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Background: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. Objective: To demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. Methods: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. Results: Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. Conclusions: SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load and immune response.

Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Results: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27–0.90). Conclusions: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.

Pleomorphic adenoma (PA) is the most common benign parotid tumor, with a well-known propensity to recur. Many factors have been advocated as prognostic, but there is no consensus on how they affect local control. We studied how PA recurrence-free survival (RFS) may be affected by the most relevant risk factors in a time-to-event analysis, comparing them with those observed in a population of non-PA (NPA). Patients undergoing parotidectomy for benign lesions between 2002 and 2018 in a single academic tertiary referral center were included. A description of patients, tumors, and treatment characteristics was performed, highlighting differences between PA and NPA. Analysis of PA RFS and relative risk factors was also conducted. Eight hundred fifty patients underwent parotidectomy for benign lesions, 455 (53.5%) for PA and 57 (6.7%) for NPA. Significant differences between PA and NPA were age at surgery, surgical procedure, and resection margins. Recurrence occurred in 3.1% of PA, with a median disease-free interval of 54 months. 2-, 5-, and 10-year RFS were 99.2, 98.5, and 93.9%, respectively. Age

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Introduction: olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.Methods: we conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).Results: dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).Conclusions: this study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Adenoid cystic carcinoma (AdCC) is a rare disease, with indolent behavior and poor long-term survival. Many studies have evaluated the role of clinical and pathological factors at presentation on the risk of recurrence. In this study we investigated whether baseline demographic, clinical, and pathological characteristics at the time of primary curative treatment could influence the prognosis of patients once local and/or distant recurrence occurred.All patients affected by primary salivary gland AdCC and treated with curative surgery from January 1997 to June 2016 were reviewed, evaluating those who later developed loco-regional recurrence and/or distant metastasis. Time from the first relapse to death (recurrent/metastatic overall survival, RMOS) was considered the outcome of interest.Out of 87 surgically treated AdCC patients, 36 relapsing lesions were included. Median ages at first presentation and recurrence were 55 and 60-year-old, respectively; 58% were females. Median disease-free-interval (DFI) was 22.0 months. Five-year RMOS was 47%. At univariate analysis, age ≥ 60-year-old (HR:2.67, p = 0.030), primary tumor lympho-vascular invasion (LVI) (HR:5.38, p = 0.003), adjuvant radiotherapy (RT) in the primary setting (HR:0.37, p = 0.043), and DFI 30 months (HR:3.94, p = 0.008) significantly affected RMOS. Multivariable analysis confirmed the presence of LVI and shorter DFI as independent risk factors.Knowledge of baseline clinicopathological features is helpful in the prognostic stratification of patients with recurrent AdCC, with LVI as the most relevant baseline factor. Adjuvant RT demonstrated its protective role on survival even once recurrence occurred, further supporting its adoption in the primary setting.

Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8+ T-cells. To this end, CD8+ T-cells counts were combined with well-established clinical variables and peripheral blood immune cell parameters. Through variable clustering, five metavariables (MV) were obtained and included descriptors of nodal (NODALMV) and primary tumor (TUMORMV) involvement, the frequency of myeloid (MYELOIDMV) or lymphoid (LYMPHOIDMV) peripheral blood immune cell populations, and the density of tumor-infiltrating CD8+ T-cells (TI-CD8MV). The clinical relevance of the MV was evaluated in the multivariable survival models. The NODALMV was significantly associated with all tested outcomes (p &lt, 0.001), the LYMPHOIDMV showed a significant association with the overall, disease-specific and distant recurrence-free survival (p &lt, 0.05) and the MYELOIDMV with the locoregional control only (p &lt, 0.001). Finally, TI-CD8MV was associated with distant recurrence-free survival (p = 0.029). Notably, the performance in terms of survival prediction of the combined effect of NODALMV and immune metavariables (LYMPHOIDMV, MYELOIDMV and TI-CD8MV) was superior to the TNM stage for most of the outcomes analyzed. These findings indicate that the analysis of the baseline host immune features are promising tools to complement clinical features, in stratifying the risk of recurrences.

