Journal of Pathology and Translational Medicine

Volume 31(4); April 1997

Original Articles

Detection of Human Papillomavirus in Lesions of Uterine Cervix Immunohistochemistry and in situ Hybridization.: Chang Soo Park, Jong Hee Nam, Jae Hyuk Lee, Jong Soon Kim, Seung Jin Oh; Korean J Pathol. 1997;31(4):289-297.

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Abstract PDF: To evaluate the detection of HPV DNA according to subtype of lesions of uterine cervix and its clinical applicability, in situ hybridization (ISH) and immunohistochemistry for HPV were performed in 189 cases of uterine cervical lesion, including 23 cases of low grade squamous intraepithelial lesion (SIL), 115 cases of high grade SIL and 51 cases of invasive carcinoma. Positive immunostaining, brown precipitate, was mainly noted in the nucleus of koilocytes in the superficial and intermediate layer. Positivity of immunostaining was 21.7% in low grade SIL, 13.0% in high grade SIL and 9.8% in invasive carcinoma. Positive reaction in ISH, red precipitate, was noted in the nucleus of not only koilocytes but also non-koilocytes in the superficial and intermediate layer, and dot precipitate was rarely identified in the nest of squamous cell carcinoma. Based on HPV subtype, 6/11 was 21.7% in low grade SIL, 16/18 was 32.2% and 39.2% in high grade SIL and invasive carcinoma, respectively. With regard to their associated HPV types, low grade SILs were heterogeneous and high grade SILs and invasive carcinomas were related with the high oncogenic risk group only. The correlation of HPV subtypes with panHPV was 91.3% in low grade SIL, 91.3% in high grade SIL and 98.0% in invasive carcinoma. These results suggest that detection of HPV infection by ISH may be a more useful method than immunohistochemistry and application of the HPV subtype probe with the panHPV probe could improve the sensitivity of ISH.

Microvessel Quantitation and Assessment of its Utility by CD34 Staining in Invasive Breast Carcinoma.: Hwa Sook Jeong, Ro Hyun Sung; Korean J Pathol. 1997;31(4):298-307.

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Abstract PDF: Tumor angiogenesis, the development of new blood vessels by tumor, is a widely observed phenomenon associated with the growth of human solid tumors. To investigate how tumor angiogenesis correlates with other prognostic features i.e. menopause status, tumor size, lymph node metastasis, mitosis, angioinvasion, estrogen receptor (ER), p53 protein expression, histologic grade and clinical stage, we counted microvessels by immunohistochemistry using antibody for CD34 antigen in 56 cases of invasive breast carcinoma (27 with and 29 without axillary lymph node metastases) and 20 cases of non-inflammatory benign breast lesion. CD34 antigen is expressed on the surface of hematopoietic progenitor cells and more sensitively expressed than factor VIII in vascular endothelial cells. Microvessel count (MVC) was performed at a single hot field of 200x magnification (0.74 mm2 per field). The results are summarized as follows; 1) The mean MVC of invasive carcinoma and benign breast lesion were 92.0+/-54.4 (range, 7-237) and 20.7+/-16.6 (range, 4-73), respectively (p<0.0001). 2) Although MVC had no correlation with all other prognostic factors i.e. menopause status, tumor size, lymph node metastasis, mitosis count, angioinvasion, ER, p53 protein expression, histologic grade, and clinical stage (p>0.05), MVC had a tendency to increase in tumors with axillary LN metastasis or without ER expression. 3) Without correlation with MVC, ER (+), angioinvasion (-) and higher histologic grade correlate to significantly higher mitosis count (p<0.0005). Also, angioinvasion correlate to a significantly higher histologic grade (p<0.05). In conclusion, angiogenesis is related to tumorigenesis, but MVC may not be related to other clinicopathologic factors.

Antibiotics-associated Pseudomembranous Colitis: A Clinico-Pathologic Analysis with Special Reference to Non-pseudomembranous Mucosal Change.: Jin Haeng Chung, Yong Il Kim; Korean J Pathol. 1997;31(4):308-313.

