Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV: the largest demographic study of 210 Danish patients.

BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly (5.4% per year) during the study period. This was explained by a significant increase in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type. CONCLUSIONS: The increased number of HPV-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010.

Impact of technology on cytology outcome in cervical cancer screening of young and older women.

Little is known about age-dependent variation in outcomes of cervical cytology with modern technologies. This population-based study evaluated age-dependent changes after routine implementation of ThinPrep and SurePath technology in two independent laboratories, and controlled for time trends in a third laboratory using manually read conventional cytology continually. Data were collected from the Danish National Health Care Registers. For each laboratory, we compared proportions of abnormal cytology defined as atypical squamous cells of undetermined significance or worse (ASCUS+) by age and technology phase. The study included 489,960 cytological samples with no recent abnormality from women aged 23-59 years, routinely screened between 1998 and 2007. Implementation of SurePath liquid-based cytology (LBC) was followed by an increase in abnormal cytology in women aged 23-29 years from 4.6 to 6.1%, relative proportion (RP): 1.31 [95% confidence interval (CI): 1.08-1.61], and a decrease in women aged 45-59 years from 2.9 to 2.0%, RP: 0.71 (95% CI: 0.60-0.83). Implementation of ThinPrep LBC was followed by a decrease in abnormal cytology both in women aged 23-29 years from 7.7 to 6.8%, RP: 0.89 (95% CI: 0.78-1.02) and in women aged 45-59 years from 3.4 to 1.0%, RP: 0.30 (95% CI: 0.24-0.37). With implementation of imaging-assisted reading, regardless of the brand of technology, the proportion of abnormality increased by around 30% in all age groups (range from 19 to 41%). In the laboratory with unchanged technology no trends in abnormality proportions were observed. The impact of LBC implementation on cytological abnormality proportions varied considerably across age groups.

Platysma and the cervical superficial musculoaponeurotic system - Comparative analysis of facial crease and platysmal band development.

OBJECTIVE: The superficial musculoaponeurotic system connects the mimic muscles to the skin, allowing mimic expressions with regional morphological architectural differences. The aim of this study was to perform an architectural analysis of the cervical platysma-skin interaction, determine the morphological implications in platysmal band development and compare the findings to the facial SMAS architectural types. METHOD: Full-thickness blocks of skin, SMAS and platysma from seven hemifaces (three male and two female) and full-thickness blocks of skin, SMAS and mimic muscles of the periorbital, perioral, forehead and midfacial regions from six hemifaces (three male and three female) of donor bodies were collected postmortem. Serial histological sections were cut and stained with Azan. After the morphological analysis, three-dimensional reconstruction of the tissue block was performed with AutoCAD. The morphological and mechanical properties of the different facial SMAS types were compared with those of the cervical SMAS. RESULTS: The architecture of the cervical SMAS (type V) consists of parallel, aligned septum fibrosus profundus and septum fibrosus superficialis tissue connected by vertical, aligned septa fibrotica commisurales tissue delimiting fatty tissue compartments transferring platysmal contractions to the skin. The facial morphological dynamic mimic pattern (SMAS types I, II and III) describes the point-by-point transfer of mimic muscle bundle contractions to the skin, explaining facial crease formation. The cervical morphological dynamic mimic pattern (SMAS type V) can be explained by dual traction force collimation over the septum fibrosus superficialis and profundus in platysmal band development. CONCLUSIONS: The cervical SMAS (type V) description supports the hypothesis that the SMAS and platysma have different morphological origins. The two different facial and cervical morphological dynamic mimic patterns support the phenotypical difference between facial fold and platysmal band development.

Expression of p53 in normal nasal mucosa and in sinonasal papillomas with and without associated carcinoma and the relation to human papillomavirus (HPV).

The aim of the present study was to investigate the expression of p53 in sinonasal papillomas, carcinomas ex papillomas and normal nasal mucosa. Furthermore, we wanted to study the expression of p53 in relation to the presence of human papilloma virus (HPV). Immunohistochemical staining was performed on 37 formalin-fixed paraffin-embedded biopsies comprising seven biopsies from normal nasal mucosa, 13 papillomas of an exophytic growth pattern, 12 papillomas of an endophytic growth pattern and five carcinomas. The level of p53 overexpression was defined as more than 5% positive nuclei. The normal nasal mucosa showed no positive nuclei. The papillomas of both exophytic and endophytic growth patterns showed scattered positive nuclei, but in all cases this was less than 5%. p53 was overexpressed in three out of five carcinomas. In conclusion, we found an overexpression of p53 in carcinomas occurring in sinonasal papillomas but not in the benign tumours of the sinonasal mucosa. Thus, this report supports the concept that p53 may have a role in the carcinogenic process in head and neck tumours.

The presence of human papillomavirus in sinonasal papillomas, demonstrated by polymerase chain reaction with consensus primers.

