Journal of Pathology and Translational Medicine

Original Article

An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes: Chang-Woo Han, Kyung-Hwa Lee, Myung Giun Noh, Jin-Myung Kim, Hyung-Seok Kim, Hyung-Sun Kim, Ra Gyung Kim, Jongwook Cho, Hyoung-Ihl Kim, Min-Cheol Lee; J Pathol Transl Med. 2017;51(3):292-305. Published online May 10, 2017; DOI: https://doi.org/10.4132/jptm.2017.02.17

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Background
Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes.
Methods
Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury.
Results
Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume.
Conclusions
Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.

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Animal models of focal ischemic stroke: brain size matters
Blazej Nowak, Piotr Rogujski, Raphael Guzman, Piotr Walczak, Anna Andrzejewska, Miroslaw Janowski
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Brief Case Report

Indolent CD56-Positive Clonal T-Cell Lymphoproliferative Disease of the Stomach Mimicking Lymphomatoid Gastropathy: Mineui Hong, Won Seog Kim, Young Hyeh Ko; Korean J Pathol. 2014;48(6):430-433. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.430

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Indolent NK cell proliferative lesion mimicking NK/T cell lymphoma in the gallbladder
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Case Reports

Soft Tissue Perineurioma : A Case Report .: Jun Mo Kim, Joon Hyuk Choi; Korean J Pathol. 2009;43(3):266-270.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.266

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Abstract PDF

Soft tissue perineurioma is a very rare tumor composed of entirely of neoplastic perineurial cells. A 54-year-old woman presented with a palpable mass in the right lower leg. The mass was excised. Grossly, the tumor measured 2.0x2.0x1.5 cm. The cut surface was well circumscribed, pale pinkish gray, and rubbery soft. Histological examination showed that the tumor was composed of spindle cells within collagenous and myxoid stroma. The tumor cells had elongated, tapering nuclei with long and thin cytoplasmic processes, and were arranged in fascicular, whorled, and storiform pattern. The tumor cells were positive for epithelial membrane antigen and collagen type IV and negative for S-100 protein. Ultrastructurally, tumor cells showed long and thin cytoplasmic processes, pinocytic vesicles, and incomplete external lamina. The diagnosis of soft tissue perineurioma was confirmed by immunohistochemical stain and ultrastructural study.

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A Soft Tissue Perineurioma and a Hybrid Tumor of Perineurioma and Schwannoma
Ji Young Park, Nam Jo Park, Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee
Korean Journal of Pathology.2012; 46(1): 75. CrossRef

Central Core Disease: A Case Report.: Ji Hoon Kim, Young S Park, Sung Hye Park, Je G Chi; Korean J Pathol. 2004;38(1):68-71.

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Abstract PDF: Central core disease is a rare autosomal dominantly inherited non-progressive congenital myopathy, which is pathologically characterized by the formation of a "core". We report a 28-year-old female with non-progressive muscle weakness, who had a hypotonic posture at birth. The developmental milestones were delayed with her first walking at 18 months of age. She could not run or walk a long distance and weight-bearing tasks were almost impossible. None of her family members showed motor symptoms. An investigation of the electromyography and nerve conduction velocity showed non-specific results. A gastrocnemius muscle biopsy revealed central cores in approximately 70% of myofibers with a type 1 myofiber predominance and deranged sarcolemmal structures. To the best of our knowledge, this is the fifth report of central core disease in the Korean literature.

Original Articles

Ultrastructural and Immunohistochemical Investigations of Exocrine and Endocrine Cells in Fetal Human Pancreas.: Jung Ran Kim, Je G Chi, Jung Hee Cho; Korean J Pathol. 1995;29(3):286-295.

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Abstract PDF: The pancreas consists of two types of tissue arising from same primitive cells, but with entirely different functions. Although the adult human pancreas and fetal islet tissue have been the subject of numerous electron microscopic studies, little is known of the ultrastructure of the developing human exocrine pancreas. The purpose of the current study is to investigate development of endo and exocrine of pancreas, especially during the middle trimester of human fetal life, which is the period of acinar cell maturation. Fresh autopsy specimens of pancreas, taken from 15 human fetuses at the 12th (n=2), 13-16th (n=5), 17-20th (n=4), 21-24th (n=2) and 25-28th (n=2) weeks of gestation, were studied electron microscopically, and immunohistochemically. Antisera against insulin, somatostatin, glucagon, pancreatic polypeptide and gastrin, were used for immunohistochemistry. By the 12th week, primitive exocrine acini were identified and these were matured rapidly in the next 6 weeks. At the 17th week stage, ultrastructural examination revealed atypical zymogen granules in the acinar cells. These became progressively less numerous in the 21-28 week period when classical zymogen granules increased upto the level of adult stage. All the endocrine cells were found at the 12th week, forming primitive or mature islets. The relative ratio of endocrine cells at the 12th week was about 35.4%, 24.9%, 39.8%, 0.5% for A, B, D & PP cell, respectively. But at the 25th to 28th week of development, the relative numbers of A and D cells decreased somewhat, whereas those of the B cells increased. The PP cells were constant. The G cells were found at the 12th week of fetal period, which appeared through out the on period.

