A comparative study of morphometric measurements of nucleoli in uveal melanomas from electron micrographs and plastic-embedded and paraffin-embedded sections

Morphometric measurements of nucleoli were done on uveal melanomas from surviving and nonsurviving patients. The melanomas were embedded in paraffin and plastic, and measurement data from Papanicolaou-stained paraffin-embedded sections, toluidine blue-stained plastic-embedded sections and scanning transmission electron micrographs (STEM) of plastic-embedded sections were compared. The results showed that one parameter, the coefficient of variation (CV) of nucleolar area, correctly classified 80% of the cases as to survival when plastic-embedded material was used and 70% of the cases when paraffin-embedded material or STEM micrographs were used. The inverse standard deviation of the nucleolar area was a better predictor of outcome than was the CV of nucleolar area only in the paraffin-embedded sections. The nucleolar measurements were most easily and rapidly performed in the plastic-embedded sections.     

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.     

Computerized histopathologic assessment of malignant potential. III. Refinements of measurement and data analysis

The nucleolar area of uveal melanomas, measured from standard hematoxylin-and-eosin-stained microslides , has been shown in previous work to correlate well with survival following enucleation of the tumor-bearing eye. Despite this correlation, the accuracy of the original system for measuring nucleolar area was affected by several sources of error: (1) the algorithm by which area was computed underestimated true area, (2) geometric and optical factors caused overestimation of nucleolar area unless measured in the center of the microscopic field of view and (3) the area of small nucleoli, as the result of several possible mechanisms, contains less useful information than the area of large nucleoli. This paper presents methods introduced to reduce error from these sources and demonstrates that the predictive value of nucleolar measurements is relatively insensitive to high levels of random variation.     

Lipomatous lesions of the parotid gland. Potential pitfalls in fine needle aspiration biopsy diagnosis

Nine cases of benign fatty tumors of the parotid studied initially by fine needle aspiration (FNA) biopsy and subsequently diagnosed by open biopsy were reviewed. All lesions presented as enlargements of the parotid gland. The cytologic diagnoses were correct in only five of the nine cases. While four of six FNA samples from lipomas were correctly diagnosed by cytology, the other two samples were classified as inadequate. Three cases of diffuse infiltration of the parotid by mature-appearing adipose tissue were cytologically characterized as "no diagnostic change" in two cases and sialosis in one case. The clinical, radiologic, cytologic and histologic features of these tumors are described to increase the familiarity of cytologists with these lesions, which may prevent unnecessary surgical intervention in some patients.     

Flow cytometric and histomorphometric analysis of limitations of clinical breast cytomorphometry

The clinical value and limitations of a previously described cytomorphometric method, based on nuclear size and anisonucleosis, for evaluation of routine fine-needle aspiration of the breast were assessed in a series of 313 histologically investigated primary breast lesions. Limitations were analyzed by histomorphometry and DNA flow cytometry in 116 consecutive cases of histologically confirmed breast carcinoma. Eighty per cent of histologically proven malignant tumours were classified cytomorphometrically as malignant and no false-positive results were encountered. For benign lesions a benign cytomorphometric classification was reached in 66% of the cases. Histomorphometry showed that on the whole the assignment of histologically malignant tumours to a non-malignant cytomorphometric classification was determined by smaller nuclei and not by sampling error. Tumours assigned to a malignant cytomorphometric classification had on average significantly higher DNA indices than did tumours not assigned to a malignant cytomorphometric classification (P less than 0.001). The mean-nuclear areas in cytomorphometry and histomorphometry were strongly correlated with DNA indices indicated by DNA flow cytometry (P less than 0.001 for both). The present findings show that this cytomorphometric method is appropriate for routine quality control of a cytological diagnosis of malignancy in FNA of the breast. However, an inconclusive result in 15-25% of the tumours is inevitable.     

Fine needle aspiration biopsy of well-differentiated liposarcoma of the neck in a young female. A case report.