The frequency of human papillomavirus (HPV) in sinonasal papillomas seems to vary considerably. The highest frequencies have been reported by investigators using in situ DNA or RNA hybridization. Few studies have used polymerase chain reaction, and in these reports the frequency of HPV detection is rather low. We have investigated the presence of HPV in sinonasal papillomas using the polymerase chain reaction with a set of degenerated consensus primers, which amplify the vast majority of the known HPV types. Human papillomavirus was found in three of 14 papillomas. By in situ hybridization the same three papillomas were positive for HPV type 6/11.

Aspergillus fumigatus fungaemia and myocarditis in a patient with acquired immunodeficiency syndrome.

Necrotizing myocarditis due to Aspergillus fumigatus was a contributory cause of death in a patient with acquired immunodeficiency syndrome and non-Hodgkin lymphoblastic malignant lymphoma of the Burkitt type. A transient remission of the lymphoma had been obtained by cytostatic treatment. A. fumigatus was isolated from blood two weeks before death, but myocarditis was not diagnosed until autopsy.

Carcinoid tumour of the breast.

A case of primary carcinoid in the female breast is reported. The patient was treated by segmental mastectomy and is without local recurrence and signs of carcinoid tumour at any other site after 3 years of observation.

Sinonasal papillomas: a report of 82 cases in Copenhagen County, including a longitudinal epidemiological and clinical study.

The present epidemiological and clinical study comprises 82 patients with sinonasal papillomas diagnosed from 1975 to 1993. Histology showed 58 cases of inverted papillomas including 5 cases of associated carcinoma, 19 cases of exophytic papilloma, and 5 cases of columnar cell papilloma. The incidence of sinonasal papillomas in Copenhagen County was 0.74 per 100,000 inhabitants per year. The inverted and columnar cell papillomas were typically located in the middle meatus with a varying degree of involvement of the adjacent sinuses. The exophytic papillomas were predominantly located multicentrically on the nasal septum. Good results of treatment, especially with regard to inverted papillomas, were not correlated to the aggressiveness of surgery. A lateral rhinotomy with medial maxillectomy was performed as primary surgery in 28 patients. In 50% of these patients there were recurrences. The preliminary results of endonasal endoscopic surgery revealed a high success rate, i.e., no recurrences in 5 cases so far. The septal papillomas were typically resected by a simple endonasal procedure. There were recurrences in 66% of these cases. The midfacial degloving procedure may be advocated instead of or as a supplement to the lateral rhinotomy if the tumor cannot be visualized sufficiently by endoscopy. Smoking may dispose to sinonasal papillomas.

Human papillomavirus and normal nasal mucosa: detection of human papillomavirus DNA in normal nasal mucosa biopsies by polymerase chain reaction and in situ hybridization.

To determine a possible etiological role of human papillomavirus (HPV) in sinonasal papillomas and squamous cell carcinomas, it is necessary to investigate normal nasal mucosa of healthy persons for the presence of HPV. The material in the present study consists of 21 biopsies taken from the inferior concha of 21 otherwise healthy persons who underwent surgery for nose fractures or nasoseptal deviations. In addition, five inferior conchae were obtained from persons who had died of non-neoplastic diseases. HPV was not detected in any of these specimens, either by polymerase chain reaction or by in situ hybridization. Histologic evaluation showed that squamous metaplasia was a common finding in the biopsies. The presence of HPV in sinonasal papillomas and carcinomas may indicate that HPV is an etiological factor in these lesions.

Human papillomavirus (HPV) in sinonasal papillomas: a study of 78 cases using in situ hybridization and polymerase chain reaction.

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.

Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998.

OBJECTIVES: To determine a putative role and relation between human papilloma virus (HPV) and p53 in the etiology of sinonasal carcinomas associated with papillomas. STUDY DESIGN: The study group consists of all patients with sinonasal carcinomas associated with papillomas diagnosed in Denmark from 1980 to 1998. After reviewing our national pathological files, tumor tissues from 36 patients were collected, comprising 15% of the total cases of sinonasal carcinomas. In 35 cases a squamous cell carcinoma was demonstrated and in one case an adenocarcinoma was evident. Inverted papilloma was associated with carcinoma in 31 cases and exophytic papillomas in 5 cases. The material was investigated for HPV using polymerase chain reaction analyses with two sets of consensus primers (GP5+/GP6+ and MY09/MY11). The HPV-positive cases were submitted to dot-blot hybridization to establish the HPV type. Using immunohistochemistry, the p53 expression was determined. A p53 overexpression is defined as positive staining in 10% or more of the tumor cells. RESULTS: Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%). P53 overexpression was not shown among the HPV-positive cases, whereas p53 overexpression was seen in 21 of the 24 (88%) examined HPV-negative cases. Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%). In addition, one case more was with p53 overexpression. CONCLUSION: An inverse relation between HPV and p53 overexpression in sinonasal carcinomas associated with inverted papillomas appears to have been demonstrated. HPV and p53 might also have an etiological role among the carcinomas associated with exophytic papillomas.

