Hye Ju Kang, Sun Young Kwon, Ahrong Kim, Woo Gyeong Kim, Eun Kyung Kim, Ae Ree Kim, Chungyeul Kim, Soo Kee Min, So Young Park, Sun Hee Sung, Hye Kyoung Yoon, Ahwon Lee, Ji Shin Lee, Hyang Im Lee, Ho Chang Lee, Sung Chul Lim, Sun Young Jun, Min Jung Jung, Chang Won Jung, Soo Youn Cho, Eun Yoon Cho, Hye Jeong Choi, So Yeon Park, Jee Yeon Kim, In Ae Park, Youngmee Kwon
J Pathol Transl Med. 2021;55(6):380-387. Published online October 6, 2021
Background Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.
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Background Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.
Methods We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.
Results Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.
Conclusions Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.
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Do Histology and Primary Tumor Location Influence Metastatic Patterns in Bladder Cancer? Hyung Kyu Park Current Oncology.2023; 30(10): 9078. CrossRef
Background Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.
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Background Cervical cytology for uterine cervical cancer screening has transitioned from conventional smear (CS) to liquid-based cytology (LBC), which has many advantages. The aim of this study was to compare the proportion of unsatisfactory specimens from CS versus LBC at multiple institutions including general hospitals and commercial laboratories.
Methods Each participating institution provided a minimum of 500 Papanicolaou (Pap) test results for analysis. Pap tests were classified according to the participating institution (commercial laboratory or general hospital) and the processing method (CS, ThinPrep, SurePath, or CellPrep). The causes of unsatisfactory results were classified as technical problems, scant cellularity, or complete obscuring factors.
Results A total of 38,956 Pap test results from eight general hospitals and three commercial laboratories were analyzed. The mean unsatisfactory rate of LBC was significantly lower than that of CS (1.26% and 3.31%, p = .018). In the LBC method, samples from general hospitals had lower unsatisfactory rates than those from commercial laboratories (0.65% vs 2.89%, p = .006). The reasons for unsatisfactory results were heterogeneous in CS. On the other hand, 66.2% of unsatisfactory results in LBC were due to the scant cellularity.
Conclusions Unsatisfactory rate of cervical cancer screening test results varies according to the institution and the processing method. LBC has a significantly lower unsatisfactory rate than CS.
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A case of malignant epithelial mesothelioma of the peritoneum diagnosed by fine needle aspiration cytology is described.
The smear showed many individually scattered or clustered large round malignant epithelial cells intermingled with relatively small nonneoplastic mesothelial and mesenchymal cells. Papillary configurations with thick fibrous core were also seen. The malignant cells were virtually reminiscent of reactive mesothelial cells but they were larger in size and had more prominent nucleoli and more frequent binucleated or multinucleated cell formations than reactive mesothelial cells. The characteristic features of malignant cell of mesothelioma compared with the metastatic adenocarcinoma were relatively uniform cellular size, prominent round nucleoli, large round vesicular nuclei with finely granular chromatin pattern, smooth nuclear membrane, abundant glassy cytoplasm rather than bubbly mucin-containing cytoplasm and fuzzy cell border.
BACKGROUND Triple negative breast cancer (TNBC) is defined as a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. Many TNBCs show a profound infiltration of tumor infiltrating lymphocytes (TILs). It is still uncertain whether these TILs are protumoral or antitumoral. Regulatory T cells (Tregs) play a role in inducing immune tolerance to antigens, and they may be selectively recruited by cancer cells. This study was conducted to evaluate the significance of TILs with an emphasis on forkhead box p3 (Foxp3), which is a marker for CD25+CD4+ Treg in TNBC. METHODS We investigated the Foxp3, CD8 and CD4 expressions in 100 cases of TNBC by immunohistochemistry and using a tissue microarray. The Foxp3 expression was divided as the high and low infiltration groups (cut-off value=20). RESULTS The high infiltration group was correlated with higher histologic and nuclear grades. However, Foxp3+ Tregs were decreased in the T3 and T4 TNBCs as compared to that of the T1 and T2 TNBCs. No significant differences were found for the nodal status, lymphovascular invasion, stage, recurrence and overall survival. CONCLUSIONS High Foxp3+ Treg infiltration in TNBC is correlated with the nuclear and histologic grades, but there was no relation to recurrence and overall survival.
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BACKGROUND To standardize renal biopsy reporting and diagnosis, The Renal Pathology Study Group of the Korean Society of Pathologists (RPSKSP) has developed a renal pathology reporting format for the native and allograft kidney. METHODS A consensus checklist of a provisional renal biopsy format was sent to all members of the RPSKSP. Feed back opinions regarding the practical application of the checklist to the diagnostic work were received. RESULTS Kidney biopsies require three essential examinations: by light microscopy, immunofluorescence (IF), and electron microscopy (EM). A final report of a renal biopsy should include information on specimen adequacy and a description of the morphologic change using a systematic semiquantitative method for each of the compartments, with optional separate IF and EM reports. CONCLUSIONS A standard renal biopsy report format is important in establishing clinicopathologic correlations, making reliable prognostic considerations, comparing the findings in sequential biopsies and evaluating the effects of therapy.
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BACKGROUND This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size < or = 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm). METHODS We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining. RESULTS Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression.
There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions. CONCLUSIONS Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.
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BACKGROUND This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis. METHODS We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC). RESULTS Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group. CONCLUSIONS Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.
