Nuclear and cell area measurements in the cytological evaluation of pleural effusions: a study of subjective assessments and morphometric measurements

Morphometric measurements of cellular area, nuclear area and nuclear:cytoplasmatic ratio were performed on single cells in pleural effusions from 15 patients with effusion caused by bronchial, ovarian, or mammary carcinoma. The results were compared with corresponding measurements on mesothelial cells in pleural effusions from 15 patients without malignant disease. Significant differences were found between the mean values from cellular area, nuclear area, and nuclear:cytoplasmatic ratios in mesothelial cells from benign effusion versus malignant cells from effusions associated with metastatic growth. Such morphometric measurements are, however, of little value in routine diagnostic work as more than 90% of the cells in the two groups showed similar values.     

CEA、CA19-9、CA125在鉴别伴有胸腔积液的良恶性肺部疾病中的应用

目的:通过对胸腔积液中癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原19-9(CA19-9)的检测,探讨各指标在对伴胸腔积液的肺部良、恶性疾病鉴别诊断中的价值.方法:应用化学发光微粒子免疫测定法对30例肺癌患者,30例良性肺部疾病患者的胸腔积液标本进行三种肿瘤标志物测定,并根据受试者工作特性(ROC)曲线建...     

Clinical and laboratory parameters in the differential diagnosis of pleural effusion secondary to tuberculosis or cancer

PURPOSE: To evaluate the clinical and laboratory characteristics of pleural effusions secondary to tuberculosis (TB) or cancer (CA). METHODS: A total of 326 patients with pleural effusion due to TB (n=182) or CA (n=144) were studied. The following parameters were analyzed: patient gender, age and pleural effusion characteristics (size, location, macroscopic fluid aspect, protein concentration, lactate dehydrogenase (DHL) and adenosine deaminase activity (ADA) and nucleated cell counts). RESULTS: Young male patients predominated in the tuberculosis group. The effusions were generally moderate in size and unilateral in both groups. Yellow-citrine fluid with higher protein (p < 0.001) levels predominated in effusions from the tuberculosis group (5.3 + 0.8 g/dL) when compared to the CA group (4.2 +/- 1.0 g/dL), whereas DHL levels were more elevated in CA (1,177 +/- 675 x 1,030 +/- 788 IU; p = 0.003) than in TB. As expected, ADA activity was higher in the TB group (107.6 +/- 44.2 x 30.6 +/- 57.5 U/L; p < 0.001). Both types of effusions presented with high nucleated cell counts, which were more pronounced in the malignant group (p < 0.001). TB effusion was characterized by a larger percentage of leukocytes and lymphocytes (p < 0.001) and a smaller number of mesothelial cells (p = 0.005). Lymphocytes and macrophages were the predominant nucleated cell in neoplastic effusions. CONCLUSION: Our results demonstrate that in lymphocytic pleural exudate obtained from patients with clinical and radiological evidence of tuberculosis, protein and ADA were the parameters that better characterize these effusions. In the same way, when the clinical suspicion is malignancy, serous-hemorrhagic lymphocytic fluid should be submitted to oncotic cytology once this easy and inexpensive exam reaches a high diagnostic performance (approximately equal 80%). In this context, we suggest thoracocentesis with fluid biochemical and cytological examination as the first diagnostic approach for these patients.     

Diagnostic efficiency of carcinoembryonic antigen and CA125 in the cytological evaluation of effusions.

