Background Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.
Methods We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.
Results CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.
Conclusions Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.
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Herpes simplex virus type 1 and 2(HSV-1, HSV-2) are the ubiquitous human pathogens responsible for a variety of afflictions, HSV-2 is one of the viruses that were suspected of promoting carcinogenesis in the uterine cervix.
Certainly, there is a need for the more sensitive and accurate laboratory techniques for HSV detection.
We examined total 80 cases of smears including 17 Tzanck smears of skin and 63 cases of Papanicolaou smears from total 77 patients with clinical impression of herpetic infections, from September, 1985 through August, 1989.
Immunohistochemical typings for HSV-1 and HSV-2 were performed together with routine cytologic findings and compared The results are as follows : 1) patients were 9 males and 33 females, and age distribution was between 5 and 71 years 2) Subjective symptoms such as ulceration, vesicle, vaginal discharge, pruritus, and pain were complained in 36 patients and 38 cases were genital herpes. Recurrence was noted in 11 cases.
3) Positive results were obtained in 42 among 80 cases.
4) Both routine cytology and imunohistochemical staining were positive in 13 cases and in 24 cases only immunohistochemical staining were positive. 5 cases were positive only in routine cytologic smears.
5) The cases that immunocytochemical stain had been performed were 37 cases, which were all positive in type 2, Among the above 37 cases, type 1 also were positive in 5 cases.
The results show that the immunoperoxidase technique is one of the rapid and reliable method to confirm the herpetic infection when suspected and that it is particularly useful when the Papanicolaou smear findings are equivocal
The origin of the stromal cell of cerebellar hemangioblastoma has long been studied electron microscopically and immunohistochemically. The results and theories about the stromal cell origin are variable and plentiful. However, the exact origin of the stromal cell remains controversial. The present study is aimed to elucidate the nature of the stromal cell of cerebellar hemangioblastoma. Ten cases of hemangioblastoma in Severance Hospital were used for immunohistochemical analysis of the stromal cell. The immunohistochemical staining of GFAP, S-100 protein, NSE, alpha-l-antichymottypsin, cytokeratin, CD 68, factor VIII related antigen, and synaptophysin were performed. The results were as follows; GFAP and S-100 protein were stained mainly but weakly in bellar capillary spindle cell and cellular process. NSE was stained mainly in foam cells, and 6 cases among them revealed strong reaction.
ct-l-antichymotrypsin was stained in a few foam cells of 5 cases. Cytokeratin, CD 68, factor VIII related antigen, and synaptophysin showed negative reaction. Based on these results, it is considered that the origin of the stromal cell is histiocytic or neurogenic rather than glial. The weak positivity of GFAP and S-100 protein may support the neurogeriic origin but ct-l-antichymotrypsin positivity does not support the possibility. The positivity of GAP and S-100 protein supports the phagocytic action of histiocytic cell and suggests histiocytic origin rather than neurogenic.
An unusual pattern of focal involvement of lymph nodes by Hodgkin's disease is described using the name Interfollicular Hodgkin's Disease. It is characterized by florid reactive follicular hyperplasia which overshadows involvement of the interfollicular zones by Hodgkin's desease. The importance of interfollicular Hodgkin's disease rests on its misdiagnosis as a benign lesion. We report a case of interfollicular Hodgkin's disease in a 34-year-old female patient in the inguinal area. The lymph nodes showed reactive follicular hyperplasia. The focal interfollicular spaces were invaded by Hodgkin's disease. The Reed-Stemberg cells stained positively with CD15 and CD30 antibody in the immunohistochemical stain. An in situ hybridization study looking for EBV was negative in these R-S cells.
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.
An immunohistochemical stain for p53 tumor suppressor gene product was performed in 59 primary lung cancers to study the relation between its expression and type of the tumor, degree of tumor differentiation,clinical stage and smoking.
The results were as follows: 1. The expression of mutant p53 protein was noted in 28 of 59 cases(47.5%) of primary lung cancers. The p53 protein was expressed in 21 of 35(60%) squamous cell carcinomas, in 6 of 21(28.6%) adenocarcinomas, and 1 of 1(100%) small cell carcinoma. There was a significant difference in expression of p53 among the different histologic types of lung cancer(p<0.05). 2. The incidence of p53 protein expression did not correlate with the degree of tumor cell differentiation or the clinical stage of lung carcinoma(p>0.05). 3. The incidence of p53 protein expression was higher in smokers(current: 75%, former: 46.2%) than in non-smokers(5.6%) and was increased in direct proportion to the pack years. There was a statistically significant correlation between p53 expression and smoking(p<0.05). The mutation of p53 gene may often be an early event in the development of lung cancer and it is suggested that the smoking known as a risk factor for the development of the lung cancer may be associated with the transformation of p53 tumor suppressor gene into mutant p53 gene or oncogene.
