Myunghee Kang, Seung Yeon Ha, Joung Ho Han, Mee Sook Roh, Se Jin Jang, Hee Jin Lee, Heae Surng Park, Geon Kook Lee, Kyo Young Lee, Jin-Haeng Chung, Yoo Duk Choi, Chang Hun Lee, Lucia Kim, Myoung Ja Chung, Soon Hee Jung, Gou Young Kim, Wan-Seop Kim
Received April 4, 2018 Accepted July 9, 2018 Published online July 16, 2018
Sang Hwa Lee, Wan Seop Kim, Yoo Duk Choi, Jeong Wook Seo, Joung Ho Han, Mi Jin Kim, Lucia Kim, Geon Kook Lee, Chang Hun Lee, Mee Hye Oh, Gou Young Kim, Sun Hee Sung, Kyo Young Lee, Sun Hee Chang, Mee Sook Rho, Han Kyeom Kim, Soon Hee Jung, Se Jin Jang, The Cardiopulmonary Pathology Study Group of Korean Society of Pathologists
J Pathol Transl Med. 2015;49(6):481-488. Published online October 13, 2015
Background Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. Methods: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. Results: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. Conclusions: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.
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BACKGROUND Telomerase activity in precancerous conditions of lung adenocarcinomas has not been well studied. This study is designed to investigate the role of telomerase in premalignant lesions of urethane-induced mouse lung adenocarcinoma. METHODS We harvested A/J mouse lung tissues at 3, 6, 9, 12, 28, 41, and 48 weeks after intraperitoneal urethane treatment, and classified each lesion in terms of histologic findings. We examined telomerase activity using a modified version of the telomeric repeat amplification protocol assay using both gel-based and enzyme linked immunosorbent assay methods. An immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) was performed. RESULTS In urethane-induced mouse lung tissues, it was sequentially developed from hyperplasia, adenoma, and eventually to adenocarcinoma. Telomerase activity began to show a positive level in tissues with no histologically visible nodule after urethane administration. It revealed a statistically significant increase in hyperplasia compared to the "control" lung tissue (p<0.05), which was proportionally elevated relative to adenoma and adenocarcinoma. There was a direct correlation between telomerase activity and the PCNA labeling index (p<0.05). CONCLUSIONS The elevation of telomerase activity in normal-appearing lung lesions is thought to be a possible marker of early detection of pulmonary adenocarcinoma.
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Thirty cases of rhabdomyosarcoma in patients under the age of 15 years were reviewed retrospectively to find out characteristics of histologic subtypes related to prognosis.
Histologic diagnosis were embryonal in 21(70%), alveolar in 7(23%) and mixed type in 2(7%). Cellular anaplasia was noted in 6 cases. Round to polygonal cells with abundant eosinophilic cytoplasmic rim or globules were most characteristic cytologic feature or rhabdomyosarcomas, being followed by myofibrils. Myxoid and edematous stroma in embryonal type and alveolar pattern in alveolar type wee nost characteristic growth pattern. Immunohistochemically, tumors were positive for desmin, actin and myoglobin in 97%, 27%, and 40%, respectively. Consequently, characteristic cytologic features are important to differentiate rhabdomyosarcomas form other kinds of small round cell tumor and growth pattern is more critical in categorizing histologic subtypes. Desmin is far more useful than actin or myoglobin in the diagnosis of rhabdomyosarcoma.
Kupffer cells are tissue macrophages (histiocytes) fixed in hepatie sinusoids. Since malignant hepatocytes are the only tumor parencymal cells of the hepatocellular carcinoma, theoretically there are no Kupffer cells within the hepatocellular carcinoma. To clarify whether it is true or not, 12 cases of hepatocellular carcinoma of the trabecular type with some extents of the non-neoplastic surrounding liver were subjected to immunoperoxidase staining for lysozyme and S-100 protein and the results are as follows.
1) Kupffer cells were stained positively by the immunoperoxidase staining for lysozyme but not for S-100 protein, indicating that they are monocyte derived macrophages. 2) Kupffer cells were also present within the hepatocellular carcinoma, but were 2-7 times fewer within the hepatocellular carcinoma than in the non-neoplastic areas (p<0.05). 3) The non-neoplastic hepatic tissue of patients with serum HBsAg shows a tendency to have more kupffer cells than those without HBsAg.
The cytologic findings in fine needle aspiration of a case of myxoid liposarcoma of the mediastinum are described. The smear and cell block of the aspirate revealed solid clusters with background of amorphous material and scattered single tumor cells. The clusters were moderately cellular and consisted of atypical lipoblasts in varying stages of differentiation and delicate plexiform capillaries. Good correlation was found between the histologic and cytologic findings in the fine needle aspirates. The differential diagnosis between myxoid liposarcoma and other myxoid soft tissue tumors is discussed.
