Validation of the Melanoma Institute of Australia's Sentinel Lymph Node Biopsy Risk Prediction Tool for Cutaneous Melanoma.

BACKGROUND: For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) is used to stage regional lymph nodes pathologically and inform prognosis, treatment, and surveillance. To reduce unnecessary surgeries, predictive tools aim to identify those at lowest risk for node-positive disease. The Melanoma Institute of Australia (MIA)'s Prediction Tool for Sentinel Node Metastasis Risk estimates risk of a positive SLNB using patient age and primary melanoma Breslow depth, histologic subtype, ulceration, mitotic rate, and lymphovascular invasion. METHODS: A single-institution validation was performed of the MIA Calculator with 982 cutaneous melanoma patients that included all relevant clinicopathologic factors and SLNB pathology outcomes. The study evaluated discrimination via receiver operating characteristic (ROC) curves, calibration via calibration plots, and clinical utility via decision curve analysis of the MIA model in various subgroups. The data were fit to MIA model parameters via a generalized linear model to assess the odds ratio of parameters in our dataset. RESULTS: The Calculator demonstrated limited discrimination based on ROC curves (C-statistic, 0.709) and consistently underestimated risk of SLN positivity. It did not provide a net benefit over SLNB performed on all patients or reduce unnecessary procedures in the risk domain of 0% to 16%. Compared with the original development and validation cohorts, the current study cohort had thinner tumors and a larger proportion of acral melanomas. CONCLUSIONS: The Calculator generally underestimated SLN positivity risk, including assessment in patients who would be counseled to forego SLNB based on a predicted risk lower than 5%. Recognition of the tool's current limitations emphasizes the need to refine it further for use in medical decision-making.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

Augmented-Reality Surgery to Guide Head and Neck Cancer Re-resection: A Feasibility and Accuracy Study.

BACKGROUND: Given the complex three-dimensional (3D) anatomy of head and neck cancer specimens, head and neck surgeons often have difficulty relocating the site of an initial positive margin to perform re-resection. This cadaveric study aimed to determine the feasibility and accuracy of augmented reality surgery to guide head and neck cancer re-resections. METHODS: This study investigated three cadaveric specimens. The head and neck resection specimen was 3D scanned and exported to the HoloLens augmented reality environment. The surgeon manually aligned the 3D specimen hologram into the resection bed. Accuracy of manual alignment and time intervals throughout the protocol were recorded. RESULTS: The 20 head and neck cancer resections performed in this study included 13 cutaneous and 7 oral cavity resections. The mean relocation error was 4 mm (range, 1-15 mm) with a standard deviation of 3.9 mm. The mean overall protocol time, from the start of 3D scanning to alignment into the resection bed, was 25.3 ± 8.9 min (range, 13.2-43.2 min). Relocation error did not differ significantly when stratified by greatest dimension of the specimen. The mean relocation error of complex oral cavity composite specimens (maxillectomy and mandibulectomy) differed significantly from that of all the other specimen types (10.7 vs 2.8; p < 0.01). CONCLUSIONS: This cadaveric study demonstrated the feasibility and accuracy of augmented reality to guide re-resection of initial positive margins in head and neck cancer surgery.

Complications of pectoralis major myo-cutaneous flap, anterolateral thigh flap and radial forearm free flap after total laryngectomy with partial pharyngectomy: A systematic review and network meta-analysis.

