Perineural invasion guided surgical management of adenoid cystic carcinoma of the pterygopalatine fossa with a proposed decision making algorithm

Perineural invasion guided surgical management of adenoid cystic carcinoma of the pterygopalatine fossa with a proposed decision making algorithm | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Perineural invasion guided surgical management of adenoid cystic carcinoma of the pterygopalatine fossa with a proposed decision making algorithm Mohammed Rami, Omar Oulghoul, Ismail El Boussouni, Mohamed Chehbouni, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9031149/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Adenoid Cystic Carcinoma (ACC) is a rare salivary malignancy characterized by indolent progression, marked neurotropism, and a high propensity for perineural invasion (PNI). Primary involvement of the pterygopalatine fossa (PPF) is exceptionally uncommon, and optimal surgical strategy remains undefined due to anatomical complexity and limited published cases. Case Presentation: We report a case of primary ACC centered in the PPF presenting with facial pain and radiologic evidence of progression along the greater palatine nerve. Sequential magnetic resonance imaging demonstrated inferior perineural spread toward the hard palate. The patient underwent a combined endoscopic endonasal and transpalatine approach to achieve complete neural pathway control. Histopathology confirmed ACC with perineural invasion and close (3 mm) margins. Postoperative adjuvant radiotherapy was administered. The patient remains disease-free at 12 month follow up. Methods and Literature Review: A focused literature review of reported PPF tumors and skull base ACC cases was performed to contextualize surgical approaches, margin management, and indications for adjuvant radiotherapy. Results and Novel Contribution: This report uniquely correlates radiologic progression, histologic confirmation of PNI, and anatomy-driven modification of the surgical approach. Based on literature synthesis and clinical findings, we propose a practical decision-making algorithm for PPF ACC management. Conclusion Perineural invasion should be considered the central determinant of surgical strategy in PPF ACC. Combined surgical corridors may be required to achieve oncologic adequacy. Multidisciplinary management including adjuvant radiotherapy is recommended in the presence of PNI or close margins. The proposed decision algorithm may assist in standardizing management of this rare skull base malignancy. adenoid cystic carcinoma pterygopalatine fossa skull base tumor endoscopic endonasal surgery transpalatine approach perineural invasion Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Adenoid cystic carcinoma (ACC) is an uncommon epithelial malignancy, accounting for approximately 1% of head and neck cancers and 10% of salivary gland tumours (Kim, Park and Kim, 2023 ). Despite its indolent clinical course, ACC demonstrates infiltrative growth, a high propensity for perineural invasion (PNI), and an established risk of late local recurrence and distant metastasis (Coca-Pelaz et al., 2015 ; Rossi, Vallurupalli and Givi, 2021 ). Neurotropic spread along cranial nerve pathways, particularly branches of the trigeminal nerve, represents a defining biological characteristic of this tumour. Primary localisation within the pterygopalatine fossa (PPF) is exceedingly rare. The PPF is a compact anatomical space connecting the nasal cavity, orbit, infratemporal fossa, nasopharynx, and middle cranial fossa. Its dense neurovascular network facilitates early neural invasion but simultaneously limits the potential to achieve wide surgical margins (Tsetsos et al., 2022 ; Zoli et al., 2025 ). Consequently, the management of ACC in this region is challenging, with most guidance derived from isolated case reports and small series (Marini et al., 2024 ; Amit et al., 2019 ). Advances in endoscopic endonasal approaches have significantly improved surgical access to the PPF (Amit et al., 2019 ; Patel et al., 2022 ), yet clear recommendations regarding approach selection in the presence of perineural spread remain limited. Inferior extension along the greater palatine nerve towards the hard palate may necessitate additional surgical corridors to achieve oncologic adequacy (Huang et al., 2023 ). In this report, we present a rare case of primary PPF ACC with radiologically documented progression along the greater palatine nerve. We correlate imaging findings, histopathologic confirmation of PNI, and surgical decision-making, and provide a focused literature review culminating in a practical, anatomy-driven decision-making algorithm. Case presentation A 53-year-old patient with no relevant medical history presented with a four-month history of left-sided facial pain, described as intermittent electric shock–like sensations with tingling, accompanied by ipsilateral otalgia and tinnitus. The patient also reported intermittent left nasal obstruction but denied epistaxis, otorrhea, visual disturbances, or neurological symptoms. The general condition was preserved, and the patient was afebrile. On anterior rhinoscopic examination, the left inferior and middle turbinates were medially displaced, limiting passage of a nasal probe. The right nasal cavity and nasopharynx appeared normal. Intraoral inspection revealed subtle bulging of the mid-portion of the left hard palate without mucosal ulceration. No cervical lymphadenopathy was palpable, and the remainder of the physical examination was unremarkable. Contrast-enhanced computed tomography (CT) of the facial bones and paranasal sinuses (Fig. 1 ) demonstrated a well-defined osteolytic lesion centered on the left pterygoid process, with lobulated margins and roughly rounded morphology. The lesion appeared hypodense on non-contrast images and exhibited heterogeneous enhancement after contrast administration, measuring approximately 28 × 24 × 29 mm in anteroposterior, transverse, and craniocaudal dimensions. Anteriorly, the tumor eroded the posterior and medial walls of the left maxillary sinus. Posterior extension obliterated the left pterygopalatine fossa with associated lysis of the medial pterygoid plate. Superiorly, the inferior orbital fissure remained uninvolved. Inferiorly, the lesion extended to the posterolateral aspect of the left hard palate, with bony erosion consistent with tumor spread along the greater palatine nerve via the greater palatine canal. Medially, the mass reached the inferior margin of the left middle meatus, causing partial obstruction of the ipsilateral choana and abutting the nasal septum. Additional findings included mild mucosal thickening of the right maxillary sinus, rightward deviation of the bony nasal septum, and preserved aeration of the frontal, sphenoid, and ethmoid sinuses. The orbital walls, cribriform plate, and nasopharynx were intact, and no significant cervical lymphadenopathy was observed. A : Axial cut showing the tumor’s extension and involvement in the infratemporal fossa (white arrow). B : Coronal cut demonstrating the invasion of the hard palate by the tumor (black arrow). Facial magnetic resonance imaging (MRI) (Fig. 2 ) demonstrated a well-circumscribed lesion centered within the left pterygopalatine fossa, resulting in expansion of the left pterygoid process. The mass had lobulated contours, showed intermediate signal intensity on T1-weighted sequences, and appeared hyperintense on T2-weighted images. Diffusion restriction was noted, and heterogeneous enhancement was observed following contrast administration. The lesion measured approximately 27 × 22 × 28 mm. Posteriorly, the tumor extended into and infiltrated the ipsilateral medial pterygoid muscle, consistent with local soft tissue involvement. A : Coronal cut, 2 months prior to surgery, showing the tumor’s localization and minimal invasion of the hard palate (white arrow). B : Coronal cut, 2 months after initial imaging and 2 days before surgery, demonstrating the rapid further invasion of the hard palate (white arrow). C : Axial cut, 2 months prior to surgery, showing the tumor’s relationship to adjacent structures (white arrow). D : Axial cut, 2 months after initial imaging, highlighting the massive and rapid invasion of the pterygoid process and pterygoid muscles (white arrow). A preoperative control magnetic resonance imaging demonstrated a slight increase in tumor size, with further invasion of the hard palate (Fig. 2 ). The patient underwent endoscopic nasal exploration and biopsy under general anesthesia. Initial nasopharyngeal inspection revealed no visible tumor. A retrograde middle meatal antrostomy was performed to access the maxillary sinus, revealing a friable mass on the medial wall, from which multiple biopsies were obtained. Histopathological examination identified a malignant epithelial neoplasm displaying tubular and cribriform patterns with stromal hyalinization. Tumor cells exhibited hyperchromatic nuclei, scant cytoplasm, and frequent mitoses. Perineural invasion was present, while vascular emboli were absent. Immunohistochemistry showed strong cytoplasmic CK7 expression, moderate-to-strong CD117 (c-KIT) positivity, nuclear p63 in basal cells, and focal pS100 staining. Ki-67 proliferation index was elevated, confirming the diagnosis of adenoid cystic carcinoma (cylindroma). Definitive