Impact of comorbidities on immediate post-operative complications in oral cavity free flap patients.

PURPOSE: To examine the relationship between comorbidities and the development of immediate post-operative complications in patients undergoing oral cavity composite resection (OCCR) with free flap (FF) reconstruction. MATERIALS AND METHODS: Retrospective analysis was completed on all consecutive OCCRs with FF reconstruction performed at a single quaternary care facility between 1999 and 2020. Comorbidities, immediate post-operative complications, patient demographics, and tumor characteristics were collected. Odds ratios (OR) with 95 % confidence intervals were calculated for associations between comorbidities and immediate post-operative complications. RESULTS: 320 patients who underwent OCCR with FF reconstruction were included. One hundred twenty-one (37.8 %) patients developed a post-operative complication during their initial hospital admission. The most common complications were non-pneumonia cardiopulmonary events (14.1 %), pneumonia (9.4 %), and wound infection (8.4 %). Other complications included flap compromise, bleeding, and fistula. On multivariate analysis, patients without comorbid conditions were less likely to develop a post-operative complication (OR 0.64; 0.41-0.98). Atrial fibrillation (OR 2.94; 1.17-7.39) and cerebrovascular disease (OR 2.28; 1.08-4.84) were associated with increased odds of developing any complications. Furthermore, cerebrovascular disease (OR: 2.33; 1.04-5.39) and peripheral vascular disease (OR: 2.7; 1.2-6.08) were independently associated with pneumonia. CONCLUSION: In this retrospective review of patients undergoing OCCR with FF reconstruction for oral cavity SCC, lack of identifiable comorbidities appeared to be protective for post-operative complications while atrial fibrillation and cerebrovascular disease were associated with increased odds of any complication. Pre-existing vascular disease was also associated with an increased risk of pneumonia.

Delayed Upper Aerodigestive Tract Perforation from Anterior Cervical Spine Hardware: Treatment and Swallowing Outcomes.

Delayed upper aerodigestive tract (UADT) perforation is a rare complication of anterior cervical spinal hardware. The purpose of this study was to investigate swallowing outcomes between treatment approaches for delayed UADT perforation. A retrospective chart review was performed on patients with anterior cervical hardware and delayed UADT perforation who were treated at a single tertiary care center between 2000 and 2020. Of the twelve patients identified, most patients presented with dysphagia (n = 9, 75%) and/or neck pain (n = 7, 58%). Perforations generally occurred at the level of C6 (n = 6, 50%) and C7 (n = 4, 33%) and spanned only one spinal level (n = 8, 67%). The majority (n = 8, 67%) of patients were past or current cigarette users. Operative approaches included primary repair (n = 5, 42%) and rotational flap (n = 4, 33%); the rotational flap harvest sites included supraclavicular fasciocutaneous (n = 2), infrahyoid muscle (n = 1), and sternocleidomastoid muscle (n = 1). While most patients demonstrated penetration and/or aspiration on first post-operative swallow study (n = 6), this resolved completely within a median time of 31 days. There were no differences in swallowing outcomes between repair approaches. Patient smoking history appears to be a clear risk factor for the development of delayed UADT perforation from anterior cervical spine hardware. A variety of techniques can be used to repair these perforations, and there were no differences in swallowing outcomes between repair approaches.

Impact of COVID-19 on presentation, staging, and treatment of head and neck mucosal squamous cell carcinoma.

