Joji Haratake

Giant cell tumor-like cholangiocarcinoma associated with systemic cholelithiasis

A cholangiocarcinoma of the hepatic hilus with an element of giant cell tumor that occurred in a 59‐year‐old man is reported. His medical history included systemic cholelithiasis and repeated operations on the biliary passages. Four years after the last operation, which was a hepatic segmentectomy, he was readmitted because of persistent fever. A computed tomography scan showed a low‐density area and stones in the hepatic hilus. He died of hepatic failure approximately 1 month later. At autopsy, a fist‐sized tumor and gallstones were found at the hepatic hilus. Histologically, the tumor mainly showed sarcomatoid features and some tubular adenocarcinoma. An element of giant cell tumor consisting of many osteo‐clast‐type giant cells also was noted. The results of immunohistochemical studies showed a positive reaction to cytokeratin and vimentin in some of the spindle‐shaped sarcomatoid cells. Sarcomatoid bile duct carcinomas are rare, as are those with osteoclast‐type giant cells. The authors also discuss the histogenesis of these giant cells. Cancer 1992: 69:2444‐2448.

Lymphoepithelial cyst of the pancreas in a 65-year-old man

A case of an extremely rare cystic lesion of the pancreas is presented. The multilocular cyst was found adjacent to the upper border of the pancreatic body, and the cyst contained bean curd lees-like substances. Histologically, the cyst wall consisted of mature keratinizing squamous epithelium and surrounding lymphoid tissue stroma, and the cyst was filled with keratinized materials. A histopathologic diagnosis of typical lymphoepithelial cyst of the pancreas, proposed by Truong et al (Am J Surg Pathol 11:899-903, 1987), was made. Its histogenesis is still unknown; however, we hypothesize that it might arise from a benign epithelial inclusion of a peripancreatic lymph node, followed by squamous metaplasia of the epithelial inclusion. We recently found a retropyloric lymph node with a squamous epithelial inclusion, which might support this hypothesis regarding the histogenesis of the cyst.

PANCREATOBLASTOMA IN JAPAN, WITH DIFFERENTIAL DIAGNOSIS FROM PAPILLARY CYSTIC TUMOR (DUCTULOACINAR ADENOMA) OF THE PANCREAS

Twelve cases of pancreatoblastoma, 7 males and 5 females, were 5 years of age in average and showed an organoid structure consisting of acinar differentiation with squamoid corpuscles. Seven cases died, but 5 lived after surgery. On the contrary, 17 cases of papillary cystic tumor, ductuloacinar adenoma of the pancreas, one male and 16 females, were 21 years of age in average and disclosed a monomorphous pseudopapillary pattern of ductuloacinar type of tumor cells with some degenerative and granulomatous changes. All of the cases had suffered no recurrence after resection. Immunohistochemically, strong positivity for α1‐antitrypsin may be associated with the autodigestive process and limited growth of this tumor. Electron microscopically, both tumors showed centroacinar and acinar types of tumor cells. Both tumor cells frequently contained well‐developed RER, zymogen‐like granules, and annulate lamellae. The ductular or acinar lumina were clear in pancreatoblastoma, but not in ductuloacinar adenoma due to degeneration. Though both tumors disclosed contiguous histogenesis, pancreatoblastoma should be differentiated from ductuloacinar adenoma, based upon the young age, almost equal sex ratio, unfavorable prognosis, high serum AFP level in three measured cases, an organoid structure containing frequent mitotic figures, and the invasive growing margin.

Familial intrahepatic cholestatic cirrhosis in young adults

Two siblings with intrahepatic cholestatic cirrhosis and their brother, who had a potentially related disease at the time of accidental death, are presented. The onset of disease occurred during adolescence in all 3 cases. The initial sign was mild jaundice or portal hypertension. There was no abnormality in the countenance, cardiovascular system, or vertebral column. Except for the brother who died from an accident, jaundice gradually increased. Death followed due to cirrhosis. Liver biopsy specimens of these 2 patients showed diminution of interlobular bile ducts with no significant cholangitis. At autopsy, the livers of the 2 patients showed biliary cirrhosis without extrahepatic biliary obstruction. In both cases there was an accessory lobe on the right hepatic lobe. Histologically, septal bile ducts showed pronounced papillary proliferations of the epithelium; there was also a decrease in the number of small interlobular bile ducts. Excess copper accumulation in the liver was ascertained. It is suggested that the disease in the 2 autopsied cases is intrahepatic cholestatic cirrhosis due to hypoplasia of the intrahepatic biliary trees.

Electron microscopical findings with special reference to cancer in rats caused by inhalation of nickel oxide.

A special exposure system was used for the inhalation of nickel oxide (NiO) aerosol by Wistar male rats. The median aerodynamic diameter and the geometric standard deviation were 1.2 μm and 2.2, respectively. A histopathological study of the rats was performed immediately, and at intervals of 12 and 20 mo after a 1-mo expsoure to NiO. Electron microscopy showed that localization of NiO particles was restricted to the lungs and that each particle had been engulfed by the alveolar macrophages. Type II pneumocytes and nonciliated bronchiolar epithelial cells (Clara cells), as well as numerous tubular myelin (surfactant) in the alveoli were prominent. In rats dissected after 12 mo, clusters of NiO particles were still present within the terminal bronchioli, alveolar walls, and lysosomes of the alveolar macrophages. Pools of tubular myelin were observed in the peribron-chial lymphatics. The Clara cells, which project into the lumen of bronchioli, showed active secretion and were filled with smooth en-doplasmic reticulum (SER) in the apical cytoplasm. In the experimental group sacrificed after 20 mo, one rat had papillary adenocarcinoma and two rats showed adenomatosis in the peripheral portion of the lung, but none in the upper respiratory tract.

