Journal of Pathology and Translational Medicine

Volume 36(5); October 2002

Original Articles

Age-related Alterations of Normal Ascending Aorta among Koreans with Special Reference to Cystic Medial Necrosis.: Tae Jung Kwon, Dong Hwan Shin, Kyung Moo Yang, Nak Eun Chung; Korean J Pathol. 2002;36(5):281-285.

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Abstract PDF: BACKGROUND
The specificity of aortic alteration in the pathogenesis of aortic dissection has been challenged. To obtain comprehensive morphologic data that may enhance the appreciation of the pathogenesis of aortic disease in normal aorta among Koreans, we performed a morphologic study of aorta with aging.
METHODS
The histologic and morphometric studies of ascending aorta without cardiovascular disease were carried out on seventy-two autopsy cases. Alcian blue-stained sections were subjected to morphometric study using image analysis system. The age range of the cases was from newborn to those who had been in their eighties.
RESULTS
The most prominent feature of aging aorta was fragmentation and loss of elastic lamellae, and expansion of interlamellar spaces. Cystic medial necrosis of varying degrees was observed in almost every specimen. On the morphometric study, the percentage area of mucoid degeneration revealed no statistically significant differences among the varying age groups. Compared to males, female subjects exhibited significant mucoid degeneration (p<0.05).
CONCLUSIONS
The alteration of elastic lamellae is increased with age. Cystic medial necrosis is not considered merely an aging phenomenon, but is enhanced in the aorta of females.

Loss of PTEN Expression in Primary Lung Cancer.: Mee Sook Roh; Korean J Pathol. 2002;36(5):286-291.

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Abstract PDF: BACKGROUND
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene, a candidate tumor suppressor, is localized to chromosome 10q23 and shares extensive homology with cytoskeletal proteins auxilin and tensin. It appears to have multifunctional roles involved in cell proliferation, migration, and invasion. The role of PTEN alteration in the lung cancer and its relationship with other suppressor genes are not well established.
METHODS
Formalin-fixed, paraffin-embedded tissues from 105 patients with diagnosed with primary lung cancer were evaluated for PTEN and p53 protein expression using immunohistochemical methods. The results of the expression pattern of PTEN were compared with clinicopathological parameters and the expression pattern of p53.
RESULTS
Forty-seven (44.8%) of 105 cases had loss of PTEN expression. Loss of PTEN expression was significantly associated with histologic type (p<0.05), but did not correlate with tumor size, lymph node metastasis, and stage. There was no significant relationship between loss of PTEN expression and p53 expression, and no significant difference in clinicopathologic characteristics between particular groups of patterns with the four possible tumor carrying PTEN/p53 phenotypes.
CONCLUSION
It is suggested that loss of PTEN expression occurs commonly in primary lung cancers and correlates with histologic type. Our results also support the proposed role of PTEN as a candidate tumor suppressor in lung cancer, and we suggest that there is a need for further study of this gene.

Detection of Helicobacter pylori in the Gastric Mucous Layer in Pediatric Patients.: You Kyung Kim, Jong Sil Lee, Hwal Woong Kim, Jeong Hee Lee, Hee Shang Youn, Gyung Hyuck Ko; Korean J Pathol. 2002;36(5):292-295.

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Abstract PDF: BACKGROUND
Helicobacter pylori is present mainly in the gastric mucous layer. However, the mucous layer, along with the bacteria, is lost during conventional tissue processing in which formalin is used for fixation. The purpose of this study is to ascertain - if the mucous layer is preserved by using Carnoy solution as a fixative - whether the detection rate of H. pylori is increased in pediatric patients.
METHODS
Five pieces of gastric mucosal tissue were obtained from the gastric antrum and the body of one hundred pediatric patients. One of the specimens was fixed with formalin. Another specimen was fixed with Carnoy solution. The tissue sections were stained with hematoxylin-eosin and immunohistochemically stained for H. pylori. For reference, a rapid urease test was performed on the remaining three specimens.
RESULTS
In the formalin-fixed tissue, the detection rate of H. pylori was 13% in the gastric antrum and 12% in the body (overall 16%). In the Carnoy solution-fixed tissue, the mucous layer was preserved and the detection rate of H. pylori was 23% in the antrum and 27% in the body (overall 28%). The positive rate of the rapid urease test was 26% in the antrum and 28% in the body (overall 29%).
CONCLUSIONS
When the number of H. pylori is small in the gastric mucosa, the bacteria may not be detected by conventional histologic methods. In that case, the detection rate of H. pylori may be increased by using Carnoy solution, rather than formalin, as a tissue fixative.

