Epidemiology, outcomes, and prognostic factors in submandibular gland carcinomas: a national DAHANCA study.

PURPOSE: The aim of this study is to present incidence, histological subtypes, survival rates, and prognostic factors based on a national cohort of patients with salivary gland carcinoma. METHODS: All Danish patients with submandibular gland carcinoma diagnosed from 1990 to 2015 (n = 206) were included and analyzed following histological re-evaluation. Data were collected by the Danish Head and Neck Cancer Group (DAHANCA). Overall, disease-specific and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 109 (53%) men and 97 (47%) women, median age 62 years (range 11-102). Adenoid cystic carcinoma was the most frequent subtype (50%). Tumour classification T1/T2 (75%) and N0 (78%) was most frequent. The mean crude incidence was 0.17/100,000/year. Most patients (n = 194, 94%) were treated with primary surgery, and 130 (67%) received postoperative radiotherapy. The 5- and 10-year survival rates were for overall survival 64% and 41%, disease-specific survival 74% and 61%, and recurrence-free survival 70% and 56%, respectively. Survival rates were higher for adenoid cystic carcinoma compared to other subtypes, but the difference was not significant in multivariate analysis. Recurrence occurred in 69 patients, and 37 (53.6%) of them had recurrence in a distant site. Advanced T-classification and regional lymph-node metastases had significant negative impact on survival rates. CONCLUSION: The incidence of submandibular gland carcinoma in Denmark was 0.17/100,000/year and stable during the time period. The most frequent subtype was adenoid cystic carcinoma. Half of the recurrences presented in a distant site, and multivariate analysis confirmed that advanced stage was independent negative prognostic factor for recurrence and survival.

Salivary gland carcinoma in Denmark: a national update and follow-up on incidence, histology, and outcome.

PURPOSE: Salivary gland carcinoma is a rare disease and studies on epidemiology and outcome require data collection over many years. The aim of this study is to present an update of incidence rates, anatomical sites, histological subtypes, and survival rates based on the Danish national cohort of salivary gland carcinoma patients. METHODS: Data from all Danish patients with salivary gland carcinoma diagnosed from 1990 to 2015 (n = 1601) were included and analyzed following histological reevaluation and reclassification. Overall, disease-specific, and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 769 men and 832 women, median age 62 years (range 6-102). The most frequent anatomic site was the parotid gland (51.8%). Adenoid cystic carcinoma was the most common subtype (24.7%). The majority had tumor classification T1/T2 (65.3%). The mean crude incidence was 1.2/100.000/year with an increase of 1.5% per year. There was no increase in age-adjusted incidence. The 5-, 10-, and 20-year survival rates were for overall survival 68, 52, and 35%, for disease-specific survival, 77, 69, and 64%, and for recurrence-free survival, 75, 64, and 51%, respectively. Age, high-grade histological subtype, advanced T-classification, cervical lymph node metastases, vascular invasion, and involved surgical margins had significantly negative impact on survival rates. CONCLUSION: The age-adjusted incidence has been stable for a period of 26 years. Multivariate analysis confirmed that histological grade, advanced stage, involved surgical margins and vascular invasion are independent negative prognostic factors. Survival rates were stationary compared to earlier reports.

Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles.

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

A "package solution" fast track program can reduce the diagnostic waiting time in head and neck cancer.

In 2007, a fast track program for patients with suspicion of head and neck cancer (HNC) was introduced in Denmark to reduce unnecessary waiting time. The program was based on so called "package solutions" including pre-booked slots for outpatient evaluation, imaging, and diagnostic surgical procedures. The purpose of this study is to present a model for fast track handling of patients suspicious of cancer in the head and neck region and to evaluate the effect of implementation on the diagnostic work up time. Patients with suspicion of HNC referred to the same university department of ENT Head and Neck Surgery during three comparable time intervals 2006-2007, 2007-2008, and 2011-2012 (groups 1-3) were investigated. We recorded the time from patient referral, to first consultation and final diagnosis. The first interval was before initiation of the "package solution", the second just after the introduction, and the third interval represents the current situation. The median time from referral to first consultation was reduced from eight calendar days in group 1 to only one day in groups 2 and 3 (p < 0.001). The combined median time from referral to the final cancer diagnosis decreased from 24 calendar days in group 1 to 7 and 10 days in groups 2 and 3, respectively (p < 0.005). The hit rate of finding malignancy was 41% in group 1, 49% in group 2, and 43% in group 3 with no difference among the groups (p = 0.13). The frequency of newly diagnosed HNC was 19% in group 1, 21% in group 2, and 17% in group 3 (p = 0.52). A "package solution" including pre-booked slots for diagnostic procedures is feasible and can significantly reduce the waiting time for patients with suspicion of HNC.