Five cases of ovarian serous borderline tumor associated with multiple peritoneal implants were analysed. The age of 5 patients ranged from 34 to 45(mean: 39) years at the time of diagnosis. Two patients presented with secondary infertility underwent hyperstimulation of the ovary under the in vitro fertilization program. One patient was presented with abdominal pain and the remaining two with lower abdominal mass accompanied by abdominal pain. Serous surface papilloma of borderline malignancy, involving one or both ovaries, was present in all 5 cases and papillary serous cystic tumor of borderline malignancy was associated simultaneously in one or both ovaries in all cases. Marked adhesions between the pelvic organs, and multiple granularities and nodularities of the omentum and peritoneum were noted. Microscopically, the peritoneal lesions were composed of noninvasive implants of tumor cells and pasmmoma bodies on the surface of entire pelvic and abdominal organs.
Flow cytometric analysis of nuclear DNA content from paraffin-embedded tissue fo primary ovarian tumor classified as aneuploidy in 3 cases and as diploidy in 2 cases. The DNA index of the aneuploid tumors ranged from 1.21 to 1.37. Four patients underwent hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy in which two were followed by chemotherapy and one case underwent bilateral salpingo-oophorectomy.
To obtain a useful method for the identification of mycobacteria in tissue section, we evaluated 118 cases of tuberculosis: 48 pulm onary, 14 lymph nodal and 56 synovial tuberculosis. Seventy nine of these cases underwent the culture study. Sections stained with anti-Mycobacterium bovis were compared with the results of the Zieh1-Neelsen stain and culture. The immunohistochemical stain for Mycobacterium bovis in al examined cases was not any more sensitive than the Zieh1-Neelsen stain(p>0.05). Neverthless, the immunohistochemical stain was a useful method for the localization of mycobacteria because of the striking contrast between its background and the wider dimension of a positive area. Immunoreactive areas demonstrated a few intact mycobacteria showing a positive reaction in the Zieh1-Neelsen stain. In conclusion, double staining method using the immunohischemical stain for Mycobacterium bovis and the Zieh1-Neelsen stain is an efficient technique in oder to confirm the diagnosis of tuberculosis.
To evaluate the correlation between the histologic grade and DNA ploidy or proliferation index/S phase fraction (SPF) of gastrointestinal stromal tumors, we performed the DNA analysis using the flow cytometry. Paraffin embedded tissue samples of 57 gastrointestinal stromal tumors were used. The sites of the tumors were: stomach (28), small intestine (23), and large intestine(6). DNA index, proliferative index, and SPF by the flow cytomery were compared with histologic grade. The histologic grade of the gastric tumors were benign (12), borderline (10), and malignant (6). Those of the small intestinal timors were benign (2), borderline (13), and malignant(8). The large intestine were borderline (2), and malignant (4). In stomach, aneuploidy was found in 25.0% of benign, 40.0% of borderline, and 100% of malignant.
And there was statistically significant correlation between the histologic grade and ploidy (p < 0.05). By contrast, small and large intestinal tumors showed more frequent aneuploidy in benign than in malignant. The proliferative index was correlated with the histologic grade in gastric tumors (p<0.05), but the SPF was not. In conclusion, the ploidy and proliferative index of gastric tumors are closely correlated to the histologic grade. However, aneuploidy in tumors of the small and large intestine were difficult to predict the malignancy.
The authors attempted to choose what has the best reproducibility and predictability for prognosis of the prostatic adenocarcinoma among four most widely used gradings methods; the Gleason's Mostofi's, Bocking and MD Anderson hospital systems. According to these gradings systems, each of two pathologists made histologic gradings of 40 consecutive prostatic adenocarcinomas which had been diagnosed with the surgically resected specimens.
Correlation between the histological grades and the clinical stages was studied and a comparison was made among each system. For the comparison, the Gleason's and MDAH systems were revised as 3 grades and adjusted to the other gradings systems. In this study, MDAH grading system yielded the highest reproducibility as represented by 90% agreement, as compared with the other systems which showed 82.5~87.5% agreement. By the Gleason's, Mostofi's and Bocking's systems, 46.2%, 23.1% and 46.2% of grade 3 tumors respectively fell under the clinical stage A. On the contrary, there were no cases of grade 3 in stage A and no cases of grade 1 in stage D, by MDAH gradings system. These results suggest that MDAH gradings system is superior to the other systems in reproducibility and for predicting the biological behavior.
We report a case of primary cardiac angiosarcoma in a 35 year-old woman. She presented with dyspnea, facial edema and neck vein distension during 1 month. The oval round large mass(8x4 cm) filling the right atrium infiltrated into the entire thickness of the lateral wall and extended to the vena cava and ventricle. The interatrial septum and pericardium seemed to be intact. Despite the surgical excision and adjuvant chemo-and radiotherapy, the patient died 8 months later due to tumor recurrence. The histologic findings of tumor varied from benign looking capillary proliferation mimicking granulation tissue to sarcoma composed of spindle cells. But anastomosing vascular channels lined by anaplastic polygonal cells and intracytoplasmic lumen containing red blood cells were characteristic findings. These tumor cells showed positive reaction to endothelial cell antigen and factor VIII-related antigen. The intercellular junctional complex and vascular channels formed by cytoplasmic process of tumor cells were identified by the ultrastructural study.
Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.
Cardiac myxoma is the most common primary tumor of the heart. The tumor contains a variety of cell types that are thought to arise from a focus of primitive pluripotential mesenchymal cells in the area of the fossa ovalis.
