Journal of Pathology and Translational Medicine

Volume 37(6); December 2003

Original Articles

Small Cell Carcinoma of the Uterine Cervix.: Jinwon Seo, Jong Sun Choi, Geunghwan Ahn; Korean J Pathol. 2003;37(6):373-378.

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Abstract PDF: BACKGROUND
Small cell carcinoma of the uterine cervix is a rare and aggressive neoplasm, for which there have been few diagnostic markers.
METHODS
Eleven cases of small cell carcinoma of the uterine cervix were retrieved from pathology files. Immunohistochemical stains were performed for two epithelial markers (cytokeratin [AE1/AE3] and epithelial membrane antigen [EMA]) and four neuroendocrine markers (neuron-specific enolase [NSE], CD56, chromogranin, and synaptophysin).
RESULTS
Of the nine cases followed up, two with initial distant metastasis died within one year. All seven remaining cases were diagnosed at stage Ib, and showed no evidence of recurrence. Nine cases were positive for one or more epithelial markers. Two cases showed positivity for epithelial markers in less than 10% of their tumor cells. The immunoreactivity for neuroendocrine markers showed variable results; four cases were reactive for chromogranin, four were positive for synaptophysin, and seven were reactive for CD56. All cases were positive for NSE.
CONCLUSIONS
A diagnostic panel of chromogranin, synaptophysin, and CD56 rather than a single marker would be useful for the diagnosis of small-cell carcinoma of the uterine cervix.

Comparison of Ziehl-Neelsen Stain and TB-PCR on Detection of Mycobacterium tuberculosisin Formalin-fixed, Paraffin-embedded Tissues of Chronic Granulomatous Inflammation.: Min Sun Cho, Shi Nae Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2003;37(6):379-383.

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Abstract PDF: BACKGROUND
TB-PCR is a faster and more sensitive method to detect mycobacterium than acid-fast bacilli (AFB) stain, which is laborious and time consuming. We compared the sensitivity and specificity of AFB stain and TB-PCR and examined the possibility of TB-PCR as a confirmative test without AFB stain in the diagnosis of tuberculosis.
METHODS
We performed Ziehl-Neelsen stain and nested PCR using a commercially available TB-PCR kit amplifying IS6110 sequence in 81 cases of paraffin-embedded tissues diagnosed as chronic granulomatous inflammation. In addition, we evaluated the morphology of granuloma and the presence of caseation necrosis.
RESULTS
Of the 81 cases studied, 22 (27.2%) and 40 (49.4%) were positive for AFB stain and TB-PCR, respectively. Of 49 cases accompanying caseation necrosis, 19 (38.8%) were AFB stain positive and 37 (75.5%) were TB-PCR positive; a result that is comparable with that of other reports. Of the 22 AFB-positive cases, 2 were TB-PCR negative.
CONCLUSION
TB-PCR is very helpful for the diagnosis of tuberculosis in routinely processed, formalin-fixed, paraffin-embedded tissue samples. Nevertheless, AFB stain should continue to be performed at the same time.

Expression of Urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Gallbladder Carcinoma.: Kee Hyung Lee, Haeng Ji Kang, Seung Yeoun Lee, Moon Hyang Park; Korean J Pathol. 2003;37(6):384-392.

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Abstract PDF: BACKGROUND
There are evidences that uPA and its inhibitor play a key role in tumor spread. We studied whether uPA and PAI-1 expressions could serve as prognostic parameters along with clinical, gross and microscopic findings in gallbladder carcinomas.
METHODS
We analyzed 42 cases of gallbladder carcinomas by immunohistochemical staining and clinicopathologic parameters.
RESULTS
uPA and PAI-1 were more frequently expressed in the adenocarcinoma than in the normal or benign gallbladder tissue. The uPA expression in the glands of low grade adenocarcinoma was significantly correlated with both distant and lymph node metastases. The uPA expression in the stroma around the low grade adenocarcinoma was significantly correlated with either distant or lymph node metastasis. The PAI-1 expression was significantly correlated with lymph node metastasis only for both distant and lymph node metastases. In multivariate analysis, the lymphatic invasion was significantly related to poor survival (p= 0.0115). In univariate analysis, the cases without lymphatic invasion had prolonged survival. Positive expression of uPA in the glands of low-grade adenocarcinoma was significantly correlated with poor survival (p=0.0391).
CONCLUSION
In conjunction with clinicopathologic findings, expressions of uPA and PAI-1 may be useful prognostic markers in gallbladder carcinomas.

