Lymph node examination by fine needle aspiration in patients with known or suspected malignancy

In a series of more than 2,500 fine needle aspirates from multiple body sites, over 200 were clinically identified as lymph nodes from patients with known or suspected malignancy. The material was obtained using the easily manipulated Aspir-Gun with a 21-gauge or 22-gauge needle and syringe. Of the 200 lymph node specimens, 100 (50%) were cytologically reported as positive for malignancy. Ninety cases had surgical pathology specimens available for comparison with the fine needle aspiration (FNA) specimens. For the 88 of these cases with satisfactory FNA specimens, evaluation of the FNA results showed a predictive value of a positive result of 96.8%. These results compare favorably with those of surgical biopsy. The malignancies present in the lymph nodes included numerous adenocarcinomas from the breast, melanoma and pulmonary small-cell carcinoma. Six cases are briefly presented in which the FNA diagnosis was more problematic. While histologic examination of tissues or organs remains the desirable benchmark of comparison, the appropriate utilization of FNA cytology to guide therapy, particularly in a patient with previously diagnosed malignancy, may obviate the need for an open biopsy. The technique is convenient for patient and physician, useful for outpatients, relatively painless and provides good correlation between cytologic morphology and histopathology.     

Fine needle aspiration cytology of focal liver lesions. Results obtained with examination of both cytologic and histologic preparations

The results of 197 consecutive fine needle aspirations (FNA) of focal liver lesions performed on 176 patients were reviewed, and the 176 single most diagnostic aspirates were analyzed in detail. The majority of specimens were obtained using a 20-gauge or 22-gauge needle with ultrasound guidance. An attempt was made to obtain both a cytologic and a tissue specimen from each aspirate. The overall accuracy of the procedure was 85%; the accuracies of the tissue and cytologic specimens were 67% and 73%, respectively. The combined procedure detected 81% of the documented malignant tumors; the tissue specimen detected 62%. Eleven tumors were identified only in the tissue specimen and 23 were identified only in the cytologic specimen. There were no false-positive diagnoses. Six of nine hepatocellular carcinomas were detected. These results show that FNA cytology is a safe, accurate, relatively noninvasive technique whose diagnostic yield may be improved by examination of both a histologic tissue and a cytologic preparation.     

Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast

X. Jing, E. Wey and C. W. Michael Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast Objective: To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma. Methods: A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed. Results: Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy. Conclusions: ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.     

Morphologic and immunocytochemical evaluation of 220 fine needle aspirates of malignant lymphoma and lymphoid hyperplasia

A total of 220 fine needle aspiration (FNA) specimens from 212 patients with clinically suspected or previously histologically confirmed lymphoma were evaluated by cytology in conjunction with immunophenotyping analysis of the aspirate; the results were compared with the histologic diagnosis made on previous or current accessions of lymph node or extranodal tissue. Smears of the aspirates were stained with the Diff-Quik and Papanicolaou stains while immunoperoxidase staining using antibodies against kappa and lambda immunoglobulin light chains and Leu-4 was routinely performed on Cytospin preparations. Where indicated, additional marker studies (including T-200, Leu-1, Leu-2a, Leu-3a + 3b, Leu-M1, B1, Leu-12, IgM, CALLA and TdT) were performed. For the non-Hodgkin's lymphomas, specimens were classified by the cytologic characteristics of the neoplastic cells according to the International Working Formulation scheme. The combination of cytologic smears and immunoperoxidase studies resulted in a diagnosis of lymphoma in 173 cases (79%). The remaining aspirates were interpreted as suspicious for lymphoma (7%), benign (10%) or inadequate for diagnosis (4%). Of the 15 suspicious aspirates, 5 proved to be Hodgkin's disease and 2 to be T-cell lymphoma by subsequent biopsy. The cause of failure in the nine inadequate aspirates were necrosis (3 cases), sclerosis (2 cases) and faulty technique (4 cases). In the cases that had concurrent tissue biopsies, no false-positive diagnoses were rendered. These results indicate that FNA used in association with immunocytochemistry is a reliable tool for establishing the diagnosis and classification of the majority of cases of lymphoma. Optimal immunoglobulin light-chain ratios for defining monoclonality in FNA specimens of B-cell lymphomas are proposed.     

