Evaluation of the VE1 Antibody in Thyroid Cytology Using Ex Vivo Papillary Thyroid Carcinoma Specimens

BACKGROUND: Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. METHODS: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. RESULTS: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. CONCLUSIONS: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use.

A superficial hyperechoic band in human articular cartilage on ultrasonography with histological correlation: preliminary observations

PURPOSE: To demonstrate the superficial hyperechoic band (SHEB) in articular cartilage by using ultrasonography (US) and to assess its correlation with histological images. METHODS: In total, 47 regions of interest (ROIs) were analyzed from six tibial osteochondral specimens (OCSs) that were obtained after total knee arthroplasty. Ultrasonograms were obtained for each OCS. Then, matching histological sections from all specimens were obtained for comparison with the ultrasonograms. Two types of histological staining were used: Safranin-O stain (SO) to identify glycosaminoglycans (GAG) and Masson's trichrome stain (MT) to identify collagen. In step 1, two observers evaluated whether there was an SHEB in each ROI. In step 2, the two observers evaluated which histological staining method correlated better with the SHEB by using the ImageJ software. RESULTS: In step 1 of the analysis, 20 out of 47 ROIs showed an SHEB (42.6%, kappa=0.579). Step 2 showed that the SHEB correlated significantly better with the topographical variation in stainability in SO staining, indicating the GAG distribution, than with MT staining, indicating the collagen distribution (P<0.05, kappa=0.722). CONCLUSION: The SHEB that is frequently seen in human articular cartilage on high-resolution US correlated better with variations in SO staining than with variations in MT staining. Thus, we suggest that a SHEB is predominantly related to changes in GAG. Identifying an SHEB by US is a promising method for assessing the thickness of articular cartilage or for monitoring early osteoarthritis.

The Significance of Caspase-Cleaved Cytokeratin 18 in Pleural Effusion / 결핵및호흡기질환

BACKGROUND: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. METHODS: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. RESULTS: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1+/-1,467.3 U/mL) than in patients with lung cancer (956.5+/-618.5 U/mL), parapneumonic effusion (689.9+/-413.6 U/mL), and transudates (273.6+/-144.5 U/mL; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues. CONCLUSION: Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues.

Sudden Unexpected Death caused by Olfactory Groove Meningioma: A Case Report / 대한법의학회지

Meningiomas, one of the most common neoplasms of the central nervous system, may be encountered incidentally during autopsy. Most of these tumors, however, are benign and hence, are not considered as the chief cause of death. Further, sudden unexpected death caused by meningioma is very unusual. Moreover, the diagnosis of an incidental meningioma as the cause of sudden death may sometimes be difficult. In the present report, we describe an autopsy case of a sudden, unexpected death due to a large olfactory groove meningioma accompanied by severe cerebral edema and tonsillar herniation.

The Characteristics of Incidental Pituitary Microadenomas in 120 Korean Forensic Autopsy Cases

To investigate the characteristics of incidental pituitary microadenomas, we examined 120 pituitary glands from Korean forensic autopsy cases, from which eight tumors were identified (incidence 6.7%). The average age of the affected subjects was 50 yr (range: 33-96 yr) with a female predominance. The maximum diameters of the tumors ranged from 0.4 to 5.4 mm (mean: 2.8 mm). Immunohistochemical analysis of pituitary hormones revealed three growth hormone-secreting adenomas, one prolactin-producing adenoma, one gonadotropin-producing adenoma, one plurihormonal adenoma, and two null cell adenomas. MIB-1 staining for Ki-67 antigen showed no positive expression. The microvessel density (MVD) of the pituitary microadenomas ranged from 2.3 to 11.6% (mean: 5.3%) and was significantly lower than that of nonneoplastic pituitary glands (11.9-20.1%, mean: 14.8%). Our study provides reference data on incidental pituitary microadenomas in the Korean population.

Cyclooxygenase-2 and p53 Expression as Prognostic Indicators in Conventional Renal Cell Carcinoma

The aim of this study was to investigate the relationship of cyclooxygenase (COX) -2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p= 0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p < 0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.

