Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising in a Salivary Sebaceous Lymphadenoma.

BACKGROUND: Lymphadenomas are rare benign tumors of the major salivary glands that are further classified as sebaceous and non-sebaceous. No association with viruses has been reported so far. Little is known about the mechanisms that allow lymphadenomas to undergo malignant transformation. Among these rare instances, there has never been a malignant transformation to Epstein-Barr virus (EBV)-associated lymphoepithelial carcinoma. METHODS: Clinical data of the reported case were retrieved from the patient's electronic medical record. Hematoxylin & eosin-stained slides, immunohistochemical tests, and in situ hybridization performed for routine diagnostic purposes were reviewed. RESULTS: We report a salivary gland sebaceous lymphadenoma in which the luminal components were mostly replaced by malignant epithelial cells with markedly atypical nuclear features. Presence of EBV was demonstrated in all components by EBER. The morphological and immunohistochemical findings were consistent with a lymphoepithelial carcinoma arising from a sebaceous lymphadenoma. CONCLUSION: We report the first case of an Epstein-Barr virus-associated lymphoepithelial carcinoma arising from a sebaceous lymphadenoma.

Predictors of prolonged treatment time intervals in oral cavity cancer.

OBJECTIVES: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals. MATERIAL AND METHODS: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy. The endpoints of interest were prolonged treatment intervals. Multivariable logistic regression was used to adjust for patient and tumour characteristics. RESULTS: Median diagnosis-to-treatment interval (DTI) and surgery to initiation of postoperative radiation therapy interval (S-PORT) were 39 days (IQR 30-54) and 64 days (IQR 54-66), respectively. Prolonged DTI was associated with older age, worse Charlson Comorbidity index scores and worse T stages. Patients with prolonged DTI had longer times to preoperative imaging reports (25 vs 9 days; P < 0.01). Time to preoperative pathology did not differ. Prolonged S-PORT was associated with longer times to pathology report (28 vs 18 days; P < 0.01), to maxillofacial consult (38 vs 15 days; P < 0.01) and to maxillofacial approval of radiation (50 vs 28 days; P < 0.01). In patients requiring medical oncology consults, those with prolonged S-PORT had longer waiting times until consultation (58 vs 38 days; P = 0.02). Multivariate analysis showed independent predictors of prolonged DTI: time to preoperative imaging; and prolonged S-PORT: time to pathology report, time to maxillofacial consult, and time to medical oncology consult. CONCLUSIONS: Strategies targeting these organizational bottlenecks may be effective for shortening treatment time intervals, hence representing potential opportunities for improving oncological outcomes in OCSCC patients.

Rapid head and neck tissue identification in thyroid and parathyroid surgery using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive imaging modality that may reproduce the microarchitecture of tissues in real-time. This study examines whether OCT can render distinct images of thyroid, parathyroid glands, adipose tissue, and lymph nodes in both healthy and pathological states. METHODS: Twenty-seven patients undergoing thyroidectomy, parathyroidectomy, and/or neck dissection for thyroid cancer were recruited prospectively for imaging prior to histopathological analysis. RESULTS: Based on 122 imaged specimens, qualitative OCT descriptions were derived for healthy thyroid, parathyroid gland, adipose tissue, and lymph node. The frequencies at which distinguishing features were present for each tissue type were 88%, 83%, 100%, and 82%. OCT appearance of pathological specimens were also described. CONCLUSIONS: Healthy neck tissues have distinct OCT appearances, which could facilitate parathyroid identification during thyroidectomies. However, images of parathyroid adenomas could be confused with those of lymph nodes, and benign and malignant thyroid nodules could not be differentiated.

Cystic masses of the lateral neck: Diagnostic value comparison between fine-needle aspiration, core-needle biopsy, and frozen section.

BACKGROUND: The usefulness of fine-needle aspiration (FNA), core-needle biopsy (CNB), and frozen section (FS) for assessing lateral cystic neck masses (LCNM) remains unclear. METHODS: A retrospective review of patients presenting with a LCNM was undertaken. RESULTS: In total, 135 patients were included. FNA had a lower sensitivity then CNB (59% vs 83%; P = .036) and FS (59% vs 93%; P = .01). FS had a better negative predictive value (NPV) when compared to FNA (92% vs 40%; P < .001) and CNB (92% vs 50%; P = .062). Positive predictive values (PPV) and sensitivities were similar among all groups. CONCLUSION: Given its adequate PPV (92%), FNA should be used initially on LCNM. Because of its high sensitivity, CNB should be considered if FNA is not diagnostic of malignancy. FS should always follow a CNB indicative of malignancy, because of low NPV. A diagnosis of malignancy on FNA, CNB, or FS strongly indicates presence of malignancy.

North-American survey on HPV-DNA and p16 testing for head and neck squamous cell carcinoma.

