Endometrial assessment with Isaacs cell sampler.

The value of the Isaacs endometrial cell sampler in the cytologic assessment of the endometrium was studied in 121 unanaesthetised patients aged over 40. Satisfactory aspirates for cytological diagnosis of endometrial state were obtained in 111 patients (91%) whereas endometrial specimens for histological diagnosis were obtained in only 89 patients (79%). In only four out of 83 cases were there diagnostic discrepancies between the aspirates and the curettings. It is concluded that the technique is safe, quick, comfortable, and reliable for assessing endometrial state. It should therefore prove valuable for screening, particularly in the management of menopausal women requiring oestrogen treatment.     

The Isaacs Endometrial Cell Sampler. An evaluation in 100 patients with postmenopausal bleeding

The Curity Isaacs Endometrial Cell Sampler was used to obtain cytologic material from 100 consecutive patients presenting with postmenopausal bleeding. It was followed by uterine curettage to obtain material for histology. Satisfactory endometrial aspiration smears were obtained from 92 patients, whereas curettage yielded endometrial tissue in only 48. Of 17 patients with histologic confirmation of malignancy, 7 had smears diagnosed as showing malignancy, and 7 had smears showing hyperplastic changes; 3 of the aspiration smears were judged to be unsatisfactory for cytologic evaluation. All the carcinomas were found in the hyperplastic, malignant or unsatisfactory smears. This technique is worthy of further study.     

Cytologic diagnosis of the papillary variant of renal-cell carcinoma

The papillary variant of renal-cell carcinoma is characterized by distinctive histologic, clinical and angiographic features. A study was undertaken to delineate the cytologic features of this tumor as it is encountered in cellular samples. Cytologic specimens containing tumor cells from eight patients who underwent resection for papillary renal-cell carcinoma were examined and compared to corresponding cytologic samples obtained from ten other patients who had nonpapillary renal-cell carcinoma. The cytologic appearance of papillary renal-cell carcinoma, which is deceptively benign, is marked by distinctive papillary structures that often resemble branched chains. The cells are usually small and contain uniform nuclei; numerous macrophages with foamy cytoplasm are often found in the background. These cytologic features were not observed in the cellular specimens from the nonpapillary renal carcinomas. We conclude that papillary renal-cell carcinoma can be confidently recognized in cytologic specimens.     

Prognostic markers in histologic and cytologic specimens of breast cancer

OBJECTIVE: To correlate histologic and cytologic specimens of breast cancer by the expression of prognostic factors, such as estrogen receptor (ER), progesterone receptor (PR) and c-erbB-2, with immunochemical staining. STUDY DESIGN: Cytologic and histologic specimens from 83 patients were analyzed for expression of ER and PR, and 30 cases were analyzed for overexpression of c-erbB-2 using a standard immunochemical method. The material used for immunocytochemical staining was taken from the needle and syringe after each aspiration and smear preparation. The material was washed into a small container with preservative solution. Immunohistochemical staining was performed on paraffin-embedded specimens. RESULTS: A significant association was found between the histologic specimens and cytologic specimens by means of the expression of immunochemical markers. The best correlation between cytologic and histologic specimens was found when using c-erbB-2. CONCLUSION: A reliable and rapid evaluation of markers for breast cancer can be achieved by immunocytochemical staining on cytologic material. A good association was found between histologic and cytologic specimens using immunostaining.     

The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.     

Optimal recovery of DNA for polymerase chain reaction-based assays from fine needle Aspirates. A comparison of four preparation types

OBJECTIVE: To assess the ideal preparation for molecular techniques applied to cytologic specimens using polymerase chain reaction (PCR) on different types of cytologic preparations with specimens obtained from fine needle aspiration biopsy (FNAB). STUDY DESIGN: Besides conventional cytologic examination, PCR was performed on 30 consecutive cases of FNAB to analyze the beta-actin gene in four types of cytologic preparations, including fresh samples, previously stained Papanicolaou and Diff-Quik routine smears and cell blocks. Cellularity and cytologic findings were correlated with PCR results. RESULTS: The beta-actin gene was successfully amplified from all cases studied. Cellularity of the samples correlated directly with PCR results except for one case of metastatic melanoma with intense pigment retention. All specimens showed equivalent results as compared to fresh samples. Generally cell blocks were less cellular and consequently less effective. CONCLUSION: All conventional cytologic preparations tested were suitable for PCR-based assays when cellularity was adequate. Alcohol-fixed and air-dried smears can be successfully used for PCR studies, providing rapid and simple specimens for molecular studies, which can add important information concerning diagnosis, prognosis and management.     

