In Korea, the quality control(QC) program forcytopathology was introduced in 1995. The program consists of a checklist for the cytolopathology departments, analysis data on all the participating institutions' QC data, including the annual data on cytologic examinations, the distribution of the gynecological cytologic diagnoses, as based on The Bethesda System 2001, and the data on cytologic-histolgical correlation of the gynecological field, and an evaluation for diagnostic accuracy. The diagnostic accuracy program has been performed 3 times per year with using gynecological, body fluid and fine needle aspiration cytologic slides. We report here on the institutional QC data and the evaluation for diagnostic accuracy since 2004, and also on the new strategy for quality control and assurance in the cytologic field. The diagnostic accuracy results of both the participating institutions and the QC committee were as follows; Category 0 and A: about 94%, Category B: 4-5%, Category C: less than 2%. As a whole, the cytologic daignostic accuracy is relatively satisfactory. In 2008, on site evaluation for pathology and cytology laboratories, as based on the "Quality Assurance Program for Pathology Services" is now going on, and a new method using virtual slides or image files for determining the diagnostic accuracy will be performed in November 2008.

Cytologic examination of the body cavity fluid is very important because the specimens represent a significant percentage of nongynecologic samples and this cytologic examination may be the first, best or only chance for making the diagnosis of an underlying malignancy. The purposes of body cavity fluid examination are to correctly identify cancer cells and if possible, to identify the tumor types and primary sites when presented with unknown primary tumor sites. The most important basic differential diagnosis is that of benign and reactive disease vs malignant disease. Reactive mesothelial cells are a consistent population in body cavity fluid, and these are the most versatile cells in the body. Due to the specific environment of the body cavity, the exfoliated reactive mesothelial cells may show significant morphologic overlap with the morphology of cancer cells. With a focus on the differential points between reactive mesothelial cells and metastatic adenocarcinoma cells, the practical diagnostic approaches, the diagnostic clues and the pitfalls to achieve a correct diagnosis are presented in this review.

Cerebrospinal fluid (CSF) cytology is based on the cytopathologic findings of other body fluids. However, CSF's cytologic features are less familiar to physicians than are those of the other body fluid's cytology because of the small number of cases. The low overall diagnostic accuracy and the presence of false positivity still remain as problems. The incidence of lymphoreticular malignancies and metastatic carcinomas are rather higher than that of primary brain tumors. In this review, the characteristic cytologic findings of conventional CSF cytology are reviewed along with a brief note on the technical preparation and diagnostic pitfalls.

Background : Second opinion diagnosis of outside pathology slides is a common practice for efficient and proper patient management. We analyzed cytology slides from outside hospitals submitted for a second opinion diagnosis to determine whether the second opinion diagnosis had any influence on patient care. Methods : We reviewed 1,153 outside cytology slides referred to Asan Medical Center for second opinions from January, 2007, to December, 2007. All cases were categorized into three groups; no diagnostic discrepancy, minor diagnostic discrepancies (no impact on the management), and major diagnostic discrepancies (significant impact on the management and subsequent follow-up). Results : The thyroid was the most common organ system (933 cases, 80.9%), Forty cases (3.6%) belonged to the major diagnostic discrepancy group and 149 cases (12.8%) to the minor discrepancy group. For validation of second opinion diagnoses in major discrepancy cases, subsequent biopsy or surgical resection specimens and clinical information were reviewed, which were available in 29 cases. The second opinion diagnoses resulted in alteration of clinical management in 21 of 29 cases. Conclusion : For all referred patients, second opinion diagnosis is important and mandatory for appropriate patient care.

We evaluated the usefulness of cervicovaginal cytology as a primary screening test by analyzing the cytologic and histological diagnoses of 2,254 women. Cervicovaginal cytology had 93.0% sensitivity, 86.1% specificity, 88.2% positive predictive value, and 91.7% of negative predictive value. Cervicovaginal cytology as a primary screening test showed much higher specificity but slightly lower sensitivity than HPV DNA testing. However, the sensitivity of cervicovaginal cytology will be improved continuously due to the development of liquid-based cytology. We regard cervicovaginal cytology as a good primary screening test for cervical intraepithelial neoplasia or carcinoma.

