Fine needle aspiration cytology of endocrine neoplasms of the pancreas. Morphologic and immunocytochemical findings in 20 cases

OBJECTIVE: To analyze the role of fine needle aspiration (FNA) cytology in the preoperative diagnosis of pancreatic endocrine neoplasms. METHODS: Cytologic and histologic diagnoses of pancreatic endocrine tumors were reviewed. A total of 20 FNA cytologic procedures from 20 patients were selected. A false positive case, a retroperitoneal paraganglioma, was also reviewed. Two groups of patients were established: (1) those in whom a surgical biopsy with an immunohistochemical study was available (n = 13), and (2) those with a pancreatic tumor in which the diagnosis was confirmed by immunocytochemical studies (n = 7). In 13 cases the pancreatic tumor was aspirated, while in 7, liver metastases were studied. The immunoexpression of chromogranin and synaptophysin was evaluated in alcohol-fixed smears from 12 and 11 cases, respectively. RESULTS: One false negative and 1 false positive diagnosis were present. In the remaining 19 cases a cytologic diagnosis of pancreatic endocrine tumor was given. Main cytologic features were: (1) a prominent cellular dissociation with many single cells and small, poorly cohesive groups; (2) intermediate to large size cells with ill-defined cytoplasm, naked or eccentric nuclei, and frequent binucleation; and (3) variable nuclear pleomorphism with the characteristic finely granular distribution of the chromatin. Immunocytochemical evidence of endocrine differentiation (chromogranin or synaptophysin) was present in the 12 cases analyzed. CONCLUSION: FNA cytology offers the possibility of a precise preoperative, noninvasive diagnosis of pancreatic endocrine tumors. Cytologic features differ considerably from those of pancreatic adenocarcinoma, allowing differentiation from nonfunctioning endocrine neoplasms. In difficult cases immunocytologic studies are very helpful.     

Fine needle aspiration cytologic findings of breast mucinous neoplasms: differential diagnosis between mucocelelike tumor and mucinous carcinoma

OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle aspiration and confirmed by histologic examination were reviewed to detect the cytologic findings helpful for the differentiation. The cytologic findings were correlated with the histologic findings. RESULTS: Cytologically, mucinous carcinomas were highly cellular and showed many single epithelial cells and variably formed epithelial cell clusters in abundant extracellular mucin. Malignant cells exhibited round, atypical nuclei; granular chromatin; and small nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered, small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial cells were present within the epithelial cell sheets. Tumor cells were usually small, with uniform, round nuclei; fine chromatin; and absence of nucleoli. CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were different in cellularity, shape of cell clusters and nuclear features, although mucocelelike tumors having a carcinoma component were similar to mucinous carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is important to make a specific diagnosis.     

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma

OBJECTIVE: To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN: Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS: In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION: Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast carcinoma.     

Neuroendocrine carcinoma of the pancreas diagnosed by aspiration cytology. A case report

Cytologic criteria for distinguishing endocrine from exocrine carcinomas of the pancreas have not been previously elucidated. A case is presented in which the diagnosis of neuroendocrine carcinoma was made on fine needle aspirates of a pancreatic mass and hepatic metastases in a 33-year-old female. Cytologically, the aspirated tumor resembled an intermediate-cell neuroendocrine carcinoma of the lung rather than the usual duct-cell adenocarcinoma of the pancreas. Histologic sections of the subsequently resected primary pancreatic mass revealed a neuroendocrine carcinoma of an intermediate-cell type. Ultrastructurally, the characteristic interlacing cytoplasmic processes with scanty granules were seen. Immunoreactive neuron-specific enolase (NSE), leuenkephalin, substance P and somatostatin were present in the tumor cells in Bouin's-fixed cell blocks of the aspirate; neuron-specific enolase, somatostatin and gastrin were detected in the paraffin-embedded sections of the resected tumor. This variant of pancreatic carcinoma merits recognition as a cytologically distinct group, which shares many of the features described in its bronchopulmonary and gastrointestinal counterparts.     