Preoperative cytologic diagnosis of primary gastrointestinal malignant lymphoma

This report is based on the review and study of primary gastrointestinal malignant lymphomas as seen in cytologic brushing and washing specimens. During a period of 12 years (1970 to 1981), a total of 2,675 patients with malignant lymphoma involving the gastrointestinal tract were seen at Memorial Sloan-Kettering Cancer Center. Of these patients, 73 were diagnosed as having primary malignant lymphoma of the gastrointestinal tract. A total of 49 preoperative cytologic specimens obtained from 29 patients with histologically confirmed primary gastrointestinal malignant lymphoma were examined and are the basis for this study. Twenty-four patients had gastric primaries; three tumors were in the colon and two were small intestinal lymphomas. Thirty-three cytologic specimens taken from 25 patients were considered diagnostic for malignant lymphoma. A positive cytologic brushing was the only diagnostic preoperative specimen for 9 of the 29 patients. Combined cytologic and biopsy specimens provided a diagnosis of malignant lymphoma for 16 patients. Cytologic washings did not add to the diagnostic accuracy. The 29 cases of malignant lymphoma reviewed here were histologically subclassified as 23 large-cell, poorly differentiated and six small-cell, well-differentiated lesions. The cytomorphologic features of malignant lymphoma as observed in gastrointestinal specimens are outlined, and differential diagnoses are discussed. Clinicopathologic implications of the cytologic findings are considered.     

Value of cytology for detecting endometrial abnormalities in climacteric women receiving hormone replacement therapy.

Over six months 113 endometrial specimens from 110 menopausal women receiving hormone replacement therapy were examined by two cytologists and two histopathologists. Specimens were obtained by aspiration with the Isaacs cell sampler immediately before Vabra suction curettage, both procedures being performed in the outpatient department without anaesthetic. The histologists agreed with each other on the classification of 85 specimens (75.2%) and the cytologists agreed on the classification of 44 (38.9%). In only 15 cases (13.3%) did all four observers agree. Of the three cases of cystic or adenomatous hyperplasia detected histologically, only one was diagnosed by cytology. Furthermore, both cases of adenocarcinoma escaped detection by cytology, though a third case--later confirmed-"was suspected by one cytologist alone. Use of the Isaacs endometrial cell sampler cannot be advocated for routine screening of women with climacteric symptoms receiving hormone replacement therapy. Efforts should be made to establish the correct dose and duration of treatment with an oestrogen-progestogen preparation in order to avoid over-stimulating the endometrium and the need for regular screening for endometrial abnormalities.     

Cytomorphology of the variants of small-cell carcinoma of the lung

Cytologic classification of subtypes of small-cell carcinoma of the lung (SCCL) was retrospectively performed on respiratory material of 90 cases of lung carcinoma cytologically diagnosed as SCCL. Additionally, the cytologic material was reexamined for the presence of variants of SCCL in 68 cases of lung carcinoma whose types had not been conclusively defined by cytology. The type of lung cytology specimens reviewed were sputa, bronchial washings and brushings and fine needle aspirations. The study included review of pretreatment tumor histology, when present, and examination of the ultrastructure of the tumor in selected cases whose type had not been well defined by histology. Subtype recognition depended on the adequacy of the specimens rather than on the type of cytologic material examined. The cytologic subtyping was generally in agreement with the histologic subtyping of the tumor, except for cases in which SCCL was combined with other types of lung carcinoma, where certain discrepancies were noted.     

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.     

Fine needle aspiration cytology of atypical carcinoid of the lung

The cytologic features of eight atypical carcinoid tumors of the lung, as observed in fine needle aspiration (FNA) specimens, are described in detail. They were compared with 21 pulmonary squamous-cell carcinomas, 16 adenocarcinomas, 5 small-cell undifferentiated carcinomas, 3 large-cell undifferentiated carcinomas and 1 typical carcinoid tumor. Atypical carcinoid tumor was easily distinguished from the other pulmonary neoplasms in most instances. Only two poorly differentiated squamous-cell carcinomas (one of which had atypical carcinoid as a component) and one small-cell undifferentiated carcinoma had similar cytologic features. One atypical carcinoid also had cytologic features similar to small-cell undifferentiated carcinoma. Because atypical carcinoid and small-cell undifferentiated carcinoma, at times, may be difficult to separate in FNA specimens, surgical resection of all stage I neoplasms with cytologic features evocative of either neoplasm is recommended.     