BACKGROUND: No consensus exists regarding the most effective reconstruction after total laryngectomy with partial pharyngectomy (TLwPP). This study aims to compare different reconstructive techniques (pectoralis major myo-cutaneous flap, PMMCF; anterolateral thigh flap, ALTF; radial forearm free flap, RFFF) after TLwPP in terms of pharyngocutaneous fistula (PCF), stenosis and feeding tube dependence (FTD) incidence. METHODS: The Scopus, PubMed/MEDLINE, Cochrane Library, and Google Scholar databases were searched. A single-arm meta-analysis was performed for PCF incidence, stenosis incidence, and FTD incidence on the entire cohort. An arm-based network analysis was conducted to compare three different surgical interventions (PMMCF, ALTF, RFFF). RESULTS: A total of 13 studies and 232 patients were included in the network meta-analysis. The lowest PCF absolute risk was measured for the RFFF (11.7%, 95% CI: 2.8%-33.4%), compared to the ALTF (13.4%, 95% CI: 4.5%-32.1%) and the PMMC (49.0%, 95% CI: 19.2%-79.3%). The RFFF showed a stenosis absolute risk of 0.0% (95% CI: 0.0%-1.1%), while a higher stenosis incidence was measured for the ALTF (5.7%, 95% CI: 0.8%-25.2%) and the PMMCF (11.6%, 95% CI: 0.8%-55.1%). The RFFF showed the lowest absolute risk of FTD incidence (6.8%, 95% CI: 0.5%-28.1%) compared to the other reconstructive techniques (PMMCF: 12.4%, 95% CI: 2.4%-42.1%; ALTF: 17.5%, 95% CI: 6.4%-38.9%). CONCLUSIONS: The RFFF seems the best choice for reconstruction of partial pharyngeal defects after TLwPP due to the lower incidence of PCF, stenosis and FTD compared to the ALTF and the PMMCF.

Molecular profiling of a primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid.

Primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next-generation sequencing. The patient is an 85-year-old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet-ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next-generation sequencing revealed a CDH1 mutation, which is known to confer signet-ring morphology in other carcinomas. Pathogenic mutations in NTRK3, CDKN1B, and PIK3CA were also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.

Positive Lymph Node Counts in American Thyroid Association Low-Risk Papillary Thyroid Carcinoma Patients.

BACKGROUND: Current American Thyroid Association (ATA) guidelines state that patients with intermediate-risk papillary thyroid cancer (PTC) may benefit from remnant ablation. One criterion for intermediate-risk classification is >5 positive lymph nodes (LNs). We investigate whether performing step-sectioning of LNs increases the metastatic detection rate, thereby influencing ATA risk of recurrence (ROR) classification. METHODS: A retrospective review was conducted of cases in which ≥ 5 LNs were removed during thyroidectomy and ≤5 LNs were found positive for PTC. Step-sectioning was performed on the original tissue blocks. All slides were re-reviewed by a senior pathologist. RESULTS: Twenty patients met study criteria. Step-sectioning significantly increased LN yield compared to standard sectioning. In total, we found 12 new positive lymph nodes; seven (58%) were in totally new lymph nodes, while five (42%) were in lymph nodes previously read as negative. All newly discovered metastases were classified as micrometastases (≤2 mm). Of the 15 patients originally classified as low-risk, the step-sectioning protocol impacted two patients (13%), increasing ROR stratification. CONCLUSION: Intensive step-sectioning reveals additional micrometastases. More detailed analysis did not identify clinically significant nodal disease likely to impact the clinical course of patients in this study. Our study supports current standards of pathology specimen handling related to LN assessment and the impact on ATA ROR classification. Nonetheless, it is important for clinicians to understand their institution's sectioning protocol utilized to report positive and total LN counts, which could impact ATA risk stratification and denote the comprehensive nature of the LN dissection that was performed.

Osteoradionecrosis of the hyoid bone complicated by pharyngocutaneous fistula: A case report and literature review.

BACKGROUND: Osteoradionecrosis (ORN) is a well-known complication following irradiation of head and neck malignancies. ORN commonly occurs in the mandible but is rarely reported in the hyoid bone. CASE PRESENTATION: A 76-year-old female with a history of oropharyngeal squamous cell carcinoma presented with pharyngocutaneous fistula 14 years after primary chemoradiation. Imaging showed necrosis of the hyoid bone. She underwent excision of the hyoid to rule out malignancy. Pathology was negative for carcinoma, but did show extensive fragmentation and bony necrosis consistent with ORN. The patient's clinical course, surgical treatment, and management considerations are discussed here. CONCLUSIONS: Hyoid ORN should remain in the differential during diagnostic workup of previously irradiated head and neck cancer patients. The presentation of a pharyngocutaneous fistula should prompt workup to rule out malignancy before assigning a diagnosis of ORN.

Septic arthritis of the sternoclavicular joint: A unique late complication after tracheostomy.

