Journal of Pathology and Translational Medicine

Volume 34(8); August 2000

Original Articles

Genotype of Epstein-Barr Virus and Comparative Genomic Hybridization Analysis of NK/T Cell Lymphoma.: Keying Eun Choi, Young Hyeh Ko; Korean J Pathol. 2000;34(8):541-549.

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Abstract PDF: NK/T cell lymphoma is a distinct clinicopathologic entity which is more prevalent in Asia than in America and Europe and is highly associated with Epstein-Barr virus (EBV) infection. Although the clinicopathologic features of the tumor have been clearly defined, genetic changes and roles of virus associated with the development and progression of tumor have not been well studied. In this study, we carried out polymerase chain reaction (PCR) for EBNA-3B, EBNA-3C, and LMP-1 30 bp deletion to investigate EBV subtype and variants in tumor tissue and performed comparative genomic hybridization (CGH) to screen chromosomal imbalances using frozen tissues from 7 patients with nasal-type NK/T cell lymphoma and 1 patient with blastic NK cell lymphoma. Of 6 cases infected with EBV, there were EBV type 1 in six, LMP-1 30 bp deletion variant in four, and LMP-1 40 bp deletion variant in one. Frequent chromosomal imbalances included deletions at 1p31-pter (4), 12q23-q24 (3), and 17p (4), and gains at 2q (5), 10q (3), and 13q34-qter (4). Blastic NK cell lymphoma displayed deletions of 9q, 7q, and 6q, similar to that of nasal-type NK/T-cell lymphoma. With these results, we assumed that candidate genes in these imbalanced chromosomal loci would provide the clue for further molecular studies to identify putative tumor suppressor genes or proto-oncogenes associated with pathogenesis of this neoplasm.

Histopathologic Findings, and p53 and K-ras Mutational Analysis in Biopsy Specimens Using Fluorescence Bronchoscopy.: Young Sik Kim, Seol Hee Park, Myung Hee Jung, Eun Chang Choi, I Yong Park, Han Kyeom Kim, Insun Kim; Korean J Pathol. 2000;34(8):550-558.

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Abstract PDF: A fluorescence bronchoscope system has been developed for detecting early lung cancer including dysplasia and carcinoma in situ. To determine the histologic findings and genetic alterations of the lung tissues, which were biopsied by the fluorescence bronchoscope, we analyzed 104 specimens from 62 heavy smokers for their histopathology, cell proliferation index, and genetic mutations of p53 and K-ras. We used immunohistochemistry for MIB-1 and p53, and PCR-SSCP and direct DNA sequencing for p53 and K-ras. The histology was variable from reactive conditions to invasive cancers, and consisted of basal cell hyperplasia (26.9%), dysplasia (4.8%), carcinoma in situ (1.9%), squamous cell carcinoma (7.7%), adenocarcinoma (4.8%), and small cell carcinoma (10.6%). The cellular proliferation index of the lesions increased as their aggressiveness increased. p53 and K-ras mutations were detected in 33.7% and 14.4% of all tissues, respectively. In dysplasia, p53 and K-ras mutations were observed in 3 of 5 and in 2 of 5 tissues, respectively. However, these genetic alterations were not found in carcinoma in situ. Interestingly, 28.6% of basal cell hyperplasia showed p53 mutations. In conclusion, these data suggest that the biopsy specimens using fluorescence bronchoscopy show variable histologic findings, ranging from reactive conditions to invasive cancers. In addition, some of the dysplastic lesions are related to p53 and K-ras mutations, although these genetic alterations are also seen in basal cell hyperplasia.

Plasminogen Activator Inhibitor-1, c-erbB2, and p53 Protein Overexpression and Prognosis in Gastric Adenocarcinoma.: Ayoung Park, So Young Jin, Dong Won Kim, Dong Wha Lee; Korean J Pathol. 2000;34(8):559-566.

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Abstract PDF: Despite its fall in incidence, gastric adenocarcinoma remains a common disease with dismal prognosis worldwide. A better understanding of its tumorigenesis and biologic properties of tumor cells related to invasion and metastasis is crucial to improving diagnosis and treatment. Conflicting results concerning the relationships between overexpression of PAI-1, c-erbB2, and p53 protein and biologic behavior of gastric carcinoma have been noted. The aim of this study was to evaluate the value of overexpression of PAI-1, c-erbB2, and p53 protein as prognostic factors in gastric adenocarcinoma. Overexpression of PAI-1, c-erbB2, and p53 protein by immunohistochemistry was correlated with variable clinicopathological parameters and patients' survival in 80 cases of gastric adenocarcinoma. Overall PAI-1 expression rate was 63.7% (51/80) and higher in advanced cancer (p=0.0003) and nodal metastasis (p=0.003) groups. Overall c-erbB2 expression rate was 43.8% (35/80) and higher in antral (p=0.03), differentiated (p=0.001), intestinal (p=0.0007), and expanding (0.03) groups. The p53 protein overexpression was 37.5% (30/80) and higher in early cancer (p=0.02), differentiated (p=0.006) and intestinal groups (p=0.009). Patients with PAI-1, c-erbB2, and p53 protein positive tumors tended to have poorer survival rates than patients with PAI-1, c-erbB2, and p53 protein negative tumors, but the difference was not statistically significant (p=0.25, 0.37, 0.52). Our data indicated that PAI-1 overexpression is one of the poor prognostic factors in gastric adenocarcinoma and c-erbB2 and p53 protein seem to be involved in the early stage of carcinogenesis of intestinal type-gastric adenocarcinoma.

