Ⅰ. INTRODUCTION
Schwannoma is a benign peripheral nerve sheath tumor, which is rarely affects salivary glands.1 Since schwannoma accounts for only about 0.5%-1.2 % of all parotid gland tumors, it is not a primary candidate in the differential diagnosis of a mass on pre-auricular, parotid gland lesion2. In addition, schwannomas often represent degenerative changes, generally referred to as “ancient changes”, which can mimic Warthin’s tumor or other cystic neoplasms on radiographic features, making pre-surgical diagnosis difficult3. This misdiagnoses can cause unexpected nerve damages during operation 4.
The term “Ancient Schwannoma” was first determined by Ackerman and Taylor in 19515. Ancient schwannomas show degenerative features like cystic changes, hyalinizing stroma, hemorrhages, and infiltration of macrophages6. Bizarre cellular atypia with hyperchromatic nuclei are often being found, mimicking malignant neoplasms7. Although ancient changes seem to be occurred because of the ischemic environment due to the growing size of the neoplasms, the pathophysiology of these degenerative changes is not fully understood8-11. Recognizing factors that can cause ancient change in schwannomas may help clinicians avoid misinterpretation of certain cases.
In here, we present a case of ancient schwannoma in parotid gland with and a literature review of parotid gland schwannoma, especially focused on a new perspective of the pathophysiology of “ancient change” on scwhannoma. Clinical and histopathologic analyses with immunohistochemistry are also included.
Ⅱ. CASE REPORT
Clinical History
A 62 years female patient visited dental hospital for the swelling of her right face. The lesion was noticed 3 months ago, without pain or any other symptoms. Well-circumscribed, 4cm sized mass was palpated on her right pre-auricular region. Computed tomography (CT) scans showed an encapsulated, well-defined mass with low internal density on the right parotid gland. (Fig1. A) She had no other specific medical histories.
Ultrasound associated core needle biopsy (CNB) was conducted to rule out any malignancy before the surgery. Ultrasound sonography showed a hypoechoic mass. (Fig. 1. B) The possibility of a benign neurogenic tumor was suggested, and excision was performed. The tumor was well-circumscribed, 6.2g in weight, 4.1X2.0X1.2cm in dimensions.(Fig. 1. C, D) Histopathological analysis confirmed the diagnosis of schwannoma on right parotid gland.
Histopathological Features
Core needle biopsy sample was consisted of cells with ovoid to spindle shaped nuceli. There were hypercellular area which showed cells with oval shaped nuclei are palisading, and hypocellular area where cells with elongated nuclei distributed in myxoid stroma. The border of cells was indistinct, dispersed with its adjacent stroma. Some hyalinized tissue and hemorrhage, hemosiderin deposition were also identified. Immunohistochemistry (IHC) analysis showed strong positive for S-100 protein, on both cytoplasm and nucleus of neoplastic cells. Basal/myoepithelial cell marker p40 was negative, likewise pancytokeratin and smooth muscle actin (SMA) were also negative, excluding myoepithelial, epithelial, and fibroblast originated neoplasms. Possibility of neurogenic tumor was suggested, but deterministic diagnosis was not conducted.
Surgical specimens showed an well circumscribed, encapsulated mass, measuring 4.1 cm x 2.0 cm x 1.2 cm in dimensions. Cut surface showed grayish and golden yellow soft tissue with clear fluid. Histopathological analysis revealed high cellular tumor with multiple cystic changes and hemorrhages.(Fig. 2. A) High cellular area (Antoni A) showed spindle shaped cells palisading, while low cellular area (Antoni B) showed spindle shaped cells haphazardly distributed in loose connective tissue.(Fig. 2. B) Vessels surrounded by hyalinized tissues were observed.(Fig2. C) Xanthomatous changed cells were also presented. IHC analysis showed strong positive reaction of S-100 on spindle shaped, neoplastic cells. (Fig. 3. A) SMA, desmin, CD34 showed negative reaction for neoplastic cells. (Fig. 3. B,C,D)
Ⅲ. DISCUSSION
Ancient change schwannoma of the salivary gland is an extremely rare entity. Although large scale cohort studies have not been conducted to determine the exact prevalence of ancient parotid schwannoma, it seems to be clear that it is not a common subtype. Since Jayarj et al. (1997) reported the first case of ancient schwannoma of the parotid gland12, only 6 cases were additionally reported to date, including the current case. Table 1 shows features of ancient schwannoma of parotid gland which has been reported to datecases. The average age of the patients ranged from 11 to 65 years (mean age, 37.6 years). 4 were male, and 3 were female, showing a male predominance. Interestingly, except the first case in 1997, all other cases occurred in the right side of the parotid gland. It may be biased due to the lack of abundant cases, as there is no reported side predominance in oral and maxillofacial schwannomas6. Although the pathogenesis of the diseases are not well defined due to the limited numbers of reports of ancient schwannoma, several factors, such as long duration period, ischemic necrosis, and traumatic injury, are suggested as etiology of the lesion.
