Fine needle aspiration of non‐small cell lung cancer: current state and future perspective

A. Fassina, R. Cappellesso, F. Simonato, C. Lanza, A. Marzari and M. Fassan Fine needle aspiration of non‐small cell lung cancer: current state and future perspective The emerging treatment revolution determined by the advent of new targeted therapies requires accurate tumour subtyping as a mandatory step in the clinical workup of patients with non‐small cell lung carcinoma (NSCLC). As a result of advanced and inoperable disease or poor performance status, in many patients, minimally invasive procedures must be employed to obtain diagnostic material. Fine needle aspiration (FNA) is a valid and widely employed alternative to either tru‐cut or open‐sky biopsy. Indeed, cytological specimens are suitable for techniques such as immunocytochemistry, mutation and microRNA analysis, and may present advantages over small biopsies especially if cell blocks are prepared and attention is paid to cytomorphology and pre‐analytic management of specimens at the time they are collected. These will allow the adequate stratification of patients into different diagnostic and prognostic classes.     

A comparative study on the different staining methods and number of specimens for the detection of acid fast bacilli

The presence of acid fast bacilli in multiple specimens was investigated comparatively with Ziehl-Neelsen (ZN) and fluorescence microscopy (FM) staining in order to determine sensitivity in detecting tuberculosis (TB). A total of 465 specimens obtained from 295 patients were analysed at Harran University Medical School Hospital between March 1998 and March 2000. The culture was employed as the reference method. Sixty-eight patients (23.1%) were diagnosed as having TB by culture. The ZN and FM staining sensitivities were 67.6% (46/68) and 85.2% (58/68) respectively. Two hundred and one patients (68.1%) submitted one specimen to the laboratory. TB positivity was detected in 42 (20.9%) of these patients by culture. The sensitivities of ZN and FM stains were found to be 61% and 83% in these patients. However, in 18 patients (6.1%) who submitted two specimens to the laboratory, the TB was positive in six of them (33.3%) and ZN and FM sensitivities were 66% and 83% respectively. When three specimens or more were collected from the patients (76 patients, 25.8%), TB positivity was determined in 20 of them (26.3%) and the sensitivities were 80% and 92% in the ZN- and FM-stained smears, respectively. Our data indicate that in the diagnosis of TB, FM has greater sensitivity than ZN. In particular, in the case of a single specimen, the diagnostic value of FM is quite significant. It is, therefore, possible to conclude that both ZN and FM staining can be used for the diagnosis of TB when there are more than two specimens. However, if only one or two specimens are available, FM staining is preferable.     

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.     

Proteome analysis in thyroid pathology

The incidence of thyroid cancer has continuously increased due to its detection in the preclinical stage. Clinical research in thyroid pathology is focusing on the development of new diagnostic tools to improve the stratification of nodules that have biological, practical and economic consequences on the management of patients. Several clinical questions related to thyroid carcinoma remain open and the use of proteomic research in the hunt for new targets with potential diagnostic applications has an important role in the solutions. Many different proteomic approaches are used to investigate thyroid lesions, including mass spectrometry profiling and imaging technologies. These approaches have been applied to different human tissues (cytological specimens, frozen sections, formalin-fixed paraffin embedded tissue or Tissue Micro Arrays). Moreover, other specimens are used for biomarker discovery, such as cell lines and the secretome. Alternative approaches, such as metabolomics and lipidomics, are also used and integrated within proteomics.     

Relationship between the cellular composition of sputum and the cytologic diagnosis of lung cancer

In 410 patients with either a primary or a metastatic malignant lung process, the cellular composition of the sputum specimens was analyzed in relation to the diagnostic accuracy of sputum cytology and in relation to anamnestic and clinical patient characteristics. In patients with primary lung cancer, sputum samples with true-positive cytologic diagnoses contained significantly more cells from the deeper airways, such as alveolar macrophages and bronchial columnar cells, than did sputum specimens with a false-negative diagnosis, even though these cell types were present in both types of specimens. In sputum samples from patients with metastatic lung malignancies, differences in cellular composition of specimens with true-positive and false-negative diagnoses were not significant.     

