize to other organs. These properties are due to genetic and/or epigenetic changes, most often mutations. Many aspects of carcinogenesis are known, but the cell of origin has been insufficiently focused on, which is unfortunate since the regulation of its growth is essential to understand the carcinogenic process and guide treatment. Similarly, the concept of cancer stem cells as cells having the ability to stop proliferation and rest in a state of dormancy and being resistant to cytotoxic drugs before “waking up” and become a highly malignant tumor recurrence, is not fully understood. Some tumors may recur after decades, a phenomenon probably also connected to cancer stem cells. The present review shows that many of these questions are related to the cell of origin as differentiated cells being long-term stimulated to proliferation.

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Malignant prediction in paragangliomas: analysis for clinical risk factors

Cited by 4 publications

References 32 publications

Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

Metastatic paraganglioma

Correctly identifying the cells of origin is essential for tailoring treatment and understanding the emergence of cancer stem cells and late metastases

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