Journal of Pathology and Translational Medicine

Sang Sook Lee

44 Articles

A Case of Intimal Sarcoma Arising in the Left Common Iliac Artery.: Ji Young Park, Kun Young Kwon, Hyoung Tae Kim, Sang Sook Lee; Korean J Pathol. 2011;45(3):311-314.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.311

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Abstract PDF: Primary tumors of the great vessels are rare. Most encountered cases are sarcomas which most commonly develop in the aorta, pulmonary artery, and inferior vena cava. We experienced an intimal sarcoma arising in the left common iliac artery in a 68-year-old male, who suffered from claudication in his left lower extremity for a year and was diagnosed as arteriosclerosis obliterans, clinically. Bypass surgery was performed on the obstructive lesion. Grossly, the vascular lumen was filled with dark hemorrhagic materials. Microscopically, the lesion showed proliferation of anaplastic spindle cells with a marked nuclear atypia, arranged haphazardly. There were numerous mitotic figures. Foci of cholesterol clefts were also found in the intima. Immunohistochemically, the tumor cells were positive for vimentin, smooth muscle actin, and cytokeratin in certain areas. Stains for CD34, desmin, myosin heavy chain, caldesmon, and S-100 protein were negative. A pathologic diagnosis was made as intimal sarcoma with myofibroblastic differentiation.

Comparative Study of Relative Value for Diagnostic Procedure of Surgical Pathology in Korea and United States.: Ilseon Hwang, Yu Na Kang, Kun Young Kwon, Sun Young Kwon, Sang Pyo Kim, Sang Sook Lee, Hye Ra Jung, Mi Sun Choe; Korean J Pathol. 2011;45(1):9-14.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.9

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BACKGROUND
Pathologic examination is a very important diagnostic procedure. It is the most important method to decide the therapeutic plan and to predict the prognosis of cancer patients. The Resource-Based Relative Value Scale (RBRVS) is a schema used to determine how much money medical providers should be paid. In Korea, a modified RBRVS has been used since the year 2000.
METHODS
We researched the July 2010 RBRVS for Korea and the US medicare. The individual Relative Evaluation Index (REI) is defined as the ratio of an individual RBRVS to the mean RBRVS. The REIs of pathologic examination in Korea and America were compared.
RESULTS
For an endoscopic biopsy specimen, the pathologic examination REI in Korea was 55.4% of the American REI. The Korean REI of a prostate biopsy (8 sites) was only 5.7% of the American REI. The Korean REI was 28.1% of the American REI for the hysterectomy for uterine myoma, and the Korean REI was 67.6% of the American REI for resection of stomach or colon cancer.
CONCLUSIONS
The RBRVS of pathologic examination in Korea remains undervalued. Considering the importance of pathologic examination in medicine, the RBRVS in Korea should be increased.

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Diminutive and Small Colorectal Polyps: The Pathologist's Perspective
Yun Kyung Kang
Clinical Endoscopy.2014; 47(5): 404. CrossRef
Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis
Yun Kyung Kang, So-Young Jin, Mee Soo Chang, Jung Yeon Kim, Gyeong Hoon Kang, Hye Seung Lee, Jin Hee Sohn, Ho Sung Park, Kye Won Kwon, Mi Jin Gu, Young Hee Maeng, Jong Eun Joo, Haeng Ji Kang, Hee Kyung Kim, Kee-Taek Jang, Mi Ja Lee, Hee Kyung Chang, Joon
Korean Journal of Pathology.2013; 47(3): 245. CrossRef

Use of Calretinin, CD56, and CD34 for Differential Diagnosis of Schwannoma and Neurofibroma.: Ji Young Park, Hoon Park, Nam Jo Park, June Sik Park, Hyun Jung Sung, Sang Sook Lee; Korean J Pathol. 2011;45(1):30-35.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.30

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Abstract PDF

BACKGROUND
It is important to differentiate between schwannomas and neurofibromas for the cases in which the histopathologic features overlap. Depending on the tumor type, surgeons can decide on a treatment method and whether to preserve or sacrifice the nerve; the possibility of malignant transformation in the case of neurofibromas also needs to be considered.
METHODS
We studied 101 cases of schwannoma and 103 cases of neurofibroma. All the hematoxylin and eosin slides for these cases were reviewed, and tissue microarrays were prepared from the representative areas. Immunohistochemical analysis was performed using antibodies for S-100 protein, calretinin, CD56 and CD34.
RESULTS
All the tumors except 3 neurofibromas were positive for the S-100 protein. Calretinin was found in 26.7% of the schwannomas (27/101), but it was not found in any of the neurofibromas. CD56 was positive in 77.2% of the schwannomas (78/101) and in 9.8% of the neurofibromas (10/102). CD34 was positive in 42.5% of the schwannomas (43/101) and in 80.2% of the neurofibromas (81/101). Statistically, calretinin was significantly specific for schwannomas (p<0.001) and CD56 was also sensitive for these tumors (p<0.001). On the other hand, a CD34 expression seemed highly sensitive (p<0.001) for neurofibromas.
CONCLUSIONS
We concluded that combined immunohistochemical analysis for calretinin, CD56, and CD34 may be very useful for differentiating schwannomas from neurofibromas.

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Lung schwannomas, an unusual entity: A series of five cases
NaziaM Walvir, RumanaH Makhdoomi, Meesa Zargar, Aiffa Aiman, Shadab Maqsood
Lung India.2023; 40(1): 70. CrossRef
A Spectrum of Histomorphological and Immunohistochemical Expression Profiles of S-100, CD56 and Calretinin in Benign Peripheral Nerve Sheath Tumours
Poornima Jaiswal, Anand CD, Jaison Jacob John
Cureus.2023;[Epub] CrossRef
An unusual diffuse CD34 staining in an olfactory groove cellular schwannoma: Case report
Marios Theologou, Jorge D. Perez Ruiz, Panagiotis Varoutis, Nicolaos Flaris, Nikolaos `Skoulios
Archivos de Neurociencias.2023;[Epub] CrossRef
An unusual diffuse CD34 staining in an olfactory groove cellular schwannoma: Case report
Marios Theologou, Jorge D. Perez Ruiz, Panagiotis Varoutis, Nicolaos Flaris, Nikolaos `Skoulios
Archivos de Neurociencias.2023;[Epub] CrossRef
Intranodal Neurofibroma: A Case Report and Literature Review
Steven H. Adams, Tara L. Huston, Daniel Lozeau
The American Journal of Dermatopathology.2022; 44(4): 306. CrossRef
A rare case of pseudoglandular schwannoma
Fadime Eda GÖKALP SATICI, Hamide SAYAR
Journal of Surgery and Medicine.2022; 6(4): 1. CrossRef
Gastric Schwannoma as an Important and Infrequent Differential Diagnosis of Gastric Mesenchymal Tumours: A Case Report and Review of Literature
Abdalla Saad Abdalla Al-Zawi, Salma Lahmadi, Saman Jalilzadeh Afshari, Ipshita Kak, Salem Alowami
Cureus.2022;[Epub] CrossRef
Spindle cell proliferations of the sigmoid colon, rectum and anus: a review with emphasis on perineurioma
Patrice Grech, John B Schofield
Histopathology.2020; 76(3): 342. CrossRef
Large retroperitoneal schwannoma: a rare cause of chronic back pain
Milan Radojkovic, Dragan Mihailovic, Miroslav Stojanovic, Danijela Radojković
Journal of International Medical Research.2018; 46(8): 3404. CrossRef
Nasal Septal Schwannoma
Hyun Jin Min, Seok Chan Hong, Kyung Soo Kim
Journal of Craniofacial Surgery.2017; 28(1): e97. CrossRef
Neurofibroma of the Colon: A Diagnostic Mimicker of Gastrointestinal Stromal Tumor
Soomin Ahn, Choon Sik Chung, Kyoung-Mee Kim
Case Reports in Gastroenterology.2016; 10(3): 674. CrossRef
Solitary Epibulbar Neurofibroma in Older Adult Patients
Thais Shiota Tanaka, Victor M. Elner, Hakan Demirci
Cornea.2015; 34(4): 475. CrossRef
Syncytial nuclear aggregates in normal placenta show increased nuclear condensation, but apoptosis and cytoskeletal redistribution are uncommon
S.J. Coleman, L. Gerza, C.J.P. Jones, C.P. Sibley, J.D. Aplin, A.E.P. Heazell
Placenta.2013; 34(5): 449. CrossRef
Analysis of syncytial nuclear aggregates in preeclampsia shows increased sectioning artefacts and decreased inter-villous bridges compared to healthy placentas
S.J. Calvert, C.J.P. Jones, C.P. Sibley, J.D. Aplin, A.E.P. Heazell
Placenta.2013; 34(12): 1251. CrossRef

Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma.: Ji Min Jeon, Hye Won Lee, Ji Young Park, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Mi Sun Choe, Yu Na Kang, Sang Pyo Kim, Sang Sook Lee, Won Il Choi, Kun Young Kwon; Korean J Pathol. 2010;44(4):397-403.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.397

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Abstract PDF

BACKGROUND
Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance.
METHODS
We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray.
RESULTS
We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128).
CONCLUSIONS
MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.