In our previous study, the combination of the concentrations of carcinoembryonic antigen (CEA) and CA125 and the findings from cytological examination in 189 benign and malignant pleural and peritoneal effusions was useful in the diagnosis/classification of malignant effusions. Sensitivity of CEA (level, greater than 5 ng/mL) was 68%; specificity was 99% for the diagnosis of malignant effusions secondary to carcinoma of the lung, breast, gastrointestinal tract, and mucinous carcinoma of the ovary. Sensitivity of CA125 (level, greater than 5000 U/mL) was 85%; specificity was 96% for the diagnosis of malignant effusions in carcinoma of the ovary, fallopian tube, and endometrium. We now expanded the study to include 840 pleural and peritoneal effusions (benign, n = 520; malignant, n = 320) and analyzed the data by the statistical method of Rudolph and colleagues. Based on new cutoff values, ie, CEA level at 6.3 ng/mL and CA125 level at 3652 U/mL, the sensitivities for detection of malignant effusions secondary to carcinomas of the lung, breast, and gastrointestinal tract and mucinous carcinoma of the ovary varied between 75% and 100%; specificity was 98%. Sensitivity of CA125 for detection of malignant effusions from müllerian epithelial carcinoma was 71%; specificity was 99%. The elevated CEA fluid level alone helped to diagnose malignant effusions of the gastrointestinal tract in 54%, breast in 19%, and lung in 16%. The high CA125 fluid level was predictive of müllerian epithelial carcinoma. Adjunctive use of CEA and CA125 levels in fluid enhances the sensitivity of cytological diagnosis and may be predictive of the primary site in patients who present with carcinoma of an unknown primary source.     

良、恶性肝病、卵巢疾病和胰腺疾病患者血清AFP、CEA、CA125和CA199水平的相关研究

目的:血清中AFP、CEA、CA125和CA199的测定研究良、恶性肝病、卵巢疾病和胰腺疾病诊断的临床意义.方法:发光免疫分析测定了52例正常对照组,68例良性肝病,65例肝癌,56例卵巢疾病和51例胰腺疾病的血清中AFP、CEA、CA125和CA199水平,批内CV＜5%,批间CV＜10%.结果:良性疾病患者的血清四项肿瘤标记物水平大致与对照组的相似(p＞0.05).原发性和继发性肝癌患者的血清CA125和CA199水平较对照组显著升高(p＜0.001).卵巢癌与胰腺癌患者也同样如此(0.001＜p＜0.05).结论:血清AFP、CEA、CA125和 CA199的联合测定是诊断和鉴别肝癌、卵巢癌和胰腺癌的最好方法.     

Infection of mesothelial cells with human herpes virus 8 in human immunodeficiency virus-infected patients with Kaposi's sarcoma, Castleman's disease, and recurrent pleural effusions.

Recurrent pleural effusions are common complications of hospitalized patients with human immunodeficiency virus (HIV) infection and may pose difficult diagnostic dilemmas. A common cause of recurrent pleural effusions in up to 30% of HIV-seropositive patients is pulmonary involvement by Kaposi's sarcoma, a human herpesvirus 8 (HHV 8)-related neoplasm. The pathogenesis of these effusions is unclear. These recurrent effusions, although benign, have shown significant mesothelial atypia/reactive changes of uncertain etiology. We attempted to evaluate these effusions morphologically and molecularly for the presence of HHV 8, with particular attention to mesothelial cells. All recurrent pleural effusions, as defined by any effusion tapped for cytological examination on more than two occasions, in HIV-positive patients at the National Institutes of Health were examined from 1998 to the present. Cases were stratified according to patients with and without histologically confirmed HHV 8 disease manifestations. Five patients with HHV 8 diseases (four with disseminated Kaposi's sarcoma and one with Castleman's disease) were identified. As a control group, five effusions from HIV-seropositive patients without known HHV 8-related diseases were identified. Cytological examination of effusions in patients with HHV 8-related diseases demonstrated atypical/markedly reactive mesothelial cells accompanied by a polymorphous background of lymphocytes. Molecular studies for B- and T-cell clonality in microdissected whole samples showed no definitive clones in these cases. Conversely, polymerase chain reaction (PCR) studies for the HHV 8 virus was positive in these samples. PCR studies on pure populations of microdissected mesothelial cells from the HHV 8-related effusions were positive for HHV 8 sequences, whereas those from HIV patients with non-HHV 8 related diseases were negative. Immunohistochemistry for HHV 8 (monoclonal antibody to latent nuclear antigen (LNA-1; ORF-73) on cellblock material demonstrated scattered positive mesothelial cells in three of the five cases of HHV 8-associated effusions. HHV 8 has been recently implicated in the pathogenesis of Kaposi's sarcoma and primary effusion lymphoma. Mesothelial cells in recurrent pleural effusions from patients with Kaposi's sarcoma and Castleman's disease appear to be infected with HHV 8. Additional studies need to be done to define the role of mesothelial cell infection in the pathogenesis of these HHV 8-associated effusions and define the prognostic significance.     

Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods to differentiate mesothelioma from benign reactive mesothelial cell proliferation and adenocarcinoma in pleural and peritoneal effusions

OBJECTIVE: To determine whether malignant mesotheliomas can be differentiated from adenocarcinomas and benign reactive mesothelial cells in pleural and peritoneal fluids using immunohistochemical analysis in conjunction with DNA ploidy analysis. DESIGN: Sixteen cases of malignant mesothelioma, including epithelial, sarcomatous, and biphasic types, were collected. DNA analysis using flow cytometry and/or image analysis was performed on paraffin-embedded tissue from 15 of the mesothelioma cases, as well as on cytospin cell preparations from samples of pleural and peritoneal fluids from cases with either cytologically proven adenocarcinoma (seven cases) or benign reactive mesothelial cells (seven cases). Immunohistochemical studies were done in 15 mesotheliomas, 5 adenocarcinomas, and 4 benign reactive mesothelial cell effusions. RESULTS: All malignant mesotheliomas tested (100%) stained positively for prekeratin, whereas stains for carcinoembryonic antigen, B72.3, Leu-M1, and Ber-EP4 were negative. Stains vimentin, epithelial membrane antigen, and CA125 were positive in 75%, 75%, and 25% of cases tested, respectively. Benign reactive mesothelial cell cases stained similarly. Adenocarcinomas were more likely to react positively with B72.3, Ber-EP4, and carcinoembryonic antigen, and negatively with vimentin. DNA analysis showed that all benign cases were diploid, while all adenocarcinomas were nondiploid. Fifty-three percent of the malignant mesotheliomas were nondiploid. Sensitivity for detection of nondiploidy was greater for image analysis than for flow cytometry (100% vs 75%). CONCLUSIONS: B72.3, Ber-EP4, carcinoembryonic antigen, and vimentin are useful immunohistochemical markers in differentiating malignant mesotheliomas from adenocarcinomas, whereas immunohistochemistry does not reliably distinguish malignant from benign hyperplastic mesothelial cells. The addition of DNA ploidy studies is useful for differentiating the latter two groups.     

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space

The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biologically active, as an anti-LTB4 antibody partially neutralized the chemotactic activity of parapneumonic, tuberculous and cancer effusions. Macrophages, neutrophils, lymphocytes, mesothelial cells and cancer cells all expressed mRNA for 5-lipoxygenase, the enzyme that initiates leukotriene synthesis leading to the production of LTB4, in exudative pleural effusions. Upon stimulation in transudative pleural effusions, pleural macrophages produced, in a time-dependent fashion, a significantly higher concentration of LTB4 than mesothelial cells. These studies demonstrate that different cell types are capable of producing LTB4 in the inflamed pleural space and that this mediator may play a crucial role in the recruitment of neutrophils into the pleural space.     

Immunocytological analysis of the Tn associated antigen 83D4 in serous effusions from patients with cancer: comparison with Tn soluble glycoprotein.