e21574 Background: From 25 to 50% of radically resected Merkel Cell Carcinomas (MCCs) develop local or distant recurrence with a 5 year Overall Survival (OS) of 35% and 13%, respectively. Due to the rarity of the disease, there are limited data about clinical/histological risk factors related to patients (pts) prognosis. Methods: We retrospectively evaluated a series of 57 MCCs pts treated with surgical curative intent at two Italian Centres from 2000 to 2020. For 43 of them, archival histological material was retrieved for further analysis. The following clinical and histological data were analyzed and related to time to relapse (TTR), OS and cancer specific survival (CSS): gender, age, Charlson Comorbidity Index value, immunodepression, surgical margins, re-excision and/or radiotherapy (RT) in case of positive margins, stage, perineural/lymphovascular infiltration, presence of inflammatory infiltrate (tumoral infiltrating lymphocyte (TILs) (> 1 positive cell per high-power field) and its composition CD3+, CD4+ T and CD8+ T cells), positivity for MCC-polyomavirus (MCCpV), Ki67 index and PDL1 expression CPS. Results: Pts were mainly female (52%), median age was 75 years (49-99), 70% were immunocompetent and 51% presented T1 stage. All pts received surgery as main treatment approach; in case of positive margins, pts received re-excision or RT, when feasible. During a median follow-up of 37 months (1- 188), 40% had a locoregional or distant recurrence. Median TTR of relapsed pts was 3 months (1-88); median OS and CSS in the whole population was 117 months (1-188) and not reached, respectively. At univariate analysis, only male gender was associated with a higher risk of relapse (HR 1.6; 1.07-2.55; p 0.02). Older age (HR 1.09; 1.04-1.14, p < 0.001), T stage ≥2 (HR 4.79, 1.99-11.53, p < 0.001) and positive margins after re-excision (HR 17.49, 1.09-279.74, p 0.043) were associated with shorter OS and negatively related to CSS. Re-excision and/or RT in cases of positive margins at diagnosis improved OS (HR 0.154, 95% CI 0.028-0.851, p = 0.032) and CSS (HR 0.15; 0.02-0.85, p 0.03). MCCpV positivity (HR 0.23, 0.08-0.62, p 0.004), TILs (HR 0.30, 0.11-0.80, p 0.017), a moderate or high content of CD3+ T cells (HR 0.33, 0.119-0.968, p 0.04), CD8+ T cells (HR 0.35, 0.12-0.99, p 0.04), and PDL1 CPS > 1 (HR 0.26, 0.08-0.82, p 0.02) resulted in longer OS. The impact of MCCpV positivity (HR 0.27; 0.08-0.88 p 0.03) and high TILs (HR 0.31, 0.09-0.99, p 0.04) was also confirmed for CSS. Conclusions: In primarily surgically treated MCCs, female gender, younger age, low T stage, positivity for MCCpV and tumoral immune cells infiltration were associated with better prognosis, as well as an aggressive management comprising re-excision and/or RT in case of positive margins.

Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic and clinical data. We perform gene expression profiling on primary ONB samples and carry out functional enrichment analysis to investigate the key pathways associated with disease-free survival (DFS). The median age is 53.5 years, all patients undergo surgery and a pure endoscopic approach is adopted in the majority of cases (81.2%). Most patients have advanced disease (stages III–IV, 81.2%) and 84.4% undergo adjuvant (chemo)radiotherapy. The median follow-up is 35 months, 11 (26.8%) patients relapse. Clinical characteristics (gender, stage and Hyams’ grade) are not associated with the outcomes. In contrast, TGF-beta binding, EMT, IFN-alpha response, angiogenesis, IL2-STAT5 and IL6-JAK-STAT3 signaling pathways are enriched in patients experiencing recurrence, and significantly associated with shorter DFS. Clustering of transcriptional profiles according to pathological features indicates two distinct molecular groups, defined by either cytokeratin-positive or -negative immunostaining. Definition of the characterizing ONB transcriptomic pathways may pave the way towards tailored treatment approaches.