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Inhibition of MUC1-C Increases ROS and Cell Death in Mouse Embryonic Stem Cells
Jeong-A Park, Sangkyu Park, Jun-Kyu Choi, Myung-Kwan Han, Younghee Lee
International Journal of Stem Cells.2020;[Epub] CrossRef
Assessing the prognostic significance of MUC4β in mucoepidermoid carcinoma of the salivary glands: An immunohistochemical study
Poonam R. Sawant, Anita Spadigam, Anita Dhupar, Shaheen Syed, Karla Carvalho
Heliyon.2019; 5(11): e02753. CrossRef
Ultrasensitive cytosensing based on an aptamer modified nanobiosensor with a bioconjugate: Detection of human non-small-cell lung cancer cells
Tanveer A. Mir, Jang-Hee Yoon, N.G. Gurudatt, Mi-Sook Won, Yoon-Bo Shim
Biosensors and Bioelectronics.2015; 74: 594. CrossRef
Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma
Su-Mi Kim, Sun-Ju Oh, Bang Hur
Korean Journal of Pathology.2012; 46(5): 429. CrossRef
MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer
Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa, Fazlul H. Sarkar
PLoS ONE.2012; 7(11): e49251. CrossRef
Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma
ILSEON HWANG, YU NA KANG, JIN YOUNG KIM, YOUNG ROK DO, HONG SUK SONG, KEON UK PARK
Experimental and Therapeutic Medicine.2012; 4(2): 311. CrossRef

Fine Needle Aspiration Cytology of Invasive Micropapillary Carcinoma of the Breast: Report of four Cases.: Sun Young Kwon, Hae Ra Jung, Yu Na Kang, Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee; Korean J Cytopathol. 2004;15(2):106-111.

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Abstract PDF: Invasive micropapillary carcinoma (IMPCa) is a rare variant of invasive ductal carcinoma of the breast. This variant is associated with a set of peculiar cytological findings and aggressive biological behaviors. In most reported cases, IMPCa has involved massive axillary lymph node metastases at the time of diagnosis. We experienced four cases of cytological features of IMPCa, all of which were verified by histological examination. Fine needle aspiration cytology (FNAC) revealed malignant epithelial cells, which formed small, oval to angulated papillary clusters, which lacked central fibrovascular cores. The histological findings of the four cases revealed both pure and mixed forms of IMPCa, composed of cohesive malignant epithelial cells, surrounded by distinctive clear spaces and separated by thin fibrous septa. All patients evidenced axillary lymph node metastases at the time of diagnosis. It is important to identify the peculiar cytological findings which would differentiate IMPCa from other diseases.

Alterations of 9p21-22 Region Encoding Genes in Primary Glioblastomas.: Hong Jik Doh, Seong Il Suh, Dong Won Kim, Il Man Kim, Man Bin Yim, Eun Ik Son, Kun Young Kwon, Sang Sook Lee, Sang Pyo Kim; Korean J Pathol. 2002;36(6):394-399.

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Abstract PDF: BACKGROUND
Glioblastomas are one of the most common and aggressive malignant glial tumors occuring in the central nervous system. This study analyzed the status of p15INK4b, p14ARF, p16INK4a, MTAP, IFNA, and IFNB genes in 36 primary glioblastomas to investigate whether the inactivation of these genes participate in primary glioblastoma tumorigenesis.
METHODS
We used polymerase chain reaction, polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) analysis, and methylation-specific PCR.
RESULTS
Homozygous deletions at the p16INK4a gene were detected in 11 cases (30.5%) of 36 primary glioblastomas, and the promoter hypermethylation was found in 3 cases (8.3%) of 36 primary glioblastomas. In mutational analysis for the p16INK4a gene by PCR/SSCP, there was no abnormal mobility-shifted band in 36 cases of primary glioblastomas. The overall frequency of p16INK4a alterations including homozygous deletion and promoter hypermethylation in 36 primary glioblastomas was 38.8% (14 of 36). Deletions of p15INK4b were noted in 4 cases (11.1%), whereas deletions of the p14ARF and MTAP genes were detected in 1 case of 36 cases of primary glioblastomas. But deletions of the INFA and B genes were not found.
CONCLUSIONS
These results suggest that alterations of the p16INK4a gene can be important mechanisms of the tumorigenesis of primary glioblastomas, and the p16INK4a gene is inactivated by mechanisms including homozygous deletion and promoter hypermethylation.

The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Factor-beta1 in Unilateral Ureteral Obstruction .: Sang Mi Han, Eun Joo Kim, Hyo Soon Jeoung, Byung Yuk Lee, Sang Sook Lee, Kwan Kyu Park, Hyun Chul Kim; Korean J Pathol. 2002;36(2):84-92.

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Abstract PDF: BACKGROUND
In unilateral ureteral obstruction (UUO), the obstructed kidney is characterized by interstitial fibrosis and an increase in transforming growth factor (TGF)-beta1. Interstitial expression of TGF-beta1 is important in tublointerstitial fibrosis. The objectives of this study is to make new ribbon-type antisense oligodeoxynucleotides (ODN) for TGF-beta1 which are resistant to exonuclease and to examine the effcets of TGF-beta1 on reducing tubulointerstitial fibrosis of the kidney.
METHODS
We introduced a new ribbon-type antisense ODN for TGF-beta1 in rats using the UUO model to block interstitial fibrosis by tail vein injection. A combination of one antisense sequences for TGF-beta1 was adopted to construct a large antisense molecule with a loop and stem. Artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ)-liposomes were used as a vector system for the delivery of antisense ODN.
RESULTS
The levels of TGF-beta1 mRNA was decreased more in the cultured mesangial cells treated with ribbon-type antisense ODN than in that of a linear-type antisense ODN for TGF-beta1. TGF-beta1 mRNA was increased markedly in the interstitium of untreated obstructed kidneys. Northem analysis revealed that the levels of TGF-beta1 mRNA were decreased in the obstructed kidneys treated with antisense ODN. The fibrosis of the obstructed kidneys treated with ribbon-type antisense ODN was dramatically less than that of the untreated group.
CONCLUSIONS
These results demonstrate that the introduction of new ribbon-type antisense ODN for TGF-beta1 may be a potential therapeutic maneuver for preventing interstitial fibrosis.

Metastatic Alveolar Soft Part Sarcoma Presented with a Dura Mass: A Case Report.: Sun Young Kwon, Hyun Chang Joo, Kun Young Kwon, Sang Sook Lee, Chul Ho Sohn, Man Bin Yim, Sang Pyo Kim; Korean J Pathol. 2001;35(2):180-183.

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Abstract PDF: Alveolar soft part sarcoma, accounting for less than 1% of all soft tissue sarcomas, is known for late metastases to the lung, bone and brain. We have examined a case of metastatic alveolar soft part sarcoma to the brain in a 34-year-old woman. Computed tomography of the brain revealed a well enhancing dura based mass of the left temporal area. The patient had a previous history of surgery for alveolar soft part sarcoma from the right thigh at the age of 24 years. She underwent total removal of the dural mass under the clinical impression of the meningioma. Grossly, a well-circumscribed, pale tan and solid mass was 3.4 x 3.2 x 2.4 cm and easily detached from the attached dura. Histologically, the tumor showed typical features of alveolar soft part sarcoma. Immunohistochemically, tumor cells were positive for muscle related antibodies. Ultrastructural examination showed rod-shaped membrane bound crystals and electron-dense granules in the cytoplasm of tumor cells.