OBJECTIVES: During the COVID-19 pandemic, maintenance of safe and timely oncologic care has been challenging. The goal of this study is to compare presenting symptoms, staging, and treatment of head and neck mucosal squamous cell carcinoma during the pandemic with an analogous timeframe one year prior. MATERIALS AND METHODS: Retrospective cohort study at a single tertiary academic center of new adult patients evaluated in a head and neck surgical oncology clinic from March -July 2019 (pre-pandemic control) and March - July 2020 (COVID-19 pandemic). RESULTS: During the pandemic, the proportion of patients with newly diagnosed malignancies increased by 5%, while the overall number of new patients decreased (n = 575) compared to the control year (n = 776). For patients with mucosal squamous cell carcinoma (SCC), median time from referral to initial clinic visit decreased from 11 days (2019) to 8 days (2020) (p = 0.0031). There was no significant difference in total number (p = 0.914) or duration (p = 0.872) of symptoms. During the pandemic, patients were more likely to present with regional nodal metastases (adjusted odds ratio (OR) 2.846, 95% CI 1.072-3.219, p = 0.028) and more advanced clinical nodal (N) staging (p = 0.011). No significant difference was seen for clinical tumor (T) (p = 0.502) or metastasis (M) staging (p = 0.278). No significant difference in pathologic T (p = 0.665), or N staging (p = 0.907) was found between the two periods. CONCLUSION: Head and neck mucosal SCC patients presented with more advanced clinical nodal disease during the early months of the COVID-19 pandemic despite no change in presenting symptoms.

Existing Predictive Models for Postoperative Pulmonary Complications Perform Poorly in a Head and Neck Surgery Population.

Postoperative pulmonary complications (PPCs) are common following major surgical procedures. Risk stratification tools have been developed to identify patients at risk for PPCs. While otolaryngology cases were included in the development of common predictive tools, they comprised small percentages in each tool. It is unclear how these tools perform in patients undergoing major head and neck surgery with free flap reconstruction. This retrospective review studied all free flap reconstructions in head and neck surgery over a 12-year period at a single institution in the southeastern US. Baseline demographic and medical information were included for each case. All cases were reviewed for development of major PPCs, including pneumonia and respiratory failure. The cohort underwent risk stratification using the ARISCAT and Gupta pulmonary risk indices. Performance of these predictive models for head and neck surgery was determined through receiver-operator curve comparison. 794 patients were identified with a median age of 62 years (IQR 41-83). Sixty-five percent were male. Forty-three (5.4%) developed pneumonia, 23 patients developed respiratory failure (2.9%), and 38 patients developed both (4.8%), resulting in a total PPC proportion of 13.1% (n = 104). Both ARISCAT and Gupta pulmonary risk indices demonstrated low discrimination to predict PPCs in head and neck free flap reconstruction, with areas under the curve of 0.60 and 0.65, respectively. Two major indices for prediction of postoperative pulmonary complications do not accurately identify risk in patients undergoing major head and neck surgery. Further studies are needed to develop predictive tools for PPCs in this high-risk population.

Free dermal fat graft reconstruction of the head and neck: An alternate reconstructive option.

OBJECTIVES: Ablative procedures of the head and neck often result in significant facial and cervical irregularities and cosmetic asymmetry. The deformity resulting from ablative procedures of the head and neck is a significant source of cosmetic morbidity and postoperative dissatisfaction. Reconstruction of post-ablative defects in the head and neck can employ a broad range of techniques, ranging from primary closure to free tissue transfer. The free dermal fat graft (FDFG) is one such option and has been used to repair volume defects of varying sizes after common head and neck procedures such as parotidectomy. However, its use is largely undocumented in the literature. We seek to further illustrate the FDFG as an alternate method of reconstruction of head and neck defects. STUDY DESIGN: Non-randomized retrospective analysis. METHODS: The medical records of all patients who underwent primary autologous abdominal FDFG reconstruction of head and neck defects by a single surgeon at Vanderbilt University Medical Center from January 1997 to August 2010 were reviewed. All patients were called in order to assess their post-operative cosmetic satisfaction. RESULTS: Sixty-two patients were analyzed. Only three patients were found to have post-operative complications directly related to the FDFG. No complications were found at the donor site. Based on a telephone survey, the majority of patients were satisfied post-operatively with their cosmetic outcomes in the primary site and donor site. CONCLUSIONS: From our experience the FDFG is a cosmetically and functionally advantageous option for reconstruction of ablative procedures of the head and neck.

Remote orbital recurrence of olfactory neuroblastoma (esthesioneuroblastoma).

