Journal of Pathology and Translational Medicine

Volume 40(6); December 2006

Original Articles

Small Airway Diseases: Clinical Characteristics and Pathological Interpretation.: Kun Young Kwon, Won Il Choi, Sung Min Ko; Korean J Pathol. 2006;40(6):389-398.

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Abstract PDF: Small airway diseases are seen in many clinical conditions. The locations of small airway diseases are small bronchioles including terminal and respiratory bronchioles, and alveolar duct. The histopathologic features of bronchiolar injury have been described variously and have led to confusing and overlapping terms. The purpose of this article is to describe the clinical characteristics and histopathologic interpretation of small airway diseases. We classify the small airway diseases as primary bronchiolar diseases, and secondary bronchiolar diseases including pulmonary parenchymal diseases, and large airway diseases with prominent bronchiolar involvement. Primary bronchiolar diseases include respiratory bronchiolitis, acute bronchiolitis, constrictive bronchiolitis, follicular bronchiolitis, diffuse panbronchiolitis, mineral dust airway diseases, and a few other variants. Pulmonary parenchymal diseases with bronchiolar involvement include respiratory bronchiolitis-associated interstitial lung disease, organizing pneumonia, hypersensitivity pneumonitis, pulmonary Langerhans' cell histiocytosis, sarcoidosis and idiopathic pulmonary fibrosis. Bronchiolar changes can also be seen in large airway diseases such as chronic bronchitis, bronchiectasis, cystic fibrosis and asthma. The patterns of bronchiolar response to various injuries are relatively limited and these patterns are generally non-specific in regard to the etiology. Appropriate interpretation and diagnosis of small airway diseases depend on judicious correlation of clinical, radiologic, and histopathologic characteristics.

Clinicopathological Analysis of Systemic Anaplastic Large Cell Lymphoma.: Soo Young Chung, Han Suk Ryu, Jae Soo Ko, Baek Youl Ryoo, Seung Sook Lee; Korean J Pathol. 2006;40(6):399-405.

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Abstract PDF: BACKGROUND
Several studies from western countries have reported variable prognoses for patients with systemic anaplastic large cell lymphoma (ALCL) depending strongly on the expression of anaplastic lymphoma kinase (ALK). However, no prognostic significance of ALK expression in Koreans was reported in a single report regarding these patients, although the number of cases was limited in that study.
METHODS
We analyzed the clinicopathological features of ALK+ ALCL and ALK- ALCL in 30 Korean patients diagnosed with primary systemic ALCL.
RESULTS
ALK expression was detected in 60% of all ALCL patients (18/30), and there was no statistical significance to ALK expression in overall survival. Patients with ALK+ ALCL were younger in age and had negative bcl-2 expression; these differences were statistically significant. Tumors positive for ALK protein and granzyme B expression, and negative for bcl-2 expression with a null-cell phenotype tended to have better survival outcomes, althought this trend failed to reach statistical significance (p<0.2), probably due to the limited number of cases in this study.
CONCLUSION
ALK protein expression and the absence of bcl-2 in tumor cells tend to result in better survival despite the failure of this trend to achieve statistical significance. Further studies that examine potential pathologic prognostic factors combined with the expression of ALK and apoptotic factors such as bcl-2 are needed. Additional larger-scale studies are also needed to conclude that ALK expression has no prognostic significance among Koreans.

Pathological Analysis of 1,000 Cases of Transrectal Ultrasoundguided Systematic Prostate Biopsy: Establishment of New Sample Processing Method and Diagnostic Utility of Immunohistochemistry.: Chang Lim Hyun, Hee Eun Lee, Haeryung Kim, Hye Seung Lee, So Yeon Park, Jin Haeng Chung, Gheeyoung Choe; Korean J Pathol. 2006;40(6):406-419.

