Bronchial Sialadenoma Papilliferum in a 10-Year-Old Boy.

Sialadenoma papilliferum (SP) is a rare salivary gland tumor mostly reported in the oral cavity. Here we describe a bronchial SP in the left upper lobe bronchus of a 10-year-old boy. At bronchoscopy, a well-circumscribed polypoid lesion protruding into the bronchial lumen was identified. The tumor was excised, but eventually, the patient had to undergo a sleeve resection after 2 recurrences. Pathology revealed a papillocystic lesion with exophytic and endophytic components. The cells lining the exophytic surface and papillary structures were columnar and squamous, and the cells lining endophytic cystic and papillary structures were cuboidal to columnar, all of which were diffusely reactive with antibodies to SOX10 protein. The presence of basal cells was demonstrated by p63 immunoreactivity. The cells failed to immunohistochemically express BRAF V600E. Fluorescence in situ hybridization analysis revealed no MAML2 or RET gene rearrangement. The patient is alive 24 years after resection with no additional recurrences. Bronchial SP needs to be recognized and distinguished from other benign and malignant salivary gland and pulmonary neoplasms so that patients can receive appropriate treatment and follow-up.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

PURPOSE: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. METHODS: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. RESULTS: Fifteen lesions (3-42 mm) were identified, predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AML contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four AL contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included ulceration, thrombosis, inflammation, myxoid change, senescent nuclei, and extramedullary hematopoiesis; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin, desmin, and/or caldesmon) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. CONCLUSION: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AML. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

"So You Made a Mistake" - The Path Forward Through Surgical Pathology Errors by Extreme Ownership and a Focus on the Patient.

Our goal for medicine is to make zero mistakes, yet the reality is that mistakes are an unfortunate part of medical practice. And when it comes to surgical pathology, it is a special case where the diagnostic "bottom line" is provided starkly and directly for all to see in the final diagnosis of the pathology report. When this diagnosis is wrong, particularly when it has serious adverse consequences for the patient, the resulting physical, mental, and emotional effects on patient, provider, pathologist, and health care system can be extremely serious. Head and neck surgical pathology, based on large second review-type studies, is a subspecialty area with average rates of major diagnostic error, but with potential for severely negative impacts on patients. Studies have shown between 1% and 7% major error rates for head and neck practice. How then, as the pathologist, can we react to and manage things when we have made a serious diagnostic mistake? Through personal experience over more than two decades, the hard-won answer is through extreme ownership and a focus on the needs of the patients, who, in the words of William J. Mayo, should have their "needs come first". The emotional impact on us as pathologists and on the clinicians we work with should also be acknowledged and managed. This article will serve as a thorough and open examination of these mistake scenarios and, focusing specifically on diagnostic errors, serve as a practical guide for what you can do, moving forward, to "make things right" to the best of your ability.

Quantifying cost-savings in the treatment of neovascular age-related macular degeneration in Aotearoa New Zealand.

AIMS: To estimate the cost-impact if faricimab were approved for the treatment of neovascular age-related macular degeneration (nAMD) in New Zealand. METHODS: A retrospective, single-centre cost-analysis study. Data on intravitreal agent and injection intervals were obtained and statistically compared. Cost estimates were based on internal facility and publicly available data. The current costs of care were compared to two scenarios: one where all eyes receive faricimab, and another where eyes receiving aflibercept switch to faricimab. RESULTS: A total of 352 eyes from 292 patients were analysed. Present values locally over 10 years were estimated at -$6,776,340 for the first scenario and $5,015,922 for the second, releasing 252 and 176 hours of clinical time per year, respectively. Nationally, the savings extrapolated to -$187,925,737 and $139,104,706, respectively. The analysis indicates significant direct cost savings for the health sector and potential reductions in patient harm due to fewer injections. CONCLUSIONS: The approval of faricimab for the treatment of nAMD could result in substantial direct cost savings for the health sector. Additional benefits include reducing patient harm and improving ophthalmic health inequalities for Maori and Pacific peoples. Further research in diverse patient populations across multiple centres is needed to estimate the magnitude of cost savings more accurately. This study highlights the potential of faricimab to alleviate the treatment burden and provide a more sustainable healthcare option for nAMD in New Zealand, especially in cases of recalcitrant nAMD, if used in a tailored and patient-specific manner alongside the existing armamentarium of treatments.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Purpose: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. Methods: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Results: Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AMLs contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four ALs contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Conclusion: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

DEK::AFF2 Fusion-Associated Squamous Cell Carcinoma: A Case Series with Literature Review on an Emerging and Challenging Entity.