Olfactory neuroblastoma is a rare and often locally aggressive malignancy that invades the orbit via local destruction. It is known to recur in a delayed fashion, particularly to the neck lymph nodes. This is a case of a 65-year-old gentleman who presents with recurrence in the orbit and a neck lymph node 19 years after treatment for his initial disease. This report describes the longest known interval in orbital recurrence and should alert the monitoring physician that extreme delays in recurrence can occur.

The osteocutaneous radial forearm free flap: A multidisciplinary review of the evidence.

The osteocutaneous radial forearm (OCRFF) is a versatile free flap option for bony defects of the head and neck, given the thinness and pliability of the forearm cutaneous paddle, pedicle length, reliability, lack of atherosclerosis, and functional concerns common to other osseous donor sites. The OCRFF was once associated with a high risk of radial fracture, in addition to concerns about the quality and durability of bone stock for osseous reconstruction, particularly for the mandible. Following the introduction of prophylactic plating of the radius, the incidence of symptomatic radial fracture has drastically decreased. Furthermore, modifications of the bony osteotomies and other evolutions of this flap harvest have increased the use of the OCRFF throughout the head and neck. Despite these advantages, the OCRFF is not widely utilized by microvascular reconstructive surgeons due to perceived limitations and risks. Herein, we present a multidisciplinary, contemporary review of the harvest technique, outcomes, and perioperative management for the OCRFF.

Comparative Outcomes for Microvascular Free Flap Monitoring Outside the Intensive Care Unit.

OBJECTIVE: There is a trend towards nonintensive care unit (ICU) or specialty ward management of select patients. Here, we examine postoperative outcomes for patients transferred to a general ward following microvascular free flap (FF) reconstruction of the head and neck. STUDY DESIGN: Retrospective quality control study. SETTING: Single tertiary care center. METHODS: Consecutive patients who underwent FF of the head and neck before and after a change in protocol from immediate postoperative monitoring in the ICU ("Pre-protocol") to the general ward setting ("Post-protocol"). Outcomes included overall length of stay (LOS), ICU LOS, FF compromise, and postoperative complications. RESULTS: A total of 150 patients were included, 70 in the pre-protocol group and 80 in the post-protocol group. There were no significant differences in age, sex, comorbidities, tumor stage, or type of FF. Mean LOS decreased from 8.18 to 7.68 days (P = .4), and mean ICU LOS decreased significantly from 5.2 to 1.7 days (P < .01). There were no significant differences in postoperative or airway-related complications (P = .6) or FF failure rate (2.9% vs 2.6%, P > .9). There was a non-significant increase in ancillary consults in the post-protocol group (45% vs 33%, P = .13) and a significant increase in rapid response team calls, a nurse-driven safety net for abnormal vitals or mental status (19% vs 3%, P = .003). CONCLUSION: We show the successful implementation of a protocol shifting care of FF patients from the ICU to a general ward postoperatively, suggesting management on the floor with less frequent flap monitoring is safe and conserves ICU beds. Additional teaching and familiarity with these patients may over time reduce the rapid response calls.

Virtual 3D Specimen Mapping in Head & Neck Oncologic Surgery.

OBJECTIVES: Virtual 3D specimen mapping of oncologic surgical specimens provides a visual record of the specimen and margin sampling sites which can be utilized in a variety of cancer care settings. Our objective was to perform a retrospective review of head and neck surgical oncology cases where the specimen was mapped post-operatively and to evaluate the utility of these 3D specimen maps amongst the multidisciplinary cancer care team. METHODS: A retrospective review of our 3D specimen model biorepository was performed. Surgical specimens were 3D scanned and then graphically annotated (or "mapped") during routine pathologic processing. The resulting 3D specimen maps were distributed to the multidisciplinary oncologic care team. Final margin status and any use of the 3D specimen maps were recorded. RESULTS: A total of 28 cases were included. Virtual 3D specimen maps were utilized by the cancer care team in 8 cases (29%), including 2 positive margin cases, 2 close margin cases, and 4 indeterminate margin cases. 3D specimen maps were used to visualize positive margin sites for pathologist-surgeon communication as a visual reference during tumor board discussions and to inform radiation treatment planning. CONCLUSION: Post-operative virtual 3D specimen mapping of oncologic specimens creates a permanent visual record of the specimen and the margins sampled and may serve as a beneficial tool for communication amongst the multidisciplinary cancer care team. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:191-197, 2024.