Encroachment on the orbital cavity represents a challenge in the management of sinonasal cancer. Criteria guiding orbital preservation lack univocal consensus. Stage of orbital involvement is best assessed through magnetic resonance imaging (MRI).Patients affected by orbit-encroaching sinonasal cancer with available preoperative MRI, receiving surgery-based treatment at the University of Brescia between May 2005 and October 2018 were included. All cases were reviewed by expert radiologists and pathologists. Diagnostic performance of MRI was calculated using pathological information as reference. Survival analysis was performed.The study included 123 patients. The orbit was abutted in 53 (43.1%) patients, whereas orbital invasion reached the periorbit in 18 (14.6%), extraconal fat and/or medial lacrimal sac in 29 (23.6%), extrinsic ocular muscles in 7 (5.7%), intraconal compartment in 4 (3.3%), and orbital apex in 12 (9.8%). Seventy-six (61.8%) patients received orbit-sparing surgery, 47 (38.2%) underwent orbital ablation (OA). Accuracy of MRI in detecting involvement by cancer was ≥80.0% for the orbital wall, extraconal fat, and muscles, and80.0% for the periorbit and intraconal compartment. Previous surgery, neoadjuvant chemotherapy, and perineural invasion decreased MRI accuracy. Age, histology, tumor grade, pT category, N status, perineural invasion, orbital invasion stage, and need for OA were found to affect prognosis. Five-year orbital dysfunction-free survival was 92.8%.Conservative management of sinonasal cancers encroaching the orbit is feasible. MRI is essential to preoperatively stage orbital invasion, yet with some limitation. Given the dismal prognosis despite aggressive surgery, neoadjuvant non-surgical therapies should be considered in patients requiring OA.

Purpose To identify potential risk factors impacting on overall survival (OS) of patients affected by lymph node metastasis from cutaneous squamous cell carcinoma (cSCC) of the head and neck (HN), with special emphasis on primary tumor characteristics and pattern of nodal recurrence (intraparotid and/or cervical). Methods A bi-institutional retrospective study on consecutive patients affected by cervical and/or intraparotid NM from HN cSCC and surgically treated with curative intent from May 2010 to January 2020 was conducted. OS was considered the outcome of interest. Results The study included 89 patients (M:F = 3.4:1; median age, 78 years; range, 22–99). Among the primary tumor characteristics, the most relevant prognostic factors were diameter ≥ 4 cm (hazard ratio [HR] = 2.56, p = 0.010) and depth of infiltration ≥ 6 mm (HR = 3.54, p = 0.027). Cervical NM was associated with worse OS (HR = 2.09, p = 0.016) compared to purely intraparotid NM (5-year OS: 60.9% vs. 28.1%, p = 0.014). At multivariable analysis, age, immunosuppression, pT3-T4 categories and a high burden of nodal disease (> 2 NM) confirmed to be independent risk factors, whereas adjuvant radiotherapy was independently associated with better outcome. Conclusion This study confirms the association of several independent prognosticators related to the patient, primary tumor, and nodal burden status. Patients with cervical NM should be considered at risk for harboring a higher number of metastatic lymph nodes.

Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma.A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-RIntra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-RAll the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.

BACKGROUND AND PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in the period from the 1970s to 2004, due to increase of infection with human papilloma virus (HPV). This study aimed to examine the role of histogram analysis of the ADC in treatment response and survival prediction of patients with oropharyngeal squamous cell carcinoma and known human papillomavirus status. MATERIALS AND METHODS: This was a retrospective single-center study. Following inclusion and exclusion criteria, data for 59 patients affected by T2–T4 (according to the 8th edition of the AJCC Cancer Staging Manual) oropharyngeal squamous cell carcinoma were retrieved. Twenty-eight had human papillomavirus–positive oropharyngeal squamous cell carcinoma, while 31 had human papillomavirus–negative oropharyngeal squamous cell carcinoma. All patients underwent a pretreatment MR imaging. Histogram analysis of ADC maps obtained by DWI (b = 0–1000 mm/s(2)) was performed on the central section of all of tumors. The minimum follow-up period was 2 years. Histogram ADC parameters were associated with progression-free survival and overall survival. Univariable and multivariable Cox models were applied to the data; P values were corrected using the Benjamini-Hochberg method. RESULTS: At univariable analysis, both human papillomavirus status and mean ADC were associated with progression-free survival (hazard ratio = 0.267, P < .05, and hazard ratio = 1.0028, P ≤ .05, respectively), while only human papillomavirus status was associated with overall survival (hazard ratio = 0.213, P ≤ .05) before correction. At multivariable analysis, no parameter was included (in fact, human papillomavirus status lost significance after correction). If we separated the patients into 2 subgroups according to human papillomavirus status, ADC entropy was associated with overall survival in the human papillomavirus–negative group (hazard ratio = 4.846, P = .01). CONCLUSIONS: ADC and human papillomavirus status are related to progression-free survival in patients treated with chemoradiation for advanced oropharyngeal squamous cell carcinoma; however, this association seems to result from the strong association between ADC and human papillomavirus status.