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Abstract PDF: The presence of volcano-shaped pseudomembrane(PM) formations above the inflamed mucosa has been referred to as the unique biopsy criterion of the pseudomembranous colitis, but PM might be lost during the bowel preparation, and such loss leads pathologists to erroneous interpretations of the endoscopic biopsy specimens. The purpose of this paper is to identify the additional diagnostic clue other than PM among various histologic features in pseudomembranous colitis. We reviewed sigmoidoscopic biopsy specimens from 13 cases of antibiotics-associated pseudomembranous colitis which was confirmed to reveal characteristic PM by endoscopy aside from the clinical history of antibiotics administration. The cases were divided into two groups: the presence of PM (n=7) and its absence (n=6). Both groups showed basically identical histology, which included features of glandular distension, epithelial necrosis, crypt abscess, regenerative glands and mucous plug within the necrotic/dilated glands. Mucous plugs within the necrotic/ dilated glands were found in all cases and seemed to be the most characteristic microscopic feature. Ten cases of resected chronic ulcerative colitis in the active stage were compared for a differential diagnosis of crypt abscess-associated mucosal change. None of them revealed necrotic gland with mucous plugs, although crypt abscess formation was common in both conditions. We conclude that presence of mucous plugs in the dilated/necrotic glands is a useful diagnostic clue even though the biopsy specimens fail to demonstrate PM.

The Significance of the Expression of p53, E-cadherin, nm23, CD44, and Tumor Angiogenesis in Colorectal Adenocarcinoma.: Sung Suk Paeng, Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(4):314-325.

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Abstract PDF: Many oncogenes and tumor supressor genes have been identified and studied in colorectal carcinoma. Among them, p53 is a tumor supressor gene and its mutation is frequently noted in human tumors. E-cadherin is a cell adhesion molecule and associated with tumor differentiation. CD44 is a cell surface glycoprotein that plays a role in cell migration and metastasis. nm23 is a gene known to lower metastatic potential of tumors and has been proposed to be a metastasis supressor gene. Tumor angiogenesis is required for the expansion of the primary tumor and metastasis and its degree is related to the potential of malignancy. We studied the expression of p53, E-cadherin, nm23, CD44 and tumor angiogenesis in 36 cases of colorectal adenocarcinomas. They were compared with previously known prognostic factors such as the stage, tumor size, depth of invasion, differentiation, presence of lymphatic or venous invasion, the lymph node and distant metastasis. The results were as follows. 1) The expression of p53 was not significantly associated with any prognostic factors. 2) The expression of E-cadherin was significantly associated with tumor differentiation. In the well differentiated adenocarcinomas, its expression was higher than in the poorly differentiated adenocarcinoma. 3) The expression of nm23 was also significantly associated with tumor differentiation. In carcinoma with lymph node metastasis, the expression of nm23 was reduced, but statistically it was not significant. 4) The expression of CD44 was higher in tumors with lymph node metastasis than in tumors without lymph node metastasis, but it was not statistically significant. 5) The degree of microvessel density was significantly associated with lymphatic invasion. According to the above results, the expression of E-cadherin and nm23 are related to the differentiation of the tumor and tumor angiogenesis is related to the lymphatic invasion of the colorectal adenocarcinoma.

The Expression of CD44H and CD44v6 in Gastric Adenocarcinoma.: Myoung Jin Ju, Hae Kyung Lee, Kwang Min Lee, Dong Kyu Chung, Choo Hong Park; Korean J Pathol. 1997;31(4):326-331.

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Abstract PDF: CD44, also known as the Hermes antigen, H-CAM, pgp-1 antigen, and extracellular matrix receptor ECM-III, is a widely distributed integral membrane protein that exists in a variety of forms with different molecular sizes ranging from 85kd to 160kd. A number of evidence implicates CD44 as a cell adhesion molecule with a possible role in tumor progression. To evaluate the possible roles of CD44 in the metastatic process of gastric carcinoma to the regional lymph nodes, we applicated immunohistochemical stains with the CD44H and CD44v6 primary antibodies onto the 2 groups of gastric adenocarcinomas. Each group was comprised of 22 primary tumors extending to the subserosa, and one group showed nodal metastasis, while the other group did not. Seventeen primary tumors (77%) out of the 22 cases with the nodal metastasis demonstrated positivity to the CD44v6, while only 9 primary tumors (41%) out of the 22 cases without nodal metastasis did. However CD44H immunoreactivity was demonstrated in tumor cells of all cases (100%) of both groups as well as in the normal cell components. These results suggest that CD44H form is not related to the metastasis to the regional lymph nodes of gastric carcinoma. However, the expression of CD44v6 seems to play a certain role in the metastatic process of the gastric carcinoma.

