Accurate assessment of the age-dependent disease risk conferred by germline variants in disease susceptibility genes is often hampered by the way the data are collected. Cohort-based data sets ...frequently contain an overrepresentation of patients (i.e. carriers of the gene variant of interest affected with the associated disease), and an underrepresentation of disease-free carriers. In order to overcome this problem, penetrance estimates can be based on family-based study designs, through the evaluation of index patients and their family members. This approach facilitates the identification of asymptomatic germline variant carriers. By adjusting for the way these family data are ascertained, an estimate for the penetrance of the pathogenic gene variant can be obtained. However, the family structure is often incomplete or missing. This complicates the estimation of the penetrance, because full adjustment of the likelihood is not possible. We present a conditional likelihood for the estimation of the penetrance of pathogenic gene variants, based on a cohort of multiple families comprising index patients, disease-free and affected non-index carriers, but with missing information on pedigree structure. The proposed estimator corrects for the ascertainment in a robust way and is shown to be more accurate than the frequently used Kaplan–Meier estimator of the penetrance function.
Purpose
Pharyngocutaneous fistula (PCF) formation and swallowing difficulties are common and troublesome complications following total laryngectomy (TL). Prior (chemo)radiotherapy ((C)RT) is thought ...to be a risk factor for these complications, but there is conflicting evidence as to whether the time interval between (C)RT and TL is important. The impact of time interval on these complications and also its impact on overall survival are investigated.
Methods
This is a retrospective case note review of all patients undergoing TL at the University Medical Center, Utrecht, The Netherlands over the 10-year period from January 2008 to December 2017. The cohort was split into those who underwent TL within a year of finishing (C)RT and those longer than 1 year.
Results
One hundred and twenty-six patients (108 males, 18 females), with a mean age of 66 underwent total laryngectomy after prior (C)RT in the study period. Overall 5-year survival was 35% with a median follow-up of 30 months. Fifty-four patients underwent laryngectomy within a year of their (C)RT versus 72 patients who had a time interval of more than one year. No differences in PCF rate, risk of dilatation or overall survival could be found between the two groups.
Conclusions
In this modern cohort, time interval between (C)RT and surgery did not impact PCF rate, risk of dilatation or overall survival.
Background. Sinonasal teratocarcinosarcoma is a rare, aggressive malignancy located almost exclusively in the nasal cavity, paranasal sinuses, or anterior skull base. Histopathological diagnosis can ...be challenging due to the heterogeneous composition. Methods. Retrospective analysis of 3 patients with sinonasal teratocarcinosarcoma diagnosed and treated at the University Medical Center Utrecht was conducted. Results. Patients presented with nasal obstruction, epistaxis, headaches, or behavioral changes. All three patients had locally advanced disease, and one had lymph node metastases. Two patients underwent surgery followed by radiotherapy, and one underwent neoadjuvant chemotherapy followed by surgery. The follow-up duration ranged from 3 to 32 months. All three patients died due to progression of their disease. Conclusion. Sinonasal teratocarcinosarcoma is characterized by rapid, aggressive local expansion. The prognosis is poor due to a high risk of metastases and locally recurrent disease. Multimodality treatment consisting of surgery, followed by (chemo)‐radiotherapy, is essential for optimizing outcomes. Neoadjuvant therapy offers a promising treatment option.
Management of functional intrathoracic sympathetic paragangliomas in succinate dehydrogenase subunit D (SDHD) mutation carriers is challenging, and there is no uniform guideline for treatment to ...date. The risks of potential malignant behavior and long-term cardiovascular morbidity have to be weighed against the risks of treatment complications. We report the multidisciplinary and shared decision-making approach that resulted in successful surgical removal of 3 paragangliomas in a SDHD mutation carrier.
Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. ...Little is known about the combination and possible interactions between the two phenomena.
In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry.
Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome.
Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.
Background
Sinonasal mucosal melanoma (MM) is a rare, aggressive melanoma subtype. Complete surgical excision, with or without adjuvant radiotherapy, remains the cornerstone of treatment and yields ...adequate locoregional control. Metastatic MM is managed similarly to metastatic cutaneous melanoma but with poorer survival. PReferentially expressed Antigen in MElanoma (PRAME) has been identified as a potential diagnostic marker and therapeutic target in the treatment of cutaneous melanoma.
Methods
Retrospective analysis of the clinical characteristics and immunohistochemical features of all sinonasal MM patients referred to the department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, between 2011 and 2021 was performed. Single nucleotide polymorphism (SNP) array and next-generation sequencing (NGS) were performed in selected cases.
Results
A total of 26 patients with an MM were included. The median follow-up duration was 15 months. At the end of follow-up, 13 patients had died due to progression of their disease, and one patient died of intercurrent disease. PRAME immunohistochemistry was performed in 23 out of 26 cases, all displaying PRAME expression. In two cases PRAME expression was present both within the melanoma cells and in melanocytes in adjacent mucosa. SNP array showed ≥ 5 copy number variants (CNV) in all tested cases, with a median of 29.5 CNVs (IQR 23.25–40). The three most common mutations identified by NGS were
NRAS
(7 cases) and
NF1
(2 cases).