Prognostic significance of Ki-67 in salivary gland carcinomas.

BACKGROUND: Salivary gland carcinomas are a heterogeneous group of tumors with varying malignant potential. In this study, we evaluated the proliferative marker Ki-67 in salivary gland carcinomas and related the Ki-67 index to clinical data. METHODS: A total of 176 salivary gland carcinomas of 13 different subtypes were stained immunohistochemically for Ki-67. The number of Ki-67 positive cells was counted and the Ki-67 index was calculated as the percentage of positive tumor cells. RESULTS: The Ki-67 median value was 26 (range 1-99). The median follow-up time was 6.9 years (range 0-19 years). The 5- and 10-year crude survival was 70% and 59%, respectively. In univariate analysis, Ki-67 index, stage, vascular invasion and tumor grade were significantly related to crude survival, but in multivariate analysis only Ki-67 index, age, and stage were independent prognostic factors. CONCLUSION: We showed that irrespective of subtyping, grading or morphological appearance of tumor, the Ki-67 index is an important and independent prognosticator. Clinical and histo-pathological data must be considered, when planning the treatment of the individual patient. We have shown that besides stage and age of the patient, Ki-67 is a strong, independent prognostic factor.

Inter- and Intrarater Reliability and Agreement Among Danish Head and Neck Pathologists Assessing Extranodal Extension in Lymph Node Metastases from Oropharyngeal Squamous Cell Carcinomas.

BACKGROUND: Extranodal extension (ENE) in lymph node metastases is one of the most important prognostic factors in head and neck squamous cell carcinomas. Studies have shown inconsistency among pathologists in the assessment of ENE. The aims of this study were: (1) to determine the interrater and intrarater reliability and agreement in the assessment of ENE among Danish pathologists and (2) to test if a standardized assessment method may increase interrater agreement. METHODS: Four Danish head and neck pathologists assessed ENE presence or absence in 120 histological slides from lymph nodes with oropharyngeal squamous cell carcinoma metastases (first round). Subsequently, guidelines were introduced to the pathologists and a new assessment was performed (second round). Finally, two of the pathologists assessed the slides to determine intrarater reliability and agreement (third round). RESULTS: Interrater kappa coefficients varied between 0.57 and 0.67 in the first round and between 0.59 and 0.72 in the second round. The intrarater agreement between round 2 and 3 was 0.88 for pathologist 1 and 0.92 for pathologist 2 with resulting kappa coefficients of 0.76 (95% CI 0.64-0.88) and 0.84 (95% CI 0.74-0.94), respectively. CONCLUSION: We found a moderate level of reliability and agreement among pathologists for ENE in lymph node metastases from oropharyngeal squamous cell carcinomas. The intrarater reliability and agreement was generally higher than interrater measures. Interrater agreement was slightly improved by standardized assessment.

Histopathological Definitions of Extranodal Extension: A Systematic Review.

Extranodal extension (ENE) is a very strong prognostic factor in head and neck squamous cell carcinoma. However, significant variance in reported incidence of ENE suggests discordance in perception of ENE among pathologists. This study aims to map the different definitions of histopathological ENE used in the literature. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Guided by the research question: "How is histopathological ENE defined?" the databases Medline, Embase, and Cochrane were systematically searched. All retrieved studies were reviewed and qualitatively analyzed. Three categories of existing definitions were formed. The systematic literature search yielded 1786 studies after removal of duplicates. Nine hundred and thirty-four full text articles were assessed for inclusion and 44 unique ENE definitions were identified and categorized 1-3; (1) simple definitions only describing a breach in the capsule (48%), (2) definitions also including a description of the perinodal tissue (43%), and (3) definitions adding a description of a specific reaction in the perinodal structure (9%). No consensus definition of ENE exists, but based on the level of details in the identified definitions, three overall categories of ENE definitions were established.