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Abstract PDF: BACKGROUND
We developed a new processing method for extended prostate needle biopsy, and evaluated diagnostic utility of routine immunohistochemistry in 1,000 consecutive unselected cases of transrectal ultrasound-guided systematic prostate biopsy.
METHODS
Four to five biopsy cores were embedded in one paraffin block. All the biopsy cores were immunohistochemically stained with basal cell markers.
RESULTS
The new sample processing method was technically perfect for making a diagnosis from extended prostate needle biopsy. Among 1,000 cases, there were 323 cases (32.3%) of adenocarcinoma, 5 cases of other malignant tumors, 9 cases of high-grade prostatic intraepithelial neoplasia without a carcinoma, and only 8 cases of atypical small acinar proliferation. Among the 323 cases of adenocarcinoma, there were 38 cases (11.8%) of microcarcinomas <0.1 cm and 101 cases (31.3%) of small adenocarcinomas <0.3 cm in length. In the needle biopsy specimens, 59 cases (18.3%) were classified as clinically insignificant carcinomas. Among them, 37 cases underwent radical prostatectomy, which turned out to be clinically significant carcinomas in 24 cases (64.9%).
CONCLUSIONS
Routinely performed immunohistochemistry combined with the new sample processing method is very effective for detecting microscopic carcinoma foci as well as differentiating carcinoma from benign conditions mimicking cancer.

Expression of VEGF, MMP-9 and Neovascularization in Relationship to the Clinical Behavior of Giant Cell Tumors of Bone.: Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Chang Woo Han, Sung Sun Kim, Sang Woo Juhng, Sung Taek Jung, Jae Hyuk Lee; Korean J Pathol. 2006;40(6):420-426.

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Abstract PDF: BACKGROUND
Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior.
METHODS
We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9.
RESULTS
The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022).
CONCLUSIONS
These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.

Expression of c-kit and Cell Cycle Regulators in Non-small Cell Lung Carcinoma.: Sun Hee Chang, Mee Joo, Hanseong Kim; Korean J Pathol. 2006;40(6):427-431.

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Abstract PDF: BACKGROUND
The abnormal expression of c-kit is implicated in the pathogenesis of a variety of solid tumors. The Rb pathway and p53 act as cell cycle regulators. The purpose of this study was to assess the expression of c-kit, Rb, p53, p16 and cyclin D1 and their relationship to clinical and pathological parameters in patients with non-small cell lung carcinomas (NSCLC(s)).
METHODS
Tissue microarrays consisting of 2 mm cores from the corresponding blocks were constructed from 54 NSCLC(s). Immunohistochemical staining for c-kit, Rb, p53, p16 and cyclin D1 was performed. C-kit immunostaining was considered positive if > or =10% of tumor cells were immunoreactive along the membrane and/or in cytoplasm. For Rb, p53, p16 and cyclin D1, tumor cells showing a nuclear staining pattern were interpreted as positive.
RESULTS
We found that c-kit was expressed in 13 (24%) cases, Rb was lost in 39 (72%) cases, p53 was expressed in 28 (52%) cases, p16 was lost in 42 (78%) cases and cyclin D1 was expressed in 33 (61%) cases. The c-kit expression was significantly higher in adenocarcinoma (39%) than in squamous cell carcinoma (8%). We did not find any correlation between c-kit, Rb, p53, p16 and cyclin D1 expression and clinicopathological parameters such as: age, tumor size, lymph node involvement, disease stage and distant metastasis. There was a direct correlation between p53 expression and Rb loss.
CONCLUSIONS
These results suggest that c-kit may be a useful therapeutic target for patients with c-kit positive tumors, and that the disruption of Rb and p53 pathways may play an important role in the development and progression of NSCLC(s).

p53, Heat Shock Protein 70 and Topoisomerase II Expression in Gallbladder Carcinoma.: Dae Cheol Kim, Mee Sook Roh, Jin Sook Jeong; Korean J Pathol. 2006;40(6):432-438.