Primary Left Atrial Myxofibrosarcoma: A case report / 대한흉부외과학회지

Primary cardiac tumor has very low incidence, especially in cases of malignancy. A 29 year old male patient visited our cardiologic clinic for recent aggrevation of dyspnea on exertion and palpitation. Echocardiography showed a large tumor in the left atrium, which suggested the left atrial myxoma. Urgent open heart surgery was taken. The operative finding was fossa ovalis based a large tumor (35 x 90 x 50 mm) that invaded the posterior wall of LA and right superior pulmonary vein directly. The tumor was excised well by simple dissection, and the final pathologic report was malignant myxofibrosarcoma. His postoperative course was smooth and he was discharged in good health. Postoperative radiation and chemotherapy had taken with satisfactory clinical outcome.

Automation of Abstract-Associated Work in Annual Scientific Meeting of Professional Society Using the Internet / 대한의료정보학회지

Abstract-associated work is a painstaking part of every annual scientific meetings of professional societies . Abstracts have to be received via mail and delivered to the editorial board committee for the committee members to screen the quality and format of the meeting presentations. There are some professional societies that use a web-based abstract receiving system but this is limited only to the reception of abstracts. The work, thus, exhausts time, money and labor. With this in mind, we developed a new automated system which is fully web-based, making possible the reception, selection and publication of the abstracts. This was first applied to the 2001 Korean Society of Pathologists Fall Meeting(http://www.pathology.or.kr/abstract.htm). The overall selecting and electronic-publishing process took only few days. In addition to the convenience, the members of society were able to not only save time but also money. In order to make this possible, an electronic abstract book and a stand-alone executable program were distributed through the Internet (http://www.pathology.or.kr/way-board/db/File_Archives/file/Path200l.EXE).

Automation of Abstract-Associated Work in Annual Scientific Meeting of Professional Society Using the Internet / 대한의료정보학회지

Abstract-associated work is a painstaking part of every annual scientific meetings of professional societies . Abstracts have to be received via mail and delivered to the editorial board committee for the committee members to screen the quality and format of the meeting presentations. There are some professional societies that use a web-based abstract receiving system but this is limited only to the reception of abstracts. The work, thus, exhausts time, money and labor. With this in mind, we developed a new automated system which is fully web-based, making possible the reception, selection and publication of the abstracts. This was first applied to the 2001 Korean Society of Pathologists Fall Meeting(http://www.pathology.or.kr/abstract.htm). The overall selecting and electronic-publishing process took only few days. In addition to the convenience, the members of society were able to not only save time but also money. In order to make this possible, an electronic abstract book and a stand-alone executable program were distributed through the Internet (http://www.pathology.or.kr/way-board/db/File_Archives/file/Path200l.EXE).

Primary Malignant Fibrous Histiocytoma of the Kidney

Primary renal malignant fibrous histiocytoma is a rare tumor of the kidney. It is clinically and radiologically indistinguishable from a renal cell carcinoma. Even following radical surgery, the tumor shows a strong predilection for local recurrence and the prognosis is generally poor. We report on a 32-year-old man with malignant fibrous histiocytoma of the kidney who remained free of recurrence for 1 year after radical nephrectomy.

Primary Malignant Fibrous Histiocytoma of the Kidney

Primary renal malignant fibrous histiocytoma is a rare tumor of the kidney. It is clinically and radiologically indistinguishable from a renal cell carcinoma. Even following radical surgery, the tumor shows a strong predilection for local recurrence and the prognosis is generally poor. We report on a 32-year-old man with malignant fibrous histiocytoma of the kidney who remained free of recurrence for 1 year after radical nephrectomy.

Clinical Significance of p53, MDM2 and Cyclin D1 Protein Expression in Patients with Multiple Myeloma / 대한혈액학회지