Conclusion
We show that expression of PRAME is common in sinonasal MM, making PRAME a useful ancillary diagnostic tool and a potential therapeutic target in sinonasal MM. The demonstrated occurrence of extensive presence of PRAME-positive melanocytes in the surrounding mucosa of sinonasal MM might explain the multifocal nature of melanoma in the (sinonasal) mucosa, and would be an extra argument for a PRAME targeting treatment in preventing local disease recurrence.
Succinate dehydrogenase B subunit (
) gene germline mutations predispose to pheochromocytomas, sympathetic paragangliomas, head and neck paragangliomas and non-paraganglionic tumors (e.g. renal cell ...carcinoma, gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study was to determine phenotypical characteristics of a large Dutch cohort of
germline mutation carriers and assess differences in clinical phenotypes related to specific
mutations.
Retrospective descriptive study.
Retrospective descriptive study in seven academic centers.
We included 194
mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%) relatives. Mean age was 44.8 ± 16.0 years. Median duration of follow-up was 2.6 years (range: 0-36). Sixty persons (30.9%) carried the exon 3 deletion and 46 (23.7%) the c.423 + 1G > A mutation. Fifty-four mutation carriers (27.8%) had one or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26 (13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%) developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic tumors. At study close, there were 111 (57.2%) unaffected mutation carriers. Statistical analyses showed no significant differences in the number and location of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas, nor in the occurrence of metastatic disease or other tumors between carriers of the two founder
mutations (exon 3 deletion vs c.423
+ 1G > A).
In this nationwide study of disease-affected and unaffected
mutation carriers, we observed a lower rate of metastatic disease and a relatively high number of head and neck paragangliomas compared with previously reported referral-based cohorts.
Background
Middle ear adenomatous neuroendocrine tumors (MEANTs) are rare temporal bone tumors. This study evaluates its clinical behavior and therapy outcome.
Method
Retrospective case review in a ...tertiary referral center evaluating histopathology, immunohistochemistry, treatment, and outcome.
Results
Nine patients were diagnosed with MEANT. One patient presented with locally invasive tumor and underwent extensive en‐bloc tumor resection with adjuvant radiotherapy. Seven of eight patients with locally non‐aggressive tumor confined to the tympanomastoid space underwent tumor resection. Two patients were disease‐free, five presented recurrence, even after apparent successful surgery. All tumors showed neuroendocrine features. Histopathology and immunohistochemistry did not yield prognostic tumor characteristics.
Conclusion
MEANTs are rare tumors with uncertain biological behavior and subsequent unpredictable clinical course. The preferred treatment is complete surgical tumor resection. They have a high tendency for recurrence, irrespective of negative intermediary surgery. As of yet, there are no prognostic biomarkers, including histopathology and immunohistochemistry.
A newly proposed classification by the European Laryngological Society (ELS) of glottic lesions by narrow-band imaging (NBI) divides their vascular patterns into longitudinal and perpendicular ones. ...The latter are further subdivided into the wide and narrow patterns. The longitudinal, wide, and narrow patterns are characteristic of benign disease, papilloma, and malignancy, respectively. The aim of the study was to investigate the diagnostic effectiveness of the classification. Forty patients with glottic lesions underwent microlaryngoscopy. The vascular patterns of all vocal cords were defined with NBI. The affected vocal cords were histologically analysed and comprised the arm (A). Unaffected vocal cords were not histologically analysed but followed-up and comprised the arm (B) and were regarded as true negatives if no suspicious changes appeared during the follow-up. The vocal cords from the arm A were categorised into the benign and malignant group according to the histologic result. The ratio of vascular patterns was determined and the groups were statistically compared using the Chi-square test and Fisher’s exact test. Perpendicular changes were observed in 36.6% (9/26) of benign diseases and in 100% (23/23) of cancer conditions (
p
< 0.001). Wide perpendicular changes appeared only in papillomas (6/6) while narrow ones mostly in malignancies (23/26) and also in benign conditions (3/26) (
p
< 0.001). The sensitivity, specificity, positive and negative predictive values, and accuracy were 100, 95, 88, 100 and 96%, respectively. The new ELS classification can be used effectively and safely to differentiate malignant from benign disease.
AbstractPatients with Inflammatory Bowel Disease (IBD) are at increased risk of developing malignancies. IBD patients with oral cavity cancer may have reduced survival compared with the general ...population. This article describes two IBD patients, non-smokers, on long-term use of mesalazine with the development of oral cavity cancer. In IBD the clinician should be aware of possible head and neck malignancies and in case of doubt a biopsy should be performed, even in the absence of standard risk factors.
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