BACKGROUND: Septic arthritis of the sternoclavicular joint is a rare infection associated with significant morbidity and mortality. Several risk factors for septic arthritis have been reported in the literature ranging from immunodeficiency to intravenous drug use. CASE PRESENTATION: A 63-year-old male previously treated for synchronous squamous cell carcinomas of the epiglottis and floor of mouth presented with tenderness and swelling of the sternoclavicular joint two months after tracheostomy decannulation. Computed tomography and bone scans confirmed the diagnosis of septic arthritis of the sternoclavicular joint. The patient's clinical course, surgical treatment, and management considerations are discussed here. CONCLUSION: Septic arthritis of the SCJ is a rare but serious infection. Once diagnosed, septic arthritis of the SCJ should be promptly treated to prevent further morbidity and mortality.

A rare primary leiomyosarcoma of the parotid gland: A case report and literature review.

BACKGROUND: Leiomyosarcoma of the head and neck region is very rare. Primary parotid leiomyosarcoma has only been reported nine times in the medical literature. METHODS: A 68-year-old female presented with a left facial mass. Physical examination revealed a firm immobile mass at the level of the left parotid tail. No facial nerve dysfunction or palpable adenopathy was noted at the time of presentation. This patient underwent a superficial parotidectomy with a facial nerve dissection and left selective neck dissection. RESULTS: Pathologic findings revealed a sarcoma of intermediate to high-grade, composed of spindle cells with herringbone pattern, eosinophilic fibrillary cytoplasm, and focal granularity. Immunohistochemistry was positive for vimentin and smooth muscle actin and negative for desmin, S100 and CD34. The findings are consistent with a leiomyosarcoma. Following complete surgical resection, adjuvant radiation therapy was administered. CONCLUSION: Primary sarcomas of the parotid gland, specifically parotid leiomyosarcomas, are extremely rare. Based on this patient's tumor size, grade and resectability, this case met the criteria for a primary leiomyosarcoma. We present only the tenth case of a primary parotid leiomyosarcoma to be reported in the English literature.

Infrared Fluorescence-guided Surgery for Tumor and Metastatic Lymph Node Detection in Head and Neck Cancer.

In patients with head and neck cancer (HNC), surgical removal of cancerous tissue presents the best overall survival rate. However, failure to obtain negative margins during resection has remained a steady concern over the past 3 decades. The need for improved tumor removal and margin assessment presents an ongoing concern for the field. While near-infrared agents have long been used in imaging, investigation of these agents for use in HNC imaging has dramatically expanded in the past decade. Targeted tracers for use in primary and metastatic lymph node detection are of particular interest, with panitumumab-IRDye800 as a major candidate in current studies. This review aims to provide an overview of intraoperative near-infrared fluorescence-guided surgery techniques used in the clinical detection of malignant tissue and sentinel lymph nodes in HNC, highlighting current applications, limitations, and future directions for use of this technology within the field. Keywords: Molecular Imaging-Cancer, Fluorescence © RSNA, 2024.

3D Printing for the Development of Palatal Defect Prosthetics.

Background: Three-dimensional (3D) printing has emerged as a promising new technology for the development of surgical prosthetics. Research in orthopedic surgery has demonstrated that using 3D printed customized prosthetics results in more precise implant placements and better patient outcomes. However, there has been little research on implementing customized 3D printed prosthetics in otolaryngology. The program sought to determine whether computed tomography (CT) serves as feasible templates to construct 3D printed palatal obturator prosthetics for defects in patients who have been treated for head and neck cancers. Observations: A retrospective review of patients with palatal defects was conducted and identified 1 patient with high quality CTs compatible with 3D modeling. CTs of the patient's craniofacial anatomy were used to develop a 3D model and a Formlabs 3B+ printer printed the palatal prosthetic. We successfully developed and produced an individualized prosthetic using CTs from a veteran with head and neck deformities caused by cancer treatment who was previously treated at the Veterans Affairs Palo Alto Health Care System. This project was successful in printing patient-specific implants using CT reproductions of the patient's craniofacial anatomy, particularly of the palate. The program was a proof of concept and the implant we created was not used on the patient. Conclusions: Customized 3D printed implants may allow otolaryngologists to enhance the performance and efficiency of surgeries and better rehabilitate and reconstruct craniofacial deformities to restore appearance and function to patients. Additional research will strive to enhance the therapeutic potential of these prosthetics to serve as low-cost, patient-specific implants.

How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck.