Fine Needle Aspiration Cytology of Pulmonary Carcinosarcoma.: Tae Jung Jang, Kwang Gil Lee, Soon Won Hong; J Pathol Transl Med. 1990;1(2):164-169.

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Abstract PDF: Carcinosarcoma is an uncommon pulmonary malignancy characterized by carcinomatous parenchyma and sarcomatous stroma. The cytologic, immunohistochemical and ultrastructural features of a case of pulmonary carcinosarcoma suspected by fine needle aspiration cytology is presented. Only bizarre spindle cells arranged in loose groups, in microtissue fragments and in a dissociate fashion were present in the aspiration smears. They were markedly positive for vimentin. The epithelial component was not found, which was probably due to marked paucity of carcinomatous component that was proved by histologic examination of the resected tumor. The diagnosis of pulmonary carcinosarcoma should be considered whenever poorly differentiated epithelial cell groups with a malignant mesenchymal component set in a myxoid background are seen in a pulmonary cytology specimen.

A Histopathologic Studies for Endometrium of Early Pregnancy.: Mi Ja Lee, Kenn Hong Kee, Chae Hong Suh, Ho Jong Jeon; Korean J Pathol. 1995;29(4):492-501.

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Abstract PDF: Endometrium of early pregnancy were compared with nonpregnant endometnum by inimunohistochemical and ultrastructural techniques with respect to glandular and stromal elements of endometrium. The results obtained were as follows: 1. The AS cell in decidua has all the features of actively secreting glandular epithelium and shows the pronounced arrays of glandular endoplasmic reticulum and moderate numbers of ribosomes ultrastructually. Therefore the AS cell indicate considerable protein production, presumably contributing to both cell gowth and the production of secretions. 2. The process of decidualization can be characterized morphologically and immunohistochemically by the accumulation of basement membrane-like materials, such as laminin and type IV collagen which may be related to the hormonal stimulation occuring during pregnancy and trophoblastic attachment. 3. The decidual cells show strong positive for vimentin and some large mature decidual cells show weakly positive for lysozyme and cti- antitrypsin, which might represent more the sequential differentiation of stromal cells into decidual cells than origin of histiocytes. 4. Immunoreactivity with S-100 protein was found in glandular and stromal cells of decidua but negative in endometrium of nonpregnant women. So some humoral factors related to pregnancy stimulate expression of S-100 protein in glandular and stromal cells of decidua.

Case Report

Pulmonary Alveolar Proteinosis: A Case Report with Diagnostic Features in Bronchoalveolar Lavage Specimen .: Seung Yeon Ha, Hyuni Cho, Young Ha Oh; J Pathol Transl Med. 2000;11(2):103-108.

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Abstract PDF: Pulmonary alveolar proteinosis(PAP) is a rare disease in which the alveolar spaces are filled with an eosinophilic, PAS-positive material, whereas the interstitial architecture of the lung usually remains unaffected. Although a definitive diagnosis is usually made by an open lung biopsy, bronchoalveolar lavage(BAL) cytology may play a decisive role in the diagnosis and therapy of these patients and may spare a patient a more invasive diagnostic procedure. The author presents a patient in whom BAL cytology specimen contained the characteristic globules of amorphous proteinaceous PAS-positive material accompanied by background of rare macrophages and inflammatory cells. Ultrastructural study using BAL specimen can confirm the diagnosis of PAP.

Original Articles

The Ultrastructural Study of Intermediate Filaments in Epithelial and Mesenchymal Tumors.: Chae Hong Suh, Keun Hong Kee; Korean J Pathol. 1993;27(4):328-338.

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Abstract PDF: The immunohistochemical results are compared with ultrastructural features of neoplastic epithelial cells and mesenchymal cells to assess whether immunohistochemistry is useful in the differential diagnosis of epithelial tumors and mesenchymal tumors. Squamous cell carcinoma and transitional cell carcinoma exhibited positive reaction for keratin, but adenocarcinoma was weakly positive reaction for keratin. Ultrastructurally, heavy bundles of tonofilaments were more frequently encountered in squamous cell carcinoma. In adenocarcinomas, the intermediate filaments were arranged randomly as nonaggregated, short filaments spread throughout the cytoplasm. Fibroblastic and fibrohistiocytic tumors, schwannomas, and neurofibromas exhibited positive reaction for vimentin and alpha-smooth muscle actin. Vimentin consisted of large aggregates of gently curved filaments that often displace other cytoplasmic constituents was noted. Fibroblastic cells with features of smooth muscle differentiation were found in granulation tissue of healing wounds, hypertrophic scars, fibromatosis, fibroma, neurofibroma and malignant fibrous histiocytoma. Smooth muscle tumors showed abundant bundles of thin filaments with dense bodies, pinocytotic vesicles and dense attachment plaques along the cell membrane. Skeletal muscle tumors showed bundles of disorganized thick and thin filaments, remnants of sarcomeres and Z-bands. From the above result, ultrastructural and immunohistochemical studies on epithelial and mesenchymal tumors were useful in tumor diagnosis sand classification.

Ultrastructural Changes in Human Gallbladder Epithelium in Acalculous and Calculous Cholecystitis.: Sung Chul Lim, Chae Hong Suh; Korean J Pathol. 1995;29(6):714-726.