Expression of Transforming Growth Factor-beta1 in Cyclosporine-Induced Nephropathy in Rats.: Yu Na Kang, Kwan Kyu Park, Mee Yul Hwang, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Hyun Chul Kim; Korean J Pathol. 2000;34(9):642-651.

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Abstract PDF: Cyclosporine nephropathy was induced by intraperitoneal injection of cyclosporine 25 mg/kg in Sprague-Dawley rats daily for 1, 4, 8, and 12 weeks to clarify the relationship between cyclosporine nephropathy and the expression of TGF-beta1 with extracellular matrix deposition. On light microscopic examination, the kidneys in the 12 week cyclosporine-treated rats showed focal or striped fibrosis, vacuolization of tubular cells, and injury of endothelial cells. Immunohistochemically, TGF-beta1 protein was strongly expressed in the cyclosporine-treated rat kidneys, especially in the glomerular endothelial cells, interstitial endothelial cells, tubular epithelial cells, and parietal cells in the Bowman's capsule of the glomerulus as well as the periglomerular arterioles. The amount of TGF-beta1 expression was correlated with the morphological change in the cyclosporine-treated rats. Extracellular matrix, such as fibronectin and collagen IV, was also expressed in the endothelial cells of the glomerulus and the interstitium. It can be concluded, therefore that TGF-beta1 protein is probably involved in the early stage of fibrogenesis in cyclosporine nephropathy. It can be postulated that cyclosporine nephropathy results from the accumulation of extracellular matrix associated with the increase of TGF-beta1 transcription. Therefore, these results could be used in reducing fibrosis in cyclosporine nephropathy.

Expression of bcl-2 and p53 Protein in Premalignant Lesion and Invasive Squamous Cell Carcinoma of the Uterine Cervix.: Hyun Chang Joo, Kwan Kyu Park, Sang Sook Lee, Eun Sook Chang, Tae Sung Lee, Soon Do Cha, Young Jae Lee; Korean J Pathol. 2000;34(4):280-287.

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Abstract PDF: In order to understand the possible involvement of bcl-2 and p53 proteins in the tumorigenesis of the cervical cancer and precancerous lesion, we studied the expression patterns of bcl-2 and p53 proteins in 25 cases of carcinoma in situ, 12 cases of microinvasive cervical carcinoma, and 37 cases of invasive cervical carcinoma, respectively. By immunohistochemistry, 76% of in situ carcinoma, 83.3% of microinvasive cervical carcinoma, and 60.9% of invasive cervical carcinoma were positive for bcl-2, while the staining of basal cell layers, columnar cells, and squamous metaplastic epithelium of normal cervical epithelium were positive for bcl-2 in 91.9%, 73.1%, and 81.8% of cases, respectively. Furthermore, two out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for bcl-2. p53 was expressed in 72.7% of condyloma or dysplasia, 12% of in situ carcinomas, 33.3% of microinvasive cervical carcinoma, and 43.5% of invasive cervical carcinomas without metastasis. Six out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for p53 immunostaining. In contrast, 5.4% of basal cells and 9.1% of squamous epithelium, and none of the columnar cells in normal cervical epithelium were positive for p53. In summary, the bcl-2 protein was highly expressed in the proliferative lesion of reserve cells, such as normal reserve cells, columnar cells, squamous metaplasia, carcinoma in situ, and microinvasive squamous cell carcinoma. p53 expression was increased in condyloma, carcinoma in situ, and invasive carcinoma where the reserve cells were non-proliferative. Based on these findings, we propose that bcl-2 and p53 protein are involved in the development and progression of uterine cervical carcinoma.

Undescended Testis in the Complete Testicular Feminization Syndrome A report of three cases.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Jung Ho Lee, Jong In Kim; Korean J Pathol. 1999;33(5):371-375.

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Abstract PDF: The testicular feminization is the most common type of male pseudohermaphroditism. Mutation of androgen receptor gene impairs normal sexual differentiation in genetic male (46, XY) and subsequently develops secondary female characteristics. We report three cases of complete testicular feminization syndrome with normal development of female external genitalia, but with blindly ended vagina and inguinal or pelvic masses. Microscopic examination of the testes and their adnexa had three components: 1) A testis composed of immature tubules, prominent Leydig cells and a spindle cell stroma resembling ovarian stroma with hamartomatous nodule or Sertoli cell adenoma, 2) a white, whorled, firm, smooth muscle body in the medial pole of the testis, and 3) a lateral adnexal cysts of varying sizes.

Signet Ring Cell Carcinoma of the Prostate A report of two cases.: Yu Na Kang, Sang Sook Lee, Tae Jin Lee, Jae Yoon Ro; Korean J Pathol. 1999;33(5):385-368.

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Abstract PDF: Primary signet ring cell carcinoma of the prostate is extremely rare and about 18 cases have been reported in the literature. We report two cases of primary signet ring cell carcinoma of the prostate, arising in 79-year-old and 65-year-old men. Both cases were the poorly differentiated adenocarcinoma of the prostate with many signet ring cells. Signet ring cells were positive for prostatic specific antigen and prostatic acid phosphatase but negative for neutral and acid mucins. In summary, the signet ring cell carcinoma of the prostate is a rare variant of poorly differentiated adenocarcinoma of the prostate. The orgin of the prostate should be considered in cases of metastatic signet ring cell carcinoma, particularly when the signet ring cells are negative for neutral and acid mucins. Prostatic specific antigen and prostatic acid phosphatase should also be performed to confirm the primary signet ring cell carcinoma of the prostate.

bcl-2 and p53 Protein Expression in Multiple Myeloma and Non-tumorous Plasma Cells A study related to survival.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Young Jae Lee; Korean J Pathol. 1999;33(3):179-186.

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Abstract PDF: The gene product of bcl-2 (B-cell leukemia/lymphoma-2) was suggested to suppress programmed cell death (apoptosis) of tumor cells and be involved in the development of multiple myeloma. However, the normal plasma cells also express the protein. It is unclear whether the expression of bcl-2 in multiple myeloma is of normal character or of regulatory adaptation in association with neoplastic transformation. p53 was also suggested to be involved in tumor progression since mutations on p53 were found in multiple myeloma. In order to find the relationship between the expression patterns of bcl-2 and p53 in tumor cells of multiple myeloma and non-neoplastic plasma cells, we examined 38 cases of multiple myeloma and 10 cases of nasal polyp immunohistochemically. Furthermore, expression of bcl-2 and p53, mitosis, clinical stage and infiltrative pattern of tumor cells in bone marrow were also evaluated in association with the survival of patients. By immunostaining with anti-bcl-2 and p53 monoclonal antibody, 37 out of 38 cases of multiple myeloma and all of 10 cases of nasal polyp were positive for bcl-2 but only 7 cases of multiple myeloma were positive for p53. Marked dysplasia, low percentage of bcl-2 expression, and increased mitoses were correlated with poor prognosis. Based on these observations, we suggest that bcl-2 and p53 are involved in tumorigenesis of multiple myeloma and the survival of patients would be influenced by dysplastic change, mitosis and degree of bcl-2 expression.

Fine Needle Aspiration Cytologic Features of Schwannomas .: Sun Young Kim, Hae Joo Nam, Jung Hee Kim, Young Rok Cho, Yu Na Kang, Sang Sook Lee; Korean J Cytopathol. 1999;10(1):55-60.

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Abstract PDF: Schwannoma is a benign encapsulated nerve sheath tumor and is histologically characterized by a mixture of Antoni type A and B tissue. A preoperative diagnosis of schwannoma by fine needle aspiration cytology or by any other means is important to preserve clinically important nerves. Therefore, it is necessary to make a specific cytological diagnosis of nerve sheath tumor. However, there are a few reports regarding cytological features of schwannoma in Korea. We experienced seven cases of solitary schwannoma and here we report their characteristic cytological features with a review of literatures. The characteristic features of schwannoma on cytology were the presence of both Antoni type A and B tissue. The cytologic findings common to all cases of schwannoma generally corresponded to the histologic findings of Antoni type A tissue, consisting of fragments of tightly cohesive fascicles with variable cellularity. Dense fibrillary substances were found, along with palisading nuclei and Verocay bodies. Individual tumor cells consisted of cohesive cells having spindle or oval nuclei, with pointed ends and indistinct cell borders. Variation in nuclear size and shape was also present. The Antoni type B consisted of scattered wavy or short spindle cells and some histiocytes and lymphocytes in the abundant myxoid background with formation of microcysts. Immunohistochemistry for S-100 protein revealed a uniformly strong positive reaction and was helpful to make more accurate diagnosis of schwannoma.

