Diagnosis of metastatic renal cell and thyroid carcinomas by intermediate filament typing and cytology of tumor cells in fine needle aspirates

Coexpression of keratin and vimentin was found in carcinoma cells of 13 fine needle aspirates of metastatic lesions that showed some cytologic features considered to be consistent with a renal or thyroid origin, but in which a large number of other possible primary sites would have to be taken into account on the basis of the morphologic evidence alone. Immunochemistry thus narrowed the cytologic differential diagnosis to thyroid, renal, endometrial and ovarian carcinomas, which are known to show true coexpression of keratin and vimentin. In most cases, clinical data available at the time of the fine needle aspiration supported the thyroid or renal origin of the carcinoma cells found in the aspirates. In two cases, which lacked significant clinical information, the diagnosis of metastatic renal cell carcinoma was provided on the basis of the combined morphologic and immunocytochemical evidence. In these two cases, computed tomography or ultrasonography revealed kidney tumors, which were removed and confirmed histologically to be clear cell carcinomas.     

Malignant melanoma in fine needle aspirates and effusions. An immunocytochemical study using monoclonal antibodies

The value of monoclonal antibodies (MAbs) for the immunodetection of keratin, vimentin and two melanoma-associated antigens recognized by NKI/C3 and NKI/Bteb for the diagnosis of malignant melanoma has been previously established on histologic preparations. In the present study, cytologic preparations from 20 fine needle aspirates and effusions from patients with malignant melanoma were evaluated using these antibodies. Twenty of 20 smears were negative for keratin, and 20 of 20 smears were positive for vimentin. Positivity for NKI/C3 was seen in 12 of 12 cases studied, and for NKI/Bteb in 12 of 13 cases. These results indicate that a panel of MAbs consisting of anti-keratin, anti-vimentin, NKI/C3 and NKI/Bteb is useful for a more accurate diagnosis of malignant melanomas on cytologic preparations. The expression of these antigens in melanoma cells in cytologic smears can be a valuable aid in the detection of primary (noncutaneous) and metastatic melanomas by fine needle aspiration.     

Cytomorphology and immunocytochemistry of fine needle aspirates from blastic non-Hodgkin's lymphomas

Fine needle aspirates from 54 consecutive patients with primary or recurrent blastic (high-grade malignant) non-Hodgkin's lymphomas (NHLs) were analyzed by cytomorphology and immunocytochemistry. The cytologic diagnoses induced follicular center-cell-derived (centroblastic or anaplastic centrocytic) lymphoma (31 cases), immunoblastic lymphoma (11 cases), lymphoblastic lymphoma (9 cases) and histiocytic lymphoma (3 cases). Immunocytochemistry showed a B-cell phenotype of the neoplastic lymphocytes in all lymphoblastic lymphomas, 29 follicle center-cell lymphomas and 4 immunoblastic lymphomas. Four of the immunoblastic lymphomas were of T-cell origin while one case was not evaluable due to necrosis. A histiocytic origin was confirmed in two of the three cases that had a cytologic diagnosis of histiocytic lymphoma; the third case was shown by immunocytochemistry to be a true Ki-1-positive large cell lymphoma. Histologic and immunohistochemical analysis were performed on surgical biopsies from 18 patients. The results were in agreement with those on the fine needle aspiration (FNA) material in 14 cases. Three lymphomas could be phenotyped on aspirated material while marker studies on excised material were inconclusive. One lymph node aspirate contained mostly necrotic cells, which were unsatisfactory for adequate immunocytochemistry. However, sections from a removed tonsil from the same patient could be used for conclusive histology and phenotyping. In conclusion, the high diagnostic accuracy of combined cytomorphologic and immunocytochemical assessment of FNA samples validates the use of the technique in the diagnostic work-up of blastic (high-grade malignant) NHLs. In fact, the diagnostic accuracy seems so high that the technique can safely be used in the final diagnosis of blastic NHLs.     

Some cytologic features of hepatocellular carcinoma as seen in fine needle aspirates

Cytologic study of fine needle aspirates in 15 cases of hepatocellular carcinoma revealed the following cellular patterns in order of decreasing frequency: trabecular, acinar and anaplastic. The most useful cytologic criteria for the identification of hepatocellular carcinoma were the similarity of tumor cells to liver cells, the prominence of nucleoli and the frequent presence of a trabecular pattern. Our study showed that the cellular changes seen in aspirated material faithfully reflect the histologic alterations seen in tissue sections. Hence, familiarity with the histology of hepatocellular carcinoma is of tremendous value in the interpretation of cytologic material.     

