Secretory carcinoma of the salivary gland, a rare entity: An international multi-institutional study.

BACKGROUND: Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases. METHODS: FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles. RESULTS: In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1). CONCLUSIONS: Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.

Prevalence of HPV Infection and p16INK4a Overexpression in Surgically Treated Laryngeal Squamous Cell Carcinoma.

Background: The mucosal high-risk (HR) human papillomavirus (HPV) is associated with oropharyngeal carcinogenesis. Aims of this study were to evaluate the prevalence of HR-HPV infection in laryngeal squamous cell carcinoma (LSCC) from different subsites, and the clinico-biological meaning of p16 overexpression. Methods: Ninety-seven LSCCs submitted to primary surgery (n = 75) or to post-irradiation salvage laryngectomy (n = 22) were evaluated for HR-HPV DNA and RNA using Luminex-based assays. p16 immunohistochemistry was performed. Results: HR-HPV DNA from HPV16 was detected in seven cases (8.75%), without significant differences between supraglottic and glottic lesions. HPV RNA was never detected. p16 overexpression correlated with HR-HPV DNA, but the kappa agreement score was poor. HPV DNA showed no impact on prognosis. p16 overexpression was associated with a better survival (OS, RFS) in primarily operated cases, while an inverse association with OS was observed in the salvage surgery group. Conclusions: HR-HPV infection appears to have a marginal role in LSCC independent of the anatomical subsite. p16 expression is deregulated in LSCC independent of HPV but displays a prognostic role in patients submitted to primary surgery. The negative predictive role of p16 overexpression in patients undergoing salvage surgery deserves more investigations for validation and elucidation of its clinical relevance.

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

Adenocarcinoma NOS arising from accessory lacrimal glands: A case report and a review of the literature.

Primary malignant epithelial tumours arising from accessory lacrimal glands (ALGs) are extremely rare, with only few cases reported in literature. They generally appear as gradually increasing masses of the upper or the lower eyelid. Only one case of primary adenocarcinoma or adenocarcinoma not otherwise specified (ACNOS) from ALGs has been reported in literature. Herein, we describe a case of ACNOS arising from ALGs with an atypical clinical presentation and review prior cases of ALGs epithelial malignancies reported in the literature. A 78-year-old man referred to our Ocular Oncology Unit for adjuvant therapy after the excision of a conjunctival tumour of the left eye with a histological diagnosis of squamous cell carcinoma. He underwent topical chemotherapy with MMC and during follow up he presented a multinodular iris mass in his left eye. The MRI of the orbit showed an ocular mass infiltrating orbital soft tissues of the inferior palpebral region with an involvement of the corresponding zygomatic cutis. We performed orbital exenteration and histological studies revealed an epithelial neoplasm with a solido-glandular growth pattern with lumens containing an eosinophilic material positive for PAS and PAS-D. The immunohistochemical findings confirmed the diagnosis of adenocarcinoma NOS from ALGs. Although ALGs epithelial malignancies are extremely uncommon, they should be considered in the differential diagnosis of ocular tumours. A vigilant approach towards these entities is required, since they can be clinically insidious and locally aggressive.

Successful Treatment of Tumor-Induced Osteomalacia by Multidisciplinary Therapy with Radiation to Intracranial Fibromyxoid Tumor.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by protein fibroblast-growth-factor-23 (FGF-23) secreting tumors. Complete tumor resection is the current standard of care for TIO; however, some patients may develop tumor recurrence. Due to the rarity of this paraneoplastic syndrome, the role of radiotherapy is unclear. This case is worth reporting because it adds to our knowledge some insights about the potential role of radiotherapy in this rare condition. Case Presentation. After multidisciplinary consultation, in July 2015, postoperative adjuvant radiotherapy was offered to a 52-year-old man with a multiple recurrent ossifying fibromyxoid tumor in the right frontal sinus causing TIO. The patient had a history of multiple bone fractures and pain since more than 20 years. The tumor had been removed in 2003 for the first time. Subsequent endoscopic resections of the tumor had been performed for recurrences of TIO in May 2012, October 2013, and July 2015. Starting from October 2015, external beam radiotherapy was delivered with a volumetric modulated arc technique to the tumor bed with a daily dose of 2 Gy up to a total dose of 60 Gy. After five years from treatment, the patient is free from local tumor relapse, TIO progression, and radiation-induced side effects. CONCLUSIONS: Radiotherapy may provide long-term TIO remission and tumor control, thus being a treatment option in cases where surgery is unfeasible or unsuccessful.

miR-9 modulates and predicts the response to radiotherapy and EGFR inhibition in HNSCC.

