Role of stereotactic radiosurgery for recurrent skull base acinic cell carcinoma: illustrative case

Abstract

BACKGROUND

Acinic cell carcinomas (AcCCs), rare malignancies of the salivary glands, often recur and metastasize, particularly in the skull base. Conventional radical resection can be invasive for skull base AcCCs adjacent to cranial nerves and major vasculature, and the effectiveness of stereotactic radiosurgery (SRS) as an alternative is not well established.

OBSERVATIONS

This case report details the application of SRS for recurrent skull base AcCCs. A 71-year-old male with a history of resection for a right mandibular AcCC 23 years earlier experienced tumor recurrence involving the right cavernous sinus and nasal cavity. He underwent endoscopic transnasal surgery followed by SRS targeting different tumor locations—the cavernous sinus to the pterygopalatine fossa, maxillary sinus, and clivus—each with a prescribed dose of 20 Gy to the 40% to 50% isodose line. After the first skull base metastasis, additional sessions of localized SRS after endoscopic surgery led to a 12-year survival without sequela.

LESSONS

This is a report indicating that SRS for skull base AcCCs can achieve favorable local control, functional preservation, and long-term survival. SRS may be suitable for skull base AcCC given the lesion’s tendency toward multiple local recurrences. Further investigation is needed to validate the treatment’s efficacy.

Acinic cell carcinomas (AcCCs) represent a rare subset of malignant neoplasms originating predominantly from the salivary glands and constitute 3% to 11% of adult parotid gland malignancies.¹ AcCCs have been considered a disease with a relatively good prognosis for malignant tumors; however, recent findings have highlighted a potential for unpredictable recurrence and metastasis and a more malignant aspect, especially in the subgroup with high-grade transformation.^2,3 Radical marginal resection is the standard treatment for AcCC, although it may be too invasive to perform in some cases. Although previous studies have indicated favorable outcomes with postoperative adjuvant radiotherapy, the treatment’s curative role in AcCC remains controversial.^2–5 The benefits of other interventions such as elective neck dissection and chemotherapy have not been conclusively established.⁶

Once AcCC metastasizes or invades the skull base, the presence of adjacent cranial nerves and major vasculatures can render curative resection challenging, because it can cause severe neurological impairment or even life-threatening complications. Consequently, skull base invasion is regarded as an adverse prognostic indicator in patients with AcCC.^7,8 Stereotactic radiosurgery (SRS) can be a viable minimally invasive treatment option because it delivers high-dose focused radiation precisely to the tumor in a single fraction.^1,9,10 However, few studies have examined the efficacy of SRS for AcCC.^1,11 Herein, we report a case of recurrent AcCC involving multiple skull base locations, in which tumors had been controlled successfully over 12 years with a combination of safe maximal resection using endoscopic transnasal surgery (ETS), followed by multiple sessions of SRS.

Illustrative Case

A 48-year-old male had presented with a swollen face due to a right mandibular mass and underwent segmental mandibulectomy with bilateral elective neck dissection, leading to pathological confirmation of an AcCC. At the age of 71 years, he developed dysesthesia in the right deep nasal cavity, and magnetic resonance imaging (MRI) revealed a large mass extending from the right sphenoid sinus to the nasal cavity and into the right middle fossa, anterior to the right cavernous sinus, and encroaching upon the right internal carotid artery (Fig. 1A). Given the skull base recurrence involving major vasculature and cranial nerves, radical resection was deemed excessively risky. Consequently, the patient underwent ETS for maximal safe tumor resection, followed by upfront adjuvant SRS targeting residual tumor invading from the cavernous sinus to the pterygopalatine fossa. Histopathological analysis confirmed the recurrent tumor as an AcCC with characteristic round nuclei and finely vacuolated cytoplasm (Fig. 1B). SRS using the Gamma knife (Elekta AB) was performed with a prescription dose of 20 Gy to a 40% isodose line (Fig. 2A). Twelve months later, the tumor recurred in the right maxillary sinus, and the second SRS with a prescription dose of 20 Gy to a 40% isodose line was performed (Fig. 2B).

FIG. 1.

Preoperative MRI (A) displaying the recurrent AcCC in the skull base region, extending from the right sphenoid sinus to the nasal cavity and into the right middle cranial fossa. Histological examination (B) with hematoxylin and eosin stain confirming typical AcCC with round nuclei and finely vacuolated cytoplasm. Original magnification ×400.

FIG. 2.

Comprehensive imaging and SRS treatment for recurrent skull base AcCCs. Radiosurgical planning for the cavernous sinus and pterygopalatine fossa lesion, showing a prescription dose of 20 Gy to the 40% isodose line (yellow line), and 16, 12, and 8 Gy (green lines, A). Radiosurgical planning for the second SRS targeting the recurrent lesion in the right maxillary sinus, with a prescription dose of 20 Gy to a 40% isodose line (B). Radiosurgical planning image for the third SRS treatment targeting the lesion in the clivus, with a prescription dose of 20 Gy to a 50% isodose line (C). The lesions remained shrunk or diminished at the last follow-up, 148 months (D), 134 months (E), and 94 months (F) after SRS.