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Abstract PDF: Cholelithiasis is defined as the presence of stones within the lumen of the gallbladder or in the extrahepatic biliary tree. Cholecystitis, secondary to gallstones, is a common surgical disorder in Korea. Detailed microscopic descriptions, particularly the ultrastructural changes, of these diseases were not available. The goal of this study was to identify the ultrastructural alterations of gallbladder epithelium in cholecystitis with and without a stone, according to the degree of severity of inflammation, and the nature of the stone. The gallbladders of the control group, and cholecystitis cases without stone and with stone were fixed and examined with routine stain, special stain, immunohistochemical stain and trans-mission electron microscopy. The number and the volume density of the mucin containing secretary granules were not significantly increased in the calculous cholecystitis cases compared with those of the acalculous cholecystitis cases. Major findings were that the calculous cholecystitis cases showed a markedly reduced total lysosome area and volume density of the lysosome compared with those of the acalculous chole-cystitis cases. The differences between the mucin secretary granules and lysosomes, according to the degree of severity of cholecystitis and the natures of gallstones, were statistically not significant.

Immunohistochemical and Ultrastructural Studies on the Histogenesis of Thyroid Undifferentiated Carcinoma.: Myoung Ja Jeong, Woo Sung Moon, Young Hye Lee, Myoung Jae Kang, Ho Yeul Choi, Sang Ho Kim, Dong Geun Lee; Korean J Pathol. 1995;29(6):756-765.

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Abstract PDF: Histologic, immunohistochemical and ultrastructural studies were performed on 6 cases of undifferentiated thyroid carcinoma to study the histogenesis of the undifferentiated thyroid carcinoma, to determine the most useful markers for diagnosing these tumors and to investigate the nature of osteoclast-like giant cells rarely observed in these tumors. For the immuno-histochemical study, a panel of antibodies to epithelial (cocktailed keratin, low molecular weight keratin, CEA), mesenchymal(vimentin, desmin, actin, FVIIIRAg) endocrine(calcitonin, chromogranin), lymphocytic(LCA), histiocytic(alpha-l-ACT, alpha-1-AT, lysozyme, CD68), and Schwann cell(S-100 protein) markers were used. The following results were obtained; 1) Well differentiated carcinoma was associated with 2 cases of spindle cell type and 1 case of giant cell type of undifferentiated thyroid carcinoma and a transitional zone between the well differentiated and undifferentiated lesions was observed. 2) All of the examined cases expressed keratin, and 3 tumors expressed CEA. 3) All the mesenchymal markers, LCA, S-100 protein, calcitonin, and chromogranin were not expressed. Vimentin was coexpressed with keratin in 4 cases. 4) Osteoclast-like giant cells were observed in 1 case of spindle cell type. They expressed CD68 but not keratin. 5) Ultrastructural study revealed the desmosomes between the tumor cells and non-neoplastic, follicular, thyroid epithelial cells. The above results indicate that undifferentiated thyroid carcinoma originates from follicular epithelial cell, keratin is the most useful marker for diagnosis of this tumor, and the osteoclast-like giant cells are histiocytic in nature and reactive, rather than neoplastic.

Ultrastructural Studies of Aortic Endothelial Injury and Regeneration.: Gium Mi Jang, Dong Hoon Kim, Jyung Sik Kwak, Tae Joong Sohn; Korean J Pathol. 1990;24(4):337-348.

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Abstract PDF: Author performed this experiment to define the most important factor preventing the intimal thickening. An endothelium of abdominal aorta in the rat was denuded by two different wires having same caliver. The degree of injury was limited to the endothelial cells in one, and extended to the internal elastic lamina in another. The results showed that at 72 hours, in the case of superficial injury, the entire injury site was covered by new regenerating cells, but in the case of disruption of the internal elastic lamina, the migrating smooth muscle cell completely reached into the intima and resulted in intemal thickening. Similar findings persisted to 1 week later. Above results suggest the most important factor preventing the intimal thickening in endothelial injury is the depth of the injury which limited within the endothelial cells without extending into the internal elastic lamina and medial smooth muscle cells.

An Anion Site Change of the Glomerular Basement Membrane on Various Glomerular Diseases.: Yu Na Kang, Kwan Kyu Park, Seung Pil Kim, Sung Bae Park, Hyun Chul Kim, Eun Sook Chang, In Soo Suh; Korean J Pathol. 1997;31(8):765-772.

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Abstract PDF: We studied the ultrastructural alteration of glomerular anionic sites in 6 patients with minimal change nephrotic syndrome, 5 patients with membranous glomerulonephritis, 4 patients with focal segmental glomerulosclerosis, and 4 patients with IgA nephropathy by staining with polyethyleneimine (PEI) as a cationic probe. The control study was examined by using a nephrectomy specimen of non-glomerular disease which had no proteinuria. This method seems to selectively stain heparan sulphate in the basement membranes and has been widely used to evaluate changes in basement membrane charge in various human diseases as well as in experimental studies. The anionic sites in the lamina rara interna and lamina densa of normal glomerular basement membrane were always less numerous and less regularly distributed than those in the lamina rara externa. Characteristic common findings in these glomeruli showed a marked decrease of glomerular anionic sites in the regions with immune-complex deposits and normal distribution in the regions with focally those being absorbed and newly forming glomerular basement membrane. They were not detected in the gap of the basement membrane and on the area of the detached overlying epithelium using the PEI method. But the foot process fusion of epithelial cells seems not to influence the loss of anionic sites on the glomerular basement membrane.