Introduction Fine-needle aspiration cytology (FNAC) is a basic step in the diagnosis of salivary gland tumors that have a wide variety of histological types. The recent Milan system for reporting salivary gland cytopathology (MSRSGC) can correlate the risk of malignancy with precise cytological features. A revised version was recently proposed to improve the surgical relevance and facilitate uniform management. Material and methods A multicenter study retrospectively used the original and revised MSRSGC criteria to classify a series of patients who received surgery after FNAC. Results We enrolled 503 patients from three tertiary centers. The risk of malignancy for the MSRSGC resulted 19.5% in cat. I, 14.3% in cat. II, 17.6% in cat. III, 3.6% in cat. IVa, 24.6% in cat. IVb, 66.7% in cat. V, and 96.8% in cat. VI. The results from the revised MSRSGC were consistent with the original values. Conclusion The MSRSGC is a promising classification system. In our opinion, the revised version of the MSRSGC supplements FNAC with some crucial clinical information and can better identify the appropriate treatment in each category.

Carcinoma showing thymic-like differentiation (CASTLE) is a rare tumor most commonly occurring in the thyroid and soft tissues of the neck. We report the first case of CASTLE occurring in the sublingual gland. The patient, a 35-year-old healthy man, presented with a submucosal lesion located in the anterior right floor of the oral cavity and an ipsilateral neck mass. The lesion had been previously investigated by neck computed tomography and ultrasound-guided fine needle aspiration cytology and diagnosed as metastatic squamous cell carcinoma. After oral cavity magnetic resonance imaging, positron emission tomography, and a non-diriment, fine needle aspiration cytology of the sublingual mass, the patient was treated as affected by a sublingual gland malignancy with removal of primary tumor and neck dissection. Morphological and immunohistochemical findings were diagnostic for primary sublingual gland CASTLE. The patient received adjuvant radiotherapy and is free of disease 2 years after treatment. We describe the pathological features of the lesion and discuss the possible differential diagnoses.

BACKGROUND AND PURPOSE: The incidence of Oropharyngeal Squampus Cell Carcinoma (OPSCC) cases is increasing especially in the Western countries due to the spreading of human papilloma virus (HPV) infection. Radiological investigations, MRI in particular, are used in the daily clinical practice to stage OPSCC. The aim of this study was to investigate the association of quantitative MR imaging features including diffusion-weighted imaging and human papillomavirus status in oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: We retrospectively analyzed 59 patients with untreated histologically proved T2–T4 oropharyngeal squamous cell carcinoma. Human papillomavirus status was determined by viral DNA detection on tissue samples. MR imaging protocol included T2-weighted, contrast-enhanced T1-weighted (volumetric interpolated brain examination), and DWI sequences. Parametric maps of apparent diffusion coefficient were obtained from DWI sequences. Texture analysis was performed on T2 and volumetric-interpolated brain examination sequences and on ADC maps. Differences in quantitative MR imaging features between tumors positive and negative for human papillomavirus and among subgroups of patients stratified by smoking status were tested using the nonparametric Mann-Whitney U test; the false discovery rate was controlled using the Benjamini-Hochberg correction; and a predictive model for human papillomavirus status was built using multivariable logistic regression. RESULTS: Twenty-eight patients had human papillomavirus-positive oropharyngeal squamous cell carcinoma, while 31 patients had human papillomavirus-negative oropharyngeal squamous cell carcinoma. Tumors positive for human papillomavirus had a significantly lower mean ADC compared with those negative for it (median, 850.87 versus median, 1033.68; P < .001). Texture features had a lower discriminatory power for human papillomavirus status. Skewness on volumetric interpolated brain examination sequences was significantly higher in the subgroup of patients positive for human papillomavirus and smokers (P = .003). A predictive model based on smoking status and mean ADC yielded a sensitivity of 83.3% and specificity 92.6% in classifying human papillomavirus status. CONCLUSIONS: ADC is significantly lower in oropharyngeal squamous cell carcinoma positive for human papillomavirus compared with oropharyngeal squamous cell carcinoma negative for it. ADC and smoking status allowed noninvasive prediction of human papillomavirus status with a good accuracy. These results should be validated and further investigated on larger prospective studies.