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Histomorphology of enteric neurons and enteric ganglia in different layers of human fetal colon Chacchu Bhattarai, Phanindra P. Poudel, Arnab Ghosh, Sneha G. Kalthur Journal of Taibah University Medical Sciences.2022; 17(4): 556. CrossRef
Diagnostic utility of Bcl-2 immunohistochemical expression in pediatric functional bowel obstruction cases with ganglionated specimens Lobna Abd El Fattah Mohamed, Nedal Ahmed Hegazy, Faten Abd El Aziz Ghazal, Ahmed Mohy El Din Zaki, Ahmed Bassiouny Radwan, Sarah Adel Hakim Annals of Pediatric Surgery.2022;[Epub] CrossRef
PTEN Immunohistochemistry Simone Antunes Terra, Pedro Luiz Toledo de Arruda Lourenção,, Maria Aparecida Marchesan Rodrigues Archives of Pathology & Laboratory Medicine.2022; 147(5): 577. CrossRef
Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells Simone Antunes Terra, Anderson Cesar Gonçalves, Pedro Luiz Toledo de Arruda Lourenção, Maria Aparecida Marchesan Rodrigues World Journal of Gastroenterology.2021; 27(44): 7649. CrossRef
Morphometric profile of large intestinal neuronal plexuses in normal perinatal autopsies and Hirschsprung disease H. Subramanian, B. A. Badhe, P. C. Toi, K. Sambandan Neurogastroenterology & Motility.2017;[Epub] CrossRef
Ji Yoon Bae, Hyung Kyung Kim, Hanna Kang, Ha Rin Cheong, Dong Eun Song, Sun Hee Sung, Heasoo Koo, Woon Sup Han, Jeong Kyong Lee, Tae Hun Kim, Kyu Won Chung, Min Sun Cho
BACKGROUND Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized. METHODS Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry. RESULTS The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load. CONCLUSIONS FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.
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Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung The Korean Journal of Pathology.2011; 45(1): 53. CrossRef
BACKGROUND Squamous cell carcinoma of the breast is very rare and it is considered to arise from metaplastic change of ductal carcinoma. Metaplastic squamous cell carcinoma (MSC) of the breast includes pure squamous cell carcinoma, metaplastic adenosquamous carcinoma and low grade adenosquamous carcinoma. Most of the cases of MSC of the breast were reported to have lymph node metastasis and this has a worse prognosis than that of conventional invasive ductal carcinoma. METHODS We collected 17 cases of MSC of the breast from 1,173 cases of breast cancer and analyzed the clinicopathological characteristics. RESULTS The age range was 31 to 69 years (mean age: 47.2).
The mean tumor size was 3.6 cm. Twelve cases (70.6%) had a negative nodal status. The majority of the cases were of a high nuclear grade (grade III: 76.5%), and a high histologic grade (grade III: 88.2%). All the cases had no amplification of HER2, and they were negative for hormonal receptors, except for 2 cases with weak positivity. All the cases showed positivity for EGFR (3+: 14 cases, 1+: 3 cases).
Clinical relapse was found in 3 patients on follow up and two of them expired due to lung and bone metastasis. CONCLUSIONS MSC is associated with high nuclear and histologic grades, a high EGFR expression and they are triple negative for ER, PR, and HER2. The EGFR immunopositivity of MSC suggests a basal-like subtype.
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Eccrine ductal and acrosyringeal metaplasia in breast carcinomas: report of eight cases Tibor Tot Virchows Archiv.2019; 474(3): 383. CrossRef
Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung The Korean Journal of Pathology.2011; 45(1): 53. CrossRef
A complex syndrome, later called as Prader-Willi syndrome, was first described in 1956 by Prader et al, and Zellweger and Schneider characterized this syndrome as hypogonadism, hypotonia, hypomentia and boesty. It is not rare in western countries and more than 400 cases have been reported until 1983. But our interest arose because of our recent experience of diffuse noncirrhotic fibrosis of the liver in a 6 year-old boy who had the clinical features of Prader-Willi syndrome. The core of liver showed destruction of most of the hepatic lobules, particularly of the acinar zone 3, and replacement bt diffuse fibrosis. The remaining liver cells underwent fatty change, and the overall changes resembled chronic sclerosing hyaline disease of the alcoholic type. Inflammation was negligible. This particular case suggests that the severe fatty change of liver could result in irreversible damage to the hepatocytes and progressive fibrosis.
Most ectopic pregnancies occur in the fallopian tubes. There have been numerous theories to explain the occurrence of ectopic pregnancy in fallopian tubes. The most commonly held view is that the passage of the fertilized ovum through the fallopian tube is delayed or hindered by chronic inflammation and its sequelae. We designed a study to evaluate the details of histopathologic changes and the location of implantation and how they relate to the clinical history. 182 fallopian tube specimens from patients who had undergone total or partial salpingectomy were examined. A high incidence of non-specific inflammation of plicae and wall of tube (31.9%) and salpingitis isthmica nodosa (12.6%) were observed. Other associated findings included acute salpingitis, complex plicae or complex hyperplasia of tubal epithelium, fibrous adhesion with ovary, endometriosis, and calcification. History of previous ectopic tubal pregnancy was found in 8 cases. The cases with serum beta-HCG value above 2,500 I.U./L (group I, n=97) were more frequently noted in those exhibiting myosalpingeal invasion of trophoblast (67 cases) than in those without invasion (30 cases). Of the 182 tubal pregnancies, 117 (64.3%) cases were found in the ampulla and 47 (25.8%) cases in isthmic location. In 117 ampullary pregnancies, the products of conception were found intraluminally in 71 cases (60.7%), and extraluminally in 34 (29.1%) cases, of which the products of conception were found entirely extraluminal. The products of conception, found both within and outside the tubal lumen, were found in 12 cases (10.2%). Of 47 tubes with isthmic pregnancies, 33 cases were intraluminal (70.2%), 12 cases were extraluminal (25.5%), and two cases were mixed (4.3%). In conclusion, significant histopathologic abnormalities accompany a majority of ectopic tubal pregnancy, and myosalpingeal invasion of trophoblast is correlated with high serum beta-HCG. Thus, it is necessary to confirm not only the ectopic placental tissue but also the accompanying details of the other histopathologic findings or the pathologic evaluation of ectopic tubal pregnancy.
Retroperitoneum is often the site of occurrence of schwannoma, but reports on schwanoma of the adrenal gland is exceptional and only 4 cases have been documented in the literature. This report is to add one such case occurred in a 53 year-old male who had anorexia, nausea and indigestion for one month. Whole body bone scan and abdominal CT scan revealed a 10 cm sized solid mass at upper pole of the left kidney. Under the impression of renal cell carcinoma, an operation was performed. The tumor was well encapsulated and appeared not to involve the kidney. The cut surfaces were light yellow and seemed to be composed of several hard lobules with areas of mucoid, cystic and calcific changes.
No adrenal gland was identified grossly. But microscopically, the tumor was found to be partly surrounded by a small portion of adrenal cortical tissue.