Quality Assurance of Intraoperative Consultation Review Analysis of 2,392 frozen sections.: Dong Hae Chung, Jae Hee Suh, On Ja Kim; Korean J Pathol. 1997;31(4):332-341.

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Abstract PDF: A retrospective quality assurance study of intraoperative consultation (frozen section) was carried out to assess the accuracy and to determine the reasons of discordance. Of 14,977 surgical pathology cases accessioned over a 6-month period in Asan Medical Center, frozen sections were done on 1,270 (8.5%) patients and 2,392 frozen sections (1.88 frozen sections/case) were performed. Discordance was noted in 106 cases (4.4%) and diagnosis was deferred in 26 cases (1.1%). All deferred cases were reviewed with the result of 53.8% justified and 46.2% unjustified. The discordant cases were divided into three categories as to their clinical significances: category A (no affect on patient care) 61.3%, B (minimal affect) 9.4%, and C (major affect) 29.2%. Of 31 category C cases, 7 cases were false positive and 24 cases were false negative. Misinterpretation (70.8%) was the leading cause of discordance, followed by sampling error (15.1%), failure to identify lesion (8.5%), and technical problem (5.7%). More than one-third (35.8%) of all discordances were of central nervous system cases. Total central nervous system cases were 403 (16.8%) with a significantly higher disordance rate (9.8%) and deferral rate (2.5%) in comparison to the other cases with 3.4% discordance rate and 0.8% deferral rate. There were 43 colorectal cancer cases of intraoperative consultation for adequacy of resectional margins. The surgical margins were between 0.4 cm and 28 cm (mean: 6.7 cm) away from the tumor and there was no tumor-positive case. The study indicates surgical pathology should 1) promote interpretative skills in cases involving minute fragments of neurosurgical cases, 2) defer the diagnosis and ask for more tissue on inadequate or inappropriate specimens and 3) give only gross opinions without unnecessary frozen section procedures in the event of simple, clear-cut cases.

Immunohistochemical Evaluation of Cathepsin D, MMP-2, and TIMP in Prostate Carcinoma.: Jung Weon Shim, Soon Ran Kim, Yun Jung Kim, Hye Kyung Ahn, Young Euy Park, Sung Sook Kim, Min Young Kim; Korean J Pathol. 1997;31(4):342-350.

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Abstract PDF: Twenty six cases of primary adenocarcinoma of the prostate, ranging from 4 to 9 according to Gleason's summing score, were studied. Immunoreactivity was evaluated using the rabbit polyclonal anti-Cathepsin D antibody (CD), a mouse monoclonal MMP-2 antibody (MMP-2), and a tissue inhibitor metalloproteinase (TIMP) in formalin-fixed, paraffin-embedded prostatic tissue. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). For CD, the tumor cells showed diffuse cytoplasmic immunoreactivity in all 26 cases (100%). For MMP-2 the tumor cells showed cytoplasmic immunoreactivity in 17 of 26 cases (65.38%). As the Gleason grade increased the expression of CD increased (P=0.0027). The reactivity of CD was significantly correlated with the Gleason's score (R=0.65637), but, the reactivity of MMP-2 was not correlated. There were no significant correlations between each of the CD and the MMP-2 scores, and stage. TIMP expression was predominantly localized in the stroma rather than in the cancer cells themselves. We believe that 1) CD and MMP-2, both immunohistochemically detectable in a majority of prostate adenocarcinoma, may play a role in determination of the invasive or metastatic property, 2) the enhanced TIMP expression in the stroma may be associated with the response to cancer invasion.

Case Reports

Malignant Solitary Fibrous Tumor of the Pleura in Mediastinum.: Yun Kyung Kang, Hyun Joo Yoo, Ho Kee Yum, Hong Sup Lee; Korean J Pathol. 1997;31(4):351-356.