Discrimination of the etiology of arytenoid fixation in cT3 laryngeal squamous cell carcinoma (SCC) is crucial for treatment planning. The aim of this retrospective study was to differentiate among possible causes of arytenoid fixation (edema, inflammation, mass effect, or tumor invasion) by analyzing related signal patterns of magnetic resonance (MR) in the posterior laryngeal compartment (PLC) and crico-arytenoid unit (CAU). Seventeen patients affected by cT3 glottic SCC with arytenoid fixation were preoperatively studied by state-of-the-art MR with surface coils. Different signal patterns were assessed in PLC subsites. Three MR signal patterns were identified: A, normal, B, T2 hyperintensity and absence of restriction on diffusion-weighted imaging (DWI), and C, intermediate T2 signal and restriction on DWI. Signal patterns were correlated with the presence or absence of CAU and PLC neoplastic invasion. Patients were submitted to open partial horizontal or total laryngectomy and surgical specimens were analyzed. Pattern A and B did not correlate with neoplastic invasion, while Pattern C strongly did (Spearman&rsquo, s coefficient = 0.779, p &lt, 0.0001, sensitivity: 100%, specificity: 78%). In conclusion, MR with surface coils is able to assess PLC/CAU involvement with satisfactory accuracy. In absence of Pattern C, arytenoid fixation is likely related to mass effect and/or inflammatory reaction and is not associated with neoplastic invasion.

Objectives: To investigate the prognostic significance of preoperative neutrophil to lymphocyte ratio (NLR) and the impact of different clinical-pathologic factors in a series of primary oral squamous cell carcinomas (OSCC). Materials and Methods: All naive OSCCs treated with upfront surgery between 2000 and 2014 were retrospectively reviewed. Patients with distant metastasis, synchronous head and neck cancer, immunological disorders, or who had received previous chemotherapy and/or radiation of the head and neck area were excluded. The main outcomes were overall (OS), disease-specific (DSS), loco-regional free (LRFS), and distant metastasis free (DMFS) survivals. Univariate (Kaplan-Meier) and multivariate (Cox regression model) analysis were performed, and nomograms developed for each outcome. NLR was analyzed as a continuous variable using restricted cubic spline multivariable Cox regression models. Results: One-hundred-eighty-two patients were included. Five-year estimates for LRFS, DMFS, DSS, and OS were 67, 83.7, 69.5, and 61.2%, respectively. NLR had a complex influence on survival and risk of recurrence: negative for very low and high values, while positive in case of intermediate ratios. At univariate analysis, T classification, 7th AJCC stage, nodal metastasis, perineural spread, and lymphovascular invasion were statistically significant. At multivariate analysis, extranodal extension (ENE) and perineural spread were the most powerful independent prognostic factors. NLR was an independent prognosticator for the risk of recurrence. In nomograms, NLR and ENE had the strongest prognostic effect. Conclusions: In OSCC, very low preoperative NLR values have a negative prognostic impact on survival and recurrence, similarly to high ratios. ENE and perineural spread are the most important clinical-pathologic prognosticators.

Primary cancer of the parotid gland (PG) is a rare disease characterized by a wide variety of histologies and subtypes. The aim of the study was to identify factors influencing survival and validate the prognostic scores (PS1 and PS2) by Vander Poorten et al. STUDY DESIGN: Retrospective cohort study.All patients with previously untreated PG epithelial malignancies who underwent surgery with curative intent from 2002 to 2015 at a single center were retrospectively reviewed.104 patients were included. Mean age was 60.2 years (range 14-88). Definitive pT staging was: 26 (25%) pT1, 19 (18.3%) pT2, 15 (14.4%) pT3, 41 (39.4%) pT4a, and 3 (2.9%) pT4b. Lateral neck nodal metastases were diagnosed in 27 (26%) patients. Five- and 10-year overall survival was 74.7% and 69.4%, respectively. Disease-specific survival at 5 and 10 years was 80.4% and 76.5%, respectively. Recurrence-free survival at 5 and 10 years was 66.9%. PS-1 and PS-2 scores correlated with prognosis. The most critical prognostic variables were grading, nodal metastases, perineural infiltration, lympho-vascular invasion, and skin infiltration.Major risk factors in primary PG carcinomas can effectively identify high-risk patients. The prognostic score by Vander Poorten et al. is a highly reliable tool to predict the prognostic profile.