Expression of bcl-2 and p53 Protein in Primary Gastric Lymphomas.: Young Rok Cho, Yu Na Kang, Sang Sook Lee, Hong Suk Song, Soo Sang Sohn, Dong Sug Kim; Korean J Pathol. 1998;32(11):978-984.

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Abstract: The bcl-2 gene is a proto-oncogene which extends cell survival by blocking apoptosis. Bcl-2 expression has been detected in many types of nodal and MALT lymphoma. The p53 gene is a tumor suppressor gene and p53 mutation is the most common genetic alteration in human malignancies. The relationship between the expression of bcl-2 and p53 protein in primary gastric lymphoma has been rarely reported. The authors investigated the expression of bcl-2 and p53 protein in 37 cases of primary gastric lymphoma by immunohistochemical method using bcl-2 and p53 monoclonal antibodies. There were five cases of low grade B-cell MALT lymphomas and thirty two cases of high grade B-cell lymphomas. Fifteen of 37 cases (41%) showed bcl-2 protein expression in the cytoplasm of tumor cells and 26 cases (70%) showed p53 protein expression in the nucleus of tumor cells. Bcl-2 protein was detected in 4 of 5 (80%) low grade MALT lymphomas, and in 11 of 32 (34%) high grade lymphomas. There was no significant correlation between bcl-2 expression and histologic grade of primary gastric lymphomas (p>0.05). p53 protein was positive in 25 of 32 (78%) high grade lymphomas, and in 1 of 5 (20%) low grade MALT lymphomas. The expression of p53 protein is significantly higher in high grade lymphoma than in low grade MALT lymphoma (p<0.05). The p53 expression in the bcl-2 negative cases (86%) was significantly higher than in the bcl-2 positive cases (47%). There was an inverse relationship between bcl-2 and p53 expression in primary gastric lymphoma. These results suggest that bcl-2 and p53 expression in primary gastric lymphoma may be involved in the transition from low grade MALT lymphoma to high grade lymphoma.

Castration-induced Apoptosis in the Rat Prostate.: Ki Kwon Kim, Sang Sook Lee; Korean J Pathol. 1998;32(6):431-442.

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Abstract: This study was carried out to investigate the morphologic findings and process of castration-induced apoptosis in the rat prostate. The experimental group was treated with bilateral orchiectomy followed by sequential sacrifices at 1, 2, 3, 4, 5, 6, 7 days and 2, 3 weeks (6 rats, respectively). Ventral prostate was extirpated and examined by light microscopic and immunohistochemical, ultrastructural observation. Apoptotic index increased by 4 days after castration and decreased thereafter. ApopTag stain revealed brownish granular pattern in the nucleus of apoptotic cells. DNA fragmentation rate was 0.5% in the control group and began to increase by 1 day after castration and reached to 11.1% by 4 days and decreased thereafter. PCNA stain showed brownish granular pattern in the nucleus of some epithelial cells of the prostatic glands. PCNA labelling index was 2.4% in the control group and reached peak by 3 days after castration and decreased thereafter. Electron microscopically, there was chromatin condensation with margination toward the nuclear membrane by 1 day after castration. Also noted were condensation of cytoplasm, dilatation of RER and nuclear fragmentation. Apoptotic bodies were formed and phagocytosed by adjacent cells and some apoptotic bodies were found in the lumen of acini. Based on these results, it can be concluded that castration-induced prostatic involution is the result of apoptosis. Detection of DNA fragmentation with ApopTag is a more a accurate method to identify not only apoptotic body formation itself but also the previous step of apoptotic body formation. PCNA labelling index to identify the cellular proliferation seems to play an active role in the early step of apoptosis and be a good tool for investigation of apoptosis.

Immunohistochemical Detection of p53 Gene Mutation in Urine Samples in the Patients with Bladder Cancer.: Sang Sook Lee, Ji Yeon Bae, Yu Na Kang, Young Rok Cho, Nam Jo Park, Seun Young Kim, Jung Hi Kim; Korean J Cytopathol. 1996;7(2):144-150.

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Abstract PDF: Although bladder cancers are very common, little is known about their molecular pathogenesis. It is known, that p53 alteration is found in about 60%p of muscleinvasive bladder cancer, necessiating aggressive therapy and poor outcome. We examined the nuclear expression of p53 protein, using D07 monoclonal antibody in the urine samples, from 31 patients with transitional cell carcinoma of the bladder to investigate the correlation of p53 overexpression with histologic grades and depth of invasion. The positive rate of p53 protein was 27%o in superficial bladder tumor, but increased up to 71% in the invasive bladder carcinomas. The overexpression of p53 protein increased according to Mostofi grading system from 18% in grade I, 45% in grade Il, and up to 100% in grade ill. The p53 expression tended to be higher in the invasive and high grade bladder cancers than in the superficial and low grade ones(p<0.05). These results suggest that immunohistochemical analysis of the urine specimen in the bladder cancer patients could be a useful method of screening for the presence of p53 mutant protein. The mutant p53 protein expression may be an indicator of bladder cancer with more proliferative potential and/or aggressive biologic behavior.

Diagnostic Application of p53 IMMUNOSTAINING in Bronchial Brush Specimens.: Sang Sook Lee, Ji Yeon Bae, Yu Na Kang, Young Rok Cho, Si Nam Kim, Nam Jo Park, Seun Young Kim, Jung Hi Kim; Korean J Cytopathol. 1996;7(2):163-168.

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Abstract PDF: Abnormalities of p53 gene are common in lung cancers and are associated with immunologically detectable p53 protein. p53 immunoreactivity is uncommon in normal cells but is frequently seen in neoplasia. Therefore, assessment of p53 expression may assist in the cytological diagnosis of malignancy. The usefulness of p53 immunostaining as a marker of malignancy in the cytological analysis of bronchial brush specimens from the patients with lung cancers was investigated in this study. A total of 71 bronchial brush samples submitted for cytologic diagnosis were immunostained with D07, a monoclonal antibody to recombinant p53 protein.
Result
ant p53 data were correlated with cytologic diagnosis and clinical information. Of the 17 smears with a benign cytodiagnosis, all were p53 negative. Of the 40 cases with a malignant cytodiagnosis(histologically confirmed), 35 were p53 positive and 5 were negative. Of the 14 cases that were cytologically suspicious but nondiagnostic for malignancy, 11 were p53 positive, 9 of which were subsequently proved to be malignant by histologic examination, and the remaining 2 cases were tuberculosis clinically. Forty four of 51 histologically confirmed lung carcinomas were p53 positive, including 25 of 28 squamous cell carcinomas, 13 of 17 small cell carcinomas, 3 of 3 adeno- carcinomas, and 3 of 3 large cell undifferentiated carcinomas. These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of bronchial brush specimens. Furthermore, we have shown the possible clinical utility of p53 immunostaining in cytopathological diagnosis, that is, as a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.

Detection of Human Papillomavirus DNA 16/18 in Cervical Adenocarcinomas by Polymerase Chain Reaction.: Sang Sook Lee, Nam Jo Park, Chong Guk Yoon; Korean J Pathol. 1995;29(4):502-510.

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Abstract PDF: Twenty-five paraffin-embedded tumor tissues were analyzed for detection of HPV 16 and 18 in cervical adenocarcinoma by polymerase chain reaction with type specific primers and by non-radioactive Southern blot hybridization for confirmation . The suitability of paraffin-embedded tissue as PCR material was confirmed by successful amplification of 100% of cervical specimens with human -globin specific primer. Eighty four percent of the cervical adenocarcinoma tissues were positive for HPV 16 and/or 18. HPV 16 positive rate was 68%, HPV 18 was 60%. The double infection with HPV 16 and 18 was found in 44%. Three cases of the negative specimen in PCR for each type of HPV DNA 16 and 18 were positive in Southern blot hybridization. The total positive rate was 92% for HPV 16 and/or HPV 18, HPV 16 positive rate was 80%. HPV 18 was 72%. The double infection with HPV 16 and 18 was 60%. These results suggest that the pattern of HPV types 16 and 18 is closely associated with carcinogenesis of cervical cancers. HPV type 18 appears to be preferentially related to cervical adenocarcinoma and the poor prognosis of these patients. Therefore, determination of HPV DNA type in cervical carcinoma patients is important in treatment and prognosis.