Radiotherapy (RT) plus the anti-EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR-9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT-induced cell death. Mechanistically, by targeting KLF5, miR-9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo. Intriguingly, high miR-9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR-9 expression correlated with Sp1 mRNA levels and high miR-9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR-9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy.

Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades.

Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.

Utility of ultrasound-guided fine needle aspiration cytology in assessing malignancy in head and neck pathology.

OBJECTIVE: Fine needle aspiration cytology (FNAC) is a well-established diagnostic procedure for head and neck masses not clearly originating from mucosal or cutaneous surfaces. We analysed head and neck masses evaluated over a 2-year period, to assess the reliability of FNAC for the evaluation of malignancy. METHODS: We enrolled all patients undergoing FNAC, from April 2013 to July 2015, in a single service of a large Italian university hospital. Relevant clinical data and ultrasonographic parameters of the lesions were recorded. We performed both conventional and thin-prep smears. Clinical presentation, ultrasonographic features and final cytology diagnoses were analysed and correlated with histology. RESULTS: The series included 301 lesions in 285 patients, with a single (94.4%) or two (5.6%) lesions. Only eight samples were considered non-diagnostic/inadequate (2.6%). Among the cases, 139 FNAC (46.1%) underwent surgery. Cytological-histological correspondence was found in 89% of the cases. Concerning malignancy, we documented less than 4% false positives and less than 2.5% false negatives, with 92.7% sensitivity and 94.6% specificity. CONCLUSION: FNAC diagnosis can be highly specific. Most importantly, it is highly reliable in assessing malignancy, thus defining the priority and guiding the management procedures.

Risk factors for pancreas and lung neuroendocrine neoplasms: a case-control study.

PURPOSE: Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN. METHODS: We conducted a case-control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information. RESULTS: Increased risk was associated with history of cancer ("other tumor", lung OR = 7.18; 95% CI: 2.55-20.20 and pancreas OR = 5.88; 95% CI: 2.43-14.22; "family history of tumor", lung OR = 2.66; 95% CI: 1.53-4.64 and pancreas OR = 1.94; 95% CI: 1.19-3.17; "family history of lung tumor", lung OR = 2.56; 95% CI: 1.05-6.24 and pancreas OR = 2.60; 95% CI: 1.13-5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15-7.89). CONCLUSIONS: Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition.

Vertical restrictive strabismus associated with proptosis: Similar clinical signs, different etiopathogenetic causes. A report of three patients.

PURPOSE: To report the different uncommon pathogenesis of three cases of severe vertical restrictive strabismus associated with progressive unilateral proptosis with similar clinical features. METHODS: Case series of three patients who presented to the Orbit Outpatient Service of Policlinico Gemelli with a history of left progressive unilateral proptosis, slowly worsening vertical strabismus and the left eye fixed in downward position. A thorough hematologic work up was performed. All patients underwent complete abdomen ultrasonography, orbital contrast enhanced magnetic resonance imaging, forced duction test under general anesthesia, and orbital biopsy. RESULTS: Patients were 30, 60, and 46 years old respectively. MRI showed left inferior rectus enlargement in two cases and superior rectus enlargement in one case, with contrast enhanced combined muscle belly and tendon enlargement in all cases. Patients underwent forced duction test, muscle weakening (in two cases), and muscle biopsy with histopathologic examination. The superior rectus appeared infiltrated by an undifferentiated high-grade pleomorphic sarcoma, whereas the two inferior recti were positive for idiopathic orbital inflammatory disease with fibrosis areas and neuromuscular choristoma, respectively. CONCLUSION: Although proptosis and acquired vertical restrictive strabismus are most commonly associated with thyroid associated orbitopathy (TAO), they can also be a manifestation of many other conditions and the differential diagnosis can be particularly challenging. The three reported cases presented indeed with similar clinical features but had three distinct underlying orbital etiologies, two of which were extremely uncommon.