Expression of p21, p53 and Ki-67, and Apoptosis in Colorectal Adenocarcinoma.: Young Euy Park, Kyung Chan Choi, Jin Hee Sohn, Young Hee Choi, Hyung Sik Shin; Korean J Pathol. 2002;36(5):296-304.

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Abstract PDF: BACKGROUND
The purpose of this study is to assess the roles of p21 protein, p53 protein, and Ki-67 expressions and apoptosis in colorectal tumorigenesis.
METHODS
Fifty-seven colorectal cancers and 15 villotubular adenomas were investigated by immunohistochemical staining for p21 protein, p53 protein, Ki-67, and in situ labeling of apoptotic cells. Clinicopathologic values (tumor size, histologic grade, Dukes stage, and lymph node metastasis) were compared with the incidence of expressions of p21 protein and p53 protein, index of Ki-67 expression, and apoptosis.
RESULTS
The incidence of p21 protein expression was decreased with lymph node metastasis (p<0.005), and that of p53 expression was increased with lymph node metastasis (p<0.005). There were no statistically significant correlations among the p21 protein or p53 protein expressions, tumor size, histologic grade and stage. The correlation between the Ki-67 labeling index and the clinicopathologic values was not statistically significant. The labeling index of apoptosis was increased with the Astler-Coller stage (p<0.05). Statistical analysis revealed a significant inverse correlation between the p21 protein and p53 protein expressions (p<0.05).
CONCLUSIONS
It is suggested that p21 protein, p53 protein and the apoptotic labeling index are useful variables for the prognostic assessment of colorectal adenocarcinoma. Down-regulation of p21 protein expression may be associated with poor prognosis. Also, the expressions of p21 protein and p53 protein may play an important role in the tumorigenesis and progression of the colorectal adenoma-carcinoma sequence.

Expression of DNA Topoisomerase II-alpha as a Proliferating Marker in Urothelial Carcinoma of Urinary Bladder based on World Health Organization/International Society of Urological Pathology Consensus Classification: A Correlation with Expression of Ki-67 and Apoptosis: Tae Jin Lee, Dong Ki Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2002;36(5):305-313.

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Abstract PDF: BACKGROUND
DNA topoisomerase II-alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relationship between the expression of DNA topoisomerase II-alpha as a proliferating marker, and the expression of Ki-67 and apoptosis in urothelial carcinoma of urinary bladder based on World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification.
METHODS
73 urothelial carcinomas of the urinary bladder after transurethral resection and 25 carcinomas after radical cystectomy were investigated for histologic grading based on WHO and WHO/ISUP consensus classification. Formalin fixed, paraffin embedded tissue of 98 specimens from 73 patients were immunohistochemically stained for DNA topoisomerase II-alpha and Ki-67, and in situ TdT-mediated dUTP-biotin nick end labeling method for evaluation of apoptotic cells was performed. For each case, a DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were determined.
RESULTS
The histologic grades of 73 cases based on the WHO grading system were 21.9% (16 cases) in grade 1, 65.8% (48 cases) in grade 2, and 12.3% (9 cases). 5.5% (4 cases) of papillary neoplasm of low malignant potential, 47.9% (35 cases) of urothelial carcinoma of low grade, and 46.6% (34 cases) in urothelial carcinoma of high grade were reclassified using the WHO/ISUP consensus classification. Histologic grades based on two grading systems were correlated to invasion and stage (p<0.05). DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were correlated to histologic grades based on two grading system and invasion. Also, the correlation of DNA topoisomerase II-alpha and Ki-67 indices, and DNA topoisomerase II-alpha and apoptotic indices were significant, respectively.
CONCLUSIONS
DNA topoisomerase II-alpha appears to be an useful marker for assessing the proliferation potential of urothelial carcinoma of in the urinary bladder.