Cytologic Analysis of Malignant Effusion.: Sang Pyo Kim, Ji Yeon Bae, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Chung Sook Kim; Korean J Cytopathol. 1995;6(2):116-124.

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Abstract PDF: Eighty cases of malignant effusion were cytologically studied to elucidate the incidence of primary tumor site and cytologic characteristics of each tumor types. Eighty fluid specimens were composed of 43 ascitic, 35 pleural, and 2 pericardial effusion and primary tumor site had been confirmed by histology. The frequent primary sites were stomach (22 cases, 28%), lung (21 cases, 26%), ovary (11 cases, 14%), liver (7 cases, 9%), and breast (4 cases, 5%). The principal malignant tumors were adenocarcinoma (56 cases, 70%), squamous cell carcinoma (7 cases, 9%), liver cell carcinoma (7 cases, 9%), small cell carcinoma (4 cases, 5%), and non-Hodgkin}s lymphoma (4 cases, 5%). The distinctive cytologic findings according to primary tumor types were as follows ; the gastric adenocarcinomas were mainly characterized by isolated cells and irregular clusters sometimes with signet ring cells. Papillary serous cystadenocarcinoma of ovary showed frequently papillary clusters and occasional psammoma bodies. Breast carcinoma of ductal type showed cell balls with smooth margins. Colonic adenocarcinoma showed rather irregular clusters or palisading pattern of cylindrical cells. Metastatic squamous cell carcinoma, liver cell carcinoma, small cell carcinoma, and non-Hodgkin}s lymphoma showed also characteristic features. These findings indicate that the cytological features observed in the great majority of malignant effusion are similar to those of primary tumor types, which are very helpful to indentify the primary tumor site.

Overexpression of Mutant p53 in Human Anaplastic Astrocytoma and Glioblastoma Multiforme.: Sang Sook Lee, Kam Rae Cho, Cheoul Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Eun Ik Sohn; Korean J Pathol. 1994;28(4):376-380.

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Abstract PDF: A total of 30 cases of cerebral gliomas, including 6 cases of low grade astrocytomas, 6 anaplasticastrocytoomas and l8 glioblastomas multiforme, was examined immunohistochemically to demonstrate the overexpression of mutant forms of p53 protein and to evaluate their relationships with histological subtypes. A p53 monoclonal antibody was applied to the routine formalin fixed, paraffin-embedded tissues for this study using microwave-assisted avidin-biotin method. Overexpression of p53 protein was identified in 4 out of 6 anaplastic astrocytomas (66.7%) and in l3 out of l8 glioblastomas multiforme (72.2%). No immunohistochemical positivity of p53 was found in adjacent normal brain tissue, gliosis and 6 cases of astrocytoma. These results suggest that overexpression of mutant p53 may be an important step in the development and progression of malignant astrocytoma, especially of the aggressive subtypes of glioma, including glioblastoma multiforme.

Detection of Chromosome Aberration in Interphase Nuclei of Tumor Cells by Nonradioactive In Situ Hybridization Using Chromosome-specific Probes.: Sang Sook Lee; Korean J Pathol. 1993;27(6):573-580.

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Abstract PDF: An improved protocol for in situ hybridization(ISH) to routinely processed, paraffin-embedded tissue sections from lung carcinoma is presented. For this study, DNA probes for alpha-satellite chromosome 7 and 17 were used. The protocol to detect numerical chromosome aberrations involved treatment of sections with 1 M sodium thiocyanate prior to pepsin digestion, resulting in reproducible ISH reactions. The effect of avidin-biotin detection system. Four layer avidin methods and triple biotin methods, using avidin-PO, goat antiavidin, biotinylated antigoat IgG, avidin-PO or anti-biotin, biotinylated antirabbit IgG, avidin-PO, markedly enhanced the intensity of positive signals. More than 80% of the tumor and stromal cells showed distinct chromosome hybridization signals in 6 micrometer-thick sections. Lung carcinoma cells showed multiple chromosome signals(2~5 spots), contrasted by one or two signals in the stromal cells in the same section. These results suggest that chromosome polysomy can be reliably detected in tissue sections using in situ hybridization. This capability will prove to be an important tool for determining the underlying genetic basis for tumor development, tissue phenotype heterogeneity and progression by allowing genetic determination to be made on paraffin-embedded tissue sections where tumor histologic architecture is preserved.

Application of Argyrophilic Nucleolar Organizer Regions(AgNORs) in the Diagnosi of Hepatocellular Carcinoma.: Cheol Hee Yun, Sang Sook Lee, Eun Sook Chang; Korean J Pathol. 1993;27(6):553-560.

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Abstract: Necleolar organizer regions(NORs) ARE LOOPS OF DNA which transcribe to ribosomal RNA by RNA polymerase I. Since NOR-associated proteins are argyrophilic, silver staining method has been used for demonstration of AgNORs. The numbers and/or configurations of NORs may reflect the activities of cells in hyperplastic and neoplastic conditions. To evaluated the applicability of AgNORs in the diagnosis of hepatocellular carcinoma, the author had performed silver staining on the routinely processed, formalin-fixed, paraffin-embedded sections of 14 cases of normal liver(control), 23 cirrhotic liver, and 21 hepatocellular carcinoma. The results are summarized as follows: 1) The mean number of AgNORs per nucleus(mAgNOR) of normal liver, cirrhotic liver and hepatocellular carcinoma was 1.45+/-0.07, 2.53+/-0.38 and 5.52+/-1.63, respectively. The difference of mAgNOR between normal and cirrhotic liver, and between cirrhotic liver and hepatocellular carcinoma was statistically significant, respectively(p<0.01). 2) The percentage of nuclei showing five or more AgNORs per nucleus(pAgNOR) was 0.07% in normal liver, 7.59% in cirrhotic liver, and 60.49% in hepatocellular carcinoma. 3) AgNORs in hepatocellular carcinoma were large, pleomorphic and irregularly clumped, in addition to increase of mAgNOR and high pAgNOR. In conclusion, the increase of mAgNOR, high pAgNOR and large, irregular AgNORs are regarded as an additional helpful finding for the histopathological diagnosis of hepatocellular carcinoma.

Detection of Numerical Chromosomal Aberration in Squamous Cell Carcinoma of the Lung by In Situ Hybridization Using #17 Centromeric Probes.: Sang Sook Lee, Seong Beom Han, Soong Kook Park; Korean J Pathol. 1993;27(5):443-458.

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Abstract PDF: This study was carried out to understand the relationship between specific chromosome changes and their phenotypic consequences at the tissue level of human lung cancers. Then paraffin-embedded human lung squamous cell carcinoma samples were investigated for in evidence of genetic alterations, using chromosome 7 and 17-specific repetitive alpha-satellite DNA probes. In situ hybridization procedure with chromosome-specific DNA probes was optimized for use on formalin-fixed paraffin-embedded lung tissue sections. The chromosome index ranged from 1.10 to 1.88(median, 1.49) for chromosome 7 and 1.20 to 1.98(median, 1.69) for chromosome 17. Normal lymphocytes and stromal cells showed one or two chromosome signals per cell in most cases. All tumors showed three or more chromosome signals per cell with range of 16.0% to 80.6% of cancer cells(median, 50.9%) for chromosome 7 and 32.7% to 84.7%(median, 69.9%) for chromosome 17. The chromosome index did not correlate with the DNA content in most cases. Chromosomes 7 and 17 were either overrepresented or underrepresented when they were compared with corresponding DNA index determined by FCM. An increase in copy number, particularly of chromosome 7 was associated with a less favorable phenotype, including high nuclear grade. In addition, chromosome alterations were differentially expressed in the different areas of the same tissue section, correlating with histologic heterogeneity. These results suggest that chromosome polysomy can be reliably detected in tissue sections using in situ hybridization. There is a strong correlation between genotypic abnormalities and tumor phenotype in human lung cancer. This capability will prove to be an important tool for determining the underlying genetic basis for tumor development, tissue phenotype heterogeneity and progression by allowing genetic determination to be made on paraffin-embedded tissue sections where tumor histologic architecture is preserved.