The role of fine needle aspiration cytology in the diagnosis of lymphoma

The accuracy of fine needle aspiration (FNA) cytology for the diagnosis of lymphoma and other hematolymphoid malignancies was investigated by a review of 158 FNA specimens from 143 patients. Patients included in the study had either a diagnosis of a hematolymphoid malignancy by FNA cytology or a biopsy diagnosis of lymphoma that was preceded by FNA cytology. Biopsy specimens were obtained from 85% of the patients. Of the 158 needle aspirates, 118 (75%) were diagnosed as lymphoma, 13 (8%) as suspicious of lymphoma, 8 (5%) as myelomas, 3 (2%) as leukemias, 12 (8%) as positive for malignancy and 4 (2%) as negative for malignancy. Two of the 118 needle aspirates diagnosed as lymphoma were false positives while 3 of 13 diagnosed as suspicious for lymphoma were found to be benign. Overall, there were four false negatives. Morphologic subclassification of the lymphomas, originally attempted for 60 needle aspirates, was identical to the histologic subclassification in 51 cases (85%). FNA cytology provided the initial diagnosis of a hematolymphoid malignancy in 51% of the cases and allowed the documentation of recurrent disease in 49%. The results demonstrate the usefulness of FNA cytology for the diagnosis and management of patients with lymphoma.     

Applications of monoclonal antibodies in clinical cytology as exemplified by studies with monoclonal antibody B72.3. The George N. Papanicolaou award lecture

The monoclonal antibody (MAb) B72.3, reactive with a high-molecular-weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been previously shown to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct for the diagnosis of carcinoma in cell blocks and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from all of 21 patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions from 41 patients. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. MAb B72.3 has recently been used with fine needle aspiration (FNA) biopsy specimens and the corresponding surgically excised tumors to determine cellular reactivity. Using the ABC immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumors were analyzed for TAG-72 expression. Positive staining with MAb B72.3 was observed in needle aspirates of 27 of 27 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, 6 of 6 adenocarcinomas of the colon and in carcinomas from other body sites. In contrast, 21 small-cell carcinomas of the lung, 13 malignant melanomas, 2 lymphomas and 2 sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B72.3. In more than 90% of these patients, the staining patterns of the tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies, it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, that is most selectively expressed in carcinomas and that may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in fine needle aspiration biopsies.     

Application of the immunoperoxidase technique to cell block preparations from fine needle aspirates

Immunocytochemistry on fine needle aspiration (FNA) material has been mainly performed on cytologic preparations; there have been few reports on the use of FNA cell blocks. This study compared the intensity scores of immunoperoxidase staining on FNA cell block preparations from 21 breast, 12 thyroid and 10 lymph node aspirates with the scores on the corresponding surgically excised specimens. FNA materials for cell blocks were fixed in formalin and embedded in agar. Ten commercially available antibodies forming three panels were studied using standard peroxidase-antiperoxidase and avidin-biotin complex techniques. In general, the staining results on the FNA cell block sections agreed with those on the surgical specimens; in addition, there were fewer aberrant positive staining results and much less background staining in the cell block sections. These phenomena were most striking with the cytokeratin antibodies. It is concluded that immunoperoxidase staining on FNA cell block preparations is reliable; the advantages of the use of cell block sections as opposed to smears are discussed.     

