Is Primary Poorly Differentiated Sarcomatoid Malignancy of the Parotid Gland Sarcomatoid Undifferentiated/Dedifferentiated Melanoma ? Report of three unusual cases diagnosed by fine needle aspiration combined with histological, immunohistochemical and molecular analyses.

INTRODUCTION: Poorly differentiated primary sarcomatoid parotid malignancies are extremely rare. These tumors have not been consistently studied by morphology, immunohistochemistry or molecular techniques. CASE PRESENTATION: We report three unusual cases of parotid gland poorly-differentiated sarcomatoid malignancy investigated by fine needle aspiration and studied histologically, by immunohistochemistry and molecular investigations. Aspirates showed poorly specific polymorphous sarcomatoid malignancy in all cases. Histologically, all cases were polymorphous high-grade malignancies, additionally one case showed epithelial structures and was finally classified as salivary carcinosarcoma. Immunohistochemistry showed classical melanocytic markers negativity but positivity for PRAME, CD10, WT1 in all three tumors and for CD56 in two tumors, which can potentially be supportive of melanocytic origin. Although not entirely specific, molecular characterization also suggested the melanocytic lineage of these tumors. CONCLUSION: Although rare, primary malignant melanoma of salivary gland was already described, but undifferentiated/dedifferentiated amelanotic forms are unknown in this localization up today. Further case reports of similar presentations are required to confirm the unequivocal primary origin of these obscure neoplasms in the parotid gland.

Carcinomas of the external auditory canal: Management and results: A multicenter REFCOR propensity score matching study.

OBJECTIVES: To analyse prognostic factors and survival outcomes of malignant tumors of the external auditory canal, to investigate the role of regional surgery, and adjuvant radiotherapy in early stages and to investigate the role of surgery in operable T4 stage. SETTING: A retrospective analysis was conducted on all patients prospectively included in the national database of the French Expertize Network for Rare ENT Cancers (REFCOR) from January 2000 to December 2016. PARTICIPANTS: 103 patients from 19 reference centers were included. A propensity score matching analysis was applied to enable comparisons between treatments. MAIN OUTCOMES AND MEASURES: Event-free survival, overall survival and factors of poor prognosis of the cohort were described. The interest of local and regional surgery and postoperative radiotherapy were evaluated. RESULTS: The factors of poor prognosis on event-free survival were immunosuppression (p = 0.002), Karnofsky status less than 90% (p = 0.02), body mass index less than 19 Kg / m2 (p = 0.0009), peripheric facial palsy (p = 0.0016), and positive margin (p = 0.0006). In early stages, locoregional surgery was associated with an increase in event-free survival (p = 0.003, HR = 0.21) versus local surgery alone, while postoperative radiotherapy was not associated with an increase in event-free survival (p = 0.86, HR = 0.91) or overall (p = 0.86, HR = 0.91). In locally advanced stages, locoregional surgery followed by radiotherapy was associated with an increase in event-free survival (p = 0.03, HR = 0.39) and overall (p = 0.02, HR = 0.34) versus chemoradiotherapy alone. CONCLUSION AND RELEVANCE: Regional surgery is recommended for early stages of cancers of the external auditory canal. In operable cases, locoregional surgery followed by radiotherapy is recommended.

Fine needle aspiration as a diagnostic modality for Warthin tumors identified as fluorodeoxyglucose positron emission tomography/computed tomography-positive.

Limited evidence exists regarding the 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (FDG) avidity of Warthin tumors, the second most common benign parotid gland tumor. This study aims to clarify this aspect by analyzing patients who underwent FDG positron emission tomography/computed tomography (PET/CT) and quantifying tumor standardized uptake values (SUV). Medical records of 29 patients with fine needle aspiration (FNA)-confirmed Warthin tumors who underwent FDG-PET/CT near the diagnosis of Warthin tumor were reviewed. Key parameters included cancer history, cytologic diagnosis of Warthin tumor, maximum SUV on FDG PET/CT, and tumor localization. Among the cohort, 18 males and 11 females (average age: 67.9 years) were included. Most patients had malignant neoplasms (lung, head and neck, breast, others). One patient had synchronous liver cancer. Three individuals had bilateral Warthin tumors, and three had bifocal tumors, resulting in 35 tumors for analysis. Tumors were located in the parotid gland (28) and vicinity (7). SUVmax for the Warthin tumors ranged from 3.6 to 26.8, with an average SUVmax of 10.1. Warthin tumors exhibit significant and variable FDG accumulation, exceeding expectations and mimicking high-grade malignancies. Awareness of this phenomenon is crucial for accurate staging and timely management. In cases of positive FDG PET/CT uptake in periparotid, perimandibular, and upper jugular areas, FNA is recommended to avoid misinterpretation or delays in management.

Safety and reliability of the internal jugular vein for venous anastomoses in head and neck oncological reconstruction: A retrospective study.