Immunochemical demonstration of keratin and vimentin in cytologic aspirates

Antibodies to intermediate filament proteins were used to characterize tumor cells present in peritoneal and pleural effusions and in thin needle aspirates from palpable lymph nodes. Metastatic adenocarcinoma cells (breast, ovary, endometrium, cervix, colon and stomach) as well as squamous-cell carcinomas and mesotheliomas stained specifically with antibodies to keratin while mesenchymally derived tumor cells (lymphomas, melanoma, fibrosarcoma and neurofibrosarcoma) were positive only for vimentin. Especially in cases of lymph node aspirates, keratin staining in cells was a direct indication of metastatic carcinoma. Antibodies to these different components of the cytoskeleton can thus be used in cytopathologic diagnosis when a definitive diagnosis cannot be made on the basis of conventional cytologic features.     

Significance of squamous cells in fine needle aspiration cytology of the breast. A review of cases in a seven-year period

OBJECTIVE: To delineate the significance of detecting squamous cells in fine needle aspiration biopsy of breast lesions. STUDY DESIGN: The authors reviewed 15 cases of fine needle aspiration cytology of the breast with a discernible number of squamous cells from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a seven-year period from the start of 1994 to the end of 2001. The cytologic features were correlated with clinical, radiologic and histologic findings, if any. RESULTS: Among the 15 fine needle aspirates of the breast with a discernible number of squamous cells, 5 of them represented metaplastic carcinoma. The remaining consisted of 3 cases of fibroepithelial tumors, 1 case of duct ectasia, 3 cases of subareolar abscess, 2 cases of sclerosed intraduct papilloma and 1 case of benign breast cyst. In general, benign squamous cells were bland looking and often associated with anucleated squames. They were mitotically inactive and could show a good maturation pattern. Tumor cell cannibalism was rare. The presence of abundant, foamy macrophages in the background suggested a benign lesion. The primary diagnosis could be deduced by recognition of other features, such as the presence of myxoid stromal tissue and papillary structures. In contrast, malignant squamous cells in metaplastic carcinoma were more pleomorphic and mitotically active. Dyskeratosis and tumor cell cannibalism were obvious. Tumor diathesis and bizarre-shaped cells were sometimes found. CONCLUSION: Squamous cells occur in fine needle aspirates from a number of benign and malignant breast lesions. Benign conditions with abundant squamous cells may sometimes mimic malignant squamous lesions and vice versa. Careful assessment of the cytologic features of squamous cells and background appearance is crucial for achieving a correct diagnosis.     

Fine needle aspiration cytology of mucoepidermoid carcinoma. A diagnostic problem

The cytomorphologic findings in fine needle aspirates from 18 cases of histologically confirmed primary mucoepidermoid carcinoma of the salivary gland were reviewed and correlated with the findings on the tissue sections. An accurate diagnosis of these tumors in fine needle aspirates was possible when all three components (i.e., epidermoid cells, intermediate cells and mucus-producing cells) were identified. The pitfalls in the cytologic diagnosis of this tumor are discussed.     

Immunocytochemistry in head and neck aspirates. Diagnostic application on direct smears in 16 problematic cases.

This report describes our experience with immunocytochemical staining of routinely processed smears in the fine needle aspiration (FNA) biopsy diagnosis of 16 tumors of the head and neck. Immunocytochemistry (ICC) was performed on alcohol-fixed or air-dried smears using commercially available monoclonal antibodies followed by a streptavidin-biotinylated peroxidase labeling method. In 12 aspirates with cytologically unclassifiable and undifferentiated cells, immunostaining for cytokeratin, leukocyte common antigen, S-100 protein and vimentin provided conclusive evidence of cell lineage. ICC permitted the correct identification and differential diagnosis of four additional tumors: a positive immunoreaction for thyroglobulin identified a metastatic Hürthle cell carcinoma of the thyroid; a coexpression of two distinct classes of intermediate filaments helped support the FNA diagnoses of a parathyroid adenoma and of a synovial sarcoma; and the double immunoreaction for CD15 and CD30 antigens helped identify Reed-Sternberg cells within an unusually suppurative harvest. Two immunostains were required for proper diagnosis in 13 cases and four in the remaining 3. In all cases but one only unstained slides were used. These data demonstrate that immunostaining can conveniently and advantageously be performed on direct smears of aspirated samples of head and neck lesions, but cases should be carefully selected for this procedure.     

