To the best of our knowledge, this is the first cases report of coexistence of CP and CFD that highlights the diagnostic and management challenges. In addition to summarize the clinicopathologic features, treatment modalities, and outcomes of the cases, we also review the existing literature on analogous event and discussed possible links of this coexistence by genetic mutation detecting and immunohistochemical study.
The incidence of coexistence of primary brain tumors of different pathologies is low and the most common association is meningioma and glioma, followed by meningioma and pituitary, for that these are the most common primary intracranial tumors . The definite pathogenesis of this coexistence remains unknown, except familial or hereditary diseases such as neurofibromatosis type 2 or multiple endocrine neoplasia 1. Several hypotheses have been advocated to explain this phenomenon including purely coincidence, surgical trauma, radiation and/or chemical exposure, and genetic predisposition, but all in debating [10–12].
Because the sellar region has complex embryonic development, it is easy to coexist with primary intracranial tumors of different cell types at the same time. However, CPs coexisting with other central nervous system neoplasms is extremely rare. To the best of knowledge, a few cases have been reported, and the most common coexisted tumors are pituitary adenomas and meningiomas. According to a latest review reported, only 22 CP patients (median age 47.0 years; 15 males 7 females) were reported associated with pituitary adenoma and 19 out of 22 were ACPs . Guofang Liu et al reported there were 8 patients (median age 62.0 years; 5 males 3females) with coexistence of CP and meningioma, and 5 out of 8 were ACPs . Similarly, in our 5 cases (median age 39 years; 5 males 1females), 3 out of 4 operative patients were ACPs. It is found that such coexistence are more likely to occur in adults and type of ACPs, with an obvious male predominance. This is obviously different from the ACP that occurs alone, which has no gender orientation and is more common in adolescents . It is indicated that there is some underlying reason for CPs coexistence with other CNS diseases rather than purely by chance and some factors may stimulate ACP cells to induce a secondary tumor formation which is quite different from PCPs.
On the other hand, FD could also occur in association with other primary brain tumors, which is in two different conditions. The first was purely accidental and coexisted with the most common brain tumor-meningiomas, of which only a few cases were reported [16, 17]. The second, coexistence with PA, which might be in accord with McCune-Albright syndrome (MAS), and there were dozens of cases had been reported. As a postzygotic disease, clinical spectrum and severity of FD varyed depending on the timing of the mutation . In addition to the classic triad, there could be a broad spectrum or atypical presentations of the MAS . Furthermore, MAS may be associated with gastrointestinal disease and breast cancer [20, 21]. Though, no GNAS mutations were detected in the CPs specimens in our cases. Their co-occurrence should not be completely excluded the possibility of atypical FD/MAS course, for immunohistochemistry staining were high expression of Gsα protein in the 3 specimens. Further studies are needed to clarify this issue.
Based on the typical clinical symptoms and imaging features, most CPs or CFDs could be diagnosed correctly. However, it is difficult to diagnose the coexistence of CP and CFD accurately and promptly before operation because the imaging features of FDs and CPs are variable and mutual influenced [22, 23]. Deformation and thickening of the skull base might make the situation more confused, especially when the two lesions adjacent to each other. However, it is important when devising a treatment strategy preoperatively to confirm which one was responsible for the clinical symptoms. In fact, in our present cases, 4 cases that underwent surgical treatment were diagnosed accurately preoperatively.
Treatment strategies for CP coexisting with CFD have yet to be established. The current standard of treatment in CP is surgical resection via a transcranial or extended endonasal endoscopic approach followed by adjuvant radiation therapy, if required for residual tumor . Given the benign nature of CFD, and all the cases were adults, observation is considered adequate for asymptomatic quiescent FD . On the other hand, all the primary symptoms such as headaches, fatigue, polydipsia and polyuria, visual impairment were diagnosed caused by CPs in all cases in our study, at present, management strategies are aimed at surgical resect the CP and regular monitoring of FD. With the progress of microsurgery and endoscope technology, the surgical obstacles and risks caused by skull hyperplasia and deformation caused by FD will be gradually reduced. Our results also show that there were no complications directly related to surgery except vision deteriorate in case 3 for preventive decompression of optic canal encased by FD. It should also be noted that FD radiotherapy may produce side effects of malignant transformation .
The prognosis of collision tumors composed of CP and PA were undefined for the small number of cases. From our experience, it is similar to sporadic CPs and long-term morbidity is associated with tumor and treatment related risk factors. Our study has some limitations. As an extremely rare condition, the total number of cases is small and more cases are needed to strengthen the reliability of data. Secondly, the deep mechanism of the coexistence of CP and CFD still needs to be further explored and verified