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Objectives The aim of this study was to determine the diagnostic accuracy of contrast-enhanced magnetic resonance imaging (CE-MRI) for the detection of perineural spread (PNS) in head and neck cancer patients. Methods A systematic review of PubMed, Embase, Scopus, Web of Science and Cochrane Library databases was performed up to May 20, 2022. We included diagnostic accuracy studies that used CE-MRI for the diagnosis of PNS in patients with head and neck cancer, using histopathology from surgical specimens as the reference standard. Potential bias and applicability of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADUS-2) tool. Pooled joint effect sizes of sensitivity and specificity were calculated by applying bivariate random-effects meta-analysis model. Results Nine studies with 259 patients were included. The pooled sensitivity and specificity of CE-MRI for detecting PNS were 89% (95% confidence interval [CI]: 73–96) and 83% (95% CI: 73–90), respectively. Stratifying by MRI strength, 1.5 T had a higher sensitivity of 97% (95% CI: 47–100) compared with 3 T, which had a sensitivity of 83% (95% CI: 72–90). Both 1.5- and 3-T MRI had a similar specificity in detecting PNS of 85% (95% CI: 63–95) and 84% (95% CI: 75–91), respectively. Conclusions CE-MRI provides good diagnostic test accuracy for the detection of PNS in head and neck cancer. Current evidence suggests 1.5-T MRI provides greater sensitivity compared with 3-T MRI. [ABSTRACT FROM AUTHOR]

We report a case of a 73-year-old woman presenting with intracranial and extracranial meningioma with perineural spread crossing the foramen rotundum and pterygopalatine fossa, primarily along the maxillary nerve. She visited our hospital with the chief complaint of the left cheek swelling. Subsequent magnetic resonance imaging revealed a well-demarcated mass containing intracranial (cavernous sinus, Meckel's cave, and middle cranial fossa) and extracranial components (pterygopalatine fossa, orbit, nasal cavity, ethmoid and sphenoid sinuses, infratemporal fossa, and buccal space) through the foramen rotundum. A biopsy specimen was obtained from the cheek mass, and the histopathological diagnosis was meningothelial meningioma. [ABSTRACT FROM AUTHOR]

Background: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines. Objective: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1. Materials and methods: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow‐up closure date was September 1, 2021. Curative‐intent surgery, curative‐intent radiotherapy, or palliative care was undertaken. Endpoints included five‐year overall, disease‐specific, and disease‐free survival from the date of treatment. Results: Five‐year Kaplan–Meier overall survival was 61.9% (95% CI 46.2%–74.3%), with disease‐specific survival of 74.6% (95% CI 58.8%–85.3%), and disease‐free survival 62.1% (95% CI 46.5%–74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease‐specific survival of 94.1% at 5 years with 82.5% disease‐free survival. Discussion: Five‐year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative‐intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival. Conclusion: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1. [ABSTRACT FROM AUTHOR]

Abstract Background Adenoid cystic carcinoma is an uncommon malignancy primarily arising from salivary glands. An extremely rare site for adenoid cystic carcinoma is the skull base. We report a case of adenoid cystic carcinoma of skull base who presented with common complaints of pain and right ear discharge. The discussion is made with emphasis on imaging evaluation simulating infective etiology with adjacent skull base osteomyelitis. Careful observation of the imaging findings and further evaluation of the patient revealed the neoplastic nature of the lesion with the final diagnosis being adenoid cystic carcinoma. Case presentation A 40-year-old female presented to our department with complaints of pain and right ear discharge since 6 months with progressive, extensive facial swelling and facial nerve palsy. The patient had undergone modified radical mastoidectomy thrice, but the details were not available. On imaging, there was a heterogenous extensive lesion extending from scalp till upper cervical region with extensive destruction of skull base and intra-cranial extension. The possibilities of temporal bone squamous cell carcinoma and extensive skull base osteomyelitis were considered. Further the biopsy of the lesion revealed adenoid cystic carcinoma. Conclusions Extensive lesions of the skull base can be of infective, neoplastic and inflammatory etiology. Distinguishing between these conditions is crucial, as they have similar imaging characteristics but require different management approaches. The presence of a lesion that displaces or destroys fascial planes, accompanied by solid mass-like enhancement, indicates a higher probability of a neoplastic origin rather than an infectious etiology. With squamous cell carcinoma being the most common neoplasm, adenoid cystic carcinoma of the skull base also needs to be understood due to its propensity for perineural spread and a high likelihood of recurrence.

