Journal of Pathology and Translational Medicine

Volume 33(6); June 1999

Original Articles

Morphologic Changes of Pulmonary Tissue Secondary to Sidestream Cigarette Smoke.: Kun Young Kwon, Ji Min Jeon, Sang Pyo Kim, Kwan Kyu Park, Dae Hyun Kim; Korean J Pathol. 1999;33(6):395-403.

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Abstract PDF: Chronic bronchiolitis is a condition associated with cigarette smoking, and later associated with pulmonary parenchymal alteration and progressive deterioration of lung function. Early respiratory bronchiolitis was produced in Sprague-Dawley rats by indirect inhalation of cigarette smoke daily in a smoke exposure chamber designed by authors for 1 month. Experimental group A (n=5) was sacrificed after having smoked 30 cigarettes, group B (n=5) after 80 cigarette, and group C (n=7) after 140 cigarettes, respectively. Examination of morphologic changes in the lungs was done on light microscope, transmission and scanning electron microscopes. Light microscopically, increase in number of goblet cells in the bronchial mucosa, brown-pigmented macrophages in the alveoli, multifocal alveolar collapse adjacent to the bronchioles, dilatation of alveolar ducts and alveolar spaces were observed. Transmission electron microscopically, irregularly shaped Clara cells, alveolar wall collapse, and focally type I epithelial cell injury were seen. Scanning electron microscopically, scattered alveolar collapse, irregular dilatation of alveolar ducts, alveolar spaces and interalveolar pores (pores of Kohn) were seen. The terminal and respiratory bronchioles showed morphological alteration of Clara cells, but no evidence of cellular bronchiolitis or bronchiolar obstruction. We conclude that sidestream smoke induces an early respiratory bronchiolitis including aggregates of brown pigmented macrophages and varying degrees of structural alteration of adjacent pulmonary parenchyma.

The Significance of Adhesion Molecules and Granzyme B in Acute Renal Allograft Rejection.: So Yeon Park, Hwal Woong Kim, Hyun Soon Lee; Korean J Pathol. 1999;33(6):404-414.

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Abstract PDF: Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are weakly expressed in normal glomerular cells and vascular endothelial cells, but not in tubules. Granzyme B is a cytotoxic granule present in activated cytotoxic T cells and natural killer cells. To determine the effect of ICAM-1 and VCAM-1 expression and granzyme B-positive cells on histologic grade of rejection, we performed the immunohistochemical study on 19 renal biopsy specimens and one nephrectomy specimen from 14 patients with acute renal allograft rejection using monoclonal antibodies against theses proteins. According to severity of rejection based on Banff classification, three biopsies were classified as borderline, 4 grade I, 12 grade II, and 1 grade III. In all the cases with acute rejection, ICAM-1 and VCAM-1 were expressed in the tubular epithelial cells. The numerical score of ICAM-1 in the tubular epithelial cells was 1.0 in borderline cases, 1.3 0.4 in grade I cases, 2.2 0.8 in grade II cases, and 3.0 in grade III case. The staining intensity of ICAM-1 in the tubular epithelial cells was increased in accordance with histologic rejection grade (P<0.05). The staining intensity of ICAM-1 and VCAM-1 in the renal tubular epithelial cells was increased in accordance with the number of T lymphocytes in the renal parenchyme (r=0.46; P<0.05, r=0.61; P<0.01). The number of granzyme B-positive cells was 6.4 1.6/HPF in borderline cases, 8.1 2.5 in grade I cases, 19.6 11.7 in grade II cases, and 53 in grade III case. The number of T lymphocytes and granzyme B-positive cells was also increased in accordance with histologic rejection grade (P<0.05). These results suggest that ICAM-1 and granzyme B-positive cells may play an important role in the induction of renal allograft rejection and that the grading of severity of these parameters may be useful to predict the prognosis of renal allograft.

The Effect of Aminoguanidine and Insulin on the Development of Insulitis and the Expression of Inducible Nitric Oxide Synthase in Multiple Low Dose Streptozotocin-induced Diabetic Mice.: Hee Kyung Chang, Ji Young Suh, Young Sik Choi, Soon Young Kim, Chang Hyun Yoo, Bang Hur, Yo Han Park; Korean J Pathol. 1999;33(6):415-421.