AIMS--To determine whether the monoclonal antibody (MoAb) 83D4, previously shown to be highly specific for carcinoma cells, can be used as an immunocytological marker to discriminate between benign and malignant cells in serous effusions; and to test for a correlation between expression of the antigen reacting with MoAb 83D4 on effusion cells and the amount of soluble 83D4 antigen in effusion fluids. METHODS--Thirty three pleural and 23 peritoneal effusions from 56 cancer patients with metastatic disease were tested for the presence of Tn associated 83D4 antigen by immunocytochemical staining, and for the presence of soluble antigen in supernatants. The patients had undergone various chemotherapy and radiation therapy protocols. RESULTS--As a result of the various types of treatment, the cytological characteristics of the cells were often modified and the antigenic epitopes may have been altered. Positive staining for 83D4 MoAb was obtained in 36 (97%) of the 37 malignant effusions, eight (73%) of 11 suspect effusions, and three (38%) of the eight apparently benign effusions (free of malignant cells). In these latter cases, cytological reassessment showed a few suspect cells in two cases. 83D4 soluble antigen was detected in 30 of 37 malignant effusions (81%), five of 11 suspected infusions (46%), and five of eight apparently benign effusions (63%). CONCLUSIONS--Immunocytochemical staining with anti-83D4 antibody is useful for differentiating reactive or atypical mesothelial cells from epithelial cells, especially in breast cancer effusions.     

Evaluation of vascular endothelial growth factor (VEGF) in neoplastic and tuberculosis effusions--preliminary results

Angiogenesis is an essential process for tumor progression and VEGF is thought to be a critical factor for this process. VEGF is also known as a strong capillary permeability inducer, what can be important for pleural effusion development. The aim of the study was the comparative analysis of VEGF concentration in pleural effusions collected from 31 patients with various type of cancer, 8 patients with tuberculosis, 5 patients with transudates. Additionally VEGF concentrations in 11 serum specimens from patients with neoplastic disease was evaluated. VEGF concentrations was determined using a sandwich enzyme-linked immunoadsorbent assay. The VEGF level in pleural transudates as well as tuberculous effusions was significantly lower than in malignant fluid. The were no differences in VEGF level in malignant pleural fluid of different origin. The correlation between VEGF concentrations in malignant pleural fluid and sera of individual patients was not found. Our results indicate that VEGF might play an important role in accumulation of pleural fluid especially that of malignant origin. VEGF level in pleural fluid differs significantly from cancer to benign group of patients what can be important for differential diagnosis of plural effusions origin.     

Regulatory T cells in malignant pleural effusions subsequent to lung carcinoma and their impact on the course of the disease

Tumors exert suppressive effects on the host immune system and tumor progression can be linked to functional impairments of immune cells. Regulatory T cells (Treg) are a subpopulation of T lymphocytes and play a key role in suppressing immune responses against autoimmune diseases and cancer.The aim of the study was to investigate the prevalence of Treg in malignant and benign pleural effusions and to evaluate the relationship between Treg frequency and disease advance. Pleural effusions from 76 patients were subjected to a routine laboratory diagnosis and analyzed by conventional cytology. Biological materials were divided into three groups: malignant pleural effusions with malignant cells, effusions from patients with malignancy but without malignant cells, and non-malignant pleural effusions.The frequency of Treg in malignant pleural effusions was significantly higher compared to non-malignant effusions. In general, the increase in Treg frequency was correlated with a decrease in the percentage of lymphocytes and an increase in T CD4+ and T CD4+ CD25+ cells. The highest percentage of Treg was observed among patients with the most advanced clinical stage of lung cancer in terms of size and location of a primary tumor, T4. A Kaplan–Meier survival analysis showed a statistically significant trend towards an adverse outcome for patients representing higher Treg counts. Overall, our results support the extraordinary potential of Treg control in future anticancer therapy.     

The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.     

胸腹水细胞端粒酶活性定性和定量检测

目的探讨端粒酶活性定量检测在诊断良恶性胸腹水中的应用价值。方法采用TRAP-银染定性方法和rrRAP-PicoGreen定量方法,对102例已确诊患者的胸腹水细胞进行端粒酶活性分析。结果恶性胸腹水细胞端粒酶活性明显高于良性胸腹水细胞,其定性检测诊断率明显高于细胞病理学。乳腺癌患者胸腹水细胞的端粒酶活性明显高于卵巢癌、肝癌患者胸腹水细胞的端粒酶活性;肺癌患者胸腹水细胞端粒酶活性明显高于肝癌。在良性胸腹水中,感染性胸腹水细胞端粒酶活性高于非感染性胸腹水。结论恶性胸腹水细胞端粒酶活性明显升高。端粒酶活性定量检测较定性检测更敏感、简便,对良恶性胸腹水的诊断和鉴别诊断有一定应用价值。     