BACKGROUND: Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. METHODS: Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). RESULTS: A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. CONCLUSIONS: Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

The Evolution of Fluorescence-Guided Surgery.

There has been continual development of fluorescent agents, imaging systems, and their applications over the past several decades. With the recent FDA approvals of 5-aminolevulinic acid, hexaminolevulinate, and pafolacianine, much of the potential that fluorescence offers for image-guided oncologic surgery is now being actualized. In this article, we review the evolution of fluorescence-guided surgery, highlight the milestones which have contributed to successful clinical translation, and examine the future of targeted fluorescence imaging.

Virtual Resection Specimen Interaction Using Augmented Reality Holograms to Guide Margin Communication and Flap Sizing.

Head and neck surgeons often have difficulty in relocating sites of positive margins due to the complex 3-dimensional (3D) anatomy of the head and neck. We introduce a new technique where resection specimens are 3D scanned with a smartphone, annotated in computer-assisted design software, and immediately visualized on augmented reality (AR) glasses. The 3D virtual specimen can be accurately superimposed onto surgical sites for orientation and sizing applications. During an operative workshop, a surgeon using AR glasses projected virtual, annotated specimen models back into the resection bed onto a cadaver within approximately 10 minutes. Colored annotations can correspond with pathologic annotations and guide the orientation of the virtual 3D specimen. The model was also overlayed onto a flap harvest site to aid in reconstructive planning. We present a new technique allowing interactive, sterile inspection of tissue specimens in AR that could facilitate communication among surgeons and pathologists and assist with reconstructive surgery.

Toll-like Receptor Agonists Are Unlikely to Provide Benefits in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has poor survival rates. Immunotherapy is the standard of care for R/M HNSCC, but objective responses occur in a minority of patients. Toll-like receptor (TLR) agonists promote antitumor immune responses and have been explored in clinical trials. METHODS: A search for clinical trials using TLR agonists in HNSCC was performed under PRISMA guidelines. Data on patient characteristics, safety, and efficacy were collected and analyzed. RESULTS: Three phase 1b trials with 40 patients and three phase 2 trials with 352 patients studying TLR8 and TLR9 agonists in combination with other treatment regimens for HNSCC were included. In phase 2 trials, there was no significant change in the objective response rate (RR = 1.13, CI 0.80-1.60) or association with increased grade 3+ adverse events (RR = 0.91, CI 0.76-1.11) associated with TLR agonist use. CONCLUSION: TLR agonists do not appear to provide additional clinical benefits or increase adverse events in the treatment of HNSCC. Given these results across multiple clinical trials and drug regimens, it is unlikely that additional trials of TLR agonists will demonstrate clinical benefits in HNSCC.

Fluorescent Molecular Imaging Can Improve Intraoperative Sentinel Margin Detection in Oral Squamous Cell Carcinoma.

In head and neck cancer, a major limitation of current intraoperative margin analysis is the ability to detect areas most likely to be positive based on specimen palpation, especially for larger specimens where sampling error limits detection of positive margins. This study aims to prospectively examine the clinical value of fluorescent molecular imaging to accurately identify "the sentinel margin," the point on a specimen at which the tumor lies closest to the resected edge in real-time during frozen section analysis. Methods: Eighteen patients with oral squamous cell carcinoma were enrolled into a prospective clinical trial and infused intravenously with 50 mg of panitumumab-IRDye800CW 1-5 d before surgery. Resected specimens were imaged in a closed-field near-infrared optical imaging system in near real-time, and custom-designed software was used to identify locations of highest fluorescence on deep and peripheral margins. The surgeon identified the sentinel margin masked to optical specimen mapping, and then the regions of highest fluorescence were identified and marked for frozen analysis. Final pathology based on specimen reconstruction was used as reference standard. Results: Resected specimens were imaged in the operating room, and fluorescence had a higher interobserver agreement with pathology (Cohen κ value 0.96) than the surgeon (Cohen κ value of 0.82) for the location of the closest margin. Plotting margin distance at the predicted sentinel margin location of each observer versus the actual closest margin distance at pathology demonstrated best correlation between fluorescence and pathology (R2 = 0.98) with surgeon (R2 = 0.75). Conclusion: Fluorescence imaging can improve identification of the sentinel margin in head and neck cancer resections, holding promise for rapid identification of positive margins and improved oncologic outcomes.

