Jun Miyagi

Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma

Primary rhabdoid tumour of the lung is rare, and histological and biological characteristics have not been fully documented. We describe three cases of primary lung rhabdoid tumour, all associated with adenocarcinoma, and investigate the histological features and biological characteristics.

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV‐infected squamous cell carcinoma and adenocarcinoma of the lung

Aims: The infiltration of Langerhans cells in adenocarcinomas and squamous cell carcinomas of the lung was examined in relation to prognostic implications and human papillomavirus (HPV) infection.

Prognostic Implication of Human Papillomavirus Infection in Squamous Cell Carcinoma of the Lung

On the subtropical island of Okinawa, squamous cell carcinoma (SCC), particularly the well-differentiated form, is the most frequent type of lung cancer, while this form is relatively rare on the Japanese mainland and in other countries. Furthermore, in Okinawa, in 1993, 80% of SCC cases of the lung were found to be infected with human papillomavirus (HPV). We studied the prognosis of SCC of the lung with HPV infection (n = 25) and compared it with non-HPV-infected SCC (n = 16). Using the Kaplan-Meier method (Wilcoxon analysis), the prognosis of HPV-infected cases was found to be better than that of the non-infected cases. In the virus-infected cases, apoptosis and infiltration of a large number of Langerhans cells were demonstrated. In addition to these findings, the virus-infected tumors were demonstrated to be histologically well-differentiated, perhaps contributing to the favorable prognosis. However, among the virus-infected cases, the type 16 virus-infected cases showed a poorer prognosis, compared to those infected with other HPV types. p53 gene mutation was also examined, and was considered to be an unfavorable prognostic factor, as reported elsewhere. However, in Okinawa, HPV-positive cases with p53 mutations showed a slightly better prognosis than did non-viral infected cases with p53 mutations. The TNM staging system was also useful for categorizing the virus-infected cases. The prognosis of stage III (A and B) cases was poor. All of our present cases received surgical treatment. Chemotherapy and radiation therapy were not performed. Such treatment, however, might be effective, because virus-infected uterine cervical carcinomas have been routinely treated with chemotherapy and radiation. Furthermore, if the immunological basis of increased Langerhans cell infiltration in HPV-infected cases is elucidated, a clinical trial with immunotherapy may be favorable for the clinical outcome.

Differences in EBNA2 and LMP-1 Carboxy Terminal Region Sequences of Epstein-Barr Virus Type A Between the Tumors in a Multiple Cancer Patient

Using PCR, type A Epstein-Barr virus (EBV) infection was demonstrated in a squamous cell carcinoma of the maxilla (in a 52-year-old man) and the tongue of the same patient 18 years later (at the age of 70). Furthermore, at the age of 72, this patient developed an EBV-infected anaplastic large cell lymphoma. Analysis of the terminal regions of the EBV genome revealed a monoclonal proliferation of EBV-infected lymphoma cells. However, sequence analysis of the EBV revealed a slight difference in the EBNA2 regions between the virus-infected lymphoma and the squamous cell carcinomas. The mutations at 48991 (G-->T) and 48998 (C-->A) were demonstrated in the lymphoma. Although the squamous cell carcinoma of the tongue occurred after an interval of 18 years, the mutation site in the carcinomas was the same, 49137 (A-->G), as compared with B95-8 strain EBV EBNA2. The mutations at 48991 and at 49137 were associated with amino acid changes, Arg-->Met and Thr-->Ala, respectively, but the alteration at 48998 was a silent mutation. Thirty-bp deletion in the LMP-1 carboxy terminal region was demonstrated in the virus-infected lymphoma, but not in the squamous cell carcinomas. On the other hand, HTLV-1 proviral DNA (tax, gag and env) was not detected in the lymphoma, nor was HPV demonstrated in the squamous cell carcinomas, although Okinawa is known as an HTLV-1 and HPV prevalence region. The T-cell receptor beta gene rearrangement was demonstrated in the lymphoma, but the t(2;5) fusion transcript was not detected using PCR. Cytogenetic analysis of the lymphoma cells showed a complex hypertriploid karyotype with 76XY. The type A EBV infection might play a role in the carcinogenesis of the tumors of our patient. Interestingly, the infected virus genome sequences, the EBNA2 and LMP-1 regions, which were closely associated with carcinogenesis in the squamous cell carcinomas and the lymphoma, showed slight differences.

The Challenge to Reduce Breast Cancer Mortality in Okinawa: Consensus of the First Okinawa Breast Oncology Meeting

Breast cancer mortality is gradually increasing in Okinawa. The 1st Okinawa Breast Oncology Meeting was held on 6 July 2012 and discussions on how to curb the rising trend were focused on breast cancer screening, adjuvant treatment, socioeconomic and geographic issues, and the problem of complementary and alternative medicine. The consensus of the 1st Okinawa Breast Oncology Meeting was that ultrasonography screening is an acceptable screening system for Okinawan women because of the geographic disadvantage of having many small islands and rural areas. Educational and economic support is needed for women in rural areas to get correct information, for access to urban areas and to be treated by evidence-based optimal therapy for breast cancer. In addition, new approaches are needed for Okinawan people to successfully educate patients to correctly interpret evidence-based information.

Experimental myelitis in BALB/cN and C57BL/6N mice caused by herpes simplex virus type 1 compared with herpes simplex virus type 2.

Intraperitoneal and footpad inoculations of herpes simplex virus type 1 (HSV) into BALB/cN (HSV-susceptible) and C57BL/6N (HSV-resistant) mice were carried out to induce experimental myelitis. Standard laboratory strains (McIntyre, F, RK, and recently Okinawa strain R1) were inoculated in mice. As a control, the HSV 2 standard laboratory strain SAV was also inoculated. The McIntyre strain was the most virulent, while the F strain was the least. RK and R1 were both moderately virulent. Myelitis was induced in BALB/cN mice after intraperitoneal and footpad inoculations of low to high doses of the McIntyre strain, and intraperitoneal inoculation of moderate and high doses of the RK and R1 strains. Symptoms of paraplegia of the hind legs and rectal and urinary incontinence were observed, but not until 3-5 hours before death. The symptoms caused by footpad inoculation were slightly different from those following intraperitoneal inoculation; rectal incontinence, in particular, was inconspicuous in the former. In the case of footpad inoculation of RK and R1, only one mouse inoculated with R1 showed symptoms and histology of myelitis. The F strain caused no symptoms. In the case of C57BL/6N mice, high dose intraperitoneal and footpad inoculations of the McIntyre strain also caused myelitis, and the symptoms were observed about 6-7 hours before death. In only one C57BL/6N mouse intraperitoneally inoculated with a high dose of R1 did symptoms appear about 6 hours before death. The same symptoms caused by intraperitoneal and footpad inoculations of HSV 2 (SAV) were observed more clearly and for a longer period (half to one day) than those caused by HSV 1 inoculation. Spinal cord necrosis was noted with McIntyre, RK and R1 inoculations, but it was not marked with randomly located foci, when compared with that caused by SAV. Further, the foci of necrosis in C57BL/6N mice were smaller than in BALB/cN mice, even when high dose McIntyre strain was used. Nuclear pyknosis and edema of the brain in the dead mice following HSV 1 inoculation were more marked than in those killed by SAV.