Apoptosis Induced by Adriamycin in HeLa Cells.: Sun Young Kim, Sang Sook Lee; Korean J Pathol. 1993;27(5):433-442.

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Abstract PDF: This study was carried out to demonstrate the mode of ADR-induced cell death(apoptosis) on the light and electron microscopic features, to measure the apoptotic index dependent on various doses of ADR, to investigate the possible mechanism of apoptosis induced by ADR, and to evaluate ISNT method for the detection of DNA strand break. HeLa cells were treated with various doses of ADR 0.1~100.0 microgram/ml and observed under the light and transmission electron microscopes at 6 hours, 1 day and 3 days after ADR treatment. In addition, DNA strand breaks induced by ADR were detected in HeLa cells using the in situ nick translation(ISNT) method. The results were as follows: 1) The cell viability of HeLa cells decreased and the apoptotic index increased following exposure to ADR in a dose-dependent manner, resulting in about 44% of apoptotic index at 100.0 microgram/ml of ADR treatment. 2) Light microscopically, HeLa cells treated with ADR showed shrinkage or condensation of nucleus and cytoplasm. There were various unclear changes showing irregular, large, delineated masses of condensed chromatin abutting on the nuclear envelopes. Later stage of apoptosis revealed contracted and condensed cytoplasm with irregular cell membrane. Electron microscopically, margination of condensed chromatin, dilatation of endoplasmic reticulum under the plasma membrane, aggregation of cytoplasmic organelles with morphologically intact mitochondria, and irregular cell surface with blebbing were observed. 3) ISNT using biotinylated dUTP exhibited strong positive nuclear staining in HeLa cells treated with ADR. There was a marked response at 10.0~20.0 microgram/ml of ADR treatment. It is concluded from the above results that the death of HeLa cells induced by ADR was apoptotic in type based on light and electron microscopic appearance. The apoptotic index correlated with the increasing dose of ADR. ISNT with biotinylated dUTP led to visible evidence of DNA strand breaks following ADR treatment of HeLa cells. ISNT can be used for detection of DNA degradation, caused by activation of endogenous endonuclease, which is an early and specific characteristic of apoptosis.

A Case of Pseudoinvasion in Peutz-Jeghers Polyposis.: Sang Pyo Kim, Sang Sook Lee, Eun Sook Chang; Korean J Pathol. 1993;27(1):72-74.

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Abstract PDF: Peutz-Jeghers polyp with pseudoinvasion is characterized by the presence of mucosal islands within muscle layer often associated with mucinous cysts. It occurs when mucosal components completely penetrate the muscularis propria, and shows no cytologic signs of malignancy. In most instances, the lesion may be the result of forces exerted during intussusception in the involved small intestine. We describe a case of Peutz-Jeghers polyposis with pseudoinvasion in a 24-year-old female patient. This patient presented with intussusception and a segmental resection of the ileum was performed. Microscopically, it disclosed a hamartomatous polyp with pseudoinvasion. There were glandular islands and mucinous cysts embedded within the bundle of muscle, layer, extending, to the subserosa. There was o evidence of cellular dysplasia or desmoplasia.

Epithelioid Hemangioendothelioma of the Lung: Report of a case.: Gyeong Hoon Kang, Yong Il Kim, Sung Koo Han, Young Soo Shim, Eui Keun Ham, Sang Kook Lee, Sang Sook Lee; Korean J Pathol. 1991;25(6):563-569.

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Abstract PDF: Intravascular bronchioloaveolar tumor is now recognized as a pulmonary form of epithelioid hemangioendothelioma, being manifested with bilateral multiple pulmonary nodules in young women. This 34-year-old woman received two occasions of open lung biopsies with interval of 1 year for diffuse nodular infiltrations in both lung fields. Repeated radiographic study 3 year later showed no significant progression of the pulmonary nodular lesions except for pleural effusion. Two occasions of open lung biopsies disclosed similar multiple discrete nodules which consisted of central acellular areas with lacuna-like ghosts and peripheral cellular zone. The tumor cells grew in micropolypoid fashion with preservation of background alveolar frame-works. Ultrastructure disclosed most of neoplastic cells presenting with the features suggestive of endothelial differentiation, and immunohistochemical study revealed the presence of cellular areas which gave positive reaction to factor VIII-related antigen. We support that this is an additional case of epithelioid hemangioendothelioma of the lung that is manifested with a multicetric intrapulmonary vascular endothelial cell growth featuring a vasoformative tendency and participation of topography-specific histologic modification.

The Spontaneously Occurred Apoptosis in Squamous Carcinoams of the Uterine Cervix.: Chan Hwan Kim, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang; Korean J Pathol. 1990;24(3):254-266.

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Abstract PDF: The apoptosis, a distinctive type of individual cell necrosis, has been considered to play a complementary but opposite role to mitosis in the regulation of animal cell populations. It can be initiated or inhibited by a variety of environmental stimuli, physiologically and pathologically. Apoptosis seems to appear in either non-neoplastic or neoplastic tissues, even malignant tumors in the state of untreatment or irradiation. This study was carried out to investigate the spontaneous occurrence of apoptosis in squamous carcinomas of the uterine cervix and its mechanisms. Light microscopically, noted were the condensation and fragmentation of individual tumor cells with formation of apoptotic bodies that were frequently phagocytosed by nearby intact tumor cells. They were commonly seen in the neighbourhood of coagulative necrosis. Electron microscopically (TEM and SEM), noted were nuclear condensation, margination toward the nuclear membrane and fragmentation of membrane-bounded apoptotic bodies that were well preserved. The intracellular apoptotic bodies were phagosomes and reduced to electron-dense lysosomal residual bodies. The conclusion obtained was as follow: Apoptosis was found in all cases of squamous carcinoma of the uterine cervix, of which the frequency was higher in tumors of poor differentiation than those of well to moderate differentiation. The process of the apoptosis is considered to pass through the step of formation of the apoptotic bodies, phagocytosis by adjoining tumor cells or histiocytes, and then degradation as lysosmal residual bodies.

Detection of Human Papillomavirus 16/18, 31/33/35 in Verrucous Carcinoma of the Larynx by In Situ Hybridization with Human Papillomavirus DNA Probes.: Ki Kwon Kim, Sang Sook Lee, June Sik Park, Seung Won Jin, U Ik Sohn; Korean J Pathol. 1990;24(2):95-102.

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Abstract PDF: Verrucous carcinoma of the larynx is a distinct and uncommon variant of well-differentiated squamous cell-carcinoma. The authors hybridized in situ a case of laryngeal verrucous carcinoma with DNA prebes to humman papillomavirus (HPV) 6, 11, 16, 18, 31, 33 and 35. The DNAs from the verrucous carcinoma of larynx hybridized with mixed DNA probes HPV-16/18 and 31/33/35. In addition, there was an evidence of HPV infection based on hybridization with mixed DNA probe HPV-6/11 in the adjacent papilloma tissue. By in situ DNA hybridization techniques, we clearly demonstrated human papillomavirus (HPV-16/18, and 31/33/35) related sequences in this neoplasm. These findings suggest the role of HPV-6/11 in the development of laryngeal papilloma ad HPV-16/18 and 31/33/35 probably on the progression to verrucous carcinoma.

Detection of Human Papillomavirus DNA by In Situ Hybridization using Biotinylated DNA Probes in Cervical Intraepithelial Neoplasias and Squamous Cell Carcinomas.: Sang Sook Lee, Ki Kwon Kim, Chai Hong Chung, Seung Won Jin, U Ik Sohn; Korean J Pathol. 1990;24(1):16-26.

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Abstract PDF: The authors examined 9 condylomas, 26 cervical intraepithelial neoplasms(CIN) and 22 invasive squamous cell carcinomas for the presence of human papillomavirus(HPV) DNA sequences by DNA-DNA in situ hybridization. In situ hybridization revealed target HPV DNA sequences mostly in the nuclei of the superficial cells from epithelium which contained either maturation or koilocytotic atypias. With the use of biotinylated HPV DNA probes 6/11, 16/18 and 31/33/35, 42 of the 57(73.7%) were positive with HPV-6/11, 23 with HPV-16/18, 32 with HPV-31/33/35 and 18 with two or more mixed probes. HPV-31/33/35 was wht most prevalent in CIN and invasive squamous cell carcinomas, follwed by HPV-16/18. The incidence of HPV DNA increased from 66.7% to 86.4% with increasing severity of the lesions from condylomas to invasive squamous cell carcinomas. Flat condyloma was most freuently accompanied by CIN.