Background: Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes. Methods: Patients were recruited from an institutional database. Semi‐structured interviews were conducted according to the Model of Pathways to Treatment. Thematic analysis was based on the four main intervals in the framework using a data‐driven analytical method. Results: Seventeen participants were interviewed. Facilitators included patients' past experiences, symptom progression, trust in healthcare professionals (HCPs), and capacity to leverage relationships. Barriers included difficult diagnoses, limited access to cancer services, lack of care coordination, and lack of awareness of PNS among primary health care providers. Conclusion: These findings emphasise the complexity early diagnosis and treatment of PNS. Interventions like clinical practice guidelines, education for HCPs, and telehealth could facilitate timely detection and management. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma is an uncommon malignancy primarily arising from salivary glands. An extremely rare site for adenoid cystic carcinoma is the skull base. We report a case of adenoid cystic carcinoma of skull base who presented with common complaints of pain and right ear discharge. The discussion is made with emphasis on imaging evaluation simulating infective etiology with adjacent skull base osteomyelitis. Careful observation of the imaging findings and further evaluation of the patient revealed the neoplastic nature of the lesion with the final diagnosis being adenoid cystic carcinoma. Case presentation: A 40-year-old female presented to our department with complaints of pain and right ear discharge since 6 months with progressive, extensive facial swelling and facial nerve palsy. The patient had undergone modified radical mastoidectomy thrice, but the details were not available. On imaging, there was a heterogenous extensive lesion extending from scalp till upper cervical region with extensive destruction of skull base and intra-cranial extension. The possibilities of temporal bone squamous cell carcinoma and extensive skull base osteomyelitis were considered. Further the biopsy of the lesion revealed adenoid cystic carcinoma. Conclusions: Extensive lesions of the skull base can be of infective, neoplastic and inflammatory etiology. Distinguishing between these conditions is crucial, as they have similar imaging characteristics but require different management approaches. The presence of a lesion that displaces or destroys fascial planes, accompanied by solid mass-like enhancement, indicates a higher probability of a neoplastic origin rather than an infectious etiology. With squamous cell carcinoma being the most common neoplasm, adenoid cystic carcinoma of the skull base also needs to be understood due to its propensity for perineural spread and a high likelihood of recurrence. [ABSTRACT FROM AUTHOR]

Extranodal diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease process and an aggressive form of non-Hodgkin's lymphoma. We present a case of multiorgan involvement of DLBCL in a patient with documented risk factors, including [ 18 F] fluorodeoxyglucose positron emission tomography/magnetic resonance imaging findings highlighting striking perineural spread involving intracranial and extracranial segments of the bilateral trigeminal nerves. [ABSTRACT FROM AUTHOR]

Abstract Background Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system. Methods This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints ( 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). Results Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2–59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen’s Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT. Conclusions PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.

Abstract Background Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes. Methods Patients were recruited from an institutional database. Semi‐structured interviews were conducted according to the Model of Pathways to Treatment. Thematic analysis was based on the four main intervals in the framework using a data‐driven analytical method. Results Seventeen participants were interviewed. Facilitators included patients' past experiences, symptom progression, trust in healthcare professionals (HCPs), and capacity to leverage relationships. Barriers included difficult diagnoses, limited access to cancer services, lack of care coordination, and lack of awareness of PNS among primary health care providers. Conclusion These findings emphasise the complexity early diagnosis and treatment of PNS. Interventions like clinical practice guidelines, education for HCPs, and telehealth could facilitate timely detection and management.

Introduction: Perineural spread (PNS) is a rare but potentially fatal consequence of cutaneous squamous cell carcinoma (cSCC) of the head and neck. We aimed to evaluate the accuracy of 3T MR neurography in detecting and defining the extent of facial nerve (VII) PNS from cSCC, and highlight characteristic radiological features in peripheral branches to improve early diagnosis. Methods: Single‐institution retrospective review of 38 patients with clinical, radiological, and/or histopathological findings consistent with VII PNS from cSCC who underwent pre‐operative 3T MR neurography. Results: Compared to histopathology (gold standard), 3T MR neurography had a sensitivity of 89% and positive predictive value of 97%. In true‐positive cases (n = 33), zonal extent was correctly identified in 100%. Seventy‐nine% had simultaneous trigeminal nerve (V) PNS, mostly involving the auriculotemporal branch of the mandibular nerve (64%). When the causative lesion was absent (n = 23), the extra‐temporal VII demonstrated asymmetrical enhancement alone (n = 6), bulky expansion (n = 8), or extra‐neural spread (n = 9). Peripheral VII branch involvement, particularly the buccal and zygomatic, was readily identified using known anatomical landmarks. Conclusion: 3T MR neurography is highly accurate in evaluating VII PNS from cSCC, and thus should be specifically requested by physicians if suspicious for disease. Coexistent V PNS was common, highlighting the need to examine V branches to allow complete treatment planning. The unique radiological patterns identified showcases disease progression. As early detection improves patient outcomes, the radiologist must look for peripheral VII involvement in specific anatomical areas, which is within the capabilities of 3T MR neurography. [ABSTRACT FROM AUTHOR]