This study aimed to assess the efficacy of utilizing the internal jugular vein (IJV) as the primary recipient site for venous anastomoses in head and neck oncological reconstruction. Patients who underwent a free flap reconstruction of the head and neck were retrospectively included. Venous anastomoses were preferentially performed less than 1 cm from the IJV, either end-to-side (EtS) on the IJV, or end-to-end (EtE) on the origin of the thyrolingofacial venous (TLF) trunk. When the pedicle length was insufficient to reach the IJV, anastomoses were performed EtE to a size-matched cervical vein. Of the 246 venous anastomoses, 216 (87.8%) were performed less than 1 cm from the IJV, including 150 EtS on the IJV (61.0%), and 66 EtE on the TLF trunk (26.8%). Thirty veins (12.1%) were anastomosed EtE on other cervical veins more than 1 cm from the IJV. Two venous thromboses occurred (0.9%) and were successfully managed after revision surgery. There was no evidence of an increased thrombosis rate in high-risk or pre-irradiated patients. These findings suggest that the internal jugular vein is safe and reliable as a first-choice recipient vessel for free flap transfers in head and neck oncological reconstruction.

A Rare Cause of SCC Antigen Elevation: Inverted Sinonasal Papilloma.

ABSTRACT: We report the case of a 68-year-old woman who underwent 18F-FDG PET/CT for squamous cell carcinoma antigen (SCC Ag) elevation in the follow-up of a uterine cervical cancer. The examination showed an FDG-avid mass of the left nasal cavity with left maxillary sinusitis and no other site of abnormal FDG uptake. Surgical resection of the nasal polyp was performed, and pathological examination of the specimen revealed an inverted sinonasal papilloma. SCC Ag returned to normal after surgery. Inverted sinonasal papilloma is a rare cause of SCC Ag elevation, which can be depicted by 18F-FDG PET/CT.

Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients.

Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.

MMP2 as an independent prognostic stratifier in oral cavity cancers.

Background: Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to determine a robust biomarker for severe OCSCC, using a biology-driven strategy. Patients and methods: Tumor and juxtatumor secretome were analyzed in a prospective discovery cohort of 37 OCSCC treated by primary surgery. Independent biomarker validation was performed by RTqPCR in a retrospective cohort of 145 patients with similar clinical features. An 18-gene signature (18 G) predictive of the response to PD-1 blockade was evaluated in the same cohort. Results: Among 29 deregulated molecules identified in a secretome analysis, including chemokines, cytokines, growth factors, and molecules related to tumor growth and tissue remodeling, only soluble MMP2 was a prognostic biomarker. In our validation cohort, high levels of MMP2 and CD276, and low levels of CXCL10 and STAT1 mRNA were associated with poor prognosis in univariate analysis (Kaplan-Meier). MMP2 (p = .001) and extra-nodal extension (ENE) (p = .006) were independent biomarkers of disease-specific survival (DSS) in multivariate analysis and defined prognostic groups with 5-year DSS ranging from 36% (MMP2highENE+) to 88% (MMP2lowENE-). The expression of 18 G was similar in the different prognostic groups, suggesting comparable responsiveness to anti-PD-1. Conclusion: High levels of MMP2 were an independent and validated prognostic biomarker, surpassing other molecules of a large panel of the tumor and immune-related processes, which may be used to select poor prognosis patients for intensified neoadjuvant or adjuvant regimens.

Biomarkers of cetuximab resistance in patients with head and neck squamous cell carcinoma.

Objective: In patients with head and neck squamous cell carcinoma (HNSCC), cetuximab [a monoclonal antibody targeting epidermal growth factor receptor (EGFR)] has been shown to improve overall survival when combined with radiotherapy in the locally advanced setting or with chemotherapy in first-line recurrent and/or metastatic (R/M) setting, respectively. While biomarkers of resistance to cetuximab have been identified in metastatic colorectal cancer, no biomarkers of efficacy have been identified in HNSCC. Here, we aimed to identify biomarkers of cetuximab sensitivity/resistance in HNSCC. Methods: HNSCC patients treated with cetuximab at the Curie Institute, for whom complete clinicopathological data and formalin-fixed paraffin-embedded (FFPE) tumor tissue collected before cetuximab treatment were available, were included. Immunohistochemistry analyses of PTEN and EGFR were performed to assess protein expression levels. PIK3CA and H/N/KRAS mutations were analyzed using high-resolution melting (HRM) and Sanger sequencing. We evaluated the predictive value of these alterations in terms of progression-free survival (PFS). Results: Hot spot activating PIK3CA and KRAS/HRAS mutations were associated with poor PFS among HNSCC patients treated with cetuximab in the first-line R/M setting, but not among HNSCC patients treated with cetuximab in combination with radiotherapy. Loss of PTEN protein expression had a negative predictive value among HNSCC patients treated with cetuximab and radiotherapy. High EGFR expression did not predict cetuximab sensitivity in our patient population. Conclusions: Hot spot activating PIK3CA and RAS mutations predicted cetuximab resistance among HNSCC patients in the first-line R/M setting, whereas loss of PTEN protein expression predicted resistance to cetuximab when combined to radiotherapy.