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Abstract PDF: In this study the effect of insulin and aminoguanidine on the expression of iNOS and the development of insulitis in the multiple low dose streptozotocin (SZ) induced diabetic (LDSD) mice was evaluated. Eighty mice (Charles-River CD-1 mice) were divided into four groups. Group I received SZ for five days. Group II received SZ for five days and was followed by insulin treatment. Group III received SZ for five days and was followed by aminoguanidine treatment. Group IV was normal control group. The blood glucose level and body weight were measured weekly. On the 35th day, pancreat ic sections were observed to evaluate the frequency and the severity of insulitis in addition to the immunohistochemical expression of iNOS in the pancreatic islets. Blood glucose levels of group IV were significantly lower than other experimental groups on the 21st, 28th, and 35th day. The difference in blood glucose levels was not statistically significant. Incidence of the insulitis was lower in group II than in groups I and III. The severity of insulitis correlated with the increase in blood glucose level only in group II. The expression of iNOS was more pronounced in group I than in groups II and III. Aminoguanidine did not inhibit development of the insulitis but decreased expression of iNOS in the pancreatic islets. Therefore it is speculated that iNOS production is one of the factors and other pathogenetic mechanisms might be involved in the development of insulitis.

DNA Sequencing of p53 Gene Mutation in Colorectal Carcinomas.: Young Ran Shim, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1999;33(6):422-433.

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Abstract PDF: Mutations in the p53 gene occur during the development of colorectal carcinomas, and play an important role in the conversion of adenoma into carcinoma. To detect the p53 gene mutation and its pattern of expression in colorectal carcinomas, polymerase chain reaction for exons 5, 6, 7, and 8, recombinant gene cloning, and automated DNA sequencing were performed with 30 fresh colorectal carcinomas. Each tissue was also analyzed by immunohistochemical staining for p53 protein. p53 protein was detected in 25 of 30 (83.3%) colorectal carcinomas by immunohistochemical study. p53 mutation was detected in 4 of 30 (13.3%) colorectal carcinomas. The distribution of these mutations among these exons investigated was as follows: Three mutations in exon 5 (66.7%) and 1 mutation in exon 7 (33.3%). One case with mutation in exon 5 had mutations at three different codons. Mutations in exon 5 were found at codon 153 (GGG to AGG: Gly to Arg), 170 (TGC to GGC: Cys to Gly), 186 (CTA to TTA: silent mutation), 158 (GCG to ACG: Ala to Thr), and 176 (ACG to ATG: Thr to Met). Mutation in exon 7 was found at codon 248 (AGG to AGA: silent mutation). Four of them were missense mutations. Two of 6 mutations were silent mutations. Five transition mutations and 1 transversion mutation were also detected. All cases with mutations by automated DNA sequencing showed positive p53 protein immunohistochemical stainining. In conclusion, p53 gene mutation was detected in 4 of 30 (13.3%) colorectal carcinomas, located in codon 153, 158, 170, 176, and 186 of exon 5 and codon 248 of exon 7. Further studies are needed to evaluate the significance of the codon 153 mutation which was not recognized in other studies on colorectal carcinomas.

Ductal Carcinoma In Situ of the Breast: Comparison of Histologic Classifications and Correlation with Histologic Grade of Coexisting Invasive Ductal Carcinoma.: Sung Ran Hong, Yee Jeong Kim, Yi Kyeong Chun, Hye Sun Kim, Hy Sook Kim; Korean J Pathol. 1999;33(6):434-442.

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Abstract PDF: Recently developed new classifications (Holland, Van Nuys, modified Lagios) of ductal carcinoma in situ (DCIS) linked to outcome have emphasized the importance of nuclear morphology rather than architecture. We have evaluated these three classifications in ductal carcinomas composed of in situ and invasive carcinomas. The reproducibility of three classifications was assessed (n=49), and the histological grade of the DCIS was compared with the histologic differentiation (modified Bloom & Richardson method) and nuclear grade (modified Black method) of the coexisting invasive ductal carcinoma (n=45). According to Holland classification, the DCIS component was poorly differentiated in 51.0%, intermediately differentiated in 40.8%, and well differentiated in 8.2%. Using the Van Nuys classification, the DCIS component was group 3 (high grade with or without necrosis) in 44.9%, group 2 (non-high grade with necrosis) in 28.6%, and group 1 (non-high grade without necrosis) in 26.5%. According to the modified Lagios classification, the DCIS component was high-grade in 42.8%, intermediate-grade in 32.7%, and low-grade in 24.5%. The histologic grades of the three classifications revealed significant correlations between Holland and Van Nuys classification (p<0.0001) and between Holland and modified Lagios classification (p<0.0001), especially in poorly differentiated/group 3/high-grade DCIS. The reproducibility of classification of the DCIS was 71.4% in the Holland, 61.2% in the Van Nuys, and 55.1% in the modified Lagios classifications. The grade of the DCIS showed significant correlation with the grade of coexisting invasive ductal carcinoma (p<0.0001), especially in poorly differentiated/group 3/high-grade DCIS. In conclusion, DCIS grade, determined by the Holland, Van Nuys or modified Lagios classifications, is closely correlated with the histologic grade of the invasive ductal component in tumors composed of in situ and invasive ductal carcinoma, and may be a useful factor to estimate clinical behavior of DCIS. In our experience the Holland classification is recommended for DCIS classification due to its high reproducibility.