The purpose of this study was to review the diagnostic accuracy of MRI in detecting perineural spreading (PNS) of head and neck tumors using histopathological or surgical evidence from the afflicted nerve as the reference standard. Previous studies in the English language published in the last 30 years were searched from PubMed and Embase databases. We included studies that used magnetic resonance imaging (MRI) (with and without contrast enhancement) to detect PNS, as well as the histological or surgical confirmation of PNS, and that reported the exact numbers of patients required for assessing diagnostic accuracy. The outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heterogeneity was assessed with the Higgins inconsistency test (I2). P-values smaller than 0.05 were considered statistically significant. A total of 11 retrospective studies were found, reporting 319 nerve samples from 245 patients. Meta-analytic estimates and their 95% confidence intervals were as follows: sensitivity 0.85 (0.70–0.95), specificity 0.85 (0.80–0.89), PPV 0.86 (0.70–0.94), and NPV 0.85 (0.71–0.93). We found statistically significant heterogeneity for sensitivity (I2 = 72%, p = 0.003) and PPV (I2 = 70%, p = 0.038), but not for NPV (I2 = 65%, p = 0.119) or specificity (I2 = 12%, p = 0.842). The most frequent MRI features of PNS were nerve enlargement and enhancement. Squamous cell carcinoma and adenoid cystic carcinoma were the most common tumor types, and the facial and trigeminal nerves were the most commonly affected nerves in PNS. Only a few studies provided examples of false MRI diagnoses. MRI demonstrated high diagnostic accuracy in depicting PNS of cranial nerves, yet this statement was based on scarce and heterogeneous evidence. [ABSTRACT FROM AUTHOR]

Perineural spread (PNS) of breast cancer to the brachial plexus is rare, with reports limited to cases only in female patients. This study aimed to determine the incidence of PNS in male compared with female patients. Adult breast cancer patients referred to a single institution between 1994 and 2022 were retrospectively reviewed for imaging or biopsy-confirmed cases of PNS to the brachial plexus. Two independent reviewers of articles published in any language between 1990 and 2022 in PubMed, Scopus, Embase, and Google Scholar performed a systematic literature review. Of the 10,466 patients with breast cancer (10,355 female, 111 male) referred to a single institution, there were 42 female patients with PNS to the brachial plexus for an estimated incidence of 0.4%. In the same time period, there were 111 male patients treated for breast cancer, including 88 patients with Klinefelter's syndrome (KS); however, there were no cases of male patients with PNS. A systematic review of the world's literature did not identify male patients with PNS to the brachial plexus. There is a lack of any reported cases of PNS of breast cancer to the brachial plexus in men or patients with KS, who have a much higher incidence of breast cancer. This may reflect either the compounding rarity of these two events or point toward a distinct hormonally-driven link between breast cancer and PNS, highlighted by the disparity in PNS incidence in men and women. [ABSTRACT FROM AUTHOR]

Background: Perineural spread (PNS) of head and neck cutaneous squamous cell carcinoma (HNcSCC) is a unique diagnostic challenge, presenting with insidious trigeminal (CN V) or facial nerve (CN VII) neuropathies without clinically discernible primary masses. These patients are often sub‐optimally investigated and misdiagnosed as Bell's palsy or trigeminal neuralgia. This case series highlights the red flags in history and pitfalls that lead to delays to diagnosis and treatment. Methods: A retrospective case series of 19 consecutive patients with complete clinical histories with HNcSCC PNS without an obvious cutaneous primary lesion at time of presentation to a quaternary head and neck centre in Australia were identified and included for analysis. Results: Fifteen had CN VII PNS, 17 had CN V PNS, and 13 had both. The overall median symptom‐to‐diagnosis time was 12‐months (IQR‐15 months). Eight patients had CN VII PNS and described progressive segmental facial nerve palsy with a median symptom‐to‐diagnosis time of 9‐months (IQR‐11.75 months). Eleven patients had primary CN V PNS and described well localized parathesia, formication or neuralgia with a median symptom‐to‐diagnosis time of 19‐months (IQR 27.5 months). Conclusion: PNS is often mistaken for benign cranial nerve dysfunction with delays in diagnosis worsening prognosis. Red flags such as progressive CN VII palsy or persistent CN V paraesthesia, numbness, formication or pain, particularly in the presence of immuno‐compromise and/or a history of facial actinopathy should raise suspicion for PNS. Gadolinium‐enhanced MR Neurography should be obtained expediently in patients with persistent/progressive CN V/CN VII palsies in patients with red flags, with low threshold for referral to a Head and Neck Surgeon. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows formolecular studies investigating drivers of PNI/PNS in the head and neck environment. Methods: A431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2. Results: The rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model's utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI. Discussion: This model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model. [ABSTRACT FROM AUTHOR]