Background : Cervicovaginal cytology is a screening test of uterine cervical cancer. The sensitivity of cervicovaginal cytology is less than 50%, but studies of cytologic/histologic correlation are limited. We analyzed the diagnostic accuracy of cervicovaginal cytology in the detection of the squamous epithelial lesions of the uterine cervix and investigate the cause of diagnostic discordance. Materials and Methods : We collected a total of 481 sets of cervicovaginal cytology and biopsies over 5 years. The cytologic diagnoses were categorized based on The Bethesda System and the histologic diagnoses were classified as negative, flat condyloma, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, or squamous cell carcinoma. Cytohistologic discrepancies were reviewed. Results: The concordance rate between the cytological and the histological diagnosis was 79.0%. The sensitivity and specificity of cervicovaginal cytology were 80.6% and 92.6%, respectively. Its positive predictive value and negative predictive value were 93.7% and 77.7%, respectively. The false negative rate was 19.4%. Among 54 false negative cytology cases, they were confirmed by histology as 50 flat condylomas, 2 CIN I, 1 CIN III, and 1 squamous cell carcinoma. The causes of false negative cytology were sampling errors in 75.6% and interpretation errors in 24.4%. The false positive rate was 7.4%. Among 15 false positive cytology cases, they were confirmed by histology as 12 atypical squamous cells of undetermined significance (ASCUS) and 3 low grade squamous intraepithelial lesions (LSIL). The cause of error was interpretation error in all cases. The overall diagnostic accuracy of cervicovaginal cytology was 85.7%. Conclusions : Cervicovaginal cytology shows high overall diagnostic accuracy and is a useful primary screen of uterine cervical cancer.

This study was performed to compare the efficacy between a DNA chip method and a Hybrid-Capture II assay (HC-II) for detecting human papillomavirus in patients with intraepithelial lesions of the uterine cervix. From May, 2005, to June, 2006, 192 patients with abnormal colposcopic findings received cervical cytology, HC-II and HPV DNA chip tests, and colposcopic biopsy or conization. We compared the results of HC-II and HPV DNA chip in conjunction with liquid based cervical cytology (LBCC) and confirmed the results of biopsy or conization. The sensitivity of the HPV DNA chip test was higher than HC-II or LBCC. The HPV DNA chip in conjunction with LBCC showed higher sensitivity than any single method and higher sensitivity than HC-II with LBCC. We confirmed that the HPV DNA chip test was more sensitive for detecting HPV in cervical lesions than HC-II, and that it would provide more useful clinical information about HPV type and its multiple infections.

Malignant mesothelioma (MM) is a highly lethal neoplasm arising in pleura and the peritoneum and a rapid and accurate diagnosis is crucial for treatment of the disease. However, the sensitivity of cytological analysis using pleural or ascitic fluid is relatively low, yielding an accurate diagnosis in only $32{\sim}79%$ of cases. We tested the diagnostic value of epigenetic alterations in body fluid cytology as a supplement to conventional methods. Paraffin-embedded tissue blocks from 21 MM patients and associated body fluid cytology slides considered no evidence of malignancy were used to test for epigenetic alteration. Using methylation-specific PCR, we detected methylation of RASSF1A and p16 in 47.6% (10/21) of both surgically resected tumor samples, respectively. Body fluid samples of MM also showed abnormal methylation of RASSF1A and p16INK4a genes in 38.1% (8/21) and 33.3% (7/21) of cases. The concordance in the rates of RASSF1A and p16INK4a gene-methylation abnormalities determined from cytology samples and tissue samples were 61.9% (13/21) and 66.7% (14/21), respectively. Combining both genes increases the sensitivity of the test to 57.1 % (12 of 21) of cases. Our results suggest that testing for methylation abnormalities in selected individual genes or gene combinations has diagnostic value as an alternative or adjunct method to conventional cytological diagnosis.