Histologically the tumor was a typical schwannoma with Verocay bodies, although modified in some extents by mucoid degeneration, cystic change, hyaline change and focal calcification. It is worthwhile to remember that the retroperitoneal schwannoma commonly had a huge size, sometimes involving the adjacent structures.
To evaluate the clinical and histopathological significance of electron dense deposits on capillary in IgA nephropathy, we reviewed and compared the clinical, laboratory, and pathological features of the patients with IgA nephropathy without loop extension of electron dense deposits(Group I, 91 cases) and IgA nephropathy with loop extension(Group II, 17cases) by ultrastructural examination using transmission electron microscope. IgA nephropathy associated with liver disease, Henoch-Schonlein purpura, systemic lupus erythematosus and the other IgA nephropathies associated with systemic diseases were excluded. The results were as follows; 1) There was no significant difference in age distribution. 2) Generalized edema was more common in group II. 3) Nephrotic ranged proteinuria(>3 g/24hr urine) was more prominent in Group II(52.9%) than Group I(8.8%). 4) Among the groups, segmental or mild deposits on the loops were noted in 13 cases, and severe and generalized deposits in 4 cases. Subendothelial deposits were noted in 6 cases, subepithelial deposits in 3 cases, subendothelial with intramembranous deposits in 1 case, subendothelial with subepithelial deposits in 1 case, intramembranous with subepithelial deposits in 2 cases, and subendothelial, subepithelial and intramembranous deposits in 4 cases. 5) The other associated ultrastructural changes of group II were diffuse effacement of foot processes with microvillous transformation, swelling or vacuolar degeneration of podocytes and glomerular endothelium. 6) According to the WHO morphologic criteria, the grade of Group II was significantly higher than Group I. From the above results, it can be concluded that the extension of electron dense deposits along the capillary loops in the cases of IgA nephropathy is highly correlated with proteinuria in the nephrotic ranged. It seems to be a poor prognostic indicator in view of the facts that it correlats with high histopathologic grading.
Gastrointestinal stromal tumor (GIST) is known as considerable controversal tumor about it's histogenesis, differentiation and biologic behavior. It is traditionally regarded as smooth muscle tumor. To evaluate and clarify the origin of tumor, we performed immunohistochemical study of 23 cases of GIST on CD34 antigen, alpha-smooth muscle actin, S-100 protein, and compared the result with 4 cases of typical leiomyoma of GI tract. The results were as follows.
CD34 antigen expression was noted in 21 cases (91.3%) of GIST, while typical leiomyoma was all negative. There were no difference of CD34 expression according to the biologic behavior. However, it's staining pattern was significantly different (p<0.05). Focal or multifocal expression was dominant in benign GIST (58.3%), while diffuse expression was dominant in malignant GIST (80%). Actin was expressed in 5 cases of benign GIST (38.5%) and 1 of malignant GIST (16.7%) focally. All typical leiomyoma showed diffuse strong positivity on alpha-smooth muscle actin. S-100 protein was expressed in 2 cases of benign GIST (16.7%) only. The pattern of CD34 expression was focal in the actin or S-100 protein positive cases. In conclusion CD34 antigen is useful marker in the separation of GIST, from typical smooth muscle tumor. Also it suggest that most GISTs are histogenetically primitive mesenchymal cell origin. However, CD34 expression was unrelated with biologic behavior of GIST.
Sialosyl Tn mucin antigen (STn) is a carbohydrate antigen of tumor associated mucin formed by the premature 2~6 sialation of N-acetylgalactosamine. STn has been expressed in several tumor types and showed prognostic significance in colonic carcinoma. The authors evaluated the expression of STn immunohistochemically and correlated its expression with clinicopathologic variables in 100 gastric cancers. In early gastric cancer, STn was expressed in 24 cases out of 50 cases (48%). In advanced gastric cancer, STn was expressed in 48 of 50 (96%). The difference in STn expression between advanced gastric cancer and early gastric cancer was statistically significant.
The difference in STn expression between tumors with lymph node metastasis and those without lymph node metastasis, between tubular adenocarcinoma and signet ring cell carcinoma, and between intestinal type and diffuse type adenocarcinoma was statistically insignificant in early or advanced gastric adenocarcinoma. These results suggest that the STn expression plays a role in the tumor progression in both early and advanced gastric adenocarcinomas.
Background : PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression. Results : Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.
Hamartoma of the breast is relatively rare benign tumor, which is a well-circumscribed mass mainly composed of fibrous stroma, a(tipose tissue, ducts and acini. Muscular hamartoma of the breast is mainly composed of smooth muscle, and is extremely rare because proper smooth muscle is normaly absent in the breast except in the nipple. We describe a rare case of muscular hamartoma of the breast in a 38-year-old woman. This tumor was located in the upper outer quadrant and a 3 x 2.5 x 2 cm sized, well-demarcated but not encapsulated mass, The mass consisted mainly of irregularly arranged smooth muscle bundles in the fibrous stroma with lobular units and admixed fat cells. The origin of smooth muscle in hamartoma is not well known.
Kyung Ja Lee, Min Sun Cho, Seung Cheol Kim, Hae Sung Moon, Hyesook Park, Shi Nae Lee, Sun Hee Sung, Ki Nam Shim, Kyung Eun Lee, Sung Ae Jung, Kwon Yoo, Hae Young Park, Soo Yeun Park, Eun Sun Yoo, Hyun Suk Suh
BACKGROUND Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia, and this is associated with reduced radiosensitivity. Furthermore, HIF-1alpha can increase a tumor's aggressiveness by promoting neoangiogenesis, cell proliferation and survival, and invasion. METHODS The expression of HIF-1alpha was was investigated by performing immunohistochemistry on the cervical tissue specimens obtained from 57 patients who had received radiotherapy combined with or without chemotherapy for stages I-III cervical squamous cell carcinoma. The staining results were compared with anemia, the stage, the radiotherapy response and patient survival by univariate and multivariate analysis. RESULTS In 57 patients, the expression of HIF-1alpha was seen in the tissue specimens of 46 patients (81.7%). Among them, 25 (54.3%), 14 (30.4%), and 7 (15.2%) of the patients' tissue specimens showed weak, moderate and strong expressions, respectively. Six patients had a partial response after radiotherapy. Twelve patients (21.1%) died of cervical cancer. The increased expression of HIF-1alpha was significantly associated (p<0.05) with the disease stage and anemia. There were significant positive correlations between the increased expression of HIF-1alpha and the poor response after radiotherapy and the patients' survival. CONCLUSIONS The present result suggests that the overexpression of HIF-1alpha in the uterine cervix could be used as a prognostic indicator for the patients treated with radiotherapy.