Expression of p21, p53 and bcl-2 Proteins in Invasive Ductal Carcinoma of the Breast.: Hyang Jeong Jo, Ki Jung Yun, Hyung Bae Moon; Korean J Pathol. 2003;37(6):393-399.

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Abstract PDF: BACKGROUND
This study was designed to investigate the prognostic significance of p21, p53, and bcl-2 proteins in invasive ductal carcinoma of the breast.
METHODS
Seventy-two cases of invasive ductal carcinoma were examined by immunohistochemical staining for p21, p53 and bcl-2 proteins. The results were correlated with clinicopathological variables, including age, tumor size, histologic grade, nuclear grade, lymph node status, estrogen receptor (ER) and progesterone receptor (PR) expression.
RESULTS
Of 72 cases, p21, p53 and bcl-2 proteins were positive in 25 (34.8%), 35 (50.0%) and 27 (37.5%), respectively. There were no statistically significant correlations between the p21 protein expression and the other clinicopathological variables. The expression of p53 protein, however, showed a significant relation to ER expression, and that of bcl-2 was positively correlated with tumor size. In survival analysis, p21, p53, and bcl-2 proteins, nuclear grade and lymph node status were associated with survival rate.
CONCLUSIONS
These results indicate that p21, p53, and bcl-2 proteins might play a role in tumorigenesis of breast carcinoma. In addition, the increased expression of p21, p53, and bcl-2 proteins could be used as factors suggesting poor prognosis in breast carcinomas.

Expression of MMP-2, MT1-MMP, and TIMP-2 mRNA in Breast Carcinomas.: Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 2003;37(6):400-406.

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Abstract PDF: BACKGROUND
The activation of proMMP-2 is induced by membrane type 1-matrix metalloproteinase (MT1-MMP), but inhibited by tissue inhibitors of matrix metalloproteinase type 2 (TIMP-2). This study was carried out to establish the pattern of mRNA expression of MMP-2, MT1-MMP, and TIMP-2 in breast carcinomas.
METHODS
Seventy-nine cases of invasive ductal carcinoma, 10 of ductal carcinoma in situ, and 10 of fibrocystic disease as a control were analysed for the expression of MMP-2, MT1-MMP, and TIMP-2 mRNA, using in situ hybridization. Correlations of the results with the clinical stage, tumor size, nodal status, and nuclear grade were analysed.
RESULTS
The expression rates of MMP-2, MT1-MMP, and TIMP-2 mRNA in invasive ductal carcinoma were 68%, 73%, and 56%, respectively. They were localized to both stromal and tumor cells, but mainly in the latter. The MMP-2 mRNA expression was significantly correlated with the clinical stage (p < 0.05), while the expression of TIMP-2 mRNA was inversely correlated with clinical stage and tumor size(p < 0.05). Significant positive correlations between MMP-2 and MT1-MMP expressions, along with inverse relationships between MMP-2 and TIMP-2, and between TIMP-2 and MT1-MMP, were also found. CONCLUSIONS: MMP-2 and TIMP-2 mRNA expressions might be useful as one of a range of prognostic parameters in breast carcinoma patients.

Prognostic Significance of P53, BCL-2 and PCNA in Diffuse Large B-Cell Lymphoma: Correlation with International Prognostic Index.: Dong chul Kim, Gyeongsin Park, Ahwon Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2003;37(6):407-412.