Purpose: To describe tumor response and cranial nerve function outcomes after administration of anti-PD-1 to patients with cutaneous squamous cell carcinoma (CSCC) with perineural spread to cranial nerves (CN) extending into the cavernous sinus. Methods: Electronic patient records from a single institution were queried for patients with CSCC of the head and neck causing diplopia (ICD-10 H53.2) who were treated with anti-PD-1. Data extracted included demographics, duration of anti-PD-1 therapy, immune-mediated adverse reactions, tumor response per adapted RECIST v1.1, and changes in CN function and symptoms (e.g., pain). All patients were prescribed cemiplimab 350 mg IV q3 weeks. Results: Four patients met inclusion criteria. They had varying degrees of pain and sensory deficits in branches of the trigeminal nerve (CN V). One, 2, 3 and 1 patients had baseline involvement of CN III, IV, VI and VII, respectively. MRI confirmed perineural cavernous sinus involvement in all patients. Duration of anti-PD-1 therapy ranged 15–60 weeks. All patients experienced an objective anti-tumor response to anti-PD-1; partial response n = 2, complete response n = 2. At a median follow-up of 22 months, responses were ongoing in all patients. All patients demonstrated improvement in ocular motility deficits and pain with resolution of symptoms in 3 and 1 patients, respectively. Conclusion: Administration of anti-PD-1 to patients with CSCC with perineural spread into the cavernous sinus can generate durable anti-tumor regressions and restore CN function, while sparing the morbidity associated with surgical resection and/or radiotherapy. Our findings add to emerging literature supporting this treatment approach for this patient population. [ABSTRACT FROM AUTHOR]

Objective:To evaluate bilateral superior and recurrent laryngeal nerves for tumor spread in patients of advanced-stage laryngeal carcinoma undergoing surgical resection.Methods:A prospective study was conducted including biopsy-proven cases of laryngeal squamous cell carcinoma (SCC) that were planned for total laryngectomy. Patients with metachronous or synchronous SCC were excluded from the study. All patients underwent total laryngectomy, where both superior and recurrent laryngeal nerves were harvested along with the specimen, and the proximal ends of the nerves were marked for reference. Perineural invasion (PNI) was assessed in nerves within the tumor and in bilateral extra-laryngeal nerves.Results:The study included 22 patients with a mean age of 58 years. Intra-tumoral PNI was found in 7 of the 22 cases (32%). The free nerve margins of superior and recurrent laryngeal nerves, which were examined from proximal to distal orientation, showed no tumor infiltration in any of the cases.Conclusion:Perineural invasion of minor nerves constitutes a major pathway of spread. On the contrary, invasion of superior or recurrent laryngeal nerves does not constitute a route for tumor spread. Hence, there is no need to extend the surgical boundary for total laryngectomy to include these major nerves separately.

IntroductionCutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment.MethodsA431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2.ResultsThe rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model’s utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI.DiscussionThis model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.

A 39-year-old lady with worsening intermittent diplopia and headaches was diagnosed with a WHO Grade I Meningothelial Meningioma with highly unusual perineural spread on imaging, making this the first reported case of this behaviour. Complete surgical resection was deemed too great a risk and the patient remains under observation. The process of perineural spread is not restricted to more aggressive brain tumours. [ABSTRACT FROM AUTHOR]

Objective: To evaluate bilateral superior and recurrent laryngeal nerves for tumor spread in patients of advanced-stage laryngeal carcinoma undergoing surgical resection. Methods: A prospective study was conducted including biopsy-proven cases of laryngeal squamous cell carcinoma (SCC) that were planned for total laryngectomy. Patients with metachronous or synchronous SCC were excluded from the study. All patients underwent total laryngectomy, where both superior and recurrent laryngeal nerves were harvested along with the specimen, and the proximal ends of the nerves were marked for reference. Perineural invasion (PNI) was assessed in nerves within the tumor and in bilateral extra-laryngeal nerves. Results: The study included 22 patients with a mean age of 58 years. Intra-tumoral PNI was found in 7 of the 22 cases (32%). The free nerve margins of superior and recurrent laryngeal nerves, which were examined from proximal to distal orientation, showed no tumor infiltration in any of the cases. Conclusion: Perineural invasion of minor nerves constitutes a major pathway of spread. On the contrary, invasion of superior or recurrent laryngeal nerves does not constitute a route for tumor spread. Hence, there is no need to extend the surgical boundary for total laryngectomy to include these major nerves separately. [ABSTRACT FROM AUTHOR]