89Zr-panitumumab Combined With 18F-FDG PET Improves Detection and Staging of Head and Neck Squamous Cell Carcinoma.

PURPOSE: Determine the safety and specificity of a tumor-targeted radiotracer (89Zr-pan) in combination with 18F-FDG PET/CT to improve diagnostic accuracy in head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: Adult patients with biopsy-proven HNSCC scheduled for standard-of-care surgery were enrolled in a clinical trial and underwent systemic administration of 89Zirconium-panitumumab and panitumumab-IRDye800 followed by preoperative 89Zr-pan PET/CT and intraoperative fluorescence imaging. The sensitivity, specificity, and AUC were evaluated. RESULTS: A total of fourteen patients were enrolled and completed the study. Four patients (28.5%) had areas of high 18F-FDG uptake outside the head and neck region with maximum standardized uptake values (SUVmax) greater than 2.0 that were not detected on 89Zr-pan PET/CT. These four patients with incidental findings underwent further workup and had no evidence of cancer on biopsy or clinical follow-up. Forty-eight lesions (primary tumor, LNs, incidental findings) with SUVmax ranging 2.0-23.6 were visualized on 18F-FDG PET/CT; 34 lesions on 89Zr-pan PET/CT with SUVmax ranging 0.9-10.5. The combined ability of 18F-FDG PET/CT and 89Zr-pan PET/CT to detect HNSCC in the whole body was improved with higher specificity of 96.3% [confidence interval (CI), 89.2%-100%] compared to 18F-FDG PET/CT alone with specificity of 74.1% (CI, 74.1%-90.6%). One possibly related grade 1 adverse event of prolonged QTc (460 ms) was reported but resolved in follow-up. CONCLUSIONS: 89Zr-pan PET/CT imaging is safe and may be valuable in discriminating incidental findings identified on 18F-FDG PET/CT from true positive lesions and in localizing metastatic LNs.

Comparative case series of exostoses and osteomas of the internal auditory canal.

Exostoses and osteomas are benign bony lesions of the auditory canal. Although common in the external auditory canal, they are rare and difficult to distinguish in the internal auditory canal (IAC). In this literature review and case presentation, we define radiologic and histologic criteria to differentiate exostoses from osteomas of the IAC. Two patients with exostoses and 1 patient with an osteoma of the IAC are described here. Patient 1 presented with disabling vertigo and was found to have bilateral exostoses with nerve impingement on the right. After removal of the right-sided exostoses via retrosigmoid craniotomy, the patient had complete resolution of her symptoms over 1 year. Patient 2 presented with bilateral pulsatile tinnitus and vertigo and was found to have bilateral IAC exostoses. Patient 3 presented with hearing loss and tinnitus, and a unilateral IAC osteoma was ultimately discovered. Because of the mild nature of their symptoms, patients 2 and 3 were managed without surgery. We show that IAC osteomas can be differentiated from exostoses by radiographic evidence of bone marrow in high-resolution computed tomography scans, or by the presence of fibrovascular channels on histologic analysis. Management of these rare entities is customized on the basis of patient symptoms.

Multifocal Parotid Oncocytic Cystadenomatosis: A Rare Process that Can Mimic Malignancy.

Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by multiple unencapsulated solid nodules of oncocytic cells derived from transformed striated ducts. MCO is a variant of salivary oncocytosis which manifests as cystically dilated striated ducts. It is difficult to obtain a definitive preoperative diagnosis of MCO; therefore, these lesions are commonly treated with surgery. We report the unique case of a 66-year-old male who previously underwent a superficial left parotidectomy for a pleomorphic adenoma. Four years later, he presented with clinical and radiographic suspicion of a multifocal recurrent pleomorphic adenoma. The patient subsequently underwent a revision parotidectomy. However, final pathology confirmed a diagnosis of MCO. Although MCO is commonly treated with surgery due to lack of a definitive preoperative diagnosis, surgery is unnecessary outside of diagnostic, functional or cosmetic considerations. Thus, if a patient with parotid oncocytosis treated by superficial parotidectomy develops disease re-manifestation in the residual deep lobe, further surgery is not indicated. There is no risk of malignant progression in this process. We report on this unusual entity as it may mimic salivary malignancy or, as in this case, recurrence of benign disease.