结核性胸膜炎患者CA125检查的临床意义

了解和评价CA125检测对结核性胸膜炎的诊断和鉴别诊断价值。结核性胸膜炎组患者137例,肺癌组患者45例,采用ELASA法检测血清和胸水CA125水平,并和对照组比较。结果表明结核性胸膜炎组和肺癌组血清和胸水CA125水平组间无显著性差异（P＆gt;0.05）,但均明显高于对照组（P＆lt;0.01）。抗结核治疗后,结核性胸膜炎组血清CA125水平降低,治疗后6个月CA125水平与对照组相比无显著性差异（P＆gt;0.05）,本文提示CA125检测对结核性胸膜炎的鉴别诊断价值有限,动态观察CA125水平变化可能对预后判断有积极意义。     

Differential expression of CD44s and CD44v3-10 in adenocarcinoma cells and reactive mesothelial cells in effusions

The detection of malignant cells in serous effusions obtained from patients diagnosed with cancer marks the presence of metastatic disease and is associated with a poor outcome. The purpose of this study was to evaluate the role of CD44s and CD44v isoforms in the distinction between mesothelial cells and malignant epithelial cells in effusions. Fifty-nine fresh pleural and peritoneal effusions were studied. These consisted of 41 specimens from patients with known gynecological neoplasms, 9 from patients diagnosed with breast adenocarcinoma, and 9 effusions from patients with various nongynecological malignancies or tumors of unknown origin. Forty-three effusions contained malignant/atypical epithelial cells, and 16 effusions were diagnosed as reactive. Three effusions contained exclusively malignant cells. Specimens were stained with anti-CD44s, v3, v5, v6, v7 and v3-10. The presence of staining in cancer cells, benign mesothelial cells and lymphocytes was evaluated. CD44s immunoreactivity was seen in 10 of 43 (23%) cases in malignant/atypical epithelial cells and in 53 of 56 (94%) cases in benign cells. In contrast, CD44v3-10 was seen in 23 of 43 (55%) cases in malignant/atypical epithelial cells and in 3 of 56 (6%) cases in benign cells. We advocate the use of CD44s and CD44v3-10 immunostaining in diagnostic evaluation of difficult serous effusions. Received: 30 August 1999 / Accepted: 8 November 1999     

Diagnostic usefulness of EMA, IMP3, and GLUT-1 for the immunocytochemical distinction of malignant cells from reactive mesothelial cells in effusion cytology using cytospin preparations

To differentiate reactive mesothelial cells (RMs) from metastatic carcinoma and malignant mesothelioma (MM) in effusion cytology is crucial for the cytologic diagnosis and the management of the patients. In the present study, the immunocytochemical staining profile of the epithelial membrane antigen (EMA), the insulin-like growth factor-II mRNA-binding protein 3 (IMP3), and the glucose transporter-1 (GLUT-1) was examined to distinguish RMs from malignant cells. A total of 171 pleural (n = 87) and peritoneal (n = 84) effusion specimens, including 50 benign effusions with RMs, 11 MM effusions, and 110 metastatic malignant effusions, were evaluated for immunocytochemistry. EMA, IMP3, monoclonal GLUT-1, and polyclonal GLUT-1 immunoreactivity were observed in 26.0%, 6.0%, 20.0%, and 18.0% of RMs, respectively. In contrast to RMs, the immunoreactivity in MM was 100%, 36.4%, 100%, and 90.9%; adenocarcinoma (AC) was 100%, 80.8%, 81.7%, and 72.1%; squamous-cell carcinoma was 83.3%, 83.3%, 83.3%, and 66.7%. EMA, IMP3, mGLUT-1, and pGLUT-1 expressions were observed in 98.4%, 65.6%, 88.5%, and 75.4% in the pleural effusion with malignant cells, and 100%, 88.3%, 78.3%, and 71.7% in ascites containing malignant cells, respectively. The findings of the present study indicate that the immunocytochemical staining for EMA, IMP3, and GLUT-1 is a useful diagnostic tool for distinguishing effusions containing malignant cells from those that contain benign cells, and in particular, we suggest that the combination of mGLUT-1 and EMA, and IMP3 and EMA are extremely useful in pleural effusion and in ascites, respectively.     