Incidence of basal cell carcinoma (BCC) with perineural invasion (PNI) ranges from 0.178 to 10% depending upon whether conventional pathology (formalin fixed, paraffin embedded) or Mohs micrographic surgery (MMS) (frozen sections) is used. To determine the incidence of BCC with PNI determined by conventional pathology versus MMS. A review of PubMed and EMBASE databases, from their inception to December 18th, 2020, identified articles that determined the incidence of BCC with PNI using conventional pathology or MMS. The general (average) incidence of BCC with PNI as determined by studies that used conventional histopathology and MMS was 0.85 and 2.51%, respectively. The observed incidence of BCC with PNI was not significantly higher using MMS compared to conventional pathology (p = 0.82). [ABSTRACT FROM AUTHOR]

The purpose of this study was to review the diagnostic accuracy of MRI in detecting perineural spreading (PNS) of head and neck tumors using histopathological or surgical evidence from the afflicted nerve as the reference standard. Previous studies in the English language published in the last 30 years were searched from PubMed and Embase databases. We included studies that used magnetic resonance imaging (MRI) (with and without contrast enhancement) to detect PNS, as well as the histological or surgical confirmation of PNS, and that reported the exact numbers of patients required for assessing diagnostic accuracy. The outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heterogeneity was assessed with the Higgins inconsistency test (I2). P-values smaller than 0.05 were considered statistically significant. A total of 11 retrospective studies were found, reporting 319 nerve samples from 245 patients. Meta-analytic estimates and their 95% confidence intervals were as follows: sensitivity 0.85 (0.70–0.95), specificity 0.85 (0.80–0.89), PPV 0.86 (0.70–0.94), and NPV 0.85 (0.71–0.93). We found statistically significant heterogeneity for sensitivity (I2 = 72%, p = 0.003) and PPV (I2 = 70%, p = 0.038), but not for NPV (I2 = 65%, p = 0.119) or specificity (I2 = 12%, p = 0.842). The most frequent MRI features of PNS were nerve enlargement and enhancement. Squamous cell carcinoma and adenoid cystic carcinoma were the most common tumor types, and the facial and trigeminal nerves were the most commonly affected nerves in PNS. Only a few studies provided examples of false MRI diagnoses. MRI demonstrated high diagnostic accuracy in depicting PNS of cranial nerves, yet this statement was based on scarce and heterogeneous evidence.

We present a case of a 78-year-old male with a primary parotid squamous cell carcinoma which spread via the left facial, trigeminal and greater auricular nerves. The patient presented with left facial droop and paraesthesia. Initial MRI scans demonstrated involvement of the trigeminal and facial nerves with no sign of a primary lesion. Abnormal enhancement within the left parotid substance on FDG PET-CT demonstrated the primary malignancy which was confirmed on histology by core biopsy. There was also focal avidity along the course of the left greater auricular nerve consistent with perineural infiltration, extending from the posterior aspect of the parotid to the left cervical plexus at C2/C3. To our knowledge, this is the second case of squamous cell carcinoma perineural spread to the greater auricular nerve imaged on FDG PET-CT scanning. This case highlights the importance of multimodality imaging correlation in the workup of primary head and neck malignancies and associated perineural spread, which is essential in adjuvant radiation therapy planning to reduce local recurrence, improve prognosis and overall survival.

Background and Purpose: Due to surgical advancements, the accurate detection of perineural disease spread has become increasingly important in the management and prognostication of head and neck cancers, though MR evaluation has thus far been limited by technical and logistic challenges. The purpose of this study was to specifically evaluate the relative capability of 3D CISS and 3D T2-SPACE imaging to delineate the proximal intracranial divisions of the normal trigeminal nerve, an area important in determining the resectability of intracranial perineural disease. Materials and methods: A single center HIPAA-compliant, IRB approved retrospective review of 40 patients with clinical temporal bone/internal auditory canal MR imaging was conducted. 20 patients with 3D CISS images and 20 patients with 3D T2-SPACE images met inclusion criteria. Two radiologists scored the sequences on a 3-point scale based on ability to visualize anatomic structures surrounding the trigeminal nerve in Meckel's cave, intracranial trigeminal divisions, skull base neuroforamina, and proximal extracranial mandibular division. Results: The following anatomic locations scored significantly better in the T2-SPACE sequence compared to the CISS sequence for both raters: intracranial V3 (p <.05), foramen ovale (p <.05), and extracranial V3 (p <.01). The average scores for the anterior Meckel's cave and foramen rotundum were higher for the T2-SPACE sequence, although not significantly. Percent interobserver agreement ranged from 50 to 90% and 65–100% for the different anatomic locations on the CISS and T2-SPACE sequences, respectively. Conclusion: 3D T2-SPACE was found to be superior to 3D CISS in the evaluation of the distal intracranial and extracranial portions of the normal trigeminal nerve. [ABSTRACT FROM AUTHOR]