Significance of Ultrastructural Electron Dense Deposits on Glomerular Capillary Loops in IgA Nephropathy.: Sun Hee Sung, Ok Kyung Kim, Woon Sup Han; Korean J Pathol. 1996;30(1):32-39.

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Abstract PDF: To evaluate the clinical and histopathological significance of electron dense deposits on capillary in IgA nephropathy, we reviewed and compared the clinical, laboratory, and pathological features of the patients with IgA nephropathy without loop extension of electron dense deposits(Group I, 91 cases) and IgA nephropathy with loop extension(Group II, 17cases) by ultrastructural examination using transmission electron microscope. IgA nephropathy associated with liver disease, Henoch-Schonlein purpura, systemic lupus erythematosus and the other IgA nephropathies associated with systemic diseases were excluded. The results were as follows; 1) There was no significant difference in age distribution. 2) Generalized edema was more common in group II. 3) Nephrotic ranged proteinuria(>3 g/24hr urine) was more prominent in Group II(52.9%) than Group I(8.8%). 4) Among the groups, segmental or mild deposits on the loops were noted in 13 cases, and severe and generalized deposits in 4 cases. Subendothelial deposits were noted in 6 cases, subepithelial deposits in 3 cases, subendothelial with intramembranous deposits in 1 case, subendothelial with subepithelial deposits in 1 case, intramembranous with subepithelial deposits in 2 cases, and subendothelial, subepithelial and intramembranous deposits in 4 cases. 5) The other associated ultrastructural changes of group II were diffuse effacement of foot processes with microvillous transformation, swelling or vacuolar degeneration of podocytes and glomerular endothelium. 6) According to the WHO morphologic criteria, the grade of Group II was significantly higher than Group I. From the above results, it can be concluded that the extension of electron dense deposits along the capillary loops in the cases of IgA nephropathy is highly correlated with proteinuria in the nephrotic ranged. It seems to be a poor prognostic indicator in view of the facts that it correlats with high histopathologic grading.

Immunohistochemical and Ultrastructural Study of Fibroblast Differentiation.: Chae Hong Suh; Korean J Pathol. 1996;30(2):106-114.

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Abstract PDF: The histogenesis of the myofibroblast continues to be a controversial issue. The most popular view is that the myofibroblast is derived directly from the fibroblast. The important role of myofibroblasts in the synthesis of collagen and in wound contraction was demonstrated initially in granulation tissue in experimental animals. Four settings are recognized in which myofibroblasts are the principal proliferative cells: reparative responses, pseudoneoplastic disorders, stromal response to neoplasia, and true neoplasms, both benign and malignant. To identify of fibroblastic cells with smooth muscle differentiation features in the nonneoplastic and neoplastic lesions, we examined a variety of histological, immunohistochemical and ultrastructural features of 7 cases of granulation tissue, 7 of hypertrophic scar, 10 of chronic persistent hepatitis, 10 of chronic active hepatitis, 7 of liver cirrhosis, 7 of fibromatosis, 42 of cervical intraepithelial neoplasia, 14 of microinvasive carcinoma, 14 of invasive carcinoma, 7 of fibroma, 20 of fibrosarcoma and 72 of malignant fibrous histiocytoma. Antibodies against alpha-smooth muscle actin and desmin were used in a biotin-streptavidin procedures. The results of immunohistochemical and electron microscopical examinations yielded virtually identical findings. The identification of fibroblastic cells with smooth muscle cell differentiation features in the desmoplastic reactions of carcinomas, fibroma, fibrosarcoma and malignant fibrous histiocytoma offers also novel diagnostic and prognostic perspectives, that might help in evaluating preneoplastic lesions and malignant lesions. So degree of proliferative myofibroblasts was helpful diagnostic aid in differentiation of chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis.

Bronchoalveolar Lavage of Pneumocystis carinii Pneumonia: Cytological and Ultrastructural Features.: Kun Young Kwon, Cheol Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; J Pathol Transl Med. 1994;5(1):1-9.

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Abstract PDF: The cytological and ultrastructural findings of Pneumocystis carinii(PC) obtained from rats by bronchoalveolar lavage(BAL) are described. All developmental forms of the PC organisms were obtained in the lavage fluid. Ultrastructurally, the cysts were almost circular in shape, and were nearly devoid of surface tubular extensions. The wall of the cyst was composed of an unit membrane, and intermediate electron lucent layer and an external electron dense layer. The cysts frequently contained intracystic bodies, so called sporozoites. Occasionally empty or collapsed cysts with no intracystic bodies, and precysts were found. Trophozoites were variable in size and shape with abundant tubular extensions along the single electron dense pellicle. BAL is a useful method for concentrating the various morphologic forms of PC organisms, and is a rapid diagnostic method for PC pneumonia.