Expression of bcl-2 and p53 Protein, and Apoptosis in Transitional Cell Carcinoma of the Bladder.: Myoung Ja Chung, Sang Su Kim, Ho Yeul Choi; Korean J Pathol. 2000;34(8):567-573.

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Abstract PDF: This study examined the expression of the bcl-2 protein in 59 cases of transitional cell carcinomas (TCCs) of the bladder and evaluated the relationship of bcl-2 and p53 with apoptosis. The cases were divided into 41 low-grade TCCs, 18 high-grade TCCs, 32 superficial TCCs, and 27 invasive TCCs. p53 and bcl-2 protein were detected by the immunohistochemical method and apoptosis was analysed by using hematoxylin-eosin stained slide. The results were as follows: bcl-2 protein was detected in 8 (14%) TCCs and all of these cases were low grade TCCs. Expression of bcl-2 protein was not correlated with clinical stage. There was no correlation between bcl-2 and p53 protein. According to the immunohistochemical results of bcl-2 and p53 protein, the cases were divided 4 groups. Apoptotic index (AI) was higher in p53 positive/ bcl-2 negative group than other groups but the significance was recognized only between p53 positive/bcl-2 negative group and p53 negative/bcl-2 negative group (p<0.05). p53 protein was detected in 20 (36%) TCCs and its expression was correlated positively with histologic grade and clinical stage (p<0.05). AI correlated positively with histologic grade and clinical stage (p<0.01). These data indicate that overexpression of bcl-2 protein is rare in TCC of the bladder and associated with low grade TCCs. Overexpression of p53 is associated with the tumor progression in the TCCs. AI correlates with p53 positivity but does not correlate with bcl-2 positivity.

Trichoblastic Fibroma: A Pathologic Analysis of 4 Cases.: Ah Won Lee, Ji Han Jung, Jin Young Yoo, Seok Jin Kang, Byung Kee Kim; Korean J Pathol. 2000;34(8):574-580.

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Abstract PDF: Trichoblastic fibroma is a benign trichogenic tumor that has both epithelial and mesenchymal components and exhibits partial follicular induction. We studied 4 cases of trichoblastic fibroma and reviewed their clinical and histologic features. Two tumors were present in the face. The remaining two were in the vulva and perianal area, respectively. The age of the patients ranged from 53 to 68 years, with an average age of 62. All were female. Histologically, the lesions showed a well circumscribed mass, located at dermo-subcutaneous junction in three patients and subcutaneous in one. They demonstrated mesenchymal induction evidenced by hair germ-like structure and perifollicular sheath. There was no connection between the tumor and epidermis. Differentiation toward hair structure led to the formation of the infundibulum through inner root sheath. Trichoblastic fibroma may be confused clinically and/or histologically with basal cell carcinoma. Identification of the mixed epithelial and mesenchymal components, and the absence of epidermal connection and cleft within the stroma are important in differentiating this benign neoplasm from basal cell carcinoma.

Telomerase Activity and Expression of Telomerase RNA in Malignant Fibrous Histiocytoma.: Jinyoung Yoo, Seok Jin Kang, Bung Kee Kim; Korean J Pathol. 2000;34(8):581-587.

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Abstract PDF: Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA onto chromosomal ends to compensate for sequence loss during replication. It has been detected in a variety of human malignancies, suggesting that such activity may play a role in the tumorigenic process. To determine whether telomerase is reactivated in malignant fibrous histiocytoma, 12 tissue samples with this tumor were analyzed for the telomerase activity by a radioactive PCR-based TRAP (telomeric repeat amplification protocol) assay. All of the tumors were further investigated for the expression of human telomerase RNA (hTR) by an in situ hybridization (ISH). Telomerase activity was detected in one (8.3%) sample. Expression of hTR was demonstrated in 7 (58.3%): one telomerase-positive and six telomerase-negatives. These data indicate that the reactivation of telomerase is an uncommon event and not an important factor involved in tumorigenesis in malignant fibrous histiocytoma. It is noteworthy that 50% of the patients with grade 2 tumors expressed hTR, suggesting that telomerase RNA may be useful as a marker for identifying tumor aggressiveness earlier than the conventional histopathologic grading scale.