PCR-based methylation testing for Prader-Willi or Angelman syndromes using archived fixed-cell suspensions

All Prader-Willi syndrome (PWS) and 75% of Angelman syndrome (AS) patients have specific DNA methylation pattern alterations that can be used for diagnostic evaluation. The methylation testing identifies a significantly higher proportion of patients as compared to fluorescence in situ hybridization (FISH)-based microdeletion analysis and is thus a useful diagnostic evaluation for clinically suspect, but FISH-negative, patients. We used two independent PCR-based protocols for methylation testing on fixed cell specimens archived after FISH analyses. Changes in DNA methylation due to the procedure of cell fixation were ruled out by testing control specimens before and after fixation. Then methylation testing was carried out on 20 standard fixed-cell supsensions from people suspected for PWS or AS. These fixed specimens were stored after negative FISH analysis for up to 4 years at 4 degrees C in 3:1 methanol/acetic acid. Methylation patterns associated with AS (one specimen) and with PWS (one specimen) were identified for both protocols. The observed methylation patterns were concordant with the phenotypes of the positive individuals and for the two protocols used. We have, thus, shown that archived fixed-cell suspensions from individuals suspected as PWS or AS that were negative for cytogenetic/FISH microdeletions, can now be re-evaluated with PCR-based methylation testing without the need for additional blood samples from the previously studied individuals.     

Benign squamous cells with pleomorphic microvilli in urine or bladder washings

Exfoliated cells in catheterized urine or bladder washings from 40 patients were observed by light microscopy (LM) and by scanning electron microscopy (SEM). The specimens from seven of these patients (six postmenopausal females and one 85-year-old male) contained squamous cells with pleomorphic microvilli (PMV) on their surfaces. Four of these cases had no bladder lesions by cystoscopic examination. Three patients had recurrent papillary transitional-cell carcinoma of the bladder, and the cytologic specimens from two of them contained transitional cells with PMV. The distinction between squamous and transitional cell is readily made by SEM, based primarily on cell shape and thickness. The presence of PMV on otherwise-benign-appearing squamous cells in urine or bladder washing specimens may be a source of confusion in the interpretation of SEM findings. The presence of PMV on exfoliated squamous cells in cytologic material from the human urinary tract does not seem to have the same diagnostic and prognostic significance as the presence of PMV on transitional cells.     

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.     

Computerized interactive morphometry as an aid in the diagnosis of pleural effusions

A morphometric study of cytologic preparations from patients with benign and malignant (mesothelioma and carcinoma) pleural effusions is reported. The routine cytologic smears from these specimens were studied with a new system of video-based computerized interactive morphometry (CIM) that allows the measurements of real-time images of cell profiles by the simple procedure of touching the two extreme points of a diameter of interest on a touch-sensitive screen. For each cell, the nuclear profile diameter (NPD) and the cytoplasmic profile diameter (CPD) are measured and categorized into classes with 2-microns intervals; the NPD/CPD ratio is also calculated. The mean NPD is calculated for the specimen after measurement of 100 cells. The data were interpreted by two independent methods: a statistical method of discriminant analysis that classifies the lesions as benign, carcinoma or mesothelioma and provides a probability statement of membership in a particular diagnostic class and an ad-hoc algorithm that categorizes the effusions as benign or malignant based on hierarchic analysis. A data base derived from study of the first 24 cases was constructed and utilized for the test classification of the second 24 cases, which were treated as specimens of unknown diagnosis. The discriminant analysis correctly classified 21 of the 24 test cases into their proper diagnostic groups. The algorithm for a computer-generated pathologic diagnosis correctly identified 47 of the 48 cases as benign or malignant. The technical advantages of video-based CIM over the existing morphometric methods are discussed.     

