Journal of Pathology and Translational Medicine

Volume 33(4); April 1999

Original Articles

The Role of MIB-1 Expression and Apoptosis in Experimental Crescentic Glomerulonephritis.: Nam Hoon Kim, Wan Seop Kim, Jung Woo Noh, Moon Hyang Park; Korean J Pathol. 1999;33(4):231-242.

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Abstract PDF: It has been postulated that programmed cell death via apoptosis may be critical for remodelling of glomeruli after inflammatory injury. To understand the regulatory mechanism of apoptosis in experimental crescentic glomerulonephritis (CGN), we examined the MIB-1 score (proliferation index, PI) and apoptotic index during the progression of experimental CGN to end-stage renal failure. CGN was induced in New Zealand White rabbits by administration of guinea pig anti-GBM IgG after sensitization with guinea pig IgG and their kidneys were analyzed for the development of crescents through sequential renal biopsies. Serum creatinine levels progressively increased in a time course until day 45. The PI in glomeruli, tubular epithelial cells, and interstitium progressively increased during the progression of experimental CGN. The mean numbers of MIB-1 positive intraglomerular nuclei (PI) were significantly correlated with degrees of crescent formation and the numbers of apoptotic cells in the glomeruli, tubules, and interstitium. Significant apoptosis was present from day 1 (15.8 10.16 cells/glomerular cross section) and increased in number with the proliferative lesions as glomerular inflammation continued. Moreover, apoptosis increased during the resolution of the glomerular inflammation, and many apoptotic cells were present in the sclerotic lesions in day 17 (18.6 12.99 cells/glomerular cross section). As glomerular inflammation subsided, cellular crescents progressed to fibrous crescents with a reduction of cellularity by day 45. On day 45, the glomerular PI and the numbers of apoptotic cells were markedly decreased. The correlations found in CGN between the creatinine level and the percentage of crescents, between the percentage of crescent and PI, and between the PI and number of apoptotic cells support the hypothesis that there is a change in the glomerular and tubulo-interstitial apoptosis under pathologic conditions. These findings indicate that apoptosis plays an essential role in the resolution of intra- and extraglomerular inflammation and in the elimination of glomerular cells within the sclerotic regions for progressive CGN. The regulation of the apoptotic phenomenon and increased PI during CGN may be important in the progression of glomerular inflammation and the development of pathologic glomerular sclerosis.

Expression of Matrix Metalloproteinase-2 and -9 in Oral Squamous Cell Carcinomas in Relation to the Histologic Invasiveness and Cellular Differentiation.: Seong Doo Hong, San Pyo Hong, Yong Sik Kim, Jae Il Lee, Chang Yun Lim; Korean J Pathol. 1999;33(4):243-250.

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Abstract PDF: A poor prognosis of oral squamous cell carcinoma (SCC) is partly due to the invasiveness and metastasis of the tumor. A key element in tumor invasion and metastasis in the degradation of extracellular matrix is matrix metalloproteinases (MMPs). This study was performed to determine the expression of MMP-2 and MMP-9 of oral SCCs with regard to the histologic invasiveness and differentiation in 5 normal oral mucosa and 36 oral SCCs. The histologic invasiveness of oral SCCs were classified into 4 grades. The differentiation of oral SCCs was divided into 3 grades. The streptavidin-biotin immunohistochemical staining, using MMP-2 and MMP-9 monoclonal antibodies, was performed to determine the expression of MMP-2 and MMP-9. The expression of MMP-2 was positive in 6 of 17 oral SCCs with weak invasiveness and was positive in 7 of 19 oral SCCs with strong invasiveness. The MMP-2 expression did not increase significantly with respect to the invasiveness of oral SCCs (P>0.05). The expression of MMP-9 was strongly positive in 6 out of 17 SCCs with weak invasiveness and was strongly positive in 14 of 19 SCCs with strong invasiveness. The MMP-9 expression increased significantly with respect to the invasiveness of oral SCCs; the stronger the expression, the stronger the invasiveness (P<0.05). The expression of MMP-9 was in 57.9% of well differentiated SCCs, 57.1% of moderately differentiated ones, and 33.3% of poorly differentiated SCCs. The expression of MMP-2 and MMP-9 did not increase significantly with respect to the histologic differentiation. We conclude that with respect to the invasiveness, the MMP-9 expression increases significantly in oral SCCs but the MMP-2 expression does not; and that with respect to the histologic differentiation, their expressions do not increase significantly. These results suggeste that MMP-9 can be used as a tool to evaluate the invasiveness of oral SCCs.