BACKGROUND: Well-differentiated liposarcomas are low grade, nonmetastasizing, malignant neoplasms composed primarily of mature adipose tissue. They are uncommon in the head and neck. CASE: A 24-year-old female presented to the ears, nose and throat clinic for evaluation of a recent, rapidly growing neck mass on the right side. Fine needle aspiration (FNA) biopsy of the mass showed that the smears had fragments of connective tissue with a mixture of mature-appearing fat traversed by bands of fibrous collagen and vessels. Nuclei within the fat and fibrous bands were mildly irregular, hyperchromatic and enlarged, with one or two small nucleoli. Infrequently present but readily identified, lipoblasts were scattered throughout the aspirate smears. A diagnosis of "atypical lipomatous neoplasm" was rendered. Subsequently, the mass was surgically removed. On histologic examination, the tumor was a well-differentiated liposarcoma. CONCLUSION: FNA biopsy of well-differentiated liposarcomas in the head and neck can present difficulties in the classification and diagnosis of this neoplasm.     

Fine needle aspiration biopsy of azoospermic testes. Could it replace histologic biopsy?

OBJECTIVE: To evaluate the possibility of replacing histologic biopsy of azoospermic testes by fine needle aspiration (FNA) for diagnostic and management purposes. STUDY DESIGN: Twenty-seven patients were examined under general anesthesia, and 53 testes were biopsied by FNA. Fifty-four testes were biopsied for histologic examination. Histology and cytology of each testis were compared to assess the discrepancy or concordance between the diagnoses. RESULTS: Twenty-seven testes showed complete concordance of cytology and histology, and 13 testes showed a mild degree of discrepancy. A severe degree of discrepancy was seen in 13 testes. In the majority of discrepant cases, FNA biopsy diagnosis was more sensitive in detecting evidence of full or advanced maturation. In one case of discrepancy, the histologic finding was Sertoli cells only, and cytology revealed focal full maturation. In vitro fertilization using sperm from this case was successful. CONCLUSION: FNA biopsy of testes in azoospermia is a fast, reliable and minimally traumatic method. The prospects for utilizing FNA biopsy material in assisted and microassisted fertilization are promising.     

Differential diagnosis of malignant intrahepatic tumors by ultrasonically guided fine needle aspiration biopsy and by laparoscopic/intraoperative biopsy. A comparative study

Thirty-six cases of ultrasonographically detected liver tumors (28 malignant and 8 benign lesions) were investigated by both fine needle aspiration (FNA) biopsy and laparoscopic or intraoperative tissue biopsy. The sensitivity of FNA biopsy in detecting a neoplasm was 85.7% while that of tissue biopsy was 82.1%. Specificity was 100% in both methods. A correct histologic diagnosis of the neoplasm could be made on the cytologic smear in only 14 cases (50.0%) due to technical and methodologic difficulties. Endoscopic and intraoperative tissue biopsy yielded sufficient material to make a definite histologic tumor diagnosis in 23 of 28 cases. Additional information on tumor spread and sequelae of liver infiltration was obtained by macroscopic tissue observations in nine cases. These results indicate that FNA biopsy is less sensitive in the classification of primary or secondary liver tumors and that tissue biopsies obtained during laparoscopy or laparotomy are required if a suspected hepatic neoplasm needs to be classified exactly to plan therapy and to establish a prognosis.     

Necrosis in thyroid nodules after fine needle aspiration biopsy. Report of two cases

Two cases of infarction of thyroid neoplasms following fine needle aspiration (FNA) biopsy are reported. Histologic study of a 2.5 x 2.5 cm nodule excised 18 days after FNA had diagnosed a Hürthle-cell neoplasm showed mainly necrotic debris and granulation tissue. While FNA made the diagnosis of a papillary carcinoma in the second case, which had had an FNA biopsy of the same nodule six years earlier, most of the nodule was fibrotic and necrotic. These two cases demonstrate the potential problems in such cases: (1) post-FNA infarction may obscure the nature of a cytologically diagnosed neoplasm, making histologic confirmation difficult, and (2) FNA of an infarcted nodule may have difficulties in obtaining diagnostic material, potentially resulting in a false-negative diagnosis. Review of the literature on thyroid infarction shows it to be a rare event, with most reported cases occurring after FNA biopsy of a neoplasm. The finding of necrosis and fibrosis in an aspirate or surgical specimen should thus suggest the presence of a neoplasm.     

