A common complaint a rare disease!

A 2-year-old previously well child presented to the emergency department with temperatures and lethargy. He was pale and looked unwell. He received a fluid bolus and was commenced on intravenous ceftriaxone. Pus was discharging from his left ear with postauricular swelling and erythema. Given clinical concerns, urgent neuroimaging was arranged.

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Laryngotracheal presentation of anaplastic thyroid carcinoma with squamous differentiation: seven cases demonstrating an under-recognized diagnostic pitfall.

AIMS: To describe a series of anaplastic thyroid carcinomas that mimicked primary head and neck squamous cell carcinoma (HNSCC) by virtue of both morphology and clinical presentation. METHODS AND RESULTS: Seven cases were identified in a 15-year period where a biopsy of an airway lesion that appeared to be squamous cell carcinoma was, in fact, anaplastic thyroid carcinoma. The tumours had squamous and/or spindle cell morphology, with only the squamous component being apparent in the airway biopsy. Some tumours arose within metaplastic (n = 3) or atypical (n = 3) epithelium, supporting the diagnosis of a primary mucosal tumour. Positive PAX8 (n = 5) and TTF-1 (n = 4) staining was identified. CONCLUSIONS: An endotracheal presentation of anaplastic thyroid carcinoma with squamous morphology may be misdiagnosed as a primary head and neck squamous cell carcinoma. PAX8 and TTF-1 expression are helpful in making the distinction, but the problem lies in suspecting a thyroid carcinoma in what appears to be a straightforward diagnosis of HNSCC.

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻8); rs1229984-ADH1B, p = 7 × 10⁻9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Outcomes from the first mouth cancer awareness and clinical check-up day in the Dublin Dental University Hospital.

PURPOSE OF THE STUDY: To increase public awareness about mouth cancer, the Dublin Dental University Hospital (DDUH) hosted an awareness day and free mouth check-up in September 2010. The messages of information, self-examination and risk management, and the importance of early detection, were available to all attendees. The role of general dental and medical practitioners in examination of the mouth was stressed. MATERIAL AND METHODS: A questionnaire regarding knowledge about the causes of and risk factors for mouth cancer, and a clinical check-up, were completed. RESULTS: A total of 1,661 individuals (675 male, 986 female) were examined. The mean age was 59.6 years. Just over one-third (36.5%) of those examined required no action, and slightly less (30%) were advised to return to their general dental or medical practitioner (GDP/GMP). Some 21% were advised about self-examination of the mouth, and 8% about smoking cessation. Of the remainder, 52 people (3.5%) were sent for a second opinion. Of these, 30 individuals were referred for further investigation, including biopsy in 27 cases. Following biopsy, five individuals were diagnosed with carcinoma in situ or carcinoma. CONCLUSIONS: The diagnosis of five people with mouth cancers, who may not otherwise have been identified for early treatment, highlights the need for regular mouth examination. It is inappropriate that such an exercise would remain the preserve of the dental teaching hospitals, and it is vital that all dentists take on the responsibility for regular mouth checks for all of their patients. More should be done to encourage those identified as high risk to visit their dentist. There is a need for recognition of the additional resources required for the detection and timely management of such cancers.

The Role of HPV in Determining Treatment, Survival, and Prognosis of Head and Neck Squamous Cell Carcinoma.

Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV's involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV's impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention.

Osteosarcoma (osteogenic sarcoma) of the jaws presenting in general dental practice - a series of four cases.

Introduction Osteosarcoma is the most common primary malignant bone tumour, usually arising in the long bones, with occurrence in the head and neck accounting for 8% of all osteosarcomas. Clinical features include swelling, pain, facial dysesthesia and abnormal mobility of teeth. Treatment consists of a combination of surgery, radiotherapy and chemotherapy.Case series Here, we present four cases of osteosarcoma of the jaws - two maxillary and two mandibular. All cases were initially assessed in the dental primary care setting before being referred for specialist opinion.Discussion The purpose of this paper is to present an overview of an uncommon but serious disease which can mimic common life-threatening dento-facial conditions. We discuss the diagnostic features, with an overview of clinical, histopathological and radiographic features.Conclusion These cases are important reminders of the potential clinical and radiographic appearance of a rare cause of facial swelling, and highlight the role of the general dental practitioner in early diagnosis and referral.

Small and Thin Oral Squamous Cell Carcinomas may Exhibit Adverse Pathologic Prognostic Features.

