Fine needle aspiration cytology(FNAC) is preferred because of simplicity, safety, and reliability in the evaluation of patients with thyroid nodule or hyperplasia. However, there are a few limitations such as false-negative or false-positive cases and non-diagnostic material. To evaluate the usefulness of FNAC in thyroid lesions, we reviewed 704 FNAC cases of thyroid nodules from 1988 to 1994 at Soonchunhyang University Hospital. The results are as follows. 1. Among 704 FNAC cases of thyroid gland, 571(81.1%) cases were benign, 12(1.7%) were suspicious, 71(10.1%) were malignancy, and 50(7.1%) were material insufficiency. The cytologic diagnoses of the benign lesions included 168 cases of follicular neoplasm, 139 cases of adenomatous goiter, 162 cases of follicular lesion such as follicular neoplasm or adenomatous goiter, 61 cases of Hashimoto's thyroiditis, 13 cases of subacute thyroiditis, and 28 cases of colloidal nodule or benign nodule. The malignant lesions included 68 cases of papillary carcinona, two medullary carcinomas and a case of metastatic colon cancer. 2. The average number of cytologic smear slides was $4.12{\pm}1.81$ in material insufficiency and $5.63{\pm}1.79$ in diagnostic cases. This difference was statistically significant(p<0.00001). 3. Histological assessment of 150 cases revealed 2 false negative and 1 false positive cases. The false negative cases were a case of marked sclerosis in papillary carcinoma and an occult case of papillary carcinoma. The false positive case resulted from pseudo-ground glass nuclei due to marked dry artifact. 4. Comparison between the FNAC and the histologic diagnosis revealed that FNAC had a sensitivity of 93.5%, a specificity of 99.2%, a false negative rate of 6.6%, a false positive rate of 0.8%, and an overall diagnostic accuracy of 98.0%. Therefore, FNAC of thyroid gland is a very reliable diagnostic method with excellent accuracy rate.

This is a retrospective review of fine-needle aspiration cytology(FNAC) smears of 153 cases of thyroid disease performed during August 1989 to July 1995, which were confirmed histologically following surgical operations. FNAC results showed 63 cases(41.2%) of adenomatous goiter, 45 cases(29.4%) of papillary carcinoma, 29 cases(19.0%) of follicular neoplasm, 4 cases(2.6%) of follicular variant of papillary carcinoma, 4 cases(2.6%) of Hashimoto's thyroiditis, 4 cases(2.6%) of $H\ddot{u}rthle$ cell neoplasm, 2 cases(1.3%) of medullary carcinoma and one case(0.7%) each of subacute thyroiditis and of anaplastic carcinoma. The overall accuracy of cytological diagnosis was 83.7%. These data strongly suggest thyroid FNAC is a reliable preoperative diagnostic tool, but FNAC has been less valuable in the diagnosis of follicular lesions than any other disease of the thyroid. Adenomatous goiter was not infrequently interpreted as follicular neoplasia that requires surgery for diagnostic conformation and vice versa. The following findings are considered to be compatible with follicular neoplasm: 1) microfollicles, 2) nuclear grooving, 3) irregularity of nuclear membrane, and 4) irregular arrangement or crowding of follicular cells in groups. The FNAC criteria of adenomatous goiter are as follows: 1) atrophic follicular cells, 2) presence of macrophages, 3) abundant colloid, and 4) large follicles. It is recommended that aspiration of thyroid lesions in order to analyse with critical clinico-pathological approach and surgery is considered only for nodules that are clinically suspicious or unresponsive to hormone therapy or when a diagnosis of follicular neoplasm is made.

Monoclonal antibody(TCM-9) against human thyroid cancers have been studied by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody(TCM-9) that is known to have strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid does not bind to native or mature human thyroglobulin(Tg). We used to TCM-9 antibody by immunohistochemical staining on 5 follicular cancer, 2 follicular adenoma, 1 follicular neoplasm with suspicious invasion, 2 papillary cancer to ascertain being of help in differentiation between follicular carcinoma and adenoma. Reactivity of TCM-9 was observed in follicular carcinoma and papillary carcinoma but not observed in follicular adenoma. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer.

The diagnostic accuracy of routine cytological preparations from effusions ranges from 60% to 70%. Immunohistochemical markers, especially tumor-associated antigens, have been successfully employed to increase diagnostic sensitivity in effusion cytology. However, more than two different antibodies in diagnosis of effusions are needed. In the view of prevalence of abnormalities of p53 gene in human malignancies we investigated the diagnostic usefulness of demonstration of p53 protein immunoreactivity in distinguishing benign changes versus malignant processes in effusions. p53 protein expression was studied immunohistochemically in 76 effusions(28 malignant and 48 benign) using anti-human p53 antibody p53 immunoreactivity was identified in 19 of 28(67.9%) malignant effusions. In contrast, no p53 immunoreactivity was observed in all benign effusions. A specificity of 100% and a sensitivity of 67.9% were observed. These results suggest that immunohistochemical detection of p53 protein seems to be helpful in distinguishing benign changes versus malignant processes in effusions, although its principal limitation is its relatively low sensitivity.