BACKGROUND: Dysregulation of cell proliferation contributes to the pathogenesis of multiple myeloma (MM) and the number of S phase plasma cells is known to be one of the most important prognostic factors in MM. We analysed the cell cycle progression in MM using the expression of G1/S phase cell cycle regulators, such as p53, murine double minutes (MDM2) and cyclin D1. METHODS: The expressions of p53, MDM2 and cyclin D1 were evaluated by immunohistochemical staining with monoclonal antibodies, using bone marrow sections obtained from 48 patients with MM and 20 normal controls. RESULTS: The expressions of p53, MDM2 and cyclin D1 were demonstrated in 17 (35.4 %), 40 (83.3%) and 28 (58.3%) of 48 patients with MM, respectively. The expressions of cyclin D1 and p53 were positively correlated each other (P<0.05). However, no significant difference in MDM2 expression was found between the cyclin D1-positive and -negative groups. All of the control group showed negative expression. The expression of cyclin D1 and p53 in patients with MM correlated well with clinical and histologic stages (P<0.05). Even if MDM2 was upregulated in most patients with MM, no correlation was found with clinical or histologic stages. Serum beta2-microglobulin levels were reversely correlated with p53 expression, not with MDM2 or cyclin D1. After chemotherapy, all 5 patients with objective response showed decreased staining of these three proteins, comparing 10 of 13 patients with partial response or treatment failure showed no change or an increased degree of staining. No differences were observed in the survival rates between the groups with and without expression of each three proteins. CONCLUSIONS: These findings suggest that the expression of p53, MDM2 and cyclin D1 was increased in patients with MM and the expression rates of p53 and cyclin D1 were increased with the progression of the clinical and histological stages. It is considered that the detection of cell cycle regulatory proteins are important for understanding the biology of the malignant plasma cells, monitoring the results of treatment and determining the prognosis in MM.

Expression of phospholiapse C isozymes in human lung cancer tissues / 결핵

BACKGROUND: Phospholipase C (PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol(DAG) and lnositol 1, 4, 5-trisphosphate(IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracelluar calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2(SH2) domain, Src homology 3(SH3) domain, and pleckstrin homology(PH) domain play crucial roles in protein translocation, lipid membrane modification and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-γ1, γ2, β1, β3, and δ1 isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-γisozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various histologic types of lung cancer tissues as compared to the normal lungs. However, the report concerning expression of various PLC isozymes in lung cancers and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. METHODS: Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients. The expression of various PLC isozymes were studied. Western bolt analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. RESULTS: In 16 of 18 squamous cell carcinomas, the expression of PLC-γ1 was increased. PLC-γ1 was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-δ1 was decreased. However, the expression of PLC-δ1 was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-δ1 was nearly absent. CONCLUSION: We found increased expression of PLC-γ1 isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-γ, activator-over-expression, and the changes observed in PLC-δ1 in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

Thyroid Acropachy / 대한정형외과학회잡지

Thyroid acropachy is a rare complication of Graves' disease, manifested by clubbing of the terminal phalanges, periosteal new bone formation and overlying soft tissue swelling, It may occur when the patient is hypothyroid, euthyroid or hyperthyroid. In most cases, it is a part of the syndrome, including exophthalmos and/or pretibial myxedema. The authors have experienced one case of thyroid acropachy and report with a review of the literature review. The patient a 56-year-old female with a characteristic feathery new bone formation on the medial side of the shaft of the left first metatarsal bone and overlying soft tissue swelling. However, there was no pretibial myxedema and clubbing of fingers. She was hypothyroid and treated with systemic corticosteroid for mild pain and persistent swelling. The treatment had temporarily improved the patient's condition.

Increased Expression of Phospholipase C-gamma1 Activator Protein, AHNAK in Human Lung Cancer Tissues / 결핵

BACKGROUND: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate(PIP2) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate(IP3) and diacylglycerol. PLC-gamma1, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-gamma1 have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by IP3, phosphatidic acid, etc. Very recently, another PLC-gamma1 activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-gamma1 activator, AHNAK, in lung cancer specimens and their paired normal. METHODS: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract. Immunohistochemical stain was performed with primary antibody against AHNAK protein. RESULTS: Twenty-two among twenty-eight lung cancer tissues showed over expression of AHNAK protein(eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomal). the resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot. CONCLUSION: The overexpression of PLC-gamma1 activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-gamma1 act in concerted manner in carcinogenesis.

Maximal Diagnostic Accuracy in Virtual Telepathology System according to Input Device and Video Signal

Varieties of telepathology system had been developed and in use, but their functional capability and diagnostic accuracy are considered to be inferior to those of conventional optical microscope. This study is intended to find out: 1) the diagnostic accuracy and reproducibility rate according to the input devices and the video signals; 2) any potential technical problems of the telepathology system; 3) any possible physical and psychological impacts. We devised a virtual telepathology system using our existing microscope equipped with CCD camera unit that has no restriction of network speed. Total fifty-five surgical pathology cases from 11 different organs were selected. Three pathologists were involved in making diagnoses. The resulting diagnostic accuracies were: 1 CCD camera with composite video signal was 86.2%; 3 CCD camera with composite video signal was 93.1%; 3 CCD camera with component video signal was 95.0%. The 3 CCD camera with component video signal resulted in 95.0% diagnostic accuracy and was superior to 1 CCD camera with composite video signal. Some technical problems noted during this study were: the visual field of the virtual telepathology system was smaller by 43% than that of microscope; the difference of cell sizes between microscope and monitor; low resolution of image. Some physical and psychological symptoms were noted.