Throughout the myxoid stroma, there are variable amounts of reticular fivers, collagen, elastic fibers and smooth muscle cells. A 38-year-old female had right atrial myxoma with multiple pulmonary infarcts. In this case, we experienced an unusual degenerative change in the tumor of granulomatous lesion consisting of hemosiderin pigments, foreign body giant cells and peculiar, spheroid, semilunar or bamboo-shaped degenerated elastic fibers. Microscopically it resembles Gamna-Gandy nodule seen in the spleen of chronic passive congestion.
Choriocarcinoma of the gastrointestinal tract is rare. Among them, that of the stomach is the most common. Six cases of choriocarcinoma of the colon were found in the review of the literature. All of these previously reported cases had multiple metastatic foci in the liver, lung, lymph nodes and the prognosis seemed to be very poor. Therefore we think that choriocarcinoma of the colon should be distinguished from conventional adenocarcinoma. A 66-year old female patient, described in this case, was operated on under the impression she was suffering from acute appendicitis. The resected ascending colon revealed extensive hemorrhagic necrosis and perforation with fibrous adhesion in the cecum.
On the cut section, the mural tumorous thickening was not definite. Histologically, the tumor showed a focus of typical adenocarcinoma arising from glandular epithelial cells, which were transformed into highly anaplastic tumor cells. There were frequent vascular invasions of tumor cells, similar to syncytiotrophoblasts. In the immunohistochemical stains, both glandular and highly anaplastic tumor cells reacted with cytokeratin. The glandular cells were also reactive for carcinoembryonic antigen (CEA) and anaplastic tumor cells for human chorionic gonadotrophin (hCG). This is the first report of choriocarcinoma of the colon in Korea. We describe this case with a review of the literature.
Pulmonary metastatic angiosarcoma usually reveals multiple nodular lesions associated with parenchymal hemorrhage. It is presented, in rare cases, as multiple emphysematous cystic lesions, complicated by pneumothorax. We experienced a case of pulmonary metastastasis from angiosarcoma of the scalp in a 58-year-old male showing multiple thin-walled emphysematous cystic lesions. The tumor cells spread along the subpleural and interlobular septa, focally surrounding the cystic lesions. This case suggests that a rare metastatic pattern seen in angiosarcoma of the scalp should be considered as a differential diagnosis of bullous emphysematous lesion.
Ovarian endometrioid adenofibroma is rare and characterized by prominent stroma. Its histologic classification is controversial but the malignant counterpart is distinguished from the borderline by the presence of confluent growth pattern of epithelium with invasion of the stroma by the endometrioid cells. A fifty-year-old woman was admitted with one month history of abdominal enlargement. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed under the clinical diagnosis of ovarian malignancy. Grossly, the righy ovary had round, encapsulated, solid and whitish gray mass which measured 9 cm in the greatest dimension and showed peripheral small cysts. Microscopic examination revealed that the tumor consisted of endometria type glands set in fibrous stroma.
The glands varied from tubules to cysts and the lining cells showed complicated architectural pattern with occasional papillary infoldings, atypical mitosis and malignant nuclear characteristics. Some cysts of glands showed intraluminal mucin products. Stromal invasions by individual epithelial cells showing malignant characteristics were often found. A brief summary of the histopathologic aspect of this tumor is presented together with review of literatures.
Apocrine carcinoma of the breast is a very rare subtype.
Although it has no clinical differences from usual ductal carcinoma of the breast, it should be categorized as a subtype of breast carcinoma because the cells of apocrine carcinoma reveal characteristic abundant eosinophillic cytoplasms with intraductal apical snouting as well as round or oval nuclei and central macronucleoli. On fine needle aspiration cytology, the cells of apocrine carcinoma have a lot of similarity to benign or reactive apocrine cells of the breast. Therefore, it is difficult to make a differential diagnosis of apocrine carcinoma from mammary neoplasms with similar cytologic findings unless the subtle cytologic differences are recognized. We report the cytologic and histologic findings of a case of apocrine carcinoma in the breast of a 40-year-old female patient.
After the fine needle aspiration cytology, she received the lumpectomy and lymph node dissection. The cellularity was moderate to high. The cytoplasmic borders of tumor cells of three-dimensional clusters were relatively distinctive, and the cytoplasm was abundant, eosinophilic, and granular.
Although the nuclear/cytoplasmic ratio was low, the nuclei of the cells were variable in size and shape with prominent macronucleoli. Histologically, it was a typical invasive apocrine carcinoma, showing numerous cytoplasmic lysosomes and mitochondriae on electron microscopy.
Although the histologic grade of astrocytic neoplasms of the brain have been used as a prognostic factor, the lack of an objective criteria is possible to create the disagreement of classification. We evaluated 25 cases of astrocytic neoplasms of brain to document the usefulness of prolifera-tive potential of tumor as a prognostic indicator and the correlation with histologic grade by Nils Ringertz.
The Ringertz's classification was relatively simple in an application among the variable systems and easy to define the differentiate from grade to grade. The examined cases were com-prised of 7 astrocytomas, 9 anaplastic astrocytomas and 9 glioblastoma multif6rmes. The prolife-rative potential of tumors were measured by Ag-NORs count, PCNA labeling index and flow cytometric analysis. The mean numbers of Ag-NORs per cell and PCNA labeling index were sig-nificantly differ among each histologic grade. In addition, abnormal DNA content and high prolif-erative index were frequently identified in anaplastic astrocytoma and glioblastoma multiforme. Therefore, the Ag-NORs counts, PCNA labeling index, DNA index and proliferative index were well correlated with the histologic grade.