Immunohistochemical and Ultrastructural Observation on Small Round Cell Tumors.: Chae Hong Suh, Jeong Yeol Yang, Sung Chul Lim, Yong Lim Kim; Korean J Pathol. 1997;31(11):1200-1213.

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Abstract: Small round cell tumors such as neuroblastoma, rhabdomyosarcoma, Ewing's tumor, malignant lymphoma and small cell carcinoma are often confused clinically and histologically. To clarify the similarites and differences and to get more information on the histogenesis among the small round cell tumors, we examined histological, immunohistochemical and ultrastructural features of ten cases of neuroblastomas, twenty Ewing's tumors, ten embryonal rhabdomyosarcomas and twelve small cell carcinomas in children and young adults. Antibodies against desmin, vimentin, cytokeratin, neuron-specific enolase, synaptophysin, neurofilament, S-100 protein, chromogranin and HBA 71 were used in biotin streptavidin procedures. The results of the immunohistochemical and electron microscopical examinations yielded virtually identical findings in each group as followings. 1) Among the twenty cases of Ewing's tumors, eighteen cases were positive in staining for HBA-71. The staining for HBA-71 was negative in neuroblastoma, embryonal rhabdomyosarcoma and small cell carcinoma. 2) Neuroblastomas had marked interdigitating cytoplasmic processes containing many microtubules and dense-core secretory granules, however, they were sparse and rare in Ewing's tumor. 3) Embryonal rhabdomyosarcoma showed actin-myosin bundles. According to differentiation, well differentiated rhabdomyosarcoma exhibited Z-band materials and external lamina. 4) Neuroblastoma showed ultrastructural evidence of a neuronal differentiation, but neuronal differentration is a sparse and rare in Ewing's tumor. This ultrastructural feature strengthens the hypothesis that Ewing's tumor is derived not only from an undifferentiated neuroectodermal stem cell but from primitive cell of neuroectodermal origin.

Immunohistochemical and Ultrastructural Studies of Gastric Smooth Muscle Tumor.: Hyang Mi Ko, Kyung Soo Kim, Jae Hyuk Lee, Woo Sik Juhng, Sang Woo Juhng; Korean J Pathol. 1996;30(3):245-254.

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Abstract PDF: To evaluate the differentiation status of smooth muscle in gastric stromal tumors which were negative for S-100 protein, immunohistochemistry using desmin, actin, myosin and vimentin was performed in 14 cases of gastric smooth muscle tumors. Ultrastructural Examination was also performed. For comparison a case of leiomyoma of the esophagus, a case of the sigmoid colon, 10 cases of the uterus were also examined. The results obtained were as follows. All gastric smooth muscle tumors showed vimentin-positivity. Six of 14 gastric smooth muscle tumors, (5 of 8 leiomyoma and 1 of 4 leiomyosarcoma) showed positivity for desmin, actin, and myosin(42.9%). All esophageal, colonic, and uterine leiomyomas showed diffuse positive reaction for desmin, actin, and myosin. Vimentin positivity was also noted in leiomyoma of the colon and uterus. Ultrastructurally, a few cells in the gastric stromal tumors had scattered microfilaments with dense bodies, subplasmalemmal dense plaques, and micropinocytic vesicles. However, most of the tumor cells did not have any of the ultrastructural features of smooth muscle differentiation. Leiomyomas of the esophagus and uterus showed many cytoplasmic microfilaments with dense bodies. These results suggest that most of the benign and malignant tumor cells of gastric stromal tumors have features of the undifferentiated cells, immunohistochemically as well as ultrastructurally, although a few cells have. It is speculated that most gastric stromal tumors may have lost their smooth muscle differentiation.

Peritoneal Diffuse Anaplastic Malignant Mesothelioma Simulating Anaplastic Carcinoma.: Mee Yon Cho, Soon Hee Jung, Woo Ick Jang, Dong Su Cha; Korean J Pathol. 1994;28(2):206-209.

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Abstract PDF: A case of diffuse malignant mesothelioma of peritoneum which was difficult to distinguish from metastatic anaplastic carcinoma or malignant melanoma was presented. The patient was a 50 year-old woman and complained of an abdominal pain and ascites for 20 days. Histologically, the tumor cells showed highly anaplastic appearance with sheet-like arrangement without any papillary or tubular structure. They stained Positive for cytokeratin and vimentin and negative for CEA, S-100 protein and melanoma associated antigen. A few cells within the tumor showed Positive reactivity to desmin. Ultrastructurally, the tumor cells had characteristic findings of mesothelioma such as long, exuberant, wavy microvilli with 10 to 12 of length/diameter ratio. The patient died 3 months after the diagnosis in spite of intraperitoneal chemotherapy.

Pathologic Findings of Mitochondrial Myopathy.: Lucia Kim, Tai Seung Kim; Korean J Pathol. 2000;34(1):77-84.