Improved transmission electron microscopy technique for the study of cytologic material

A modification of the technique of Coleman et al for the preparation of single cells in cytologic specimens for electron microscopy (EM) is described. By employing materials in the initial cytologic processing that are useful for EM, such as a paraformaldehyde-glutaraldehyde fixative, lactated Ringer's solution as a rinsing medium, glycerol as a mounting medium and cacodylate buffer for removal of coverslips, the use of alcohol fixatives and standard mounting media could be avoided. This preserved the cytoplasmic detail, which is usually degenerated in cells removed from cytologic specimens and processed for EM.     

Immunocytochemical characterization of large-cell carcinomas of the lung. Role, limitations and technical considerations.

To clarify the use of cytologic preparations, particularly those previously stained by the Papanicolaou method, for the immunocytochemical evaluation of large-cell carcinomas (LCCs), 37 cytologic preparations from cases diagnosed as LCC were examined using a battery of immunocytochemical stains for keratin, chromogranin, common leukocyte antigen (CLA) and B72.3. Thirty-two specimens were from the thoracopulmonary region (12 fine needle aspirates of the lung, 7 bronchial brushings, 5 bronchial washings, 2 sputa and 6 pleural fluids); the remaining specimens were fine needle aspirates of 3 lymph nodes, 1 vertebral body and 1 liver. Of the specimens analyzed, 30 of 37 were positive for keratin and 7 of 35 were positive for B72.3 (6 were positive for both). Only 1 of 37 was positive for CLA while none of 37 was positive for chromogranin. Six specimens showed no reaction with either keratin, B72.3 or chromogranin. These results confirm that the majority of LCCs consist of epithelial cells of either a squamous or an adenocarcinomatous type. They also show that immunocytochemistry is a useful diagnostic adjunct that can be applied to cytologic preparations previously stained by the Papanicolaou method; this is important since immunostaining is often considered after undifferentiated malignant cells are encountered in a previously stained preparation. However, a thorough understanding of some technical limitations is critical in the evaluation of the results of this technique when it is applied to cytologic specimens.     

Thyroid Cytology and Risk of Thyroid Cancer: Differences Among Indeterminate Specimens

ObjectiveTo assess the potential for stratification of indeterminate cytologic findings on fine-needle aspiration (FNA) of thyroid nodules in an effort to improve therapeutic strategies.MethodsWe attempted to determine the malignant risk associated with various indeterminate FNA cytologic patterns by correlation of specimens with the final histologic diagnosis. For this analysis, we identified 294 computerized medical records of surgically treated thyroid nodules during a 5-year period at our institution with the corresponding FNA cytology reports available.ResultsOf the 294 surgical cases, 162 with a positive or indeterminate cytologic report were selected, reviewed, and classified. Of 52 patients with positive cytologic findings on FNA, 51 (98%) had a final histologic report of a malignant thyroid nodule. Of 110 patients with indeterminate specimens, 30 (27%) had a final histologic diagnosis of thyroid carcinoma. The presence of nuclear atypia was predictive of thyroid carcinoma in 75% of patients, a Hürthle cell cytologic pattern was associated with a malignant thyroid nodule in 33%, and a hypercellular smear was suggestive of malignant involvement in 26% of cases. The lowest rate of malignant potential was associated with cytologic microfollicular and scant colloid alone subtype (6%).ConclusionThe results of this study show that indeterminate thyroid cytologic specimens can be subdivided into groups with different malignant risks. A microfollicular cytologic pattern in the absence of a hypercellular smear or nuclear atypia does not support a recommendation of surgical treatment. A malignant cytologic diagnosis has a high positive predictive value for detection of thyroid cancer. (Endocr Pract. 2004;10:330-334)     

Overexpression of HER2/neu oncoprotein in cytologic specimens

OBJECTIVE: To assess the rate of HER2/neu overexpression in cytologic specimens by immunocytochemistry (ICC) and compare these results in matched surgical specimens by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), when available. STUDY DESIGN: All cytologic specimens processed for HER2/neu evaluation by ICC (72 cases) and available corresponding histologic specimens (16 cases) were retrieved from our files. ICC was applied to previously Papanicolaou stained, routine fine needle aspirations specimens (64 cases) and cytocentrifuged, alcohol-fixed, fluid specimens (8 cases). FISH was performed on 6 histologic specimens. RESULTS: Overexpression of HER2/neu was seen in 7/22 breast cancers (31.8%), 3/18 pulmonary adenocarcinomas (16.6%), 2/5 colorectal adenocarcinomas (40%), 1/2 adenocarcinomas of the biliary system (50%), 1/3 thyroid papillary carcinomas (33.3%) and 1/3 prostate adenocarcinomas (33.3%). Sixteen cases had IHC in matched histologic specimens: 14 (87.5%) cases were concordant (11 negative and 3 positive in both specimens), 1 case was negative in the cytologic specimen and positive in the histologic specimen (with no amplification by FISH), and 1 case was positive in the cytologic specimen and negative in the histologic specimen (not informative by FISH). CONCLUSION: Our data suggest that overexpression of HER2/neu oncoprotein can be successfully detected in routine cytologic specimens, providing a simple, fast and cost-effective method of selecting patients for specific treatment.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Cytology of bladder papilloma