So called pseudosarcoma of the esophagus is an extremely rare polypoid malignant tumor and a number of cases, totaling 19 cases have been reported in world literatures until 1985. The presenting case is an unique one of pseudosarcoma of the esophagus and we illustrated all microscopic features with mapping, immunoperoxidase stain for cytokeratin and electron microscopic findings to clarify the histogenesis of spindle cells. It is postulated that the spindle cells of pseudosarcoma are transformed from squamous carcinoma cells based on (1) morphological similarity between squamous epithelial cells and spindle cells, (2) positive reaction of immunoperoxidase staining for cytokeratin in the adjacent normal esophageal mucosa, squamous cell carcinoma, spindle cells and giant cells and (3) presence of transformation zone.
The present study is aimed to investigate the clinical and pathologic features of GI lymphomas and the immunocytochemical characteristics, using 71 cases of primary GI lymphomas examined at the Department of Pathology, Yonsei University College of Medicine, Youngdong Serverance Hospital and Yonsei University Wonju College of Medicine from January, 1976 to December, 1985. Results obtained were as follows: 1) Sixty eight cases were Non-Hodgkin's lymphoma and 3 Hodgkin's lymphoma. Surgical resection was done in 58 patients and surgical biopsy in 13.
2) The primary sites of the tumors were stomach, small intestine, ileocecal area and large intestine in a descending order of frequency. 3) The mean age at the time of diagnosis was 45 years. The tumor of the small intestine was generally detected in the younger age and that of the large intestine in the older age. The overall male to female ratio was 1.9 : 1. 4) Abdominal pain was the most common presenting symptom irrespective of the sites of the tumor.
Duration of the symptoms were evenly distributed from hours to 12 monthes. 5) The size of the tumors was less than 10 cm in the largest dimension in most of the cases (79.3%). The gross types of the GI lymphomas were ulcerative (27.6%), polypoid (20.7%), multinodulated (17.2%) and diffuse thickening. The rate of lymph node involvement was 44.4% in tumors confined to the serosa, while 82.6% in tumors with serosal penetrations. 6) Classification of 68 cases of Non-Hodgkin's lymphoma according to Working Formulation revealed 50 cases of intermediate grade, 13 cases of high grade and 5 cases of low grade. According to Rappaport classification, all were diffuse types, among which diffuse histiocytic type was the most common. According to Lukes-Collins classification, 60 cases were B cell types, 4 cases genuine histiocytes types and 3 cases T cell types.
Most of the gastric and intestinal lymphomas belonged to the follicular center cell (small and large cleaved, large cleaved) types. 7) Immunoperoxidase stains were done in 55 cases of malignant lymphomas. Thirty (65.9%) of 47 B cell lymphomas revealed a positivity for B cell markers. Twenty three (48.9%) of them showed a monoclonality, in which kappa/IgG pattern was most frequently demonstrated. Four cases of true histiocytic lymphomas were positive for alpha-1-antichymotrypsin and lysozyme, the former of which was seemed to be a more sensitive marker for histiocytic differentiation. An attempt was made to evaluate the significance of the degree of reactive histiocytic infiltrates within the lymphoma in relation to the progosis, but correlation could not be made because of the limited cases.
A case of diffuse malignant mesothelioma of peritoneum which was difficult to distinguish from metastatic anaplastic carcinoma or malignant melanoma was presented. The patient was a 50 year-old woman and complained of an abdominal pain and ascites for 20 days. Histologically, the tumor cells showed highly anaplastic appearance with sheet-like arrangement without any papillary or tubular structure. They stained Positive for cytokeratin and vimentin and negative for CEA, S-100 protein and melanoma associated antigen. A few cells within the tumor showed Positive reactivity to desmin. Ultrastructurally, the tumor cells had characteristic findings of mesothelioma such as long, exuberant, wavy microvilli with 10 to 12 of length/diameter ratio. The patient died 3 months after the diagnosis in spite of intraperitoneal chemotherapy.
BACKGROUND The anaphase promoting complex (APC) promotes the degradation of mitotic cyclins as well as other substrates involved in sister chromatid adhesion. This study was carried out to examine the relationship between the APC expression and the clinicopathological variables, in an attempt to determine the role of the APC in the proliferation of lung cancer and to evaluate the possibility of an aberrant APC function in surgically resected squamous cell carcinomas and adenocarcinomas of the lung. METHODS Immunohistochemical staining was performed for APC, Ki-67, cyclin B1, Cdc2, MMP-2 and VEGF in 55 cases of squamous cell carcinoma and 34 cases of adenocarcinoma of the lung, using the avidin-biotin-peroxidase method. RESULTS The immunohistochemical stains for APC revealed a positive reaction in 49 cases (55.1%). The APC expression level was higher in the cyclin B1-positive group (p= 0.01), the Cdc2-positive group (p=0.001), the MMP-2-positive group (p=0.03), the group with lymph node metastasis (61.4% vs 48.9%), and the group with stage II/III cancer (60.7%) compared with those with stage I (42.9%). CONCLUSIONS The APC may have an aberrant function, such as a change in its role in controlling the cell cycle, and might be associated with the invasiveness and proliferation of tumor cells.
