To the best of our knowledge, this is the first study to show the utility of ADC values for predicting intracranial epidermoid tumor recurrence. Epidermoid tumors are slow-growing tumors often involving the posterior fossa, such as the CPA, and cause neurologic deficits when leading to mass effects or stretching onto adjacent neurovascular structures [5,8,12]. Although there are no established treatment guidelines, maximal safe surgical resection is generally conducted, and reoperation is often considered for recurrent cases. Due to its benign nature and pathologic simplicity, many studies related to intracranial epidermoid tumors focus on surgical techniques, cranial nerve function preservation, and recurrence after surgery [2,5,8,12,18-21]. The EOR was shown to be a significant prognostic factor for recurrence in these studies, but there are no known preoperative factors that can predict tumor behavior. ADC values have been used to represent tumor characteristics in several central nervous system tumors [15,22,23], and DWI sequence is always taken for detection of epidermoid tumor recurrence . Thus, in the present study, we analyzed 23 patients using ADC values, hypothesizing that they could be useful in predicting the recurrence of intracranial epidermoid tumors.
There have been many debates about the optimum extent of resection in intracranial epidermoid tumors [2,5,8,25]. The proliferation of stratified squamous epithelium is considered to be the cause of tumor recurrence, leading to accumulation of acellular debris such as keratin, protein, and lipid [1,8,9]. Considering the pathogenesis of this tumor, many studies have revealed that complete excision, including of the tumor capsule, reduces the risk of recurrence compared with STR [2,5,8]. Our case series confirms that patients treated with total resection showed lower recurrence rates than those treated with non-total resection (P = 0.036). While many neurosurgeons attempt GTR to minimize the recurrence rate, surgical morbidity must also be considered. The capsule can be highly adherent to adjacent critical neurovascular structures, and excessive surgical resection can lead to serious complications such as cranial nerve palsy and infarction [2,8,18]. Thus, some authors support intentional STR if an attempt at GTR seems too risky, especially in older patients with significant medical comorbidities [8,20].
A recent meta-analysis reported that the recurrence rate of intracranial epidermoid tumors is roughly one in ten patients, and some studies showed no recurrence even after subtotal resection . However, several studies included in that meta-analysis obtained follow-up imaging only when symptoms occurred and did not perform MRI annually, which might make their interpretation problematic [2,19,26]. In the current study, we annually repeated MRI studies to radiologically screen for tumor recurrence, and we found that most STR cases do recur, most recurrences occurring within 2 years of surgery. Our results also show that younger age is significantly correlated with higher probability of tumor recurrence. Although epidermoid tumors generally show benign behavior when GTR is achieved, it should be emphasized that they can often recur after STR, as our study shows. Therefore, the optimum EOR should be tailored for each patient considering recurrence risk, age, comorbidities, and surgical morbidities. For instance, most patients, in particular younger ones, should receive GTR to reduce the recurrence rate, but STR might be chosen to avoid perceived morbidities while being aware of the recurrence risk.
Some remnant epidermoid tumors have a benign course without recurrence, but some do recur even after GTR . The understanding of the natural course of this tumor is still limited and a grading system to distinguish its characteristics is not even available, due to its pathological simplicity. It is generally thought to grow slowly and to be benign, but some cases recur rapidly and rarely undergo malignant transformation . Several studies have also reported that ‘white epidermoid tumors’ have more protein components within the capsules than others [6,28]. That is, there are differences in the characteristics of epidermoid tumors, such as in the production and accumulation of their components, although they are all classified as “intracranial epidermoid tumors”. To reflect these differences, we measured the ADC values using preoperative DWI because the ADC has been shown to represent the nature of the tumor in several brain tumors [13-15]. Diffusion measurements reflect intra- and extra-cellular water motion and could indicate tumor characteristics . We found that the mean ADC values ranged roughly from 750 to 1500 (10–6 mm2/s), and the minimum ADC values ranged from 600 to 1200 (10–6 mm2/s), which is consistent with previous epidermoid ADC studies [16,30,31]. We focused on the minimum ADC values because the tumor ROIs often contain cerebrospinal fluid, which could increase the maximum and mean ADC values. We also distinguished intracranial extradural epidermoid tumors and convexity tumors from cisternal and ventricular tumors, which tend to spread into the subarachnoid space, and classified them into the “limited” and “extensive” types, respectively. Limited type epidermoid tumors have low ADC values with well circumscribed margins in a limited space, and were totally removed without difficulty in our cases, again consistently with previous reports [16,17]. However, extensive type epidermoid tumors, such as those located in the CPA area, have variable ADC values and prognosis.
Using these ADC values, we analyzed whether they reflected tumor behavior and could be predictive factors in intracranial epidermoid tumors of the extensive type. Our results show that the minimum ADC values in the recurrence group were significantly lower than in the stable group. Moreover, cases with minimum ADC values lower than the cutoff showed significantly shorter RFS (mean 19.1 months) than those with higher values (mean 50.6 months). That is, we could predict the prognosis of intracranial epidermoid tumors using their preoperative ADC maps. These findings are similar to those of previous reports showing that aggressive clival chordoma and high-grade meningioma and glioma have lower ADC values than those of less aggressive or low-grade tumors [13-15]. Therefore, close MRI follow-up is recommended for cases with minimum ADC values lower than the cutoff to screen for recurrence after surgery.
There are several limitations to this study. First, its design was retrospective, with a small sample size. Intracranial epidermoid tumor is a rare disease, making large-scale prospective studies difficult. Second, the follow-up period was not long enough, considering the benign behavior of intracranial epidermoid tumors. Although all cases of recurrence, except for one, occurred within 2 years, a further long-term follow-up investigation is required in the future. Third, most tumors were located in the CPA area rather than in the parasellar region. Fourth, there were no cases of malignant transformation, and we could not analyze their ADC values. Despite these limitations, our results suggest that preoperative ADC values could be useful in predicting the recurrence of intracranial epidermoid tumors. In this respect, our study is the first to analyze the significance of ADC values as recurrence predictors in intracranial epidermoid tumors.
In conclusion, we found that minimum ADC values and age were significantly lower in the recurrence group than in the stable group. Minimum ADC values lower than the cutoff value of 804.5×10-6 mm2/s and patients younger than 40 years showed significantly poorer RFS than those with higher ADC values and older than 40 years. Thus, preoperative ADC values can be useful in predicting the recurrence of intracranial epidermoid tumor as well as in diagnosis.