Primary Intraosseous Granular Cell Tumor of the Sphenoid and Central Skull Base in a Pediatric Patient.

BACKGROUND: Granular cell tumors occur in all ages and many anatomic sites. In the craniofacial region, they typically arise in soft tissue, not bone. We present a primary intra-osseous granular cell tumor of the sphenoid and central skull base arising in a 12- year- old girl. CASE REPORT: A 12-year-old female with sickle cell disease and Jeavons syndrome presented with seizures. Imaging and partial resection revealed an expansile benign granular cell tumor (GCT) involving the sphenoid body, pterygoid process, and central skull base. The disease has remained stable after 36-month follow up. DISCUSSION: GCT primarily involving the osseous sphenoid/skull base has not been previously reported in a child. Although mostly benign, some are aggressive, with malignant transformation in 1-2%. Surgery is the mainstay of treatment, but in the skull base this may be limited by adjacent critical structures. Decision-making is guided by anatomic extent, histology, and clinical behavior.

Longitudinal treatment outcomes of recurrent clival chordomas: a single-center retrospective study.

OBJECTIVE: The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. METHODS: A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors' institution between 1990 and 2022. RESULTS: A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18-79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36-62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1-8), and the median (IQR) time to the first recurrence was 29 (9-51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0-245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54-82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038-0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01-1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11-51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. CONCLUSIONS: Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

Skull Base Tumors.

OBJECTIVE: This article reviews the presenting features, molecular characteristics, diagnosis, and management of selected skull base tumors, including meningiomas, vestibular schwannomas, pituitary neuroendocrine tumors, craniopharyngiomas, chordomas, ecchordosis physaliphora, chondrosarcomas, esthesioneuroblastomas, and paragangliomas. LATEST DEVELOPMENTS: Skull base tumors pose a management challenge given their complex location and, as a result, the tumors and treatment can result in significant morbidity. In most cases, surgery, radiation therapy, or both yield high rates of disease control, but the use of these therapies may be limited by the surgical accessibility of these tumors and their proximity to critical structures. The World Health Organization classification of pituitary neuroendocrine tumors was updated in 2022. Scientific advances have led to an enhanced understanding of the genetic drivers of many types of skull base tumors and have revealed several potentially targetable genetic alterations. This information is being leveraged in the design of ongoing clinical trials, with the hope of rendering these challenging tumors treatable through less invasive and morbid measures. ESSENTIAL POINTS: Tumors involving the skull base are heterogeneous and may arise from bony structures, cranial nerves, the meninges, the sinonasal tract, the pituitary gland, or embryonic tissues. Treatment often requires a multidisciplinary approach, with participation from radiation oncologists, medical oncologists, neuro-oncologists, and surgical specialists, including neurosurgeons, otolaryngologists, and head and neck surgeons. Treatment has largely centered around surgical resection, when feasible, and the use of first-line or salvage radiation therapy, with chemotherapy, targeted therapy, or both considered in selected settings. Our growing understanding of the molecular drivers of these diseases may facilitate future expansion of pharmacologic options to treat skull base tumors.

MRI Diagnosis of Clival Cancer and Sixth Nerve Palsy.

