Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation
Abstract Background Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activat...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4467-6 |
| _version_ | 1818658031538274304 |
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| author | Marta Espinosa Juan Maria Roldán-Romero Ignacio Duran Enrique de Álava María Apellaniz-Ruiz Alberto Cascón Carmen Garrigos Mercedes Robledo Cristina Rodriguez-Antona |
| author_facet | Marta Espinosa Juan Maria Roldán-Romero Ignacio Duran Enrique de Álava María Apellaniz-Ruiz Alberto Cascón Carmen Garrigos Mercedes Robledo Cristina Rodriguez-Antona |
| author_sort | Marta Espinosa |
| collection | DOAJ |
| description | Abstract Background Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined. Case presentation Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36 months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation. Conclusion NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs. |
| first_indexed | 2024-12-17T03:50:54Z |
| format | Article |
| id | doaj.art-2bd539ec21a8436dba069747c6d59b14 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-17T03:50:54Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-2bd539ec21a8436dba069747c6d59b142022-12-21T22:04:45ZengBMCBMC Cancer1471-24072018-05-011811510.1186/s12885-018-4467-6Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutationMarta Espinosa0Juan Maria Roldán-Romero1Ignacio Duran2Enrique de Álava3María Apellaniz-Ruiz4Alberto Cascón5Carmen Garrigos6Mercedes Robledo7Cristina Rodriguez-Antona8Medical Oncology Department, Hospital Virgen del Rocío, Servicio de Oncología MedicaHereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)Medical Oncology Department, Hospital Virgen del Rocío, Servicio de Oncología MedicaPathology Department, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla-CIBERONCHereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaHereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO)Abstract Background Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined. Case presentation Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36 months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation. Conclusion NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs.http://link.springer.com/article/10.1186/s12885-018-4467-6Renal epithelioid angiomyolipomaSirolimusTSC2 mutationmTOR pathway activation |
| spellingShingle | Marta Espinosa Juan Maria Roldán-Romero Ignacio Duran Enrique de Álava María Apellaniz-Ruiz Alberto Cascón Carmen Garrigos Mercedes Robledo Cristina Rodriguez-Antona Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation BMC Cancer Renal epithelioid angiomyolipoma Sirolimus TSC2 mutation mTOR pathway activation |
| title | Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation |
| title_full | Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation |
| title_fullStr | Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation |
| title_full_unstemmed | Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation |
| title_short | Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation |
| title_sort | advanced sporadic renal epithelioid angiomyolipoma case report of an extraordinary response to sirolimus linked to tsc2 mutation |
| topic | Renal epithelioid angiomyolipoma Sirolimus TSC2 mutation mTOR pathway activation |
| url | http://link.springer.com/article/10.1186/s12885-018-4467-6 |
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