Urothelial carcinoma accounts for 90% of all the cases of bladder cancer. Although many cases can be easily managed by local excision, urothelial carcinoma rather frequently recurs, tends to progress to muscle invasion, and requires regular follow-ups. Urine cytology is a main approach for the follow-up of bladder tumors. It is noninvasive, but it has low sensitivity of around 50% with using the conventional cytospin preparation. Liquid-based cytology (LBC) has been developed as a replacement for the conventional technique. We compared the cytomorphometric parameters of $ThinPrep^{(R)}$ and cytospin preparation urine cytology to see whether there are definite differences between the two methods and which technique allows malignant cells to be more effectively discriminated from benign cells. The nuclear-to-cytoplasmic ratio value, as measured by digital image analysis, was efficient for differentiating malignant and benign urothelial cells, and this was irrespective of the preparation method and the tumor grade. Neither the $ThinPrep^{(R)}$ nor the conventional preparation cytology was definitely superior for distinguishing malignant cells from benign cells by cytomorphometric analysis of the adequately preserved cells. However, the $ThinPrep^{(R)}$ preparation showed significant advantages when considering the better preservation and cellularity with a clear background.

Fine needle aspiration (FNA) cytology is the decisive test in the pre-operative diagnostics of thyroid nodules. Here we share our institutional experience about thyroid aspiration and give suggestions for suspicious cytology results. Three hundred twenty-two cases in 270 patients (mean age 47.4 years, 243 women and 27 men) who underwent thyroidectomy were reviewed. Among the 322 cases, the FNA diagnosis of "positive for malignancy" was 87 cases (27.0%), "suggestive of malignancy" 30 cases (9.3%), "suspicious for malignancy" 61 cases (18.9%), "negative for malignancy" 102 cases (31.7%), and "unsatisfactory smear" 42 cases (13.0%). Eighty seven cases (100%) out of "positive for malignancy", 29 cases (96.7%) out of "suggestive of malignancy", and 39 cases (64.0%) out of "suspicious for malignancy" were papillary carcinoma (148 cases, 95.5%), or follicular carcinoma (2 cases, 1.3%), or metastatic carcinoma (1 case, 0.6%). Seventeen patients who had only negative or unsatisfactory cytology underwent thyroidectomy and nine cases (52.9%) were papillary carcinoma. We suggest that: the cytology diagnosis of "suggestive of malignancy" could be regarded as "positive for malignancy", the cytology diagnosis of "suspicious of malignancy" should be carefully correlated with clinico-radiologic manifestation, and even a negative or unsatisfactory smear should be carefully followed up.

Fine-needle aspiration cytology (FNAC) cannot differentiate follicular adenoma from follicular carcinoma since this distinction can only be based on the presence of capsular or vascular invasion, and this can￢not be detected on a cytologic smear. The goal of this study was to define the diagnostic cytologic findings of follicular neoplasm and the possibility of diagnosing follicular neoplasm by performing FNAC. The cases of histologically diagnosed follicular adenoma and follicular carcinoma on the thyroidectomy specimens were retrieved. Among them, the cases with preoperative FNAC that was done within 3 months of the operation were finally selected. Then we reviewed the FNAC and histologic slides of 19 cases: 9 follicular adenomas and 10 follicular carcinomas. Our results suggest that for cases of follicular neoplasm, the aspirates show high or abundant cellularity, frequent follicle formation and occasional cellular atypism of the follicular cells. However, the atypism is more pronounced and more frequently noticed in the cases of follicular carcinoma, which reveals more higher anisocytosis (7/10, 70%), nuclear pleomorphism (9/10, 90%), coarse clumping of chromatin (8/10, 80%) and cellular overlapping (8/10, 80%).