BACKGROUND: Imaging diagnosis of clival cancer may be difficult, in part because of normal variation in marrow signal with aging. Identifying whether clival cancer has damaged the sixth cranial nerve is a further challenge because minimal clival abnormalities could impinge on the nerve, which travels very close to the clivus. METHODS: Two neuroradiologists, who were unaware of previous imaging and clinical diagnoses, reviewed MRI studies of 25 patients with cancer but no clival involvement and no sixth nerve palsy, 24 patients with clival cancer but without sixth nerve palsy, and 31 patients with clival cancer and sixth nerve palsy. The radiologists were tasked with determining whether there was clival cancer, whether there was a sixth nerve palsy and its laterality, and with indicating the pulse sequences used to make those determinations. RESULTS: Both neuroradiologists correctly identified all 25 cases with a normal clivus. In about half of those cases, they depended on finding a homogeneously bright marrow signal; in the remaining cases, they excluded cancer by determining that the clivus was not expanded and that there were no focal signal abnormalities. Both neuroradiologists correctly identified clival cancer in 54 (98%) of the 55 cases with and without sixth nerve palsy. In doing so, they relied mostly on clival expansion but also on focal signal abnormalities. Both neuroradiologists were at least 80% correct in identifying a sixth nerve palsy, but they often incorrectly identified a palsy in patients who did not have one. When there was a one-sided signal abnormality or the clivus was expanded in one direction, both neuroradiologists were accurate in identifying the side of the sixth nerve palsy. CONCLUSION: Current MRI pulse sequences allow accurate differentiation of a normal from a cancerous clivus. When the marrow signal is not homogeneously bright in adults, cancer can be diagnosed on the basis of clival expansion or focal signal abnormalities. MRI is less accurate in predicting the presence of a sixth nerve palsy. However, the side of a unilateral palsy can be predicted when the clivus is clearly expanded in one direction or there is a focal signal abnormality on one side.

Stimulated Raman Histology for Rapid Intra-Operative Diagnosis of Sinonasal and Skull Base Tumors.

OBJECTIVE: Intra-operative stimulated Raman histology (SRH) is a novel technology that uses laser spectroscopy and color-matching algorithms to create images similar to the formalin-fixed paraffin-embedded (FFPE) section. We aim to assess the accuracy of SRH in a novel range of sinonasal and skull base tumors. METHODS: Select patients undergoing sinonasal and skull base surgery using the Invenio Imaging™ Nio™ Laser Imaging SRH system between June 2020 and September 2021 were assessed. The SRH images were reviewed for pathologic features similar to frozen section (FS) and FFPE. Time taken for results and diagnostic concordance was assessed. RESULTS: Sixty-seven SRH images from 7 tumor types in 12 patients were assessed. Pathologies included squamous cell carcinoma, rhabdomyosarcoma, inverted papilloma, adenoid cystic carcinoma, SMARCB1-deficient sinonasal carcinoma, mucosal melanoma, metastatic colonic adenocarcinoma, and meningioma. Tumor was identified in 100% of lesional specimens, with characteristic diagnostic features readily appreciable on SRH. Median time for diagnosis was significantly faster for SRH (4.3 min) versus FS (44.5 min; p = <.0001). Where SRH sample site matched precisely to FS (n = 32/67, 47.8%), the same diagnosis was confirmed in 93.8%. Sensitivity, specificity, precision, and overall accuracy of SRH were 93.3%, 94.1%, 93.8%, and 93.3%, respectively. Near-perfect concordance was seen between SRH and FS (Cohen's kappa [κ] = 0.89). CONCLUSION: Stimulated Raman histology can rapidly produce images similar to FFPE H&E in sinonasal and skull base tumors. This technology has the potential to act as an adjunct or alternative to standard FS. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2142-2147, 2022.

[Skull base metastases with cranial nerve deficits : Clinical profile of a severe disease]. / Schädelbasismetastasen mit Hirnnervenaffektionen : Klinischer Steckbrief einer schwerwiegenden Erkrankung.

BACKGROUND AND PURPOSE: Skull base metastases are a severe complication of various malignant tumors. If cranial nerves are involved even small lesions can cause significant symptoms. Specific clinical characteristics like neurological symptoms, associated primary tumors, prognosis and optimal treatment are poorly defined and are systematically described in this article. METHODS: In a monocentric retrospective study patients with skull base metastases and cranial nerve deficits who received treatment between 2006 and 2018 were analyzed concerning clinical characteristics at initial diagnosis, treatment and course of the disease. RESULTS: In this study 45 patients with skull base metastases and cranial nerve deficits were included. The most frequent primary tumors were prostate cancer (27%), breast cancer (22%) and multiple myeloma (16%). The most involved cranial nerves were trigeminal nerve (42%), oculomomotor nerve (33%) and facial nerve (27%). Of the patients 84% had additional bone metastases outside the skull base. Dural infiltration or meningeal carcinomatosis were each observed in 13% of the patients. After radiotherapy cranial nerve deficits remained stable in 61% of all cases and in 22% symptoms improved. Median overall survival from treatment was 8 months (range 0.4-51 months). Patients with dose-escalated radiotherapy appeared to live longer (16.4 months vs. 4.7 months). This effect persisted in a multivariate analysis including the Karnofsky index, number of metastases, primary tumor and radiation dose (HR 0.37, p = 0.02). CONCLUSION: Skull base metastases with cranial nerve deficits are complex diseases with poor prognosis. Precise diagnosis and treatment are required. Further research is needed to improve treatment.