Flow cytometric DNA analysis of renal-cell carcinoma. A study of fine needle aspiration biopsies in comparison with multiple surgical samples

The flow cytometric (FCM) DNA analysis of fine needle aspiration (FNA) biopsy material was compared with the DNA analysis of multiple surgical biopsy material from 44 renal-cell carcinomas. Twenty tumors were heterogeneous with respect to their DNA content. Eleven of the 17 tumors that had both diploid and aneuploid tumor cell clones in the surgical specimens gave a diploid DNA content in the aspiration biopsies; the other 6 cases showed aneuploidy in the aspirate. The fine needle aspirates from 18 homogeneously diploid tumors and 9 tumors with an aneuploid DNA content in all eight surgical samples revealed DNA indices similar to those found in the surgical samples. These findings show that aneuploid clones of renal-cell carcinoma can remain undetected by the use of FNA biopsy as a method for obtaining samples for FCM DNA analysis.     

Histological examination of clots from cytological specimens: is this a worthwhile procedure?

A comparison of conventional cytology and clot histology was made on 174 serous fluids, fine needle aspirates (FNA) and other non‐gynaecological specimens. In eight cases (4.5%) this clot material contained malignant cells or cells suspicious of malignancy despite the absence of suspicious or malignant cells in conventionally prepared smears from the same specimen. In 11 cases (6.3%) the clot was negative, although conventional smears contained malignant or suspicious cells. A χ² test showed that there was no statistically significant difference between the number of positive diagnostic scores in each group with χ² of 0.223 (degrees of freedom=1), P=0.637. Examination of clot material from serous fluids and FNA aspirates is as effective as examination of conventional cytological preparations. Processing of clots from cytological aspirates for histological examination should be more widely adopted, and is applicable in all cytopathology laboratories.     

Fine needle aspiration of the breast. Importance of the aspirator

All 503 fine needle aspirations (FNAs) of the breast performed over a three-year period at the Medical Center Hospital of Vermont were analyzed. There were 93 aspirates diagnosed as "positive," all of which were from patients eventually shown to have cancer. However, there were 38 patients with primary carcinoma in which the FNA was not diagnosed as positive, for a diagnostic failure rate of 31.4%. In order to determine the possible effect of technique as practiced by an experienced aspirator in diminishing such diagnostic failures, we compared 190 aspirates obtained by a single individual with 193 aspirates obtained by 15 individuals in the same community. For the single experienced aspirator, the technical failure rate was 9.8% whereas in the group with many aspirators it was 45.9%. This finding confirms that, although fine needle aspiration of the breast is considered easy to perform, skill on the part of the aspirator is important for satisfactory results.     

Diagnostic pitfalls in the fine needle aspiration of thyroid nodules. A study of 555 cases in Chinese patients

The diagnostic value and limitations of fine needle aspiration (FNA) were determined by examining 555 palpable thyroid nodules in Chinese patients who had a definitive diagnosis established by thyroidectomy (529 cases) or large-needle biopsy (26 cases). Of the aspirates, 97.8% were satisfactory for cytologic examination. The overall malignancy rate was 20%. FNA detected 73 (74.5%) of 98 primary malignant tumors and 9 (90%) of 10 metastatic tumors. Diagnostic errors were most commonly due to inadequate specimens and cystic lesions. Cystic fluid, present in one-third of all lesions, was associated with a malignant nodule in 13% of the cases. FNA was most valuable for detecting papillary carcinomas; it may at times suggest the likelihood of a follicular carcinoma.     

Masquerades of malignancy: a review of 4,241 aspirates from the breast

A total of 4,241 aspirates from the breast were obtained by fine needle aspiration biopsy. Of the 3,809 benign lesions, 61 (1.6%) were interpreted as possibly malignant. In all, excisional biopsy, not mastectomy, was recommended as the next procedure. More than 50% of these misdiagnoses were from aspirates of fibrocystic disease, 15% were from fibroadenomas, and the remainder were from gynecomastia, solitary papillomas, periareolar hyperplasia, pregnancy hyperplasia and granulation tissue. Most errors were based on specimens that were insufficiently cellular or whose poorly preserved cells lacked the majority of the criteria of malignancy.     