Immunohistochemical localization of prekeratin filaments in benign and malignant cells in effusions. Comparison with intermediate filament distribution by electron microscopy.

An immunoperoxidase technique employing antibody to prekeratin was used to study distribution and pattern of staining of prekeratin filaments in cytological smears obtained from 42 specimens of pleural and peritoneal effusions (27 benign, 15 malignant). The smears were either air-dried or ethanol-fixed. Both benign and malignant mesothelial cells showed distinctive peripheral or perinuclear staining patterns which differed from the characteristic arborizing pattern in adenocarcinoma cells. The ultrastructure of these 2 cell types studied in 27 body fluids (12 benign, 15 malignant) and in 13 malignant tumors (3 mesotheliomas, 10 adenocarcinomas) showed a distinctive localizaton of intermediate filaments which corresponded to and could explain the pattern of staining obtained using the immunoperoxidase technique. The immunohistochemical and ultrastructural findings appeared characteristic for benign and malignant mesothelial cells as well as for adenocarcinoma cells, and could be used as markers to differentiate mesothelial tumors and reactive mesothelial cells from adenocarcinomas.     

Hyperplastic mesothelial cells in lymph nodes: Report of six cases of a benign process that can simulate metastatic involvement by mesothelioma or carcinoma

We report six cases of hyperplastic mesothelial cells located in the sinuses of lymph nodes. All patients but one had a concurrent serosal fluid collection (two pericardial, two pleural, one abdominal) at the time of the lymph node biopsy. All effusions cleared with treatment of the underlying disorder, which included lymphoproliferative processes, congestive heart failure, and inflammatory diseases (Dressler syndrome, vasculitis, and glomerulonephritis). Four cases were associated with vascular prominence of the involved nodal sinuses, a feature that may reflect the cause of the underlying effusion or support the transient persistence of benign mesothelial cells in lymph nodes. Two cases were characterized by distention of the nodal sinuses by sheets of mitotically active mesothelial cells. The differential diagnosis includes metastatic carcinoma, keratin-positive dendritic cells native to lymph nodes, and metastatic malignant mesothelioma. Because the latter shares both clinical and morphological features with cases of benign mesothelial cells in lymph nodes, we believe that this distinction may not always be possible in a given biopsy specimen and therefore that careful clinical follow-up is required in such cases.     

Cytologic clue of so-called nodular histiocytic hyperplasia of the pleura

So-called "nodular histiocytic hyperplasia" (NHH) is a benign histiocytic lesion caused by mechanical irritation, inflammation, and tumor. Frequently, it has been confused with mesothelial lesions and other malignant neoplasms. The diagnostic clue is proliferating cells in the lesion showing diffuse, strong immunoreactivity against the histiocytic marker, CD68. Recently, we encountered a case of so-called NHH of the pleura and confused it with various malignant neoplasms on histologic examination. An 80-yr-old Korean female presented with ascites, pleural effusions, and nodules on the pleural base. Both ascites and pleural effusion tapping smears displayed moderate cellularity, vaguely nodular cellular aggregates mainly composed of mononuclear cells with bland morphology, entrapped mesothelial cells, and background lymphocytes. Pleural biopsy demonstrated vaguely nodular, compact cellular aggregates of reactive histiocytes which were immunoreactive against CD68. Based on our case, cytologic examination as well as immunohistochemical study should be stressed in the case of so-called NHH. They can provide us more credible morphologic clues to reach a more accurate diagnosis than histologic examination alone, and we can avoid invasive procedures or unnecessary therapies to patients. To our best knowledge, this is the first report describing the cytologic features of so-called NHH in the English-language literature.