Hiroyuki Shibuya

Primary prostatic carcinoid tumor with intracytoplasmic prostatic acid phosphatase and prostate-specific antigen

A case of prostatic carcinoid tumor with lymph node metastases is reported. The patient was a 78-year-old male who died in ventricular fibrillation. At autopsy, a 2 X 2 cm, white, irregular tumor was found in the prostate and there were several enlarged para-aortic lymph nodes. Both specimens contained a characteristic carcinoid tumor. Argyrophil stains revealed strong positivity in the primary as well as in the metastatic tumors. Electron micrographs prepared from formalin-fixed tissue demonstrated numerous membrane-bound dense-core granules. Immunoperoxidase-labeled antibodies against both prostatic acid phosphatase and prostate-specific antigen localized in the tumor cells. The ultrastructural and immunohistochemical results support differentiation of the tumor cells toward both prostatic epithelial cells and endocrine cells. We believe that this is the first reported case of a prostatic carcinoid tumor in which specific prostatic tissue markers have been demonstrated in the tumor cells.

Experimental candidiasis in iron overload

In an attempt to study the influence of iron overload on deep mycotic infection, experimental candidiasis was induced in mice. One group received intravenous injections of colloidal iron (60 mg/kg weight) for three consecutive days before intravenous inoculation of Candida albicans spores (1×107). The other received the same number of Candida spores without iron overload. The animals in both groups were observed for 28 days.The Candida lesions, regardless of iron administration, were located mainly in the kidney. There was a marked difference in mortality between the two groups, i.e., 40% in the group without iron administration and 80% in the group with it. The higher mortality rate in the latter group may be explained by following reasons: (1) increased serum iron and iron saturation (iron is essential to the growth of Candida), (2) decreased phagocytic activity against intravenously inoculated Candida because of the saturation of the phagocytic cells by the preceding colloidal iron administration and (3) enhanced proliferation of Candida, which tends to involve the kidney, exposed to abundant iron in the kidney due to increased excretion.The current experiment showed that excessive iron clearly promoted the proliferation of intravenously inoculated Candida in vivo.

MULTIPLE PRIMARY MALIGNANT FIBROUS HISTIOCYTOMA OF THE STOMACH AND SMALL INTESTINE

A case of multicentric malignant fibrous histiocytoma of the stomach and small intestine is reported. The patient was a 60‐year‐old man who had total gastrectomy under an impression of a gastric carcinoma. The resected stomach revealed a large polypoid mass in the antral portion at the greater curvature. Three months later, he developed ileus and an 80 cm segment of the jejunum was removed. It contained two polypoid masses identical to that seen in the stomach. The tumors showed, in addition to the characteristic light microscopic appearances, strong positivity for alpha‐1‐antitrypsin by an immunoperoxidase technique, indicating the diagnosis of malignant fibrous histiocytoma (MFH). Electron microscopic findings were also consistent with MFH. We believe that this is the first well‐documented case of MFH arising from the stomach and small intestine, to the best of our knowledge.

GASTRIC SMALL CELL UNDIFFERENTIATED CARCINOMA WITH ADENO and SQUAMOUS CELL CARCINOMA COMPONENTS

A unique gastric tumor is reported. A large portion of the tumor consisted of a diffuse sheet of undifferentiated cells reminiscent of a small cell undifferentiated carcinoma. The tumor cells showed a few dense core granules and a poorly developed attachment apparatus by electron microscopy. In addition, small portions of the tumor showed adenocarcinoma and squamous cell carcinoma. Another noteworthy finding was that some of the metastatic hepatic nodules consisted of relatively monotonous polygonal cells with a distinct cord‐like pattern showing argentafflnity and argyrophilia which were indicative of an atypical carcinoid. This case is a rare example of a gastric tumor with differentiation towards endocrine as well as adeno and squamous cell carcinoma. ACTA PATHOL. JPN. 35 : 473–480, 1985.