Testicular germ cell tumors. Classification based on fine needle aspiration biopsy

Fine needle aspiration (FNA) biopsy was performed preoperatively on 13 patients with testicular germ cell tumors. The cytologic typing of the tumors was based on the presence or absence of seminoma, embryonal carcinoma, yolk-sac tumor, choriocarcinoma and teratoma in the aspirate. The cytologic findings showed good agreement with the histologic findings. Only four cases showed a single type of tumor; the other nine cases showed as many as four different tumor components. A few characteristic cytologic features proved to be sufficient for tumor typing; this suggests that FNA biopsy cytology can also be useful in identifying metastatic germ cell tumors in extra-gonadal sites.     

Assessment of fine needle aspiration as a screening test for occult prostatic carcinoma

As part of an ongoing study of objective parameters of prognostic value in prostatic carcinoma, a routine procedure was developed to aspirate all prostates prior to surgery. These targets were different from those of other workers in the field of prostatic fine needle aspiration (FNA), who generally advocate that FNA be confined to suspicious nodules. The aspirations were performed by a large group of practicing urologists who had no special training in prostatic FNA except for guidelines provided by their peers and information available in the literature. This approach permitted an assessment of the performance of FNA as a screening test rather than as a diagnostic procedure. During the period from January 1983 to February 1987, 1,683 patients had prostatic FNAs performed (plus subsequent histologic study). The following diagnoses were rendered: "inadequate/scanty specimen" in 625 cases (37%), "negative/atypical" in 844 cases (50%) and "suspicious/positive" in 214 cases (13%). Histologic examination showed stage A1 prostatic adenocarcinoma in 18 patients. The cytologic diagnoses on these 18 patients were inadequate/scanty in 3 (17%), negative/atypical in 13 (72%) and suspicious/positive in 2 (11%). Of the 214 patients with a positive/suspicious diagnosis by FNA, the diagnosis of prostatic carcinoma was confirmed by tissue evidence in 200; the other 14 patients had either no evidence of prostatic carcinoma on surgical biopsy (needle biopsy/transurethral resection/suprapubic prostatectomy) or had no surgical biopsy. Eight of the 14 patients developed clinical evidence of carcinoma, 1 died of urinary bladder carcinoma and 1 was lost to follow-up. In the remaining four patients, there is still no evidence of prostatic carcinoma after about one-and-one-half years of follow-up. These results indicate that (1) specialized training is required in order to obtain adequate smears by prostatic FNA; (2) prostatic FNA is not a good screening technique for detecting stage A1 prostatic carcinoma; and (3) a positive diagnosis by prostatic FNA, even when not confirmed by tissue biopsy, is still an indication of disease.     

Percutaneous core needle biopsy vs. fine needle aspiration in diagnosing benign lung lesions.

OBJECTIVE: To determine the diagnostic value of percutaneous core needle biopsy (PCNB) in comparison with fine needle aspiration (FNA) in patients with benign pulmonary lesions. STUDY DESIGN: A retrospective review was undertaken of computed tomography-guided PCNBs and FNAs performed between 1988 and 1997. Both FNA and PCNB biopsies were carried out sequentially at the same visit in every patient. RESULTS: A specific benign diagnosis was made in 10/60 cases (16.7%) by FNA and in 49/60 (81.7%) by PCNB. PCNB findings resulted in significant modification of the diagnosis established by FNA. The only significant complication encountered was pneumothorax, at a rate of 11.7%, which is compatible with that reported in the literature for complications induced by FNA alone. CONCLUSION: Radiologically guided PCNB is a safe procedure, can provide sufficient histologic material for a specific diagnosis of peripheral lung disease and can avoid more-invasive surgical procedures in many cases. Our experience demonstrated that the histologic analysis provided by PCNB can greatly increase the diagnostic accuracy in benign pulmonary diseases as compared with the yield of FNA.     