surgical treatment was performed under general anesthesia with orotracheal intubation. The patient was positioned supine. The procedure was planned as a combined endonasal endoscopic and transpalatine approach, in order to achieve optimal exposure and oncologic control of the tumor within the pterygopalatine fossa and its inferior extension to the hard palate. The first stage was performed through an endonasal endoscopic approach (Fig. 3 ). Nasal preparation was achieved using xylometazoline-soaked packing, followed by the introduction of a rigid endoscope. Initial exploration revealed synechiae between the nasal septum and the inferior turbinate, which were released. A middle and inferior turbinectomy was then performed to improve surgical exposure. A medial maxillectomy was carried out, including sectioning of the nasolacrimal duct. The sphenopalatine artery was identified and coagulated. A Endoscopic view after removal of the inferior and middle turbinates and medial maxillectomy, exposing the tumor centered on the medial pterygoid process. B Exposure of the pterygoid processes and the buccal fat pad. C : Drilling of the infiltrated portion of the medial pterygoid after detaching the endonasal part of the tumor. T : Tumor , MT : Middle turbinate , S : Septum , SPA : Sphenopalatine artery , RPX : Rhinopharynx , BF : Buccal fat pad , MP : Medial pterygoid , ML : Lateral pterygoid. The tumor, originating from the posterior medial wall of the left maxillary sinus, extended inferiorly to the nasal floor and posteriorly into the pterygopalatine fossa. Tumor resection started at the posterior maxillary wall and medial pterygoid plate, which was infiltrated. Drilling of the infiltrated pterygoid plate and base continued until healthy bone was reached. Lateral tumor extension involved the buccal fat pad, which was resected for clear margins. The tumor did not extend beyond the base of the sphenoid sinus superiorly. Posterolaterally, infiltration of the medial pterygoid muscle was noted and resected. Inferiorly, the tumor followed the greater palatine nerve and infiltrated the hard palate. A second stage was performed via an endobuccal transpalatine approach due to the inferior palatal involvement (Fig. 4 ). After placement of a mouth gag, a midline palatal incision was made, and a posteriorly based palatal flap was raised. Significant lysis of the palatal bone was noted, and drilling was performed to reach healthy bone margins. Resection included the inferior portion of the medial pterygoid process, residual medial pterygoid muscle, and pterygoid hamulus, with additional drilling of the alveolo-maxillary bone. A Tracing the incision using a monopolar cautery. B Elevation of the palate flap; discovery of the bone defect caused by the tumor, followed by drilling of the infiltrated portion around the defect. C Removal of the tumor, detached via the endonasal approach, along with its palatal portion. D : Removal of the infiltrated part of the palatal mucosal flap. HP : Hard palate , NC : Nasal cavity , T : Tumor , IM : Infiltrated palatal mucosa . Additionally, the patient underwent an endoscopic dacryocystorhinostomy at the end of the procedure to bypass the injured and sacrificed lacrimal duct. Reconstruction was performed using a mucosa–muscle flap, 3 cm wide and 6 cm long, harvested from the inner aspect of the cheek. The flap comprised the jugal mucosa and the buccinator muscle, with its base positioned anteriorly and a posterior hinge to repair the palatal defect. Nasal packing was applied at the end of the procedure, and meticulous hemostasis was achieved (Fig. 5 ). A Harvesting of the flap (dotted line). B Elevation of the flap. C : Suturing the flap to the defect and closure of the flap’s initial site. F : Flap , D : Defect. The postoperative course was uneventful, and definitive histopathological examination confirmed the same histological subtype. Histopathological examination of the resected specimen revealed a 3-mm margin at the closest site along the greater palatine nerve. Although this is considered a close margin in head and neck oncology, the resection encompassed the entire documented neural pathway of tumor spread, achieving oncologic adequacy while preserving surrounding critical structures. This margin status informed the decision for adjuvant therapy. Given the presence of perineural invasion and the close surgical margin, the patient underwent adjuvant radiotherapy. Intensity-modulated radiotherapy (IMRT) was delivered to the PPF and involved neural pathways, optimizing locoregional control while sparing adjacent critical structures. The treatment was well tolerated without acute complications. The patient was closely monitored with periodic clinical evaluation and MRI imaging every 3–6 months. At one-year follow-up, there was no evidence of local recurrence or distant metastasis, and the patient remained asymptomatic. Long-term surveillance is planned due to ACC’s potential for delayed recurrence. Discussion Adenoid Cystic Carcinoma (ACC) is a rare epithelial malignancy characterized by indolent yet infiltrative growth, marked neurotropism, and a well-documented risk of late recurrence and distant metastasis. Although ACC most frequently arises from major and minor salivary glands, primary involvement of deep skull base spaces such as the pterygopalatine fossa (PPF) remains exceptionally uncommon (Marini et al., 2024 ; Tsetsos et al., 2022 ). The PPF constitutes a compact neurovascular crossroads communicating with the nasal cavity, orbit, infratemporal fossa, nasopharynx, and middle cranial fossa. Its anatomical complexity explains why tumors in this region frequently present with subtle or nonspecific symptoms, often delaying diagnosis (Tsetsos et al., 2022 ; Zoli et al., 2025 ). Facial pain, paresthesia, and referred otalgia—as observed in our patient—are classical manifestations of perineural invasion (PNI), a defining biological hallmark of ACC (Coca-Pelaz et al., 2015 ; Rodriguez Russo et al., 2021). Perineural invasion is not merely a histopathologic finding in ACC but a dominant route of tumor progression. Spread along branches of the maxillary division of the trigeminal nerve (V2), including the greater palatine nerve, has been well documented in both clinical and radiologic studies (Deng et al., 2024 ; Ginsberg and DeMonte, 1998 ). Ginsberg and DeMonte demonstrated cavernous sinus extension of palatal ACC via neural pathways, emphasizing the predictable neuroanatomical routes of dissemination (Ginsberg and DeMonte, 1998 ). Recent MRI-based analyses confirm that high-resolution imaging is essential for identifying subtle perineural spread and guiding surgical planning (Deng et al., 2024 ). In our case, sequential MRI demonstrated progression along the greater palatine canal toward the hard palate within a short interval, with subsequent histologic confirmation of PNI. This radiologic–pathologic correlation highlights the importance of neural pathway mapping when evaluating suspected PPF malignancies. Complete surgical resection with negative margins remains the cornerstone of ACC management (Coca-Pelaz et al., 2015 ; Rossi, Vallurupalli and Givi, 2021 ). However, in skull base locations such as the PPF, achieving wide margins is frequently limited by anatomical constraints. Advances in endoscopic skull base surgery have expanded access to the PPF. Amit et al. reported favorable oncologic outcomes for selected malignant skull base tumors treated via endoscopic endonasal approaches (Amit et al., 2019 ). Detailed anatomical studies have further refined endoscopic access to the PPF and infratemporal fossa (Patel et al., 2022 ). Nevertheless, purely endoscopic approaches may be insufficient when tumor extension follows neural pathways inferiorly toward the hard palate. Combined surgical corridors have therefore been advocated in selected cases to ensure complete resection while preserving oncologic principles (Huang et al., 2023 ; Zoli et al., 2025 ). In our patient, inferior tumor extension along the greater palatine nerve mandated a transpalatine component to achieve complete neural tract control and adequate bony margins. The combined endonasal endoscopic and transpalatine approach allowed circumferential exposure of the PPF, medial pterygoid plate, and palatal floor. Rather than representing technical novelty alone, this strategy was dictated by the documented perineural spread pattern, reinforcing the concept of nerve-directed surgical planning in ACC. Margin status remains a critical prognostic determinant in ACC. Due to its infiltrative and neurotropic nature, microscopic extension beyond visible tumor borders is common (Coca-Pelaz et al., 2015 ; Rossi, Vallurupalli and Givi, 2021 ). Although wide margins are ideal, skull base anatomy often limits the extent of resection. A margin of 3 mm, as obtained in our case, is considered close in head and neck oncology but may be acceptable when combined with adjuvant radiotherapy. Coca-Pelaz et al. emphasized that negative margins and multimodal treatment significantly influence local control in ACC (Coca-Pelaz et al., 2015 ). Similarly, Rossi et al. identified close margins and perineural invasion as important risk factors for recurrence (Rossi, Vallurupalli and Givi, 2021 ). Adjuvant radiotherapy is widely recommended in the presence of PNI, close or positive margins, or advanced-stage