Cytopathologic features of pituitary carcinoma with cervical vertebral bone metastasis: a case report

BACKGROUND: Pituitary carcinomas are extremely rare tumors of the adenohypophysis. The presence of craniospinal and/or systemic extracranial metastases is the only reliable criterion for the diagnosis of pituitary carcinoma. To date, only 2 cases have been reported correctly by fine needle aspiration biopsy (FNAB). We present an additional case of pituitary carcinoma with FNAB features. CASE: A 60-year-old woman presented with clinical features of Cushing's disease and a pituitary tumor. She underwent transsphenoidal resection of the tumor. The initial diagnosis was an adrenocorticotrophic hormone (ACTH)-producing invasive pituitary adenoma. The patient presented again with neck pain 6 years after the operation. Magnetic resonance imaging revealed metastatic tumor masses at the level of C5-C6 of the cervical vertebrae. Intraoperative fine needle aspiration and incomplete excision of metastatic tumors were performed. Cytologically, tumor cells were composed of a combination of loose groups and single cells. Neoplastic cells had a relatively monotonous appearance and displayed characteristic neuroendocrine tumor features. Immunocytochemistry from cell block sections revealed AE1/ AE3, synaptophysin chromogranin A and ACTH positivity in the tumor cells. CONCLUSION: Pituitary carcinoma with extracranial systemic metastases demonstrates typical neuroendocrine features on fine needle aspiration. In the differential diagnosis, metastatic neuroendocrine carcinomas should be kept in mind. In the absence of sufficient clinical data, these 2 entities cannot be distinguished correctly through the cytologic features.     

Fine needle aspiration cytology of ductal breast carcinoma with neuroendocrine differentiation. Review of eight cases with histologic correlation

OBJECTIVE: To describe the fine needle aspiration cytology findings of ductal breast carcinoma with neuroendocrine differentiation and correlate them with the histologic appearance. STUDY DESIGN: We reviewed the cytologic features of eight cases of ductal carcinoma with neuroendocrine differentiation in the files of Pamela Youde Nethersole Eastern Hospital during the three-year period 1998-2000. Immunohistochemical study for neuroendocrine markers was performed, with ultrastructural correlation. RESULTS: All cases showed similar cytologic features. The smears were of moderate to high cellularity with predominantly dispersed or loosely cohesive tumor cells. The carcinoma cells were mostly of low cytologic grade. They possessed round and relatively uniform, eccentric nuclei; finely stippled chromatin; sometimes small, distinct nucleoli; and discrete cell borders. Abundant eosinophilic and focally granular cytoplasm was a common finding. In some of the cases there was accentuation of staining in the paranuclear region; it correlated with aggregates of dense core neurosecretory granules seen ultrastructurally. Mucoid substance was seen in the background in some of the aspirates. Histologic examination of the tumors showed invasive ductal carcinoma with an organoid growth pattern and sometimes mucinous component. The neuroendocrine differentiation was confirmed immunohistochemically. CONCLUSION: Although this subtype of ductal carcinoma probably carries no significant prognostic value per se, it has distinct cytologic features, rendering preoperative diagnosis possible. Recognition of this entity is important in order to avoid the misdiagnosis of neuroendocrine tumor metastatic to the breast.     

Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). CASE: A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. CONCLUSION: Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.     

Oncocytic tumor of the pancreas. Report of a case with aspiration cytology

The fine needle aspiration (FNA) cytologic findings in a case of pancreatic oncocytoma are reported, and the differential diagnoses are discussed. The FNA picture was consistent with an oncocytic, acinar or islet cell neoplasm; electron microscopy was required to make the definitive diagnosis. The partially cystic tumor measured 7 cm and occurred in the head of the pancreas in a 63-year-old man with symptoms related to compression of the common bile duct. The clinical findings in this and a few other known cases indicate that the malignant potential of pancreatic oncocytoma may be low. Thus, it is important to distinguish this type of tumor from the cytologically similar acinar carcinoma of the pancreas, which has a poor prognosis in general.     

Elastase-1-secreting acinar cell carcinoma of the pancreas. A cytologic, electron microscopic and histochemical study

A case of acinar cell carcinoma of the pancreas was diagnosed by fine needle aspiration cytology during surgery. The cytologic characteristics of this neoplasm are described. Electron microscopy disclosed numerous zymogen granules in the tumor while histochemistry demonstrated the presence of elastase-1. Serum elastase-1 levels were markedly elevated. The cytologic differential diagnosis of pancreatic tumors is discussed.     

Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas

Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series.     

