A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: the largest registry-based study to date.

The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13-2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11-0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01-1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90-1.08). In conclusion, the observed increase in the number of HPV-positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000-2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.

Expression of anaplastic lymphoma kinase in Merkel cell carcinomas.

This study examines the presence of anaplastic lymphoma kinase protein and anaplastic lymphoma kinase gene rearrangements in Merkel cell carcinomas. A total of 32 cases of Merkel cell carcinomas and 12 cases of small cell lung carcinomas were analyzed. Immunohistochemistry was performed using 3 different anaplastic lymphoma kinase antibody clones (D5F3, 5A4, and anaplastic lymphoma kinase 1). Tumors were divided into high (intensity score 2-3+ in ≥25% of the tumor cells) and low expressors (all other positive expression patterns). Anaplastic lymphoma kinase reactivity in Merkel cell carcinoma was observed in 93.8% (30/32) with clone D5F3, 87.5% (28/32) with clone 5A4, and 12.5% (4/32) with clone anaplastic lymphoma kinase 1. One small cell lung carcinoma (1/12; 8.3%) showed anaplastic lymphoma kinase low expression with clone D5F3. Anaplastic lymphoma kinase high expression was observed in 81.3% (26/32) of the Merkel cell carcinomas with clone D5F3, 71.9% (23/32) with clone 5A4, and none with clone anaplastic lymphoma kinase 1. The specificity of anaplastic lymphoma kinase expression in Merkel cell carcinoma versus small cell lung carcinoma was 91.7% with clone D5F3 and 100% with the clones 5A4 and anaplastic lymphoma kinase 1. Interphase fluorescence in situ hybridization with the anaplastic lymphoma kinase dual-color, break-apart rearrangement probe was performed on 10 randomly selected Merkel cell carcinoma anaplastic lymphoma kinase high expressors. No rearrangement or other cytogenetic aberration of the anaplastic lymphoma kinase gene locus was identified. In conclusion, the anaplastic lymphoma kinase protein was detected with high frequency in Merkel cell carcinomas and was useful in distinguishing Merkel cell carcinoma from small cell lung carcinoma. No correlation with anaplastic lymphoma kinase rearrangement was found. Our findings could have important therapeutic consequences for patients, but the role of anaplastic lymphoma kinase in the pathogenesis of Merkel cell carcinoma needs to be further elucidated.

Novel de novo BRCA2 mutation in a patient with a family history of breast cancer.

BACKGROUND: BRCA2 germ-line mutations predispose to breast and ovarian cancer. Mutations are widespread and unclassified splice variants are frequently encountered. We describe the parental origin and functional characterization of a novel de novo BRCA2 splice site mutation found in a patient exhibiting a ductal carcinoma at the age of 40. METHODS: Variations were identified by denaturing high performance liquid chromatography (dHPLC) and sequencing of the BRCA1 and BRCA2 genes. The effect of the mutation on splicing was examined by exon trapping in COS-7 cells and by RT-PCR on RNA isolated from whole blood. The paternity was determined by single nucleotide polymorphism (SNP) microarray analysis. Parental origin of the de novo mutation was determined by establishing mutation-SNP haplotypes by variant specific PCR, while de novo and mosaic status was investigated by sequencing of DNA from leucocytes and carcinoma tissue. RESULTS: A novel BRCA2 variant in the splice donor site of exon 21 (nucleotide 8982+1 G-->A/c.8754+1 G-->A) was identified. Exon trapping showed that the mutation activates a cryptic splice site 46 base pairs 3' of exon 21, resulting in the inclusion of a premature stop codon and synthesis of a truncated BRCA2 protein. The aberrant splicing was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. The mutation was not found in any of the patient's parents or in the mother's carcinoma, showing it is a de novo mutation. Variant specific PCR indicates that the mutation arose in the male germ-line. CONCLUSION: We conclude that the novel BRCA2 splice variant is a de novo mutation introduced in the male spermatozoa that can be classified as a disease causing mutation.

[Colon ileus caused by endometriosis]. / Colonileus som følge af endometriose.

A case history of acute obstruction of the sigmoid colon caused by endometriosis in a 35-year-old woman is described. Endometriosis occasionally causes relative stenoses of the bowel, whereas total obstruction is rarely seen. Obstruction of the sigmoid colon is often caused by malignancy, but sometimes other causes must be considered.

[Inflammatory pseudotumour of the liver]. / Inflammatorisk pseudotumor i leveren.

A case study of inflammatory pseudotumour of the liver (IPL) is related. The patient presented with symptoms, biochemistry and ultrasonic findings highly indicative of a malignant disease. However, a core needle biopsy revealed inflammatory pseudotumour of the liver, an infrequent diagnosis with only about 200 cases to be found in the literature. This case illustrates the importance of core biopsy from focal processes, since IPL is a benign condition with a strong tendency to spontaneous regression.