PURPOSE: DEK::AFF2 fusion-associated squamous cell carcinoma (DEK::AFF2 SCC), also reported in the literature as low-grade papillary sinonasal (Schneiderian) carcinoma (LGPSC), is a rare, primarily bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), especially on small or limited biopsy, often leading to misdiagnosis. DEK::AFF2 SCC is devoid of the underlying mutually exclusive EGFR or KRAS driver mutations of SP, suggesting it may represent a distinct unique entity. METHODS: In this study, we conducted a retrospective search of "unusual" SP reported either as atypical, dysplastic, or suspicious for malignant transformation at our institution in the last 13 years (2010-2023), to identify potential cases of DEK::AFF2 SCC. RESULTS: Of the 201 SP cases during this time period, 30 "unusual" SP cases were identified. On morphologic review of these 30 cases, 6 were worrisome for DEK::AFF2 SCC and were selected for AFF2 immunohistochemical stain (IHC), of which 3 cases were positive. All 3 AFF2 IHC positive cases were also positive for DEK::AFF2 fusion by fluorescence in situ hybridization (FISH), thereby, confirming IHC results. CONCLUSIONS: This study highlights that AFF2 IHC can be an invaluable surrogate marker to FISH in identifying DEK::AFF2 SCC in challenging cases to avoid misdiagnosis. Detailed clinical and pathologic data were collected to gain a better understanding of this emerging challenging entity. A literature review was performed to enrich our knowledge of DEK::AFF2 SCC.

Augmented Reality-Guided Frozen Section Analysis: Bringing the Pathologist From the Laboratory to the Operating Room.

Due to the anatomic complexity of the head and neck and variable proximity between laboratory and operating room (OR), effective communication during frozen section analysis (FSA) between surgeons and pathologists is challenging. This proof-of-concept study investigates an augmented reality (AR) protocol that allows pathologists to virtually join the OR from the laboratory. Head and neck cancer specimens were scanned ex vivo using a 3-dimensional scanner and uploaded into an AR platform. Eight head and neck specimens were discussed by surgeons and pathologists in an AR environment. AR-guided intraoperative consultation was used for specimen orientation and discussion of FSA margin sampling sites. One patient had positive initial margins on FSA and was re-resected to negative final margins. AR-guided FSA is possible and allows pathologists to join the operating from any location for intraoperative discussion.

Visual pathology reports for improved collaboration at multidisciplinary head and neck tumor board.

PURPOSE: Multidisciplinary tumor boards (TB) are the standard for discussing complex head and neck cancer cases. During TB, imaging and microscopic pathology is reviewed, but there is typically no visualization of the resected cancer. METHODS: A pilot study was conducted to investigate the utility of visual pathology reports at weekly TB for 10 consecutive weeks. Faculty-level participants completed a pre-survey and post-survey to assess understanding of resected cancer specimens. RESULTS: Providers (n = 25) across seven medical specialties completed pre-survey and post-survey. Following intervention, providers reported significant improvement in understanding of anatomic orientation of the specimen and sites of margin sampling (mean 47.4-96.1, p < 0.001), ability to locate the site of a positive margin (mean 69.5-91.1, p < 0.001), and confidence in treatment plans created (mean 69.5-89.2, p < 0.001) with the addition of visual pathology reports. CONCLUSIONS: Visual pathology reports improve provider understanding of resected cancer specimens at multidisciplinary TB.

Put the Vanc Down, Flip It and Reverse It: Comparison of Vancomycin and Daptomycin Health Care Utilization and Cost in Outpatient Parenteral Antimicrobial Therapy.

