Shigeru Hatakeyama

Chronic manganese poisoning: A neuropathological study with determination of manganese distribution in the brain

SummaryAn autopsy case of a 52-year-old man suffering from chronic manganese poisoning (CMP) is reported with determination of the manganese distribution in the brain. The patient had been working in a manganese ore crushing plant since 1965. In 1967 he began to complain of difficulties in walking and diminished libido. Later, he developed various neuro-psychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, “cock-walk”, increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of knee jerks. The major neuro-pathological change was degeneration of the basal ganglia, in which the pallidum was severely affected. The pallidum discolsed a loss and degeneration of nerve cells, which was especially marked in the medial segment, a prominent decrease of myelinated fibers, and moderate astrocytic proliferation. The substantia nigra was intact. Distribution of manganese in the brain of the present case of CMP was determined using flameless atomic absorption spectrometry and compared with control cases and also a case of Parkinsons disease (PD). There was no significant difference between the control cases and the case of PD in average concentration of manganese and its ditribution in the brain. The present case of CMP showed no elevation in average concentration of manganese in the brain. However, there were some changes in its distribution. Thus, the continuance of neurological disorders in CMP is not linked to an elevated manganese concentration itself in the brain. CMP appears to be different from PD in neuropathology and manganese behavior in brain.

Gastrointestinal amyloid deposition in AL (primary or myeloma-associated) and AA (secondary) amyloidosis: Diagnostic value of gastric biopsy

Gastrointestinal amyloid deposition was investigated in 21 autopsy cases of nonhereditary systemic amyloidosis, 18 of the AL (primary or myeloma-associated) type and three of the AA (secondary) type. Vascular deposition of amyloid, most apparent in the submucosa, was found in all cases. Parenchymal deposition was observed mainly in the muscularis mucosae and muscularis externa in the AL type, and in the lamina propria mucosae in the AA type. Comparison of amyloid deposition in the stomach and rectum revealed no differences for the AA type. In the AL type, however, deposition in the lamina propria mucosae and muscularis mucosae was more frequent and marked in the wall of the stomach than in the rectum. Thus, gastric biopsy would be more valuable than rectal biopsy in the diagnosis of AL amyloidosis.

Experimental allergic orchitis in mice

Experimental allergic orchids was induced in (C57BL/6J × A/J)F1 mice by two injections of syngeneic testicular homogenate emulsified with adjuvants immediately followed by intravenous injection of pertussis vaccine, at a 2 week interval. Histologically, in the initial stage there was occasional focal degeneration and desquamation of both spermatogonia and Sertoli cells within limited parts of the seminiferous tubules, in the peripheral region of the testis. No inflammatory change was present. In some cases, however, inflammatory reaction in the rete testis and focal lymphocytic infiltration in the interstitium were also observed. Subsequently, marked infiltration of lymphocytes, monocytes, and polymorphs were found not only in the testes, but also in rete testis and epididymis. In later stages the inflammatory reaction gradually subsided, but the testes became atrophic due to progression of spermatogenic arrest. Many tubules were lined only with monolayers of Sertoli cells, surrounded by hyperplastic Leydig cells in the interstitium. At 5 months after the 2nd immunization, there was still variable depression of spermatogenesis and hyperplasia of Leydig cells with scattered fibrous scars in the seminiferous tubules, although good regeneration of germ cells appeared in some tubules. Immunological studies revealed that lymphocytes obtained from mice bearing developed orchitis showed a significantly enhanced response in the mixed culture with syngeneic testicular cells, and suggest that cellular immunity plays an important role in the induction of experimental allergic orchitis in mice.

MUCOEPIDERMOID CARCINOMA OF THE THYMIC REGION

A case of mucoepidermold carcinoma in thymus in a 59‐year‐old Japanese female is presented. She died of cardiac tamponade due to tumor invasion after a 5 years clinical course. At autopsy the main tumor was found in the thymic region with metastases to the sternum, regional lymph nodes, pericardial, and left pleural cavity. The mucoepidermold carcinoma might be probably originated from a hens egg‐sized cyst which was located in the upper posterior aspect of the tumor‐Involved thymus. No teratomatous components were present. The cyst was most likely to be of thymic or bronchogenic cyst origin, though it was not determined, in view of the lining with pseudo‐stratified ciliated columnar epithelium of the cystic wall and the surrounding with the thymic tissue outside. Moreover, there was thymic hyperplasia with germinal center that was compatible with SLE‐like symptoms in her past history and autoimmune nature of the autopsy findings of pulmonary fibrosis.

AGE‐ASSOCIATED CHANGES IN MICROVASCULATURE OF HUMAN ADULT TESTIS

Age‐associated architectural changes of the human testicular micro‐vasculature from 70 autopsy cases were stereoscopically examined with a silicone‐rubber injection technique. In the testis of a young subject, the interlobular main arteries run straight. The coiling phenomena of the interlobular centripetal or centrifugal arteries, which are commonly seen in adult testis, have been so far considered as physiological transformation of the vasculature. It was confirmed that the coiling changes in the interlobular main arteries of the human testis appear as an age‐dependent alteration of the vasculature closely related to the volume of the gland. The practical importance of the spiralling or coiling of arteries is that it results in a considerable reduction of blood flow. The age‐related coiling of the interlobular arteries is virtually accompanied by varying degrees of collapse of the peritubular capillary networks. The reduction of blood supply to the seminiferous tubules plays an active role in promoting aging of the testis. These stereoscopical observations of age‐related transfiguration of testicular microvasculature were ascertained also by histometrical examinations.