Value of the filter imprint technique in aspiration biopsy cytology

In 468 fine needle aspiration (FNA) biopsies, after smearing of the aspirate on glass slides, additional material was obtained by flushing the needle with a fixative. The cells were collected on Millipore filters, from which imprints were prepared. The filter imprints were found to be sufficiently cellular in 60% of the cases, which reduced by 33 (7.3%) the number of cases with unsatisfactory aspirates. Diagnostic specificity and sensitivity were not influenced by the technique. The filter imprint technique was of particular value in breast aspirates.     

Fine needle aspiration cytology of clear cell sarcoma. Report of a case with immunocytochemical, immunohistochemical and ultrastructural studies.

Cytologic findings of clear cell sarcoma obtained by fine needle aspiration (FNA) of a tumor are described. The tumor probably originated in the retroperitoneal tissue, and the diagnosis was confirmed histologically by open biopsy. Percutaneous needle aspirates of the intraabdominal tumor and touch preparations obtained from the open biopsy specimen revealed numerous atypical cells with an extremely hyperchromatic nucleus, prominent nucleoli and clear cytoplasm. The cytoplasm was rich in glycogen. The immunocytochemical technique demonstrated S-100 protein and neuron-specific enolase in the cytoplasm, both of which were exhibited also in the histologic specimen. Clear cell sarcoma is a rare tumor of soft tissue, and to our knowledge, detailed cytologic appearances of this tumor obtained by FNA have not been reported. In addition, the present tumor was unique in location. It is possible to diagnose clear cell sarcoma accurately on an FNA cytologic specimen if the periodic acid-Schiff stain and immunocytochemical technique are utilized in addition to the routine Papanicolaou method.     

C-Erbb-2 Expression and Dna Ploidy Status In Breast Cancer Cells Obtained By Fine Needle Aspiration (Fna)

The aim of this study was to determine the relative rate of c-erbB-2 oncoprotein immuno-detection on matched fine needle aspiration (FNA) smears and surgical specimens of breast cancer, and to correlate the c-erbB-2 expression with the assessment of the DNA ploidy status. the expression of c-erbB-2 oncoprotein was evaluated using an immunoalkaline phosphatase technique in 49 breast aspirates (four benign and 45 malignant lesions) and 21 matched surgical specimens. the DNA ploidy status was assessed by densitometric techniques on Feulgen-stained smears. Fifty-eight per cent of the smears obtained from 45 malignant lesions and 43% of the 21 corresponding paraffin sections contained cells that were stained by the antibody. the higher incidence of c-erbB-2 expression on smears seems to be due mainly to the better antigen preservation in the fresh cytological preparations. the correlation between c-erbB-2 oncogene expression and DNA ploidy assessment showed an increased incidence of oncogene expression in aneuploid tumours (71% vs 29%; P > 0.05).     

Thoracic fine needle aspiration biopsy versus fine needle cutting biopsy. A comparative study of 40 patients

The fine needle aspiration (FNA) biopsy findings were compared with the results of fine needle cutting (FNC) biopsy in 40 patients. The lesions (38 pulmonary nodules, 1 mediastinal mass and one lytic rib lesion) were biopsied with 22-gauge Greene and 21-gauge E-Z-EM needles through a 19-gauge needle guide. The FNA biopsy findings were based on smears and cell blocks of material obtained with the Greene needles while the FNC biopsy findings were based on tissue cores obtained by the E-Z-EM needles. In 83% of the cases, both techniques yielded specimens with similar cellularity; in seven cases, the FNA samples were more cellular. Malignancy was diagnosed in 80% of the patients: by both techniques in 26 patients, by FNA biopsy only in 5 patients and by FNC biopsy only in 1 patient. The sensitivity of FNA biopsy was higher than that of FNC biopsy (96.8% vs. 84.3%). The specificity and predictive value of positive results were 100% for both techniques. The predictive value of negative results was higher for FNA biopsy (88.8% vs. 54.5%). The majority of FNC biopsy tissue cores consisted mostly of clotted blood, lung tissue and/or fibrous tissue and did not facilitate or improve the diagnosis. Those data suggest that the contribution of FNC biopsy to the diagnosis of thoracic neoplasms is very limited and that the performance of FNC biopsy with an E-Z-EM needle in addition to or instead of FNA biopsy is not justified.     