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Abstract PDF: Mitochondrial myopathy (MM) has been applied to muscle disease in which mitochondria have abnormal structure, function or both. To characterize the pathologic findings of MM, we examined the ultrastructural and histochemical findings of 24 cases of MM. The ultrastructures of the MM were characterized by abnormal mitochondria in number (pleoconia) and size (megaconia), and showed predominant accumulation of mitochondria in the subsarcolemmal space of myofibers in all cases. Mitochondria contained abnormally shaped cristae (concentric form and gyriform) in 79% of cases. Paracrystalline inclusion which was known to be a characteristics of MM were seen only in 7 cases (29%). Electron dense deposits were more frequently found (77%) in abnormal mitochondria of chronic progressive external opthalmoplegia and Kearn-Sayre syndrome. But, other findings were not specific for the specific clinical entities. On succinate dehydrogenase (SDH) stain, ragged red fibers (RRF) showed more intense positivity than modified Gomori-trichrome stain and definite strong reactive products were present along the periphery of myofibers which showed normal findings on modified Gomori-trichrome stain. In conclusion, ultrastructural findings such as mitochondria showing pleoconia with megaconia, and bizarre shaped cristae may be helpful for the diagnosis of MM and SDH stain is more useful for identification of RRF than modified Gomori-trichrome stains.

Smooth Muscle Tumors of the Stomach : A clinicopathologic analysis of 46 cases.: Mee Soo Chagn, Yong Il Kim, Woo Ho Kim; Korean J Pathol. 1991;25(5):418-426.

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Abstract: This study was undertaken to characterize the clinicopathologic features of smooth muscle tumors of the stomach with additional regard to recent controversy over the gastrointestinal smooth mscle tumors. A total of 46 consecutive cases(47 tumors) of surgically resected or excised gastric smooth muscle tumors, were assessed for review. The criteria for malignancy applied in this study were one of the followings; (1) 5 or more mitoses/10 HPF or (2) 1-4 mitoses/10 HPF with tumor cell necrosis and 5 cm or greater in tumor size. The tumors were classified as ordinary leiomyoma in 24 cases(25 tumors), epithelioid leiomyoma in 3, cellular leiomyoma in 6, ordinary leiomyosarcoma in 10, myxoid leiomyosarcoma in 2, and epithelioid leiomyosarcoma in 1. Of the 46 cases, 13 cases(28%) were categorized as malignant smooth muscle tumor. But immunohistochemical study for S-100 protein, desmin and vimentin(5 cases), and ultrastructural study(2 cases) support that myogenic or neurogenic differentiation is evident simultaneously within the same tumor, regardless of malignancy, and that even the differentiated tumor cells seem to express such direction toward immature smooth muscle cell or nerve cell.

An Ultrastructural Study of Bleomycin-Induced Interstitial Pulmonary Fibrosis in the Rat.: Seung Che Cho, Kwan Kyu Park, Kun Young Kwon, Eun Sook Chang; Korean J Pathol. 1991;25(6):539-550.

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Abstract PDF: This study was carried out to investigate the mechanisms of interstitial pulmonary fibrosis of rats after the intratracheal administration of bleomycin. Both lungs after bleomycin injection were examined by light and electron microscopy. The results are as follows: Light microscopically, 1 or 2 weeks after bleomycin injection acute and chronic inflammatory infiltrates and edema in the interstitium and alveolar spaces were observed. Proliferation of alveolar type II pneumocytes was also found at 4 to 6 weeks after bleomycin injection, chronic inflammatory infiltrates with interstitial fibrous thickening were noted. Electron microscopically, the number of type II pneumocytes and irregular lamellar bodies were increased and blunted microvilli were noted at 2 weeks. 4 to 8 weeks, proliferation of fibroblasts with deposition of abundant collagen fibrils in the thickened interstitium revealing irregular or collapsed alveolar spaces were observed. Based on these findings, it can be concluded that bleomycin-induced interstitial pulmonary fibrosis is considered to pass from an early acute inflammation of the interstitium and alveolar spaces to an interstitial fibroblast proliferation and collagen deposition to the length of the period after injection.

Ultrastructural In Situ Hybridization Method for Detection of Oncogenic Viruses.: Keun Hong Kee, Chul Hee Choi, Ho Jong Jeon; Korean J Pathol. 1996;30(8):687-698.

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Abstract PDF: In situ hybridization (ISH) is a standard method for localizing DNA or RNA sequences in tissue or cell preperation. The technique was developed at the electron-microscopic level, and enables the precise subcellular localization. A method was developed for detection of specific viral DNA. We have tested various methods and technique to detect specific viral DNA through ISH at the electron microscopic level. Postembedding method of ultrastructural ISH was developed and successfully applied for the detection of human papillomavirus type 16 in squamous cell carcinoma of the uterine cervix and Epstein-Barr virus in EBV-infected leukemia cell line. The following results are made. The best results were obtained using 0.2% glutaraldehyde and 4% paraformaldehyde fixed tissue or cell block. The labelling was best observed on Unicryl resin and Lowicryl K4M resin sections. Epon sections showed no reactivity. Thin sections of Unicryl resin were more easier than Lowicryl K4M resin. Enzymatic predigestion with proteinase K, pepsin and trypsind gave good results. However, high concentration of these produce poor results due to excessive destruction of the cellular components. Alkali treatment with 0.5N sodium hydroxide produced successful results in denaturation of target DNA. The labelling density of gold particles was independent of incubation time or temperature in hybridization step. The viral DNA labelling was localized mainly within the nucleus, both within and at the edge of electron dense regions, and below the nuclear membrane. And the labelling was seen in the form of a dense, roughly spherical shape. In conclusion, the best results are obtained by the conditions that tissue fixed by 0.2% glutaraldehyde and 4% paraformaldehyde solution, embedded with Unicryl resin, protein denaturation by 0.1ul/ml proteinase K, DNA denaturation by 0.5N sodium hydroxide, and reaction with DNA probe.