disease (Coca-Pelaz et al., 2015 ; Rodriguez Russo et al., 2021; Rossi, Vallurupalli and Givi, 2021 ). Contemporary skull base series highlight the importance of multidisciplinary management integrating surgery and postoperative radiotherapy to optimize locoregional control (Zoli et al., 2025 ). In our case, confirmed perineural invasion and a 3-mm margin prompted multidisciplinary tumor board discussion, leading to postoperative radiotherapy. The patient completed treatment without complications and remains disease-free at 12-month follow-up based on clinical examination and MRI surveillance. While ACC is known for late recurrence, this favorable intermediate outcome supports the validity of the multimodal approach. Only a limited number of primary ACC cases centered in the PPF have been reported. Marini et al. described a rare PPF ACC case managed primarily with radiotherapy (Marini et al., 2024 ). Tsetsos et al., in a systematic review of primary PPF tumors, confirmed the rarity of malignant epithelial neoplasms in this compartment and highlighted the predominance of isolated case reports (Tsetsos et al., 2022 ). Compared with previously published cases (Table 1 ), the present report uniquely documents radiologic progression along the greater palatine canal with histopathologic confirmation of PNI, directly influencing surgical strategy and adjuvant treatment decisions. This case therefore contributes not merely as an additional report of rarity, but as an anatomy-driven oncologic management model for ACC of the PPF. Table 1 Reported Cases of Primary ACC of the Pterygopalatine Fossa Author Year Surgical Approach PNI Adjuvant RT Outcome Marini et al. 2024 Non-surgical (RT/CT) Yes Yes Disease control Tsetsos et al. (Review) 2022 Various Reported Variable Review Amit et al. 2019 Endoscopic skull base Variable Yes Favorable LC Present case 2026 Combined endonasal + transpalatine Yes Yes Disease-free at 12 months Achieving negative surgical margins in ACC is a critical determinant of long-term control. Although ACC’s infiltrative behavior and tendency for subclinical spread complicate margin assessment, negative margins have been associated with lower local recurrence rates in sinonasal and skull base malignancies. Close (< 5 mm) or positive margins necessitate careful consideration for additional therapy, particularly when anatomical constraints limit wider resection (Rossi, Vallurupalli and Givi, 2021 ). Given ACC’s propensity for perineural infiltration and local recurrence, adjuvant radiotherapy is recommended in cases with PNI, close or positive margins, or advanced T stage. Intensity-modulated radiotherapy and other advanced radiotherapeutic techniques have been shown to improve locoregional control in head and neck ACC, especially when integrated into a multimodal treatment plan (Rodriguez Russo et al., 2021). Decision-Making Algorithm for Surgical and Adjuvant Management Based on the clinical course and literature synthesis, we propose an anatomy-driven decision-making algorithm for the management of adenoid cystic carcinoma (ACC) of the pterygopalatine fossa (PPF). The initial step involves high-resolution MRI evaluation with specific assessment for perineural invasion (PNI) along branches of the maxillary nerve (V2), particularly the greater palatine nerve. If imaging demonstrates a localized PPF lesion without inferior neural extension, a purely endoscopic endonasal approach may be sufficient to achieve oncologically adequate resection, as supported by contemporary skull base series (Amit et al., 2019 ; Patel et al., 2022 ; Arosio et al., 2025 ). Conversely, if radiologic or intraoperative findings confirm tumor extension along the greater palatine canal or toward the hard palate, a combined endoscopic endonasal and transpalatine approach should be considered. This strategy allows en bloc resection of the involved neural pathway and improves the likelihood of achieving negative margins while maintaining minimally invasive principles (Huang et al., 2023 ; Zoli et al., 2025 ). Following resection, margin status becomes the critical determinant of adjuvant therapy: Negative margins without high-risk features → close surveillance. Close margins (≤ 3 mm), positive margins, or confirmed perineural invasion → recommendation for adjuvant radiotherapy, in accordance with established ACC management principles (Coca-Pelaz et al., 2015 ; Rodriguez Russo et al., 2021; Rossi, Vallurupalli and Givi, 2021 ). Finally, long-term radiologic surveillance is mandatory due to the well-recognized propensity of ACC for delayed local recurrence and distant metastasis. Although our patient remains disease-free at 12 months, extended follow-up is essential to confirm durable oncologic control. Flowchart illustrating management based on MRI-detected perineural invasion. Localized lesions may be treated with endoscopic endonasal resection, while inferior neural extension requires a combined endonasal and transpalatine approach. Postoperative margins guide adjuvant radiotherapy, and long-term MRI follow-up is recommended. Limitations and Future Directions While this report provides a detailed, anatomy-driven approach to PPF ACC management, it represents a single case with intermediate follow-up. Adenoid cystic carcinoma is well-known for its potential for late local recurrence and distant metastasis, sometimes occurring several years after treatment; therefore, conclusions regarding long-term oncologic outcomes must be drawn cautiously. Additionally, although the proposed decision-making algorithm is grounded in literature synthesis and clinical rationale, its generalizability requires validation in larger patient cohorts or multicenter studies. Prospective collection of cases with long-term follow-up would be valuable to confirm the applicability of nerve-directed surgical strategies and the predictive value of margin status in guiding adjuvant therapy. Conclusion Primary adenoid cystic carcinoma of the pterygopalatine fossa is an exceptionally rare malignancy in which perineural invasion represents the dominant driver of tumor progression and the principal determinant of surgical planning. This case demonstrates that radiologic identification of neural pathway extension—particularly along the greater palatine nerve—should directly influence selection of surgical approach. When inferior perineural spread is present, a combined endoscopic endonasal and transpalatine strategy may be required to achieve oncologic control. Close margins and confirmed perineural invasion warrant multidisciplinary evaluation and consideration of adjuvant radiotherapy. Although the present patient remains disease-free at 12 months, prolonged surveillance is mandatory due to the known potential for delayed recurrence in ACC. By integrating clinical findings with current literature, we propose a structured decision-making algorithm to assist in standardizing management of this rare skull base entity. Emphasizing perineural invasion as the central therapeutic determinant may improve surgical precision and oncologic outcomes in future cases. Declarations Ethical approval: This study was approved by the Ethics Committee of the Mohammed VI University Hospital Center, Marrakech, and the Faculty of Medicine and Pharmacy of Cadi Ayyad University, Marrakech, Morocco. Consent to participate: Written informed consent was obtained from the patient to participate in this study. Consent for publication: Written informed consent was obtained from the patient for the publication of this case report and accompanying images. Competing interests: The authors declare that they have no competing interests. Clinical trial number: Not applicable. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution YR performed the surgery, led the clinical management, and prepared the manuscript. YL, RM, IE, OO, and MC contributed to case documentation, imaging interpretation, and literature review. YR and AR supervised the clinical management and critically revised the manuscript. All authors reviewed and approved the final version of the manuscript. Acknowledgements: The authors thank the Department of Otolaryngology – Head and Neck Surgery, Mohammed VI University Hospital Center, Marrakech, for their support in the clinical management of this case. Data Availability All data generated or analysed during this study are included in this published article. Further information is available from the corresponding author upon reasonable request. References Amit M, Na’ara S, Sharma K, Ramer N, Ramer I, & Gil Z. Endoscopic endonasal approach for malignant tumors of the skull base. Head Neck. 2019;41(10):3581–9. 10.1002/hed.25825 . Arosio AD, Coden E, Lambertoni A, Sileo G, Dalfino G, Monti G, Daloiso A, Gaudioso P, Ferrari M, Nicolai P, Castelnuovo P, Bignami M. Surgical margin assessment and prognostic impact in sinonasal cancers: a systematic review and meta-analysis. Acta Otorhinolaryngol Ital. 2025;45(1):S25–55. 10.14639/0392-100X-suppl.1-45-2025-N1127 . Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL et al. 2015, ‘Adenoid cystic carcinoma of the head and neck—An update’, Oral Oncology , vol. 51, no. 7, pp. 652–661. 10.1016/j.oraloncology.2015.04.005 Deng J, Zhang J, Li Y, & Wang X. 2024, ‘MRI features and perineural spread patterns of adenoid cystic carcinoma in the head and neck’, European Archives of Oto-Rhino-Laryngology , vol. 281, no. 2, pp. 987–995. 