Masao Kishikawa

Skin tumor risk among atomic-bomb survivors in Japan

Objectives: Elevated risks of skin cancer following high doses of ionizing radiation have long been known. Recent reports on atomic-bomb survivors indicate that nonmelanoma skin cancer can be induced at low to medium doses. We studied atomic-bomb survivors to determine the effects of radiation on specific histologic types of skin cancer and to describe the dose-response relationship.Methods: Cases of melanoma, nonmelanoma skin cancers, and Bowens disease were ascertained between 1958 and 1987 for the 80,000 cohort members through the population-based Hiroshima and Nagasaki (Japan) tumor registries augmented by searches of other records.Results: An excess of basal cell carcinoma (n=80), with some suggestion of a non-linear dose-response, was observed. The excess risk decreased markedly as age at exposure increased, and there was no evidence for an interaction between ionizing and ultraviolet radiation. No dose-response was found for squamous cell carcinoma (n=69). The excess relative risk point-estimates were large, but statistically nonsignificant for both melanoma (n=10) and Bowens disease (n=26).Conclusions: The basal layer of the epidermis appears to be quite sensitive to radiation carcinogenesis, particularly at a young age. The suprabasal layer seems to be more resistant, as shown by the lack of an association for squamous cell carcinomas.

Clinical and epidemiologic characteristics of first primary tumors of the central nervous system and related organs among atomic bomb survivors in Hiroshima and Nagasaki, 1958–1995†

Analysis conducted in the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki found a significant dose‐related excess of tumors of the central nervous system (CNS) and the pituitary gland. The objective of the current study was to evaluate clinical and epidemiologic characteristics of first primary tumors of the CNS and the pituitary gland in this cohort and to compare them with characteristics among other populations.

EXPRESSION OF THE SMALL HEAT SHOCK PROTEIN (HSP) 27 IN HUMAN ASTROCYTOMAS CORRELATES WITH HISTOLOGIC GRADES AND TUMOR GROWTH FRACTIONS

Summary1. Cellular expression and distribution of the stress response small heat shock protein 27 (hsp27) in 39 high-grade astrocytomas (27 glioblastoma multiformes, 12 anaplastic astrocytomas) and in 27 low-grade astrocytomas (grade I–II) were analyzed immunohistochemically.2. The correlation between hsp27 expression and tumor growth fractions of the astrocytomas was examined following Ki-67 immunostaining.3. The hsp27 staining was cell cytoplasmic. The hsp27 immunopositive rate was significantly higher in high-grade astrocytomas; the rates were 74% for glioblastomas, 58% for anaplastic astrocytomas, and 37% for low-grade astrocytomas. The small and large tumor cells, especially in glioblastomas, multinucleated tumor giant cells, tumor cells in the pseudopalisading and necrotic areas, cells of the microvascular endothelial proliferations, and tumor vascular smooth muscles were usually hsp27 positive. The mean percentage of hsp27-positive cells was significantly higher in the glioblastomas alone and in the combined high-grade astrocytomas, compared to the low-grade, and in recurrent rather than in primary high-grade astrocytomas.4. The high-grade astrocytomas had a highly statistical significant Ki-67 labeling index. The Ki-67 labeling indices were significantly higher in the hsp27-positive than the hsp27-negative astrocytomas, irrespective of the histological grade. In the high-grade astrocytomas with a Ki-67 labeling index of five and above, 81% of those tumors were hsp27 positive.5. Thus, a large number of human astrocytomas express hsp27, and hsp27 expression correlates with histological grades of astrocytoma and with tumor growth fractions. This being the case, hsp27 is likely to have a role in the growth of human astrocytomas.

Primary chondrosarcoma of the lung. A clinicopathologic study.

Background. Primary pulmonary chondrosarcoma is a rare neoplasm. A 73‐year‐old Japanese man had chondrosarcoma in the right lung. The tumor was considered to be of pulmonary origin because of the absence of extrapulmonary primary lesions for 2 years after lung resection.

Extracranial metastasis of glioblastoma with sarcomatous component

A case of glioblastoma with sarcomatous component is presented. Craniotomy was performed with total resection of the left occipital tumor. The patient received radiotherapy postoperatively but developed extracranial metastases only two months after the first surgical procedure.