Wnt/ß-catenin signaling is a therapeutic target in anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/ß-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF-wildtype ATC and a lack of effective treatment for BRAFV600EATC. Our aim is to identify whether Wnt inhibitors could be potential therapeutic agents for ATC patients with limited treatment options. METHODS: In this Institutional Review Board-approved study, we utilize a cohort of 32 ATCs and 20 non-neoplastic multinodular goiters (MNG). We also use 4 ATC spheroid cell lines (THJ-16T, THJ-21T, THJ-29T, and THJ-11T) and two primary patient-derived ATC organoid cultures (VWL-T5 and VWL-T60). Finally, we use a murine xenograft mouse model of ATC for in vivo treatment studies. RESULTS: Using a large patient cohort, we demonstrate that this near-universal Wnt signaling activation is associated with ligand expression- rather than being mutationally-driven. We show that pyrvinium pamoate, a potent Wnt inhibitor, exhibits in vitro efficacy against both ATC cell lines and primary patient-derived ATC organoids VWL-T5 (p < 0.05) and VWL-T60 (p < 0.01) Finally, using a murine xenograft model of ATC, we show that pyrvinium significantly delays the growth of ATC tumors in THJ-16T (p < 0.005) and THJ-21T (p < 0.001). CONCLUSIONS: We tested Wnt inhibitor treatment, both in vitro and in vivo, as a potential novel therapy for this highly lethal disease. Future large-scale studies utilizing multiple Wnt inhibitors will lay the foundation for the development of these novel therapies for patients with ATC.

Association of social vulnerability on survival, treatment, and presentation in oral cavity cancer.

OBJECTIVE: This study utilized a population database to investigate how social environments are associated with outcomes including stage at diagnosis, multimodal treatment, and disease-specific survival for oral cavity squamous cell carcinomas. METHODS: Retrospective analysis of adults with oral cavity squamous cell carcinoma between 2007 and 2016 from the Surveillance, Epidemiology, End Results (SEER) registry was performed. The CDC's social vulnerability index (SVI) was used to characterize social vulnerability at the county level. Predictors of disease-specific survival, stage at diagnosis, and use of multimodal therapy were identified using Cox regression and logistic regression. RESULTS: Our analysis included 17 043 patients. On adjusted models, patients in the highest SVI quartile (most social vulnerability) exhibited worse disease-specific survival compared to the lowest quartile (HR 1.24, 95% CI 1.12-1.37, p < 0.001), and were more likely to be diagnosed at later stages (OR 1.24, 95% CI 1.11-1.38, p < 0.001) and less likely to receive multimodal therapy (OR 0.84, 95% CI 0.77-0.99, p = 0.037). CONCLUSION: High social vulnerability was associated with worse disease-specific survival and disease presentation in oral cavity cancer patients.

Utility of PET-CT in Newly Diagnosed HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To compare the utility of positron emission tomography-computed tomography (PET-CT) versus contrasted CT neck combined with routine chest imaging for disease staging and treatment planning in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) with clinically evident sites of primary disease. METHODS: All adult patients with primary HPV-associated OPSCC at a single quaternary care cancer center from 2018 to 2019 were reviewed, and those with images available for re-review were included. Primary outcomes included concordance in clinical staging between the 2 imaging modalities of interest (PET-CT vs CT), as well as independent agreement of each with pathologic staging. Analysis was performed via ordinal logistic regression. A secondary outcome was treatment selection after diagnostic imaging, analyzed via chi-squared testing. RESULTS: In total, 100 patients were included for evaluation, of which 89% were male, 91% Caucasian, and mean age was 61.2 years (SD 9.6). Clinical disease staging agreed between imaging modalities in 95% of cases (54 of 57 patients). Pathologic staging agreed with clinical staging from CT neck in 93% of cases (25 of 27 patients; P = .004), and with PET-CT in 82% (14 of 17 patients; P =.003). No differences were observed between the 2 imaging modalities for subsequent treatment selection (P = .39). CONCLUSION: In uncomplicated HPV-associated OPSCC, CT offers equivalent diagnostic accuracy to that of combined whole-body PET-CT for clinical staging, and has no appreciable impact on treatment selection. A reduced reliance on routine PET-CT during initial workup of HPV-associated OPSCC may be favorable for otherwise healthy patients with clinically evident sites of primary disease.