A challenging case of sporadic melanocytoma of the jugular foramen.

BACKGROUND: The jugular foramen (JF) can be the site of several tumours. Paragangliomas, schwannomas and meningiomas are the most commonly reported. We describe a case of melanocytoma originating from the JF and presenting with an accessory nerve palsy. ILLUSTRATIVE CASE: A 48-year-old woman presented with a 6-month history of cervical and left shoulder pain with wasting and weakness of the left trapezius. A Magnetic Resonance Imaging (MRI) showed a T1-hyperintense, T2-isointense, heterogeneously enhancing lesion involving the left JF and extending into the cerebello-medullary and cerebello-pontine cisterns. A retrosigmoid craniotomy was performed and a near-total removal achieved. The accessory nerve was involved by tumour and could not be preserved. Given the diagnostic uncertainty between melanotic schwannoma, metastatic melanoma and meningeal melanocytoma, next generation sequencing and genome-wide DNA methylation arrays were performed, documenting a mutation in GNA11 (c.6226A>T, p. Gln209Leu) and a methylation profile consistent with melanocytoma. The patient underwent adjuvant fractionated radiotherapy of the tumour remnant. A follow-up MRI 4 years after surgery did not show any tumour recurrence. CONCLUSIONS: The differential diagnosis of skull base pigmented tumours can be challenging, particularly when they occur in unusual locations such as the JF. They can be misdiagnosed given their similar clinical, neuroradiological and pathological features if anatomy of the site of origin is not carefully considered and molecular tests are not performed, leading to erroneous treatment and follow-up planning.

Multi-Disciplinary Skull Base Conference and its Effects on Patient Management.

OBJECTIVE: Examine the effects of a multi-disciplinary skull base conference (MDSBC) on the management of patients seen for skull base pathology in a neurotology clinic. METHODS: Retrospective case review of patients who were seen in a neurotology clinic at a tertiary academic medical center for pathology of the lateral skull base and were discussed at an MDSBC between July 2019 and February 2020. Patient characteristics, nature of the skull base pathology, and pre- and post-MDSBC plan of care was categorized. RESULTS: A total of 82 patients with pathology of the lateral skull base were discussed at a MDSBC during an 8-month study period. About 54 (65.9%) had a mass in the internal auditory canal and/or cerebellopontine angle while 28 (34.1%) had other pathology of the lateral skull base. Forty-nine (59.8%) were new patients and 33 (40.2%) were established. The management plan changed in 11 (13.4%, 7.4-22.6 95% CI) patients as a result of the skull base conference discussion. The planned management changed from some form of treatment to observation in 4 patients, and changed from observation to some form of treatment in 4 patients. For 3 patients who underwent surgery, the planned approach was altered. CONCLUSIONS: For a significant proportion of patients with pathology of the lateral skull base, the management plan changed as a result of discussion at an MDSBC. Although participants of a MDSBC would agree of its importance, it is unclear how an MDSBC affects patient outcomes.

Petroclival Meningioma Leading to Trigeminal Neuralgia: A Kawase Approach Application.