We performed a histopathologic and immunohistochemical study of 23 cases of surgically resected large cell undifferentiated carcinoma(LCUC) of the lung. The relative incidence of LCUC was 7.6% among the total resected cases of primary lung cancer over 7 years(1987-1993). The mean age of the patients was 56 years and 21 cases were male. The mean size of the mass was 5 cm and 11 cases were located peripherally. According to the histologic features, LCUC could be divided into three groups: squamous cell carcinoma-like(6 cases), adenocarcinoma-like(13 cases), and small cell carcinoma-like(4 cases) groups. The histologic differences were related to the variations of the immunohistochemical properties, but there were no differences in prognosis among these groups.
Immunoreactivity to cytokeratin(CAM 5.2) was demonstrated in 22/23(96%). Carcinoembryonic antigen was positive in 13/23(57%). Neuron specific enolase and chromogranin were positive in 11/23(48%) and 5/23(22%), respectively. Vimentin was seen in 11/23(48%). From these observations, we could subclassify them by their immunologic phenotypes; exocrine features in 6/23(26%), neuroendocrine(NE) features in 4/23(17%), both exocrine and NE phenotypes in 7/23(30%), and 6 cases(26%) showed neither phenotype. The group with NE features showed a worse prognosis(P<0.05) and immunoreactivity for vimentin was also related to a worse prognosis(P<0.05). These findings imply that the immunohistochemical properties of LCUC are closely related to the histopathologic features. The groups, subdivided by histology and immunoreactivity, showed no prognostic difference except for the NE differentiation and reaction for vimentin.
In this study, the prevalence of Hepatitis B virus(HBV) DNA in the needle biopsied paraffin embedded liver tissues of chronic hepatitis B patients by rapid nested PCR was examined. DNA was extracted by NaOH with boiling, and amplified by rapid air thermocycler with glass capillary tubes and nested PCR with two primer sets specific for the surface and the core genes of HBV. The PCR results were compared to that of serum HBeAg, serum HBV DNA by dot blot hybridization with a radioactive DNA probe, and tissue immunohistochemical (HBsAg/ HBcAg) studies. Among 44 patients with chronic hepatitis with serum HBsAg positivity, HBV DNA could be detected by PCR in 43 liver tissues (98%).
This results were comparable to the positive rates of 94%(31/33) for serum HBV DNA, 80%(35/44) for serum HBeAg, and 59%(26/44) and 75%(33/44) for tissue HBsAg and HBcAg, respectively. The accordance rate between tissue PCR and serum DNA probe testing was 91%. The results indicate that HBV DNA detection by rapid nested PCR of paraffin embedded liver tissues by needle biopsy is a more sensitive method to detect the HBV DNA carrier than the serum HBeAg or tissue HBsAg/HBcAg status, and is well correlated with the result of serum HBV DNA probe testing. Therefore this method is a practical indicator for the diagnosis and replication status in retrospective analysis.
Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions.
Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.
A large body of evidence indicates that Helicobacter pylori is involved in the pathogenesis of chronic gastritis and peptic ulcers. Several techniques are currently used for detecting H. pylori. Recently the immunohistochemical method was introduced for rapid detection of H. pylori. To compare the result of the immunohistochemical method with those obtained by microbiologic methods, we glean formalin fixed, paraffin embbeded gastric and duodenal biopsy specimens from 85 patients with upper gastrointestinal symptoms. We set fifty cases which H. pylori was cultivated and identified by Gram stain as Group I, and thirty-five cases without H.
pylori in Gram stain and culture as Group II. The results were as follows. 1) The sensitivity and the specificity of immunohistochemical method were 94% and 80% compared with the microbiologic method. Positive and negative predictive value of the immunohistochemical method were respectively 87% and 90%. However, in seven cases of Group II, H. pylori were identified by immunohistichemical method. 2) Immunohistochemical staining exhibited bacteria that were present in the mucus layer, the surface of the gastric mucosa and metaplastic gastric epithelium in duodenum. With reference to the distribution and density of H. pylori in Group I and II, a significant correlation existed between microbiologic results and bacterial load of the biopsy specimen (p<0.01). 3) Chronic inflammation of gastric biopsies were seen in all 45 H. pylori-positive cases(100%) and 16 out of 19 H. pylori-negative cases(84%). The degree of chronic inflammation was more severe in positive cases than negative cases. Activity of inflammation was seen 98% of H. pylori-positive cases and 16% of H. pylori-negative cases. Intestinal metaplasia was seen 40% of H.
pylori-positive cases and 58% of H. pylori-negative cases.
