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Jung, Lee, Choi, Cha, Kim, Koh, and Suh: Perineural Involvement in Benign Mixed Tumor
Perineural invasion is a diagnostic clue of malignancy and may be indicative of a poor prognosis. Perineural involvement of a benign tumor is diagnostically confusing, however, and should not be considered a malignant feature. We report a case of benign mixed tumor of the salivary gland with two foci of perineural involvement. A 31-year-old man complained of a right parotid mass which had been present for three months. He had no relevant medical history. On physical examination, there was a movable, round mass that was not accompanied by tenderness or redness. Computed tomography revealed an ovoid mass in the deep lobe of the right parotid gland with strong, early, heterogeneous enhancement. There was no evidence of tumor invasion into the surrounding tissue. Right parotidectomy was carried out; the specimen was a well-demarcated, firm, ovoid mass (2.5×2.0×1.5 cm). Grossly, the mass was grayish-tan and solid, with multifocal hemorrhages. Microscopic findings were those of a typical benign mixed tumor of the salivary gland, consisting of mixed epithelial and myoepithelial cells with chondromyxoid stroma. No lymphovascular invasion was identified. Interestingly, two foci of small tumor cell nests were present around and within nerve twigs, which were located in the subcapsular space and the fibrous tumor capsule (Fig. 1). Five months after the operation, neither recurrence nor metastasis was evident on follow-up examination. Perineural invasion is an important pathologic feature of malignancy and is related to poor outcome. However, certain benign neoplasms and reactive conditions can reveal perineural involvement. Mixed tumor is the most common type of salivary gland tumors and, in most patients, is benign, except for rare secondary malignant transformation. Typical features of malignancy are infiltrative growth, nuclear pleomorphism, atypical mitosis, necrosis, and lymphovascular or perineural invasion. The presented case had perineural involvement of benign tumor cells; otherwise it exhibited characteristics of a benign mixed tumor. The important thing to consider here is the significance of perineural involvement in the biologic behavior of the tumor. Perineural involvement of benign lesions has been documented not only in the head and neck, but also in other sites. Benign mammary glandular deposits in nerves were first described by Ali and Epstein1 and other cases of benign tumor deposits of the breast, prostate, pancreas, gallbladder, endometrium, and skin have been reported in the literature. There have been no reported cases of benign mixed tumor of salivary gland with perineural involvement in Korea. Although the cause and mechanism of perineural involvement cannot be clearly defined, Skidmore et al.2 suggested a mechanical stress origin for perineural involvement of benign tumors, but theories regarding the mechanism of its development have yet to be proven. In the present case, fine needle aspiration was performed on the tumor a month prior to the operation, which may be a potential cause of mechanical stress. In conclusion, a histologically-benign mixed tumor of the salivary gland with perineural involvement should not be diagnosed as a malignant tumor without other evidence of malignancy.


No potential conflict of interest relevant to this article was reported.


1. Ali TZ, Epstein JI. Perineural involvement by benign prostatic glands on needle biopsy. Am J Surg Pathol 2005; 29: 1159–1163. PMID: 16096404.
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2. Skidmore RA, Woosley JT, Tomsick RS. Renaut bodies: benign disease process mimicking neurotropic tumor infiltration. Dermatol Surg 1996; 22: 969–971. PMID: 9063513.
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Fig. 1
Histologic findings. Two peripheral nerve twigs with perineural (A) and neural (B) tumor involvement in the subcapsular space and the fibrous tumor capsule.
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