Nobuki Sakaguchi

A case of von Recklinghausen's disease with bilateral pheochromocytoma-malignant peripheral nerve sheath tumors of the adrenal and gastrointestinal autonomic nerve tumors.

A 48-year-old man with neurofibromatosis type 1 presented with chest pain, paroxysmal hypertension, tachycardia, and progressive respiratory insufficiency. Clinical investigation displayed calcified tumors in the anterior mediastinum and pararenal region. Histological examination at autopsy revealed composite tumors consisting of pheochromocytoma and malignant peripheral nerve sheath tumor (MPNST) at two sites: the left adrenal gland and the region surrounding the inferior vena cava, probably corresponding to the right adrenal gland. The MPNST component showed a varied histological appearance, including hyalinized bands with polygonal cells, a cartilaginous and myxoid stroma, a hemangiopericytomatous architecture, and a fibrosarcomatous structure, which suggested osteosarcoma, chondrosarcoma, angiosarcoma, and fibrosarcoma, respectively. In addition, based on the ultrastructural findings, the gastrointestinal tract was involved with mesenchymal tumors showing neurogenic differentiation. These lesions suggest the divergent cellular differentiation of neural crest-derived cells to mesenchymal elements as well as neuroectodermal neoplasms.

Improved detection of medically important fungi by immunoperoxidase staining with polyclonal antibodies

This study was performed to identify pathological fungi of eight species [Aspergillus fumigatus, Candida albicans, Torulopsis (Candida) glabrata, Cryptococcus neoformans, Fusarium anthophilum, Rhizopus oryzae, Sporothrix schenckii and Trichosporon beigelii] in formalin-fixed, paraffin-embedded tissue sections by indirect immunoperoxidase staining. Mature albino rabbits were immunized with formalin-killed organisms. Antibodies were prepared by precipitation. Immunoperoxidase staining was applied to the paraffin-embedded tissue sections of experimentally infected mice and human autopsy and surgical specimens. Although the cell walls of each fungus stained clearly, many cross-reactivities appeared. However, it was possible to obtain specificity for the eight species by absorption and dilution of the antisera.

Malignant granular cell tumor of the esophagus

Sir, We have recently encountered an interesting case of a malignant granular cell tumor of the esophagus. The patient was a 71-year-old man who died of malignant granular cell tumor of the esophagus with pleural effusion and multiple liver metastases. The patient presented complaining of dysphagia for the past 10 months. A barium swallow showed a filling defect in the lower part of esophagus. Esophagogastroendoscopy showed a submucosal tumor with central ulceration located 35 cm distal from the incisor teeth. The computed tomography scan (CT) of his chest revealed a solid tumor mass measuring 6 4 cm in diameter with obstruction in the mid-esophagus. Biopsies of this area demonstrated a granular cell tumor. The patient subsequently underwent an esophagogastrectomy. The resected esophagus revealed a submucosal tumor in the mid-esophagus. It was a poorly defined mass, measuring 10 5 cm in length, with circumferential involvement. At the cut surface, the tumor was white, firm and involved beyond the proper muscle layer into the adventitia. Microscopically, tumor cells mainly grew in the submucosa and infiltrated beyond the proper muscle layer into the adventitia. The surgical margin was free of tumor cells. Pseudoepitheliomatous hyperplasia of the squamous epithelium overlying esophageal tumor was present. The tumor cells were arranged in small clusters divided by thin fibrous connective tissue septa (Fig. 1). The tumor cells showed oval, polygonal or spindle-shaped cytoplasm with abundant eosinophilic cytoplasmic granules (Fig. 1). Occasional mitotic figures were seen (mitotic index: 0.3%) (Fig. 1). In some areas, the tumor cells showed nuclear pleomorphism with prominent nuclear atypia. Small necrotic foci were present. Ovalshaped tumor cells with small blunt nuclei were noted to proliferate in the lamina propria, just beneath the esophageal epithelium. Lymph-node metastasis was not observed. Immunohistochemically, most tumor cells were positive for S-100 protein (Dako, CA, USA), keratan sulfate (Seikagaku Kogyo, Japan), neuron specific enolase (Dako), CD68 (Dako), and vimentin (Dako), and about one-third of tumor cells were positive for CD57 (Beckton Dickinson, CA, USA). Collagen type IV (Dako) was demonstrated around nests of tumor cells. The tumor cells showed no reactivity for carcinoembryonic antigen (Dako), myelin basic protein (Dako), CD34 (Dako), c-kit (Dako), chromogranin A (Dako), synaptophysin (Dako) and p53 (Dako). The tumor cells showed a higher Ki67 value (8.3%€2.1) than five cases of benign granular cell tumors used as controls (3.3%€2.9). In addition, the tumor cells with small blunt nuclei in the lamina propria, just beneath the esophageal epithelium, showed lower proliferative activity than the tumor cells showing pleoA. Yoshizawa · S. Kanai Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan