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Abstract PDF: BACKGROUND
The present study was designed to investigate the expression of p53, Heat Shock Protein 70 (HSP70), and Topoisomerase (Topo) II alpha in the preneoplastic lesions and carcinomas of the gallbladder (GB) and to assess the correlation between the expression of these proteins and the clinicopathologic parameters by performing immunohistochemistry.
METHODS
The immunohistochemical expressions of p53, HSP70 and Topo II alpha were evaluated in 38 gallbladder carcinomas and 3 adenomas. Fifteen CIS(s) and 8 dysplasias that were located adjacent to invasive carcinomas were also studied.
RESULTS
A p53 expression was identified in 22 (57.9%) of the 38 GB carcinomas, in 9 (64.3%) of 14 CISs, and in none of the 8 dysplasias and 3 adenomas. A HSP70 expression was found in 11 (29%) of the 38 carcinomas, in 11 (78.6%) of 14 CIS(s), and in 4 (57.2%) of 7 dysplasias. A Topo II alpha expression was present in 36 (94.7%) of the 38 carcinomas, in 13 (92.9%) of 14 CIS(s), in 7 (100%) of 7 dysplasias and in 3 (100%) of 3 adenomas. p53 overexpression was related to the T stage of the primary tumor, while HSP70 and Topo II alpha were not related to any of the clinicopathologic parameters.
CONCLUSION
p53 may be involved in GB carcinogenesis and in the progression of cancer. p53 may be also helpful for making the differential diagnosis between dysplasia and CIS. A further large study is needed to better elucidate the roles of HSP70 and Topo II alpha in GB carcinogenesis.

Comparison of Efficacy of Human Papilloma Virus Genotyping Assays using Restriction Fragment Mass Polymorphism and DNA Chip Analysis in Patients with Abnormal Pap Smear and Uterine Cervical Cancer.: Hyun Jae Chung, Sung Nam Kim, Eun Hee Lee, Mi Sun Jee, Min A Kim, Sun Young Hwang, Hee Jung Cho, Soo Ok Kim, Sun Pyo Hong; Korean J Pathol. 2006;40(6):439-447.

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Abstract PDF: BACKGROUND
High-risk human papilloma virus (HPV) infection is the primary cause of cervical cancer; there is a need for more sensitive and reliable methods for HPV genotyping to use as screening tools for early detection and intervention. METHODS: A novel MALDI-TOF MSbased assay, termed Restriction Fragment Mass Polymorphism (RFMP) was developed for multiple HPV genotyping. Its performance was compared with DNA chip technology. The study was based on 164 cases classified as normal (n=40), ASCUS (n=53) and invasive squamous cell carcinoma (SCC, n=71) by a PAP smear and/or cervical colposcopic biopsy.
RESULTS
High-risk genotypes were detected in 7.5%, 47.2% and 97.2% in normal, ASCUS and SCC groups by RFMP, and in 20.0%, 41.5% and 90.1% using DNA chip technology, respectively. The results showed substantial concordance, with a kappa coefficient of 0.688, between the methods. Diagnostic sensitivity and specificity for cervical cancer were found to be 97.2% and 92.2% with RFMP and 90.1% and 80.0% using DNA chip microarrays.
CONCLUSIONS
RFMP and DNA chip technologies were shown to be reliable methods for HPV genotyping with a high concordance. The improved sensitivity and specificity should make RFMP a viable option for the management of women with cervical neoplastic lesions.

Case Reports

Ectopic Sebaceous Glands in the Esophagus: A Case Report.: Jung Ha Shin, Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2006;40(6):448-451.

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Abstract PDF: There are few reports of the endoscopic and histological features of ectopic sebaceous glands in the esophagus. Recently we observed a 2 mm whitish flat elevated nodule in the lower esophagus. A biopsy was taken under the clinical impression of a papilloma or ulcer scar. Histology revealed normal esophageal mucosa with mature ectopic sebaceous glands located in the lamina propria with no visible hair follicles. We report this case with a brief review of the literature related to the histological findings and histogenesis of esophageal ectopic sebaceous glands.

Ovarian and Pituitary Metastasis from Adenocarcinoma of the Lung: A Case Report.: Yun Kyung Kang; Korean J Pathol. 2006;40(6):452-455.

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Abstract PDF: Ovarian metastasis as the first manifestation of a lung adenocarcinoma is an exceptionally rare condition and is often difficult to distinguish from primary ovarian carcinoma. Metastatic cancers of the pituitary gland are also very rarely recognized. This case concerns a 30-year-old woman who exhibited a unilateral ovarian mass that was initially diagnosed as a well- to moderately- differentiated mucinous adenocarcinoma. A month later, she was found to have a lung cancer. A year later, she developed a solitary pituitary mass. After immunohistochemical staining for thyroid transcription factor-1 (TTF-1), she was diagnosed with pulmonary adenocarcinoma with metastases to her right ovary and pituitary gland. This could be the first case of primary lung adenocarcinoma metastasis to two unusual secondary sites, the ovary and pituitary gland, without widespread systemic metastasis. In the differential diagnosis of an ovarian adenocarcinoma, metastatic carcinoma from the lung should be considered. Immunohistochemical staining for TTF-1 would be helpful as well.