Silver-binding nucleoli and nucleolar organizer regions in fine needle aspiration cytology of the breast

Silver staining was used to demonstrate nucleoli and nucleolar organizer regions (NORs) in cytopreparations from breast fine needle aspiration (FNA) biopsies, with the resulting black dots being a combination of silver-binding nucleoli and dispersed NORs. Discrete black dots in 200 nuclei were manually counted in 25 silver-stained biopsies; the cytologic diagnoses were made on routine Papanicolaou-stained cytopreparations from the same aspirates. Although malignant breast lesions showed higher counts than did benign breast disease, an overlap of one malignant and three benign lesions occurred. Therefore, the method cannot be recommended for reliably discriminating between malignant and benign routine breast specimens obtained by FNA; it may have some value in assessing tumor behavior.     

Fine needle aspiration of poorly defined indurated and well-defined breast lesions: a cytopathologic comparative study

OBJECTIVE: To compare the cytologic findings and diagnoses of breast fine needle aspiration (FNA) samples of well-defined lesions (WDL) with those of poorly defined indurated lesions. STUDY DESIGN: We examined 371 consecutive breast FNA specimens obtained without diagnostic image guidance. Fifty-eight lesions were described by the examining pathologists as PDILs, and the remaining 313 lesions were described as WDLs. RESULTS: Compared with WDLs, PDILs were more likely to yield hypocellular specimens deemed unsatisfactory for diagnostic evaluation (37.9% vs. 14.1%). However, a substantial number of atypical, suspicious for malignancy and malignant cases (12.1%, 5.2%, and 13.8%, respectively) were identified with PDILs. In addition, benign diagnoses were more frequently rendered with aspirates of WDLs, compared with PDILs (47.9% vs. 31.0%). In our study, FNAs of PDILs were more often diagnostic in white women < 49 years of age and in lesions measuring > 2 cm. CONCLUSION: Given the relatively high frequency of malignant, suspicious and atypical lesions detected with PDILs, FNA is a suitable first diagnostic approach for PDILs, especially considering the relatively low cost and simplicity of FNA procedures without diagnostic imaging guidance.     

Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit

Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit
A breast FNA cytology service for palpable breast lumps was commenced in 1989 using the cytospin method. Over the following 6 years 2314 aspirates were received. The results were audited in detail in 1990, 1991/1992 and 1994. Multidisciplinary clinical audit meetings followed each audit cycle. Practice change was agreed after each audit. Each audit cycle was followed by demonstrable improvement in the complete sensitivity of the technique, being respectively 79%, 88% and 96%. The cytospin method is a viable alternative to the conventional smear method.     

Immunoperoxidase staining of fine needle aspiration specimens previously stained by the Papanicolaou technique

The use of immunoperoxidase techniques was investigated in 21 fine needle aspiration (FNA) cytology smears that had been previously stained by the Papanicolaou technique. The retrospectively selected slides were destained before applying the immunostain, utilizing antisera to calcitonin, prostatic acid phosphatase (PrAP), prostate-specific antigen (PSA), alpha-lactalbumin (AL), S-100 protein (S-100), carcinoembryonic antigen (CEA), common leukocyte antigen (LA), epithelial membrane antigen (EMA) and alpha-fetoprotein (AFP). Positive results were obtained with six of nine small-cell carcinomas of the lung stained with EMA, all three colonic carcinomas stained with CEA, one of two prostatic carcinomas stained with PSA and PrAP, one of two lymphomas stained with LA and the one medullary thyroid carcinoma stained with calcitonin. Negative staining results were observed in the one melanoma stained with S-100, the two breast carcinomas stained with AL and the one hepatocellular carcinoma stained with AFP. These results indicate that immunostaining can be a helpful diagnostic tool in diagnosing some fine needle aspirates using smears previously stained with the Papanicolaou stain.