Histological, Enzyme Histochemical, and Electron Microscopic studies of the Rat Kidney Following Administration of Folic Acid.: Myoung Jae Kang, Woo Sung Moon, Dong Geun Lee, Ho Yeul Choi, Sang Ho Kim, Kyu Hyuk Cho; Korean J Pathol. 1994;28(5):449-459.

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Abstract PDF: To investigate the morphologic evidence of acute renal failure by folate, histological, histochemical (PAS), enzyme histochemical (Na-K-ATPase, G6PD, and ALP), and ultrastructural studies were performed. The results are as follows: l) Oliguria was most severe 3 hours after folate and the urine volume was 24.8% that of the control group. 2) Histologically, dilatation of tubules, degeneration and focal necrosis of the cortical tubules, and PAS(+) droplets in the tubular lumen were noted. And also frequent mitoses, mild interstital connective tissue proliferation, and neutrophilic infiltrates were observed in the late stage. 3) On enzyme histochemical examination, the activities of Na-K-ATPase and ALP were decreased, but G6PD activity was increased in comparison with the control group. 4) The ultrastructural studies revealed cytoplasmic vacuoles, apical cytoplasmic blebbing, dense bodies, mildly swollen mitochondria, dilated endoplasmic reticulum, loss bf brush border of the proximal tubules, and loss of microvilli of the thin limb of Henle's loop. Later, marked attenuation or loss of infoldings of basal plasma membrane of the cortical tubules was recognized. According to above results, the cause of acute renal failure by late is thought to be the injuries of tubular epithelial cells including sodium pump secondary to tubular obstruction.

Case Reports

Ultrastructural Findings of Hereditary Sensory and Autonomic Neuropathies, Type IV and II.: Jai Hyang Go, Yeon Lim Suh; Korean J Pathol. 1998;32(7):535-539.

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Abstract: Hereditary sensory and autonomic neuropathies (HSAN) are disorders of hereditary neuropathy mainly affecting sensation and also accompanying autonomic nervous system dysfunction. They are divided into five subtypes based on inheritance pattern and clinical manifestation. Among HSAN, type II is characterized by autosomal recessive inheritance, presentation at later stage of life, slow progression and mainly sensation abnormalities. The main pathology of the peripheral nerve is the absence of myelinated nerve fibers. Type IV is very rare disorder and only a few cases have been reported. It is characterized by autosomal recessive inheritance, presentation at birth as failure to thrive, retarded motor development, unexplained pyrexia and rapidly progressive and severe clinical course. The main pathology of the peripheral nerve is a loss of unmyelinated and small myelinated nerve fibers. We report two cases of type IV and one case of type II especially focusing on ultrastructural findings, which are characteristic of and diagnostic for HSAN.

Malignant Granular Cell Tumor of the Shoulder: A case report.: Jae Hun Chung, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Cheol Lee; Korean J Pathol. 2000;34(6):475-479.

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Abstract PDF: A malignant granular cell tumor (MGCT) occurred in the left shoulder of a 62-year-old man. The patient underwent wide marginal excision followed by chemotherapy and radiotherapy. A metastatic tumor was identified in the axillary lymph node 22 months after the excision of the shoulder mass. The primary tumor was a poorly circumscribed mass measuring 5 5 4 cm. On cut section, it was a solid mass with yellowish tan color. Histologically, both primary and metastatic tumor consisted of polygonal cells with abundant granular cytoplasm and a vesicular nucleus with a prominent nucleolus. Two to three mitotic figures per ten high power fields at 200 were counted. Tumor cells were weakly stained with periodic acid-Schiff (PAS) preparation both before and after diastase digestion, and were positive for S-100 protein, neuron-specific enolase (NSE), and vimentin. By electron microscopy, the cytoplasm was filled with numerous autophagolysosomes containing myelin figures, mitochondria, and fragmented rough endoplasmic reticula. Basal laminae and angulated bodies were also noted. These findings suggest schwannian differentiation of this tumor.

Original Articles

The Effects of Cyclosporine A on Minimal Change Nephrosis and Focal Segmental Glomerulosclerosis Induced by Administration of Puromycin Aminonucleoside in Rats.: Sun Hee Sung; Korean J Pathol. 1996;30(11):981-997.