Expression of p53 and Rb Proteins in Invasive Ductal Carcinoma of the Breast.: Hyun Jin Son, Han Sang Yoon, Myoung Jae Kang; Korean J Pathol. 1999;33(6):443-449.

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Abstract PDF: Inactivation of tumor suppressor genes may play an important role in many human cancers including breast. This study was done to determine the relationship between the expression of p53 and Rb protein and prognostic factors such as histopathologic differentiation, tumor size, and lymph node metastasis. In 57 cases of breast invasive ductal carcinomas, the immunohistochemical staining with p53 and Rb protein gave the following results: p53 protein was detected in 45.6% (26/57) of cases. Tumors with large size, poor differentiation or lymph node metastases tended to show increased expression of p53 protein. However, p53 protein expression did not show any significant correlation with prognostic factors such as tumor size (p value 0.25), histologic grade (p value 0.75), and positive lymph node status (p value 0.26). Rb protein was detected in 57.9% (33/57) of cases. Rb protein also did not show any significant correlation with prognostic factors such as tumor size (p value 0.56), histologic grade (p value 0.71), and positive lymph node status (p value 0.98). There was no significant correlation between p53 expression and Rb protein expression (p value 0.80).

Case Reports

Metastatic Adenocarcinoma with Mucin Emboli in the Lung: A case report.: Chung Yeul Kim, Kwang Il Kim, Sung Hwan Park, Eung Suk Lee, Han Kygum Kim; Korean J Pathol. 1999;33(6):450-452.

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Abstract PDF: Lung is known as a vulnerable organ to metastatic tumors. Metastasis occurs mainly through lymphatics but seldom via blood vessels. Adenocarcinoma with mucin emboli is very rare. Primary foci reported in the literature were breast, lung, ovary and pancreas. A lung biopsy from a 60-year-old male patient showed floating mucin associated with metastatic adenocarcinoma to the lung in the blood vessels. The tumor cells spreaded along the vascular endothelium as if they were vascular endothelial cells. The tumor cells and mucin in the vessel were strong positive for PAS staining. Elastic and immunohistochemical staining for smooth muscle actin highlighted the vascular wall in the mucin containing structure with infarction of the lung. The primary focus was identified in the pancreatic head through the abdominal ultra-sonographic and computer-tomographic examination.

Combined Epithelial-Myoepithelial Carcinoma and Basal Cell Adenocarcinoma of the Parotid Gland: A case report.: Young Kyung Bae, Dong Sug Kim, Jang Soo Suh, Jae Yun Ro; Korean J Pathol. 1999;33(6):453-456.

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Abstract PDF: Epithelial-myoepithelial carcinoma and basal cell adenocarcinoma are uncommon, low-grade malignant epithelial neoplasms of salivary gland. They occur predominantly in the parotid glands with frequent recurrences and occasional distant metastases. We report an unusual case of combined epithelial-myoepithelial carcinoma and basal cell adenocarcinoma within the same mass of the parotid gland in a 32-year-old woman. To the best of our knowledge, this is the first such a combined carcinoma case.

Papillary Serous Cystadenoma of Borderline Malignancy Arising from a Paramesonephric Parovarian Cyst: A case report.: Ji Han Jung, Youn Soo Lee, Seok Jin Kang, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1999;33(6):457-459.

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Abstract PDF: Primary malignant parovarian epithelial tumors are extremely rare, with only 56 cases previously reported in the world literature. Most parovarian epithelial tumors are of paramesonephric (Mullerian) origin. In this article, we report the first case in the Korean literature of papillary serous cystadenoma of borderline malignancy from paramesonephric parovarian cyst. This case presented here is of particular interest since this neoplasm is rare. A 48-year-old female underwent a hysterectomy with bilateral adnexectomy and pelvic lymph node dissection for a cystic tumor of the right parovarian area. The tumor, measuring 13 cm in diameter, was apart from the ovaries, fallopian tubes and uterus. The cyst wall had well-developed smooth muscle layers. The cyst was lined with mildly atypical ciliated and non-ciliated low columnar cells compatible with those of paramesonephric origin. From the inner surface of the cyst several cauliflower-like structures projected into the lumen. They were of a predominantly papillary architecture covered by atypical epithelial cells with piling-up and occasional glandular growth. No destructive stromal invasion was identified.