Lymphoid follicles and aggregates were seen in 47%(27 cases) of H. pylori-positive cases. Among 47%, cases with lymphoid follicles were 9%(4 cases) and cases with lymphoid aggregates were 38%(17 cases). In H. pylori-negative cases, lymphoid follicles and aggregates were seen in 16%(3 cases).
It is possible to obtain samples from most of the individuals who underwent the endoscopy in Korea. And this method is simple, rapid and sensitive. We conclude that the immunohistochemical method is another useful diagnostic tool for detection of Helicobacter pylori.
We reviewed 86 thymic epithelial tumors and reclassified them according to the Kirchner and Muller- Hermelink classification. They were subtyped as medullary, mixed, predominantly cortical (organoid), cortical, well differentiated thymic carcinoma, and poorly differentiated thymic carcinoma. The frequency of each subtype was determined and histologic findings were related to stage and myasthenia gravis. Immunohistochemical stains for bcl-2 protein as a marker for medullary thymocytes and MIC-2 protein as a marker for cortical thymocytes were performed in each case. The stages and association of myasthenia gravis was significantly different in each subtypes. The results of this study demonstrate that this histogenetic classification is clinically applicable. The bcl-2 protein was specifically demonstrated in lymphocytes within areas of medullary differentiation and MIC-2 protein in cortical differentiation. The expression of bcl-2 and MIC-2 proteins lend histogenetic support for this new classification of thymoma. Bcl-2 protein is strongly expressed in tumor epithelial cells of every case of poorly differentiated thymic carcinoma whereas the other types of thymic epithelial tumors do not show epithelial expression of this protein. The strong expression of bcl-2 protein in tumor epithelium may be considered as a predictor of aggressive behavior in thymic epithelial tumors.
Cytologic diagnosis of reactive or malignant effusion is sometimes difficult. Espe- cially, differentiation of benign reactive mesothelial cells from malignant cells in body effusion is more difficult. Recently, immunohistochemistry has been used to diagnose difficult cases. Phospholipase C(PLC)-gamma 1 is one of the isoenzyme of the PLC which plays central role in signal transduction involving cellular growth, differentiation and transformation by phosphorylating many protein component. Increased expression of PLC-gamma 1 in human breast carcinoma, colorectal carcinoma and stomach cancers are reported. To evaluate the efficacy of positive PLC-gamma 1 immunostaining in the diagnosis of malignancy in effusions, paraffin-embedded cell blocks of pleural fluid and ascites from 10 patients(5 metastatic adenocarcinomas, and 5 reactive mesothelial cells) were immunostained with a monoclonal antibody to PLC-gamma 1.
PLC-gamma 1 immuostained all the adenocarcinomas in cell block(5/5) with intense membrane pattern, however, none of the reactive mesothelial proliferations stained with the diagnostic membrane pattern. Thus, our study strongly supports the conclusion that PLC-gamma 1 immunopositivity is likely to become a useful adjunct for the diagnosis of malignancy in effusions.
The pancreas consists of two types of tissue arising from same primitive cells, but with entirely different functions.
Although the adult human pancreas and fetal islet tissue have been the subject of numerous electron microscopic studies, little is known of the ultrastructure of the developing human exocrine pancreas. The purpose of the current study is to investigate development of endo and exocrine of pancreas, especially during the middle trimester of human fetal life, which is the period of acinar cell maturation. Fresh autopsy specimens of pancreas, taken from 15 human fetuses at the 12th (n=2), 13-16th (n=5), 17-20th (n=4), 21-24th (n=2) and 25-28th (n=2) weeks of gestation, were studied electron microscopically, and immunohistochemically. Antisera against insulin, somatostatin, glucagon, pancreatic polypeptide and gastrin, were used for immunohistochemistry. By the 12th week, primitive exocrine acini were identified and these were matured rapidly in the next 6 weeks. At the 17th week stage, ultrastructural examination revealed atypical zymogen granules in the acinar cells. These became progressively less numerous in the 21-28 week period when classical zymogen granules increased upto the level of adult stage.
All the endocrine cells were found at the 12th week, forming primitive or mature islets. The relative ratio of endocrine cells at the 12th week was about 35.4%, 24.9%, 39.8%, 0.5% for A, B, D & PP cell, respectively. But at the 25th to 28th week of development, the relative numbers of A and D cells decreased somewhat, whereas those of the B cells increased.
The PP cells were constant. The G cells were found at the 12th week of fetal period, which appeared through out the on period.