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.     

Fine needle aspiration biopsy in the diagnosis of intrathoracic masses.

During a 3.5-year period (January 1, 1987, to June 30, 1990) 420 percutaneous fine needle aspiration (FNA) biopsies were performed on 390 patients (309 males, 81 females) suffering from one or more intrathoracic, radiologically visible lesions. Aspirations were carried out using 21- or 23-gauge Chiba needles under fluoroscopic or computed tomographic control. The aspirates were used to make minibiopsies and cytologic smears. Diagnosis was possible in 373 cases (95.64%): on the first pass in 344 cases, on the second in 28 cases and on the third in 1. In 17 cases (4.36%) the aspirate was inadequate for diagnosis. There were complications in 10 cases (2.56%) (9 pneumothorax and 1 hemophtysis) requiring intensive care. The 373 percutaneous FNA biopsy diagnoses included 256 malignant tumors (68.63%), of which 234 were primary and 22 were secondary, and 117 benign lesions (31.37%), 5 of them neoplastic and 112 nonneoplastic. Three hundred two of 373 percutaneous FNA biopsy diagnoses were followed (80.96%). One hundred twenty-three follow-ups were histologic (40.73%), including secondary tumors, which could be compared with the primary histotype. Twenty-eight follow-ups were cytologic (9.27%), and 151 were clinical (50.00%), using progression of the disease or the beginning of chemoradiotherapy as a criterion for malignancy and a stable condition or regression of the lesion with nononcologic medical treatment as a criterion for benignity. Percutaneous FNA biopsy diagnoses were confirmed in 288 cases (221 true positives and 67 true negatives) and unconfirmed in 14 (1 false positive and 13 false negatives). Specificity, sensitivity, negative predictive value, positive predictive value and total diagnostic accuracy were, respectively, 98.52, 94.44, 83.75, 99.54 and 95.36%. The histologic typing accuracy of percutaneous FNA biopsy on 70 specimens of surgically removed malignant epithelial neoplasias was 70.00%. These results confirm that percutaneous FNA biopsy is a reliable method of diagnosing intrathoracic masses and reduces the need for diagnostic thoracotomy.     

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.     

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.     

Ultrasound-guided fine needle aspiration cytology of impalpable breast lesions in a rural setting. Comparison of cytology with imaging and final outcome

OBJECTIVE: To analyze the effectiveness of fine needle aspiration (FNA) cytology in a multidisciplinary setting in rural Australia and to compare the imaging (mammographic and ultrasound) appearances and cytomorphologic findings with the final outcome. STUDY DESIGN: Prospective analysis of ultrasound-guided FNA cytology results from 426 women, aged 40-86 years, with screening-detected mammographic abnormalities. Cases of microcalcification, assessed mainly by stereotactatic core biopsy, were not included in the study. The FNAs were performed at a rural breast screening and assessment program in New South Wales, Australia, over a three-year period between May 1993 and May 1996. RESULTS: Imaging, FNA and combined imaging and FNA results from 426 women were as follows. The imaging diagnoses included 176 (41%) benign, 34 (8%) probably benign, 17 (4%) equivocal, 104 (24%) suspicious and 95 (23%) malignant cases. The FNA findings showed 59 (14%) no epithelial cells seen (nondiagnostic), 175 (41%) benign, 36 (8%) atypical, 41 (10%) suspicious and 115 (27%) malignant. Combined imaging and cytologic results comprised 224 (52.6%) benign, 10 (2.3%) atypical/equivocal, 59 (13.9%) suspicious and 133 (31.2%) malignant cases. All the malignant cases, by combined assessment, had malignant histology, and all the benign cases behaved in a benign fashion. In 80% of the suspicious lesions, the histologic diagnosis was malignant, but only 10% of the atypical/equivocal lesions had malignant histology. The positive predictive value of diagnosis of malignancy by combined imaging and FNA was 100%, and the false negative rate was 0%. CONCLUSION: Despite the recent surge in the popularity of core biopsy, FNA cytology of impalpable, mammographically detected lesions, when practiced in a multidisciplinary setting, is an extremely accurate test with high sensitivity, specificity, predictive values and efficacy. FNA cytology of the breast is a well-tolerated, relatively noninvasive test with a very low risk of complications. The sensitivity and positive predictive values for malignant and suspicious mammographic categories are also very high.     