Directional, Vacuum-Assisted Stereotactic Biopsy of Nonpalpable Breast Lesions with Surgical Correlation.: Sung Chul Lim, Young Sook Kim, Sneige Nour; Korean J Pathol. 2002;36(5):314-322.

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Abstract PDF: BACKGROUND
The vacuum suction probe is an alternative to the 14-gauge needle and automatic gun for performing stereotactic core needle biopsies. This study assesses the accuracy of the directional, vacuum-assisted stereotactic biopsy (DVAB) of nonpalpable breast lesions. Materials and METHODS: Four hundred and thirty DVABs were performed on 412 patients between January 1998 and December 2000. Using 11-gauge or 14-gauge needles, six to 22 core samples (mean=13) per lesion were obtained. One hundred and fifty-five lesions were subsequently excised, and 223 patients with benign diagnoses had mammographic follow-ups. The results of the DVABs and surgeries were reviewed and correlated.
RESULTS
The results of the DVABs and surgeries were concordant in 98 of 113 cases and discordant in 15 cases, including 15 cases for which DVAB results indicated ductal carcinoma in situ (DCIS) but surgery yielded invasive carcinoma. The overall sensitivity, specificity, and positive and negative predictive values of the DVABs were 99.3%, 100%, 100%, and 99.7%, respectively. The positive predictive value for the presence of invasion was 100% and the negative predictive value was 81%. Histologic comparison was performed in 19 of 31 atypical ductal hyperplasias (ADHs) diagnosed with DVAB. Of the 19 ADHs, histologic findings showed DCIS in one, ADH in 9, atypical lobular hyperplasia in one, and no residual lesions in 8. Cases with less than 3 lobules were involved with ADH, or cases with more than 50% of microcalcification retrieved were all adequately diagnosed. Only 17 of 240 benign lesions diagnosed with DVAB were subsequently excised. These were confirmed to be ADH in three of the cases, and other benign diagnoses were confirmed in 14 of the cases. The others were confirmed to be benign lesions upon mammographic follow-up. Lesions less than 1.0 cm in maximal diameter can be removed completely by DVAB.
CONCLUSION
DVAB reduced the number of underestimated infiltrating tumors, but still, significant cases were found to be invasive. ADH diagnosed with DVAB does not require subsequent surgery for a rule-out diagnosis of carcinoma, if the sampling is adequate and less than 3 lobules are involved with ADH. Lesions less than 1.0 cm in maximal diameter can be removed completely by DVAB. Benign lesions diagnosed with DVAB did not require subsequent surgery, so DVAB can reduce the probability of unnecessary surgery for benign lesions and/or small lesions.

E-cadherin Expression in Distinguishing Ductal and Lobular Carcinomas of the Breast.: Eun Deok Chang, An Hi Lee, Eun Jung Lee, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2002;36(5):323-327.

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Abstract PDF: BACKGROUND
Most breast carcinomas are easily categorized as ductal or lobular. However, in some cases the distinction can be difficult since some tumors may have intermediate features of these two. Prior studies suggest that E-cadherin is useful to classify tumors as ductal or lobular, as it is lost in lobular but not in ductal carcinomas.
METHODS
We studied the histologic features and E-cadherin expression by immunohistochemistry in 57 cases of breast carcinomas, which were divided into three groups based on histology. Group 1 included 4 cases of infiltrating lobular carcinoma (IFL) and 1 case of lobular carcinoma in situ (LCIS) (n=5). Group 2 included infiltrating ductal carcinoma (IFD) with some features of IFL (n=48). Group 3 included a solid type of intraductal carcinoma (DCIS) (n=4). E-cadherin staining was scored as negative or positive.
RESULTS
All 5 cases from group 1 were E-cadherin negative, and all 4 DCIS cases were positive. Only 2 (0.04%) of the 48 cases from group 2 were E-cadherin negative.
CONCLUSIONS
Our findings suggest that the majority of cases with morphologically IFD with some IFL features are ductal. E-cadherin immunostaining is of value in helping to characterize breast carcinomas with indeterminate morphologic features.

Molecular Subtypes of Primary Glioblastoma Identified by Gene Expression Profiling.: Ghee Young Choe, S Mischel Paul; Korean J Pathol. 2002;36(5):328-337.