Characterizing gender trends in head and neck fellowship graduates from 2008 to 2018.

OBJECTIVES: Evaluation of potential gender gaps among Head and Neck (H&N) surgeons can highlight areas for increased support of female H&N surgeons and improve gender diversity within the subspecialty. To evaluate gender trends in representation and career trajectory among recent H&N surgery fellowship graduates. METHODS: This cross-sectional analysis included graduates from Head and Neck Surgery fellowships accredited by the American Head and Neck Society (AHNS) from 2008 to 2018. Additional demographic data was collected via publicly available websites including gender, years in practice, practice location, type of practice, h-index, and academic rank. The primary outcomes were the proportion of female Head and Neck fellowship graduates and gender trends in career trajectory and academic productivity (via h-index). RESULTS: Between 2008 and 2018, 449 surgeons graduated from Head and Neck surgery fellowship with females comprising 99 of 449 graduates (22%). Female representation increased from 1 of 30 (3%) graduates in 2008 to 17 of 52 (33%) in 2018. A proportionally similar number of women graduating fellowship also practiced in an academic setting (23%). There were fewer female assistant, associate and full professors compared with their male counterparts. Women had lower h-indices compared with men even when controlling for years in practice (mean 11.4 vs. 8.2, p < 0.03). CONCLUSION: Despite the increase in women graduating from H&N surgery fellowships, gender disparities within academic rank and academic productivity as measured by h-index remain. While a proportional number of women completing fellowship are entering academic practice, additional investigation and support is needed to address the potential gender gaps identified within academic H&N surgery.

Preoperative Predictors of Free Flap Failure.

OBJECTIVE: Microvascular free tissue transfer is an important reconstructive option for defects of the head and neck. The present study aims to identify preoperative patient- and tumor-specific characteristics, laboratory values, and other risk factors associated with early free flap failure. STUDY DESIGN: Retrospective cohort study of 1070 patients. SETTING: Head and neck surgical oncology service at a tertiary care center from 2005 to 2019. METHODS: Demographics, comorbidities, preoperative laboratory values, treatment history, and cancer stage were collected for consecutive patients who underwent free flap reconstruction of the head and neck and experienced early free flap failure (<8 days from surgery). RESULTS: In 1070 patients, the prevalence of early free flap failure was 3.8% (n = 41). Female sex (odds ratio [OR], 2.58; 95% CI, 1.36-4.99), presence of peripheral vascular disease (OR, 2.78; 95% CI, 1.05-6.57), and elevated preoperative platelet count (OR, 2.67; 95% CI, 1.20-5.47) were independently associated with risk of early free flap failure. CONCLUSION: Female sex, peripheral vascular disease, and preoperative thrombocytosis are all strong predictors of early free flap failure. This suggests that hypercoagulability and poor vessel quality may predispose patients to flap loss. Patients with elevated platelets or peripheral vascular disease warrant careful reconstructive decision making and close monitoring in the perioperative period.

Head and Neck Necrotizing Fasciitis: Abbreviated SOFA Score Associated With Death and Infection Spread.