10.1007/s00405-023-08241-7 Ginsberg LE, DeMonte F. Palatal adenoid cystic carcinoma: cavernous sinus extension demonstrated by MR imaging. AJNR Am J Neuroradiol. 1998;19(4):665–7. 10.1055/s-2008-1058589 . Huang X, Zhang L, Li H, Chen Y. Combined endoscopic and transoral approaches for pterygopalatine and infratemporal fossa tumors. J Neurol Surg Part B: Skull Base. 2023;84(5):517–24. 10.1055/s-0042-1751264 . Kim YH, Park YW, Kim HJ. 2023, ‘Clinical characteristics and prognostic factors of adenoid cystic carcinoma in the head and neck: a contemporary review’, Cancers (Basel) , vol. 15, no. 6, 1789. 10.3390/cancers15061789 Marini K, Garefis K, Skliris JP, Skitotomidou E, Astreinidou A, Hajiioannou J, Argyriou N, Florou V. Adenoid cystic carcinoma of pterygopalatine fossa: report of a rare case. Indian J Otolaryngol Head Neck Surg. 2024;76(4):3493–6. 10.1007/s12070-024-04582-2 . Patel KS, Komotar RJ, Starke RM, Anand VK, Schwartz TH. 2022, ‘Endoscopic approaches to the pterygopalatine fossa and infratemporal fossa: surgical anatomy and clinical applications’, Neurosurgical Focus , vol. 52, no. 2, E6. 10.3171/2021.11.FOCUS21623 Rodriguez-Russo CA, Junn JC, Yom SS, Bakst RL. 2021, ‘Radiation therapy for adenoid cystic carcinoma of the head and neck’, Cancers , vol. 13, 6335. 10.3390/cancers13246335 Rossi M, Vallurupalli M, Givi B. Adenoid cystic carcinoma: current concepts and future directions. Curr Oncol Rep. 2021;23(8):93. 10.1007/s11912-021-01088-7 . Tsetsos N, Poutoglidis A, Vlachtsis K, Stavrakas M, & Nikolaou A. Primary tumors of the pterygopalatine fossa: a systematic review of case reports and case series. Auris Nasus Larynx. 2022;49(5):703–12. 10.1016/j.anl.2021.11.006 . Zoli M, Mazzatenta D, Pasquini E, Frank G. 2025, ‘Multidisciplinary management of malignant tumors of the pterygopalatine fossa and infratemporal fossa’, World Neurosurgery , vol. 186, pp. 123–132. 10.1016/j.wneu.2024.10.045 Additional Declarations No competing interests reported. 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Center","correspondingAuthor":false,"prefix":"","firstName":"Omar","middleName":"","lastName":"Oulghoul","suffix":""},{"id":627266219,"identity":"f8fc6dd2-7cd0-469c-8c94-b352abb5853e","order_by":2,"name":"Ismail El Boussouni","email":"","orcid":"","institution":"Mohammed VI University Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Ismail","middleName":"El","lastName":"Boussouni","suffix":""},{"id":627266220,"identity":"af51ef85-5c80-400a-9590-9ebe64c96d93","order_by":3,"name":"Mohamed Chehbouni","email":"","orcid":"","institution":"Mohammed VI University Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Chehbouni","suffix":""},{"id":627266222,"identity":"b799f3b7-9ede-4293-9e73-344222094918","order_by":4,"name":"Youssef Lakhdar","email":"","orcid":"","institution":"Mohammed VI University Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Youssef","middleName":"","lastName":"Lakhdar","suffix":""},{"id":627266223,"identity":"e37e7d2d-6c8e-44e7-b423-b2216c23c82c","order_by":5,"name":"Youssef Rochdi","email":"","orcid":"","institution":"Mohammed VI University Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Youssef","middleName":"","lastName":"Rochdi","suffix":""},{"id":627266224,"identity":"fd6dc09f-6674-428e-9095-41cb2a65adc2","order_by":6,"name":"Abdelaziz Raji","email":"","orcid":"","institution":"Mohammed VI University Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Abdelaziz","middleName":"","lastName":"Raji","suffix":""}],"badges":[],"createdAt":"2026-03-04 14:08:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9031149/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9031149/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107834200,"identity":"1ef4838c-ebd8-4bcd-b40b-69daf2f5582a","added_by":"auto","created_at":"2026-04-26 15:43:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1032911,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eFacial CT scan imaging of the tumor, 2 months prior to surgery.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eA:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Axial cut showing the tumor’s extension and involvement in the infratemporal fossa (white arrow). \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eB:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Coronal cut demonstrating the invasion of the hard palate by the tumor (black arrow).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/ef0a2df3c89e5c0803ef9cac.png"},{"id":107869555,"identity":"ea4347f2-4394-4b8a-93a5-2838e143438a","added_by":"auto","created_at":"2026-04-27 07:37:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":814515,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eT2-weighted facial MRI imaging of the tumor.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eA:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Coronal cut, 2 months prior to surgery, showing the tumor’s localization and minimal invasion of the hard palate (white arrow). \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eB:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Coronal cut, 2 months after initial imaging and 2 days before surgery, demonstrating the rapid further invasion of the hard palate (white arrow).\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eC:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Axial cut, 2 months prior to surgery, showing the tumor’s relationship to adjacent structures (white arrow).\u003c/em\u003e\u003cem\u003e\u003cstrong\u003eD:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Axial cut, 2 months after initial imaging, highlighting the massive and rapid invasion of the pterygoid process and pterygoid muscles (white arrow).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/dbbcffc16e380f408957cd49.png"},{"id":107869556,"identity":"800f09c2-99c8-4c36-a5ba-0360e7cafdf4","added_by":"auto","created_at":"2026-04-27 07:37:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":868167,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eFirst stage of the surgery, removing the nasal portion of the tumor via an endonasal endoscopic approach.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eA:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Endoscopic view after removal of the inferior and middle turbinates and medial maxillectomy, exposing the tumor centered on the medial pterygoid process.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eB:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Exposure of the pterygoid processes and the buccal fat pad.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eC:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Drilling of the infiltrated portion of the medial pterygoid after detaching the endonasal part of the tumor.\u003c/em\u003e\u003cem\u003e\u003cstrong\u003eT:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Tumor, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eMT:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eMiddle turbinate, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eS:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Septum, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eSPA:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eSphenopalatine artery, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eRPX:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Rhinopharynx, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eBF:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eBuccal fat pad, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eMP:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Medial pterygoid, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eML:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eLateral pterygoid.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/83aa7b97e3ae9a8c6fa0a2a6.png"},{"id":107870811,"identity":"7c975865-d73d-4931-8790-350f723917bc","added_by":"auto","created_at":"2026-04-27 07:40:48","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1008439,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eOral step of the surgery.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eA:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Tracing the incision using a monopolar cautery.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eB:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Elevation of the palate flap; discovery of the bone defect caused by the tumor, followed by drilling of the infiltrated portion around the defect.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eC:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Removal of the tumor, detached via the endonasal approach, along with its palatal portion.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eD:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Removal of the infiltrated part of the palatal mucosal flap. \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eHP:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Hard palate, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eNC:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Nasal cavity, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eT:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003eTumor, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eIM:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Infiltrated palatal mucosa\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/b0f9e7d5175c1d6917adaa14.png"},{"id":107834203,"identity":"1fc87b81-e619-48d4-960d-480b43a2d585","added_by":"auto","created_at":"2026-04-26 15:43:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":948706,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eReconstruction of the palate using a mucosa–muscle flap from the inner aspect of the cheek.