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Abstract PDF: BACKGROUND
The over-expression of the epidermal growth factor receptor (EGFR) occurs in nearly 50% of primary glioblastoma multiforme (GBM). Disruption of multiple signaling pathways is a critical factor in regulating the biological and clinical behavior of GBMs. In the future, therapy that specifically targets these disrupted pathways may represent the best potential treatment for patients with GBM. Large scale gene expression profiling provides a powerful approach to identify these disrupted genetic pathways and to uncover previously unknown molecular subtypes.
METHODS
We used 13 cases of primary GBM biopsy samples obtained from untreated patients and Affymetrix high-density oligonucleotide arrays to identify novel subsets of primary GBMs.
RESULTS
We showed that the expression of 90 genes differentiate EGFR+ from EGFR non-expressing (EGFR-) de novo GBMs, including expression of a number of potentially targetable molecules that act as growth/survival factors for GBMs. We also demonstrated the presence of two additional molecular subtypes of primary GBMs, including one characterized by the coordinate upregulation of contiguous genes on chromosome 12q13-15, which has a distinct global gene expression profile and expresses both astrocytic and oligodendroglial genes.
CONCLUSION
We have shown that there are EGFR+ primary GBMs, GBMs with coordinate upregulation of genes on chromosome 12q13-15, and primary GBMs lacking either alteration. Moreover, they have distinct transcriptional profiles. Our findings strongly suggest that the three GBMs are biologically different tumor types, despite their identical microscopic appearance, and provide an important first step in developing a molecular taxonomy of GBMs.

Case Reports

Partial Trisomy 13 (Patau Syndrome): An Autopsy Report.: Kyung Chan Choi, Hyung Sik Shin, Young Euy Park, Jung Lae Seo, Sung Won Lee, Eu Sun Ro, Yong Pil Kim; Korean J Pathol. 2002;36(5):338-340.

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Abstract PDF: Trisomy 13 (Patau syndrome) is rare and usually fatal if contracted within the first six months of life. We report a case of a male fetus with the typical features of Patau syndrome. He was terminated in a 27-year-old mother at the gestational age of 32+4 weeks. In chromsomal analysis by GTG banding technique, the karyotype of the fetus was 46,XY,rec(13) dup(13q)inv(13)(p13q21.3)(=partial trisomy 13q); and his mother's karyotype was 46,XX, inv(13)(p13q21.3)(=pericentric inversion). His father had normal karyotype, 46,XY. Ultrasonography showed fluid-nature content, which was occupying the entire intracranium, but preserving the brain stem and cerebellum. Postmortem examination disclosed holoprosencephaly, hydrocephalus, a single nostril, bilateral anophthalmia, ventricular septal defect, and a single umbilical artery.

Lipoma of Rectum: A Case Report.: Sung Chul Lim, Hye Keun Oh, Young Don Min; Korean J Pathol. 2002;36(5):341-343.

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Abstract PDF: Gastrointestinal lipomas are rare and are most common in the right colon. They are in opposite distribution of predilection site in comparison to adenocarcinomas and adenomatous polyps. The peak incidence for lipoma of the large bowel is in the sixth decade when there is a high incidence of colorectal carcinoma. Because of their location and the age of the patients at presentation, large bowel lipomas are usually treated on the basis of a presumptive malignant diagnosis. A 79-year-old male is presented with a 1-year history of rectal bleeding. Colonoscopy demonstrated a pedunculated mass nearly obstructing the rectum. Anterior resection was performed. The mass consisted of submucosal lobulated mature fatty tissue with ulcerated mucosa. The authors describe a case of a submucosal lipoma of the rectum with review of literatures.

Fibrolamellar Hepatocellular Carcinoma with Cytokeratin 7 Expression: A Case Report.: Mi Jung Kim, Eun Yoon Cho, Mi Sun Choe, Eun Sil Yu; Korean J Pathol. 2002;36(5):344-347.