Mechanisms of Acinar Cell Deletion in Rat Pancreas Following Experimental Duct Ligation.: Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee, Chai Hong Chung; Korean J Pathol. 1989;23(1):51-64.

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Abstract PDF: This study was carried out to investigate the mechanisms of acinar cell deletion, leading to the pancreatic atrophy of rat pancreas after experimental duct ligation. Fifty-seven male Sprague-Dawley rats, maintained on a stock diet, weighing 200 gm, in average, were divided into 2 experimental groups. Group 1. Control group. Six rats. Abdominal cavity was opened and closed without further treatment. Group 2. Fifty-one rats. Animals were treated with partial ligation of the pancratic ducts according to the procedure developed by Hultquist followed by sequential sacrifices at: 1 hour (3 rats), 3 hours (3 rats), 6 hours (6 rast), 12 hours (3 rats) and 24 hours (8 rats); 2 days (8 rats), 3 days (3 rats), 4 days (3 rats) and 5 days (5 rats); 1 week (3 rats), 2 weeks (3 rats) and 8 weeks (3 rats); after partial ligation was extirpated and examined by both light and electron microscopy. The results obtained were as follows: Light microscopically, noted were an interstitial edema and focal necrosis of the pancreatic tissue along with fine vacuolization and depletion of the zymogen granules in the acinar cell cytoplasms and condensation of the acinar cell nucleus. These changes were observed by 2 days after ligation. At about the same time, one can observe the dense body, identified to be apoptotic body, in the acinar cell which were found to be decreased in quantity. By 5 days after ligation, no recognizable acinar cells left in the collagenous stroma except intercalated ducts. Conspicuous stroma except intercalated ducts. Conspicuous stromal hyalinization, thereafter. Electron microscopically (TEM and SEM), nuclear condensation and margination toward the nuclear membrane was noted by 6 hours after duct ligation. By 24 hors sporadic membrane-bounded apoptotic bodies appeared in the acinar cells, the number of which reaching to the peak by 3 days after ligation. These apoptotic bodies were found to be phagocytosed by either intraepithelial mononuclear phagocytes or adjoining acinar cells. It can be concluded, therefore: That orderly remodeling of pancreatic exocrine tissue during atrophy is effected by rapid deletion of acinar cells by apoptosis.

Immunohistochemical Application of Leukocyte Common Antigen and Epithelial Membrane Antigen in the Diagnosis of Large Cell Undifferentiated Tumors.: Chan Hwan Kim, Sang Sook Lee, Chai Hong Chung; Korean J Pathol. 1988;22(3):215-221.

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Abstract PDF: A total of 42 cases undifferentiated large cell tumors were stained by immunoperoxidase techniques using antibodies against leukocyte common antigen (LCA) and epithelial membrane antigen (EMA). In 18 of the 21 cases studied, initially diagnosed as malignant lymphoma or Hodgkin's disease, reactivity with monoclonal anti-LCA (and noreactivity with monoclonal anti-EMA)indicated that the tumor was a lymphomas. The remaining 3 cases gave the reverse reaction pattern and therefore were classified as carcinoma. One out of 16 cases diagnosed as undifferentiated carcinoma proved to be a case of mialignant lymphoma in 5 patients in whom the original diagnosis was uncertain, a definite diagnosis was possible in all cases and 3 of these proved to be large cell lymphoma; the remainders, undifferentiated carcinoma. It is suggested that the staining of undifferentiated human neoplasms using combinations of antibodies reactive with epithelial and lymphoid cells may result in much greater diagnostic accuracy.

Carcinoma In Situ of the Urinary Bladder with Transitional Cell Carcinoma of Prostate: A Histopathologic Study and Mapping of the Urothelial Lesions.: Seung Pyo Hong, Sang Sook Lee, Chai Hong Chung; Korean J Pathol. 1987;21(3):199-206.

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Abstract PDF: A 63-year-old male patient with extensive carcinoma in situ of the urinary bladder was found to have unsuspected transitional cell carcinoma of the prostate. Mapping of the totally embedded radical cystectomy specimen demonstrated diffuse, multifocal, epithelial abnormalities, ranging from mucosal atypia to the nonpapillary carcinoma in situ with extension to the urethra, prostatic ducts and glands, seminal vesicles and ureter, probably reflecting individual urothelial susceptibility in reaction to carcinogenic stimulus. The importance of prostatic assessment in the evaluation of the patient with carcinoma in situ of the urinary bladder is emphasized.

Immunohistochemical Demonstration of Fibronectin in Paraquat-Induced Interstitial Fibrosis of Adult Human Lung.: Seung Pyo Hong, Sang Sook Lee, Chai Hong Chung; Korean J Pathol. 1987;21(3):138-143.

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Abstract PDF: We studied distribution of fibronectin in paraquat-induced adult fibrotic lung by indirect immunofluorescence and indirect immunoperoxidase methods, using affinity-purified antifibronectin IgG peroxidase conjugates and antifibronectin IgG FITC conjugates. In contrast to the relative paucity of staining in normal lung, there was a marked increase in interstitial staining for fibronectin in this fibrotic lung. This marked alterations in the apparent amounts and distribution of fibronectin in fibrotic human lung suggest its involvement in the cellular events accompanying human lung fibrosis.

Mechanisms of Experimental Pulmonary Fibrosis Following Paraquat Toxicity.: Sang Sook Lee, Chai Hong Chung, Tae Jung Sohn; Korean J Pathol. 1987;21(3):111-137.

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Abstract PDF: This study was carried out to investigate the intricate mechanisms of intraalveolar fibrosis, leading to the alveolar structural remodeling, of rat lungs treated with paraquat. Sixty-three male Sprague-Dawley rats, maintained on a stock diet, weighing 200.0 gm, average, were divided into 4 experimental groups. Group 1. Control group (10 rats). Intraperitoneal injections of 2-4 ml normal saline only. Group 2(13 rats). 10, 20, 25, 30 and 40 mg per kg of body weight was administered intraperitoneally. Animals were sacificed 5 hours. 1 and 3 days after paraquat treatment. Group 3(16 rats). 20, 25, 30 and 40 mg per kg of body weight was administered to the animal, and animals died 2-5 days after paraquat administration. Group 4(24 rats). The same amount of paraquat was administered to the animal as in the group 2. Animals were sacrificed 1, 2, 6, 8 and 10 weeks after paraquat treatment. Sacrificed animal lung was examined by gross, light-microscopic, immunohistochemical, ultrastructural observation, along with cellular and chemical analyses of bronchoalveolar lavage fluid. The results were as follows: Grossly, 6 rats of chronic stage (1-10 weeks survival) developed multiple wedge-shaped scars on both lungs. These scars were situated mainly along the bronchial trees, blood vessels and subpleural regions. Light microscopically, the salient features found of the chronic stage lungs were intraalveolar fibrosis. Intraluminal buds or polypoid masses projecting into the alveolar lumen and ducts. Elsewhere, loose connective tissue masses were found to fuse together to alveolar wall, obliterating the alveolar spaces with resultant severe alveolar structural remodeling. Immunohistochemically, fibronectin was found in the center of intraalveolar buds and polypoid mass, projecting into the alveolar lumen, and in the adjacent proliferating alveolar macrophages. An attempt to measure the amount of fibronectin in the bronchoalveolar lavage fluid failed. Electron microscopically, the chronic stage lung revealed marked proliferation of both alveolar macrophages and fibroblasts in the alveolar spaces, the latter containing actin-like microfilaments and collagen fibers arranged in bundles and spirals. In areas, myofibroblasts and smooth muscle cells also present. Cellular analysis of the bronchoalveolar lavage fluid in chronic stage lungs revealed no significant findings. It can be concluded, therefore: That intraalveolar fibrosis of the paraquat-treated lungs of the rat is probably mediated by intraalveolar migrations of the interstitial cells, the main task force being the connective tissue cells, passing through the defects created in the epithelial lining surface to its basement membrane, which were inflicted upon the alveolar wall by paraquat toxicity. Fibronectin, released by activated alveolar macrophages, may be responsible for the migrations of fibroblasts and myofibroblasts into the alveolar spaces to form the intraalveolar fibrosis with subsequent alveolar structural remodeling,

Multiple Primary Malignant Tumors: 39 cases.: Sun Young Kim, Sang Pyo Kim, Jong Min Chae, Sang Sook Lee, Eun Sook Chang, Chai Hong Chung; Korean J Pathol. 1987;21(2):67-74.