Duration Period
The duration periods were various, ranging from 3 months to 20 years, although the patient with 20 years duration history mentioned that the lesion had begun to grow 2 years ago. Current case has the shortest duration time, having only 3 months of history, suggesting of no clear association between duration period and the development of ancient schawnnnoma. The size of the tumors was about 46.4 mm in length, although one case exceedingly shows large size of the tumor, measuring 95mm in length. Hyalinization and infiltration of siderophages and histiocytes showed variable features depend on the case, while cystic degenerative changes occurred in all cases.
However, considering the mean duration time of schwannoma in parotid gland was 29.46 months13, it is noticeable that the ancient change can occur without the old duration history, since 2 cases of ancient schwannoma arose in each 3 and 6 months.
Ischemic Necrosis
The size of the tumor, also another factor that can influence the ischemic condition of the tumor, did not seem to be directly related with the ancient degenerative change. Considering that the average size of schwannomas occurring in parotid gland was 35.5 ±16.7 mm13, schwannomas with ancient change seem to have no differences in size manner.
Isobe et al. reported that the average size of the ancient schwannoma was 71.4mm (ranging from 3 cm to 14 cm)14. Gabnhane et al. also reported that the average size of ancient schwannoma was 115mm, showing a relatively larger size than classical schwannomas, which have a mean size of 34mm15. Otherwise, in the oral region, these size differences become ambiguous. The mean size of ancient shcwannomas in the oral region was 21.9 mm 16, whereas the mean size of the total schwannoma in the oral region was 13.2mm with a standard deviation of 11.2mm6. These results suggest that the location of the tumor can be a more important factor than the size itself to be the ancient schwannoma. It is noticeable that the parotid gland ancient schwannomas have no differences in size, representing the anatomical characteristics of parotid gland can mask the size change of the ancient schwannoma.
Traumatic Injury
Another considerable factor that can cause degenerative changes is fine needle aspiration biopsy (FNAB) or core needle biopsy (CNB) prior to the surgical procedure. Five cases of parotid gland ancient schwannomas were examined by FNAB or CNB before the surgical excision of the tumor, including the current case. This suggests that the rapid degenerative change observed in three months may be caused by this operational procedure, potentially acting as a traumatic injury to the tumor. It has been reported that in thyroid tissue, chronic degenerative changes induced by FNAB can occur within 3 weeks, suggesting that histologic alteration can be progress rapidly as in the current case17. In reported cases of parotid gland pleomorphic adenoma and Warthin’s tumor, cystic and xanthogranulomatous changes occurred as a reactive process induced by the FNAB manipulation18,19. From this perspective, it can be considered that the FNAB or CNB can cause rapid degenerative change in parotid gland schwannoma.
There are several limitations to estimate the precise mechanism of ancient change of parotid gland schwannoma due to the lack of cases, while the factors described above, seems to play a role in this degenerative conversion. Therefore, it is reasonable to consider that a degenerative transformation has occurred in the case of a tumor presenting with an enlarged size, a long duration of periods, or especially, a history of traumatic injury such as FNAB or CNB. In such cases, it is important to exercise caution in order to avoid misdiagnosis as a malignant entity.