OBJECTIVES: Human papillomavirus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) have been shown to have a significantly better prognosis and response to current treatment modalities. Current guidelines recommend systematic HPV-DNA and/or p16 testing on HNSCCs, although treatment approach should not be directed by test results. The objectives of this study were to (1) assess whether HPV-DNA and/or p16 status are systematically evaluated across North American otolaryngologists-head and neck surgeons and (2) whether the status is used to direct treatment approach. MATERIALS AND METHODS: A 15-question online survey was sent to three associations: the Association of Oto-rhino-laryngology-Head and Neck Surgery of Quebec, the Canadian Society of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society. RESULTS: Sixty-seven percent of respondents systematically test for HPV-DNA and/or p16 on HNSCC sites, while 58.3% report using test results to direct treatment for oropharyngeal cancers. A lack of official guidelines was the primary reason (81.8%) physicians did not use test results to direct treatment. Academic centre physicians (83.3%) and physicians with ⩾50% oncologic practice (87.6%) were more likely to test for HPV-DNA and/or p16 in HNSCC compared to non-academic centre physicians (39.7%) and physicians with <50% oncologic practices (51.4%) (p<0.001). Cost of the tests (69.2%), lack of relevance (46.1%) and time constraints (30.8%) were the primary reasons HPV-DNA and/or p16 were not tested. CONCLUSION: The majority of North American respondents in this survey systematically test for HPV-DNA and/or p16 in HNSCC sites, and most indicate that test results influence their treatment approach for oropharyngeal cancers.

Hepatoid adenocarcinoma of the anterior skull base: a case report.

We report the first case of hepatoid adenocarcinoma of the skull base, as well as the first reported case in the head and neck region. Hepatoid adenocarcinoma is a rare, aggressive, extrahepatic malignancy with a distinct morphological similarity to hepatocellular carcinoma, in the absence of primary hepatic disease. A 45-year-old man presented with sinus headaches and retro-orbital pain and was found to have a nasopharyngeal mass on endoscopy and a large, destructive sinonasal mass extending intracranially on imaging. Histo- and cytopathological features were similar to hepatocellular carcinoma, and the cells were immunoreactive for α-fetoprotein, epithelial membrane antigen, periodic acid-Schiff, cytokeratin (CK)8/18, CK19, and S100.

Matrigel improves functional properties of primary human salivary gland cells.

Currently, there is no effective treatment available to patients with irreversible loss of functional salivary acini caused by Sjogren's syndrome or after radiotherapy for head and neck cancer. A tissue-engineered artificial salivary gland would help these patients. The graft cells for this device must establish tight junctions in addition to being of fluid-secretory nature. This study analyzed a graft source from human salivary glands (huSG) cultured on Matrigel. Cells were obtained from parotid and submandibular glands, expanded in vitro, and then plated on either Matrigel-coated (2 mg/mL) or uncoated culture dish. Immunohistochemistry, transmission electron microscopy, quantitative real-time-polymerase chain reaction, Western blot, and transepithelial electrical resistance were employed. On Matrigel, huSG cells adopted an acinar phenotype by forming three-dimensional acinar-like units (within 24 h of plating) as well as a monolayer of cells. On uncoated surfaces (plastic), huSG cells only formed monolayers of ductal cells. Both types of culture conditions allowed huSG cells to express tight junction proteins (claudin-1, -2, -3, -4; occludin; JAM-A; and ZO-1) and adequate transepithelial electrical resistance. Importantly, 99% of huSG cells on Matrigel expressed α-amylase and the water channel protein Aquaporin-5, as compared to <5% of huSG cells on plastic. Transmission electron microscopy confirmed an acinar phenotype with many secretory granules. Matrigel increased the secretion of α-amylase two to five folds into the media, downregulated certain salivary genes, and regulated the translation of acinar proteins. This three-dimensional in vitro serum-free cell culture method allows the organization and differentiation of huSG cells into salivary cells with an acinar phenotype.

Value of thyroid incidentalomas on positron emission tomographic scans among thyroidectomy patients.

OBJECTIVES: To evaluate the preoperative predictive value of a positive positron emission tomographic (PET) scan with respect to malignancy in future thyroidectomy candidates, particularly when the fine-needle aspiration biopsy (FNAB) results in indeterminate findings, and to establish the efficiency with which this can be incorporated as a preoperative marker and potentially contribute to a standardized scoring system for thyroid nodule patients. METHODS: This retrospective study examined 1048 thyroidectomy patients, of whom 45 underwent PET with computed tomography for unrelated reasons, among which 13 results were focally positive. The final pathology was evaluated and compared to this result to determine the correlation. RESULTS: All patients with positive PET results were shown postthyroidectomy to have a thyroid malignancy (13 of 13), corresponding to a positive predictive value of 100%. There was no correlation between a negative PET scan and malignancy, however. When integrating the PET scan criteria in the McGill Scoring System, 4 of these 13 were shifted into a high chance of malignancy group, allowing a more accurate assessment of their risk than they might have previously received. CONCLUSION: In comparison with previous data, our results indicate a strong relationship between a positive PET scan and malignancy. If available and used in conjunction with the other preoperative diagnostic tools (outlined by the McGill Thyroid Nodule Scoring System), this test can hold significant merit in determining a therapeutic strategy, particularly in the face of an indeterminate FNAB.