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eA:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Harvesting of the flap (dotted line).\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eB:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Elevation of the flap.\u003cbr\u003e\n \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eC:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Suturing the flap to the defect and closure of the flap’s initial site.\u003c/em\u003e\u003cem\u003e\u003cstrong\u003eF:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Flap, \u003c/em\u003e\u003cem\u003e\u003cstrong\u003eD:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Defect.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/29b15b01ddd2228e739e8e55.png"},{"id":107869979,"identity":"52e9b984-e69b-4ff5-bd20-3bc924afe215","added_by":"auto","created_at":"2026-04-27 07:38:34","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":388927,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDecision-Making Algorithm for ACC of the Pterygopalatine Fossa.\u003c/strong\u003e\u003cbr\u003e\nFlowchart illustrating management based on MRI-detected perineural invasion. Localized lesions may be treated with endoscopic endonasal resection, while inferior neural extension requires a combined endonasal and transpalatine approach. Postoperative margins guide adjuvant radiotherapy, and long-term MRI follow-up is recommended.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/77be492fcf8f0f5c0a520bf9.png"},{"id":108181064,"identity":"7d484bec-e80c-42d4-ab98-d820e96577f0","added_by":"auto","created_at":"2026-04-30 08:56:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6874441,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9031149/v1/c1bd6df1-7e64-4371-a4de-a20558fddc2e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Perineural invasion guided surgical management of adenoid cystic carcinoma of the pterygopalatine fossa with a proposed decision making algorithm","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdenoid cystic carcinoma (ACC) is an uncommon epithelial malignancy, accounting for approximately 1% of head and neck cancers and 10% of salivary gland tumours (Kim, Park and Kim, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Despite its indolent clinical course, ACC demonstrates infiltrative growth, a high propensity for perineural invasion (PNI), and an established risk of late local recurrence and distant metastasis (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Neurotropic spread along cranial nerve pathways, particularly branches of the trigeminal nerve, represents a defining biological characteristic of this tumour.\u003c/p\u003e \u003cp\u003ePrimary localisation within the pterygopalatine fossa (PPF) is exceedingly rare. The PPF is a compact anatomical space connecting the nasal cavity, orbit, infratemporal fossa, nasopharynx, and middle cranial fossa. Its dense neurovascular network facilitates early neural invasion but simultaneously limits the potential to achieve wide surgical margins (Tsetsos et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Zoli et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Consequently, the management of ACC in this region is challenging, with most guidance derived from isolated case reports and small series (Marini et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Amit et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdvances in endoscopic endonasal approaches have significantly improved surgical access to the PPF (Amit et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Patel et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), yet clear recommendations regarding approach selection in the presence of perineural spread remain limited. Inferior extension along the greater palatine nerve towards the hard palate may necessitate additional surgical corridors to achieve oncologic adequacy (Huang et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). In this report, we present a rare case of primary PPF ACC with radiologically documented progression along the greater palatine nerve. We correlate imaging findings, histopathologic confirmation of PNI, and surgical decision-making, and provide a focused literature review culminating in a practical, anatomy-driven decision-making algorithm.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 53-year-old patient with no relevant medical history presented with a four-month history of left-sided facial pain, described as intermittent electric shock\u0026ndash;like sensations with tingling, accompanied by ipsilateral otalgia and tinnitus. The patient also reported intermittent left nasal obstruction but denied epistaxis, otorrhea, visual disturbances, or neurological symptoms. The general condition was preserved, and the patient was afebrile.\u003c/p\u003e \u003cp\u003eOn anterior rhinoscopic examination, the left inferior and middle turbinates were medially displaced, limiting passage of a nasal probe. The right nasal cavity and nasopharynx appeared normal. Intraoral inspection revealed subtle bulging of the mid-portion of the left hard palate without mucosal ulceration. No cervical lymphadenopathy was palpable, and the remainder of the physical examination was unremarkable.\u003c/p\u003e \u003cp\u003eContrast-enhanced computed tomography (CT) of the facial bones and paranasal sinuses (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) demonstrated a well-defined osteolytic lesion centered on the left pterygoid process, with lobulated margins and roughly rounded morphology. The lesion appeared hypodense on non-contrast images and exhibited heterogeneous enhancement after contrast administration, measuring approximately 28 \u0026times; 24 \u0026times; 29 mm in anteroposterior, transverse, and craniocaudal dimensions. Anteriorly, the tumor eroded the posterior and medial walls of the left maxillary sinus. Posterior extension obliterated the left pterygopalatine fossa with associated lysis of the medial pterygoid plate.\u003c/p\u003e \u003cp\u003eSuperiorly, the inferior orbital fissure remained uninvolved. Inferiorly, the lesion extended to the posterolateral aspect of the left hard palate, with bony erosion consistent with tumor spread along the greater palatine nerve via the greater palatine canal. Medially, the mass reached the inferior margin of the left middle meatus, causing partial obstruction of the ipsilateral choana and abutting the nasal septum. Additional findings included mild mucosal thickening of the right maxillary sinus, rightward deviation of the bony nasal septum, and preserved aeration of the frontal, sphenoid, and ethmoid sinuses. The orbital walls, cribriform plate, and nasopharynx were intact, and no significant cervical lymphadenopathy was observed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eA\u003c/b\u003e: \u003cem\u003eAxial cut showing the tumor\u0026rsquo;s extension and involvement in the infratemporal fossa (white arrow).\u003c/em\u003e \u003cb\u003eB\u003c/b\u003e: \u003cem\u003eCoronal cut demonstrating the invasion of the hard palate by the tumor (black arrow).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eFacial magnetic resonance imaging (MRI) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) demonstrated a well-circumscribed lesion centered within the left pterygopalatine fossa, resulting in expansion of the left pterygoid process. The mass had lobulated contours, showed intermediate signal intensity on T1-weighted sequences, and appeared hyperintense on T2-weighted images. Diffusion restriction was noted, and heterogeneous enhancement was observed following contrast administration. The lesion measured approximately 27 \u0026times; 22 \u0026times; 28 mm. Posteriorly, the tumor extended into and infiltrated the ipsilateral medial pterygoid muscle, consistent with local soft tissue involvement.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eA\u003c/b\u003e: \u003cem\u003eCoronal cut, 2 months prior to surgery, showing the tumor\u0026rsquo;s localization and minimal invasion of the hard palate (white arrow).\u003c/em\u003e \u003cb\u003eB\u003c/b\u003e: \u003cem\u003eCoronal cut, 2 months after initial imaging and 2 days before surgery, demonstrating the rapid further invasion of the hard palate (white arrow).\u003c/em\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eC\u003c/b\u003e: \u003cem\u003eAxial cut, 2 months prior to surgery, showing the tumor\u0026rsquo;s relationship to adjacent structures (white arrow).\u003c/em\u003e\u003cb\u003eD\u003c/b\u003e: \u003cem\u003eAxial cut, 2 months after initial imaging, highlighting the massive and rapid invasion of the pterygoid process and pterygoid muscles (white arrow).