Acoustic neuroma natural history

Natural History
The natural history of untreated acoustic neuromas is unpredictable. In a study of in vivo and in vitro growth models, Charabi states that any attempt to elucidate the natural history of acoustic neuromas must have as its basis a clear understanding of the environment in which the disease develops. This includes an understanding of the normal anatomy and histology of the vestibulocochlear nerve, growth factors, histological changes, and factors that determine rates and patterns of tumor growth. It has been well documented in the literature that some tumors grow, some regress, some do not grow at all, and some display a variable pattern of growth. Serial radiographic studies on patients who are not surgical candidates or who refuse surgery have provided some insight into the natural history of tumor expansion. However, factors such as loss of inhibitor regulation, local growth factors, and other cell cycle regulators that may help predict tumor growth have not yet been identified. Several growth factors, including nerve growth factor, glial growth factor, platelet-derived growth factor, basic fibroblast growth factor, transforming growth factor-β, epidermal growth factor, and vascular endothelial growth factor have been proposed as potentially playing a role in the pathogenesis of acoustic neuromas, but all require further evaluation.In addition, no consistent correlation has been found between growth rate of acoustic neuromas and patient age or tumor size. Studies using monoclonal antibody assays have, however, shown that clinical growth rates will correlate with the fraction of cells found in the proliferative phase of the cell cycle. Studies using the monoclonal antibody Ki-67, proliferating cell nuclear antigen (PCNA, and DNA flow cytometric analysis have been used to examine the growth rate and proliferative potential of acoustic neuromas.

Some studies have shown that tumor growth rate at the start of follow-up is a good predictor of future tumor growth rate. Many studies have shown that the rate of tumor growth in a given patient is consistent over the course of the disease and is established during the first one to three years of observation. However, serial imaging follow-up should not be terminated based solely on tumor quiescence, as some acoustic neuroma patients do experience a delayed onset of tumor growth.

It has been shown that tumors larger than 20 mm are statistically more likely to grow. Another study found a statistically significant inverse relationship between tumor size and patient age. Other studies have reported a tendency for higher growth rate in larger tumors and in younger patients. Nevertheless, it is not possible to demonstrate any pathoanatomic feature of acoustic neuroma that correlates with the clinical course of the tumor.

Studies have examined the proportion of acoustic neuroma patients who experienced tumor growth. Growth varied widely from 15-90% of the cases followed. In studies examining the growth rate of acoustic neuromas, the mean annual tumor growth rates ranged between 0.7 and 4.8 mm per year. Recent studies have shown that slow to medium growth of acoustic neuromas is in the range of 0.2 to 2.3 mm/year. A growth rate of >2 mm per year is seen in only 22-29% of untreated acoustic neuromas. In comparison, a fast tumor growth rate pattern is considered to be approximately 10 mm per year. Methods of calculating tumor growth include tumor diameter measurement and tumor volume calculation. The results of two studies of tumor growth based on tumor diameter did not differ from the results based on tumor volume. However, some studies have demonstrated more accurate tumor growth measurements using tumor volume calculations.

It is important to note that potentially less than 1 percent of acoustic neuromas demonstrate enough growth to become clinically active, which is indicative of a very slow or arrested growth. The emergence of gadolinium-enhanced magnetic resonance imaging (MRI) has allowed the detection of smaller and often asymptomatic tumors as small as 2 mm in diameter. As a result, the likelihood of finding an acoustic neuroma that would have never become clinically significant has increased enormously.

Tumors that exhibit enough growth to become clinically active encroach on the vestibulocochlear nerve and are likely to cause unilateral high-frequency sensorineural hearing loss, tinnitus], [[disequilibrium, or vertigo and as a result are at increased risk of being diagnosed. Features that can potentially distinguish tumors with fast tumor growth from those with slow or arrested growth include the influence of growth factors such as the neuregulin-1 (NRG-1) and/or neuregulin-2 (NRG-2 proteins, as well as angiogenic factors. Also, tumor vascularity, the presence of inflammation in the Antoni type B cellular areas, a variation in basal apoptosis rates of acoustic neuroma schwannoma cells, and a possible hormonal influence may also be factors influencing tumor growth rate. Additional features of fast-growing tumors include the presence of Antoni B tissues containing extratumoral or intratumoral cystic components, the over-expression or amplification of G1 regulators of the cell cycle such as cyclin D1and cyclin D3, and the expression of erbB2 and erbB3 membrane tyrosine kinases. When examining risk factors that may increase the likelihood of tumor diagnosis, the only endogenous or exogenous factors associated with the features of fastgrowing tumors are patient sex and repeated environmental insults to the vestibulocochlear nerve that may lead to chronic inflammation. Proinflammatory cytokines such as IL-6, IL-1β, and TNF-α may initiate an inflammatory response after loud noise exposure and thus may be involved in cochlear damage.

Risk Stratification and Prognosis

 * Acoustic neuromas are not cancerous and do not spread to other parts of the body
 * Once treated it is unusual for them to grow back
 * Some untreated neuromas can grow aggresively and cause damage to nerve, ear, and brain tissue