Diagnosis and Treatment of influenza--clinical investigation on viral shedding in children with influenza

Children with influenza usually shed viruses from the several days before onset of clinical symptoms, and viruses are isolated for one or two weeks after onset. Point-of-care rapid diagnostic tests are useful to guide use of antiviral agents, appears over 90% sensitivity and specificity for influenza A with nasopharyngeal specimens compared with cell culture. The detection limits of these test kits are 103 pfu or over, so it is necessary to consider viral load in clinical specimens for diagnosis with these kits. Viral load are decreased after the start of antiviral agents, but influenza viruses are isolated in more than half of pediatric patients when fever get down, and resistant viruses are detected in some of these patients. It is very important for influenza control to investigate on viral shedding and resistant viruses.     

Cytologic findings in vitreous fluids. Analysis of 74 specimens

OBJECTIVE: To review the cytologic findings of vitreous specimens and propose a simplified approach to them. STUDY DESIGN: Seventy-four vitreous specimens from 60 patients obtained either during a pars plana vitrectomy or by vitreous aspiration were reviewed. Clinical correlation was obtained on all patients. RESULTS: Findings suggestive of a specific disorder were present in 30 specimens (41%); cytologic examination of the remaining 44 showed nonspecific changes. A lymphoproliferative disorder, the intraocular malignancy suspected most often in this series, was identified in eight specimens (11%). Large cell lymphomas were evident in 5 specimens, 2 specimens were suspicious for lymphoma, and 1 specimen was consistent with plasmacytoma. Twelve specimens (16%) contained hemorrhage. In rare instances, specific infectious agents, such as parasites (5%), bacteria (1%) and fungi (3%), could be identified. The diagnosis of viral infections required ancillary studies. Lens fragments were identified in four cases (5%), and a diagnosis of lens-induced endophthalmitis could be rendered in one case (1%). Changes consistent with sarcoidosis were present in 3% of cases. CONCLUSION: Based on this experience with vitreous specimens submitted for clinical reasons, we found that they could be divided into three broad diagnostic categories: inflammation/infection (54 specimens/41 patients), hemorrhage (12 specimens/12 patients) and malignancy (8 specimens/7 patients).     

Mycobacterium tuberculosis DNA in tissue affected by sarcoidosis.

OBJECTIVE--To investigate the prevalence of Mycobacterium tuberculosis DNA in granulomatous tissues from patients with sarcoidosis and from controls matched for age, sex, and tissue by using the polymerase chain reaction. DESIGN--Single blind control trial. SUBJECTS--16 patients with sarcoidosis who had undergone diagnostic biopsy of lung, skin, or lymph node and 16 patients with squamous cell carcinoma or Hodgkin''s disease to act as controls. In addition, four lung specimens infected with M tuberculosis were included as positive controls. RESULTS--M tuberculosis DNA was present in sarcoid tissues containing granulomas from seven of the 16 patients and one of the 16 matched controls. Two of the four specimens known to be infected with M tuberculosis were positive in the controlled experiment. CONCLUSION--These figures suggest that M tuberculosis DNA is detected as readily in patients with sarcoidosis as in patients with frankly tuberculous tissues and imply that M tuberculosis may be linked to the cause of sarcoidosis.     

Prostatic acid phosphatase immunoperoxidase staining of cytologically positive effusions associated with adenocarcinomas of the prostate and neoplasms of undetermined origin

An immunoperoxidase staining technique was employed in an effort to demonstrate prostatic acid phosphatase in sections of the effusion cell blocks in a retrospective investigation of the incidence of malignant prostatic cells in body cavity effusions in 33 patients with histologically confirmed prostatic cancer. An attempt was also made to identify the prostate as a possible anatomic site of origin in 26 patients with an unknown primary but with cytologically positive fluids. Neoplastic cells were identified in the effusion specimens in 21.2% of the patients with confirmed prostatic cancer; the sources, however, were either primary or metastatic carcinomas of nonprostatic origin. None of the cytologic specimens in this study demonstrated a positive prostate-specific acid phosphatase staining reaction, as did the prostatic metastases to the lungs used as controls.     