We report a case of aggressive angiomyxoma in ischiorectal fossa of a 39-year-old women. The tumor is characterized by relatively large size(13 x 11 cm), grossly gelatinous appearance and locally infiltrative nature. Microscopically, it consists of many variable sized blood vessels and spindle or stellate cells widely separated in myxoid or collagenous stroma. Immunohistochemical stains reveal that the tumor cells are strongly positive for actin and desmin. Electron microscopic findings are that of a few cells dispersed in abundant intercellular substance and collagen bundles. These cells form irregular cytoplasmic process without basal lamina and contain endoplasmic reticulum having cistern.
The cells of glomerular mesangium is composed mostly of intrinsic contractile mesangial cells and a few macrophages.
Injury to the mesangium is central to many glomerular diseases. This study was aimed to evaluate and compare the expressions of alpha-smooth muscle actin (ASMA) and lysozyme in the mesangium of various human glomerular diseases and also of according to the severity of their progressions. We performed immunohistochemical and transmission electromicroscopic examinations in 51 cases of renal biopsy including 5 normal kidneys. The results were as follows; (1) ASMA staining was negligible in normal glomeruli. (2) Increased ASMA staining was observed in the mesangium of glomeruli from all specimens of primary glomerular disease, regardless of their diagnosis. (3) The staining intensity of ASMA in mesangium was mild in minimal change disease and membranous glomerulonephritis, and strong in focal segmental glomerulosclerosis (FSGS), diffuse mesangial hypercellularity, membranoproliferative glomerulonephritis (MPGN), and IgA nephropathy (IgAN). (4) The staining intensity of ASMA have no correlation with mesangial immune deposits. (5) The staining intensity of ASMA in mesangium was inversely correlated with the disease progression in FSGS and IgAN. (6) Glomeruli showing global or segmental sclerosis invariably lacked ASMA. (7) Compared with ASMA, the mesangial cells with lysozyme expression were very rare, even though it was in proportion to ASMA staining.
Interstitial ASMA expression was confined to fibrotic area in various glomerular diseases. In conclusion, the expression of ASMA and lysozyme in mesangium are increased in a variety of glomerular diseases, regardless of disease entity. Their intensity was in proportion to the mesangial cell proliferation. In progressive glomerulonephritis, such as IgAN and FSGS, the increased expression of ASMA was prominent in the early lesion, and decreased with the progression of the glomerular sclerosis.
BACKGROUND Histologic progressive changes of bile duct epithelium with hyperplasia, dysplasia and cholangiocarcinoma could be caused by hepatolithiasis. To be clarified as a neoplastic process, this histologic process should be evaluated with various aspects of cell biology. METHODS Immunohistochemical study of proliferating cell nuclear antigen (PCNA) was performed on 45 cases (10; normal, 15; hyperplasia, 14; low-grade dysplasia:LGD, 6; high-grade dysplasia: HGD) of hepatolithiasis and 10 cases (all HGD) of hepatolithiasis with cholangiocarcinoma. RESULTS In the hepatolithiasis, mean PCNA labelling indices (LI) of normal, hyperplasia, LGD and HGD of major intrahepatic bile duct epithelium were 24.5+/-4.3, 51.5+/-0.1, 62.0+/-.4 and 84.7+/-.3, respectively and gradually increased. Mean LI of PCNA in HGD of major intrahepatic bile duct epithelium of hepatolithiasis with cholangiocarcinoma was 68.7+/-.7, which was similar to that of LGD in hepatolithiasis without cholangiocarcinoma. CONCLUSIONS Histologic transformation through hyperplasia, dysplasia and carcinoma in major intrahepatic bile duct epithelium of hepatolithiasis may be a neoplastic process if these histologic changes are evaluated in the cellular proliferation aspect.
In view of the possible role of portal circulation in hematogenous spread of Candida species, a case of hepatic candidiasis occurred in an eight-year-old child with acute lymphoblastic leukemia (ALL) treated by chemotherapy is presented. Symptoms and signs referable to the hepatic disease in this patient included hepatomegaly, icteric sclera and abdominal pain. There were no particular manifestations suggestive of deep mycotic involvement of any sepcific organs or tissues other than the liver. Culture of the blood was negative for one month. On the 24th hospital day the patient died with the presumptive diagnosis of ALL, disseminated intravascular coagulation, acute renal failure, pulmonary edema, cholecystitis and oral thrush. A needle necropsy was performed and revealed fungal aggregates replacing the large foci of hepatic cell loss. It is suggested that, when the gastrointestinal tract serves as the portal of entry, the liver could be the visceral organ involved first in the course of disseminated candidiasis.
Glomerulosclerosis is a common outcome in various progressive glomerular diseases, and results from accumulation of extracellular matrices.
Depending on the disease progression the extracellular matrices show quantitative and qualitative alterations. Tenascin is a significant extracellular matrix glycoprotein that expresses in normal and pathologic tissue of varying organs including kidney. We performed immunohistochemical staining for tenascin using 30 cases of renal biopsy specimens diagnosed as IgA nephropathy to study the alteration of tenascin expression in IgA nephropathy according to the histologic grading. The results were as follows; 1. The more high histologic grade, the more increase of tenascin was found in the glomerulus. 2. Tenascin was increased in proportion to the mesangial matrix. 3. The staining of tenascin was more intense in glomerular sclerotic area and was increased in proportion to the progression of sclerosis. 4.
Cellular crescents showed strong positivity for tenascin. 5. Tenascin was increased in proportion to the degree of interstitial fibrosis in renal cortex. In conclusion, tenascin is an important extracellular matrix component which is significantly increased in both glomerulus and cortical interstitium according to the progress of the disease in IgA nephropathy.