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Abstract PDF: Thirty nine cases of multiple primary malignant tumors examined at the Department of Pathology, Keimyung University School of Medicine during the period from November 1974 through March 1986 were analysed clinicopathologically. The findings are as follows: 1) Thirty nine cases had synchronous lesion and six cases metachronous lesion. The second primary malignancy occurred mean 4.7 years after the first malignancy in patients with metachronous lesion. 2) The age at diagnosis of the first malignancy ranged from 26 to 76 years, the average being 51.8 years. The male-female ratio was slightly less than 1:1.2. 3) The most commonly involved site in multicentric origin was gastrointestinal tract (44.4%) with all adenocarcinoma and the second urogenital system (29.6%). In cases of different tissues or organs (11 cases), ovary was the most frequent site (5 cases), followed by cervix (4 cases). 4) Multiple primary malignant tumors of urogenital system were all eight cases and six cases among them (75%) had smoking and drinking habits. 5) The detailed informations about possible environmental, familial and host factors necessary for the investigation of multiple primary tumors were lacking in most cases. Therefore, the history taking with special attention to these factors must be carefully recorded. And also, we suggest that in the high-risk individuals, careful follow-up and thorough search for early cancer detection or prevention should be taken.

Male Pseudohermaphroditism Associated with Bochdalek Diaphragmatic Hernia: An autopsy case report.: Eun Sil Yu, Je Geun Chi, Sang Sook Lee; Korean J Pathol. 1986;20(4):470-474.

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Abstract PDF: An autopsy case of male pseudohermaphrodite associated with Bochdalek diaphragmatic hernia is reported. This newborn infant showed a large clitoris and hypospadic urethra which was the only opening in the perineum except for the anus. There were urethrovaginal fistula and uterus didelphys. The adrenals were slightly larger than normal, but microscopically did not show any features of cortical hyperplasia. Well formed testes were found and were histologically unremarkable. In addition, Bochdalek type of diaphragmatic hernia was present, associated with severe left lung hypoplasia and massively herniated abdominal organs into the chest cavity, shifting the mediastinum considerably and eventually led to death in a few minutes after birth. The pathogenesis of genital anomaly and diaphragmatic hernia is briefly discussed and it is suggested that this type of genital abnormality might be due to defect of testicular M llerian inhibitor factor and can be categorized as incomplete male pseudohermaphroditism.

Carcinosarcoma of the gallbladder: Report of a case.: Sun Young Kim, Sang Sook Lee, Jong Min Chae, Chai Hong Chung; Korean J Pathol. 1986;20(3):362-368.

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Abstract: Carcinosarcoma, often referred to as "malignant mixed tumor" is a rare neoplasm, but this tumor occurs in various organs, including the gallbladder. We report herein a carcinosarcoma of the gallbladder which consisted of adenocarcinomatous and undifferentiated sarcomatous ares, the latter differentiating towards abundant osteoid and calcified but nonlamellated bony trabeculae formation. There are 18 reported cases of this type tumor of the gallbladder in the literature.

A Simple Storage and Retrieval System for Pathologic Diagnoses Using the Apple II(R) Computer.: Sang Sook Lee, Chi Hwan Lee, June Sik Park; Korean J Pathol. 1986;20(2):184-186.

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Abstract PDF: The coding and filing of pathologic diagnoses have been heavy tasks; however with the availability of inexpensive microcomputer, a system may be developed that permits storage and retrieval to be performed efficiently. With Apple II(R) computer system and SNOP coding, a simple program using dBASE-II and QUICKCODE computer program can be created to include the following informations: accession number, chart number, sex and age of patients and 2 diagnosis codes. Once SNOP coding is carried out by medical staff, a secretary or clerk can enter the informations into the microcomputer. Data may be searched on any combination of the above parameters.

Metastatic Ovarian Carcinoma: Clinicopathologic analysis of 33 cases.: Dong Suck Kim, Sang Sook Lee, Jong Min Chae, Eun Sook Chang, Chai Hong Chung; Korean J Pathol. 1986;20(2):178-183.

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Abstract PDF: Thirty three cases of metastatic ovarian carcinoma were analysed cilincopathologically. The patient's age ranged from 20 to 68 years, the average being 44.3. Most ovarian tumors were bilateral and asymmertically enlarged, firm and occsaionally multicystic. Histologic examination revealed adenocarcinoma in 31 cases, of which Krukenberg tumors in 14; squamous cell carcinoma in 2. The most common primary site was gasrtointestinal(75.8%), followed by genital, breast and gallbaldder. Most Krukenberg tumors were originated from poorly differentiated adenocarcinoma of stomach. The ovarian and primary carcinomas were synchronously diagnosed in 15 cases, while in 3 cases the primary carcinoma was not round until the ovarian tumor had been removed.

Classification of Gallstones and their Characteristics.: Sang Sook Lee, Eun Sook Chang, Chai Hong Chung; Korean J Pathol. 1986;20(2):157-164.

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Abstract PDF: Total 481 cases of gallstones from Korean patients operated at Keimyung University Dongsan Hospital during the last 6 years were classified by macroscopic view according to the classification of Sato, et al and reviewed with a special reference to age, sex, and kinds and sites of gallstones. Gallstrones were present predominatly in the age of 50-60 years, the average 52. Sex ratio (M:F) was nearly equal, being 1:1.05. Gallbladder was the most frequent site, comprising 53.2%, followed by common bile duct, 23.3% and intrahepatic location, 3.7%. Macroscopic classification revealed pigment gallstones in 53.0% (calcium bilirubinate, 41.8%; black, 11.2%); cholesterol gallstones in 36.2%, of which mixed stone being 33.1%. Cholesterol gallstones occurred predominantly in 50-60 years of age with a prediletion to females. On the contrary, elderly persons more than 60 years of age had calciu bilirubinate stones. No sex difference was found in the calcium bilirubinate stones. Eightly-six percent of cholesterol gallstones were present in the gallbladder only. Common bile duct stones were mostly composed of pigment gallstones in 80.4%.

Proliferating and Malignant Brenner Tumors of the Overy: Report of 2 cases.: Sang Sook Lee, Eun Sook Chang, Chai Hong Chung; Korean J Pathol. 1986;20(1):77-83.

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Abstract PDF: Two unusual and rare forms of Brenner tumor are reported and the literatures are reviewed. The one, "proliferating" Brenner tumor, morphologically resembling low grade papillary transitional cell carcinoma of urinary bladder and regarded as a third variant intermediate between the benign and malignant forms; the other, malignant Brenner tumor of right ovary, corresponding to grade III transitional cell carcinoma of urinarybladder with areas of invasive squamous cell carcinoma and benign Brenner tumor of left ovary, combined with bilateral cystic teratomas. These tumors give additional support to the concept that Brenner tumors are composted of epithelium of urinary tract(urothelial) type.

Metastasis of Carcinoma to Carcinoma.: Sang Sook Lee, Jae Y Ro; Korean J Cytopathol. 1985;19(4):453-457.

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Abstract PDF: Two unusual cases of metastasis of carcinoma to carcinoma are reported. The initial malignancies, an adenocarcinoma of the rectum and a duct carcinoma of the breast, were found to have metastasis to a clear cell carcinoma of the kidney. The various theories on the peculiar tendency for the renal cell carcinoma to be the most common host tumor for other primary carcinoma are commented upon briefly.

Ovarian Pregnancy: 12 cases analysis.: Kwan Kyu Park, Sang Sook Lee, Eun Sook Chang, Chae Hong Chung; Korean J Cytopathol. 1985;19(3):339-344.

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Abstract PDF: From January, 1972 to August 1983, 12 cases of ovarian pregnancy out of 1202 total ectopic pregnancy were studied and the incidence constituted 0.9%. The gross and microscopic findings were reviewed according to gross description and gross photographs, and microscopic description and reviewing all microscopic slides. All cases were shown to meet Spiegelberg's criteria for primary ovarian pregnancy.

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