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Abstract PDF: Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma (HCC). A 26-year-old female presented a hepatic mass and mild elevation of liver enzymes. Viral markers were negative, and levels of tumor markers were normal. Radiologically, the mass was well demarcated with central dot-like calcification and hypervascularity. Under the diagnosis of hepatocellular carcinoma, right lobectomy was performed. The tumor was grayish yellow with central fibrosis and focal hemorrhage and invaded a septal bile duct. Non-neoplastic liver was unremarkable. Microscopically, the tumor consisted of large polygonal cells in sheets, cords, and pseudoglands that were interwound by dense collagenous stroma. Tumor cells had abundant deeply eosinophilic cytoplasm and large nuclei with prominent nucleoli. Intracellular bile pigments and pale bodies were present. Tumor cells were diffusely immunostained for cytokeratin 7 (CK7), but not for cytokeratin 20 (CK20). Strong expression of CK7 in the present case suggests dual differentiation of FLC.

Disseminated Systemic Candidiasis and Aspergillosis in a Liver Transplant Patient: An Autopsy Report.: Na Rae Kim, Dae Su Kim, Young Hyeh Ko, Sung Joo Kim; Korean J Pathol. 2002;36(5):348-352.

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Abstract PDF: Postoperative complications of liver transplantation include rejection, infection, hepatic vascular thrombus, and primary graft failure, etc. Among them, fungal infection shows nonspecific clinical symptoms and overlapping laboratory findings with variable etiologies causing post-transplant hepatic dysfunction. Therefore, early diagnosis of fungal infection is not easy. Here, we report an autopsy case of disseminated candidiasis and aspergillosis in a liver transplant patient. The case was at first misinterpreted as acute cellular rejection on biopsy because the histology of predominantly cellular infiltration, ductulitis and endothelialitis were similar to those of acute cellular rejection. On autopsy, the liver, lung and kidney showed multifocal hemorrhagic infarcts due to intra-arterial fungal emboli, which were composed mostly of candida species and a minor fraction of aspergillus. Fungal thrombi invading portal vein, intrahepatic arterioles with subsequent coagulation necrosis, venulitis and ductulitis were ascribed to the misdiagnosis on biopsies. It is unusual that systemic candidiasis, unlike aspergillosis, involves large arteries.

Renal Angiomyolipoma with Vascular Leiomyomatous Features: A Case Report.: Na Rae Kim, Yeon Lim Suh; Korean J Pathol. 2002;36(5):353-356.

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Abstract PDF: Angiomyolipoma is the most common mesenchymal tumor of the kidney. It occurs sporadically and is associated with tuberous sclerosis. It can appear in any organs, but most commonly in the kidney, and it appears slightly more in females. Angiomyolipoma is pathologically composed of three heterogeneous components of blood vessels, smooth muscle cells and fat cells of varying proportion, which occasionally make several unusual histologic variants. We describe a variant of renal angiomyolipoma simulating vascular leiomyoma on routine hematoxylin-eosin stain; prominent thick-walled blood vessels interspersed with proliferation of smooth muscle cells and total absence of fat cells. Perivascular spindle-shaped smooth muscle cells were reactive for smooth muscle actin, desmin and HMB-45 immunostains. This case illustrates vascular leiomyoma-like angiomyolipoma, which was finally diagnosed on the basis of HMB-45 immunostain, and also raises a question about the real existence of renal vascular leiomyoma.

Chordoid Glioma: A Report of Two Cases.: Eun Jung Park, Hyun Sik O, Min Cheol Lee; Korean J Pathol. 2002;36(5):357-361.

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Abstract PDF: Chordoid glioma mainly occurs in the third ventricle, pineal gland, hypothalamus, and suprasella. We report two cases of chordoid gliomas of the third ventricles in adult males. Histologically, the tumors consisted of cords and clusters of oval to polygonal epitheliod cells with abundant cytoplasm. The backgrounds of the tumor show mucinous and lymphoplasmacytic infiltrates. Immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein and negative for epithelial membrane antigen, cytokeratin and neurofilament protein. Histopathologic diagnosis of chordoid glioma should be made judiciously by differentiating them from other chordoid or epithelial tumors of the central nervous system.

Letter

Calcium Pyrophosphate Dihydrate Crystal Deposition Disease (Pseudogout) of the Elbow Presenting as A Tumor-Like Mass.: Eun Deok Chang, An Hi Lee, Je Hoon Lee, Chang Suk Kang; Korean J Pathol. 2002;36(5):362-363.

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Abstract: No abstract available.

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