Gastric-type mucinous carcinoma of the cervix and its precursors – historical overview

The emerging concept of gastric-type mucinous carcinoma (GAS) of the uterine cervix has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papillomavirus (HPV). GAS is included as a variant of mucinous carcinoma in the 2014 World Health Organization classification, and its recognition has provoked a discussion on endocervical adenocarcinoma as a single entity such that endocervical adenocarcinoma is now divided into HPV-associated and HPV-independent groups. This article reviews historical and conceptual aspects of GAS and its precursors, starting with minimal deviation adenocarcinoma (MDA), through the ensuing confusion, up to the recent paradigm shift in cervical adenocarcinoma subclassification. The gastric immunophenotype of MDA was demonstrated by a Japanese group in 1998 using the HIK1083 antibody, which recognises gastric pyloric gland mucin, and this elucidated the pathogenesis of this particular tumour. However, this information resulted in overdiagnosis of lobular endocervical glandular hyperplasia (LEGH), first described in 1999 and which represents pyloric gland metaplasia (PGM), as malignant. In the early 2000s the relationship between MDA and LEGH/PGM became a matter of controversy. In 2007 HIK1083 immunohistochemistry extended the morphological spectrum of endocervical adenocarcinoma showing gastric differentiation beyond MDA, which resulted in the proposal of GAS as a distinct entity including MDA as its very well-differentiated subtype. GAS is now considered to be an aggressive and chemoresistant neoplasm that is not related to high-risk HPV. The LEGH/PGM–GAS sequence is currently regarded as an HPV-independent pathway of carcinogenesis. Understanding the underlying molecular events in this process is key to the development of biomarkers for early detection and molecular targeted therapy.     

CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.     

Case report of periodontal disease with periodic neutropenia

A case of periodic neutropenia with specific symptoms of gingiva and alveolar bone loss in primary dentition is reported. The patient was a boy, and it was followed between the ages of 3- and 9 years-old. At the period of neutropenia he was suffered from recurrent redness, swelling and bleeding of the gingiva, and also with cold-like symptoms with fever. Although the cause of these symptoms was not definite at first, even in medical exploration, we could diagnose this disease as periodic neutropenia by the process of dental therapy. By alveolar bone resorption, pocket formation and severe tooth mobility, the patient had lost more than half of his primary teeth at the end of 2 years after the initial examination. However throughout this period we motivated and instructed the patient and his mother how to brush his teeth. His oral hygiene was improved in the mixed and permanent dentition stages. Then there was no evidence of bone resorption around the teeth of the permanent dentition stage, but recurrent gingival symptoms are continuing now. The specific feature of this case is found in the gingival findings. There was no ulceration of the oral mucosa, but a bright red jelly-like appearance was found periodically in the area of the marginal and attached gingiva. The junction between the reddened attached gingiva and the alveolar mucosa was well-defined. The serial examination of peripheral blood in this case revealed the cycle of neutropenia as 16 to 21 days. During this examination, and at the almost time of neutropenia of this patient, hyperplasia of monocytes and lymphocytes occurred. In this situation there was no clinical signs except for gingival redness. However at other times, generally marked signs were recurrent. This may have occurred due to the lack of both neutrophils and monocytes. From the above results we think that periodic neutropenia may be diagnosed first in the dental clinic by the distinctive redness in the gingival area as one specific sign of this disease. We also think that plaque control procedures may retain the teeth.     

Children's dental health: British expatriate residents in Tokyo, Japan

AIM: To identify in expatriate British parents resident in Tokyo, Japan, their levels of dental health knowledge, patterns of dental health behaviour, and caries status of their children compared to Japanese children. METHODS: 223 parents with children at one school were asked to complete a structured questionnaire. Data were collected on: parental knowledge and behaviours with respect to caries prevention, and sweet consumption of the children. The caries status of the children was established by a clinical examination, using standard criteria. RESULTS: The questionnaire response rate was 66.8%. The mean age of the children was 7.6 years (range 3-11 years). The responses related to 51 British, 21 Japanese, and 20 children who had British and Japanese mixed parents. 33% of British and none of Japanese children had sweet foods frequently. Fluoridated toothpaste was used by 67% of British and 10% of Japanese children. British parents knew about dental caries more than Japanese. 13% of British and 38% of Japanese children were found in the higher caries experience group. CONCLUSION: Parental access to information in the UK and to fluoridated toothpaste in Japan could have helped to prevent dental caries in these expatriate British children.