Expression of Matrix Metalloproteinase-1,2,3 and Type IV Collagen in Gastric Adenocarcinoma: Influence on Lymph Node Metastasis and Prognosis.: Eun Sun Jung, Byung Gee Kim, Jo Hyun Park, Sang In Shim; Korean J Pathol. 1999;33(4):251-258.

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Abstract PDF: Matrix metalloproteinases are believed to play an important role in tumor invasion and metastasis. But little is known about the role of them in the gastric adenocarcinoma. We investigated the expression of matrix metalloproteinase-1,2,3 in eighty paraffin blocks of the primary gastric adenocarcinoma tissues with immunohistochemistry and analysed their correlation with lymph node metastasis and survival. MMP-1,2,3 were expressed most intensely in the fibroblasts around the tumor stroma. In our study the increased immunoreactivity of MMP-2 only showed statistically significant correlation with lymph node metastasis (P=0.0517, Odd's ratio=2.274). But MMP-1,2,3 all were correlated with survival. Type IV collagen was observed in the vascular basement membranes and tumor basement membranes and showed statistically significant correlation with lymph node metastasis (P=0.0002, Odd's ratio=0.194) and prognosis (P=0.0001). The immunoreactivity of MMP-2 and type IV collagen was inversely correlated (Kendall's Tau-b correlation = 0.37482, P=0.0001). Our results suggest that in human gastric adenocarcinoma the increased immunoreactivity of MMP-2 and the decreased immunoreactivity of type IV collagen has an important role in lymph node metastasis and prognosis. MMP-1,3 are not correlated with lymph node metastasis but correlated with survival. The mechanism responsible for the production of MMP by the host fibroblasts remains obscure and requires further investigation.

Case Reports

Chromophobe Renal Cell Carcinoma.: Yeong Jin Choi, Tae Kon Hwang, Youn Soo Lee, Eun Jung Lee, Seok Jin Kang, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1999;33(4):259-266.

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Abstract PDF: We report 13 chromophobe renal cell carcinomas (10.8%) observed among 120 renal cell carcinomas in adults. The average age was 53 (range: 34-72) years old, and 6 were males and 7 females. The mean tumor size was 10 (range: 5-17) cm, mean nuclear grade 2.4, and mean Robson's stage was 1.9. There were two distinct histologic variants; typical variant (n=9) and eosinophilic variant (n=4). Both of them showed typical light microscopic features and positive reaction with Hale's colloidal iron and carbonic anhydrase II, a marker protein of intercalated cells of renal collecting ducts. A strong positive immunoreactivity for epithelial membrane antigen was noted in the cytoplasm in 12 of 13 tumors. Numerous microvesicles, 180~440 nm in diameter, were identified ultrastructurally. DNA aneuploidy was found in 3 out of 10 cases. Neither local recurrence nor metastasis have been identified during the following period of 4~144 (mean 48) months.

Invasive Micropapillary Carcinoma of the Breast: A clinicopathologic study of 16 cases.: Young Kyung Bae, Dong Sug Kim, Mi Jin Kim, Soo Jung Lee; Korean J Pathol. 1999;33(4):267-273.

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Abstract PDF: Invasive micropapillary carcinoma is a recently defined unusual variant of invasive breast carcinoma characterized by the formation of micropapillae within clear spaces separated by delicate fibrocollagenous stroma. This study was designed to examine clinicopathologic features of invasive micropapillary carcinoma of the breast. Sixteen cases of invasive micropapillary carcinoma were retrieved from the files of the Department of Pathology, Yeungnam University College of Medicine. We evaluated their clinicopathologic findings including patients' age, tumor size, nuclear grade, vascular invasion, axillary lymph node status, presence of extensive intraductal carcinoma, estrogen and progesterone receptors, p53, c-erbB-2, MIB-1 labelling index and follow-up data and compared this results with those of 292 cases of invasive ductal carcinoma, not otherwise specified. The incidence of invasive micropapillary carcinoma was 4.2% of all invasive breast carcinoma, and the mean age of the patients was 46 years. Nine cases were pure form (over 75% of micropapillary growth pattern in the tumor) and seven cases were mixed form. The results of clinicopathologic findings, except vascular invasion and axillary lymph node status, of the 16 cases of invasive micropapillary carcinoma were not different from those of the 292 cases of invasive ductal carcinoma, not otherwise specified (p>0.05). However, the rate of vascular invasion and axillary lymph node metastasis was significantly higher in invasive micropapillary carcinoma (p <0.05). Of 16 cases, five cases had distant metastasis during follow-up period, and one patient died of cancer. Although the mechanism of higher vascular invasion and lymph node metastasis in micropapillary growth pattern could not be determined, we propose that invasive micropapillary carcinoma should be recognized as a separate entity with increased risks of vascular invasion and axillary lymph node metastsis.