Multiple Angiomyolipoma of the Liver: Report of a Case with Diagnosis by Fine Needle Aspiration Cytology / 대한세포병리학회지

Angiomyolipoma(AML) of the liver is a rare benign tumor; about 60 cases, almost solitary, have been reported. We present here a extremely rare case of multiple AML in the liver diagnosed by fine needle aspiration cytology (FNAC). Two large masses were found in a 51 year-old woman complaining of abdominal discomfort by computed tomography and several smaller masses are scattered in the liver. FNAC was performed, showing bundles of spindle shaped smooth muscle cells intermingled with mature fat cells. FNAC may be a valuable method for definitive diagnosis of hepatic AML. The diagnosis was further confirmed by histologic examination with immunohistochemical studies.

The Arthroscopic Treatment of Lipoma Arborescens of Knee: A Case Report

Lipoma arborescens is a rare intra-articular lesion consisting of a villous lipomatous proliferation of the synovial lining. We experienced one case of lipoma arborescens of knee which was associated with avascular necrosis of femoral head. This case report draws the attention to history, physical findings, MR images, pathologic findings and arthroscopic appearance of this rare lesion. Arthro;copically, the lesion appears as a synovial lesion with numerous fatty-appearing globules and villous projections. Although the etiology is unknown, lipoma arborescens has been described in association with osteoarthritis, rheumatoid arthritis and diabetes mellitus. MR imaging is diagnostic choice to differentiate the lesion from rheumatoid arthritis, pigmented villonodular synovitis and synovial chondromatosis in those patients who present with chronic, swollen and painfui joint. Arthroscopic removal was effective in this case and we think that treatment choice of this lesion is arthroscopic removal.

Internet Use for the Evaluation of Medical Learning / 한국의학교육

There are many ways to evaluate the learning achievement of medical students. We are familiar with the problems related to the traditional laboratory course practical examinations of pathology and histology courses, which deal with morphology heavily. In order to overcome the limitations inherent to the traditional evaluation methods, we used Internet for the written and practical examinations for the pathology course. Two tests were conducted on the internet with thirty medical students. Each student used his/her personal computer, which was connected to Local Area Network(LAN), in the computer laboratory. The examinee entered the Pathology Department home page(address: http://ajoupath. ajou.ac.kr) and took their tests made up of descriptive and multiple choice questions including related gross and microscopic images. Common Gateway Interface(CGI) program of Perl language was used for automatic scoring and analysis of the multiple choice questions. The server computer in the Pathology Department scored the results instantaneously upon the answer selection and push down of the "send" button by the examinee. Furthermore, the computer program was capable of providing data regarding how many students got the correct answer and the degree of difficulty for each item. The students were requested to provide hand-written descriptions for the questions requiring descriptive answers, because of the technical limitation. We believe that the tests on the internet were performed successfully. The "dreadful" old fashioned examination using timer were no longer needed because high quality gross and microscopic images on the monitor were available for the examinee. We believe that the internet is very useful for the comprehensive evaluation of the medical students' learning achievement.

Clavicula Pro Humero Procedure for an Osteosarcoma in the Proximal Humerus: A case report / 대한정형외과학회잡지

Osteosarcoma is one of the most common malignant bone tumors except for multiple myeloma. The current managements of the osteosarcoma patients include preoperative chemotherapy, definitive operation and postoperative chemotherapy with tremendous improved oncologic results by lots of Orthopedic Oncologists. The definitive operations are either limb-salvage operations or amputation. Limb-salvage operations include autograft, allograft, tumor prosthesis, or its combination. However, we have a difficulty to use allograft due to Korean traditonal customs. Authors managed the 6 year-old female patient with the osteosarcoma on the proximal metaphysis of the right humerus by wide-margin resection and reconstruction with a clavicula pro humero procedure with an excellent result, which technique was devised and developed by W. Winkelmann in Germany.