Surgical treatment of the neck in patients with salivary gland carcinoma.

BACKGROUND: Elective neck dissection (END) in patients with salivary gland carcinoma is controversial and there are no universally accepted guidelines. METHODS: Patients were identified from the Danish Head and Neck Cancer Group. Between 2006 and 2015, 259 patients with primary salivary gland carcinoma were treated with END. Variables potentially associated with regional metastases were analyzed using logistic regression. Neck recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Occult metastases were found in 36 of the patients treated with END (14%) and were particularly frequent among patients with T3/T4 tumors and high-grade histology tumors. In multivariate analyses, high-grade histology and vascular invasion were associated with occult metastases. CONCLUSION: We recommend END of levels II and III for patients with high-grade or unknown histological grade tumors, and for T3/T4 tumors. Levels I, II, and III should be included in END in patients with submandibular, sublingual, or minor salivary gland carcinomas.

Prognostic scoring models in parotid gland carcinoma.

BACKGROUND: The aim was to identify prognostic factors and test three prognostic scoring models that predicted the risk of recurrence in patients with parotid gland carcinoma. METHODS: All Danish patients with parotid gland carcinoma, treated with curative intent, from 1990 to 2015 (n = 726) were included. Potential prognostic factors were evaluated using Cox regression and competing risk analyses. The concordance of each prognostic model was estimated using Harrel's C index. RESULTS: The study population consisted of 344 men and 382 women, with a median age of 63 years. Age above 60 years, high grade histology, T3/T4 tumor, regional lymph node metastases, and involved surgical margins were all associated with a significant reduction in recurrence-free survival. The prognostic model that agreed best with actual outcomes had a C-index of 0.76. CONCLUSION: Prognostic scoring models may improve individualized follow-up strategies after curatively intended treatment for patients with parotid gland carcinoma.

Granulomatous inflammation in lymph nodes of the head and neck-a retrospective analysis of causes in a population with very low incidence of tuberculosis.

The purpose of this study was to investigate the risk of the patient having: (1) TB, (2) sarcoidosis, (3) atypical mycobacteria, or (4) malignant disease, if FNAC or histology from a cervical lymph node shows granulomatous inflammation (GI). And to elucidate clinical characteristics associated with these causes of GI, patients with a pathological diagnosis of GI in head and neck lymph nodes were identified though a search of the Danish national pathology database. Charts were reviewed to identify the final clinical diagnosis and specific clinical characteristics. For the most common clinical diagnoses, association to clinical characteristics was analyzed using logistic regression (Odense University Hospital January 2006 to December 2015). We included 121 patients. Clinical diagnoses fell into the following categories: sarcoidosis (26%), tuberculosis (TB) (22%), cat scratch disease (6%), atypical mycobacteriosis (7%), malignancy (2%), and other (4%). In 33% of cases, the diagnosis was unknown. In the pediatric group, atypical mycobacteriosis was the most frequent clinical diagnosis (50%). TB and sarcoidosis were dependent variables in regression analysis. Characteristics significantly related to TB were histology showing necrotizing GI, gland localization in level 3-6, and origin other than Danish and TB being the tentative diagnosis. Characteristics significantly related to sarcoidosis were histology showing non-necrotizing GI, gland localization in level 3-6, the patient being of Danish origin, and unknown duration of symptoms. TB and sarcoidosis were the most common clinical diagnoses, and they were associated with specific clinical characteristics. In a third of cases, a specific clinical diagnosis was never given.

Variability in Medullary Thyroid Carcinoma in RET L790F Carriers: A Case Comparison Study of Index Patients.

Background: Previous studies have suggested that the variability in age of onset and aggressiveness of medullary thyroid carcinoma (MTC) in patients with multiple endocrine neoplasia type 2A (MEN 2A) carrying the same REarranged during Transfection (RET) mutation may be caused by additional RET germline variants or somatic variants. Methods: This study was a retrospective case comparison study of all MEN 2A index patients (n = 2) with the RET L790F germline mutation in Denmark. Whole blood and MTC tissue were analyzed for RET germline variants and other somatic variants (>500), respectively. Results: Patient 1 presented with MTC (T1aN1bM0) at age 14 years, while patient 2 presented with MTC (T1bN0M0) at age 70 years. No germline RET germline variants nor other variants were found to explain this MTC variability. Conclusions: We could not confirm the previously reported finding of a somatic RET variant as likely responsible for the early onset and aggressiveness of MTC in a RET germline mutation carrier. Also, we found no RET germline variants that could explain the MTC variability among our index patients. We did, however, identify a somatic FLT3 R387Q variant with an unknown potential as genetic modifier. Further large-scale studies are needed to investigate genetic modifiers in RET L790F carriers.