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Abstract PDF: Cyclosporine A(CsA) is known as a potent immunosupressive agent, and recently its supressive effects of proteinuria in minimal change nephrotic syndrome, and other glomerular diseases have been demonstrated. But the mechanism of supression of proteinuria is not clear. This study aimed to investigate the mechanism of supression of proteinuria in puromycin aminonucleoside (PAN) induced minimal change nephrosis(MCN), by a single dose of PAN, and focal segmental glomerulosclerosis(FSG) by long term repeated administration of PAN with unilateral nephrectomy in Sprague-Dawley rats, using transmission electron microscopy. We also analysed the effects of CsA on the histopathologic changes such as glomerular sclerosis, and subtypes of infiltrated mononuclear cells in glomeruli and renal interstitium. The results are as follows: Marked proteinuria was developed in MCN and FSG groups. It was significantly reduced by administration of CsA. BUN and creatinine were significantly increased in FSG with the administration of CsA, compared with FSG without CsA. On ultrastructural examination, MCN group showed effacement of foot processes, and microvillous transformation. Occasional focal detatchment of podocytes from the GBM, vacuolar degeneration, and electron dense droplets in the podocytes were also seen. The latter findings were remarkably reduced by CsA. The Above ultrastructural findings, seen in the MCN group, were more severe in the FSG groups. On comparison of ultrastructural fingings of FSG with or without CsA groups, severe vacuolar degeneration, abundant electron dense granules, and focal detatchment of foot processes were more frequently seen in FSG groups and they were significantly reduced by CsA. But irregularity and thickening of GBM were deepend in FSG with CsA group. There were no significant differences of glomerular sclerosis, adhesion to the Bowman's capsules in both the MCN and the FSG groups by administration of CsA. Foamy degeneration of endothelial and mesangial cells, epithelial proliferation, hyalinosis and mononuclear infiltration were significantly reduced by CsA in FSG groups. Microcalcification was commonly seen in CsA administrated groups. The main sutype of infiltrated mononuclear cells in glomeruli and interstitium were monocytes in FSG groups. The proportion of T cells were higher in interstitium by disease progression and it was significantly decreased by CsA. On conclusion the most important ultrastructural changes, regarded as the main mechanism of supression of proteinuria is that the CsA stabilize the podocytes, by preventing vacuolar degeneration and focal detatchment. But CsA does not influence the progression of glomerular sclerosis in PAN induced nephrosis.

Ultrastructural Study of Amiodarone-Associated Lung Injury.: Eun Yung Kim, Sang Han Lee, Yoon Kyung Sohn, Tae Joong Sohn; Korean J Pathol. 1995;29(1):10-23.

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Abstract PDF: Amiodarone, an antiarrhythmic drug, may exert pulmonary toxicity in some patients but the pathogenesis is not clear. This study was carried out to investigate the pathogenetic mechanism of pulmonary injury induced by amiodarone at dose of 100 mg/kg/day given to rats by intraperitoneal injection for 3 weeks. And the preventive effects of concomitantly injected steroid (10 mg/kg/day) on amiodarone induced pulmonary injury was also studied using bronchoalveolar lavage, light microscopy and transmission electron microscopy. The results obtained were summarized as follows: Mild lymphocytosis of bronchoalveolar lavage fluid was found in all experimental groups. Intracytoplasmic lamellar body formation was found in all types of pulmonary cells and type II pneumocytes revealed the earliest abnormal lamellar body formation. The capillary endothelial cells showed cellular swelling and detachment from underlying basement membrane at early phase of experiment and the edema of alveolar wall and interstitium were noted. Interstitial fibrosis and proliferation of type II pneumocytes were noted at late phase. The lungs of steroid injected groups revealed accumulation of lamellar bodies in all types of pulmonary cells but interstitial fibrosis was not occurred. These findings support the concept that amiodarone is responsible for a drug-induced phospholipidosis and directly toxic to pulmonary endothelial and epithelial cells. And steroid may regress the progression of amiodarone induced pulmonary injury.

Clonal Analysis of Neurofibroma by PCR Amplification of HUMARA Gene.: Jae Hyuk Lee, Seung Sang Han, Hyun Sik Oh, Yoo Duk Choi, Hyun Joong Kim, Kyung Hwa Lee, Jong Hee Nam, Chan Choi, Sang Woo Juhng; Korean J Pathol. 2003;37(6):421-428.

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Abstract PDF: BACKGROUND
While neurofibromas have generally been regarded as polyclonal hyperplastic lesions, it remains unclear whether the tumor is a true neoplasm or a hyperplastic lesion.
METHODS
Determination of clonality by X chromosome inactivation pattern was investigated in twenty-one cases of neurofibroma employing enzyme digestion and PCR of the HUMARA gene. The histological, immunohistochemical, and ultrastructural characteristics of the tumors were also examined.
RESULTS
Immunohistochemically, most of the tumor cells showed vimentin and S-100 protein positivity. Axons were demonstrated by neurofilament protein positivity and were seen mainly at the periphery and rarely in the central portion of the tumor. Ultrastructurally, the tumors were composed of a variety of cell types: perineurial cells, Schwann cells, fibroblasts, and axons. X chromosome inactivation analysis was completed on thirteen out of fifteen cases in which DNA was successfully extracted. Of thirteen neurofibromas that were heterozygous at the HUMARA loci, eleven showed a polyclonal pattern. The remaining two cases were considered as indeterminate for clonality because of unequal band intensity and failure to obtain the normal control DNA.
CONCLUSION
The results from this study suggest that neurofibromas are polyclonal in origin and might be a neoplastic lesion comprising non-neoplastic cells among constituent components.

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