Eighty-four urinary cytology specimens from 51 patients known to have bladder papilloma were reviewed and compared with 30 specimens from patients without neoplastic urologic disease, 12 specimens from patients later found to have papillomas that were unsuspected at the time of examination and 6 specimens from patients with a history of papilloma but no present evidence of the disease. No specific findings were identified that could be used to make a cytologic diagnosis of papilloma. However, the specimens from patients with papilloma were likely to contain an increased number of exfoliated epithelial cells, including atypically shaped cells that were small and round or, less frequently, elongated; they were also likely to contain a small number of red blood cells. This combination of cytologic findings yielded a pattern that can be described as consistent with or suggestive of papilloma in the appropriate clinical setting. It is not diagnostic since the absence of this cytologic pattern does not rule out papilloma, and the same cytologic features can be found (less frequently) in patients with other urologic diseases.     

Analysis of immunoglobulin and T-cell receptor gene rearrangement in cytologic specimens

Recombinant DNA techniques to detect the rearrangement of genes encoding immunoglobulins and T-cell-antigen receptors have been used to identify clonality in lymphoid lesions. To determine the utility of such techniques in cytologic specimens, DNA was analyzed in 24 effusions and 6 fine needle aspirates. Immunophenotypic studies were also performed on the 19 specimens with suspected hematopoietic malignancies. Sufficient material for DNA analysis was present in 28 of the 30 specimens. Immunoglobulin or T-cell-receptor gene rearrangement was present in 13 specimens with atypical cytologic findings; DNA studies provided more information than did the immunologic studies in 3 cases. One T-cell malignancy showed T-cell receptor and heavy-chain gene rearrangement, and one B-cell malignancy showed immunoglobulin and T-cell receptor gene rearrangement. In all patients except one with no evidence of gene rearrangement, the morphologic and immunologic studies also favored a reactive process. Control specimens showed a germline configuration. This study demonstrated that DNA gene rearrangement studies are feasible on many cytologic specimens and may be useful in diagnostically difficult cases.     

Intraocular tumors. A cytopathologic study

The cytologic characteristics and histopathologic correlates of common ocular tumors were examined using (1) cytologic and histologic specimens prepared from enucleated eyes with retinoblastoma and melanoma, (2) cytologic specimens prepared from clinically obtained intraocular fluids from eyes with lymphoma, metastatic adenocarcinoma and retinoblastoma and (3) cytologic specimens prepared from orbital aspirates and cerebrospinal fluids from a patient in whom retinoblastoma had spread to the orbit and central nervous system. Retinoblastoma cells occurred singly and in clusters and were associated with abundant necrotic debris and portions of capillaries with perivascular tumor infiltrates. Melanoma cells frequently had prominent nucleoli and variable amounts of fine cytoplasmic pigmentation and were found individually and in groups. Lymphoma cells were noncohesive, with scant cytoplasm. Metastatic intraocular adenocarcinoma cells had well-defined borders, multiple nucleoli and vacuolated cytoplasm. In general, the cellular morphology in the cytologic and tissue preparations of the intraocular tumors correlated well with each other. The findings suggest that common primary and metastatic intraocular tumors can be differentiated in cytologic preparations.     

The Isaacs cell sampler: an alternative to curettage.

The Isaacs cell sampler was tested in 150 women (102 of them postmenopausal) referred for curettage. The results of cytological testing of material obtained with the sampler were compared with histological findings from curettage performed immediately afterwards. Satisfactory aspirates for cytological diagnoses were obtained in 141 patients and satisfactory material for histological diagnosis in 124. In the 102 postmenopausal patients the cytological method yielded 94 satisfactory specimens, while curettage yielded only 76. All the 17 carcinomas were diagnosed cytologically. Of the 12 cases of premalignant change, nine were diagnosed cytologically; two cytologically diagnosed premalignant cases did not, however, yield satisfactory material by curettage. The Isaacs cell sampler is a simple and reliable way of diagnosing malignancies. Further investigation is needed to define the cytological criteria for diagnosing premalignant cases, but as the material is well preserved accuracy should improve with increasing experience. The method should be valuable in screening women having oestrogen substitution therapy.