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) represents a diverse spectrum of clinical presentation, morphology, and genetic and molecular alterations, and shows variable prognoses and responses to therapy. The International Prognosis Index (IPI) is widely used to predict prognosis but is not precise.
METHODS
Thirty-nine cases of DLBCL were classified into low- and high-risk groups according to IPI and were analyzed for their p53, BCL-2, BCL-6 and PCNA expression profile by immunohistochemical staining and overall survival rate.
RESULTS
The mean age of the 39 patients, 23 males and 16 females, was 52.6 years. There were 23 cases (59.0%) in the low-risk group and 16 (41.0%) in the high-risk group. p53, BCL-2, BCL-6 and PCNA expression was higher in the high-risk group than in the low-risk group, but only the differences in p53 and BCL-2 expression were statistically significant (p < 0.05).
CONCLUSION
The p53 and BCL-2 protein expression in DLBCL may supplement IPI in predicting the prognosis of DLBCL patients.

Neurofilament Protein Subtype Expression in Neuronal Migration Disorders.: Hyun Sik Oh, Yoo Duk Choi, Hyun Joong Kim, Kyung Hwa Lee, Myoung Kyu Kim, Young Jong Woo, Jae Hyu Kim, Min Cheol Lee; Korean J Pathol. 2003;37(6):413-420.

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Abstract PDF: BACKGROUND
Neuronal migration disorder (NMD) is one of the causes of medically intractable epilepsy. As neurosurgical treatments for medically intractable epilepsy have expanded recently, precise histopathologic diagnosis is required. Histopathologic grading of NMD is important due to its association with neocortical development and expectation of prognosis. Many studies revealed abnormalities of neuronal cytoskeletal protein in abnormal neuronal cells of NMD.
METHODS
We performed immunohistochemical staining for neurofilament protein (NF) subtypes, one of the neuronal cytoskeletal proteins, and investigated the staining pattern of specific cells in each grade of NMD.
RESULTS
NF-L was more intensely labeled in perikarya, dendrites, and axons of normal or small sized dysplastic neurons, cytomegalic neurons, and balloon cells than of normal-looking neurons. Furthermore, positive reaction was more intense in high-grade lesion. NF-H and NF-M were mainly positive in the axons of gray and white matter and weakly positive in a few cytomegalic neurons and some balloon cells.
CONCLUSION
NF-L is a better marker than NF-H and NF-M for the detection of normal or small sized dysplastic neurons, cytomegalic neurons, and balloon cells and for grading of NMD.

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

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

Case Reports

Malignant Mixed Mullerian Tumor of Fallopian Tube with Multiple Distinct Heterologous Components.: Beom Jin Lim, Jae Wook Kim, Woo Ick Yang, Nam Hoon Cho; Korean J Pathol. 2003;37(6):429-431.

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Abstract PDF: We experienced a case of primary malignant mixed mullerian tumors (MMMT) of the fallopian tube of FIGO stage I. In addition to endometrioid adenocarcinomas, multiple apparent heterologous elements encompassing myxoid chondrosarcoma, osteosarcoma, myxoid liposarcoma and well differentiated angiosarcoma were recognized as separate nodules. These findings have not been described previously in MMMTs of the female genital tract.

Primary Diffuse Large B-cell Lymphoma of the Prostate: A Case Report.: Dong chul Kim, Gyeongsin Park, Ahwon Lee, Kyungja Han, Chang Suk Kang; Korean J Pathol. 2003;37(6):432-434.

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Abstract PDF: Primary lymphomas of the prostate are extremely rare and can mimic other more common prostatic lesions clinically. We report a case of primary diffuse large B-cell lymphoma of the prostate in an 81-year-old man. The patient presented with voiding difficulty as an initial symptom and enlargement of the prostate on rectal digital examination. Transurethral prostatic resection was performed. On microscopic examination, atypical lymphoid cells infiltrated and replaced the prostatic parenchyma. The tumor cells had large nuclei with irregular nuclear membrane and vesicular clumped chromatin. Nucleoli were not distinct and the cells had scanty cytoplasm. Immunohistochemically, the tumor cells were immunoreactive for CD20 and CD79a but not reactive for CD5, BCL-2 and BCL-6. Histopathological diagnosis was diffuse large B-cell lymphoma of the prostate. The patient received 5 cycles of chemotherapy after histologic diagnosis but died from pulmonary and scrotal metastases 6 months later.