Adenomatoid tumor of the uterus.

A case of adenomatoid tumor of the uterus of a 49-year-old woman is described. The tumor was unusually large and atypically located in the fundus of the uterus. Adenomatoid tumors in genitals are benign but may macroscopically resemble a malignant tumor. As recurrence does not occur simple excision is sufficient.

Carcinomas occurring in papillomas of the nasal septum associated with human papilloma virus (HPV).

Carcinomas arising in pre-existing sinonasal papillomas of the nasal septum are rare. To our knowledge only one case has been reported. We report two cases of carcinomas occurring in septal papillomas. In the first case a carcinoma developed in an exophytic papilloma 16 years after the first operation for a papilloma. In the second case a carcinoma was present at the first presentation within an inverted papilloma, and a metastasis had also developed. In the first case HPV type 6/11 was demonstrated by in-situ hybridisation and PCR in the original papilloma as well as in the recurrent papilloma and in the carcinoma. In the second case HPV type 18 was found in the nasal lesion as well as in the metastasis. All samples were examined for Epstein-Barr virus (EBV) by PCR, but with negative results. We believe that case one is the first reported case of carcinomatous transformation within an exophytic septal papilloma.

Tracheobronchial involvement of laryngeal papillomatosis at onset.

A case of adult onset laryngeal papillomas with tracheal and bronchial involvement present at onset is presented. The presence of human papilloma virus (HPV) DNA type 6/11 is demonstrated by in situ hybridization.

[Occurrence of lung cancer in Denmark 1943-1986. Reliability of the cancer registry]. / Forekomsten af lungekraeft i Danmark 1943-1986. Cancerregisterets pålidelighed.

A rise in the number of adenocarcinomas of the lung and a fall in squamous cell carcinomas are seen in Denmark since 1978; a change based on a growing number of lung cancers among women with an excess of adenocarcinomas. A fall in the frequency of autopsies in Denmark will entail the loss of an essential control of the quality of diagnosis of lung cancer, primary or secondary, and make future descriptive studies difficult to interpret. The validity of morphologic diagnosis of lung cancer as recorded by the Danish Cancer Registry during 1943-1986 was assessed. We extracted a stratified random sample of 5% of all recorded cases prior to 1978, these were then recorded according to the ICD-O classification. Cases after 1978 were originally coded in the Registry according to ICD-O, here we checked the coding against the original reports. The information on morphology prior to 1978 was too inprecise to merit evaluation of trends and proportionate distributions by morphology. After 1978 data was adequate, and after 1983 very precise.

Ultraconservative management of appendiceal abscess.

An appendiceal abscess is usually treated conservatively. Drainage of the abscess is instituted if this treatment is unsuccessful. Some surgeons practise immediate appendectomy and abscess drainage. An alternative ultraconservative approach whereby abscess drainage is avoided has been reviewed retrospectively. Twenty-eight patients were treated by observation only. They remained in hospital for between 1 and 36 days (median 10 days) until their signs and symptoms disappeared. No patient required surgery or developed complications in hospital. One patient developed acute appendicitis 10 days after discharge. One developed a recurrent abscess. Another group of 19 patients were treated over the same period of time by immediate operation. Ten developed postoperative complications. Hospitalization ranged from 4 to 36 days (median 8 days). Ultraconservative management of appendiceal abscess is a safe and effective alternative to immediate surgery, or ultrasound- or computed tomographic-guided drainage.

Hepatic effects of dietary weight loss in morbidly obese subjects.

This prospective study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet. Fourty-one morbidly obese, non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg. Fatty change improved (p less than 0.001), but 24% of the patients developed slight portal inflammation (p = 0.039) or slight portal fibrosis (p = 0.063). Patients developing portal fibrosis had a higher degree of fatty change at entry (p = 0.029), a more pronounced reduction of fatty change (p = 0.014) and a faster weight loss (p = 0.026). Liver biochemistry, which was of no individual diagnostic value, improved. It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions.

Flutamide-induced liver failure.

Two cases of clinically manifest liver failure in patients with metastatic prostatic cancer treated with the non-steroidal antiandrogen flutamide combined with a luteinizing hormone-releasing hormone analogue are described. One patient developed severe hepatic insufficiency with jaundice, ascites and hepatic coma. The condition reversed after discontinuation of flutamide. The other patient only became jaundiced with a biochemical cholestatic pattern. Previous reports of hepatic adverse reactions only include elevated transaminase levels without clinical manifestations. The morphological lesions in the liver biopsy and the clinical condition may be due to a reversible interaction with metabolic processes in the hepatocytes.