McGill Thyroid Nodule Score (MTNS): "rating the risk," a novel predictive scheme for cancer risk determination.

OBJECTIVE: There are presently a great number of publications pertaining to the clinical risk factors associated with thyroid cancer. These studies deal mostly with a single feature from either patient demographics, physical examination, laboratory values, imaging, or cytology. We sought to create a novel scoring system that integrates the diagnostic indices of each of these clinical features for carcinoma. METHODS: A retrospective analysis of 1047 consecutive thyroidectomy patients was performed. Each patient was assigned a cancer risk score according to a newly devised 22-variable scoring scheme termed the McGill Thyroid Nodule Score (MTNS). The MTNS was developed by a multidisciplinary team of endocrinologists, thyroid surgeons, and pathologists using already established evidence-based risk factors for thyroid cancer. RESULTS: The exact incidence of malignancy was calculated for each MTNS score based on final pathology. The incidence for scores of 1 to 3 was 27%, of 4 to 7 was 32%, of 8 was 39%, of 9 to 11 was 63%, of 12 to 13 was 88%, and of 14 to 18 was 93%. All (130 of 130) patients with a score ≥ 19 had carcinoma. A score ≤ 8 correlated with a 32% (115 of 357) risk of thyroid cancer, whereas a score > 8 implied an 86% (417 of 487) risk. CONCLUSION: Our data suggest that a combined scoring system, the MTNS, can serve as an accurate predictor of the risk for thyroid cancer in a specific thyroid nodule. This will help physicians better formulate management decisions accordingly.

Ultrasound-guided fine-needle aspiration thyroid biopsies in the otolaryngology clinic.

OBJECTIVE: To assess the efficacy of ultrasound-guided thyroid fine-needle aspiration biopsies (USFNABs) performed in the office setting by an otolaryngologist and to evaluate the specimen adequacy of USFNABs performed in patients whose initial palpation-guided fine-needle aspiration biopsies (PGFNABs) were nondiagnostic. DESIGN: Retrospective chart review. SETTING: Royal Victoria Hospital-McGill University Health Centre, Montreal. METHODS: This is a retrospective analysis of 76 USFNABs performed by an otolaryngologist on consecutive patients over a 6-month period. Each patient had a previous nondiagnostic PGFNAB. Biopsies were performed using a 20-gauge fine needle with a Mylab25 Biosound Esoate ultrasound machine. Samples were then classified according to the adequacy of sample and pathologic findings. MAIN OUTCOME MEASURE: Specimen adequacy rate. RESULTS: Sixty-six patients underwent 76 USFNABs. The sample included 57 females and 9 males (mean age 51.1 and 55.4 years, respectively). The specimen adequacy rate was 90.8% (69 of 76). Among the adequate specimens, 2 (2.6%) were malignant, 6 (7.9%) were suspicious for malignancy, 43 (56.6%) were benign, and 18 (23.7%) were follicular or Hürthle cell lesions (indeterminate). CONCLUSION: Our experience demonstrates that USFNAB performed in the clinic by an otolaryngologist is a promising tool for improving specimen adequacy for nodules initially classified as nondiagnostic. USFNAB also avoids the need for radiologic consultation, thus improving efficacy in the workup of nodules.

The role of sentinel lymph node biopsy in differentiated thyroid carcinoma.

OBJECTIVE: To determine whether sentinel lymph node (SLN) biopsy can accurately predict central compartment metastasis in patients with differentiated thyroid carcinoma. DESIGN: Prospective clinical study. SETTING: Academic tertiary care center. PATIENTS: Ninety-eight patients (82 women and 16 men; mean age, 48.3 years) underwent a total thyroidectomy and central compartment dissection. INTERVENTION: Peritumoral injection of methylene blue dye, 1%, followed by SLN biopsy. MAIN OUTCOME MEASURES: The final pathology report established the presence of metastasis among SLNs and lymph nodes that did not stain blue (non-SLNs [NSLNs]). RESULTS: Differentiated thyroid carcinoma was found in 75 of 98 patients (77%). Seventy of 75 patients with differentiated thyroid carcinoma presented with SLNs and/or NSLNs within the central compartment. Fifteen of 70 patients had metastasis-positive SLNs, while 55 had metastasis-negative SLNs. Six of 15 patients with positive SLNs also had positive NSLNs. No patients with negative SLNs were found to have positive NSLNs. Sentinal lymph node status was a highly significant predictor of NSLN result (Fisher exact test, P < .001). The accuracy, sensitivity, specificity, and positive and negative predictive values of SLN biopsy were 87%, 100%, 86%, 40%, and 100%, respectively. CONCLUSIONS: To our knowledge, this is the largest series of SLN biopsy in patients with differentiated thyroid carcinoma. Our experience suggests that this is an accurate and noninvasive means to identify subclinical lymph node metastasis. Because negative SLNs correlate strongly with a negative central compartment (100% in this study, P < .001), this technique can be used as an intraoperative guide when determining the extent of surgery necessary in cervical level VI.