Should a neck dissection be performed on patients with cN0 adenoid cystic carcinoma? A REFCOR propensity score matching study.

BACKGROUND: Patterns of nodal involvement in adenoid cystic carcinoma (ACC) of the head and neck have not been sufficiently assessed to guide a decision of prophylactic neck dissection (ND). The objective of this study is to analyse the influence of ND on event-free survival (EFS) for patients with cN0 ACC. PATIENTS AND METHODS: A multicentre prospective study was conducted between 2009 and 2018. Patients presenting cN0 non-metastatic ACC on any site, and who received surgery on the tumour, were included. EFS was the main judgement criterion. A comparative survival analysis between the groups that received a ND versus those that did not was performed, using a propensity score. Analyses were carried out using the R software. RESULTS: Between 2009 and 2018, 322 patients with cN0 ACC were included, out of which 58% were female. The average age was 53 years. Tumours were in minor salivary glands in 58% of cases, and 52% had T3/T4 stages. ND was performed on 46% of patients. Out of them, seven had histological lymph node invasion, out of which six had tumour infiltration in the mucosa of oral cavity. After propensity score, the median EFS for N0 patients with ND was 72 months (95% Confidence Interval (CI) [48-81]), compared to 73 months (95% CI [52-85]) for patients without ND (HR = 1.33; 95% CI [0.82-2.16]; p = 0.2). CONCLUSION: ND of cN0 patients does not provide any benefit on EFS, which suggests that its application on such patients is not necessary.

Immune gene expression in head and neck squamous cell carcinoma patients.

BACKGROUND: Nivolumab and pembrolizumab targeting programmed cell death protein 1 (PD-1) have recently been approved among patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who failed platinum therapy. We aimed to evaluate the prognostic value of selected immune gene expression in HNSCC. PATIENTS AND METHODS: We retrospectively assessed the expression of 46 immune-related genes and immune-cell subpopulation genes including immune checkpoints by real-time polymerase chain reaction among 96 patients with HNSCC who underwent primary surgery at Institut Curie between 1990 and 2006. Univariate and multivariate analyses were performed to assess the prognostic value of dysregulated genes. RESULTS: The Median age of the population was 56 years [range: 35-78]. Primary tumour location was oral cavity (45%), oropharynx (21%), larynx (18%) and hypopharynx (17%). Twelve patients (13%) had an oropharyngeal human papillomavirus-positive tumour. Most significantly overexpressed immune-related genes were TNFRSF9/4-1BB (77%), IDO1 (75%), TNFSF4/OX40L (74%) and TNFRSF18/GITR (74%), and immune-cell subpopulation gene was FOXP3 (62%). Eighty-five percent of tumours analysed overexpressed actionable immunity genes, including PD-1/PD-L1, TIGIT, OX40/OX40L and/or CTLA4. Among the immune-related genes, high OX40L mRNA level (p = 0.0009) and low PD-1 mRNA level (p = 0.004) were associated with the highest risk of recurrence. Among the immune-cell subpopulation genes, patients with high PDGFRB mRNA level (p < 0.0001) and low CD3E (p = 0.0009) or CD8A mRNA levels (p = 0.004) were also at the highest risk of recurrence. CONCLUSIONS: OX40L and PDGFRB overexpression was associated with poor outcomes, whereas PD-1 overexpression was associated with good prognosis in patients with HNSCC treated with primary surgery, suggesting their relevance as potential prognostic biomarkers and major therapeutic targets.

Acellular fish skin matrix on thin-skin graft donor sites: a preliminary study.

OBJECTIVE: Surgery for head and neck cancer often requires free flap reconstructions, whose harvesting site often requires a thin-skin graft. Wounds from the thin-skin donor site are comparable to an intermediate or deep second-degree burn. This is uncomfortable and can lead to complications such as a long healing time, local infections and pain. Since they are reproducible, these wounds may serve as a model for an objective assessment of new healing medical devices. The acellular fish skin matrix is a new medical device designed to improve healing quality and time. METHODS: We compared the outcomes between standard procedure and the use of this matrix placed on the split-thickness skin graft (STSG) donor site, in patients operated on in our centre for radial forearm free flap reconstruction for head and neck wounds. RESULTS: There were 21 patients included. The healing time was halved when using the acellular fish skin matrix, from 68 to 32 days on average. Acellular fish skin matrix reduced pain levels and local infection. The visual analogue pain scale (VAS) was ≥3 at five days (p=0.0034) and infection rate reduced from 60% to 0% (p=0.0039). CONCLUSION: These results are extremely encouraging. However, it is important to take into account the relatively high cost of this matrix for its future indications. A larger study including an overall cost estimation and an assessment on different wound types would be interesting, to better target the indications of the acellular fish skin matrix.