Most glomerular lesions are associated with qualitative and quantitative alterations of the extracellular matrix components, having relation to progressive glomerular sclerosis. We aimed to investigate the characteristic alteraltions in distribution of extracellular matrix components, such as fibronectin, laminin, collagen type III and IV in human glomerular diseases by immunohistochemical method. The materials included are 3 nephrectomy as normal control, 51 renal biopsies and I autopsy; 3 normal, 5 minimal change disease, 5 minimal change disease with minimal mesangial lgA deposit, 5 benign recurrent hematuria, 10 focal segmental glomerulosclerosis, 15 lgA nephropathy, 10 membranoproliferative glomerulonephritis, 2 diffuse mesangial sclerosis of infancy. Type IV collagen and laminin were present normally in the mesangium, GBM, TBM and interstitial vessels, and were increased at the portion of increased mesangial matrix, of sclerosis and thickened GBM in cases of lgA nephropathy, membranoproliferative glomerulonephritis, focal segmental glomrulosclerosis and diffuse mesangial sclerosis in the proportion to the glomerular damage. Type III collagen was absent in the normal glomeruli, but was detectable focally and segmentally in cases of membranoproliferative glomerulonephritis, IgA nephropathy and focal segmental glomerulosclerosis at the sclerotic portion. Fibronectin was normally detectable mainly in the mesangium, and partly and incompletely in GBM, and was increased at the portion of increased mesangial matrix, sclerosis and thickened GBM in cases of focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, IgA nephropathy and diffuse mesangial sclerosis, but was diminshed at the old slcerotic portion or global sclerosis. The expression of these antibodies in cases of minimal change disease, minimal change disease with minimal mesangial IgA deposit, benign recurrent hematuria was not different, quantitatively and qualitatively, from that of normal glomeruli. These findings suggest that progressive glomerular sclerosis was due to the increase of extraceuular matrix components such as type IV collagen, laminin, fibronectin and new appearance of type III collagen, and the expression was in proportion to the degree of sclerosis, but had no relation to the disease entity.
Neonatal hepatitis(NH) and congenital extrahepatic biliary atresia(BA) are two major causes of neonatal cholestasis.
The method of therapeutic trials for each disease is essentially different. Nonetheless it is very difficult to differentiate these diseases histologically, since most of the hepatic changes are mutual in both of them. This study is to aimed to find out major differences between the two by scoring various histological parameters. A total of 63 consecutive liver biopsies taken from 54 patients with suggested NH and BA were examined by applying morphometric scoring system. The detailed clinical histories, laboratory data including serology for HBsAg and TORCH infection and radiologic operative findings were reviewed. Among 54 patients, 27 were diagnosed as NH and 20 as BA. In two cases, features of both diseases were coexistent. The pathological diagnosis was not compatible with the final diagnosis in 5 cases(10.7%). In all of these 5 cases, biopsy had been performed at the age of one to two months. The seropositivity for TORCH was 59.3%(16.27) in NH, but 25.0%(5/20) in BA. Serum AST, ALT and alpha-fetoprotein values were higher in NH, and total bilirubin in BA. Of various histological parameters, scores of portal fibrosis, bile duct and ductular proliferation and bile thrombi were much higher in BA, and at the age of less than 2 months, extramedullary hemopoiesis(EMH) was found much more frequently in NH. Giant cell transformation of hepatocytes(GCT) was more commonly observed in NH. The numbers of GCT and EMH were particulary plentiful when the patients' sera were positive for HBsAg or TORCH. These results indicate that portal fibrosis, biliary proliferation and bile thrombi are the three major histologic features of BA, and therefore erroneous histological diagnosis may ensue when scores of those features are low as in some early BA.
Melanosis coli is characterized by a dark brownish discoloration of the colonic mucosa. Its pathogenesis is still unknown. Recently it was proposed that the apoptosis of mucosal epithelium due to habitual use of laxatives play an important role for induction of melanosis coli. We studied clinicopathologic aspects of 12 cases of melanosis coli and analysed the histochemical and immunohistochemical characteristics of them. Results are as follows. : Mean patient's age was 53.5, and the male:female ratio was 4:8.
Nine patients had a history of constipation, and all of these had administrated various kinds of laxatives. The severity of discoloration was correlated with the duration of constipation and age. There was no difference of anatomical distribution in colon. Other remarkable mucosal lesions were not accompanied. On pathologic examination, all cases showed frequent yellow-brown pigment laden cells in lamina propria. These pigments were positive for periodic acid Schiff stains, Fontana Masson stains, and Victoria blue stains, however they were negative for prussian blue stain.
On immunohistochemical stainings pigmented cells were positive for CD68, and negative for S-100 protein and neuron specific enolase. These results indicate that they are macrophages. On ultrastructural examination pigmented cytoplasms were filled with variable sized electron dense granules including irregulary round deformed membranous structures, lipid vacuoles. Apoptosis of mucosal epithelium was noted in 5 cases. These findings suggest that apoptosis is the significant pathologic process in the progression of some cases of melanosis coli.
We report the clinical course and autopsy findings of a 19-year-old girl with endodermal sinus tumor involving the thalamus, hypothalamus, and basal ganglia. The patient initially had tonic-clonic seizures with abnormal signal involving the right hippocampus, amygdala, basal ganglia, putamen, and dentate gyrus. The signal intensity of the posterior pituitary on T1-weighted images was decreased at the time of admission, which was not associated with clinical symptoms of diabetes insipidus (DI). A huge tumor mass as well as central DI developed within 10 months. The postmortem examination showed gliosis with calcification involving the right basal ganglia, internal capsule, and white matter, in addition to a tumor mass involving the thalamus, hypothalamus, and basal ganglia. Dissemination of tumor cells in the leptomeninges and the gliotic area and hydrocephalus were also noted.
To know the correlation between glomerular and tubulointerstitial lesion and to define the characteristics of interstitial inflammatory cell in IgA nephropathy and classified according to WHO classification and graded tubulointerstitial lesion as mild, moderate and severe.