Although bladder cancers are very common, little is known about their molecular pathogenesis. It is known that p53 alteration is found in about 60% of muscle-invasive bladder cancer, necessiating aggressive therapy and poor outcome. We examined the nuclear expression of p53 protein, using D07 monoclonal antibody in the urine samples from 31 patients with transitional cell carcinoma of the bladder to investigate the correlation of p53 overexpression with histologic grades and depth of invasion. The positive rate of p53 protein was 27% in superficial bladder tumor, but increased up to 71% in the invasive bladder carcinomas. The overexpression of p53 protein increased according to Mostofi grading system from 18% in grade I, 45% in grade II, and up to 100% in grade III. The p53 expression tended to be higher in the invasive and high grade bladder cancers than in the superficial and low grade ones(p<0.05). These results suggest that immunohistochemical analysis of the urine specimen in the bladder cancer patients could be a useful method of screening for the presence of p53 mutant protein. The mutant p53 protein expression may be an indicator of bladder cancer with more proliferative potential and/or aggressive biologic behavior.

Phyllodes tumor(PT) is a rare distinctive fibroepithelial breast tumor that occasionally shows unpredictable clinical behavior. Wide excision should be the primary treatment of PT and enucleation, the standard procedure for fibroadenoma(FA), is proscribed due to high frequency of local recurrence. Therefore an accurate preoperative diagnosis of PT is essential in order to ensure proper surgical treatment. However, the differentiation between benign PT and FA is often difficult on the basis of cytologic findings. In an attempt to better understand the cytologic features of benign PT and possibly to differentiate PT from FA on the findings of fine needle aspiration(FNA) smears, we reviewed cytologic smears from 22 histologically diagnosed cases each of benign PT and FA, respectively. The cytologic features assessed were cellularity and atypia of both epithelial and stromal components, and shape of epithelial cell clusters. Atypia of stromal cells was more frequent in PT, while blunt branching pattern of epithelial cells was more frequent in FA. The specific cytologic diagnosis of PT is not possible in many cases, but the abundance of stromal cells with moderate nuclear atypia in the correct clinical setting such as older age and larger size(>4cm) allows the diagnosis.

Fine needle aspiration(FNA) is an effective tool in diagnosing mammary carcinoma. We experienced 7 cases of histologically confirmed mammary mucinous carcinoma among 3,052 aspirated cases of breast from 1992 to 1996 in Asan Medical Center. The average age of the patient was 48(33-64) years. The mean size of the lesions was $1.6(0.7{\sim}3)cm$, and they were palpated as well-defined, firm to hard masses. The cytologic features that may be useful in making a FNA diagnosis of mucinous carcinoma of the breast were analysed. Mucinous background and tumor cell clusters with occasional single cells were observed in all cases. Among them, two cases showed abundant scattered single cells, whereas only few single cells were seen in the other two cases. Tumor cells exhibited mild pleomorphism in four cases and moderate pleomorphism in three cases. Nucleoli tended to be not prominent and are observed in three cases, rarely noted in other three cases and not seen in one. There was microcalcification in four cases(57%). In conclusion, mucinous background and clustered tumor cells showing mild to moderate pleomorphism with characteristic clinical findings allow us to diagnose mucinous carcinoma of the breast.

Abnormalities of p53 gene are common in lung cancers and are associated with immunologically detectable p53 protein. p53 immunoreactivity is uncommon in normal cells but is frequently seen in neoplasia. Therefore, assessment of p53 expression may assist in the cytological diagnosis of malignancy. The usefulness of p53 immunostaining as a marker of malignancy in the cytological analysis of bronchial brush specimens from the patients with lung cancers was investigated in this study. A total of 71 bronchial brush samples submitted for cytologic diagnosis were immunostained with D07, a monoclonal antibody to recombinant p53 protein. Resultant p53 data were correlated with cytologic diagnosis and clinical information. Of the 17 smears with a benign cytodiagnosis, all were p53 negative. Of the 40 cases with a malignant cytodiagnosis (histologically confirmed), 35 were p53 positive and 5 were negative. Of the 14 cases that were cytologically suspicious but nondiagnostic for malignancy, 11 were p53 positive, 9 of which were subsequently proved to be malignant by histologic examination, and the remaining 2 cases were tuberculosis clinically. Forty four of 51 histologically confirmed lung carcinomas were p53 positive, including 25 of 28 squamous cell carcinomas, 13 of 17 small cell carcinomas, 3 of 3 adenocarcinomas, and 3 of 3 large cell undifferentiated carcinomas. These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of bronchial brush specimens. Furthermore, we have shown the possible clinical utility of p53 immunostaining in cytopathological diagnosis, that is, as a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.