As flow cytometric analysis using paraffin-embedded tissue was developed by Hedley et al in 1983, retrospective study with large amount of archival material was possible. Many literatures reported that the result of paraffin embedded tissue was compatible with that of fresh tissue. We compared the DNA histograms of 26 cases of colorectal adenocarcinoma in which the analysis was done in both fresh and paraffin-embedded tissues. Aneuploidy in fresh and paraffin-embed-ded tissues was 73.0% and 50.0%, respectively. The concordance rate of fresh and paraffin-em-bedded tissues was 76.8% and six interpreters were agreed in 73.0% of the cases. Because flow cytometric DNA analysis using fresh tissues can detect more aneuploid population than in paraffin-embedded tissue, the former is strongly recommeded in DNA ploidy study. Also careful observation using standard criteria may improve the interpretation of DNA histogram.
BACKGROUND The role of the anaphase-promoting complex (APC) is to promote the degradation of mitotic cyclins and other substrates involved in sister chromatid adhesions. The APC appears to be responsible for the degradation of cyclin B and may have a potential role in the loss of control concerning cell proliferation in mammalian cells. However, a direct link between the defects in the APC components and oncogenesis has not been estabilished. This study investigates the relationship between APC expression and variable prognostic factors in invasive ductal carcinoma of the breast. METHODS We evaluated 108 cases of invasive ductal carcinoma surgically resected from January, 1996 to May, 2000 at Wonju Christian Hospital, Wonju College of Medicine, Yonsei University. Immunohistochemical stains for APC, estrogen receptor, and Ki-67 were done in paraffin sections using the avidin-biotin complex method. The results were compared with clinical and pathologic parameters and flow cytometric DNA analysis factors. RESULTS Forty cases (37.0%) showed immunopositive reactions for APC. The APC positivity in histologic grades 1, 2, and 3 were 28 cases (84.4%), 33 cases (60.0%), and 7 cases (35.0%), respectively (p=0.0011). The APC expressions in cases with the number of mitosis of less than 10, 10-19, and more than 20 per 10 high power fields, were noted in 37 cases (75.5%), 26 cases (63.4%), and 5 cases (27.8%), respectively (p=0.0016). The mean value of the Ki-67 labeling index was 221.7 in the APC-positive group and 317.9 in the APC-negative group (p= 0.0091). DNA flow cytometric analysis revealed higher APC expressions in cases with diploid patterns (p=0.0095). The APC expression rate increased significantly with decreasing histologic grade, with decreasing mitotic activity, in cases with a low Ki-67 labeling index, and those in the diploid group (p<0.05). The APC expression was not statistically correlated with clinical stage, tumor size, and estrogen receptor status. CONCLUSIONS These findings suggest that positive APC expression may be considered as a good prognostic factor of invasive ductal carcinoma, and loss of APC expression may be related with the progression of breast cancer.
Non-Hodgkin's malignant lymphoma is a relatively frequent lymphoreticular malignancy, and has been reported to constitute up to 5.2% of all malignant tumors in Korean patients. Various morphologic classifications of non-Hodgkin's lymphoma have been proposed, and among them, the Rappaport's classification has been most widely accepted. In 1982, a National Cancer Institute sponsored study on classification led to the creation of the Working Formulation in an attempt to resolve the controversy anddebate regarding the various classifications of non-Hodgkin's lymphoma. Angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis are lymphoreticular proliferative disorders which have reported to transform to malignant lymphoma. The purpose of the present study is to reclassify non-Hodgkin's lymphomas according to the Working Formulation and to investigate the histopathological and immunocytochemical characteristics of angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis. This study reviewed 300 cases of nodal and extranodal non-Hodgkin's lymphoma, 26 cases of polymorphic reticulosis, and 7 cases of angioimmunoblastic lymphadenopathy with dysproteinemia examined in the Departments of Pathology, Yonsei University College of Medicine, Youngdong Severance Hospital and Yonsei University Wonju College of Medicine from January 1977 to December 1986. In non-Hodgkin's lymphoma, each case was classified according to the Working Formulation and the Rappaport classification. All angioimmunoblastic lymphadenopathy with dysproteinemia and polymorphic reticulosis cases were subjected to histopathological analysis and a review of the clinical records. Immunocytochemical studies were done using kappa and lambda chains for B-cell markers and alpha-1-antichymotrypsin for histiocytic marker. The results obtained were as follows; 1) Among 300 cases of non-Hodgkin's lymphoma, the primarily involved tumor sites were the lymph nodes (141 cases), the gastrointestinal tract (67 cases), and the tonsils (32 cases) in descending order of frequency. 2) Using the Working Formulation, intermediategrade lymphomas occurred in 66.4% of the patients, and the most common subtype was "diffuse, large cell" (32.7%). By the Rappaport classification, 3 patients had nodular lymphomas, and "diffuse, histiocytic" was the most common subtype. 3) Infarction was present in 32 cases in which the "diffuse, lagre cell" type was most frequently associated. 4) In immunoperoxidase stains of 7 cases of angioimmunoblastic lymphadenopathy with dysproteinemia, proliferating immunoblasts revealed a polyclonal positivity for kappa and lambda chains. Atypical reticulocytes present in 26 cases of polymorphic reticulosis revealed a negativity for kappa, lambda and alpha-1-antichymotrypsin.