Lysosomal storage and advanced senescence in the brain of LAMP-2-deficient Danon disease.

Danon et al. first described two 16-year-old boys with cardiomegaly, proximal myopathy and mental retardation as ‘‘lysosomal glycogen storage disease with normal acid maltase’’ in 1981 [2]. In 2000, Nishino et al. [6] identified that lysosome-associated membrane protein type 2 (LAMP-2) is the responsible gene for Danon disease. Despite the presence of mental retardation, the neuropathological findings have not yet been described. Moreover, one of the splice-variants, LAMP-2A, serves as a receptor for chaperone-mediated autophagy (CMA) which is implicated in neurodegenerative disorders [1]. Here we report an autopsy case of genetically confirmed Danon disease with an exon-6-skipping mutation (Nishino et al., patient 3) [6]. A genetic confirmation of LAMP-2 deficiency and clinical manifestations of this case were described previously [4, 6]. Briefly, he was born at fullterm without any abnormalities. In childhood, he was in low-performing schools. At age of 22, dilated cardiomyopathy was diagnosed and a pacemaker was implanted. At age of 26, the full-scale intelligence quotient was 60. He expired from cardiac failure at age of 31. His mother had been diagnosed with cardiomyopathy and liver disease, and had died of heart failure at age of 52. The macroscopic appearance of the brain did not exhibit any abnormality. Microscopically, pale granular neurons were found particularly in the nucleus basalis of Meynert and cranial nerve nuclei such as oculomotor, dorsal vagal and hypoglossal nuclei (Fig. 1b–d, k; Suppl Table 1). Although neuronal loss was not noted, mild astrocytosis was seen in the basal ganglia, hippocampus and brainstem. In addition, neurons containing lipofuscinlike granules were remarkable (Suppl. Table 1). The distribution of these neurons was different from that of pale Electronic supplementary material The online version of this article (doi:10.1007/s00401-012-1075-4) contains supplementary material, which is available to authorized users.

An Autopsy Case of Peritoneal Malignant Mesothelioma in a Radiation Technologist

A case of peritoneal maligant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, welt developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane‐bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mosothelioma. Acta Pathol Jpn 40: 57–62, 1990.

Biological half-time in rats exposed to nickel monosulfide (amorphous) aerosol by inhalation

This study reports the biological half-time of amorphous nickel monosulfide(NiS(A)) aerosol retained in rat lungs. Wistar male rats were exposed to NiS(A) aerosols (mass median aerodynamic diameter: 4.0 μm) for a single 4 h exposure, or for 7 h/d, 5 d/wk for 1 mo. The average exposure concentrations were controlled at 107 mg/m3 for the single exposure and at 8.8 mg/m3 for the repeated exposures by a dust generator consisting of a continuous fluidized bed with an overflow pipe and a screw feeder. After the exposures, the nickel contents in the rat organs, blood, and urine were measured and histopathological examinations were performed. The biological half time of NiS(A) in rat lungs was 20 h, which was extremely shorter than 21 mo of green nickel oxide (NiO(G)). There were no malignant tumors in any of the exposure groups.

ADULT T-CELL LEUKEMIA COMPLICATED BY HYPERCALCEMIA

Three autopsy cases of Adult T‐cell leukemia (ATL) complicated by a severe hypercalcemia are presented. In two of them, the hypercalcemia itself was the direct cause of death. There was no evidence of an increase of serum PTH in all three cases. Prostaglandins were within normal range in two of them. By a bioassay, a bone‐resorbing factor, osteoclast activating factor (OAF)‐like substance, was demonstrated in the culture medium of leukemic cells from one patient. Also, various degrees of osteoclastic activation were found in the bones of all three patients by the postmortem examination. It may be that the hypercalcemia occurring in cases of ATL is partly caused by the humoral factor, which is released from leukemic cells and activates a bone resorption by osteoclasts. Similar cases in which a significant activation of osteoclasts was practically demonstrated by histopathologic examination in addition to the detection of a bone‐resorbing factor have been rarely reported. ACTA PATHOL. JPN. 35 : 437–448, 1985.

A CLINICOPATHOLOGICAL REVIEW OF 12 AUTOPSIED CASES OF ADULT T-CELL LEUKEMIA

Twelve autopsied cases with adult T‐cell leukemia (ATL) were reviewed clinicopathologically. The prognosis of three cases who had suffered from severe cutaneous lesions was much better than that of the other nine cases with no or negligible cutaneous lesions. The surface marker of leukemic cells from six cases was ordinary inducer/helper phenotype (OKT4+ and 8‐), but in one case leukemic cells showed OKT4+ and 8+. In another case, a significant amount of leukemic cell infiltration was found in the thymic cortex. Calcium content in the bone of ATL cases was lower than that of the patients without ATL (control group), and six cases with ATL (50%) were complicated by severe hypercalcemia. Neither adenoma nor hyperplasia of the parathyroid glands was found in any case. In most severely hypercalcemic patients, bone trabeculae were actively absorbed by numerous osteoclasts and partly replaced by fibrous tissues. In two normocalcemic patients, skeletal calcium content was also markedly reduced by osteoporosis, but the activation of osteoclasts was inconspicuous. It was speculated that the manner of bone resorption in ATL cases was diverse and there were some clinicopathological subtypes in ATL from the viewpoints of cutaneous lesions, hypercalcemia, and bone lesions.