Background: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. Methods: Retrospective analysis of 167 Australian patients with primary and peri‐temporal bone cSCC. Results: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post‐operative radiotherapy (n = 146, 87.4%), 5‐year disease‐free survival, locoregional recurrence‐free survival, disease‐specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre‐auricular tumors, salvage surgery, tumor size (≥40 mm medial‐lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. Conclusion: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre‐auricular cancers is required given poorer associated survival outcomes. [ABSTRACT FROM AUTHOR]

Aim: To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS). Method: Retrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high‐volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco‐regional failure and survival data were obtained. Results: Forty‐five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43–90). Median follow‐up was 16.1 months (range 1–107). The trigeminal nerve was most frequently involved (n = 30, 66.6%) followed by facial nerve (n = 13, 28.9%). Most patients underwent surgery followed by radiotherapy (n = 33, 73%) and eight received definitive radiotherapy. The median overall survival (OS) was 4.5 years (95% CI 3.71–5.38), median disease‐specific survival 5.1 years (95% CI 4.21–5.97) and median disease‐free survival (DFS) was 1.7 years (95% CI 1.11–2.22). The estimated 5‐year OS and DFS were 45% and 25%, respectively. Patients treated with surgery and adjuvant radiotherapy with a clear proximal nerve margin had favourable DFS (P = 0.035) and trended towards better OS (P = 0.134) compared with patients with an involved nerve margin. Patients treated surgically with involved proximal nerve margins had similar outcomes compared with patients with treated definitive radiotherapy (HR 0.80, 95% CI 0.29–2.22, P = 0.664). Conclusion: The likelihood of achieving a clear proximal nerve margin should be a strong consideration in the selection of appropriate patients for primary surgery [ABSTRACT FROM AUTHOR]

Purpose: The association between salivary gland carcinomas and adjacent osseous changes in the head and neck region is not clear. We evaluated the frequency and imaging features of such changes and investigated the specific characteristics of salivary gland carcinomas associated with them. Methods: A total of 118 patients with histologically proven salivary gland carcinomas were retrospectively reviewed. The imaging characteristics of osseous changes were sorted into three categories based on computed tomography images: sclerotic change, erosive change, and lytic change. The frequency of all these osseous changes and any one of them was compared between different pathologies using Fisher's exact test. Odds ratios were calculated to evaluate the association between these changes and perineural spread. Results: Osseous changes were found in 21 (18%) of 118 cases. Among these, seven (6%) cases were with sclerotic, nine (8%) with erosive, and nine (8%) with lytic changes (four with mixed change). Adenoid cystic carcinoma showed a significantly higher frequency of sclerotic and erosive changes, and either osseous change, than the other salivary gland carcinomas (p < 0.001 for each). Sclerotic changes were only present in the adenoid cystic carcinomas. Perineural spread was a significant factor in showing higher osseous change frequencies (odds ratio = 3.98, p = 0.006). Conclusion: Among salivary gland carcinomas in the head and neck region, adenoid cystic carcinomas had a significantly higher frequency of adjacent osseous changes, especially sclerotic changes, than other salivary gland carcinomas. [ABSTRACT FROM AUTHOR]

We report a case of a 73-year-old woman presenting with intracranial and extracranial meningioma with perineural spread crossing the foramen rotundum and pterygopalatine fossa, primarily along the maxillary nerve. She visited our hospital with the chief complaint of the left cheek swelling. Subsequent magnetic resonance imaging revealed a well-demarcated mass containing intracranial (cavernous sinus, Meckel's cave, and middle cranial fossa) and extracranial components (pterygopalatine fossa, orbit, nasal cavity, ethmoid and sphenoid sinuses, infratemporal fossa, and buccal space) through the foramen rotundum. A biopsy specimen was obtained from the cheek mass, and the histopathological diagnosis was meningothelial meningioma., Competing Interests: There are no conflicts of interest., (© 2024 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science.)