Histologic characteristics of skin cancer in Hiroshima and Nagasaki: Background incidence and radiation effects

Skin cancers, though rare in Japan, have reportedly been on the rise, but little else is known about epidemiologic features of different histologic types of skin cancer. The Life Span Study cohort, which consists of 93,700 atomic‐bomb survivors, many of whom were exposed to negligibly low radiation doses, and 26,600 people not exposed to radiation, enables a population‐based study of spontaneous as well as radiation‐related cancer risk. Skin tumor incident cases diagnosed between 1958 and 1987 were ascertained by linkage to the Hiroshima and Nagasaki tumor registries augmented by searches of other data sources. Study pathologists reviewed tumor specimens and pathology reports and classified tumors using the World Health Organization classification scheme. They identified 274 primary incident skin cancers, of which 106 were basal cell carcinoma (BCC), 81 were squamous cell carcinoma (SCC), and 14 were malignant melanomas. Background incidence rates and radiation effects were assessed by Poisson regression models allowing for the effects of demographic and other covariates. BCC and SCC background incidence rates were both about 3 per 100,000 per year. BCCs were mainly on the head/neck (81%), whereas SCCs occurred most frequently on the arms/legs (45%) and head/neck (29%), consistent with the presumed role played by solar UV exposure in skin cancer. The BCC rates increased significantly between 1958 and 1987, whereas the SCC rates remained unchanged. The excess absolute risk of BCC per unit skin surface area related to atomic‐bomb radiation exposure did not differ between UV‐exposed and shielded parts of the body, suggesting the additivity of the radiation‐related and background BCC risks.

Primary Adrenal Lymphoma with Chromosomal Abnormalities

Lymphomas developing in the adrenal glands are rare. Twenty-one cases of primary adrenal lymphomas have been reported in the English literature, but no cytogenetic data were given. We had the opportunity to examine three cases of primary adrenal lymphoma characterized by the B cell phenotype. Samples for histologic and immunohistologic diagnosis were obtained from postmortem examination in cases 1 and 2, and with an ultrasound-guided needle biopsy in cases 2 and 3. In all 3 cases, histologic examination of adrenal masses showed diffuse medium-sized cleaved lymphoma cells, which were positive for L-26, an immunohistochemical B cell marker. Endocrine studies showed adrenal insufficiency in 1 case. Cytogenetic examination showed clonal abnormalities, including 8q24 in case 1 and 14q32 in case 2, similar to those observed in nodal B cell lymphoma.

Immunohistochemical expression of the estrogen receptor‐related antigen (ER‐D5) in human intracranial tumors

Background. Expression of the estrogen receptor‐related antigen (ER‐D5) has been reported in some normal and neoplastic tissues. The authors evaluated the expression of ER‐D5 in 143 intracranial tumors of different histologic types.

Age-related changes in basal dendrite and dendritic spine of hippocampal pyramidal neurons (CA1) among SAMP1TA/Ngs : quantitative analysis by the rapid Golgi method

It has been confirmed that a substrain of the senescence-accelerated mouse SAMP1TA/Ngs develops learning disturbance-like behavior at 3 months of age, exhibits almost normal behavior at 5 months, and manifests learning disturbance at 7 months. The changes with age in basal dendrites and dendritic spines of CA1 pyramidal neurons were quantitatively evaluated by the Golgi method using male SAMP1TA/Ngs. The correlation between the change in learning ability and the morphometry was examined. The number of dendritic spines in the 3- and 7-month-old groups was significantly lower than that in the 5-month-old group. It is presumed that the disturbance in acquisition of learning ability at 3 months of age is secondary to the immaturity of neurons, while the learning disturbance at 7 months of age is due to neuronal aging. This substrain, which is characterized by the impairment of acquired learning ability due to senescence, is useful as a model for studies on human brain dysfunction associated with senescence.

Skin Cancer Incidence among Atomic Bomb Survivors from 1958 to 1996

The radiation risk of skin cancer by histological types has been evaluated in the atomic bomb survivors. We examined 80,158 of the 120,321 cohort members who had their radiation dose estimated by the latest dosimetry system (DS02). Potential skin tumors diagnosed from 1958 to 1996 were reviewed by a panel of pathologists, and radiation risk of the first primary skin cancer was analyzed by histological types using a Poisson regression model. A significant excess relative risk (ERR) of basal cell carcinoma (BCC) (n = 123) was estimated at 1 Gy (0.74, 95% confidence interval (CI): 0.26, 1.6) for those age 30 at exposure and age 70 at observation based on a linear-threshold model with a threshold dose of 0.63 Gy (95% CI: 0.32, 0.89) and a slope of 2.0 (95% CI: 0.69, 4.3). The estimated risks were 15, 5.7, 1.3 and 0.9 for age at exposure of 0–9, 10–19, 20–39, over 40 years, respectively, and the risk increased 11% with each one-year decrease in age at exposure. The ERR for squamous cell carcinoma (SCC) in situ (n = 64) using a linear model was estimated as 0.71 (95% CI: 0.063, 1.9). However, there were no significant dose responses for malignant melanoma (n = 10), SCC (n = 114), Paget disease (n = 10) or other skin cancers (n = 15). The significant linear radiation risk for BCC with a threshold at 0.63 Gy suggested that the basal cells of the epidermis had a threshold sensitivity to ionizing radiation, especially for young persons at the time of exposure.