The cytologic diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) has become one of the common causes of false negative diagnoses when performing fine needle aspiration cytology (FNAC) of the thyroid gland. We retrospectively reviewed all the aspirates for which a diagnosis of FVPTC had been made based on the surgically excised specimens, regardless of the cytologic diagnosis. 145 FNACs was performed in 135 patients. The cytologic diagnoses were categorized as 2 unsatisfactory specimens (1.4%), 16 benign (11.0%), 49 atypical (33.8%) and 78 malignant lesions (53.8%). The tumor cells consistently showed significant nuclear overlapping, irregular nuclei and fine chromatin in all cases; however, nuclear grooves and inclusions were scarce. Galectin-3 immunostaining was performed on the cell blocks of 65 cases and this was positive for 45 cases (69.2%). The results of our study demonstrate that the determination of minimal cytologic criteria is needed to raise the sensitivity of detecting FVPTC by FNAC, and galectin-3 immunostaining is useful to make decisions on the surgical treatment of cytologically atypical thyroid nodules.

Malakoplakia is an uncommon chronic granulomatous inflammation that usually involves the urinary and gastrointestinal tracts, but rarely affects the female genital tract. We experienced a case of malakoplakia in a cervicovaginal smear in a 54-year-old woman. Colposcopic examination showed a friable, easily bleeding tissue in the uterine cervix and the vaginal fornix. The cervicovaginal smear consisted of numerous isolated histiocytes, polymorphonuclear leukocytes, lymphocytes, and plasma cells. The histiocytes had an abundant, granular, and degenerated cytoplasm with inflammatory cell debris. Michaelis-Gutmann bodies were readily identified.

T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell lymphoproliferative disorder with a post-thymic mature T-cell phenotype. The disease is characterized by rapidly rising lymphocytosis, lym-phadenopathy, and splenomegaly. The clinical course is usually aggressive and progresses with frequent skin lesions and serous effusions. In 25% of cases, leukemic cells are small and tumor cells may not have a discrete nucleolus under light microscopy. Although the presence of characteristic cytoplasmic protrusions or blebs in tumor cells is a common morphologic finding in the peripheral blood film irrespective of the nuclear features, small cell variants lacking the typical nuclear features can cause diagnostic problems in clinical cytology. Furthermore, the small leukemic cells can share some cytologic findings with lymphocyte-rich serous effusions caused by non-neoplastic reactive lymphocytosis as well as other small lymphocytic lymphoproliferative disorders. Here, we describe the cytological findings of ascitic fluid complicated by small cell variant T-PLL in a 54-year-old man, the cytology of which was initially interpreted as small lymphocytic malignancy such as small lymphocytic lymphoma/chronic lymphocytic leukemia.

Epithelial-myoepithelial carcinoma (EMC) is a rare low grade malignant tumor of the salivary glands and it shows a characteristic biphasic population of epithelium and myoepithelium. It shows various cytologic and histologic features, so making an exact diagnosis is difficult. We report here on two cases of epithelial-myoepithelial carcinoma arising from the parotid gland and we compare the cytologic findings of the aspirated samples with the histologic findings of the tumors. We think the finding of mixed pattern of large, clear myoepithelia and small epithelia is the most valuable finding in the diagnosis of EMC.

We report here a case of a gastrointestinal stromal tumor (GIST) in the stomach that was diagnosed by endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNA). A 67 year old male patient underwent regular check-ups for five years due to the presence of a submucosal tumor that was found in the fundus of the stomach incidentally. EUS-FNA was performed to evaluate the tumor, which had increased in size from 1 cm to 2.8cm. A cytologic smear revealed cohesive sheets or clusters of spindle cells with elongated nuclei. Immunohistochemical staining revealed a strong positive reaction for c-kit and CD34, without any reaction for smooth muscle actin and Ki-67. Therefore, a diagnosis of GIST was made.