This study was peformed in order to evaluate the usefulness of the crush cytologic features and differential diagnosis between meningiomas and schwannomas in the central nervous system. Deeply seated and unusually located meningiomas and schwannomas with equivocal or erroneous frozen section diagnosis can be correctly diagnosed cytologically in crush preparations. Twenty-four meningiomas and nine schwannomas were studied by frozen section and crush preparation technique. These tumors displayed distinctive cytologic features. in meningiomas, the tumor tissue fragments were easy to crush, and the tumor cells were arranged in small clusters, flat sheets, papilla-like, whorling pattern or singly. Individual tumor cells displayed round or oval nuclei with finely granular chromatin pattern and inconspicuous small nucleoli. Occasionally psammoma bodies, nuclear pseudoinclusion or nuclear grooves were found. In schwannomas, tissue fragments were hard in consistency and difficult to crush. The crushed tissue presented as thick, irregular fragments with shard borders. The cells showed ill-defined cytoplasm and round, oval, cigar-shaped or curved nuclei. It is important to emphasize that the smear pattern under low-power view and cytologic features are helpful in discriminating between these two tumors.

Intraoperative cytologic examination of intracranial tumors using crush preparation provides useful information in operative decision making. The diminutive nature of many biopsy specimens, particularly those obtained by stereotactic neurosurgical procedures emphasizes the importance of combining the cytologic smear method with conventional frozen section interpretation. The great advantage of the cytologic smear method resides in its suitability for the study of minute fragments of tissue, allowing retention of the majority of the specimen for optimal processing. We present the cytologic features of 3 cases of intracranial germ cell tumors(2 germinomas and 1 endodermal sinus tumor), using crush preparation during intraoperative diagnosis and compare them with histologic findings. The cytologic features of the germ cell tumors were similar to those of the respective gonadal counterparts. The cytologic differential diagnosis of both types of germ cell tumors is described.

Metastatic melanoma is often difficult to diagnose morphologically. However, the prognostic and therapeutic decision in cases of metastatic melanoma depends upon the morphologic documentation of the metastatic disease, which may rapidly and accurately be done by cytologic methods such as aspiration cytology of clinically suspicious lesion. Cytological features of 12 metastatic melanoma are described. Evaluation for melanin pigment, background composition, cytoplasmic vacuoles, intranuclear inclusions, bi- or multinucleated cells, eccentric nuclei, nucleoli, and degree of cellular cohesion were made. the presence of melanin pigment, prominent nucleoli, intranuclear cytoplasmic inclusions, lack of cell cohesion, and eccentric nuclei are the important and useful cytologic features in the diagnosis of metastatic melanoma. Bi or multinucleated cells, cytoplasmic vacuoles, and bloody background are also frequently found in smears from metastatic melanoma.

The principal significance of the urothelial changes caused by polyomavirus activation is in an erroneous diagnosis of urothelial cancer; however, the clue to their benign nature is the smooth structureless nuclear configuration and the relative paucity of affected cells. Though virologic studies and electron microscopy are usually needed to firmly establish the diagnosis, cytology is the most readily available and rapid means of establishing a presumptive diagnosis of human polyomavirus infection. A urine specimen of a 24-year-old man with hemorrhagic cystitis beginning two months after bone marrow transplantation for acute myeloblastic leukemia(M2) was submitted for cytologic evaluation. Cytologic findings revealed a few inclusion-bearing epithelial cells intermingled with erythrocytes, neutrophils, lymphocytes, and macrophages. Most of the inclusion-bearing fells had large, round to ovoid nuclei almost completely filled with homogeneous dark, basophilic inclusion. The chromatin was clumped along the periphery and the cytoplasm was mostly degenerated. The other cells exhibited irregular inclusions attached to the nuclear membrane surrounded by an indistinct halo. These findings were consistent with polyomavirus infection.