Immunological Backbone of Uveal Melanoma: Is There a Rationale for Immunotherapy?

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease.

Pembrolizumab as first-line treatment for metastatic uveal melanoma.

BACKGROUND: No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease. PATIENTS AND METHODS: In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed. RESULTS: Seventeen patients were enrolled. A median of 8 cycles were administered (range 2-28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869-0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3-4 side effects. CONCLUSIONS: The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.

The New World Health Organization Classification for Pancreatic Neuroendocrine Neoplasia.

Based on the 2010 version, the 2017 World Health Organization (WHO 2017) classification is for pancreatic neuroendocrine neoplasms (PanNEN). The WHO 2017 classification introduces the novel well-differentiated neuroendocrine tumor of high grade (NET G3). A sharp distinction between NET and poorly differentiated neuroendocrine carcinoma (NEC) is emphasized to highlight substantial biological differences. Further changes comprise the definition of mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN), to accommodate all grades of both neoplasm components, and the abolition of preneoplastic lesions given their rarity in the pancreas. The 2017 American Joint Cancer Committee classification (AJCC 2017) adopts such a classification for all digestive sites.

Orbital Desmoid-Type Fibromatosis: A Case Report and Literature Review.

PURPOSE: Desmoid-type fibromatosis is a benign fibrous neoplasia originating from connective tissue, fascial planes, and musculoaponeurotic structures of the muscles. Currently, there is no evidence-based treatment approach available for desmoid fibromatosis. In this article, a case of a patient in the pediatric age affected by desmoid fibromatosis localized in the orbit is presented. The aim of the article is to describe this unusual and rare location for the desmoid fibromatosis and outline the principle phases in the decision-making process and the therapeutic alternatives for a patient affected by desmoid fibromatosis. METHODS: The protocol of this review included study objectives, search strategy, and selection criteria. The primary end point of this study was to analyze the head and neck desmoid fibromatosis. The secondary end point was to identify the available therapies and assess their specific indications. RESULTS: The mean age of patients was 18.9 years ranging from 0 to 66, and 52% were female. A bimodal age distribution was observed, and two age peaks were identified: 0-14 years (57%) and 28-42 years (18%). The most common involved areas were the mandible (25%) followed by the neck (21%). In 86% of the cases, the treatment was the surgical resection of the disease, and only in 5% of the cases, the surgical resection was followed by adjuvant radiotherapy. CONCLUSION: The orbital location is extremely rare, especially in the pediatric population. The management of desmoid fibromatosis is based on the function preservation and the maintenance of a good quality of life, but in case of symptomatic patients or aggressive course of the disease or risk of functional damages, the surgical approach may be considered. Therapeutic alternatives to surgical resection are radiotherapy and systemic therapy.

Cyto-histology in NET: what is necessary today and what is the future?

The carcinoid as originally described is part of the relatively large family of neuroendocrine neoplasia found in almost every organ. Historical reasons back their current definitions. Neuroendocrine cancer is most frequently observed in the lung and the digestive tract. In the lung is defined as carcinoid (typical and atypical) for well differentiated, low to intermediate grade, and small cell and large cell neuroendocrine carcinoma for poorly differentiated, high grade. In the digestive system are respectively defined as neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) of small and large cell types. Grading and staging are developed for their clinical classification by the World Health Organization (WHO) and the American Joint Committee on Cancer (AJCC). In both anatomical sites the morphological features are overlapping, with bland histology for carcinoid and NET, and aggressive features with extensive necrosis, severe atypia and abundant, atypical mitoses for high grade cancer types. Such features are also essential diagnostic clues in cytological preparations. The confirmation of the neuroendocrine signature by immunohistochemistry is mandatory for the diagnosis; a minimum panel comprising chromogranin A and synaptophysin is recommended in the digestive system. In addition, the application of grading requires the mitotic count and or spotty necrosis assessment for lung, or the mitotic count and the Ki67 assessment in the digestive system.