Diagnostic Efficacy of Cell Block Immunohistochemistry,Smear Cytology,and Liquid-Based Cytology in Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Lesions: A Single-Institution Experience

Background

The diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology varies widely depending on the treatment method of the specimens. The present study aimed to evaluate the diagnostic efficacy of cell block (CB) immunohistochemistry, smear cytology (SC), and liquid-based cytology (LBC) in patients with pancreatic lesions without consulting an on-site cytopathologist.

Methods

This study prospectively enrolled 72 patients with pancreatic lesions. The EUS-FNA specimens were examined by SC, LBC, and CB immunohistochemistry. The diagnostic efficacy of the 3 methods was then compared. Patients’ final diagnosis was confirmed by surgical resection specimens, diagnostic imaging, and clinical follow-up.

Results

Our results included 60 malignant and 12 benign pancreatic lesions. The diagnostic sensitivity (90%), negative predictive value (66.7%), and accuracy (91.7%) of CB immunohistochemistry were significantly higher than those of SC (70.0%, 30.0%, and 75.0%, respectively) and LBC (73.3%, 31.6%, and 77.8%, respectively) (all P<0.05). The combination of CB and SC, or CB and LBC, did not significantly increase the efficacy compared to CB immunohistochemistry alone.

Conclusion

Our findings suggest that in the absence of an on-site cytopathologist, CB immunohistochemistry on EUS-FNA specimens offers a higher diagnostic efficacy in patients with pancreatic lesions than does SC and LBC.     

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.     

Comparison of the pick-and-smear and Saccomanno methods for sputum cytologic analysis

The two methods of preparing sputum specimens for cytologic study, the (fresh) pick-and-smear technique and the (blended) Saccomanno technique, were compared using 249 consecutive specimens. Two slides were prepared for each specimen by each technique. Of the specimens, 103 showed squamous metaplasia, carcinoma in situ or carcinoma. A semiquantitative rating system (0 to 4+) was used to determine the number of diagnostic cells for each method for those 103 cases. More diagnostic cells were found on the Saccomanno preparations (217) than on the fresh preparations (154). There were 121 diagnostic cells in the Saccomanno preparations versus 95 diagnostic cells in the fresh preparations from 63 squamous metaplasias; 7 versus 3 for the preparations from 5 carcinomas in situ; 64 versus 42 from 28 squamous cell carcinomas; 3 versus 1 from 1 large cell undiffernomas; and 12 diagnostic cells in Saccomanno preparations versus 5 in fresh preparations from 3 small cell cancers. Twelve squamous metaplasias, two carcinomas in situ, four squamous carcinomas, one adenocarcinoma and one small cell cancer had no diagnostic cells on the fresh preparations; four squamous metaplasias and one squamous carcinoma had no diagnostic cells on the Saccomanno preparations. More diagnostic information and fewer false-negative results were achieved with the Saccomanno technique.     

Nonaspiration fine needle cytology. Application of a new technique to nodular thyroid disease

The basic principle underlying fine needle aspiration (FNA) is the aspiration of cellular material from target masses, often utilizing fairly high suction pressures. The procedure requires a needle and a syringe, advisedly held in a syringe holder, enabling single-handed suction to be exercised. Mastery of the technique is variable, with few operators acquiring consistent skill. A new technique, pioneered in France but essentially unpublicized, eliminates active aspiration, replacing it by the principle of capillary suction of fluid or semifluid material into a thin channel (a fine needle). This nonaspiration sampling method was tested in a consecutive series of 50 solid thyroid nodules. Simultaneously performed conventional FNAs served as controls. Cell samples were cytologically assessed as unsuitable, diagnostic/adequate or diagnostic/superior, without knowledge of the sampling method employed. Diagnostically superior specimens were obtained significantly more frequently by the nonaspiration technique in 36 benign lesions and 13 neoplasms. The method of nonaspiration fine needle cytology ("cytopuncture") is described and illustrated, and the implications for its use in other sites are discussed.     

Realities of diagnosing Helicobacter pylori infection in clinical practice: a case for non-invasive indirect methodologies.