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Abstract PDF: Solitary fibrous tumors (SFTs) most often involve the pleura and also may encompass the peritoneum and nonserosal sites. They occur as solitary encapsulated tumors and pursue a relatively benign clinical course. The usual criteria for malignancy are high cellularity, mitotic activity (more than 4 per 10 high-power fields), cellular pleomorphism, hemorrhage and necrosis as well as infiltrative growth. We report a case of malignant SFT of pleura who presented with an anterior mediastinal mass. Grossly, it was a 10x8x6.5 cm sized, encapsulated and well-demarcated, solid neoplasm with areas of extensive necrosis. Microscopically, parallel or haphazard arrangement of spindle cells with variable degrees of collagenous background were noted. Storiform fascicle formation, hemangiopericytoma-like pattern, and epithelioid cell clusters were often intermingled. Nodular areas with high cellularity and mitotic activity (> or =10/10 HPFs) were scattered throughout the neoplasm, however no definite cellular pleomorphism was encountered. Tumor cells were immunoreactive for vimentin and CD-34, which distinguished them from the mesothelial cells. Electron microscopically, they revealed fibroblastic and myofibroblastic differentiation.

Ectopic Paragonimiasis Presented as Multiple Colonic and Liver Masses.: Hye Sung Kim, Young Soo Lee, Yun Kyung Kang, Hye Kyung Lee, Jun Hee Kim, Hyuk Sang Lee; Korean J Pathol. 1997;31(4):357-360.

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Abstract PDF: Ectopic paragonimiasis has been diagnosed in many organs such as the mesentery, ovary, pleura, central nervous system, subcutis and very rarely in the liver. However, simultaneous involvement of the colon and liver, which mimics colonic cancer with liver metastasis, is quite unusual, and to our knowledge has never been reported. Our case is a 63 year old woman who visited our hospital because of upper abdominal pain. Radiologically, space occupying lesions were detected in the transverse colon, mesocolon and left hepatic lobe. After the radical presection, they were proved to be an ectopic paragonimiasis forming multiple cavitary parasitic granulomas with Charcot-Leyden crystals and degenerating eggs.

Potter's Syndrome with Adult Polycystic Renal Disease: An autopsy case report.: Hwa Sook Jeong, Beom Soo Park, Geon Kook Lee; Korean J Pathol. 1997;31(4):361-365.

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Abstract PDF: Potter's syndrome including bilateral renal agenesis or polycystic renal disease, bilateral pulmonary hypoplasia and characteristic face was first described in 1946. Although a great number of cases of Potter's syndrome was reported, Potter's syndrome with adult polycystic kidney disease(Potter type III) was very rarely found. In this report, we described an autopsy case of Potter's syndrome having adult polycystic kidneys disease, bilateral pulmonary hypoplasia and characteristic face in conjunction with multiple hepatic cysts, features of congenital hepatic fibrosis and a pancreatic cyst. Microscopically, all cysts were lined by cuboidal epithelial cells, showing positive for epithelial membrane antigen and cytokeratins.

Acute Interstitial Pneumonia (Hamman-Rich Syndrome): An Autopsy Case.: Han Kyeom Kim, Ae Ree Kim, Min Ji Jeoung, Won Hee Seo, Jee yeoun Lee, Su Hyun Park; Korean J Pathol. 1997;31(4):366-374.

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Abstract PDF: Acute interstitial pneumonia is a fulminant disease of unknown etiology that usually occurs in a previously healthy person and produces the histologic findings of the organizing phase of diffuse alveolar damage. We experienced an autopsy case of acute interstitial pneumonia of unknown etiology. The patient was a 48 year old man who had been healthy and had not been exposed to organic dusts or other toxic materials. The chief complaints represented were dyspnea and a dry cough for several weeks before hospitalization, and the chest radiographs showed bilateral interstitial infiltrates. Patchy consolidation of air space was also identified and ground-glass attenuation similar to those described in ARDS was detected on high-resolution computed tomography. Steroid pulse therapy, mechanical ventilation, and antibiotics for superimposed bacterial infection were performed, but the symptoms did not improve and the patient died of generalized respiratory insufficiency and severe hypoxemia 2 1/2 months after hospitalization. At autopsy the macroscopic and microscopic findings were confined mainly to the lungs. On the whole, both lungs were firm in consistency and the external surface showed a cobblestone appearance. The cut surface showed almost complete replacement of the normal lung parenchyma with gray to yellow fibrous tissue with a little residual functional area remaining. The pathology of both open lung biopsy and autopsy tissue showed marked hyperplasia of type II pneumocytes, hyaline membrane formation, thickening of the alveolar wall due to extensive fibroblast proliferation, and relatively abundant young collagen deposition in the interstitium. An immunohistochemical stain for cytokeratin revealed epithelial hyperplasia and showed that the alveolar spaces were markedly shrunken by fibrous tissue.