Paraffin-embedded 5u sections were stained with UCHL-l, L26 and CD68 antibodies. More than 20 fields were examined in each case under the high power microscopy and the number of positive cells were counted. There was positive correlation between the severity of glomerular and that of tubulointerstitial lesion. The mostcommoninflammatory cells in the interstitiuin were UCHL-l positive cells followed by CD68 and L26 positive cells. As the WHO grade or tubulointerstitial lesion increased, the numbers of positive cells were increased in all three groups. The proportion of UCHL-1 Positive cells were increased in cases with high WHO grade whereas that of L26 positive cells incases with severe tubulointerstitial lesion Proteinuria was correlated with the degree of inflammatory cell infiltration, especially with that of L26 positive cells.
To provide ideas for the recognition of neonatal and infantile liver diseases caused by cytomegalovirus(CMV) infection, histopathological examinations were made on hepatic tissues obtained by biopsy or autopsy from 23 patients. All patients were sero-positive for IgM anti CMV and had no other known or suggested etiologic factors for their liver disease. There were five different types of liver diseases: 8 cases of giant cell hepatitis(34.8%), 4 cases of biliary atresia(17.4%), 5 cases of biliary atresia with changes of neonatal hepatitis(21.7%), 4 cases of diffuse hepatic fibrosis(17.4%) and 2 cases of hepatic necrosis with CMV inclusion(8.7%). The diffuse hepatic fibrosis involved both the hepatic lobules and portal areas without evidences of regeneration. This type of liver disease appeared to be a chronic progressive illness that began during the first week of life, and in 3 of 4 cases, the liver biopsy was dong at 5 to 9 months after birth. The two patients showing CMV inclusion in their liver were premature of debilitated, and died within I month after birth. Diffuse hepatic necrosis as well as the cytomegalic change of bile duct epithelium was characteristic. The findings suggest that the pattern of CMV liver disease depends on the major site of hepatic injury, the status of status of patient's defense mechanism and the chronicity of illness.
Mullerian adenosarcoma is a tumor composed of a mixture of glandular and stromal elements in which the glandular component appear to be neoplastic but, histologically, benign with the stromal component showing varying degrees of malingancy. We report a case of ovarian m llerian adenosarcoma with sex cord stroma differentiation in the stromal components. A 57 year-old female who presented with palpable mass in the right lower abdomen had undergone through salingo-oophorectomy. Grossly, the ovary was multicystic, and partly showed a solid appearance with multiple polypoid projections into the dilated cystic spaces. On microscopic examination, the tumor consisted of benign to borderline epithelial glands that were lined by variety of mullerian epithelia and sarcomatous component with sex cord-stromal elements, which include sertoliform tubules, Leydig cell like clusters, and granulosa cells.
Angiogenesis is an essential requirement for development, progression, and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) is one of the important angiogenic factors. Recently the role of angiogenesis has been known in premalignant lesions. This study was performed to determine whether the angiogenesis and VEGF expression were increased in association with histological grade of cervical intraepithelial neoplasia (CIN) and to see the relationship between the angiogenesis and VEGF.
Immunostainings for factor VIII and VEGF were performed on 52 cases of cervical neoplasia (12 cases of CIN I, 11 cases of CIN II, 15 cases of CIN III, 7 cases of microinvasive squamous cell carcinoma, and 7 cases of invasive carcinoma) and 5 cases of normal cervix. The results showed a significant increase of microvessel count from normal cervix through CIN grades to invasive squamous cell cacinoma. VEGF expression was increased in proportion to the CIN grades. There was no significant correlation between microvessel count and VEGF expression. In conclusion, the tumor angiogenesis is an early event in tumorigenesis of uterine cervix. In addition, no significant relationship between the microvessel count and VEGF expression in CIN suggests the possibility of other growth factors affecting mainly angiogenesis of premalignant lesion of uterine cervix.
BACKGROUND KAI-1 is a metastasis suppressor gene. We have evaluated the correlationbetween KAI-1 protein expression in ductal carcinomas of the breast and axillary lymph nodemetastasis. METHODS The expression of KAI-1 protein was confirmed by immunohistochemistryto examine breast tissues of ductal carcinomas from 50 patients with nodal metastasisand from 53 patients without metastasis. Western blot analysis was performed on fresh frozenbreast tissues from 17 cases with nodal metastasis and from 19 cases without metastasis. RESULTS Immunohistochemical KAI-1 protein expression was decreased or negative in 39out of 50 cases with metastasis (78%), compared with 8 out of 53 cases with no metastasis(15.1%). The difference was statistically significant (p<0.05). Immunohistochemical KAI-1protein expression was significantly decreased in cases with higher modified Black's nucleargrade (p=0.027) and larger tumor size (p=0.039). Western blot analysis showed positivebands at 29.5 kDa in 8 out of 19 cases without metastasis (42.1%), and none of the 17 caseswith metastasis showed positive bands (p=0.0024). CONCLUSION These results suggest thepossibility that KAl-1 might play a major role of a metastasis suppressor gene in addition tothe part it plays in the growth and progression of human breast ductal carcinoma. In addition, the decreased expression of KAI-1 protein in breast ductal carcinomas could be used as afactor suggesting poor prognosis.
The number of Kupffer cells was evaluated in hepatocellular carcinomas, including 18 primary lesions, 3 tumor emboli within the portal vein radicles and 4 metastatic lesions and in non-neoplastic liver adjacent to the primary lesions, to persue the origin of Kupffer cells dwelling in hepatocellular carcinoma. Hepatocellular carcinomas of the sinusoidal(trabecular) type were carefully selected, and excluded were those carcinomas which showed inflammation or other changes evoking inflammation. The immunohistochemical stains for CD 68 and lysozyme were done to identify Kupffer cells and to draw the mean Kupffer cell number per high power microscopic field of each lesion. Kupffer cell was most numerous in primary lesions followed by tumor emboli and still fewer in metastatic lesions. The Kupffer cell number in the primary lesions of hepatocellular carcinoma was in turn smaller than that of the adjacent non-neoplastic liver. The results suggest that, during the early neoplastic transformation, sinusoids of the non-neoplastic liver could creep into the carcinomatous tissue accompanying Kupffer cells.
Infantile form of histiocytosis X is commonly presented as multiorgan desseminated form such as Letterer-Siwe disease.