Ultrasound Molecular Imaging With BR55 in Patients With Breast and Ovarian Lesions: First-in-Human Results.

Purpose We performed a first-in-human clinical trial on ultrasound molecular imaging (USMI) in patients with breast and ovarian lesions using a clinical-grade contrast agent (kinase insert domain receptor [KDR] -targeted contrast microbubble [MBKDR]) that is targeted at the KDR, one of the key regulators of neoangiogenesis in cancer. The aim of this study was to assess whether USMI using MBKDR is safe and allows assessment of KDR expression using immunohistochemistry (IHC) as the gold standard. Methods Twenty-four women (age 48 to 79 years) with focal ovarian lesions and 21 women (age 34 to 66 years) with focal breast lesions were injected intravenously with MBKDR (0.03 to 0.08 mL/kg of body weight), and USMI of the lesions was performed starting 5 minutes after injection up to 29 minutes. Blood pressure, ECG, oxygen levels, heart rate, CBC, and metabolic panel were obtained before and after MBKDR administration. Persistent focal MBKDR binding on USMI was assessed. Patients underwent surgical resection of the target lesions, and tissues were stained for CD31 and KDR by IHC. Results USMI with MBKDR was well tolerated by all patients without safety concerns. Among the 40 patients included in the analysis, KDR expression on IHC matched well with imaging signal on USMI in 93% of breast and 85% of ovarian malignant lesions. Strong KDR-targeted USMI signal was present in 77% of malignant ovarian lesions, with no targeted signal seen in 78% of benign ovarian lesions. Similarly, strong targeted signal was seen in 93% of malignant breast lesions with no targeted signal present in 67% of benign breast lesions. Conclusion USMI with MBKDR is clinically feasible and safe, and KDR-targeted USMI signal matches well with KDR expression on IHC. This study lays the foundation for a new field of clinical USMI in cancer.

Cavernous venous malformation (cavernous hemangioma) of the orbit: Current concepts and a review of the literature.

The cavernous venous malformation of the orbit, previously called cavernous hemangioma, is the most common primary orbital lesion of adults. Cavernous venous malformation occurs more often in women and typically presents in the fourth and fifth decades of life. It is a benign vascular malformation characterized by a well-defined capsule and numerous large vascular channels. The most common sign of cavernous venous malformation is progressive axial proptosis from the preferential involvement of the intraconal orbital space. Optic nerve damage and other signs of orbital pathology may be present, with a variable degree of visual impairment. The combination of ultrasound, computed tomography, and magnetic resonance imaging leads to an accurate diagnosis in the vast majority of cases. Surgical and nonsurgical treatments are required in case of symptomatic lesions, with a characteristic multidisciplinary management influencing optimal outcome. Orbitotomy represents the traditional surgical approach. Recently, the endoscopic transnasal approach to the orbital cavity has gained interest, representing a feasible and safe, less-invasive surgical technique for the management of cavernous venous malformation.

The impact of FNAC in the management of salivary gland lesions: Institutional experiences leading to a risk-based classification scheme.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has proven its value as an essential step in the diagnosis of salivary gland lesions. Although the majority of salivary gland lesions, especially those that are common and benign, can be diagnosed with ease on FNAC, limited cellularity and morphologic lesion heterogeneity can pose diagnostic challenges and lead to false-positive and false-negative diagnoses. This study presents the institutional experience of FNAC of salivary gland lesions from 2 academic centers. METHODS: A retrospective analysis was conducted on 1729 salivary gland FNAC specimens that were diagnosed over an 8-year period from January 2008 to March 2015. All samples were processed either with liquid-based cytology alone or in combination with air-dried, Diff-Quik-stained or alcohol-fixed, Papanicolaou-stained smears. RESULTS: Surgical excision was performed in 709 of 1749 FNACs (41%) that were diagnosed as nondiagnostic/inadequate (n = 29), benign (n = 111), neoplasm (n = 453), atypical (n = 15), suspicious for malignancy (n = 28), and malignant (n = 73). The overall concordance between cytologic and histologic diagnoses was 92.2%, with 91.8% concordance in the benign category and 89.5% concordance in cases diagnosed as suspicious for malignancy and malignant. The most frequent benign and malignant lesions were pleomorphic adenoma and squamous cell carcinoma, respectively. There were 46 false-negative and 13 false-positive results, leading to an overall specificity of 97.6% and diagnostic accuracy of 91.3%. CONCLUSIONS: FNAC is a reliable diagnostic modality for the diagnosis and management of salivary gland lesions based on its high specificity and diagnostic accuracy. Cancer Cytopathol 2016;124:388-96. © 2016 American Cancer Society.