Intussusception of the appendix: A report of three cases with different clinical and pathologic features

Three cases of intussusception of the appendix (IA) with distinctive pathologic changes were reported. All patients were women with different clinical presentations. Grossly, a complete intussusception was found in one case (case 1), while the others (cases 2 and 3) showed a partial intussusception. In case 1, almost the total segment of the appendix bearing the villous adenoma with focal malignant transformation became completely telescoped into the cecum. In case 2, no underlying appendiceal lesion was disclosed. In case 3, appendiceal endometriosis was found as the point of traction. Awareness of such a rare complication associated with various appendiceal lesions provides a clue for making an accurate diagnosis and selecting appropriate surgical management.

Ultrastructural study of Cryptococcus neoformans by quick-freezing and deep-etching method

The three-dimensional ultrastructure ofCryptococcus neoformans was studied by quick-freezing and deep-etching (QF-DE) method.C. neoformans, strain CDC551, was cultured on agar. The viable yeast cells (107 cells) were inoculated into each mouse from the tail vein. Three weeks after the inoculation, the brains of the mice were perfused with fixatives, quickly frozen, freeze-fractured, deeply etched and rotary shadowed with platinum and carbon. In addition, the viable cells ofC. neoformans on agar were picked up and quickly frozen, and replica membranes were prepared as described above. The ultrastructure ofC. neoformans was three-dimensionally demonstrated by the QF-DE method. The capsule was composed of fine meshworks of microfibrils (10–13 nm in diameter), which were directly attached to the cell walls. The capsule of the in vivo yeasts (yeast cells in the brain lesion) was thicker than that of the in vitro yeasts (yeast cells on agar culture). At the outer part of the cell wall, a particle-accumulating layer was observed. This layer in vivo was thicker than that in vitro. Occasionally, the yeast cells were ingested by phagocytes in the mouse brain. Although the cytoplasm of such yeast cells was destroyed, the capsular meshworks were well preserved. The ultrastructure of the capsule was the same both in cultured and phagocytized yeasts in the cystic lesions of the brains. This lack of morphological changes of the capsular meshworks suggests that they are resistant to the digestion by phagocytes. This stability of capsular structures may provide one of the important pathogenic factors in cystic lesions byC. neoformans.

A rat model of hypereosinophilic syndrome.

Hypereosinophilia‐occurring rats without chemical and antigen treatment have been maintained in our laboratory. The rat, Matsumoto Eosinophilia Shinshu (mes), showed hypereosinophilia at the age of 9 weeks or older and developed eosinophil‐related inflammatory lesions in many organs. These lesions included: aortitis, granulomatous lesion in the mesenteric lymph node, inflammatory fibroid polyp of the stomach and pulmonary vasculitis with septal infiltration. These lesions were involved with cellular infiltration of eosinophils and macrophages, and deposition of eosinophilic crystals which immunohistologically showed major basic protein and eosinophilic peroxidase derived from eosinophilic lysosomal constituents. Although the distribution of lesions in mes is a little different from that of hypereosinophilic syndrome (HES) in humans, in that endomyocardial fibrosis appears in HES while aortitis appears in mes, mes is probably comparable with HES. The present paper describes the pathological aspects of the lesions in mes and discusses the pathogenesis of tissue injury related to eosinophilic infiltration.