Congenital Mesoblastic Nephroma.: Seok Hoon Jeon, Seung Sam Paik, Nam Hoon Kim, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(4):375-378.

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Abstract PDF: Mesoblastic nephroma is an important differential diagnosis of a renal mass occurring in the neonatal period or in early childhood. It is a rare monomorphous congenital renal neoplasm most commonly recognized during the first 3 months of life. With the widespread application of ultrasound imaging, many cases are recognized prior to birth. We report a case of mesoblastic nephroma detected by ultrasonograph at 36 weeks of intrauterine fetal life and removed after birth. It showed a well circumscribed, grayish white, solid mass measuring 4x3x2 cm. The tumor was predominantly a classic type with a focal cellular pattern. Immunohistochemical and electron microscopic studies were done.

Crohn's Disease Involving Small Intestine and Colon: 2 cases report.: Shi Nae Lee, Sun Hee Chang, Hee Soo Yoon, Hea Soo Koo, Ok Kyung Kim, Ryung Ah Lee, Eung Beum Park; Korean J Pathol. 1997;31(4):379-382.

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Abstract PDF: Crohn's disease was originally described as a small bowel disorder and has been known to involve the large bowel in approximately 40% of all cases with or without concomitant ileal component. We describe two cases of Crohn's diseas of small intestine and colon with a summary of differential diagnosis with ulcerative colitis. Both cases were originally diagnosed and treated as ileal tuberculosis. Grossly, there were skip lesions in both cases with prominent pseudopolyps and ulcerations in colon. Also noted were typical serpentine lesions in ileum as well as in colon. Microscopically, transmural inflammation was confirmed and one case showed scattered noncaseating granulomas in the wall. Submucosal edema and fibrosis with thickening of the wall was not prominent in colon. Polymerase chain reaction performed on paraffin block for the demonstration of Mycobacterium tuberculosis in one case showed negative reaction.

Clear Cell Ependymoma.: Jae Hee Suh, Seung Mo Hong, In Chul Lee; Korean J Pathol. 1997;31(4):383-387.

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Abstract PDF: The clear cell variant of ependymoma is a rare, recently described, intracranial tumor which is composed of clear neoplastic ependymal cells. Clear cell ependymomas may share characteristic histologic features of oligodendrogliomas or central neurocytomas; striking nuclear uniformity, perinuclear halos, and numerous angulated capillaries. In contrast to oligodendrogliomas, however, clear cell ependymomas are noninfiltrating tumors with sharp boundaries. Perivascular pseudorosette formation is frequent. Oligodendrogliomas are usually nonreactive for GFAP compared to diffuse immunoreactivity of clear cell ependymoma. Central neurocytomas may also be differentiated by their immunoreactivity for synaptophysin. This is a case of clear cell ependymoma in a 40-year-old man. By computed tomography and magnetic resonance imaging scans, a well circumscribed cystic tumor with mural nodule was demonstrated in the right frontal lobe. It was 6cm in diameter and well enhanced. Histologically, it was sharply demarcated from the brain parenchyma. The cystic wall was lined by atypical ependymal cells, which "transformed" to clear cells in the solid area. The cells had uniform nuclei and perinuclear halos. Mitotic figures and necrotic foci were focally present. The cells were immunoreactive for glial fibrillary acidic protein (GFAP), while synaptophysin was negative. Electron microscopy revealed densely packed polyheadral cells with scant organelles and well developed intercellular junctions.

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