Carcinoma Showing Thymus-Like Differentiation (CASTLE) of the Thyroid Gland: A case report.: Mi Jin Gu, Young Ran Shim, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1999;33(6):460-462.

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Abstract PDF: Carcinoma Showing Thymus-Like Differentiation (CASTLE) is a rare tumor, which occurs in the thyroid gland and surrounding soft tissue, or soft tissue of the neck. It is thought to originate from ectopic thymus or branchial pouch remnants. We report a case of CASTLE of the thyroid gland in a 42-year-old woman. Grossly, a nodular, partly well demarcated, grayish yellow, 3.0 2.0 cm sized, solid mass was found in the right thyroid gland. Microscopically, the tumor was divided into lobules of variable size and shape, nests and cords with thin and thick fibrous septa which were infiltrated by lymphocytes and plasma cells. The tumor cells were large, polygonal and had vesicular nuclei with prominent nucleoli and eosinophilic cytoplasm. Some cells, especially in the central portion of the nests had abundant eosinophilic cytoplasm and showed squamoid feature.

Adrenocortical Oncocytoma: A case report.: Hee Joung Cha, Yeon Lim Suh, Jung Hyun Yang; Korean J Pathol. 1999;33(6):463-466.

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Abstract PDF: Adrenal gland is a rare location for an oncocytic neoplasm. In English literature less than 10 cases of adrenocortical oncocytoma have been reported. We have experienced a case of adrenocortical oncocytoma in a 35-year-old man which was detected incidentally during the ultra-sonographic evaluation of the abdomen for a routine physical examination. This case did not demonstrate any clinical evidence of adrenocortical abnomalities, such as virilization or hypertension. Grossly, the tumor was light to dark tan on cut surface. Light-microscopic examination revealed tumor cells with abundant lipid- sparse eosinophilic cytoplasm and occasional pleomorphic nuclei. Mitotic figures were less than 5/50 HPFs. Tumor cells were positive for vimentin but negative for pancytokeratin, CAM 5.2, chromogranin and synaptophysin. Ultrastructural examination demonstrated abundant mitochondria containing occasional intramitochondrial dense bodies or inclusions.

Intraosseous Lipoma A report of four cases.: Hye Jeong Choi, Mi Jin Gu, Joon Hyuk Choi, Duk Seop Shin, Kil Ho Cho; Korean J Pathol. 1999;33(6):467-470.

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Abstract PDF: Intraosseous lipoma is a very rare primary tumor of the bone. We report four cases of intraosseous lipoma. The patient ranged in age from 34 to 59-year-old (median age: 35 year-old). There were three men and one woman. All of four cases presented with pain. The involved bones were calcaneus in two cases, tibia in one case and ilium in one case, respectively. In all cases plain x-ray film revealed well-defined lytic lesion. Their size ranged 2 to 4.5 cm (mean size: 3.5 cm). Histologic examination showed mature adipose tissue. Three cases showed secondary changes such as atrophic bone, fat necrosis, fibrosis, dystrophic calcification, and reactive ischemic bone formation. The clinicopathologic and roentgenographic correlation are necessary in establishing correct diagnosis of this tumor.

Choroidal Metastasis of Adenocarcinoma of the Lung: A case report.: Seong Hwan Park, Ju Han Lee, Jeong Seok Moon, Jong Sang Choi; Korean J Pathol. 1999;33(6):471-473.

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Abstract PDF: Choroidal metastatic carcinoma is very rare. We recently experienced a case of lung adenocarcinoma which presented to the clinic with ocular symptoms. This 57-year-old Korean male patient visited the department of ophthalmology due to decreased visual acuity and pain of the left eye. On MRI scan, a nodule was attached to the retina of the left eyeball. On simple chest radiograph, a large amount of pleural effusion was noted in the left pleural cavity. Emergency enucleation of the left eyeball was done with an impression of malignant melanoma causing an intractable ocular pain. Grossly, the lesion in the eyeball was rising from the choroid. On histologic examination, tumor cells formed many irregular, small gland-like structures. The tumor cells showed alcian blue-positive mucin in the cytoplasm and glandular lumens and were positive for CEA. Chest CT scan was performed postoperatively and showed a huge mass in the left lower lobe and multiple nodular opacities in both lung fields. Bronchoscopic biopsy revealed moderately differentiated adenocarcinoma similar to that of the eyeball.

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