Angiosarcoma of the bone is rare with an incidence of 0.13%.
It may be solitary or multiple. Its cytologic findings by FNA have rarely been reported. We report a case of angiosarcoma of the rib in a 66 year-old man. FNA revealed single or clusters of round to oval shaped cells in a hemorrhagic and myxoid background. The large central nuclei had irregular nuclear membrane, chromatin clumping and prominent nucleoli. The cytoplasm was scanty with an eosinophilic distinct cytoplasmic border.
Erythrophagocytosis by malignant cells was also found.
Histopathologic examination confirmed the diagnosis of angiosarcoma revealing irregular and com- plex anastomosing vascular channels lined by malignant round tumor cells, protruding into the lumen. Immunohistochemical staining revealed diffuse strong positive reaction to factor VIII-related antigen and CD31.
This study was undertaken to elucidate the short-term effect of iron on the hyperplastic lesions of experimental hepatocarcinogenesis. The Solt-Farber's resistant hepatocyte model was chosen for the experiment, and Sprague-Dawley rats wee divided into six groups: normal control, iron-rich diet administration with or without hydroxyquinoline. The iron content, microscopic changes, bromodeoxyuridine(BrdU) labelling index and the DNA polidy were studied. In the carcinogen administered group, oval cell proliferation and consecutive hyperplastic lesions of hepatocyte developed regardless of iron administration. The hepatic iron content was increased rimarkably by iron administration, but gradually decreased as the hyperplastic lesions developed in carcinogen administered groups. Although the administration of iron without carcinogen induced hepatic accumulation of stainable iron, the hyperplastic lesions appeared to be lack of it. BrdU labelling indices of the oval cells and the hyperplastic lesions of hepatocyte were very high and were not significantly altered by iron administration. Most liver cells had diploid or tetraploid DNA content, but there was an increase of diploidy as the development of hyperplastic lesions regardless of iron administration. The results indicate that the chemical carcinogen-induced hyperplastic lesions of hepatocyte do not accumulate iron, and that short-term iron administration does not affect the development of hyperplastic lesions and their proliferative activity and DNA ploidy.
Immunohistochemical analysis of 24 paraffin-embedded osteosarcomas was studied to evaluate the expression of simple cytokeratin, basal cytokeratin and epithelial membrane antigen(EMA) according to the histologic subtypes and anatomical locations. Mean age of the patients was 18 years. Anatomical locations of the tumors were femur(8), tibia(10), humerus(4), lumbar spine(1), and zygomatic arch(1). Histologic subtypes included osteoblastic(14), fibroblastic(4), chondroblastic(4), epithelioid(1), and mixed osteoblastic and fibroblastic(1). All were positive in the immunohistochemical stain for vimentin. The expression of cytokeratin and/or EMA was found in 10 cases(41.7%) regardless of anatomical locations and histologic subtypes.
Positive immunoreaction for EMA was demonstrated in osteoblastic(5), chondroblastic(2), epithelioid(1), and mixed osteoblastic and fibroblastic(1) types. Osteoblastic (2), chondroblastic(2), and epithelioid(1) types among them also showed immunoreactivity with anti-simple cytokeratin monoclonal antibody, NCL-5D3. The expression of basal cytokeratin (NCL-LL002) was found in two osteoblastic, one chondroblastic, one epithelioid, and one mixed osteoblastic and fibroblastic types. These findings indicate that cytokeratin and EMA immunoreactivity can not be regarded as an absolute specific marker of the epithelial origin of tumor and may also occur in osteosarcoma.
A case of cervical chordoma diagnosed by fine needle aspiration is discussed. A 41year-old male was admitted due to dyspnea on neck flexion. Radiologic image revealed a retrotracheal superior mediastinal solid mass. Aspiration cytology showed many clusters of oval or large polygonal cells having abundant eosinophilic or bubbly cytoplasm in an amorphous blue-gray mucoid background. The nuclei were round and showed size variation, coarse granular chromatin, and indistinct nucleoli. Some cells contained brown granular pigments in the cytoplasm. Mitoses were rarely found. The cytoplasm was strongly positive for PAS stain.
Immunohistochemical stains using cell block revealed positive reaction for cytokerain, EMA, vimentin, and S-100 protein. The confirmative diagnosis was made by following excisional biopsy. Electron microscopic study revealed large pools of intracytoplasmic glycogen and microfilaments. This is the first case of cervical chordoma diagnosed by aspiration cytology to our knowledge in Korean literature.