Intravascular fasciitis of the forearm vein: A case report with immunohistochemical characterization

Intravascular fasciitis is a very unusual variant of nodular fasciitis. A unique case of this lesion occurring in the proximal portion of the superficial vein of the forearm in an otherwise healthy 26‐year‐old man is reported. The intravascular polypoid lesion grew longitudinally along the vascular lumen, was loosely attached to the intimal layer, and was partly anchored beyond the internal elastic lamina into the medial smooth muscle layer. However, extravascular involvement was absent. The histological features were identical to those observed in ordinary cellular nodular fasciitis. Because of its myofibroblastic phenotype exhibited by highly proliferative spindle cells, certain intimomedial myofibroblasts are thought to be the indigenous source of this unique fibroproliferative lesion. Unless the diagnosis of intravascular fasciitis is considered and appropriate differential markers examined, it may be confused with other intravascular lesions, such as intravascular leiomyoma, intravenous pyogenic granuloma, organized thrombus and, even, fibromuscular dysplasia if it arises in the arteries. A simple excision is considered curable. Even so, two recurrent cases have been documented to date.

Ultrastructural study of hepatic granulomas induced by Cryptococcus neoformans by quick-freezing and deep-etching method

SummaryThe ultrastructure of hepatic granulomas induced byCryptococcus (C.) neoformans was studied by a quick-freezing and deep-etching (QF-DE) method. Viable yeast cells were inoculated intravenously into rats and the livers were prepared for QF-DE replicas. Two cytoskeletal components were identified in the cytoplasm of macrophages composing the cryptococcal granulomas. These were: intermediate filaments, mainly located in the perinuclear region, and actin filaments, which were extensively decorated with myosin subfragment 1 (S1) and formed networks in the peripheral portion of the cytoplasm. In addition, two types of macrophage pseudopodia were observed in the granulomas. These were cobble stone-like pseudopodia at the yeast-macrophages contact areas, and thin, long and occasionally interdigitating pseudopodia in which actin filaments were consistently observed. Dense networks of actin filaments were also seen in pseudopodia protruding into the tight structure of the capsule ofC. neoformans. These results suggest a role for actin filaments as one of the main factors in the force generating system of the phagocytic process.

Intravascular granuloma induced by intravenous inoculation of Cryptococcus neoformans

In rodents an intravenous administration of viableCryptococcus (C.) neoformans cells frequently resulted in attachment of intravascular cryptococcal granulomas to inner walls of the large to medium-sized veins of various organs, including the lungs, liver and spleen. In order to elucidate the pathogenesis of granulomatous changes, the cells composing the intravascular granulomas were observed by electron microscopic peroxidase (PO) cytochemistry. The granuloma composing cells could be divided into the following four types according to the pattern of endogenous peroxidase activity: exudate macrophage (Mφ, type I), PO-negative Mφ (type II), resident Mφ (type III) and other inflammatory cells (type IV). In the intravenous granulomas of the lung, the percentages of composed cells were 39.0% for type I, 57.9% for type II, 0% for type III and 3.1% for type IV. By contrast, in the interstitial granulomas in the lung, type III Mφs, possibly derived from alveolar Mφs, played a significant role in granuloma formation. This may indicate that the intravascular granuloma is almost composed of macrophages derived from monocytes rather than alveolar macrophages. The expression of ICAM-1 on endothelia of the pulmonary veins was examined by immunoelectron microscopy. An immunogold labeling index was significantly augmented on the surface of endothelia in response to intravenous challenge ofC. neoformans. The intravascular granuloma demonstrates that the monocytes develop into the granuloma-composing macrophages and suppress the cryptococcal activities even hi the peripheral blood resulting in an assistance of endothelial functions.

Histological diversity of vasculitic lesions in MPO–ANCA‐positive autopsy cases

To investigate the variety of histological features of vasculitic lesions in myeloperoxidase‐specific antineutrophil cytoplasmic antibody (pANCA)‐related vasculitis, retrospective pathological analysis was done on 13 autopsy cases, collected from 1990 to 1998 at five hospitals. These cases were classified into three groups: (i) pulmonary–renal syndrome characterized by capillaritis of lung and glomeruli with occasional small‐vessel arteritis and/or phlebitis; (ii) glomerular capillaritis without pulmonary involvement associated with significant small‐vessel arteritis; and (iii) extensive distribution of small‐vessel arteritis with no capillary involvement. The results suggest that pANCA‐related vasculitis encompasses a wide variety of vasculitic syndromes, including pulmonary–renal syndrome, microscopic polyarteritis nodosa, and classic polyarteritis nodosa. pANCA may contribute to pathogenesis in all of these cases.