Intraocular metastasis of medullary thyroid carcinoma investigated by transscleral fine-needle aspiration. A case report and review of the literature.

Medullary thyroid carcinoma occurs in a sporadic setting and may also be inherited in an autosomal dominant fashion, which is related with germline mutations of the RET gene. Metastases are often present at the time of a diagnosis-most frequently within the cervical lymph nodes, followed by the liver, lungs, and bones. Intraocular metastases are extremely rare. We present a case of choroidal metastasis as a first presentation of disease progression in a patient with Multiple Endocrine Neoplasia type 2A syndrome (MEN2A) who had undergone thyroidectomy 33 years earlier for medullary thyroid carcinoma. Transscleral aspirate smears showed necrotic malignant cells suggesting amelanotic malignant melanoma or metastatic neuroendocrine tumor. The similar cells were found on parotid fine-needle aspiration. The diagnosis of metastatic medullary thyroid carcinoma was definitely established on the parotidectomy specimen based on its characteristic morphological and immunohistochemical features. This is the only case of ocular metastasis from medullary thyroid carcinoma found in the English literature that was investigated by pathological examination using transscleral fine-needle aspiration biopsy.

Long-term quality of life and psycho-social outcomes after oropharyngeal cancer surgery and radial forearm free-flap reconstruction: A GETTEC prospective multicentric study.

OBJECTIVE: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction. METHODS: Patients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis. RESULTS: A total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score ≥ 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores. CONCLUSIONS: Psychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.

Cytological investigation of a first case of basal cell adenocarcinoma arising in the minor salivary glands. Case report and review of the literature.

Basal cell adenocarcinoma (BCAC) of salivary glands is uncommon low-grade malignancy. Only 19 cases of preoperative cytology were reported up to date. We present here a new case of BCAC arising in the minor salivary gland. Tumor was composed of clustered or isolated roundish, dark cells with small and regular nuclei. Chromatin was dusty with small nucleoli. Cytoplasm was gray and scant. Clusters showed typical and characteristic basal architecture with peripheral palisading neighboring eosinophilic basal membranes. A false-negative diagnosis of basal cell adenoma was rendered. In our knowledge it is the first cytological description of BCAC arising in the minor salivary gland.

Fascia Temporalis Free Flap for Cricotracheal Reconstruction: A Novel Approach.

BACKGROUND: The aim of tracheal reconstruction is to provide an airtight and noncollapsible airway covered with a suitable epithelial lining. To date, no ideal treatment is available for large tracheal defects. METHODS: We report 4 patients who underwent one-stage reconstruction for a cricotracheal stenosis with a free temporoparietal fascia flap and costal cartilage grafts. RESULTS: Closure of tracheostoma was achieved for all patients. The main advantage of this flap compared with the free radial forearm flap is that it supplies a more suitable lining allowing the reepithelialization process with respiratory epithelium. CONCLUSIONS: This one-stage procedure provides a reliable construct to substitute for large tracheal defects, even in areas previously exposed to an operation or radiotherapy.

Idiopathic bilateral vocal cord paralysis in infants: Case series and literature review.

OBJECTIVES/HYPOTHESIS: Vocal fold paralysis is the second most common congenital laryngeal anomaly in newborns. Bilateral paralysis is a severe condition and often remains of unknown etiology. We report our experience of congenital idiopathic bilateral vocal fold paralysis in newborns and infants, and discuss the therapeutic options. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was carried out at a single tertiary referral center over a 15-year period of children presenting with congenital idiopathic bilateral laryngeal paralysis (CIBP). RESULTS: Twenty-six patients were identified and managed over period of the study (mean follow-up, 6.7 years). A tracheostomy was eventually performed in 14 patients, 12 during the neonatal period. Endoscopic treatment was performed in 16 patients and an external approach in five patients after endoscopic failure. Three patients were managed by watchful waiting. Spontaneous recovery occurred in 16 patients (median age, 14.5 months), including nine with a tracheostomy. Decannulation was achieved in 12 patients (median age, 42 months), and noninvasive positive pressure ventilation (NPPV) was applied in six patients. CONCLUSIONS: Only inhomogeneous series of pediatric bilateral laryngeal palsies have been published so far, making it difficult to identify prognostic and predictive markers, as well as therapeutic guidelines. Focusing on CIBP, our data suggest that the management strategy must take into account the possibility of a delayed spontaneous recovery. NPPV is an interesting therapeutic tool in this situation. A systematic somatic assessment is mandatory to look for associated conditions.