Inflammatory myofibroblastic tumor, also known as inflammatory fibrosarcoma, has been frequently diagnosed as inflammatory pseudotumor. Although there are six cases reported as inflammatory pseudotumors or inflammatory myofibroblastic tumors in the lung, no cases of pulmonary inflammatory myofibroblastic tumor with features of inflammatory fibrosarcoma have been reported in Korea. We experienced a case of inflammatory myofibroblastic tumor (inflammatory fibrosarcoma)characterized by high cellularity, severe nuclear pleomorphism, necrosis, or increased mitoticcounts. A 31-year-old male patient with a solitary pulmonary nodule on the routine chest x-rayreceived a right lower lobectomy. The tumor was an ovoid solid mass with multifocal necrosis, showing diffuse irregular proliferation of spindle cells with high cellularity and focal nuclear pleomorphism, admixed with dense lymphoplasmacytic cells. Although spindle cells are focally immunoreactivefor smooth muscle actin, the ultrastructural examination failed to demonstrate smooth muscledifferentiation. In cases of inflammatory myofibroblastic tumor (inflammatory fibrosarcoma), a completeexcision and close follow-up without radical surgery, radiation, or chemotherapy are needed.
We present an autopsy case of signet ring cell carcinoma of urinary bladder which underwent widespread metastsis through nearly entire organ. The patient, 45-year old male, suffered from hematuria, dysuria and flank pain for 6 months. Under the diagnosis of the signet ring cell carcinoma by the cystoscopic biopsy, radical cystectomy and ileocutaneous ureteral division were performed. But he died after 11-months after the diagnosis. The autopsy confirmed the widespread metastasis at the lung, kidney, adrenal gland, parathyroid gland, heart, stomach, ileum, spine, rib and meninges. The preveously resected urinary bladder discolosed the well defined fungating mass at the dome and anterio-lateral portion without apparent evidence of the remnant of the urachus. Histologically, the signet ring cells were predominent and focally mucinous pool floating the signet ring cells was noted. We could find several foci of the well differentiated adenocarcinoma and poorly differentiated adenocarcinomas. The above findings may reflect that the origin of carcinoma may be from the multipotential transitional cell epithelium.
Neuroblastoma, ganglioneuroblastoma and ganglioneuroma are derived from primordial neural crest cells and can be conceptualized as three different maturational manifestations of a common neoplasm. To assess the validity of immunohistochemistry and DNA Ploidy in the diagnosis of neuroblastic tumor in terms of prognostication, histologic and immunohistochemical evaluation with NB-84, neuron specific enolase(NSE) and S-100 protein and flow Cytometric DNA analysis were done on 21 neuroblastomas and 19 ganglioneuromas. Thirteen of 21 neuroblastomas were undifferentiated and 8 differentiating in type. Eleven of the 19 ganglioneuromas were mature in type and 8 had immature foci. Eighty one percent of neuroblastomas were positive for NB-84, 100% for NSE and 67% for S-100 protein, respectively. All ganglioneuromas were positive for NSE and S-100 protein, in contrast, only immature foci in ganglioneuroma were positive for NB-84. B-84 reacted positively with undifferentiated and differentiating neuroblasts including neuropil but not with mature ganglion cells. In contrast, NSE reacted positively with all components of neuroblastic tumor and S-100 protein mainly with cells of Schwannian differentiation. Three of eight(37.5%) differentiating neuroblastomas were strongly positive for NB-84 in contrast with seven of thirteen(53.8%) undifferentiated tumors, reflecting that undifferentiated cells tended to be positive for NB-84 in neuroblastoma.
Twenty two percent of neuroblastoma showed diploidy and 78% aneuploidy including 11% of near-diploidy. Seven of eight(87.5%) differentiating neuroblastomas in contrast with seven of ten(70%) undifferentiated tumors showed aneuploidy.
By contrast, 53% of ganglioneuroma showed diploidy and 47% aneuploidy with DNA index ranged from 1.12 to 1.19. Three of nine(33.3%) mature ganglioneuromas in contrast with five of eight(62.5%) ganglioneuromas with immature foci showed aneupolidy. Differentiating neuroblastoma tended to be aneuploid and ganglioneuroma with immature foci tended to be near-diploid. In conclusion, immunohistochemistry for NB-84, NSE and S-100 protein is useful for confirming neuronal, both neuronal and Schwannian, and Schwannian differentiation, respectively. Immunohistochemistry together with flow cytometric DNA analysis would be helpful to confirm the immature foci in ganglioneuroma.
The prognosis of malignant ovarian tumor is poorer than that of borderline malignant ovarian tumor, Therefore an accurate diagnosis and estimation of the biologic behavior of the tumor are necessary for proper management of the patient.
The histologic investigation of the tumor may provide information on the estimation of the malignant potential of tumor cells, but it may be a questionable method because of the subjective determination of tumor grade. Quantification of proliferative activity of tumor cells may play a role as an objective method to provide an estimation of the malignant potential of tumor cells. An evaluation of histologic findings was done on 84 cases of ovarian mucinous and serous tumors that were surgically resected and diagnosed during the period from January 1981 through July 1992. The proliferating cell nuclear antigen (PCN A) labelling index estimated from the immunohistochemical stain for PCN A and the Sphase fraction and porliferative index obtained from flow cytometric DN A analysis were assessed each other with histologic findings. The results are as follows: The presence of aneuploidy in malignant tumors was statistically significant as compared with benign tumors.