BACKGROUND: Trigeminal neuralgia is defined by paroxysmal pain on the trigeminal nerve territory. The petroclival meningioma presents with trigeminal neuralgia in less than 5% of the cases. We report a case of a petroclival meningioma that encased the fifth nerve and was resected through a Kawase approach. CLINICAL PRESENTATION: A 67-year-old female patient presented paroxysmal shock pain in malar and ocular region with progressive worsening, evolving with daily crises despite the use of carbamazepine. On neurologic examination the patient was oriented, with no strength or coordination impairments. Cranial nerves exam showed left V1, V2, and V3 thermal and pain hypoesthesia, without allodynia. Normal strength in masticatory muscles was observed. Magnetic resonance imaging revealed a petroclival lesion with hypersign on T2 and contrast enhancement, suggestive of a meningioma. The tumor encased the trigeminal nerve at the entrance of the Meckel's cave. A temporal craniotomy with middle fossa peeling and anterior petrosectomy (Kawase approach) was performed and a Simpson II resection was achieved. The patient evolved with transient sixth nerve palsy, recovering completely after 3 months. During a follow-up of 5 years there was no evidence of tumor recurrence and the patient is free from pain without medication. CONCLUSIONS: The Kawase approach is an interesting access for petroclival tumor resection.

Outcomes and Patterns of Care in Adult Skull Base Chondrosarcoma Patients in the United States.

BACKGROUND: Chondrosarcomas of the skull base are rare intracranial tumors of chondroid origin. The rarity of these lesions has made it difficult to form a consensus on optimal treatment regimens. The aim of this study was to provide a comprehensive analysis of prognostic factors, treatment modalities, and survival outcomes in patients with chondrosarcoma of the skull base. METHODS: Patients with diagnosis codes for chondrosarcoma of the skull base were queried from the National Cancer Database for the years 2004-2016. Outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. RESULTS: A total of 718 patients with chondrosarcoma of the skull base were identified. Mean overall survival (OS) in these patients was 10.7 years. Older age and presence of metastases were associated with worsened OS. Of patients, 83.3% received surgical intervention, and both partial resection and radical resection were associated with significantly improved OS (P < 0.001). Neither radiotherapy nor chemotherapy improved OS; however, patients who received proton-based radiation and patients who received high-dose radiation (≥6000 cGy) had significantly improved OS compared with patients who received traditional radiation. CONCLUSIONS: In the largest study to our knowledge of skull base chondrosarcoma to date, both partial resection and radical resection significantly improved OS, thus supporting the goal of maximal safe resection to preserve vital neurovascular structures without sacrificing outcome. In patients who received radiotherapy, proton-based modalities and high-dose radiation were associated with increased OS.

The importance of flaps in reconstruction of locoregionally advanced lateral skull-base cancer defects: a tertiary otorhinolaryngology referral centre experience.

BACKGROUND: The aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer. PATIENTS AND METHODS: The retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made. RESULTS: Twelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive. CONCLUSIONS: Favourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.

Intracranial Solitary Fibrous Tumor of the Skull Base: 2 Cases and Systematic Review of the Literature.

BACKGROUND: Intracranial solitary fibrous tumors (ISFTs) are rare neoplasms of mesenchymal origin that originate from the meninges. ISFTs of the skull base can be challenging to treat, as resection can be complicated by skull base anatomy. We present 2 cases of ISFT, the first manifesting with compressive cranial neuropathy from Meckel cave involvement and the second a posterior fossa lesion causing symptomatic hydrocephalus. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed database was queried with title/abstract keywords "intracranial," "solitary fibrous tumor," "hemangiopericytoma," "SFT," and "HPC." Search results were reviewed to exclude cases not involving the skull base. References from all selected articles were reviewed for potential additional cases. Patient demographic and clinical data from 58 identified skull base cases were collected for qualitative synthesis. RESULTS: Visual disturbances were the most common presenting symptom (30 cases, 52%) followed by headache (22 cases, 38%). The most common site of involvement was the sellar/parasellar region (18 cases, 31%) followed by middle fossa/temporal bone (14 cases, 24%). Resection was performed in 55 cases; gross total resection was reported in 26 cases (45%) and subtotal resection was reported in 21 cases (36%). Tumor recurrence was documented in 15 cases (26%) with median and mean follow-up periods of 16 and 29.9 months, respectively. CONCLUSIONS: We discuss presentation, imaging, histopathology, and management considerations for ISFTs while highlighting the potentially complex nature of skull base lesions and need for multidisciplinary approach to treatment.

Anatomical variations of clivus: a descriptive anatomical study.