Lymph node involvement of histiocytosis X is usually accompanied by adjacent bone or skin lesion. Solitary nodal eosinophilic granuloma without evidence of other organ involvement is very rare. A case herein report is a 11 month-old female infant presented with fever and palpable both inguinal lymph nodes. There was neither skin lesion nor hepatosplenomegaly. Laboratory evaluation was within normal range except increased alkaline phosphatase and many neutrophils in urine. Radiologic examination revealed no remarkable bone lesions. And she showed good clinical outcome without evidence of other organ involvements. On microscopic examination of inguinal lymph node it was replaced by infiltration of histiocytes mainly along the sinusoid. Some of histiocytes showed morphologic features of "histiocytosis X cell" having nuclear grooves or multilobulation. Multinulceated giant cells were frequently see. Numerous eosinphils were also infiltrated and showed multifocal microabscess formation. Immunohistochemical staining revealed that majority of histiocytes were postitive for S-100 protein but multinucleated histriocytes, phagocytic histiocytes and those around the abscess were positive for macrophage marker, suck as CD68 and alpha-1-antichymotrypsin. Interestingly some histiocytes showed positivity for both S-100 protein and macrophage marker. These results suggest that histiocytosis X is proliferative disorder of phenotypically heterogenous population of histiocytes in contrast to the theory that it is a proliferative disorder of Langerhans cells.
Cyclosporine A(CsA) is known as a potent immunosupressive agent, and recently its supressive effects of proteinuria in minimal change nephrotic syndrome, and other glomerular diseases have been demonstrated. But the mechanism of supression of proteinuria is not clear. This study aimed to investigate the mechanism of supression of proteinuria in puromycin aminonucleoside (PAN) induced minimal change nephrosis(MCN), by a single dose of PAN, and focal segmental glomerulosclerosis(FSG) by long term repeated administration of PAN with unilateral nephrectomy in Sprague-Dawley rats, using transmission electron microscopy. We also analysed the effects of CsA on the histopathologic changes such as glomerular sclerosis, and subtypes of infiltrated mononuclear cells in glomeruli and renal interstitium. The results are as follows: Marked proteinuria was developed in MCN and FSG groups. It was significantly reduced by administration of CsA. BUN and creatinine were significantly increased in FSG with the administration of CsA, compared with FSG without CsA. On ultrastructural examination, MCN group showed effacement of foot processes, and microvillous transformation. Occasional focal detatchment of podocytes from the GBM, vacuolar degeneration, and electron dense droplets in the podocytes were also seen. The latter findings were remarkably reduced by CsA. The Above ultrastructural findings, seen in the MCN group, were more severe in the FSG groups. On comparison of ultrastructural fingings of FSG with or without CsA groups, severe vacuolar degeneration, abundant electron dense granules, and focal detatchment of foot processes were more frequently seen in FSG groups and they were significantly reduced by CsA. But irregularity and thickening of GBM were deepend in FSG with CsA group. There were no significant differences of glomerular sclerosis, adhesion to the Bowman's capsules in both the MCN and the FSG groups by administration of CsA.
Foamy degeneration of endothelial and mesangial cells, epithelial proliferation, hyalinosis and mononuclear infiltration were significantly reduced by CsA in FSG groups. Microcalcification was commonly seen in CsA administrated groups. The main sutype of infiltrated mononuclear cells in glomeruli and interstitium were monocytes in FSG groups. The proportion of T cells were higher in interstitium by disease progression and it was significantly decreased by CsA. On conclusion the most important ultrastructural changes, regarded as the main mechanism of supression of proteinuria is that the CsA stabilize the podocytes, by preventing vacuolar degeneration and focal detatchment. But CsA does not influence the progression of glomerular sclerosis in PAN induced nephrosis.
Yi Kyeong Chun, Hye Sun Kim, Yee Jeong Kim, Sung Ran Hong, Hy Sook Kim, Byung Jun Park, Sung Su Kang, Ji Hyun Lee, Sung Kong Lee, Sun Hee Sung, Woon Sup Han
Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH).
Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found.
There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.
Mutant form of the p53 gene product is abnormally accumulated in the nuclei of the tumor cells due to prolonged half life, and readily detected by immunohisto- chemical methods. To determine the positivity rate of p53 in body cavity fluid according the primary site and histological types of tumors and the utility of p53 immunostaining as an adjunct in the diagnosis of malignancy, we reviewed 69 effusions, including pleural effusion, ascitic fluid, and pericardial fluid, that were diagnosed as overt malignancy and 21 effusions of suspicious malignancy.
Immuno- histochemistry was performed on paraffin-embedded cell blocks using a monoclonal antibody to p53 supressor gene product(Clone DO7) and a standard avidin-biotin complex technique with a citrate buffer antigen retrieval solution.
The results were as follows; of the 46 pleural effusions with overt malignancy, 22 were immunopositive for p53 protein; of the 21 ascitic fluids with overt malignancy, 5 were positive for p53. Positivity rates according to the primary sites of tumors were 18 of 34(52.9%), 8 of 21(38.1%), 1 of 9(11.1%) cases of the tumors of the lung, GI tract, and ovary, respectively. According to the histologic types of lung cancer, 11 cases(61.6%) were positive out of 18 adenocarcinomas, 2 of 5 large cell undifferentiated carcinomas, and 1 of 2 small cell undifferentiated carcinomas. Of 21 cases of suspicious malignancy, 6 were positive for p53 and all of them(6/6) were confirmed as adeno- carcinoma of the lung or GI tract. These findings indicate that p53 immunostaining using paraffin embedded cell block is useful diagnostic and prognostic marker in body fluid cytology although negative immunostaining does not exclude malignancy.
BACKGROUND TB-PCR is a faster and more sensitive method to detect mycobacterium than acid-fast bacilli (AFB) stain, which is laborious and time consuming. We compared the sensitivity and specificity of AFB stain and TB-PCR and examined the possibility of TB-PCR as a confirmative test without AFB stain in the diagnosis of tuberculosis. METHODS We performed Ziehl-Neelsen stain and nested PCR using a commercially available TB-PCR kit amplifying IS6110 sequence in 81 cases of paraffin-embedded tissues diagnosed as chronic granulomatous inflammation. In addition, we evaluated the morphology of granuloma and the presence of caseation necrosis. RESULTS Of the 81 cases studied, 22 (27.2%) and 40 (49.4%) were positive for AFB stain and TB-PCR, respectively. Of 49 cases accompanying caseation necrosis, 19 (38.8%) were AFB stain positive and 37 (75.5%) were TB-PCR positive; a result that is comparable with that of other reports. Of the 22 AFB-positive cases, 2 were TB-PCR negative. CONCLUSION TB-PCR is very helpful for the diagnosis of tuberculosis in routinely processed, formalin-fixed, paraffin-embedded tissue samples. Nevertheless, AFB stain should continue to be performed at the same time.