Original Article

Correlation between Expression of p53 Protein and Prognostic Factors in Meningiomas.: Kyeong Mee Park, Jin Ye Yoo, Hye Jae Cho; Korean J Pathol. 1999;33(4):274-280.

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Abstract PDF: Mutation of p53 tumor suppressor gene is now recognized as the most frequent genetic alteration in human neoplasms. Although meningiomas are common intracranial tumors, little is known about the clinical significance of p53 abnormalities in meningiomas. We studied 31 cases of meningioma to investigate the significance of p53 protein expression in meningiomas and its relationships with histological and clinical parameters and proliferative activity. Classical and atypical meningiomas were 16 (51.6%) and 15 cases (43.4%), respectively. p53 protein expression was detected in 4 (25.0%) of 16 classical, and 12 (80.0%) of 15 atypical meningiomas. p53 protein expression was correlated with Ki-67 staining index, atypical type, high histologic score, sheet pattern of the neoplastic cells, vascular proliferation, and male patient (p<0.05). In conclusion, immunohistochemical evaluation of p53 protein and histologic score of meningiomas are useful in assessing the prognosis.

Case Reports

Spontaneous Pneumothorax as a Complication of Pulmonary Metastasis of Osteosarcoma A case report.: Min Kyung Kim, Bong Kyung Shin, Wha Eun Oh, Ae Ree Kim, Nam Hee Won, Jong Sang Choi; Korean J Pathol. 1999;33(4):281-284.

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Abstract PDF: Spontaneous pneumothorax is a known, but relatively rare complication of pulmonary metastases of sarcoma. A 19-year-old man was presented with chest pain and dyspnea for three days and was diagnosed as left pneumothorax. After bleb resection, microscopic examination revealed metastatic osteosarcoma forming subpleural fistula and dystrophic calcification. Four years ago, he had had limb salvage operation and chemotherapy for osteosarcoma of left femur. After two and a half years he had a bleb resection for right pneumothorax without any evidence of metastasis. Six months later, he was found to have a 4x3cm sized lung mass in the right lower lobe. After lobectomy, he was diagnosed as pulmonary metastasis of osteosarcoma. Pneumothorax is the common complication of metastatic osteosarcoma to the lung and it may be presented before the pulmonary metastasis is clinically evident. It is important to recognize a pneumothorax of the patients with osteosarcoma as a possible sign of metastases.

Primary Pulmonary Hodgkin's Lymphoma: A case report.: Mi Seon Kwon, Kyo Young Lee, Chang Suk Kang, Byung Kee Kim, Sang In Shim, Myeong Im Ahn, Chi Hong Kim; Korean J Pathol. 1999;33(4):285-287.

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Abstract PDF: Primary pulmonary Hodgkin's lymphoma is a rare but distinct entity to be distinguished from nodal Hodgkin's lymphoma and from lymphomas involving lung secondarily. This lymphoma affects women more frequently than men, and typically involves superior portions of the lung. This case is reported to illustrate the clinical, radiographic and anatomic characteristics of the primary pulmonary Hodgkin's lymphoma. A 34-year-old woman presented for the evaluation of hemoptysis. A chest CT revealed a large poorly defined mass in the medial aspect of the right upper lobe, extending to the right mediastinum and trachea. The microscopic examination of the biopsied lesion revealed fibroblastic stroma infiltrated by a mixture of lymphocytes, histiocytes, and eosinophils. The clinical impression was inflammatory pseudotumor, presumably due to slightly favorable response to corticosteroid therapy. Two months later the patient's symptoms worsened despite the steroid therapy and a lobectomy was done. The specimen showed a soft to firm, pale yellow, ill defined mass, 10.0 8.0 cm, involving the visceral pleura. A few satellite nodules around the main mass were noted. The histologic findings were consistent with Hodgkin's lymphoma, nodular sclerosis type.

Herpes Simplex Esophagitis: A report of two cases.: Eun Ha Jung, Hae Kyung Ahn, Jin Hee Sohn; Korean J Pathol. 1999;33(4):288-291.

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Abstract PDF: Herpes simplex esophagitis has been recognized with increased frequency as an opportunistic infection in immunosuppressed or debilitated patients. However, it is also documented as self-limited esophagitis in apparently healthy patients. We report two cases of herpetic esophagitis diagnosed by biopsies. One case was noted in an immunocompetent patient having gastric peptic ulcer who had clinical improvement with symptomatic treatment. And the other was noted in an immunosuppressed patient having chemotherapy for gastric carcinoma who had resolution of symptoms with acyclovir therapy. Histologically, esophageal mucosa exhibited erosion and inflammatory cellular exudate with intranuclear eosinophilic inclusions in the epithelial cells. These were confirmed by the PCR and immunohistochemical stain for herpes simplex virus using a biopsy material.