Immunocytochemical detection of estrogen receptors by staining with monoclonal antibodies on cytologic specimens of human breast cancer

A study was undertaken to test the possibility of determining the estrogen receptor (ER) content in human breast cancers by staining with commercial specific monoclonal antibodies (MAbs) on cytologic specimens (touch imprints and fine needle aspirates). The aspirates were suspended in a cell culture medium and cytocentrifuged onto slides to preserve their morphologic characteristics and to allow a proper immunocytochemical staining for ERs. MAb staining for ER was also performed on the respective surgical samples. The staining of cytologic samples for ER showed 100% specificity and 95% sensitivity in comparison to the staining of the histologic samples. Moreover, comparison of the percentage of stained cells in the cytologic specimens to the ER content in the respective surgical specimens, as assayed by the dextran-coated charcoal method, showed the MAb staining of cytologic samples to have 94% specificity and 100% sensitivity. These results support the reliability of MAb staining for ERs in cytologic samples and suggest that it could be the assay of choice in particular clinical settings in the evaluation of primary and recurrent breast cancers.     

Immunocytochemical localization of polyclonal carcinoembryonic antigen in hepatocellular carcinomas.

Hepatocellular carcinomas exhibit a unique canalicular immunocytochemical staining pattern with polyclonal antibodies directed against carcinoembryonic antigen (pCEA). The use of this method to facilitate a definitive diagnosis of hepatocellular carcinoma on fine needle aspirates of the liver was evaluated using aspirates and the corresponding core biopsy samples from nine cases. Immunoperoxidase staining with pCEA produced an identical canalicular staining pattern in 6 (66%) of 9 aspirates and 6 (75%) of 8 biopsy samples. The negative results in three aspirates may be due to their lack of the tissue fragments necessary to show this staining pattern. These findings indicate that the expression of this unique immunocytochemical staining pattern may aid in the diagnosis of primary hepatocellular carcinoma by fine needle aspiration cytology.     

Endothelial cells help in the diagnosis of primary versus metastatic carcinoma of the liver in fine needle aspirates. An immunofluorescence study with vimentin and endothelial cell-specific antibodies

Fine needle aspirates of 5 primary hepatocellular carcinomas and 24 carcinomas metastatic to the liver were studied using vimentin and endothelial cell-specific monoclonal antibodies. Numerous endothelial cells dispersed and in bundles overlying clumps of tumor cells were positively stained by both antibodies in smears of primary hepatocellular carcinomas while such cells were rare or absent in metastatic carcinomas, with the exception of clear cell carcinoma of the kidney. It is concluded that endothelial cells, if present in large numbers in fine needle aspirates of a hepatic carcinoma and arranged in bundles that envelope the clumps of tumor cells, can (1) suggest the presence of a primary hepatocarcinoma and (2) narrow the differential diagnosis with the most common metastatic cancers to renal cell carcinoma.     

Polyclonal carcinoembryonic antigen staining in the cytologic differential diagnosis of primary and metastatic hepatic malignancies.

In order to assess the utility of immunocytochemical staining of bile canaliculi with a polyclonal antiserum to carcinoembryonic antigen (pCEA) in the differentiation of primary hepatocellular carcinomas from metastatic malignancies, pCEA staining was performed on fine needle aspiration specimens from hepatic lesions in 60 patients. The original cytologic diagnoses were hepatocellular carcinoma in 22 patients, metastatic neoplasm or cholangiocarcinoma in 27 patients and benign hepatocytes in 11 cases. The cytologic diagnoses of malignancy were confirmed by surgical excision, autopsy or clinical investigations in 82% of the patients. Follow-up data, supported by pCEA staining, reversed the original cytologic diagnosis in three cases. Bile canalicular pCEA staining was identified in 18 of 22 cases of hepatocellular carcinoma and in all 11 benign hepatocellular aspirates. All 27 cases of metastatic malignancy or cholangiocarcinoma were negative for canalicular pCEA staining, although 11 cases exhibited cytoplasmic staining. Interpretation of pCEA staining was not affected by the intermingling of malignant cells and benign hepatocytes. Predictive values were 100% for a positive test and 87% for a negative test. These findings indicate that staining with pCEA antiserum is a useful adjunct in the differential cytologic diagnosis of malignant hepatic lesions.     