We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site interfering with assessment of WPOI5 in small tumors. We reviewed all OSCCs ≤ 20 mm size and ≤ 10 mm depth reported at our institution over a 5-year period. Tumor maximum dimension, depth, perineural invasion (PNI), lymphovascular invasion (LVI), worst pattern of invasion (WPOI), and nodal status were recorded. Out of 95 cases, there were 44 (46.3%) small and 78 (82.1%) thin OSCCs. Depth and WPOI were significant factors in predicting nodal disease. There were 41 (43.2%) OSCC that were small and thin, of which 9.8% had PNI, none had LVI, and 61% had WPOI 4 or 5. Their rate of PNI and of nodal disease was similar to the other early OSCC. Assessment of WPOI5 at a biopsy site was only a problem in 2/38 cases. In early OSCC, depth and WPOI are important factors in predicting nodal disease. The very earliest OSCC (small and thin) have a similar rate of PNI and of nodal disease to other early OSCC, suggesting that while there may be a tendency to de-escalate treatment, these small tumours should be managed in the same way as for all early OSCC. In addition, the presence of scarring due to a biopsy in very small carcinomas rarely affects assessment of WPOI5.

The Potential of Raman Spectroscopy in the Diagnosis of Dysplastic and Malignant Oral Lesions.

Early diagnosis, treatment and/or surveillance of oral premalignant lesions are important in preventing progression to oral squamous cell carcinoma (OSCC). The current gold standard is through histopathological diagnosis, which is limited by inter- and intra-observer errors and sampling errors. The objective of this work was to use Raman spectroscopy to discriminate between benign, mild, moderate and severe dysplasia and OSCC in formalin fixed paraffin preserved (FFPP) tissues. The study included 72 different pathologies from which 17 were benign lesions, 20 mildly dysplastic, 20 moderately dysplastic, 10 severely dysplastic and 5 invasive OSCC. The glass substrate and paraffin wax background were digitally removed and PLSDA with LOPO cross-validation was used to differentiate the pathologies. OSCC could be differentiated from the other pathologies with an accuracy of 70%, while the accuracy of the classifier for benign, moderate and severe dysplasia was ~60%. The accuracy of the classifier was lowest for mild dysplasia (~46%). The main discriminating features were increased nucleic acid contributions and decreased protein and lipid contributions in the epithelium and decreased collagen contributions in the connective tissue. Smoking and the presence of inflammation were found to significantly influence the Raman classification with respective accuracies of 76% and 94%.

Biomedical applications of vibrational spectroscopy: Oral cancer diagnostics.

Vibrational spectroscopy, based on either infrared absorption or Raman scattering, has attracted increasing attention for biomedical applications. Proof of concept explorations for diagnosis of oral potentially malignant disorders and cancer are reviewed, and recent advances critically appraised. Specific examples of applications of Raman microspectroscopy for analysis of histological, cytological and saliva samples are presented for illustrative purposes, and the future prospects, ultimately for routine, chairside in vivo screening are discussed.

FOXA1 is a potential oncogene in anaplastic thyroid carcinoma.

PURPOSE: FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas. EXPERIMENTAL DESIGN: We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors. In addition, we examined the role of FOXA1 in the proliferation of an undifferentiated thyroid carcinoma cell line by short hairpin RNA-mediated silencing. RESULTS: We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC). In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases. Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing. CONCLUSIONS: FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line. Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.

The detection of oral cancer and potentially malignant disorders in Ireland: An observational study of 100 cases.

OBJECTIVE: To describe the diagnostic details of a sample of histologically diagnosed malignant and potentially malignant oral lesions from Ireland; to examine how these lesions were first detected, and by whom; and to determine whether factors influenced how these lesions were detected, who detected them, and the type of lesion diagnosed. METHODS: A retrospective review was carried out of the clinical notes relating to oral lesions histologically diagnosed as squamous cell carcinoma (SCC), carcinoma in-situ, or epithelial dysplasia from biopsies performed in hospital-based specialist units and submitted to a diagnostic pathology service based in Dublin, Ireland, between June and December 2015. In addition to sex, age, and smoking status, details were collected relating to the diagnosis, how the lesion was detected, and by whom. RESULTS: There were 100 cases reviewed: SCC (29), carcinoma in-situ (5), and epithelial dysplasia (66). There were 49 opportunistic findings: dentists detected 47 (94 percent), and 51 presenting complaints: primary care physicians (PCPs) detected 30 (60 percent). There was a lower likelihood of opportunistic findings among males (odds ratio 0.41; 95 percent CI 0.18, 0.91). CONCLUSIONS: Dentists in Ireland detected significant proportions of malignant and potentially malignant oral lesions as opportunistic findings, although opportunistic findings were less likely to occur among male patients.