Immunohistochemical localization of endothelin‐1, endothelin‐3 and endothelin receptors in human pheochromocytoma and paraganglioma

Endothelln (ET) and its receptor system have been shown to exert varlous biological effects on dlfferent types of cells In addition to their well‐known vasoconstrictor activity. Recently ET‐1, ET‐3 and the ET3 receptor have been shown to play an Important role In the development of neural crest‐derived cells and, in this context, pheochromocytomas have been reported to harbor ET‐1. Endothelin‐3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the Immunohistochemical localization of ET‐1/big ET‐1, ET‐3/big ET‐3 and the ETA and ETB receptors were lnvestigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra‐adrenal paragangliomas. Endothelin‐lhig ET‐1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET‐3hIg ET‐3 was detected in 10 pheochromocytomas (31%) and three paragangllomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and In eight paragangllomas (73%), whlle the ETB receptor was found in 25 pheochromocytomas (78%) and In eight paragangllomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin‐immunoreactive tumor cells were dlstrlbuted focally or In a manner scattered, whlle receptor‐immunostained tumor cells were distributed wlth a focal pattern for the ETa receptor and wlth a focal or diffuse pattern for the ETB receptor. Endothelln and its receptor coexlsted In the same tumor in 21 of 28 ET‐posltive pheochromocytomas and in eight of 10 ET‐positlve paragangliomas. In additlon, seven pheochromocytomas and two paragangllomas revealed posltivlty of the receptor(s) irrespective of the absence of ET‐immunoreactlvlty. In concluslon, ET and Its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglloma. From the highly frequent expression of this system or the receptor(s), ET‐receptor‐mediated slgnal transduction of these tumors concernlng growth and/or cell survival Is expected, although definite blological slgniflcance of thls llgand‐receptor system in these tumors awaits further Investigation.

MUCORMYCOSIS IN DIABETIC KETOACIDOSIS: Role of Unbound Iron Binding Capacity of Transferrin

Increased susceptibility to Rhizopus oryzae in diabetes was investigated using mice in which diabetic ketoacidosis was experimentally induced. All of the diabetic mice which had developed ketoacidosis died within four days after inoculation of R. oryzae and their serum UIBCs (Unbound iron binding capacity) were significantly lower than those of the normal control mice. This study suggested that the decreased serum UIBC produced by diabetic ketoacidosis enhances the growth of R. oryzae in vivo. ACTA PATHOL. JPN. 36: 1507‐1512, 1986.

DISSEMINATED FUNGAL INFECTION A Review of 20 Autopsy Cases

In the study of disseminated fungal infection, in consecutive autopsy cases between 1974 and 1982, we have found this infection in 20 cases (2.55% in all autopsy cases and 16.8% of deep‐seated fungal infection). Candidiasis was present in 11 cases, aspergillosis in 8 cases, and mucormycosis and cryptococcosis in 1 case each. One case showed the disseminated infection by both Candida and Aspergillus. All of the 20 cases had underlying disorders. Hematologic disorders were most frequent and were present in 15 cases. In contrast to the small yellow disseminated foci of candidiasis, the lesion by Aspergillus and Mucor were relatively larger, hemorrhagic, and necrotic. Cryptococcal lesion showed a small gelatinous appearance. All of the fungal lesion were devoid of significant inflammatory reaction. Lymphocytopenia (less than 500/mm3) was present in 13 cases out of 16 cases (not examined in the remaining 4 cases). Eight cases had long‐standing indwelling intravenous catheters, including two cases in which the catheters apparently played an important role in the development of disseminated candidiasis. Ante‐mortem diagnosis was established or suspected in only seven cases. Possible means of the prevention of fungal infection is also discussed. ACTA PATHOL. JPN. 34: 1201–1208. 1984.

Systemic Amyloidosis Associated With Factor X Deficiency

An autopsy case of amyloidosis associated with factor X deficiency is reported. The patient showed a markedly decreased level of factor X (9% normal) and an extremely shortened half‐life of intravenously infused factor X. Amyloid deposition was present in most of the visceral organs with special involvement of the liver and spleen. The amyloid in this case was thought to be AL protein, since it was potassium‐permanganate‐resistent and a small amount of Bence Jones protein was detected after dimethyl sulfoxide therapy. Electron microscopic study revealed a typical appearance of amyloid fibrils radiating from invaginated cell membrane of Kupffer cells, which may indicate rather rapid turnover of the amyloid. Rapidity and severity of amyloid deposition, especially in the liver and spleen, may play an important role in the development of the factor X deficiency associated with systemic amyloidosis. ACTA PATHOL. JPN. 34: 639–647, 1984.