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.
A case of fine needle aspiration cytology of an osteoclastic giant cell tumor of pancreas, which is an uncommon variant of ductal adenocarcinoma, is described. Aspirated tumor cells were characterized by three populations: (1) bland osteoclast like giant cells with multiple small, round nuclei with distinct nucleoli, and abundant cytoplasm, (2) individually scattered or loosely clustered medium sized mononuclear tumor cells, having fine chromatin, smooth nuclear membrane, often prominent nucleoli, and high N/C ratio, (3) bland or atypical spindle shaped cells. Osteoid like lacy material was also seen on cell block section. The immunohistochemical studies using paraffin embedded cell block section showed positivities for vimentin and lysozyme in both giant and mononuclear tumor cells. However, they were negative for cytokeratin, epithelial membrane antigen, S-100 protein, carcinoembryonic antigen, and p53.
The infant kidney is more vulnerable to infections than the adult kidney. It is common that acute pyelonephritis (APN) during infancy and early childhood manifests growth retardation of kidney, ultimately leading to chronic renal failure. However, little is known about the pathogenesis of renal growth retardation in APN in youth. To understand the mechanism underlying the cortical lesions, urinary tract infection was induced in infant rats. To induce ascending APN, saline solution containing Escherichia coli (ATCC No. 25922) 107 bacteria/ml was infused into the bladder through the 16 gage silicone cannula in three-week-old weaning Sprague Dawley rats (weight 50~60 g, n=66). In the normal control group (n=20), saline was infused. Experimental groups were divided according to the treatment into the APN group (APN without any treatment, n=23) and TRX group (APN with ceftriaxone treatment, n=23).
After performing the histopathologic examination, including inflammatory score, fibrosis score, and tubular atrophy score, we measured the apoptosis index in the tubular cells of noninflammatory cortical area at post-infection week 1 and 3 by the in situ TUNEL method. Kidney weight was significantly decreased in the APN group compared with the normal group at postinfection week 1 and 3. In the APN group, tubulointerstitial inflammation with heavy neutrophilic infiltration was found mainly in the upper and lower poles of the kidney in both the first and third week groups. Fibrosis was dominant in the third week of the APN group. However, inflammation and fibrosis were not significantly improved by TRX treatment. The apoptotic index of tubular cells was significantly increased in noninflammatory cortical area in the first week of both APN and TRX groups. It decreased near the normal control value in the third week.
TGF-beta1 protein expression was localized in the inflammatory area. There was no TGF-beta1 expression in the tubules of the noninflammatory area. These findings suggest that renal growth retardation in experimentally induced APN in infant rats is related not only with the inflammatory reaction itself but also with the increased apoptosis of tubular cells in noninflammatory area. Ceftriaxone alone does not eliminate the inflammation nor prevent growth retardation effectively.
Transitional cell carcinoma of the urinary bladder is the most common cancer of the urinary tract and is characterized by frequent recurrence. Like the other malignant tumor, the genetic alterations leading to neoplastic transformation of the urothelium are related with the activation of oncogenes and loss of functional tumor suppressor genes.
Cyclin D1 is a putative protooncogene as cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumor. In this study we performed immunohistochemical stainings of cyclin D1 and p53 in both primary and recurrent transitional cell carcinomas of urinary bladder from 56 patients including 20 cases of recurrent tumor, and compared their results with histopathologic features. The results were as follows. Cyclin D1 immunoreactivity was found in 10 of 10 cases (100%) of grade 1, 25 of 41 (61%) cases of grade 2, and 11 of 25 (44%) cases of grade 3 transitional cell carcinomas. p53 immunoreactivity was found in 40% of grade 1, 63% of grade 2, and 87% of grade 3 lesions. Cyclin D1 expression was significantly higher in Ta and T1 lesions than T2 to T4 by pathologic tumor stage.
Conversely p53 immunoreactivity was increased in proportion to the T classification. Cyclin D1 was de creased in recurrent transitional cell carcinomas, compared with primary transitional cell carcinomas. However, there was no statistical significance.
In conclusion, cyclin D1 immunoreactivity is associated with low histologic grade and low tumor stage. And there is inverse relationship between the cyclin D1 and p53 overexpression.
BACKGROUND The relationship between hepatoliths and cholangiocarcinoma is etiologically unclear. However, histogenetic sequencing with hyperplasia, dysplasia and carcinoma can occur in the bile ducts of hepatolithiasis. METHODS We studied 55 cases of hepatolithiasis and examined the specimens of resected liver tissue with a microscope.
The growth patterns of bile duct epithelium were divided into four types: flat, tufting, micropapillary and papillary. The dysplasia was also divided into low-grade dysplasia (LGD) and high-grade dysplasia (HGD). RESULTS Of 55 cases of hepatolithiasis, 30 cases (54.6%) were of the flat pattern, 13 cases (23.6%) the micropapillary pattern, and 11 cases (20%) the tufting pattern. Epithelial hyperplasia was noted in only 36 cases (65.5%) in the large bile ducts, but dysplastic changes were found in 19 cases. Of 19 cases of dysplasia, LGD was present in 14 cases (25.5% of total 55 cases) an HGD in 5 cases (9% of total 55 cases). The epithelial hyperplasia showed histologic growth of the flat pattern in 29 cases out of 36 cases. But LGD (14 cases) had 6 cases of the tufting pattern and 7 cases of the micropapillary pattern. HGD (5 cases) revealed 4 cases of the micropapillary pattern with one case of the tufting pattern. CONCLUSION This study suggests that sequences of hyperplasia, low-grade dysplasia and high-grade dysplasia can play a role in the carcinogenesis of bile duct epithelium in hepatolithiasis with the histologic pattern changing from flat to micropapillary growth.