Cytologic findings in noninvasive intraductal papillary-mucinous carcinoma of the pancreas. A report of two cases

BACKGROUND: Intraductal papillary-mucinous carcinoma of the pancreas is a new diagnostic term proposed by the 1996 World Health Organization classification of the exocrine pancreas. So far, there have been only a few reports concerning its cytologic findings, especially in noninvasive cases. CASES: The clinical and cytohistologic findings in two cases of noninvasive intraductal papillary-mucinous carcinoma of the pancreas were reviewed. Cytologic specimens were obtained from pure pancreatic juice in the dilated main pancreatic duct during the operation (case 1) and during endoscopic retrograde pancreatography (ERP) (case 2). Both cases showed three-dimensionally or individually scattered tumor cells with an increased nuclear/cytoplasmic ratio and prominent nucleoli. CONCLUSION: Our cases suggest that pancreatic juice cytology during ERP or surgery is useful in diagnosing pancreatic cancers and that it may detect noninvasive intraductal papillary-mucinous carcinoma of the pancreas.     

Fine needle aspiration cytology of apocrine carcinoma of the breast. Review of cases in a three-year period

OBJECTIVE: To describe the fine needle aspiration cytology findings of apocrine carcinoma of breast and correlate them with the histologic appearance. STUDY DESIGN: The author reviewed the fine needle aspiration cytology findings of two cases of pure apocrine carcinoma of the breast in the files of Pamela Youde Nethersole Eastern Hospital during a three-year period, 1998-2000. RESULTS: The cytologic findings in both cases were similar. The smears were of moderate to high cellularity, consisting of predominantly dispersed or loosely cohesive tumor cells in a focally granular background. The carcinoma cells contained abundant, dense to granular cytoplasm; round or oval and sometimes eccentrically located nuclei; a smooth nuclear outline; evenly dispersed chromatin; and solitary macronucleoli. The cell borders were mostly discrete. In contrast to benign apocrine cells, the malignant cells showed nuclear overlapping, more frequent nuclear pleomorphism, increased nuclear/cytoplasmic ratios and occasional mitotic figures. Histologic examination of the excised specimens showed extensive, solid apocrine carcinoma in situ with focal stromal invasion. CONCLUSION: Apocrine carcinoma, a subtype of breast carcinoma characterized mainly by its cytologic features, needs to be distinguished from benign apocrine lesions or other eosinophilic and granular cell tumors of the breast. Recognition of the subtle cytologic differences renders a definitive preoperative diagnosis possible.     

Low-grade cribriform ductal carcinoma in situ of the breast. Fine needle aspiration cytology in three cases.

This paper presents the cytologic features of fine needle aspiration biopsy specimens from three cases of ductal carcinoma in situ characterized by small and uniform tumor cells growing in a predominantly cribriform pattern without comedo necrosis (low-grade cribriform ductal carcinoma in situ). On cytology, most of the tumor cells were clustered in three-dimensional ductal structures. Occasionally in the clusters the tumor cells were seen bordering central lumina, quite similar to the architecture in histology. A few single tumor cells and no myoepithelium were seen. The background was clear or slightly hemorrhagic, without necrosis. The tumor cells were uniform and had a cylindroid shape, with round or oval nuclei. Morphometrically the mean largest nuclear diameter was 1.5-1.6 times that of a red blood cell. The chromatin was finely granular, with a minute nucleolus and slight condensation along the nuclear membrane. In cut sections all three tumors showed strong immunoreactivity for neuron-specific enolase. Unless the cribriform growth pattern is recognized in the smear, the cytologic diagnosis of this entity is difficult.     

Cytology of basaloid squamous carcinoma of the bronchus. A case report

BACKGROUND: The cytologic appearance of basaloid squamous carcinoma (BSC) arising in the lower respiratory tract has not been described very well because of its rarity. This article describes a surgical case of bronchial BSC and provides the first documentation of the sputum and imprint cytologic features of the tumor. CASE: A 74-year-old man presented with hemoptysis. An abnormal intrabronchial mass was revealed by computed tomography and bronchoscopy. Preoperative cytology and biopsy showed that the mass was composed of small, round, atypical cells, but correct diagnosis was difficult. Under a tentative diagnosis of small round cell carcinoma, a right lobectomy was performed. The resected tumor was composed of small cells showing peripheral palisading and partial epidermoid differentiation. There was no glandular differentiation. Focal necrosis was also noted. Immunohistochemical markers for smooth muscle and neuroendocrine cells were negative. The tumor was eventually diagnosed as BSC or basaloid carcinoma (BC) with squamous differentiation. CONCLUSION: It is important to recognize this disease, especially when undetermined small round cell carcinoma is noted in cytologic specimens, in order to properly assess prognosis. Cytologic detection of nuclear palisading of the neoplastic cells, one of the hallmarks of the disease, may be difficult, however, careful examination to reveal neoplastic cells showing squamous differentiation appears helpful for diagnosis.     