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eA preoperative control magnetic resonance imaging demonstrated a slight increase in tumor size, with further invasion of the hard palate (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe patient underwent endoscopic nasal exploration and biopsy under general anesthesia. Initial nasopharyngeal inspection revealed no visible tumor. A retrograde middle meatal antrostomy was performed to access the maxillary sinus, revealing a friable mass on the medial wall, from which multiple biopsies were obtained.\u003c/p\u003e \u003cp\u003eHistopathological examination identified a malignant epithelial neoplasm displaying tubular and cribriform patterns with stromal hyalinization. Tumor cells exhibited hyperchromatic nuclei, scant cytoplasm, and frequent mitoses. Perineural invasion was present, while vascular emboli were absent. Immunohistochemistry showed strong cytoplasmic CK7 expression, moderate-to-strong CD117 (c-KIT) positivity, nuclear p63 in basal cells, and focal pS100 staining. Ki-67 proliferation index was elevated, confirming the diagnosis of adenoid cystic carcinoma (cylindroma).\u003c/p\u003e \u003cp\u003eDefinitive surgical treatment was performed under general anesthesia with orotracheal intubation. The patient was positioned supine. The procedure was planned as a combined endonasal endoscopic and transpalatine approach, in order to achieve optimal exposure and oncologic control of the tumor within the pterygopalatine fossa and its inferior extension to the hard palate.\u003c/p\u003e \u003cp\u003eThe first stage was performed through an endonasal endoscopic approach (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Nasal preparation was achieved using xylometazoline-soaked packing, followed by the introduction of a rigid endoscope. Initial exploration revealed synechiae between the nasal septum and the inferior turbinate, which were released. A middle and inferior turbinectomy was then performed to improve surgical exposure. A medial maxillectomy was carried out, including sectioning of the nasolacrimal duct. The sphenopalatine artery was identified and coagulated.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eA\u003c/strong\u003e \u003cp\u003e \u003cem\u003eEndoscopic view after removal of the inferior and middle turbinates and medial maxillectomy, exposing the tumor centered on the medial pterygoid process.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eB\u003c/strong\u003e \u003cp\u003e \u003cem\u003eExposure of the pterygoid processes and the buccal fat pad.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eC\u003c/b\u003e: \u003cem\u003eDrilling of the infiltrated portion of the medial pterygoid after detaching the endonasal part of the tumor.\u003c/em\u003e\u003cb\u003eT\u003c/b\u003e: \u003cem\u003eTumor\u003c/em\u003e, \u003cb\u003eMT\u003c/b\u003e: \u003cem\u003eMiddle turbinate\u003c/em\u003e, \u003cb\u003eS\u003c/b\u003e: \u003cem\u003eSeptum\u003c/em\u003e, \u003cb\u003eSPA\u003c/b\u003e: \u003cem\u003eSphenopalatine artery\u003c/em\u003e, \u003cb\u003eRPX\u003c/b\u003e: \u003cem\u003eRhinopharynx\u003c/em\u003e, \u003cb\u003eBF\u003c/b\u003e: \u003cem\u003eBuccal fat pad\u003c/em\u003e, \u003cb\u003eMP\u003c/b\u003e: \u003cem\u003eMedial pterygoid\u003c/em\u003e, \u003cb\u003eML\u003c/b\u003e: \u003cem\u003eLateral pterygoid.\u003c/em\u003e\u003c/p\u003e \u003cp\u003eThe tumor, originating from the posterior medial wall of the left maxillary sinus, extended inferiorly to the nasal floor and posteriorly into the pterygopalatine fossa. Tumor resection started at the posterior maxillary wall and medial pterygoid plate, which was infiltrated. Drilling of the infiltrated pterygoid plate and base continued until healthy bone was reached. Lateral tumor extension involved the buccal fat pad, which was resected for clear margins. The tumor did not extend beyond the base of the sphenoid sinus superiorly. Posterolaterally, infiltration of the medial pterygoid muscle was noted and resected. Inferiorly, the tumor followed the greater palatine nerve and infiltrated the hard palate.\u003c/p\u003e \u003cp\u003eA second stage was performed via an endobuccal transpalatine approach due to the inferior palatal involvement (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). After placement of a mouth gag, a midline palatal incision was made, and a posteriorly based palatal flap was raised. Significant lysis of the palatal bone was noted, and drilling was performed to reach healthy bone margins. Resection included the inferior portion of the medial pterygoid process, residual medial pterygoid muscle, and pterygoid hamulus, with additional drilling of the alveolo-maxillary bone.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eA\u003c/strong\u003e \u003cp\u003e \u003cem\u003eTracing the incision using a monopolar cautery.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eB\u003c/strong\u003e \u003cp\u003e \u003cem\u003eElevation of the palate flap; discovery of the bone defect caused by the tumor, followed by drilling of the infiltrated portion around the defect.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eC\u003c/strong\u003e \u003cp\u003e \u003cem\u003eRemoval of the tumor, detached via the endonasal approach, along with its palatal portion.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eD\u003c/b\u003e: \u003cem\u003eRemoval of the infiltrated part of the palatal mucosal flap.\u003c/em\u003e \u003cb\u003eHP\u003c/b\u003e: \u003cem\u003eHard palate\u003c/em\u003e, \u003cb\u003eNC\u003c/b\u003e: \u003cem\u003eNasal cavity\u003c/em\u003e, \u003cb\u003eT\u003c/b\u003e: \u003cem\u003eTumor\u003c/em\u003e, \u003cb\u003eIM\u003c/b\u003e: \u003cem\u003eInfiltrated palatal mucosa\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eAdditionally, the patient underwent an endoscopic dacryocystorhinostomy at the end of the procedure to bypass the injured and sacrificed lacrimal duct.\u003c/p\u003e \u003cp\u003eReconstruction was performed using a mucosa\u0026ndash;muscle flap, 3 cm wide and 6 cm long, harvested from the inner aspect of the cheek. The flap comprised the jugal mucosa and the buccinator muscle, with its base positioned anteriorly and a posterior hinge to repair the palatal defect. Nasal packing was applied at the end of the procedure, and meticulous hemostasis was achieved (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eA\u003c/strong\u003e \u003cp\u003e \u003cem\u003eHarvesting of the flap (dotted line).\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eB\u003c/strong\u003e \u003cp\u003e \u003cem\u003eElevation of the flap.\u003c/em\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eC\u003c/b\u003e: \u003cem\u003eSuturing the flap to the defect and closure of the flap\u0026rsquo;s initial site.\u003c/em\u003e\u003cb\u003eF\u003c/b\u003e: \u003cem\u003eFlap\u003c/em\u003e, \u003cb\u003eD\u003c/b\u003e: \u003cem\u003eDefect.\u003c/em\u003e\u003c/p\u003e \u003cp\u003eThe postoperative course was uneventful, and definitive histopathological examination confirmed the same histological subtype.\u003c/p\u003e \u003cp\u003eHistopathological examination of the resected specimen revealed a 3-mm margin at the closest site along the greater palatine nerve. Although this is considered a close margin in head and neck oncology, the resection encompassed the entire documented neural pathway of tumor spread, achieving oncologic adequacy while preserving surrounding critical structures. This margin status informed the decision for adjuvant therapy.\u003c/p\u003e \u003cp\u003eGiven the presence of perineural invasion and the close surgical margin, the patient underwent adjuvant radiotherapy. Intensity-modulated radiotherapy (IMRT) was delivered to the PPF and involved neural pathways, optimizing locoregional control while sparing adjacent critical structures. The treatment was well tolerated without acute complications.\u003c/p\u003e \u003cp\u003eThe patient was closely monitored with periodic clinical evaluation and MRI imaging every 3\u0026ndash;6 months. At one-year follow-up, there was no evidence of local recurrence or distant metastasis, and the patient remained asymptomatic. Long-term surveillance is planned due to ACC\u0026rsquo;s potential for delayed recurrence.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAdenoid Cystic Carcinoma (ACC) is a rare epithelial malignancy characterized by indolent yet infiltrative growth, marked neurotropism, and a well-documented risk of late recurrence and distant metastasis. Although ACC most frequently arises from major and minor salivary glands, primary involvement of deep skull base spaces such as the pterygopalatine fossa (PPF) remains exceptionally uncommon (Marini et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Tsetsos et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe PPF constitutes a compact neurovascular crossroads communicating with the nasal cavity, orbit, infratemporal fossa, nasopharynx, and middle cranial fossa. Its anatomical complexity explains why tumors in this region frequently present with subtle or nonspecific symptoms, often delaying diagnosis (Tsetsos et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Zoli et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Facial pain, paresthesia, and referred otalgia\u0026mdash;as observed in our patient\u0026mdash;are classical manifestations of perineural invasion (PNI), a defining biological hallmark of ACC (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Rodriguez Russo et al., 2021).