Pathology in Irish medical education.

Pathology is the study of disease and is an important component in medical education. However, with medical curriculum reform, its role and contribution to medical courses is under potential threat. We surveyed the status of pathology in all six Irish medical schools. Information was received from five direct undergraduate and four graduate entry programmes. Pathology was recognisable as a core subject in all but one of the medical schools, was generally taught in years two or three, and the greatest contact hours were for histopathology (44-102 hours). Lectures were the most common teaching modality, and all used single best or extended matching answer multiple-choice questions as part of assessments. Currently, pathology is very visible in Irish medical education but needs to remain relevant with the move to theme and case-based teaching. There is heavy reliance on lectures and on non-academic/full-time hospital staff to deliver teaching, which may not be sustainable.

Data Set for the Reporting of Carcinomas of the Nasal Cavity and Paranasal Sinuses: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic multi-institutional intercountry data collection to guide cancer care in the future. This data set has been developed by the collaborative efforts of an international multidisciplinary panel of experts involved in the care of patients with carcinomas of the nasal cavity and paranasal sinuses (sinonasal tract). The nasal cavity and paranasal sinuses (including frontal, sphenoid, ethmoid, and maxillary sinuses) comprise a very complex anatomic area of the head and neck, affected by a sometimes bewildering array of neoplasms. Management of malignancies in this anatomic region involves complex surgery because of the anatomic confines and close proximity to many vital structures. Given a multidisciplinary approach, the standardized reporting of the carcinomas that develop in this anatomic region include both required (core) and recommended (noncore) elements in pathology reporting in order to be able to identify critical prognostic factors, often requiring clinical and radiologic correlation. A summary of the International Collaboration on Cancer Reporting guidelines and clinically relevant elements, along with additional explanatory notes, are provided, based on evidentiary support from the literature, set in the context of practical application.

p16(INK4A) genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas.

Head and neck squamous cell carcinoma (HNSCC) typically affects male smokers older than 55 years. Recently, an increase in the incidence of HNSCC in young adults has been recognized, many of them nonsmokers and females. Functional inactivation of p16 is known to be a common event in HNSCC, mainly by either deletion or methylation. A previous study by this group has shown that p16 deletions in HNSCC are significantly associated with age. The primary objective of this study was to evaluate additional molecular alterations of p16 in HNSCC, specifically in relation to age, site, and human papillomavirus (HPV) status. Patients ranging in age from 22 to 76 years with HNSCC were prospectively identified (n = 24). Methylation-specific polymerase chain reaction and immunohistochemistry were used to evaluate p16 gene inactivation and p16 protein expression, respectively. HPV 16 status was determined for each case. Overall, p16 inactivation was a frequent event detected in 46% of cases. Methylation of p16 was more often detected in females than males (P = .05). All cases showing p16 methylation were from the anterior tongue, and 75% of them were young patients. The results indicate that p16 methylation is a more common event in those younger than 40 years in contrast to p16 deletions, which are more common in those older than 40 years. Consequently, it appears that specific modes of inactivation of p16 in HNSCC are related to specific patient risk profiles. Interestingly, HPV 16 messenger RNA was detected exclusively in HNSCC from the base of tongue lesions and was only found in males. This differs from the patient profile of HNSCC in the young, which affects the anterior tongue and commonly females, thus, making it highly unlikely that this virus is a primary causative agent of HNSCC in these young adults.

Right atrial paraganglioma: an unusual primary cardiac tumour.

We present a case of an unusual presentation of a rare primary cardiac tumour. There are no more than 50 previously reported cases of primary cardiac paraganglioma in the world literature and only a small proportion of these involve the right side of the heart. Diagnosis is difficult and surgical management is varied and complex.

Oral lymphangiectasias and Crohn's disease: two case reports.

Lymphangiectasias, or acquired lymphangiomas, are rare in the oral cavity, more typically occurring on the skin or the genital area and, to our knowledge, have not been reported previously in association with Crohn's disease. Lymphangiectasias can occur at any age and develop secondary to chronic obstruction of the lymphatics. This differentiates them from congenital lymphangiomas, which are congenital malformations of the lymphatic system. We present 2 cases of oral lymphangiectasias associated with Crohn's disease, one of which was treated successfully with cryotherapy.