PURPOSE: The clivus is a part of the sphenoid bone. It may show some anatomical variations such as fossa navicularis magna (FNM), canalis basilaris medianus (CBM) and craniopharyngeal canal (CPC). These variations have been associated with conditions like meningitis and tumors of skull base. Inadequate information about these structures may pose a risk of inaccurate diagnosis resulting in unwarranted interventional procedures. Hence, the knowledge about the prevalence of these variations is important. Thus, the objective of this study was to determine the prevalence of fossa navicularis magna, craniopharyngeal canal and canalis basilaris medianus and its types utilizing cone-beam computed tomography (CBCT) images. METHODS: Retrospectively, a total of 350 CBCT scans were evaluated for the presence of FNM, CBM, its types and CPC. The analysis was done by two observers independently. Cohen's kappa statistics was used to determine the interobserver agreement. RESULTS: FNM was noted in 19.4% cases, CBM in 9.7% cases, whereas CPC was not identified in any case. Type 5 was the most common type of CBM. There was no significant difference (p > 0.05) between genders and age groups for the prevalence and a highly significant (p < 0.01) substantial agreement between observers for the prevalence of FNM and highly significant (p < 0.01) moderate agreement for the prevalence of CBM and its types was obtained. CONCLUSION: FNM, CBM, CPC, albeit rare anatomical variations of clivus, knowledge of these structures is important for radiologists, anatomists and surgeons to avoid misdiagnosis and provide awareness to the individual of a higher possibility of meningitis or tumors of the skull base.

Radiation-induced intracranial osteosarcoma of the anterior skull base after treatment of esthesioneuroblastoma.

Esthesioneuroblastoma (ENB) is an uncommon sinonasal cancer of the olfactory neuroepithelium that is typically treated with surgical resection followed by radiation therapy. Radiation-induced intracranial osteosarcoma of the skull base is a rare but devastating long-term complication of radiation therapy in this region. Here, we present a case of an 82-year-old patient who developed radiation-induced osteosarcoma of the anterior skull base and paranasal sinuses 10 years after radiation therapy following resection of an ENB. Older patients may be at risk of developing this complication earlier and with a worse prognosis relative to younger patients. Treating physicians/surgeons should be aware of this devastating complication. Patients who are treated with high-dose radiation therapy in this region should be followed for many years.

Microsurgical versus endoscopic trans-sphenoidal approaches for clivus chordoma: a pooled and meta-analysis.

Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5 years and 35% at 10 years. We conducted a pooled and meta-analysis comparing recurrence rate, post-operative-complications, and survival in patients undergoing either microsurgical (MA) or endoscopic approaches (EA). Search of literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical series of clivus chordomas published between January 1990 and March 2018 on Pubmed, Scopus, and Cochrane. Two different statistical analyses have been performed: a pooled analysis and a single-arm meta-analysis of overall recurrence rate and subgroup meta-analysis of complications in the subgroups open surgery and endoscopic surgery. After full-text screening, a total of 58 articles were included in the pooled analysis and 27 studies were included for the study-level meta-analysis. Pooled analysis-the extent of resection was the only association that remained significant (subtotal: HR = 2.18, p = 0.004; partial: HR = 4.40, p < 0.001). Recurrence was more prevalent among the surgical patients (45.5%) compared to endoscopic ones (23.7%). Meta-analysis-results of the cumulative meta-analysis showed an overall rate of recurrence of 25.6%. MA recurrence rate was 31.8% (99% CI 14-52.8), EA recurrence rate was 19.4% (5.4-39.2). CSF leak rate for the endoscopic group was 10.3% (99%CI 5-17.3) and 9.5% (99%CI 1.2-24.6) for the open surgery group. The partial removal versus total removal has an influence on recurrence rate (p < 0.001). MA recurrence rate was 31.8%; EA recurrence rate was 19.4%. The extent of resection is confirmed as a statistically significant factor affecting the risk for recurrence both with the pooled analysis and with the meta-analysis. Meta-analysis demonstrated that older patients tend to recur more than young patients, especially in surgical group.