Fine needle aspiration cytology of pancreatoblastoma with immunocytochemical and ultrastructural studies

The cytologic features of a pancreatoblastoma (infantile adenocarcinoma), a rare pancreatic neoplasm of childhood, are described. Fine needle aspiration (FNA) under ultrasound guidance produced a hypercellular specimen consisting of numerous oval-to-cuboidal cells that had a moderate amount of granular cytoplasm. Spindle-shaped, elongated and triangular-shaped epithelial cells were also seen, along with smaller cells that had a higher nuclear/cytoplasmic ratio and a denser cytoplasm. In addition, there were abundant fragments of stroma present, including some surrounded by epithelial cells. Immunoperoxidase studies performed on the aspirated material revealed positive staining of the epithelial cells for cytokeratin (AE1/3), including high and low molecular weight cytokeratin, carcinoembryonic antigen, neuron-specific enolase and alpha-1-antitrypsin. Ultrastructural examination demonstrated epithelial cells containing either large electron-dense zymogen granules in the range of 400 nm to 600 nm or small dense neuroendocrine granules measuring from 100 nm to 200 nm. This finding, in concert with the immunocytochemical studies, supported a "blastemal" cell origin with bidirectional differentiation for this unusual pancreatic neoplasm and enabled a specific preoperative diagnosis of pancreatoblastoma to be made. The differential diagnosis of pancreatoblastoma from other pediatric neoplasms involving the pancreas, including neuroendocrine tumors and neoplasms of acinar cell derivation, is presented. We believe that the FNA cytologic findings can lead to a correct diagnosis of pancreatoblastoma, especially when coupled with immunocytochemical and ultrastructural studies performed on the aspirated material.     

Small cell undifferentiated carcinoma of the parotid gland. Cytologic, histologic, immunohistochemical and ultrastructural features of a neuroendocrine variant

A case of primary small cell undifferentiated carcinoma (SCUC) of the parotid gland, diagnosed initially by fine needle aspiration (FNA) cytology and confirmed by histology, immunohistochemistry and transmission electron microscopy (TEM), is presented. The FNA cytologic features that enabled an accurate diagnosis of this rare salivary gland tumor included nuclear granularity and markedly angular nuclear molding of numerous small cells that were usually present as large syncytia in an inflammatory background. Numerous mitotic figures were also present in this vascular lesion. These features were also evident in the surgical specimens. Immunohistochemistry demonstrated neuron-specific enolase positivity while TEM demonstrated intracytoplasmic neurosecretory granules in this case, indicating a neuroendocrine derivation for this neoplasm instead of the more usual origin of salivary gland SCUCs in ductal epithelial or myoepithelial tissue.     

Cytomorphologic features of Merkel cell carcinoma in fine needle aspiration biopsies. A study of two atypical cases

OBJECTIVE: To report atypical cytomorphologic features in fine needle aspiration biopsies (FNABs) from two cases of Merkel cell carcinoma (MCC), a primary neuroendocrine neoplasm of skin. STUDY DESIGN: Retrospective review of FNABs with histologic correlation from six patients with MCC and a report of findings from two whose smears showed atypical features. RESULTS: Typically the aspirates produce highly cellular smears of loosely clustered and individual, relatively monomorphic, small tumor cells with round to oval, regularly contoured nuclei. In two of our cases, the tumor cell nuclei exhibited a spectrum of pleomorphism ranging from moderately complex nuclear membranes with cleaves, indentations and protrusions in one case to large, markedly bizarre, convoluted nuclei and multinucleate tumor cells in the extreme case. Both cases were primary neoplasms, and the diagnosis was based on clinical, histologic and immunohistochemical data. Additionally, electron microscopy was performed on the tumor with bizarre nuclei and demonstrated rare, dense core neurosecretory granules and paranuclear bundles of intermediate filaments.     