Necrotizing Vasculitis of the Gallbladder: A case report.: Ah Won Lee, Youn Soo Lee, Seok Jin Kang, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1999;33(4):292-294.

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Abstract PDF: We report a case of necrotizing arteritis involving the gallbladder. This case was clinically diagnosed as cholelithiasis with cholecystitis, and necrotizing arteritis was found in the surgically resected specimen. Vascular changes were similar to those seen in classic polyarteritis nodosa, involving medium-sized muscular arteries and characterized by fibrinoid necrosis and panarterial and periarterial inflammation varying from active to resolving stages. Acute cholecystitis is a rare initial clinical manifestation of the systemic vasculitis. If acute cholecystitis is found in the absence of obvious cause, careful examination is essential. Since steroid therapy improves the prognosis in the systemic vasculitis, clinicians and pathologists should be aware of this unusual lesion.

Solitary Fibrous Tumor of the Scrotum: A case report.: Jung Weon Shim, Jae Y Ro; Korean J Pathol. 1999;33(4):295-298.

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Abstract PDF: Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that usually arises in the pleura and has been recently reported from unusual locations. We present a case of SFT that occurred in the scrotum. The patient was a 38-year-old man who presented with a painless, left, scrotal mass of five years' duration. Scrotal sonography and pelvic CT scan showed a soft-tissue mass of 11 cm in diameter. The resected tumor measured 11 8 7 cm and was well demarcated from the surrounding soft tissue. The cut surface revealed homogenously grayish-white and gelatinous appearance. No hemorrhage or necrosis was found. Microscopically, the tumor showed hypercellular spindle cell areas intermixed with hypocellular areas lying in a myxoid or collagenous stroma. The spindle cells had no mitosis or low mitotic figures, and little or no nuclear atypia. They exhibited a variety of growth patterns, including "patternless" pattern, and a prominent vasculature with hemangiopericytic pattern. Vimentin, CD34, and bcl-2 protein immunoreactivity were observed. Characteristic histologic and immunohistochemical features of this lesion were consistent with SFT. To arrive at a correct diagnosis of this lesion, especially when it occurs in unusual sites, immunohistochemical study including CD34 & bcl-2 protein is required in addition to characteristic histologic features.

Adenoid Cystic Carcinoma of the Breast: A case report.: Eun Ha Jung, Hye Rim Park, Jin Hee Sohn; Korean J Pathol. 1999;33(4):299-302.

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Abstract PDF: Adenoid cystic carcinoma (ACC) of the breast is an uncommon carcinoma accounting for less than 1% of the breast carcinoma. This type of carcinoma has a distinctive histology, such as cylindromatous, cribriform, glandlike space and solid pattern in the variable proportion. Prognosis is favorable with rare recurrence or metastasis and the guideline for therapy is not well established. We experienced a case of ACC of right breast in the 48 year-old woman. Cytologically, it showed numerous three-dimensional, well outlined cell clusters with central core of homogeneous, eosinophilic material. The mass was well demarcated, firm and measured 2.5 2.5 2 cm. Cut surface was yellowish white and granular with focal necrosis. Histologically, the tumor was composed of cylindromatous, adenoid and solid area with marked cellular atypia. Focal invasion was identified in the adipose tissue around the tumor. Histologic and nuclear grade was III by Kleer's grade. Nodal metastasis was not found.

Congenital Fiber Type Disproportion Myopathy: A case report .: Sung Hye Park, Kwang Kuk Kim, Suk Yoon Kang, Shin Kwang Kang; Korean J Pathol. 1999;33(4):303-306.

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Abstract PDF: Authors report a typical case of congenital fiber type disproportion (CFTD) with unique clinicopathologic characteristics. The patient was a 13-year-old boy who presented with weakness of lower extremities, especially proximal muscle, since his infancy. He has suffered from severe scoliosis which got worse since the age of 12. He showed mild dysarthria, high arched palate, and fish face. All routine laboratory data were within normal limits. EMG findings suggested myopathy. The muscle biopsy revealed fiber type disproportion with type 1 predominance. While most of the type 1 myofibers were atrophic or normal in size, the type 2 fibers showed universal hypertrophy. The difference of mean diameter between the larger and the smaller fibers was 27.9%. The patient's clinicopathologic settings fulfilled the criteria of CFTD.

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