Pseudohyperplastic prostatic adenocarcinoma is a rare histologic variant of prostatic adenocarcinoma that resembles benign nodular hyperplasia. Immunohistochemistry can verify the absence of basal cells, but it is frequently admixed with conventional adenocarcinoma. Because fine needle aspiration cytology is rarely performed in primary prostatic adenocarcinoma, the cytology of the pseudohyperplastic variant has not been described. We experienced a case of metastatic pseudohyperplastic adenocarcinoma in a pulmonary nodule of 75-year-old man. The cytologic smear was mostly composed of large, flat sheets with elongated branching papillae in a clean background. The sheets showed a well-defined honeycomb appearance of tall columnar, regularly arranged monotonous cells with little cytologic atypia. In subsequent prostatic biopsy, pseudohyperplastic variants were identified together with conventional adenocarcinoma of Gleason's grade 3 and 4. The cytologic features of pulmonary nodules were identical to those of pseudohyperplastic components of prostatic adenocarcinoma.

Angiomyolipoma of the liver is a rare benign tumor that's composed of variable mixtures of adipose tissue, smooth muscle and thick-walled blood vessels. We report here on the imprint cytologic features of a hepatic angiomyolipoma in a 47-year-old man. The smears showed spindle and epithelioid tumor cells in clusters, trabeculae and single cells. The spindle cells had elongated, cigar-shaped nuclei with finely granular chromatin and fibrillary cytoplasm. The epithelioid cells had round nuclei with a moderate amount of cytoplasm. Any adipose tissue was not found. Immunohistochemically, both the spindle and epithelioid cells revealed cytoplasmic positivity for smooth muscle actin and HMB-45.

The recent WHO classification has recognized mucinous tubular and spindle cell carcinoma (MTSCC) as a distinct entity of renal cell carcinoma, exhibiting a mixed pattern of tubules and a surrounding spindle cell proliferation within a myxoid stroma, with low-grade nuclear features. A 51-year-old woman had an incidentally discovered renal mass. Radiologic examination revealed a large, well defined mass in the lower pole of the right kidney; a right radical nephrectomy was performed. Imprint cytologic smears from fresh surgical specimens showed cellular, cohesive clusters with thick, broad trabecular arrangements and branching structures. On high power fields, the tumor was composed of round-to-oval low-grade nuclei with vesicular chromatin and small nucleoli. The tumor cells had indistinct borders and pale, eosinophilic cytoplasm, In some areas, round-to-elongated tubular structures and spindle cell patterns were noted. Chronic inflammatory cell infiltration was noted, along with a mucinous back-ground and occasional psammoma bodies. Neither significant cytologic atypia nor mitosis was seen.

Hibernoma is a rare, benign adipose tumor composed of brown fat cells with eosinophilic granular or multivacuolated cytoplasm. The cytologic features of hibernoma have been rarely reported and may mimic other polygonal cell neoplasms. We report the imprint cytologic features of a case of hibernoma in the left thigh of a 68-year-old woman. Microscopic examination showed large, round, or polygonal brown fat cells. The cells were arranged in fragments or clusters. The nuclei were uniformly round with finely granular chrornatin. The cytoplasm was multivacuolated or univacuolated. The abundant eosinophilic granular cytoplasm was also present. No nuclear atypia were present. Immunohistochemical staining showed that cells were positive for S-100 protein.

Adenocarcinomas with micropapillary patterns are generally aggressive and show lymphotropism. Only a few reports on pulmonary adenocarcinoma with micropapillary patterns have described cytologic findings. A 70-year-old Korean woman was admitted to the hospital because of intermittent dry cough and chest pain. Cytology after bronchial washing showed neoplastic cells in small, angulated, cohesive clusters consisting of 3-20 cells without a fibrovascular core. The resected right middle lobe showed a tumor occupying almost the entire lobe. Histologically, about 90% of neoplastic cells proliferated with micro papillary morphology in the background of bronchioloalveolar carcinoma. Cytologic smears of a bronchial washing showing tumor cells in small, cohesive clusters without a fibrovascular core may indicate an adenocarcinoma with micropapillary pattern.