Endothelin-1 Driving Osteosclerosis and Meningiomatosis in Intraosseous Meningioma

Presentation Number: SAT 325
Date of Presentation: April 1st, 2017

Jenna L. Sarvaideo*1, Jasmin Kristianto2, Jennifer M Connelly3 and Robert Daniel Blank1
1Medical College of Wisconsin, Milwaukee, WI, 2University of Wisconsin-Madison, Madison, WI, 3Medical College of Wisconsin



Endothelin-1 (ET-1) has been identified as a mediator of osteoblastic bone metastases by stimulating osteoblast proliferation and new bone formation (1). Expression of ET-1 has been found in human meningiomas and thought to play a role in tumoral growth (2). Osteosclerosis in the presence of meningiomas is occasionally seen, but it is unknown how often. It has not previously been associated with ET-1. It is here we illustrate the potential role of ET-1 in both osteosclerosis and meningiomatosis.

Clinical case

A 48-year-old woman with past medical history of meningioma diagnosed in 2001 s/p bifrontal meningioma resection was referred for hyperostosis seen on imaging. She was doing well until early 2016 when she noted a painful bump on right temple that did not resolve. Imaging revealed multiple, sclerotic, expansile osseous lesions. Appearance on CT head most suggestive of multiple intraosseous meningiomas or meningiomatosis.

She had a history of obesity, hypertension, hyperlipidemia and depression. Medications included atorvastatin, bupropion, citalopram, black cohosh, ferrous sulfate, losartan/hydrochlorothiazide, nebivolol, potassium chloride, probiotic and vitamin D3. She was a non-smoker and drank alcohol occasionally. She was employed. Her family history was notable for hypertension and arthritis. There was no family history of endocrine diseases, fractures, bone disorders or cancer. On exam, she was alert and oriented to time, place and person. Her memory, behavior, speech and language were normal. There was a bony protuberance of the right temple that was non-tender to palpation. There were postsurgical changes from prior craniotomy. She did not have torus palatinus. The remainder of her exam was unremarkable.

The head CT was reviewed. The most important lesion was adjacent to the left cavernous sinus, which had led to left optic atrophy. There was also a lesion present in the right temporal region corresponding to the palpable mass appreciated on exam. A DXA scan was ordered to evaluate skeletal mass, which did not show evidence of generalized osteosclerosis. Her highest Z-score was 1.4.

A tissue block from patient’s prior neurosurgery was obtained and stained for RUNX2 and ET-1. Her tumor was found to produce ET-1. She was referred for radiation, but pharmacologic blockage of ET signaling might be considered if standard treatments fail.


Tumor production of ET-1 may promote osteoblastogenesis by downregulating dickkopf homolog 1 (DKK1), which allows Wnt signaling pathway activation and osteoblast differentiation (1). Furthermore, ET-1 along with other growth factors and cytokines contributes to angiogenesis and tumor growth (2). In this case we identified ET-1 produced by our patient’s meningioma as a probable contributor to both osteosclerosis and meningiomatosis.


Disclosure: RDB: Investigator, Novo Nordisk, Contributor, Up To Date, N/A, Abbvie. Nothing to Disclose: JLS, JK, JMC