Forty-two months after the first SRS (at age 75 years), marginal recurrence at the prior ETS site was identified in the clivus, which was resected via an ETS followed by the third SRS in an upfront adjuvant fashion (20 Gy to a 50% isodose line; Fig. 2C). Since the first SRS, the patient had developed three marginal/remote recurrent tumors over 12 years, all of which were controlled successfully with additional sessions of SRS; these tumors showed a significant reduction in size without adverse radiation events for 148, 136, and 94 months, respectively, at the last follow-up (Fig. 2D, E, and F). The patient developed multiple bone metastases at 30 months after the last SRS, necessitating chemotherapy with denosumab and local palliative radiation. Subsequently, he underwent left partial lung resection for metastatic disease 49 months after the last SRS. At the last follow-up (83 years old, 35 years since the initial AcCC diagnosis and 12 years after the first skull base metastasis), he maintained a favorable, healthy status without neurological deficits.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

Emerging literature underscores several factors associated with a poor prognosis in AcCC, including tumor proliferative capacity, extracapsular extension, positive surgical margins, and perineural or perivascular invasion.^7,8 Additionally, it has been reported that although AcCCs can take approximately 10 years to invade or metastasize to the skull base, such progression often leads to a 50% mortality rate within 2 years.¹ These findings indicate that radical resection is highly challenging and prognosis is poor in patients with skull base invasion of AcCCs, suggesting that a minimally invasive yet effective treatment modality could be ideal.

Few articles have reported curative radiotherapy for primary AcCC, and the treatment’s efficacy remains controversial.^2,3,12 For the treatment of skull base AcCC, two studies reported that conformal radiation therapy and intensity-modulated radiation therapy were applied for local tumor control and led to survival for several years; these cases may indicate that some AcCCs exhibit radiosensitivity.^1,13 Nevertheless, given the tenacious tendency to recur, repeat extensive radiotherapy to the skull base might jeopardize adjacent cranial nerves and brain tissues.^14,15 In this regard, SRS would be a reasonable option because of its accurate high-dose radiation with its steep dose fall-off. This report details SRS for skull base invasion of AcCCs, and it is significant given the achievement of a long-term survival of 12 years from the skull base metastasis with SRS-based management. Breen et al.¹ also reported four patients for whom SRS had been applied to skull base AcCCs without observed adverse radiation effects, as in this report.

Regarding radiosurgical dose, the best optimal dose remains to be determined. In the present case, we prescribed 20 Gy for each treatment, achieving favorable tumor shrinkage with the preservation of neurological function. Breen et al.¹ previously reported good tumor control using doses of 14 to 15 Gy; however, the details of the follow-up after SRS were not documented. On the other hand, SRS for other salivary gland malignancies were reported with doses of 15 to 20 Gy.^1,9,10,16 Given the potential for long-term survival in cases of AcCC, we considered the possibility that reducing the prescription dose might lower the chances of achieving long-term tumor control and prescribed a higher dose of 20 Gy. Naturally, the exposure of surrounding normal tissues to radiation during treatment is also a concern, underscoring the need for a careful balance between the risks and benefits. The effectiveness of SRS indicates a potential for reducing invasiveness in therapeutic approaches for recurrent AcCC. In other words, instead of relying on invasive surgical methods, as was previously common, a less invasive treatment strategy focusing on SRS and endonasal surgeries may be beneficial for skull base AcCC. Although this report is based on a single case, necessitating further research, the ability to maintain neurological status and control the tumor over 12 years is promising.

Systemic therapy could also be considered for advanced AcCC; however, comprehensive evidence has yet to be established.^17–19 Recent genomic studies have identified several potential therapeutic targets, raising expectations for precision medicine.^20,21 In this patient, the systemic therapy with denosumab was used solely for bone metastases, given the absence of identifiable therapeutic molecular targets. Further research with case accumulation is imperative for a more profound understanding of AcCC genomic profiles.

Lessons

This case report details the successful application of SRS in recurrent skull base AcCC, achieving a remarkable long-term survival with effective local control and preservation of neurological function. The report highlights the complementary role of SRS and maximal safe resection via ETS, aiming to reduce tumor volume through a less invasive approach. Further research with a larger patient cohort is essential to clarify the role of SRS role in managing skull base AcCC.

Author Contributions

Conception and design: Umekawa, Yoshihira, Shin, Katano. Acquisition of data: Umekawa, Yoshihira, Shin, Kikuchi, Katano, Shinozaki-Ushiku. Analysis and interpretation of data: Umekawa, Kondo, Katano, Shinozaki-Ushiku. Drafting the article: Umekawa, Yoshihira, Hasegawa, Shin, Kikuchi. Critically revising the article: Umekawa, Shinya, Hasegawa, Shin, Y Saito, Kondo, Katano, Shinozaki-Ushiku. Reviewed submitted version of manuscript: Umekawa, Yoshihira, Shinya, Kikuchi, Y Saito, Kondo, Katano, Shinozaki-Ushiku, N Saito. Approved the final version of the manuscript on behalf of all authors: Umekawa. Study supervision: Shinya, Hasegawa, Shin.