Invasive sinus aspergillosis is a rare life-threatening condition usually found in immunocompromised patients. The fungus spreads from paranasal sinuses into the central nervous system by direct extension or through blood vessels. Perineural spread is an uncommon mechanism of spread in invasive aspergillosis. A mycotic aneurysm is a dangerous complication of invasive sinus aspergillosis because of its insidious development and is often diagnosed only post-mortem after causing fatal intracranial hemorrhage. Intracranial vascular complications of invasive sinus aspergillosis require prompt recognition and treatment and should always be considered when a diagnosis of CNS aspergillosis is made. We present a case of invasive sinus aspergillosis in an apparently immunocompetent patient that manifested with a brain abscess, perineural spread of the infection, and mycotic aneurysm of the vertebral artery with subsequent rupture and fatal subarachnoid hemorrhage. This case highlights the possibility of perineural spread and hemorrhagic complications in invasive cerebral aspergillosis.

Background. Perineural spread of head and neck tumors is linked to a worse chance of survival as well as a higher risk of local recurrence and metastasis. Particle emission tomography/computed tomography (PET/CT) using 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) is part of the work-up and follow-up of many afflicted patients, and radiologists play an essential role in the assessment and management of head and neck cancer. Objectives. The purpose of the current study was to investigate the diagnostic performance of 18F-FDG PET in detecting perineural spread among patients with head and neck tumors through a meta-analysis. Materials and methods. Relevant articles were searched using appropriate keywords from PubMed, MEDLINE and PubMed Central (PMC) databases. Retrospective and prospective studies were included as per the predefined PICOS criteria. Demographic summary and event data for diagnostic accuracy of 18F-FDG PET were determined, and odds ratio (OR), sensitivity, specificity, likelihood ratios, and predictive values were calculated using RevMan software. The bias risk was analyzed with Egger's and Begg's tests using MedCalc software. Results. Fourteen clinical trials performed between 2000 and 2021, with 977 head and neck cancer patients with perineural spread, were included according to the inclusion criteria. Included studies used 18F-FDG PET imaging of tumors and reported its high sensitivity. In the current study, we obtained the pooled OR = 3.088 (95% confidence interval (95% CI): [1.486; 6.419]), pooled sensitivity of 91.7%, pooled specificity of 92.35%, positive predictive value (PPV) of 92.27%, negative predictive value (NPV) of 91.13%, positive likelihood ratio of 7.45, negative likelihood ratio of 0.28, disease prevalence of 95.8%, and accuracy of 91.5%. Data was heterogeneous, with Q value of 33.8%, degrees of freedom (df) value of 13, I2 value of 61.5% (31.23-78.5), and p-value = 0.0013. The risk of publication bias was low, with a p = 0.7490 (Egger's test) and p = 0.7843 (Begg's test). Conclusions. The present meta-analysis highly recommends 18F-FDG PET as an effective imaging method for patients with head and neck tumors with perineural spread. [ABSTRACT FROM AUTHOR]

Intradural extramedullary metastasis from breast carcinoma is a rare occurrence. Furthermore, patients with primary breast carcinoma presenting with neurological symptoms in the first place are even rarer, which was the case in our patient. A 60-year-old woman presented with left upper limb monoparesis for 2 years and rapidly progressive weakness in the left lower limb for 1 week. The patient was evaluated and investigated to find primary left breast carcinoma with metastasis to multiple sites including C5-T1 intradural extramedullary spread. The patient was treated surgically, and decompression and tissue diagnosis were achieved to form a base for starting adjuvant therapy and safeguarding further neurological deterioration due to cord compression. In advanced metastatic cancer, preservation of neurologic function is the goal of surgical treatment. Thorough evaluation of patients presenting with a neurological deficit is always mandatory. Patient education is equally important for palliative treatment as well as to help reduce the burden of metastatic diseases. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To describe outcomes of advanced head and neck cutaneous squamous cell carcinoma (cSCC) with clinical perineural invasion (cPNI) treated with immune checkpoint inhibitor (ICI) therapy, and to describe post‐treatment radiographic findings in the context of clinical response to treatment using a new grading system. Study Design: Retrospective chart review. Methods: Retrospective chart review was performed for 11 patients treated with ICI for head and neck cSCC with cPNI of large named nerves. The primary outcome was response to treatment as defined by radiographic and clinical evidence. Clinical responses were defined as improvement in symptoms of neuropathic pain, hypoesthesia, nerve weakness, or decrease in visible tumor. Imaging studies were graded based on a new classification system for perineural invasion and reviewed by two neuroradiologists since RECISTv1.1 is inadequate to adjudicate response in these patients. Results: Nine (82%) patients had radiographic perineural disease control on ICI. Eight patients had improved radiographic perineural disease and one had stable disease. Of these, complete resolution of radiographic evidence of perineural disease was seen in only one patient. Seven (64%) patients had clinical responses, with either improved or stable radiographic disease. Conclusions: ICI therapy is a viable treatment option for head and neck cSCC with cPNI. Radiographic and clinical evidence of response correlate well, with improvement in neuropathic pain being the most sensitive clinical marker of response. Even with favorable findings on repeat imaging and stable clinical course, complete resolution of perineural thickening and enhancement is rare. A grading system for classifying changes in perineural disease over time is proposed. Level of Evidence: 4 Laryngoscope, 132:1213–1218, 2022 [ABSTRACT FROM AUTHOR]