Synovial Cysts in the Temporomandibular Joint: a Case Report and Critical Review of the Literature.

BACKGROUND: Synovial cysts of the temporomandibular joint are rare and treatment is based on consensus from cases reporting unilateral successful outcomes. A patient with a synovial cyst is presented, treated with successful surgical excision of the cyst, but without remission of joint symptoms. Furthermore, the case is supplemented by a critical, literature review. METHODS: This case report deals with a patient with a synovial cyst that presented with temporomandibular joint (TMJ) pain and reduced mouth opening. Magnetic resonance imaging verified a TMJ cyst. RESULTS: Surgical excision removed the synovial cyst, and the patient was followed-up for 4 years, with no recurrence of the cyst. Despite successful excision of the cyst, the symptoms did not subside, and the patient is still in treatment. The critical, literature review found 23 case reports describing 24 synovial cysts. In addition, 4 cases were included as their synovial cysts were erroneously described as ganglion cysts. In 4 cases, histological diagnosis could not be confirmed, and they were excluded. All cases described treatment by surgical excision without recurrence. The reported median follow-up was 10 months and postoperative TMJ symptoms were rarely examined or described. CONCLUSIONS: The temporomandibular joint symptoms may persist despite successful removal of the synovial cyst. Furthermore, the 4 identified synovial cysts, mislabelled as ganglion cysts, represents almost a quarter of the cases of the reported synovial cysts. Correct labelling and reporting of synovial cysts are still imperative to describe the diverse aspects of treatment outcomes following surgical excision.

Incidental and Non-incidental Papillary Thyroid Microcarcinoma in Denmark 1996-2015: A national study on incidence, outcome and thoughts on active surveillance.

BACKGROUND: Incidental and non-incidental papillary microcarcinomas (PMC) are associated with different outcomes and treatment options may vary. The least favourable outcome is typically seen when carcinoma is suspected prior to surgery. Only a few studies have addressed the prognosis based on the way of detection for PMC, and they have been limited to retrospective single-center studies. We hypothesize that the "way of detection" may predict prognosis. The aim was to calculate the incidence and outcome of PMC based on the way of detection and to identify patients that may be suitable for active surveillance. METHOD: This national cohort study consists of 803 patients diagnosed with PMC in Denmark from 1996 to 2015. Patients were identified from the DATHYRCA database and allocated into groups according to the way of detection leading to surgery: Incidental at surgery (n = 527), non-incidental with symptoms suspected from the index tumor (n = 134) and non-incidental with symptoms suspected from a metastasis (n = 142). RESULTS: Age-standardized incidence rates increased from 0.35 per 100,000 per year in 1996 to 1.19 per 100,000 per year in 2015. A significant rise in incidence was found for both the incidental group and non-incidental group with symptoms suspected from a metastasis. Recurrence free survival was significantly worse for patients with suspicion of metastasis prior to surgery than patient groups without. No difference in mortality was found between groups. CONCLUSION: PMC patients without suspicion of metastasis have the same low risk of recurrence as incidental cases and may be candidates for active surveillance.

Up-front F18-FDG PET/CT in suspected salivary gland carcinoma.