Vancomycin and daptomycin are frequently used in outpatient parenteral antimicrobial therapy (OPAT). We analyze health care utilization and cost to the health care system for vancomycin vs daptomycin in the outpatient setting and find that vancomycin results in significantly higher health care utilization and similar cost per course compared with daptomycin in OPAT.

Pharmacokinetic evaluation of ibrexafungerp for the treatment of vulvovaginal candidiasis and beyond.

INTRODUCTION: Ibrexafungerp is a new triterpenoid antifungal agent with activity against a variety of fungal species, including Aspergillus spp. and echinocandin-resistant Candida spp. AREAS COVERED: This evaluation will summarize currently available clinical evidence on the use of ibrexafungerp in the treatment/prevention of vulvovaginal candidiasis (VVC) and detail the mechanism of action, pharmacokinetic/pharmacodynamic parameters, and ongoing/latest research involving ibrexafungerp. EXPERT OPINION: The evidence involving the utilization of ibrexafungerp for the treatment of VVC shows that it is superior when compared to placebo and has comparable clinical cure rates when compared with fluconazole. Ibrexafungerp demonstrates reliable coverage against several Candida spp. including echinocandin-resistant strains, Candida auris, and Aspergillus spp. For VVC, a dose of 300 mg (two 150 mg tablets) twice daily is recommended and does not require dose adjustments based on renal or hepatic function. The use of ibrexafungerp outside of VVC is currently under study with several ongoing trials showing promising interim data.

Indications and Outcomes of Emergency Keratoplasty in a Major New Zealand Eye Tertiary Referral Center, 2000 to 2021.

PURPOSE: To report the indications and outcomes of emergency keratoplasty over a 21-year period in Greenlane Clinical Centre, the major tertiary eye referral center in Auckland, New Zealand (Aotearoa). METHODS: A retrospective review of medical records of all emergency keratoplasties performed in Greenlane Clinical Centre from January 2000 to September 2021 was conducted. Demographic, preoperative, intraoperative, and 1-year postoperative data were collected. RESULTS: Emergency keratoplasty was performed in 102 eyes of 97 patients (54 men), comprising 5.6% of transplants performed (N = 1830) in this period. The mean age was 53 years (range = 4-95 years, SD = 20). Patients of Maori ethnicity were overrepresented (31%). Corneal perforation was present in 90% of eyes, and microbial keratitis was the most common indication. Bacteria were the most commonly isolated organisms (38%). The mean preoperative and 12-month postoperative best potential corrected distance visual acuity was 1.6 and 1.2 (logMAR), respectively. All cases of therapeutic keratoplasty achieved initial therapeutic success, with no eyes lost or requiring repeat emergency keratoplasty. Complications included nonhealing epithelial defects (19%), cataract (19%), glaucoma (15%), allograft rejection (13%), and corneal melting (5%). Fifteen cases (15%) had documented graft failure at 12 months. Multivariate analysis revealed that younger age was the only statistically significant factor associated with failure at 12 months. CONCLUSIONS: Emergency keratoplasty was the indication for 5.6% of keratoplasties performed. Our results compare favorably with those in the literature, possibly because of early intervention and lower incidence of fungal keratitis. The reported overrepresentation of Maori has important implications for health access and delivery in New Zealand.

Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.

SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features. A mouse model engineered for KrasG12D expression in the adult oral epithelium induced benign papillomas, however the combination of KrasG12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4- mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFß signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Utility of beta-lactam allergy assessment in patients receiving vancomycin for surgical prophylaxis.

Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.

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.

Dalba Got Back? Use of Dalbavancin for the Treatment of Vertebral Osteomyelitis.

Data evaluating dalbavancin use for vertebral osteomyelitis remain limited. In our retrospective cohort, 29 of 34 (85.3%) patients completed their dalbavancin course. Adverse reactions occurred for 6 (17.6%) and infection recurrence in 3 (8.8%) within 90 days. Dalbavancin appears to be safe and well-tolerated for vertebral osteomyelitis.

Salivary gland adenoid cystic carcinoma in the U.S population: Importance of grade, site of metastases, and adjuvant radiation for survival.