Primary Mucosal Desmoplastic Melanoma of Gingiva: A Case Report.: Gawon Choi, Jeong Won Kim, Soon Yuhl Nam, Kyung Ja Cho; Korean J Pathol. 2006;40(6):456-460.

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Abstract PDF: Desmoplastic melanoma (DM) is a rare malignant melanoma variant. Although DM mainly affects the skin chronically exposed to the sun, a small number of mucosal DM have been reported. Primary mucosal DM is difficult to diagnose because of its rarity and atypical histopathologic features. Here, we report a case of DM in a 52 year-old female who presented with a right cervical mass and upper gingival pigmentation. A CT scan revealed an ill-defined infiltrative mass 2 cm in size under the pigmented mucosa. She subsequently underwent a partial maxillectomy with neck dissection. Gross examination revealed that the mass exhibited a grayish white fibrotic cut surface and that the maxillary bone had been destroyed. Microscopically, the main mass was composed of cigar-shaped or wavy spindle cells with desmoplastic stroma under the melanoma in situ. The diagnosis of DM was confirmed immunohistochemically with S100 protein positivity and HMB45 negativity. The patient has survived for 29 months after the operation with a presumed metastatic focus.

Undifferentiated Carcinoma Arising in a Choledochal Cyst: A Case Report.: Hee Eun Lee, Chang Lim Hyun, You Jeong Lee, Hye Sil Seol, Ja June Jang; Korean J Pathol. 2006;40(6):461-465.

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Abstract PDF: An association between choledochal cyst and carcinoma is well established. Here, we report an extremely rare case of undifferentiated carcinoma exhibiting extensive sarcomatous features arising in a choledochal cyst. The patient in our case had a radiologically confirmed choledochal cyst and anomalous pancreaticobiliary ductal union, and mild wall thickening in the cyst was observed on endoscopic retrograde cholangiopancreatography. The patient underwent common bile duct excision and cholecystectomy. In the choledochal cyst, a nodule measuring 1.5x1 cm was detected. The lesion was composed of atypical, spindle-shaped and large, round pleomorphic tumor cells simulating sarcoma. Neither glandular nor squamous differentiation was observed. These cells were immunoreactive for both vimentin and cytokeratin by immunohistochemistry. These histologic and immunohistochemical findings were consistent with undifferentiated carcinoma, spindle and giant cell type, according to the WHO classification.

Eosinophilic Cytoplasmic Globules in Papillary Renal Cell Carcinoma: A Case Report.: Ok Ran Shin, Jae Young Park, Hae Kyung Lee, Young Seok Lee, Chang Hee Han, Sung Hak Kang, Kyo Young Lee, Yeong Jin Choi; Korean J Pathol. 2006;40(6):466-468.

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Abstract PDF: Eosinophilic cytoplasmic globules may be seen in a variety of neoplastic and nonneoplastic conditions and are most often associated with alpha-1-antitrypsin deficiency, several pathologic liver conditions and yolk sac tumors. A few cases of eosinophilic cytoplasmic globules in renal cell carcinoma have been reported but there has only been one report of papillary type. We report another case of papillary renal cell carcinoma with eosinophilic cytoplasmic globules, which is similar to a Mallory body but with different properties.

Polycystic Kidney Disease Presenting as Subarachnoid Hemorrhage Due to Ruptured Cerebral Aneurysm: An Autopsy Case.: Yoo Duk Choi, Han Young Lee, Youn Shin Kim; Korean J Pathol. 2006;40(6):469-471.

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Abstract PDF: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by multiple expanding cysts in both kidneys, and they ultimately destroy the renal parenchyma and cause renal failure. Intracranial aneurysms are found in approximately 10% to 15% of ADPKD patients. Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm is a frequent complication in patients with ADPKD and it makes up a considerable proportion of the causes of death in this group of patients. We report here an autopsy case of polycystic kidney disease that was morphologically identical to ADPKD, and the patients had presented after death with SAH due to a ruptured cerebral aneurysm.

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