Expression of Neuron Specific Enolase, Chromogranin, and Synaptophysin in Peripheral Neuroblastic Tumors.: Hyung Seok Kim, Jae Ha Hwang, Jong Jae Jung, Min Cheol Lee; Korean J Pathol. 2000;34(8):588-596.

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Abstract PDF: The presence and distribution of pan-neuroendocrine markers such as neuron-specific enolase (NSE), chromogranin (CG), and synaptophysin (SYP) were investigated by immunohistochemistry in 15 cases of neuroblastic tumors, including four cases of neuroblastomas, six cases of ganglioneuroblastomas, and five cases of ganglioneuromas. Three cases of normal sympathetic ganglion were used for the normal control group. NSE was observed in all cases and both in ganglion cells and in neuropils. NSE was detected not only in the majority of the neuroblasts showing signs of differentiation, but also in some poorly differentiated neuroblasts. All cases of neuroblastic tumors were positive for CG, however, some variability of staining intensity and distribution patterns were noted. CG was found mainly in differentiated neuroblasts with enlarged cytoplasm and nuclei along the periphery of the perikaria, and was also found in the perinuclear regions of some undifferentiated cells. SYP was positive in 9 of 11 cases. In all of the 9 cases, SYP was detected in some differentiating neuroblasts and differentiated neuroblasts, as well as the mature ganglion cells. However, it has scarcely stained in dot or granular pattern. Two CG-negative tumors were also negative for SYP. Our data indicate that antibodies against NSE and CG are helpful as a diagnostic aid for neuroblastic tumors.

Case Reports

Pigmented Mediastinal Paraganglioma: A case report.: Seong Ho Kim, Yoon Hee Jin, Eun Kyung Hong, Moon Hyang Park; Korean J Pathol. 2000;34(8):597-600.

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Abstract PDF: Pigmented extraadrenal paraganglioma is an unusual neoplasm that has rarely been reported in the literature. Based on histochemical staining or electron microscopy, pigment has been classified as lipofuscin, neuromelanin or true melanin. We report a case of pigmented extraadrenal paraganglioma in the posterior mediastinum of a 70-year-old woman. Histologically, the tumor had a characteristic organoid architecture of "zellballen" pattern with rich delicate microvasculature. Tumor cells contained numerous coarse brown-black pigment granules. Ultrastructurally, the tumor showed abundant large electron-dense pigment granules that vary in size and shape and smaller membrane-bound neurosecretory granules. The larger granules were consistent with neuromelanin or lipofuscin. Histochemically, the pigment is most likely neuromelanin, which is a waste product of catecholamine metabolism.

Inflammatory Myofibroblastic Tumor of the Maxillary Sinus: A case report.: Hyun Jin Son, Seung O Ko, Myoung Ja Chung, Ho Yeul Choi; Korean J Pathol. 2000;34(8):601-604.

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Abstract PDF: Inflammatory myofibroblastic tumor (IMT) is a space occupying lesion which is composed of myofibroblasts, plasma cells, and lymphocytes. IMT of the maxillary sinus is rare and its etiology is unknown. We present a case of inflammatory myofibroblastic tumor occurring in the right maxillary sinus of a 57-year-old woman. Radiologically, this tumor was interpreted as malignant neoplasm. On histologic examination, bundles of spindle cells were admixed with inflammatory cells including mature plasma cells and lymphocytes. On the basis of the immunohistochemical findings and ultrastructural features, we recognized that the intervening spindle cells were myofibroblasts. We discussed etiology and prognostic factors of this tumor.

Perianal Granuloma Caused by a Female Pinworm (Enterobius vermicularis): A case report.: Seok hyung Kim, Je Geun Chi; Korean J Pathol. 2000;34(8):605-607.

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Abstract PDF: The intestinal nematode Enterobius vermicularis is the most common metazoan endoparasite in humans, with humans being the only host. But complicated perianal granulomas due to Enterobius are unusual. The literature reports only 13 previous cases of enterobiasis presenting as perianal mass or abscess. We describe an additional case of a perianal mass caused by granulomatous inflammation containing Enterobius vermicularis eggs and dead bodies in a 7-year-old boy. The lesion was located in the anus and measured 2 1 cm. Clinical impression was lipoma and excisional biopsy was done. Microscopic examination revealed necrotizing granuloma which contained several 50~60 20~30 micrometer sized eggs which were identified as those of Enterobius vermicularis. The adult worm could not be identified with clarity due to necrosis.

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