Fine needle aspiration of the liver

A total of 81 transhepatic fine needle aspiration (FNA) biopsies were performed on 78 patients to rule out focal or diffuse neoplastic disease; 87.6% were performed with ultrasound guidance, 6.1% with CT guidance, 3.7% intraoperatively and 1 using fluoroscopy during percutaneous transhepatic cholangiography. Smears of the aspirated samples were cytologically evaluated with clinical and radiologic correlation; in addition, histologic examination of cell blocks was performed in 46% of the cases, ultrastructural examination in 34% of the cases and peroxidase-antiperoxidase staining in 3 cases. Ultrastructural definition of the type of malignancy was possible in 24 cases (29%). Minor complications in two patients were pain and tenderness at the puncture site. The sensitivity for malignancy was 91%, the specificity was 100%, the predictive value of positive results was 100%, and the predictive value of negative results was 73%. This series demonstrates that FNA biopsy with ultrasound guidance can provide an accurate diagnosis of malignancy and may preempt a lengthy workup in the search for a primary tumor.     

Cytodiagnosis of bone tumors by fine needle aspiration

A retrospective study was undertaken of bone lesions examined by preoperative fine needle aspiration (FNA) cytology in our hospital during the ten-year period from 1970 to 1979. The 430 cytologically examined lesions were classified into three groups: inflammatory lesions, tumorlike lesions and tumors. A total of 54 patients had undergone surgery, with most of the lesions in those cases proven to be tumors or tumorlike by histologic study. Correlation between the histologic and FNA cytologic findings showed complete compatibility in 76% of the cases, partial compatibility in 13% and incompatibility in 11%. It is concluded that FNA biopsy is appropriate for identifying bone tumors and tumorlike lesions if sufficient numbers of tumor cells are obtained for morphologic examination. Although aspiration cytodiagnosis can be of considerable value in the recognition of certain bone lesions, it cannot replace formal tissue biopsy in the diagnosis of primary bone neoplasms. The morphology of several common bone tumors is described in detail and their differential diagnosis is discussed.     

Fine needle aspiration cytology of lactating adenoma of the breast. A comparative light microscopic and morphometric study

Six cases of lactating adenoma of the female breast diagnosed by fine needle aspiration (FNA) were reviewed. The FNA cytologic diagnostic features included a usually moderately cellular aspirate with an abundant foamy background material, intact epithelial lobules or acini and small groups and solitary epithelial cells that contained uniform nuclei, fine chromatin and prominent nucleoli. When present, the cytoplasm was finely vacuolated or wispy; many nuclei appeared stripped of their cytoplasm. These features were compared light microscopically with the cytopathologic features of six cases of invasive well-differentiated ductal adenocarcinoma, seven cases of invasive lobular carcinoma, one case of granulocytic sarcoma and one case of primary histiocytic lymphoma of the breast. In addition, cytomorphometric analysis demonstrated no statistically significant differences in the nuclear areas of lactating adenoma as compared with those of well-differentiated ductal carcinoma and lobular carcinoma.