Specific tumor markers in diagnostic cytology. Immunoperoxidase studies of carcinoembryonic antigen, lysozyme and other tissue antigens in effusions, washes and aspirates

The immunoperoxidase technique was used to identify specific tumor markers in exfoliated cells in fine needle aspirates and body fluids. Carcinoembryonic antigen (CEA) and lysozyme staining was evaluated in cytocentrifuge preparations from 42 malignant effusions and aspirates and 16 benign effusions. Reactive mesothelial cells were negative for CEA and lysozyme or showed faint peripheral cytoplasmic staining. Malignant cells from 50% of the adenocarcinomas studied were positive for CEA. All tumors studied were negative for lysozyme. These staining patterns are helpful in the differential diagnosis of reactive mesothelial and adenocarcinoma cells, a frequent diagnostic dilemma. Moreover, demonstration of specific tumor antigens (e.g., prostatic acid phosphatase, calcitonin and immunoglobulin) helped define the origin of metastatic malignancy in selected cases. Estrogen receptor activity was also identified in tumor cells using this technique. Immunoperoxidase was helpful in the evaluation of malignant cytologic specimens from patients with more than one tumor. Interpretation of staining patterns is discussed, with reference to the limitations of the technique. Immunoperoxidase methods maintain cytologic detail, are readily adaptable to diagnostic cytology and increase the specificity of cytologic diagnosis.     

Fine needle aspiration cytology of neuroendocrine tumors of the pancreas. A cytologic, immunocytochemical and electron microscopic study.

We report the fine needle aspiration cytology findings in six cases of neuroendocrine tumor of the pancreas. Three cases were from the pancreas, two from hepatic metastases and one from a peripancreatic lymph node metastasis. The cytologic features that permitted a preoperative diagnosis of pancreatic neuroendocrine tumor were: a cellular aspirate; numerous isolated cells and irregular, loose, dyshesive cellular aggregates; minimal nuclear pleomorphism; infrequent mitoses; fine, evenly dispersed nuclear chromatin with occasional inconspicuous nucleoli; a scant-moderate amount of granular, amphophilic, well-defined cytoplasm; clustering of tumor cells around segments of capillaries; and rosette formation. The differential diagnosis includes cells derived from normal pancreatic acini, islet cell hyperplasia, acinic cell carcinoma, well-differentiated pancreatic adenocarcinoma, metastatic small cell undifferentiated carcinoma of the lung, pancreatic small cell anaplastic carcinoma and malignant lymphoma. The application of immunocytochemistry to cytologic smears can be easily and reliably performed to confirm the neuroendocrine nature of the tumor and identify the specific type of polypeptide hormone or hormones produced by these tumors. Four aspirates showed immunoreactivity for chromogranin, and one was positive for gastrin. Cells of a lipid-rich neuroendocrine tumor were negative for chromogranin; however, the tissue section contained neuron specific enolase, and neurosecretory granules were demonstrated by electron microscopy.     

Fine needle aspiration cytology of collecting duct carcinoma of the kidney: report of a case with distinctive features and differential diagnosis

BACKGROUND: The relative rarity of collecting duct carcinoma (CDC) of the kidney in conjunction with a lack of distinctive cytologic features is a diagnostic challenge for any cytopathologist when dealing with such a tumor on fine needle aspiration cytology. In previous cytologic reports, CDC is not well characterized, and the features overlapped with those of high grade renal cell carcinoma (RCC). Because of the differences in behavior and treatment from conventional RCC, it is important to attempt to diagnose this tumor correctly. CASE: The cytologic findings of CDC in a 56-year-old woman were distinctive and not emphasized previously. Ductal/tubular differentiation, prominent desmoplastic stromal component, neutrophilic infiltration and the presence of numerous tubules ranging from benign to dysplastic and frankly malignant were notable features of this tumor. The expression of high-molecular-weight cytokeratin and Ulex europaeus agglutinin helped to confirm the diagnosis. CONCLUSION: The present case highlights several characteristic cytologic features that were useful in suggesting the diagnosis of CDC on fine needle aspiration cytology. Immunohistochemical stains, such as high-molecular-weight cytokeratin and lectin, helped to confirm the diagnosis.     

Carcinoembryonic antigen content in fine needle aspirates of the lung. A diagnostic adjunct to cytology.