Glassy cell carcinoma is an unusual neoplasm of the uterine cervix that accounts for $1{\sim}2%$ of all cervical malignancy. It is a rapidly progressive and biologically aggressive disease with poor response to therapy. This tumor is considered to be a poorly differentiated mixed adenosquamous carcinoma. The cytologic findings are characterized by tumor cells arranged predominantly in syncytial like aggregates and an inflammatory background. The tumor cells have moderate amounts of eosinophilic or amphophilic cytoplasm, which is often finely granular. The nuclei are relatively large and have fine chromatin with prominent eosinophilic nucleoli. Cytologically, glassy cell carcinoma is most likely to be confused with large cell nonkeratinizing squamous cell carcinoma and with atypical reparative cells. Herein, we report three cases of glassy cell carcinoma of the uterine cervix diagnosed by cervicovaginal smear and confirmed by histologic section with review of literatures.

Metaplastic carcinoma of the breast is a morphologically heterogenous group of neoplasms characterized by ductal adenocarcinoma with extensive squamous differentiation, a spindle-cell pattern of growth, and/or heterologous mesenchymal elements. We experienced a case of metaplastic carcinoma diagnosed by fine needle aspiration(FNA) and confirmed by radical mastectomy in a 46 year-old woman. The FNA cytologic findings included atypical squamous cells with kertinization tying singly and in clusters in a necrotic background. In addition, scattered spindle cells with pleomorphic large nuclei and prominent nucleoli were present in a hemorrhagic and necrotic background. The histopathologic findings showed moderately differentiated squamous cell carcinoma and highly pleomorphic sarcoma with chondroid component. The immunohistochemical stain revealed focal positive reaction for cytokeratin as well as diffuse reactivity for vimentin in the sarcomatous area.

Angiosarcoma of the bone is rare with an incidence of 0.13%. It may be solitary or multiple. Its cytologic findings by FNA have rarely been reported. We report a case of angiosarcoma of the rib in a 66 year-old man. FNA revealed single or clusters of round to oval shaped cells in a hemorrhagic and myxoid background. The large central nuclei had irregular nuclear membrane, chromatin clumping and prominent nucleoli. The cytoplasm was scanty with an eosinophilic distinct cytoplasmic border. Erythrophagocytosis by malignant cells was also found. Histopathologic examination confirmed the diagnosis of angiosarcoma revealing irregular and complex anastomosing vascular channels lined by malignant round tumor cells, protruding into the lumen. Immunohistochemical staining revealed diffuse strong positive reaction to factor VIII-related antigen and CD31.

Medullary carcinoma of the thyroid gland is a malignant neuroendocrine tumor arising from calcitonin producing-parafollicular cells. The tumor is clinically divided into sporadic and familial form, constituting about 80% and 20%, respectively. Recently, we experienced a case of unilateral and solitary sporadic medullary carcinoma of the left thyroid gland. The patient was a 9 year-old female, who presented with a palpable mass on the anterior lateral neck of 8 months duration without any familial and personal history of neuroendocrine disease. The cytopathologic findings showed spindle cells and plasmacytoid cells in the background of colloid-like materal. The nuclei were eccentrically located, mildly hyperchromatic and pleomorphic, showing speckled chromatin pattern without nuclear inclusion or prominent nucleoli. The cytoplasm was abundant and had a pale granular cyanophilic appearance. No amyloid materal could be identified.

We describe two cases of metastatic Wilms' tumor in the lung with emphasis on the cytologic features of specimens obtained by needle aspiration. One of them was extrarenal Wilms' tumor. The findings were correlated with the histopathologic features of the primary lesion. Cellular components in the fine needle aspiration cytology (FNAC) slides included blastemal, epithelial, stromal and inflammatory cells with immature tubular differentiation and rosette formation. Recognition of these cellular components in FNAC smears help in establishing FNAC diagnosis of Wilms' tumor. The blastemal cells were represented by small to medium sized cells with scanty cytoplasm having ill-defined borders and round to slightly oval nuclei with evenly dispersed chromatin and small marginated nucleoli. They were seen in our two cases. The differential diagnosis includes neuroblastoma, malignant lymphoma, malignant rhabdoid tumor, clear cell sarcoma, Ewing's sarcoma and embryonal rhabdomyosarcoma. In conclusion, making a definite cytologic diagnosis of metastatic Wilms' tumor may be possible by light and electron microscopy and immunohistochemical staining. The above findings may contribute to the diagnosis of FNAC of metastatic Wilms' tumor.

We experienced a case of well-differentiated acinic cell carcinoma of the parotid gland in a 65 year-old woman, which was correctly diagnosed preoperatively by fine needle aspiration(FNA) cytology. FNA cytology smears showed clusters or sheets of monomorphic acinic cells having reticulated or finely vacuolated basophilic or acidophilic cytoplasm. The cellular population was homogeneous or slightly polymorphic, having centrally located, round nuclei with finely reticular chromatin and inconspicuous nucleoli. Herein we report this case with its histologic features and review of literatures.