OBJECTIVE: To investigate whether a 18F-FDG PET/CT (PET/CT)-based diagnostic strategy adds decisive new information compared to conventional imaging in the evaluation of salivary gland tumours and the detection of cervical lymph node metastases, distant metastases, and synchronous cancer in patients with salivary gland carcinoma. METHODS: The study was a blinded prospective cohort study. Data were collected consecutively through almost 3 years. All patients underwent conventional imaging-magnetic resonance imaging (MRI) and chest X-ray (CXR)-in addition to PET/CT prior to surgery. Final diagnosis was obtained by histopathology. MRI/CXR and PET/CT were interpreted separately by experienced radiologists and nuclear medicine physicians. Interpretation included evaluation of tumour site, cervical lymph node metastases, distant metastases, and synchronous cancer. RESULTS: Ninety-one patients were included in the study. Thirty-three patients had primary salivary gland carcinoma and eight had cervical lymph node metastases. With PET/CT, the sensitivity was 92% and specificity 29% regarding tumour site. With MRI/CXR, the sensitivity and specificity were 90% and 26%, respectively. Regarding cervical lymph node metastases in patients with salivary gland carcinoma, the sensitivity with PET/CT was 100% and with MRI/CXR 50%. PET/CT diagnosed distant metastases in five patients, while MRI/CXR detected these in two patients. Finally, PET/CT diagnosed two synchronous cancers, whereas MRI/CXR did not detect any synchronous cancers. CONCLUSIONS: Compared with MRI/CXR PET/CT did not improve discrimination of benign from malignant salivary gland lesions. However, PET/CT may be advantageous in primary staging and in the detection of distant metastases and synchronous cancers.

Laryngeal precursor lesions: Interrater and intrarater reliability of histopathological assessment.

OBJECTIVE: The World Health Organization classification (WHOC) 2017 of low-grade versus high-grade laryngeal dysplasia recently replaced the previous WHOC 2005 of mild, moderate, and severe dysplasia and carcinoma in situ. Our objectives were to compare the interrater agreement of the WHOC 2017 with that of the WHOC 2005 and to test the intra-rater agreement of the WHOC 2005. METHODS: Two expert head and neck pathologists rated 211 tissue samples that were initially diagnosed with laryngeal precursor lesions. The samples were rated twice according to the WHOC 2005 and once according to the WHOC 2017; estimates of interrater and intrarater agreements were calculated with kappa statistics. RESULTS: The crude intrarater agreements using the WHOC 2005 were 0.93 for rater 1 and 0.62 for rater 2. The corresponding unweighted kappa values were 0.90 (95% confidence interval [CI], 0.86-0.95) for rater 1 and 0.43 (95% CI, 0.35-0.54) for rater 2, whereas the standard linear weighted kappa values were 0.93 (95% CI, 0.90-0.97) for rater 1 and 0.60 (95% CI, 0.53-0.69) for rater 2. The crude interrater agreement for the WHOC 2005 was 0.57, with a corresponding unweighted kappa value 0.38 (95% CI, 0.31-0.48) and a standard linear weighted kappa value 0.52 (95% CI, 0.42-0.60). The crude interrater agreement for the WHOC 2017 was 0.83, with a corresponding unweighted kappa value 0.45 (95% CI, 0.31-0.59) and a standard linear weighted kappa value 0.46 (95% CI, 0.30-0.60). CONCLUSION: Our results indicate difficulties in providing reliable diagnosis of laryngeal precursor lesions, even with experienced head and neck pathologists and the application of a newly revised classification system. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2375-2379, 2018.

Thyroid fine-needle aspiration and The Bethesda Classification System.

INTRODUCTION: Fine-needle aspiration (FNA) is a cornerstone in diagnosing thyroid nodules. For decades, Danish FNA has been categorised into the groups: "FNA not performed", "Inadequate", "Cystic", "Inconclusive", "Benign", "Suspicious", "Malignant" and "Information missing". Internationally, The Bethesda Classification System (TBCS) is increasingly accepted, especially owing to a detailed specification of FNA suspicious for malignancy. The Danish "Suspicious" group is very broad and includes atypia, follicular neoplasia and FNA suspicious of other malignancies. The purpose of this study was to apply TBCS to the Danish "Suspicious" FNA group and to estimate the frequency of malignancy in the individual Bethesda groups (BG). METHODS: This descriptive study is based on a prospective cohort from the THYKIR database. It includes 479 patients with a "Suspicious" FNA and surgical treatment in The Region of Southern Denmark from 2001 to 2013. Based on pathology records, FNA was classified according to the TBCS. Malignancy was determined by the histological diagnosis from the THYKIR database. RESULTS: The Danish "Suspicious" group was allocated to the BG I, II, III, IV, V and VI with a malignancy risk of 36.4%, 13.3%, 17.2%, 16.1%, 55.3% and 88.2%, respectively. CONCLUSIONS: The Danish "Suspicious" group contains a broad spectrum of BG with varying malignancy risk. The results indicate a need for standardisation of the Danish FNA classification. A national introduction of the TBCS might secure an international and comparable standard. FUNDING: none. TRIAL REGISTRATION: not relevant.