Evaluation of the Added Value of Diffusion-Weighted Imaging to Conventional Magnetic Resonance Imaging in Pancreatic Neuroendocrine Tumors and Comparison With 68Ga-DOTANOC Positron Emission Tomography/Computed Tomography.

OBJECTIVES: The aims of this study were to investigate the added value of diffusion-weighted imaging (DWI) in pancreatic neuroendocrine tumor (pNET) evaluation and to compare magnetic resonance imaging (MRI) to Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) results. METHODS: Morphological MRI (T2-weighted [T2-w] + contrast-enhanced [CE] T1-w) and DWI (T2-w + DWI) and Ga-DOTANOC PET/CT in 25 patients/30 pNETs were retrospectively evaluated. Per-patient and per-lesion detection rates (pDR and lDR, respectively) were calculated. Apparent diffusion coefficient values were compared among pNET and surrounding and normal pancreas (control group, 18 patients). Apparent diffusion coefficient and standardized uptake value (SUV) values were compared among different grading and staging groups. RESULTS: No statistically significant differences in PET/CT and MRI session detection rates were found (morphological MRI and DW-MRI, 88% pDR and 87% lDR; combined evaluation, 92% pDR and 90% lDR; Ga-DOTANOC PET/CT, 88% pDR and 80% lDR). Consensus reading (morphological/DW-MRI + PET/CT) improved pDR and lDR (100%). Apparent diffusion coefficient mean value was significantly lower compared with surrounding and normal parenchyma (P < 0.01). The apparent diffusion coefficient and SUV values of pNETs among different grading and staging groups were not statistically different. CONCLUSIONS: Conventional MRI, DW-MRI + T2-w sequences, and Ga-DOTANOC PET/CT can be alternative tools in pNET detection. Diffusion-weighted MRI could be valuable in patients with clinical suspicion but negative conventional imaging findings. However, the consensus reading of the 3 techniques seems the best approach.

HPV and EBV Infections in Neck Metastases from Occult Primary Squamous Cell Carcinoma: Another Virus-Related Neoplastic Disease in the Head and Neck Region.

BACKGROUND: Approximately 1-9 % of all head and neck squamous cell carcinomas are neck metastases from clinically undetectable primary tumors. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are proven carcinogenic factors that are associated with oropharyngeal squamous cell carcinoma and nasopharyngeal carcinoma, respectively. In the present study, we evaluated the prevalence of these viruses in neck metastases from unknown primary squamous cell carcinoma. METHODS: We evaluated fresh samples from a consecutive series of 22 neck dissections for metastases from unknown primary squamous cell carcinoma obtained between 2010 and 2012 at a single institution. The samples were tested for the presence of HPV E6 and E7 mRNA and EBV DNA. RESULTS: Oncogenic viral infections were detected in 12 cases (54 % total; 2 HPV18, 5 HPV16, 2 EBV infection, and 3 EBV/HPV16 coinfections). The most frequent primarily involved neck level in our series was IIA (70 %), which had the highest prevalence of viral infection (66 %). We did not find any other significant correlations between virus detection and clinicopathologic parameters or prognosis. DISCUSSION: Neck metastasis from unknown primary squamous cell carcinoma could be another virus-related malignancy in the head and neck region, along with nasopharyngeal and oropharyngeal carcinoma. An evaluation of the impact of viral infection on patient prognosis and sensitivities to different treatment modalities could modify our prognostic assessments and treatment planning. Furthermore, virus detection would have a decisive impact on diagnostic/decisional algorithms, especially if detection methods are implemented on cytologic samples (e.g., thin prep).