Carcinoembryonic Antigen (CEA) was measured in 59 consecutive fine needle aspirates (FNAs) of the lung from 58 patients to determine if the CEA content would enhance the sensitivity of the cytologic diagnosis. Twenty-eight males and 30 females with tumors 1-40 cm in diameter were studied. Final diagnoses were correlated with the clinical history, radiologic studies, tissue (when available) and follow-up. Image-guided FNAs were performed by radiologists using a 22-gauge Chiba needle and 20-mL syringe with one to four passes per specimen. Cytologic examination included rapid assessment in the radiology suite and a final diagnosis in 24 hours. CEA was measured by enzyme immunoassay using monoclonal antibody. Nine benign aspirates and 50 malignant aspirates were diagnosed. The sensitivity of cytology was 86% and specificity, 100%. Using 5 ng/mL as the cutoff, the sensitivity of CEA for malignant aspirates was 50% and specificity, 90%. The combined sensitivity of CEA and cytology was 95%. The mean CEA in malignant aspirates was 131 ng/mL and in benign aspirates, 2.41. The highest mean CEA was seen in adenocarcinoma, 402.6 ng/mL. Lower CEA content was seen in epidermoid carcinoma (58.6 ng/mL), large cell carcinoma (8.09), oat cell carcinoma, metastatic carcinoma of the kidney and breast, thymoma and lymphoma (each less than 1 ng/mL). Elevated CEA alone was diagnostic in two aspirates of bronchioloalveolar carcinoma; carcinoma with an unknown primary source, three; and large cell carcinoma, one. The adjunctive use of CEA in FNAs of the lung enhances the sensitivity of the cytologic diagnosis.     

Carcinosarcoma of the palate: report of a case with a diagnosis of sarcomatoid metastasis by fine needle aspiration cytology

BACKGROUND: Carcinosarcoma (sarcomatoid carcinoma) is a rare tumor with a high predilection for the aerodigestive tract. Cytologic diagnosis of metastatic carcinosarcoma has been reported in very few cases. CASE: An 84-year-old woman presented with a 2-cm-diameter, right cervical lymph node that was referred for fine needle aspiration cytology (FNAC). She had received radiotherapy for a palatal squamous cell carcinoma 2 years earlier. The FNAC smears had a sarcomatoid appearance. Repeat fine needle aspiration was performed, with cytologic and immunocytochemical staining. Careful consideration of the cytologic and immunophenotypic features led to an impression of carcinosarcoma. Histologic sections of the palatal biopsy that had been previously diagnosed as squamous cell carcinoma were reviewed, and a final diagnosis of carcinosarcoma was established. CONCLUSION: Metastasis of rare lesions, such as carcinosarcoma may be confusing and difficult to diagnose on FNAC, especially when the cytologic sample shows a predominantly sarcomatoid component. The difficulty is compounded when the sarcomatoid component happens to have been overlooked on the initial histologic assessment. With representative cytologic sampling, immunocytochemical staining and review of the histologic material, the correct diagnosis was achieved in this case.     

Fine needle aspiration cytologic findings in four cases of pilomatrixoma (calcifying epithelioma of Malherbe).

Four cases of pilomatrixoma studied by fine needle aspiration (FNA) biopsy prior to resection and histologic diagnosis were reviewed to identify the cytologic features useful in making the FNA cytodiagnosis. Cytopathology had initially correctly diagnosed two cases while misdiagnosing one as a carcinoma and one as a suspected carcinoma. The aspirates from all cases contained either clustered or isolated basaloid cells, with variably sized nuclei and prominent nucleoli. "Ghost cells" were also present in most smears stained with the Giemsa stain and could thus be very helpful for making the FNA diagnosis of pilomatrixoma. The occurrence of either foreign-body giant cells or calcium deposits in the aspirates could also contribute to suggesting the correct diagnosis of pilomatrixoma in some cases.     

Intranuclear inclusions in fine needle aspirates of bronchial low grade mucoepidermoid carcinoma with clear cell change: a report of two cases

BACKGROUND: Mucoepidermoid carcinoma of the bronchus is a rare neoplasm that can be recognized on histology as well as cytology by the presence of three characteristic cell types: mucus secreting, epidermoid and intermediate. We encountered two cases displaying unusual cytologic features, including clear intranuclear inclusions. CASES: Two females, aged 33 and 39, presented with an intrabronchial tumor and pulmonary parenchymatous mass, respectively. Fine needle aspiration of both tumors showed similar cytologic features, with a dominant population of cells with bland nuclei and wide cytoplasm, and frequent intranuclear inclusions. A minor component of mucus-secreting cells was also recognized. Histologically, both tumors corresponded to the clear cell variant of mucoepidermoid carcinoma. CONCLUSION: The cytologic picture in our cases has not been described previously in fine needle aspirates of mucoepidermoid carcinoma, in neither the bronchus nor salivary gland. The differential diagnosis of a monotonous population of epithelial cells with intranuclear inclusions involves bronchioloalveolar carcinoma, but the absence of the characteristic sheet pattern, as well as the clinical and image findings, excludes this possibility. The lack of atypia and intrabronchial location limits the scope to carcinoid and salivary gland-type tumors of the bronchus. Since we were aware of the possibility of unusual cytologic presentations of mucoepidermoid carcinomas, search for different cellular populations suggested the precise diagnosis.