\u003c/p\u003e \u003cp\u003ePerineural invasion is not merely a histopathologic finding in ACC but a dominant route of tumor progression. Spread along branches of the maxillary division of the trigeminal nerve (V2), including the greater palatine nerve, has been well documented in both clinical and radiologic studies (Deng et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Ginsberg and DeMonte, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e1998\u003c/span\u003e). Ginsberg and DeMonte demonstrated cavernous sinus extension of palatal ACC via neural pathways, emphasizing the predictable neuroanatomical routes of dissemination (Ginsberg and DeMonte, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e1998\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent MRI-based analyses confirm that high-resolution imaging is essential for identifying subtle perineural spread and guiding surgical planning (Deng et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In our case, sequential MRI demonstrated progression along the greater palatine canal toward the hard palate within a short interval, with subsequent histologic confirmation of PNI. This radiologic\u0026ndash;pathologic correlation highlights the importance of neural pathway mapping when evaluating suspected PPF malignancies.\u003c/p\u003e \u003cp\u003eComplete surgical resection with negative margins remains the cornerstone of ACC management (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, in skull base locations such as the PPF, achieving wide margins is frequently limited by anatomical constraints.\u003c/p\u003e \u003cp\u003eAdvances in endoscopic skull base surgery have expanded access to the PPF. Amit et al. reported favorable oncologic outcomes for selected malignant skull base tumors treated via endoscopic endonasal approaches (Amit et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Detailed anatomical studies have further refined endoscopic access to the PPF and infratemporal fossa (Patel et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNevertheless, purely endoscopic approaches may be insufficient when tumor extension follows neural pathways inferiorly toward the hard palate. Combined surgical corridors have therefore been advocated in selected cases to ensure complete resection while preserving oncologic principles (Huang et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Zoli et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our patient, inferior tumor extension along the greater palatine nerve mandated a transpalatine component to achieve complete neural tract control and adequate bony margins. The combined endonasal endoscopic and transpalatine approach allowed circumferential exposure of the PPF, medial pterygoid plate, and palatal floor. Rather than representing technical novelty alone, this strategy was dictated by the documented perineural spread pattern, reinforcing the concept of nerve-directed surgical planning in ACC.\u003c/p\u003e \u003cp\u003eMargin status remains a critical prognostic determinant in ACC. Due to its infiltrative and neurotropic nature, microscopic extension beyond visible tumor borders is common (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough wide margins are ideal, skull base anatomy often limits the extent of resection. A margin of 3 mm, as obtained in our case, is considered close in head and neck oncology but may be acceptable when combined with adjuvant radiotherapy. Coca-Pelaz et al. emphasized that negative margins and multimodal treatment significantly influence local control in ACC (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Similarly, Rossi et al. identified close margins and perineural invasion as important risk factors for recurrence (Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdjuvant radiotherapy is widely recommended in the presence of PNI, close or positive margins, or advanced-stage disease (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Rodriguez Russo et al., 2021; Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Contemporary skull base series highlight the importance of multidisciplinary management integrating surgery and postoperative radiotherapy to optimize locoregional control (Zoli et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our case, confirmed perineural invasion and a 3-mm margin prompted multidisciplinary tumor board discussion, leading to postoperative radiotherapy. The patient completed treatment without complications and remains disease-free at 12-month follow-up based on clinical examination and MRI surveillance. While ACC is known for late recurrence, this favorable intermediate outcome supports the validity of the multimodal approach.\u003c/p\u003e \u003cp\u003eOnly a limited number of primary ACC cases centered in the PPF have been reported. Marini et al. described a rare PPF ACC case managed primarily with radiotherapy (Marini et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Tsetsos et al., in a systematic review of primary PPF tumors, confirmed the rarity of malignant epithelial neoplasms in this compartment and highlighted the predominance of isolated case reports (Tsetsos et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCompared with previously published cases (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), the present report uniquely documents radiologic progression along the greater palatine canal with histopathologic confirmation of PNI, directly influencing surgical strategy and adjuvant treatment decisions. This case therefore contributes not merely as an additional report of rarity, but as an anatomy-driven oncologic management model for ACC of the PPF.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReported Cases of Primary ACC of the Pterygopalatine Fossa\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgical Approach\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePNI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjuvant RT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarini et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-surgical (RT/CT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDisease control\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTsetsos et al. (Review)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVarious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReview\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmit et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEndoscopic skull base\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFavorable LC\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCombined endonasal\u0026thinsp;+\u0026thinsp;transpalatine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDisease-free at 12 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAchieving negative surgical margins in ACC is a critical determinant of long-term control. Although ACC\u0026rsquo;s infiltrative behavior and tendency for subclinical spread complicate margin assessment, negative margins have been associated with lower local recurrence rates in sinonasal and skull base malignancies. Close (\u0026lt;\u0026thinsp;5 mm) or positive margins necessitate careful consideration for additional therapy, particularly when anatomical constraints limit wider resection (Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven ACC\u0026rsquo;s propensity for perineural infiltration and local recurrence, adjuvant radiotherapy is recommended in cases with PNI, close or positive margins, or advanced T stage. Intensity-modulated radiotherapy and other advanced radiotherapeutic techniques have been shown to improve locoregional control in head and neck ACC, especially when integrated into a multimodal treatment plan (Rodriguez Russo et al., 2021).\u003c/p\u003e\n\u003ch3\u003eDecision-Making Algorithm for Surgical and Adjuvant Management\u003c/h3\u003e\n\u003cp\u003eBased on the clinical course and literature synthesis, we propose an anatomy-driven decision-making algorithm for the management of adenoid cystic carcinoma (ACC) of the pterygopalatine fossa (PPF).\u003c/p\u003e \u003cp\u003eThe initial step involves high-resolution MRI evaluation with specific assessment for perineural invasion (PNI) along branches of the maxillary nerve (V2), particularly the greater palatine nerve.\u003c/p\u003e \u003cp\u003eIf imaging demonstrates a localized PPF lesion without inferior neural extension, a purely endoscopic endonasal approach may be sufficient to achieve oncologically adequate resection, as supported by contemporary skull base series (Amit et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Patel et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Arosio et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConversely, if radiologic or intraoperative findings confirm tumor extension along the greater palatine canal or toward the hard palate, a combined endoscopic endonasal and transpalatine approach should be considered. This strategy allows en bloc resection of the involved neural pathway and improves the likelihood of achieving negative margins while maintaining minimally invasive principles (Huang et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Zoli et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFollowing resection, margin status becomes the critical determinant of adjuvant therapy:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eNegative margins without high-risk features \u0026rarr; close surveillance.