Anaplastic thyroid carcinoma in Denmark 1996-2012: A national prospective study of 219 patients.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC patients. METHODS: A cohort study based on prospective data from the national Danish thyroid cancer database DATHYRCA and the national Danish Pathology Register including 219 patients diagnosed from 1996 to 2012, whom were followed until death or through September 2014. RESULTS: We found the median age in the 7th decade, the majority of patients being women presenting with a growing mass at the neck, diagnosed with stage T4b disease. At diagnosis, 56% of the patients had lymph node metastasis and 38% distant metastasis. We observed one- and five-year survival of 20.7% and 11.0%, respectively. Both univariate and multivariate analyses showed age (above 73.6 years), respiratory impairment, T4b stage, and distant metastasis at diagnosis to be significant prognostic factors. Further, introduction of a national fast track cancer program increased survival nearly two-fold. CONCLUSION: As new information, our study adds "respiratory impairment at diagnosis" and "introduction of a national fast track cancer program" to the list of already established prognostic indicators for ATC.

MicroRNA dysregulation in adenoid cystic carcinoma of the salivary gland in relation to prognosis and gene fusion status: a cohort study.

Adenoid cystic carcinoma (ACC) is among the most frequent malignancies of the salivary gland, and is notorious for its prolonged clinical course characterized by frequent recurrences often years after initial treatment. No molecular marker has been shown to have independent prognostic value in ACC, including characteristic gene fusions involving MYB, MYBL1, and NFIB. MicroRNA has been shown to be associated with clinical outcome in numerous malignancies, including one study of ACC, warranting further validation of this class of markers in this disease. Here, we investigate the prognostic value of microRNA in two ACC cohorts: a training cohort (n = 64) and a validation cohort (n = 120) with microarray and qPCR. In the training cohort, multivariate analysis of microarray data found high expression of hsa-miR-6835-3p to be associated with reduced recurrence-free survival (RFS) (p = 0.016). Measuring the highest ranking microRNAs identified in survival analysis in the same cohort, qPCR identified high expression of hsa-miR-4676 to be associated with reduced overall survival (OS) and high expression of hsa-mir-1180 to be associated with improved RFS. This was not confirmed in the validation cohort, in which qPCR identified high expression of hsa-mir-21, hsa-mir-181a-2, and hsa-mir-152 to be associated with reduced OS and high expression of hsa-miR-374c to be associated with improved RFS. Interestingly, two distinct subsets of ACC separated in microRNA expression irrespective of gene fusion status, but without significant difference in outcome. Collectively, qPCR identified several microRNAs associated with OS and RFS, and different subsets of ACC separated according to microRNA expression, suggestive of ACC being a heterogeneous group of malignancies in its microRNA profile.

Risk of malignancy in fine-needle aspiration biopsy in patients with thyroid nodules.

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) is the cornerstone of thyroid nodule evaluation. In most cases, FNAB can discriminate between benign and malignant disease. In other cases, it is only indicative of malignancy and the results are considered "suspicious". In Denmark, thyroid FNAB results are categorised into six groups: "inadequate", "cystic", "inconclusive", "benign", "suspicious" and "malignant". The risk of malignancy in the Danish "suspicious" group is of interest for patients as well as doctors participating in the diagnosis and treatment. The Danish Thyroid Surgery Database (THYKIR) registers preoperative thyroid FNAB and final histology. The aim of this study was to assess the malignancy risk among patients with a suspicious thyroid FNAB according to the Danish criteria and to identify possible predictors of malignant histology. METHODS: A prospective cohort counting 483 patients with a "suspicious" thyroid FNAB who had been treated surgically in The Region of Southern Denmark in the 2001-2013 period was retrieved from the THYKIR database. RESULTS: The risk of malignancy in the Danish thyroid FNAB "suspicious" group is 22%. Serum thyroid-stimulating hormone outside the normal range and vocal cord palsy may be patient-related predictors of malignancy. CONCLUSION: Awaiting the introduction of reliable tools for preoperative evaluation, the current practice with histo-logical clarification of the "suspicious" thyroid FNAB seems justified. FUNDING: none. TRIAL REGISTRATION: not relevant.