OBJECTIVES/HYPOTHESIS Pretreatment biopsy is crucial in histology-based management of malignant nasoethmoidal tumors, because misdiagnosis can lead to inadequate therapeutic planning. Factors influencing the reliability of biopsy were retrospectively investigated in a tertiary referral center. STUDY DESIGN Retrospective case series. METHODS All patients who underwent biopsy, staging magnetic resonance, surgery, and histologic diagnosis for nasoethmoidal tumors in our hospital were retrospectively evaluated. Histologic discrepancy, histology, procedure for biopsy (biopsy under local anesthesia [OB], biopsy under local anesthesia and sedation [SB], or under general anesthesia [GB]), site of the lesion, and the biopsy volume were analyzed. Biopsy reliability rate (BRR) (preoperative biopsy confirmed after surgical treatment) and concordance rate (CR) (postoperative diagnosis identified in preoperative biopsy) were calculated. Univariate and multivariate statistical analyses were used to identify factors influencing histologic discrepancies. RESULTS Seventy-seven patients were included. Five (6.5%) minor and eight (10.4%) major histologic discrepancies were observed (16.9%). OB and SB showed significantly lower biopsy volumes than GB (P

Flow cytometric DNA analysis is an important prognostic tool in breast cancer. We evaluated the possibility of performing DNA analysis on cell suspensions obtained by scraping the cut surface of breast tumors; 31 breast tumor nodules, including six benign and 25 malignant lesions, were studied. From each case, cell suspensions acquired by mechanical mincing of a fresh frozen tissue fragment and by two different scrapings (central and peripheral) from the cut surface of the tumor were analyzed via flow cytometry. In all cases, comparison of the DNA histograms for three samples showed no significant differences in the appearance of debris or in the value of coefficient of variation of the G0-G1 peak. All benign nodules showed a normal DNA stemline in all specimens. In 23 of 25 cases of breast carcinoma, the ploidy of the three preparations was similar, with a concordance in 12/14 (85, 71%) cases in DNA nondiploid tumors. Linear regression analysis showed a good correlation in DNA index between either scraping sample and the tissue fragment (r = .955 and r = .905). The results indicate that the scraping technique provides excellent cell suspensions and DNA histograms comparable to those obtained from mechanical mincing of tissue fragments. The technique minimizes preparation time and avoids consuming much tissue and, thus, is the method of choice when very small cancers have to be analyzed.

Metastatic involvement of the larynx by distant malignancies is a rare event that can occur by hematogenous or lymphogenous spread through a retrograde or anterograde route. Only 143 cases of secondary laryngeal tumors have been reported in the literature. Metastases from cutaneous melanoma and renal carcinoma are the most common, whereas only sporadic cases stemming from lung and colon adenocarcinoma have been documented. The authors report a case of lung adenocarcinoma and two cases of colonic adenocarcinoma metastatic to the larynx and discuss the problems related to the pathogenesis, diagnosis, and management of secondary laryngeal neoplasms.

Carcinoma cuniculatum is a rare variant of squamous cell carcinoma. The clinical presentation is usually a non-verrucous exophytic plaque or tumor of the plantar region with a penetration in the deep tissues. Histological examination shows a proliferation of well-differentiated keratinocytes. We describe a patient affected by a slowly enlarging tumoral lesion overlying the fifth metatarsum of the left foot. Clinical examination and radiological investigations suggested a chronic osteomyelitis and a first histological examination of a punch biopsy was suggestive of a pseudo-epitheliomatous hyperplasia. The patient underwent several cycles with systemic antibiotics without improvement. Finally, the fifth metatarso was amputated and the skin lesion was completely removed. The histological examination of the whole operatory mass allowed a diagnosis of carcinoma cuniculatum invading the bone. Electronic supplementary material The online version of this article (doi:10.1007/s13555-015-0090-5) contains supplementary material, which is available to authorized users.

We report the case of a boy with low expression of HLA class I molecules on peripheral blood mononuclear cells, which is associated with immunodeficiency. The patient, who had a Marfan-like phenotype, had chronic deep skin ulcers and sinobronchiectasis. Immunohistologic examination of the ulcerated skin showed a dense perivascular infiltrate composed of normal mature lymphocytes and macrophages. All cells in the infiltrate showed an apparently normal expression of HLA class I molecules, but intraepidermal dendritic Langerhans' cells were negative for CD1a, an antigen that is a highly specific marker for these cells and is abundantly expressed in some self-healing forms of cutaneous lesions. It is therefore speculated that a defective expression of CD1a molecules can contribute to the chronic persistence of deep skin ulcers, which have already been reported in association with defective expression of HLA class I molecules.