Fine needle aspiration of pancreatic cystic epithelial neoplasms.

Pancreatic cystic epithelial neoplasms present diagnostic challenges in cytology. An accurate diagnosis is important since the prognosis and treatment may vary. We report the cytologic features in fine needle aspirates of four cases of cystic neoplasms of the pancreas (two micro-cystic adenomas, one mucinous cystic neoplasm and one mucinous cystadenocarcinoma). Smears were evaluated as to their cellularity, content and predominant cell type. Aspirates from the microcystic adenomas yielded hypocellular material with rare strips of cuboidal cells having bland nuclei and pale cytoplasm. No mucinous material was identified in the background, but the cells stained positively with periodic acid-Schiff stain. Smears from the mucinous cystic neoplasm were moderately cellular and contained abundant mucinous material. The columnar epithelial cells were arranged in tight sheets, clusters and strips. Most cells had benign nuclear features with focal mild nuclear atypia. Key cytologic findings noted in the mucinous cystadenocarcinoma were moderate cellularity, loose clusters of cells, single cells, overt malignant nuclear features and occasional signet ring cells. Pancreatic pseudocysts can be distinguished from pancreatic cystic epithelial neoplasms by the predominance of histiocytes and inflammatory cells and absence or paucity of epithelial cells. To differentiate microcystic adenomas from mucinous cystic neoplasms, the above criteria coupled with periodic acid-Schiff and mucin staining should effectively differentiate these diagnostic entities.     

Combined use of brushing cytology and endoscopic retrograde pancreatography for the early detection of pancreatic cancer

Seventy-two cases of pancreatic cancer were examined by brushing cytology combined with endoscopic retrograde pancreatography. The results of this combined method were better than those reported for the exfoliative cytologic study of pancreatic fluid. The method detected a minute cancer of the main pancreatic duct that was not detected with any other method. The cells obtained by this technique had very well-preserved cytoplasm and nuclear chromatin, which facilitated making a correct diagnosis. Though this method can be applied only to the main pancreatic duct, it is effective for the diagnosis of ductal cell carcinoma, especially those located at the head of the pancreas, which is the most common site for pancreatic cancer. It is a safe procedure, with no complications seen in this series. The differentiation of carcinoma cells from the benign atypical cells of chronic pancreatitis is illustrated and emphasized.     

Immunocytologic diagnosis of small-cell lung cancer in imprint smears.

Imprints of histologic or autopsy specimens from 12 small-cell lung cancers (SCLCs), 82 non-SCLCs (50 adenocarcinomas, 25 squamous-cell carcinomas, 1 adenosquamous carcinoma and 6 large-cell carcinomas), 2 carcinoid tumors, 1 malignant lymphoma and 8 metastatic carcinomas were examined immunocytologically for the presence of cluster 1 SCLC antigen (neural-cell adhesion molecule: N-CAM), chromogranin A, Leu-7, neuron-specific enolase (NSE) and gastrin-releasing peptide (GRP). The monoclonal antibodies NCC-LU-243 and NCC-LU-246, which are reactive with cluster 1 SCLC antigen/N-CAM, diffusely stained the cell membranes of all SCLCs and carcinoid tumors (100%) and diffusely and focally stained those of two of the large-cell carcinomas, two of the adenocarcinomas, two of the squamous-cell carcinomas and the one adenosquamous carcinoma. Malignant lymphoma and metastatic carcinoma were negative for this antigen. A few cases of large-cell carcinoma, adenocarcinoma, squamous-cell carcinoma and adenosquamous carcinoma were also stained with these antibodies, which may indicate a neuroendocrine differentiation. However, these tumors were different from SCLCs in that their positive tumor cell population was definitely smaller than that in SCLC, in which almost all tumor cells were positive. This confirmed the usefulness of antibodies against cluster 1 SCLC antigen for the immunocytologic diagnosis of SCLC and carcinoid tumor in imprint smears. Chromogranin A, GRP, NSE and Leu-7 were not useful in immunocytologically differentiating the imprints from these cases since only a few tumor cells were reactive with these antibodies. The antibodies against cluster 1 SCLC antigen/N-CAM can also be applied to cytologic preparations of sputum, pleural fluid and fine needle aspirates stained routinely by the Papanicolaou method since the antigen is preserved in such alcohol-fixed smears.