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eClose margins (\u0026le;\u0026thinsp;3 mm), positive margins, or confirmed perineural invasion \u0026rarr; recommendation for adjuvant radiotherapy, in accordance with established ACC management principles (Coca-Pelaz et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Rodriguez Russo et al., 2021; Rossi, Vallurupalli and Givi, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFinally, long-term radiologic surveillance is mandatory due to the well-recognized propensity of ACC for delayed local recurrence and distant metastasis. Although our patient remains disease-free at 12 months, extended follow-up is essential to confirm durable oncologic control.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFlowchart illustrating management based on MRI-detected perineural invasion. Localized lesions may be treated with endoscopic endonasal resection, while inferior neural extension requires a combined endonasal and transpalatine approach. Postoperative margins guide adjuvant radiotherapy, and long-term MRI follow-up is recommended.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLimitations and Future Directions\u003c/strong\u003e \u003cp\u003eWhile this report provides a detailed, anatomy-driven approach to PPF ACC management, it represents a single case with intermediate follow-up. Adenoid cystic carcinoma is well-known for its potential for late local recurrence and distant metastasis, sometimes occurring several years after treatment; therefore, conclusions regarding long-term oncologic outcomes must be drawn cautiously. Additionally, although the proposed decision-making algorithm is grounded in literature synthesis and clinical rationale, its generalizability requires validation in larger patient cohorts or multicenter studies. Prospective collection of cases with long-term follow-up would be valuable to confirm the applicability of nerve-directed surgical strategies and the predictive value of margin status in guiding adjuvant therapy.\u003c/p\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePrimary adenoid cystic carcinoma of the pterygopalatine fossa is an exceptionally rare malignancy in which perineural invasion represents the dominant driver of tumor progression and the principal determinant of surgical planning.\u003c/p\u003e \u003cp\u003eThis case demonstrates that radiologic identification of neural pathway extension\u0026mdash;particularly along the greater palatine nerve\u0026mdash;should directly influence selection of surgical approach. When inferior perineural spread is present, a combined endoscopic endonasal and transpalatine strategy may be required to achieve oncologic control.\u003c/p\u003e \u003cp\u003eClose margins and confirmed perineural invasion warrant multidisciplinary evaluation and consideration of adjuvant radiotherapy. Although the present patient remains disease-free at 12 months, prolonged surveillance is mandatory due to the known potential for delayed recurrence in ACC.\u003c/p\u003e \u003cp\u003eBy integrating clinical findings with current literature, we propose a structured decision-making algorithm to assist in standardizing management of this rare skull base entity. Emphasizing perineural invasion as the central therapeutic determinant may improve surgical precision and oncologic outcomes in future cases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthical approval:\u003c/strong\u003e \u003cp\u003eThis study was approved by the Ethics Committee of the Mohammed VI University Hospital Center, Marrakech, and the Faculty of Medicine and Pharmacy of Cadi Ayyad University, Marrakech, Morocco.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to participate:\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patient to participate in this study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report and accompanying images.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eClinical trial number:\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYR performed the surgery, led the clinical management, and prepared the manuscript. YL, RM, IE, OO, and MC contributed to case documentation, imaging interpretation, and literature review. YR and AR supervised the clinical management and critically revised the manuscript. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eThe authors thank the Department of Otolaryngology \u0026ndash; Head and Neck Surgery, Mohammed VI University Hospital Center, Marrakech, for their support in the clinical management of this case.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analysed during this study are included in this published article. Further information is available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmit M, Na\u0026rsquo;ara S, Sharma K, Ramer N, Ramer I, \u0026amp; Gil Z. 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Auris Nasus Larynx. 2022;49(5):703\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.anl.2021.11.006\u003c/span\u003e\u003cspan address=\"10.1016/j.anl.2021.11.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZoli M, Mazzatenta D, Pasquini E, Frank G. 2025, \u0026lsquo;Multidisciplinary management of malignant tumors of the pterygopalatine fossa and infratemporal fossa\u0026rsquo;, \u003cem\u003eWorld Neurosurgery\u003c/em\u003e, vol. 186, pp. 123\u0026ndash;132. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2024.10.045\u003c/span\u003e\u003cspan address=\"10.1016/j.wneu.2024.10.045\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"adenoid cystic carcinoma, pterygopalatine fossa, skull base tumor, endoscopic endonasal surgery, transpalatine approach, perineural invasion","lastPublishedDoi":"10.21203/rs.3.rs-9031149/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9031149/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAdenoid Cystic Carcinoma (ACC) is a rare salivary malignancy characterized by indolent progression, marked neurotropism, and a high propensity for perineural invasion (PNI). Primary involvement of the pterygopalatine fossa (PPF) is exceptionally uncommon, and optimal surgical strategy remains undefined due to anatomical complexity and limited published cases.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe report a case of primary ACC centered in the PPF presenting with facial pain and radiologic evidence of progression along the greater palatine nerve. Sequential magnetic resonance imaging demonstrated inferior perineural spread toward the hard palate. The patient underwent a combined endoscopic endonasal and transpalatine approach to achieve complete neural pathway control. Histopathology confirmed ACC with perineural invasion and close (3 mm) margins. Postoperative adjuvant radiotherapy was administered. The patient remains disease-free at 12 month follow up.\u003c/p\u003e\u003ch2\u003eMethods and Literature Review:\u003c/h2\u003e \u003cp\u003eA focused literature review of reported PPF tumors and skull base ACC cases was performed to contextualize surgical approaches, margin management, and indications for adjuvant radiotherapy.\u003c/p\u003e\u003ch2\u003eResults and Novel Contribution:\u003c/h2\u003e \u003cp\u003eThis report uniquely correlates radiologic progression, histologic confirmation of PNI, and anatomy-driven modification of the surgical approach. Based on literature synthesis and clinical findings, we propose a practical decision-making algorithm for PPF ACC management.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePerineural invasion should be considered the central determinant of surgical strategy in PPF ACC. Combined surgical corridors may be required to achieve oncologic adequacy. Multidisciplinary management including adjuvant radiotherapy is recommended in the presence of PNI or close margins. The proposed decision algorithm may assist in standardizing management of this rare skull base malignancy.\u003c/p\u003e","manuscriptTitle":"Perineural invasion guided surgical management of adenoid cystic carcinoma of the pterygopalatine fossa with a proposed decision making algorithm","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-26 15:43:25","doi":"10.21203/rs.3.rs-9031149/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-28T10:30:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335589088052256486085286906718298390702","date":"2026-04-19T16:58:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-18T13:51:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"328416235671556942543019752315183583513","date":"2026-04-17T16:07:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-16T18:19:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-16T18:17:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-25T11:54:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-24T11:30:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2026-03-24T11:26:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b9345df1-f726-4efa-b77e-ebe5ae4e5508","owner":[],"postedDate":"April 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-26T15:43:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-26 15:43:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9031149","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9031149","identity":"rs-9031149","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}