BACKGROUND: The current, arbitrarily defined gold standard for the diagnosis of H. pylori infection requires histologic examination of two specially stained antral biopsy specimens. However, routine histology is potentially limited in general clinical practice by both sampling and observer error. The current study was designed to examine the diagnostic performance of invasive and non-invasive H. pylori detection methods that would likely be available in general clinical practice. METHODS: The diagnostic performance of rotating clinical pathology faculty using thiazine staining was compared with that of an expert gastrointestinal pathologist in 38 patients. In situ hybridization stains of adjacent biopsy cuts were also examined by the expert pathologist for further comparison. Receiver operator characteristic (ROC) analysis was performed to evaluate whether the diagnostic performance of the expert pathologist differed depending upon the histologic method employed. A similar analysis was made to evaluate the diagnostic performance of pathology trainees relative to the expert. In the absence of an established invasive gold standard, non-invasive testing methods (rapid serum antibodies, formal Elisa antibodies and carbon-14 urea breath testing) were evaluated in 74 patients by comparison with a gold standard defined using a combination of diagnostic tests. RESULTS: Using either rapid urease testing of biopsy specimens or urea breath testing as the gold standard for comparison, the diagnostic performance of the rotating clinical pathology faculty was inferior to that of the expert gastrointestinal pathologist especially with regard to specificity (e.g., 69 percent for the former versus 88 percent, with the latter relative to rapid urease testing). Although interpretation of in situ hybridization staining by the expert appeared to have an even higher specificity, ROC analysis failed to show a difference. The mean ROC areas for thiazine and in situ hybridization staining for trainee pathologists relative to the expert were 0.88 and 0.94, respectively. In untreated patients, urea breath testing had a sensitivity and specificity of 100 percent as compared with thiazine staining with a sensitivity of 83 percent and a specificity of 97 percent. Post-therapy, breath testing had a sensitivity of 100 percent but a specificity of only 86 percent as compared with invasive testing with a sensitivity and specificity of 100 percent. Rapid serum antibody testing and formal Elisa antibody testing agreed in 93 percent of cases (Kappa 0.78) with the rapid test being correct in three of the four disagreements. CONCLUSIONS: The current study illustrates a number of realities regarding H. pylori diagnosis. There is no diagnostic gold standard in general clinical practice. Accurate interpretation of specially stained slides is a learned activity with a tendency towards overdiagnosis early on. Urea breath testing is likely to be the diagnostic method of choice for untreated patients in general clinical practice although antibody testing is almost as accurate. Rapid antibody tests are at least as accurate as formal Elisa antibody tests. Urea breath testing is useful for confirming cure after therapy, but false-positive results may occur in some patients.     

Book review

Abstract

Exfoliative cytology is a minimally invasive technique for obtaining oral cell specimens from patients for diagnostic purposes. Classical applications of oral cytology studies, such as oral candidiasis, have been extended to include oral precancerous and cancerous lesions. A number of analytical methods are available for studying cytology specimens. The development of molecular analysis techniques, the oral cancer etiopathogenic process, and improvements in liquid-based exfoliative cytology are leading to renewed interest in exfoliative cytology. Results sometimes are disputed, so the aim of our review was to clarify the applicability of exfoliative cytology to the diagnosis of oral precancerous and cancerous lesions.     

Fine needle aspiration biopsy in uveal melanoma

Fine needle aspiration (FNA) biopsies were performed in a series of patients with uveal tumors. Cytopathologic examination established the correct diagnosis in 26 of 29 uveal melanomas. FNA biopsy was able to exclude the diagnosis of a malignant neoplasm in five nonmelanoma tumefactions. Histologic and FNA cytologic typing of melanomas as epithelioid or predominantly spindle cell showed good agreement, with the same classifications made in 14 of 18 cases. FNA biopsy specimens also proved to be adequate for DNA-content and cell-cycling studies. The cessation of cell cycling in successfully irradiated melanomas may be useful in establishing the postradiation status of tumors that have questionable growths after therapy, as was shown using FNA samples in three such cases in this study. The results of this study show that FNA biopsy is a useful diagnostic adjunct in patients with atypical lesions that require therapy.