Masachika Iseki

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.

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.

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 renal angiosarcoma: A case report and review of the literature

Primary renal angiosarcoma is very rare. To our knowledge, only 15 cases have been reported to date. A 77‐year‐old Japanese man with a unilateral kidney presented with massive hematuria followed by renal failure. A renal tumor was suspected and a left nephrectomy was performed. The histopathological diagnosis was angiosarcoma of the kidney. A hemorrhagic tumor measuring 10 × 5 cm and clotted blood was found in the modularly area. The atypical tumor cells had a sinusoidal and solid appearance, and showed Immunohistochemically positive reactions for some of the endothelial markers. The patient died about 21 months after the nephrectomy and the autopsy revealed massive metastases to the liver and retroperitoneum. One of the differential diagnoses of the case was anglomyolipoma, because the tumor cells were relatively bland in their histological appearance with entrapped fat cells in the pelvic area. Fifteen case reports with titles that included the term ‘hemangiosarcoma/anglosarcoma’, ‘hemangioendothelloma/endothelloma’ or ‘vascular sarcoma’ of the kidney were reviewed and compared to the present case.

Immunohistochemical expression of E-cadherin in metastatic brain tumors

The adhesion molecule E-cadherin has been shown to influence malignant transformation of tumors, including local and distant metastases. We examined the expression of E-cadherin to determine its relationship to the development of metastasis in metastatic brain tumors. Immunohistochemistry for E-cadherin and Ki-67 was carried out in 76 formalin-fixed, paraffin-embedded archival specimens of metastatic brain tumors and in 14 corresponding available primary tumors from patients who received treatment for metastatic brain tumors. The primary tumors were mainly lung cancers (51.3%), followed by gastrointestinal tumors (28.9%). E-cadherin was expressed in 62 (81.5%) of 76 cases examined. In metastatic adenocarcinomas, a consistent tendency for E-cadherin expression was noted, regardless of the degree of differentiation or the extent of spread of the disease (P=0.4). There was a direct correlation between E-cadherin expression and high MIB-1 index in all metastatic brain tumors (P=0.0007). Pairwise analysis in 14 primary tumors and the corresponding metastatic specimens revealed high E-cadherin and MIB-1 staining in metastatic brain tumors. These results provide a unique association between E-cadherin, systemic metastasis, and proliferation potential in metastatic brain tumors.

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.

Thymolipoma with striated myoid cells: histological, immunohistochemical, and ultrastructural study

A large asymptomatic anterior mediastinal thymolipoma, discovered by chest radiograph during a regular check-up for company employees, was excised from a 33-year-old Japanese man. On immunohistochemical and electron-microscopic examination, clusters of myoglobin-positive cells with cytoplasmic Z band structures were found scattered in the medulla. Myoid cells have been previously seen in the normal thymus as well as in thymic hyperplasia, thymoma, and in the thymus of patients with myasthenia gravis. To our knowledge, this is the first reported instance of myoid cells in a thymolipoma.

A histopathological study on senile changes in the human olfactory bulb.

Senile changes in the human olfactory bulb were studied histopathologically in 133 individuals ranging in age from 40 to 91 years with a mean age of 64.3 years. Neurofibrillary tangles (NFTs) in the olfactory bulb were observed in 47 subjects aged over 50 years. The frequency of NFTs was 35.3% (47/133) in total and 40.5% (47/116) among subjects 50 years of age or older. The frequency of individuals with NFTs increased linearly with age. Senile plaques (SPs) were observed in 5 individuals over 60 years old at a frequency of 3.8% (5/133) in total and 5.7% (5/88) among individuals 60 years old or more. Granulovacuolar degeneration was rarely seen, and amyloid angiopathy was not recognized. Senile changes in the hippocampus and parahippocampal gyrus were also examined. In some cases, the frequencies of NFTs and SPs in the hippocampal region were not identical to those in the olfactory bulb. However, it was not apparent whether senile changes first appear in the olfactory bulb or in the hippocampal region.

A Clinicopathologic Study of Tumors and Tumor-like Lesions of the Penis

A total of 147 specimens from 93 patients with penile lesions were examined at Nagasaki University Hospital during a 27‐year period from 1961 to 1987. The most frequent malignant tumor was squamous cell carcinoma (SCC, 33 cases, 35.5%), followed by extramammary Pagets disease, transitional cell carcinoma, and Bowens disease. The benign tumors and tumor‐like lesions included condylorna acuminatum, cyst of the genitoperineal raphe, and lymphangioma. SCC of the penis accounted for less than 0.1% of all specimens and less than 0.62% of malignant tumors in men filed at our hospital. True phimosis accompanied 81.5% of the SCC cases. The 5‐and 10‐year survival rates for SCC were 77.2% and 71.3% respectively. Two patients died of penile SCC. It was considered that an absence of both keratohyaline granules in the granular layer and melanin pigment in the basal layer can serve as a useful histologic indicator for diagnosis of well differentiated SCCs that are otherwise difficult to identify.

Anaplastic Ependymoma of the Spinal Cord in Childhood A Case Report

We report a 6‐year‐old girl with anaplastic ependymoma probably originating in the region of the conus medullaris and probably spreading retrogradely to the region of the interventricular foramen (Monro) through the cere‐brospinal fluid (CSF). Since ependymoma of the spinal cord rarely occurs in children, and retrograde spreading is extremely rare, the histological features and mechanism of metastasis of the tumor are discussed.