Multifocal Epithelioid Angiosarcoma of the Stomach: A Case Report.: Kyeongmee Park, Sungjig Lim, Jungyeon Kim, Young Jin Yuh, Sung Rok Kim, Hong Yong Kim; Korean J Pathol. 2003;37(6):435-437.

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Abstract PDF: Angiosarcoma is a very rare neoplasm, and even more so in the gastrointestinal tract where its distinction from adenocarcinoma may be extremely difficult. We report a case of multifocal epithelioid angiosarcoma of the stomach in a 65-year-old woman. Histologically, the tumor foci were composed of haphazard, anastomosing channels lined by malignant endothelial cells with epithelioid features. Those neoplastic cells stained positive for CD31, CD34, and factor VIII-related antigen.

Endometrial Mucinous Adenocarcinoma with Extensive Squamous Differentiation: A Case Report.: Ho chang Lee, Pil Gyu Hwang, Soo Youn Cho, Young S Park, In Ae Park; Korean J Pathol. 2003;37(6):438-441.

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Abstract PDF: Endometrial mucinous adenocarcinoma occurs in 1-9% of endometrial adenocarcinomas and adenocarcinoma with squamous differentiation in approximately 25%. We report a rare case of mucinous adenocarcinoma with squamous differentiation in a 53-year-old woman. Curetting biopsies of the endometrial lesion were taken twice after hormone replacement therapy, which lasted for four months. Because the squamous differentiation was so extensive, the initial diagnosis based on each curetting specimen was squamous papilloma. A total hysterectomy was performed and the tumor was revealed to be a mucinous adenocarcinoma with squamous differentiation. We subsequently discussed the pathogenesis and prognosis of this type of tumor.

Down Syndrome Associated with Testicular Seminoma: A Case Report.: Na Rae Kim, Jae Gul Chung, Hyun Yee Cho; Korean J Pathol. 2003;37(6):442-445.

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Abstract PDF: Individuals with Down syndrome have a susceptibility to neoplastic transformation, increased risk of chronic leukemia and central nervous system tumors. Recently, an increased number of cases of testicular germ cell tumors have been reported in individuals with Down syndrome, with more than forty cases in the literature. Here we report the first Korean case of seminoma with Down syndrome, in a 19-year-old institutionalized man who presented with painful scrotal swelling. Percutaneous needle biopsy showed histology of seminoma with invasion to the adjacent epididymis. Both testes were orthotopic. He underwent orchiectomy of the affected side, and the surgical staging was stage I seminoma with complete resection. We emphasize that the physician and nursing staff should be aware of the increased incidence of testicular seminoma in Down syndrome, because testicular seminoma might be misinterpreted as a scrotal infection with subsequent needle biopsy, which is contraindicated to avoid possible lymphatic metastasis.

Biliary Papillomatosis: A Report of Two Cases.: Mi Jin Gu, Joon Hyuk Choi; Korean J Pathol. 2003;37(6):446-450.

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Abstract PDF: We report two cases of biliary papillomatosis, a rare disease which is characterized by multiple, papillary adenomas of the intrahepatic and/or extrahepatic bile ducts.
Case
s 1 and 2 were a 45-year-old woman and a 61-year-old woman, respectively, with upper abdominal pain. Abdominal computed tomography scan of case 1 revealed a 4-cm sized cystic and solid mass within the dilatated intrahepatic bile duct. Hepatobiliary ultrasonography of case 2 showed dilatation of the main intrahepatic and common bile duct with nonshadowing echogenic material. Soft, friable papillary masses were noted grossly in the dilated intrahepatic bile duct. Microscopically, the tumor was composed of papillary structures, most of which were lined by a layer of tall columnar cells. Complex papillary fronds with pseudostratification, cellular atypia, structural atypia and foci of invasion were noted in case 2. The p53 expression increased in the dysplastic and carcinomatous area and was correlated with the Ki-67 labeling index.

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