Glycogen storage disease confined to the heart with deficient activity of cardiac phosphorylase kinase: A new type of glycogen storage disease

The case of a male infant with marked deposition of glycogen, confined to the heart, is presented. Clinically, prominent cardiomegaly had been evident from immediately after birth until the infants death due to heart failure. There were no significant clinical manifestations in other organs, including liver and skeletal muscle, during the clinical course. Autopsy revealed abnormal deposition of normally structured glycogen in the heart, but no deposition in the liver, skeletal muscle, or other systemic organs. This unusual pattern of glycogen deposition was also confirmed by measurement of the glycogen content of each organ. This is the first report of glycogen storage disease confined to the heart. Enzymatic analysis revealed no decrease in the activities of acid maltase, amylo-1,6-glucosidase, and phosphorylase in the heart or in the liver or skeletal muscle. However, phosphorylase kinase activity was not detectable in the heart, although high activity levels were observed in the liver and skeletal muscle. In this case the inborn error of metabolism responsible for the isolated deposition of glycogen in heart muscle may have been due to a deficiency of cardiac phosphorylase kinase.

A STUDY ON THE INTERSTITIAL CELLS OF THE HUMAN TESTIS, ESPECIALLY ON THEIR FINE-STRUCTURAL PATHOLOGY†

BOUIN and ANCEL (1904) were the first to suggest hormonal activity of the cells and at present time it is believed that both the testicular interstitial cells and the adrenal cortex are two major androgen sources of the body. Although their cytomorphology at light-optical level has been described in detail by STIEVE (1930), MUSSE EN (1932) and SNIFPEN (1950), a dynamic morphological analysis of their hormon secretion has been only lately attempted by means of electron microscopy and cytochemistry. There have been several investigations on the ultrastructure of the testicular interstitial cells of man, rat, rabbit and opossum. However, a fine structural study of the cells in human beings under various endocrinological status has not been reported until now. In order to understand the cytological changes in response to functional alteration on the whole, the author examined human biopsy materials from a series representing varying ages and diseases referring to the hormonal and clinical findings.

Long-lasting impairment of immune and endocrine systems of offspring induced by injection of dexamethasone into pregnant mice.

Dexamethasone was injected daily (2.5 and 5 micrograms/day) into pregnant mice from the 8th gestational day until delivery, and their offspring were examined in terms of body weight, organ histopathology, immunological function, and serum hormone level. Two different postnatal patterns were observed among the treated offspring: one pattern showing a wasting appearance and death within 1 week, and the other showing retardation of growth without any wasting appearance. In the latter, the offspring showed an immunologically impaired antibody-forming capacity to T-cell-dependent antigen (SRBC) and cell-mediated cytolytic T-cell activity. Histologically, the lymphoid tissues, thyroid, and adrenals of these offspring are atrophied and their serum thyroxine (T4) levels were significantly reduced. These results suggest that intrauterine exposure of the fetus to dexamethasone can disrupt the normal development and function of endocrine and immune organs which can lead to early death or retardation of growth after birth.

Carcinosarcoma of the Submandibular Gland

We present a rare case of submandibular gland carcinosarcoma occurring in a 45 year old male patient. His clinical history revealed that the carcinosarcoma had developed from a carcinoma ex mixed tumor in three years. In spite of repeated resection, intensive chemotherapy and irradiation, the tumor recurred and grew rapidly, and the patient died of hemothorax caused by rupture of a pulmonary metastatic tumor. The fourth recurrent tumor and autopsy specimens showed features of carcinosarcoma consisting of three tumor components, i.e., undifferentiated carcinoma, and chondrosarcomatous and osteosar‐comatous growth. The metastatic nodules in both lungs and pulmonary hilar lymph nodes showed the same pattern. Immunohistochemically, the chondrosarcomatous cells were positive for vimentin and S 100 protein, and for epithelial markers such as epithelial membrane antigen (EMA) and cytokeratin (MA 902). Undifferentiated carcinoma cells, on the other hand, were partially positive for muscle actin other than cytokeratin (KL 1). Ultrastructur‐ally, desmosome like structures were seen in the chondrosarcomatous cells. These findings suggest that the sarcomatous lesions might have originated from epithelial cells. Acta Pathol Jpn 40: 827 831, 1990.

Vascular changes of methotrexate-related disseminated necrotizing leukoencephalopathy

SummaryWe investigated cerebral lesions of methotrexate (MTX)-related disseminated necrotizing leukoencephalopathy (DNL) in two autopsy cases of leukemia by the reconstruction technique of the serial sections and thick sections (700–800 μm) stained with silver impregnation to detect the topographic relation between the vascular changes and parenchymal lesions. We revealed the vascular changes, such as fibrinoid degeneration, hyalinized thickening of the vascular wall, dilatation of lumen and stenosis due to swelling of the endothelial cells and exsudation in the wall, particularly prominent in venules and capillaries of venous side in the territory of the superficial medullary veins. There were no remarkable changes in the arteries, except for the moderate endothelial swelling of arteriolar capillaries. The parenchymal lesions were topographically associated with these vascular changes, and the small necrotic foci confluented each other and formed large irregular necrotic foci. We considered that the DNL may be ascribed to dyshoric damage of the veins and capillaries of the venous side and that the mechanism of vascular injury was probably due to the prolonged direct action of intrathecal MTX on the vessels.