BACKGROUND: Adenoid cystic carcinoma (AdCC) is a rare and relatively heterogenous salivary gland malignancy, for which there is debate regarding grading, and clinical prognostic factors, including the role of adjuvant radiotherapy. METHODS: Surveillance, Epidemiology, and End Results (SEER) data were reviewed for AdCC cases from 2000 to 2018. RESULTS: A total of 1978 patients with AdCC were identified. Most patients were between 50 and 59 years of age (21.4 %), female (59.9 %), and Caucasian (76.8 %). Most tumors were localized at presentation (44.3 %), and moderately differentiated (or grade II) (43.7 %). Overall and DSS 5-year survival rates were 70.7 % (95 % CI, 69.9-78.8), and 78.6 % (95 % CI, 77.6-79.6). The best overall 5-year survival rate was observed for those treated with surgery plus radiation, 76.8 % (95 % CI, 75.5-78.1). Multivariate analysis revealed male sex, age > 65 (H.R. 2.659 (95 % CI,2.291-3.098), p < .001), grade III/IV (H.R.5.172 (95 % CI, 3.418-7.824), p < .001), nodal metastasis, distant metastasis (H.R. 2.400 (95 % CI, 2.178-2.645), p < .001), chemotherapy only, and combination therapy as negative prognostic factors, and receiving surgery plus radiation therapy (H.R.0.586 (95 % CI, 0.505-0.679), p < .001) as a positive prognostic factor. When limited just to the lungs, had much better survival than those patients with distant metastases to other sites such as the bones and liver (p < .001). CONCLUSION: This SEER study identifies grade, particularly III and IV, to be the strongest single predictor of worse survival. Patients did best when treated with surgery and postoperative radiotherapy. These results can inform future management of patients with this challenging cancer type.

Assessing the feasibility of a multimodal liquid biopsy for the diagnosis of HPV-associated oropharyngeal squamous cell carcinoma.

OBJECTIVES: In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue. RESULTS: Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67. CONCLUSIONS: Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation.

Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma.

Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.

Identification of Optimal Tissue-Marking Dye Color for Pathological Evaluation in Fluorescence Imaging Using IRDye800CW.

PURPOSE: Fluorescence-guided surgery using a tumor-specific antibody-dye conjugate is useful in various cancer types. Fluorescence imaging is a valuable tool both intraoperatively and postoperatively for ex vivo imaging. The color of inks used for tumor specimens during ex vivo specimen processing in pathology is an important consideration for fluorescence imaging since the absorption/emission of the dyes may interfere with the fluorescent dye. This study assesses suitable ink colors for use specifically with IRDye800CW fluorescence imaging. PROCEDURES: Eight tissue-marking inks or dyes (TMDs) commonly used for pathological evaluation were assessed. Agarose tissue-mimicking phantoms containing Panitumumab-IRDye800CW were used as an initial model. Mean fluorescence intensity was measured at 800 nm using both Pearl Trilogy as a closed-field fluorescence imaging system and pde-neo II as an open-field fluorescence imaging system before and after TMD application. An in vivo mouse xenograft model using the human head and neck squamous cell carcinoma FaDu cell line was then used in conjunction with TMDs. RESULTS: The retained IRDye800CW fluorescence on Pearl Trilogy was as follows: yellow at 91.0 ± 4.5%, red at 90.6 ± 2.7%, orange at 88.2 ± 2.2%, violet at 56.6 ± 1.1%, lime at 40.9 ± 1.8%, green at 19.3 ± 2.8%, black at 13.3 ± 0.6%, and blue at 8.1 ± 0.2%. The retained IRDye800CW fluorescence on pde-neo II was as follows: yellow at 86.5 ± 6.4%, red at 77.0 ± 6.2%, orange at 76.9 ± 2.8%, lime at 72.5 ± 9.5%, violet at 59.7 ± 0.4%, green at 30.1 ± 6.9%, black at 17.0 ± 2.7%, and blue at 6.7 ± 1.7%. The retained IRDye800CW fluorescence in yellow and blue TMDs was 42.1 ± 14.9% and 0.2 ± 0.2%, respectively in the mouse experiment (p = 0.039). CONCLUSION: Yellow, red, and orange TMDs should be used, and blue and black TMDs should be avoided for evaluating tumor specimens through fluorescence imaging using IRDye800CW.

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.