Objective: Describe features unique to head and neck (H&N) necrotizing fasciitis (NF) compared to other anatomic regions and specify a prognostic score associated with death and descending necrotizing mediastinitis (DNM). Study Design: Retrospective cohort. Setting: Tertiary care, level 1 trauma center. Methods: A single-institution database identified 399 confirmed cases of NF between 2006 and 2021, 33 of which involved the H&N. Patients with confirmed H&N NF were sorted into cohorts based on clinical outcomes, with the "poor" outcomes group defined by death and/or DNM. Results: Thirty-three patients with H&N NF were included. Compared to NF of other regions, patients with H&N NF had a significantly lower mortality rate (6.06% vs 20.8%, p = .041) and significantly lower rates of obesity (27.3% vs 63.7%, p < .001) and hypertension (42.4% vs 60.9%, p = .038). Within the H&N group, there were 2 deaths (6.06%) and 8 cases of DNM (24.2%). Diabetes was associated with poor outcomes (p = .047), as was an abbreviated sequential organ failure assessment score for necrotizing fasciitis (nfSOFA) of 2 or greater (p = .015). Conclusion: H&N NF is unique among other forms of NF, with a lower mortality rate and lower rates of obesity and hypertension in affected patients. Within the H&N cohort, worse outcomes were associated with diabetes as well as a nfSOFA score of 2 or greater. Timely surgical debridement alongside broad-spectrum antibiotics remains the mainstay of treatment for NF; however, this simple prognostic score may play a role during the early stages of care for patients with H&N NF.

The computer-aided design margin: Ex vivo 3D specimen mapping to improve communication between surgeons and pathologists.

BACKGROUND: Numerous challenges exist in determining surgical margin status. Communication between surgeons and pathologists is crucial for specimen orientation and accurate margin assessment. METHODS: A prospective study to determine feasibility of incorporating three-dimensional (3D) scanning into surgical pathology workflow was performed. A structured-light 3D scanner captured the photorealistic surface topography of fresh surgical specimens. Computer-aided design (CAD) software was used to document sites of margin sampling and sectioning. Surveys were distributed among faculty and staff stakeholders to assess feasibility. RESULTS: A series of 40 cases were 3D-scanned. Median image acquisition time was 8 min. The majority of respondents agreed that the experimental 3D system helped achieve clearer communication. 3D specimen maps assisted in the communication of a focally positive or close margin in 4 of 17 cases. CONCLUSIONS: Routine 3D scanning and specimen mapping is feasible and represents an innovative approach to intraoperative and final pathology documentation, margin analysis, and surgeon-pathologist communication.

A Multi-institutional Analysis of Late Complications in Scapula, Fibula, and Osteocutaneous Radial Forearm Free Flaps.

OBJECTIVES: (1) Evaluate the association of flap type with late complications in patients undergoing osseous head and neck reconstruction with the fibula free flap (FFF), osteocutaneous radial forearm free flap (OCRFFF), and scapula free flap (SFF). (2) Compare the prevalence of late complications based on minimum duration of follow-up. STUDY DESIGN: Retrospective cohort study. SETTING: Multiple academic medical centers. METHODS: Patients undergoing FFF, OCRFFF, or SFF with ≥6-month follow-up were stratified by type of flap performed. The association of flap type with late complications was analyzed via univariable and multivariable logistic regression, controlling for relevant clinical risk factors. Additionally, the frequency of late complications by minimum duration of follow-up was assessed. RESULTS: A total of 617 patients were analyzed: 312 (50.6%) FFF, 230 (37.3%) OCRFFFF, and 75 (12.2%) SFF. As compared with the SFF, the FFF (adjusted odds ratio [aOR], 3.05; 95% CI, 1.61-5.80) and OCRFFF (aOR, 2.17; 95% CI, 1.12-4.22) were independently associated with greater odds of overall late recipient site wound complications. The SFF was independently associated with the lowest odds of hardware exposure when compared with the FFF (aOR, 2.61; 95% CI, 1.27-5.41) and OCRFFF (aOR, 2.38; 95% CI, 1.11-5.12). The frequency of late complications rose as minimum duration of follow-up increased until plateauing at 36 months. CONCLUSIONS: This multi-institutional study suggests that the long-term complication profile of the SFF and OCRFFF compares favorably to the FFF. The SFF may be associated with the fewest overall late recipient site complications and hardware exposure, while the FFF may be associated with the most of these 3 options.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.

Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.