Background: The post COVID craniofacial mucormycosis was found to emerge since the second wave of the COVID pandemics. It was called black fungus as it was associated with high mortality rate. Objective: To describe combined computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of post COVID craniofacial mucormycosis for accurate diagnosis and determination of the extent of involvement. Patients and Methods: The main source of data for this study was the archived CT and MRI imaging of the patients referred to the department of Radiology, Ain Shams University Hospitals. Results: Our study population presented with craniofacial symptoms within 1-8 weeks from COVID-19 infection. The study revealed strong association between history of ICU admission, high doses of corticosteroids, oxygen administration and sever imaging MRI features of fungal sinusitis. Fungal invasion is not necessary to be through bony destruction. Conclusion: The severest form of fungal sinusitis was found to be more commonly associated with ICU admission, usage of high doses of corticosteroids as well as patients who needed O2 therapy, the usage of contrast enhanced MRI should be combined with CT for assessment of disease extension as well as bony invasion. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck. Methods: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019. Results: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post‐operative radiotherapy. In these patients, 5‐year disease‐free survival, disease‐specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes. Conclusion: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post‐operative radiotherapy remains the mainstay treatment. Outcomes are improved in early‐stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited. Methods: Retrospective review of 13 patients with PNS receiving anti‐PD‐1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi‐Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET). Results: Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8–2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3–4 treatment related adverse events. Conclusions: This case series supports developing evidence for anti‐PD‐1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population. [ABSTRACT FROM AUTHOR]

Perineural spread (PNS) from pelvic carcinoma has been regarded as a pathway to muscle and bone metastasis. However, few cases have been reported, especially in patients with bladder carcinoma. In the present report, we discuss a case of diffuse cancer involvement in the muscle 5 years after radical cystectomy for advanced bladder carcinoma. Careful observation of temporal changes on medical images confirmed PNS as the pathway to muscle metastasis (i.e., primary PNS). Our report presents early and post-treatment CT, MRI and FDG-PET/CT findings of PNS from the bladder carcinoma.

Perineural spread (PNS) through the facial nerve is a well-recognized pathway of spread in parotid cancers. Negative margins in the facial nerve are important in the total extirpation of cancer. We report a case of mucoepidermoid carcinoma of the parotid which was involving only the upper temporofacial division of the facial nerve at the periphery clinically and per-operatively. The upper trunk was divided at about 3cm away from the tumor at its junction with the lower trunk and the nerve was grossly normal. To our surprise disease was extending at this distance as a PNS in the frozen section analysis. This unexpected finding made the resection margin positive and we had to sacrifice the main trunk of the facial nerve as back as possible in the parotidectomy field for a negative margin in the nerve which was confirmed with frozen section again. The case emphasizes the importance of microscopic margin assessment of facial nerve in parotid cancers with the involvement of nerve at branches, even if imaging is negative or gross disease is not seen at the cut end or distant from the tumor-involved area. [ABSTRACT FROM AUTHOR]

Perineural spread (PNS) to cranial nerves (CNs) by cutaneous malignancies is difficult to diagnose given the indolent course and often late or absent findings on brain imaging. A 68-year-old white man with multiple cranial neuropathies secondary to PNS by squamous cell carcinoma had negative high-quality neuroimaging for 5.25 years. He first developed left facial numbness, followed 39 months later by a left CN VI palsy. Subsequent examinations over 2 years showed involvement of left seventh, right trigeminal V1–V3, and right sixth, and bilateral third nerve palsies. Repeat high-quality brain magnetic resonance imaging (MRIs) during this time showed no identifiable CNs abnormality. Full body positron emission tomography imaging and cerebrospinal fluid studies were normal. 5.25 years after initial sensory symptom onset, MRI showed new enhancement along the right mandibular branch of the trigeminal nerve with foramen ovale widening. Autopsy showed squamous cell carcinoma within both CNs sixth. A long interval to diagnosis of PNS is associated with high morbidity, emphasizing the need for earlier methods of detection when clinical suspicion is high.