Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation

BMC Cancer
Marta EspinosaCristina Rodríguez-Antona

Abstract

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. 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. NGS on a...Continue Reading

References

Jan 31, 2003·Annals of Human Genetics·D J Kwiatkowski
Jan 6, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nicholas WolffJames Brugarolas
Jan 6, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew J WagnerRobert G Maki
Mar 19, 2011·Japanese Journal of Clinical Oncology·Kohei ShitaraKei Muro
Aug 28, 2012·Science·Gopa IyerDavid B Solit
Aug 29, 2012·International Journal of Cancer. Journal International Du Cancer·Mark A DicksonIzabela A Malinowska
Sep 5, 2012·World Journal of Surgical Oncology·Constantine GennatasDionysios Voros
Dec 5, 2012·BJU International·Andrew R Lienert, David Nicol
Jan 26, 2013·International Journal of Urology : Official Journal of the Japanese Urological Association·Jin KohnoOsamu Ogawa
Feb 6, 2013·International Journal of Urology : Official Journal of the Japanese Urological Association·Yoji Nagashima
Apr 20, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Wenlei HeSatish K Tickoo
Oct 9, 2014·The New England Journal of Medicine·Nikhil WagleJochen H Lorch
Aug 19, 2015·Canadian Urological Association Journal = Journal De L'Association Des Urologues Du Canada·Elvan Caglar CitakDemir Apaydin
Feb 3, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David J KwiatkowskiSabina Signoretti
Apr 8, 2017·Cell·Robert A Saxton, David M Sabatini

❮ Previous
Next ❯

Citations

Jan 11, 2019·Chinese Medical Journal·Yu-Jing HuangMeng-Jun Liang
Jul 25, 2019·International Journal of Cancer. Journal International Du Cancer·Juan M Roldan-RomeroUNKNOWN Spanish Oncology Genitourinary Group (SOGUG)
Feb 13, 2021·Frontiers in Oncology·Gang GuoXu Zhang
Aug 28, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F MoseleF André

❮ Previous
Next ❯

Methods Mentioned

BETA
surgical resection

Software Mentioned

Integrative Genomics Viewer
COSMIC

Related Concepts

Related Feeds

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.