The borderline malignant tumors showed no significant difference between the number of diploidy and aneuploidy.
The PCNA labelling index, S-phase fraction and proliferative index tended to increase as the histologic grade of tumors went up. They were higher in malignant tumors than in others. The PCN A labelling index, S-phase fraction and proliferative index were higher in tumors with aneuploidy than in those with diploidy. In contrast to borderline malignant tumors, the PCNA labelling index in malignant tumors revealed a significant relation with the mitotic index. The S-phase fraction and proliferative index showed, in malignant tumors, a close correlation with the architectural grade and nucleolar grade, but not in borderline malignant tumors. Considering these results, the presence of aneuploidy, PCNA label.
A pathological study was performed on four cases of infantile hemangioendothelioma of the liver. All the patients were between the age of 1 -5 months and the tumors were typical hemangio-endotheliomas, type 1. The tumors were composed basically of two components; the endothelial cell proliferation and the myxoid matrix. The endothelial cells were cytologically innocuous and formed vascular channels of varying sizes and shapes from capillary to sinusoidal and cavernous vessels. Fibrosis of the matrix, albeit not a major component of the tumor, was found particularly near the center. Immunohistochemically, CD31 was expressed strongly in almost all endothelial cells, in contrast to the stain for von Willebrand factor which was only focally and weakly positive. Alpha-fetoprotein was expressed in hepatocytes within the tumor or in hepatocytes around the tumor. Intratumoral bile duct structures were located mainly at peripheral portion. The results indicated that the type I infantile hemangioendothelioma is a tumor of endothelial cells and myxoid stroma, and that the endothelial cells undergo gradual maturation to form sinusoidal and cavernous vessels in accordance with gradual fibrosis of the myxoid stroma.
E-cadherin is a calcium-dependent epithelial adhesion molecule which plays a role in the initial step of invasion of cancer cells. The step that follows the migration of separated tumor cells is a proteolytic lysis of basement membrane and extracellular matrix by protease of epithelial and endothelial cells such as matrix metalloproteinase (MMP). Vascular endothelial growth factor (VEGF) is known to be an endothelial cell-specific powerful mitogen as well as a vascular permeability factor. This study is aimed to evaluate the correlation between expression of these factors and pathologic or clinical variables and the roles and prognostic significance of those factors in squmous cell carcinoma and adenocarcinoma of the lung.
Immunohistochemical stains were performed for E-cadherin, MMP-2, and VEGF in surgically resected specimens from 90 patients with squmous cell carcinoma and adenocarcinoma of the lung. Mean age of the patients was 59.7 years. Histologic type was categorized into 56 cases of squamous cell carcinoma and 34 cases of adenocarcinoma. Mean survival period of the 35 patients was 54 months. The immunohistochemical stains for E-cadherin, MMP-2, and VEGF revealed positive reaction in 67 cases (74.4%), 43 cases (47.8%), and 34 cases (37.8%), respectively. The expression of E-cadherin was higher in adenocarcinoma (82.4%) than in squamous cell carcinoma (69.6%). MMP-2 was expressed in the tumor cells, especially those invading into the surrounding stroma. The expression of MMP-2 was significantly correlated with the survival rate (p<0.05).
The expression of VEGF in the tumor cells was significantly higher in cases with lymph node metastasis (p<0.05). In conclusion, these findings suggest that the expression of MMP-2 and VEGF predict poor prognosis of patients with squmous cell carcinoma and adenocarcinoma of the lung and that VEGF may play a role in tumor metastasis.
The thickness of the glomerular basement membrane may vary not only in glomerular disease, but also in normal persons according to age and sex. But there has been no data on the normal thickness of the basement membrane in Korea. This study was designed to determine the glomerular basement membrane thickness as a reference value according to age and sex, in 50 cases of minimal change disease obtained from patients aged 2~67 years. Measurement of glomerular basement membrane was made on electron micrograph using an image analyzer. The thickness of each case was estimated by the arithmetic and harmonic mean methods. The mean thickness of the glomerular basement membrane was 291.9 47.9 nm by harmonic mean method and 284.2 43.7 nm by arithmetic mean method. And the harmonic mean thickness of the glomerular basement membrane according to age was 249.1 32.5 nm (1~5 years), 256.6 45.3 nm (6~10 years), 279.2 57.9 nm (11~15 years), 303.2 43.8 nm (16~20 years), 335.3 37.5 nm (21~30 years), and 291.1 22.5 nm (over 30 years), respectively. There was a trend that the thickness of glomerular basement membranes increased with the age till 30 years of age. There was no significant sex-related difference. In conclusion, the mean glomerular basement membrane thickness is comparable to the data from western people and shows a trend of increasing thickness according to the age.
We report a case of a 41-year-old female patient who suffered from the acute abdominal pain for several hours after eating raw sea-fishes. After the fibergastroscopy and the abdominal C-T scan, the clinicians found a gastric submucosal mass and performed the explolaparotomy to get an wedge of stomach. Sections revealed a larva surrounded by phlegmonous inflammation with intense eosinophilic infiltration in the widened gastic submucosa. The larva presented the characteristics of the Anisakis: two lateral chords with renette cell, thich smooth cuticle and well developed musculature.