Wilms' tumor. Role of fine needle aspiration and DNA ploidy by image analysis in prognostication

OBJECTIVE: To evaluate the utility of cytomorphologic features and DNA ploidy estimation in fine needle aspirates (FNAs), from Wilms' tumors for prognostication. STUDY DESIGN: Twenty-three cases of Wilms' tumor having FNA and follow-up data were selected. Cytomorphology was analyzed by two observers. DNA ploidy was determined in 19 cases by image cytometry by destaining Papanicolaou-stained slides and restaining with Feulgen stain. Various parameters and patient outcomes were compared, and statistical evaluation was done. RESULTS: Poor outcome (12/23 cases) was associated with age < 2 years (P = .01), severe pleomorphism of blastemal cells (4/23 cases, P < .05), very large nucleoli (5/23 cases, P = .075), atypical mitosis (6/23 cases, P = .032) and aneuploidy/tetraploidy of tumor cells (6/29 cases, P = .005). Term unfavorable cytology is proposed when a combination of severe pleomorphism, very large nucleoli and atypical mitosis is seen in FNA smears. Four Wilms' tumor FNAs were characterized as showing unfavorable cytology, and all had a poor outcome (P = .0351). Three of the six cases with aneuploid/tetraploid features also showed unfavorable cytology. CONCLUSION: Unfavorable cytology and aneuploidy/tetraploidy in FNA smears of Wilms' tumor are associated with a poor prognosis.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

Worrisome histologic alterations following fine needle aspiration of the thyroid

OBJECTIVE: To investigate worrisome histologic alterations following fine needle aspiration (FNA) of the thyroid (WHAFFT). STUDY DESIGN: Of 1,890 FNA thyroid cases, 265 underwent surgical excision. The histologic sections of these cases were studied for WHAFFT lesions. Thirty control cases were also studied. RESULTS: WHAFFT lesions were present in 38.49% of cases. Acute lesions were seen in 30 and chronic in 72 cases. Control cases did not show WHAFFT lesions. The common lesions were hemorrhage and fibrosis. Worrisome lesions, like nuclear atypia, vascular changes, capsular pseudoinvasion and metaplasia, were present in 32 (12.07%) cases. CONCLUSION: Considering the large number of FNAs and reduction in the number of thyroid excisions, the advantages of FNA are manifold as compared to the few diagnostic problems. Misdiagnosis can be avoided with awareness of WHAFFT lesions.     

Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas

Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series.     

Metanephric adenoma vs. Wilms' tumor: a report of 2 cases with diagnosis by fine needle aspiration and cytologic comparisons

BACKGROUND: Metanephric adenoma (MA) is a rare benign renal neoplasm that can occur at any age, whereas, Wilms' tumor (WT) is the most common malignant renal neoplasm in children and is occasionally seen in adults. CASES: In case 1, a 26-year-old male had a left renal mass. Fine needle aspiration (FNA) showed 3-dimensional sheets of cells with nuclear overlapping, molding, irregular nuclear membrane and distinct nucleoli. Frequent mitotic figures could be seen. The cytologic differential diagnosis included Wilms' tumor, neuroectodermal tumor and metanephric adenoma. Nephrectomy revealed Wilms' tumor. In case 2, a 24-year-old female presented with erythrocytosis and a right renal mass. FNA showed small, uniform cells with smooth nuclear membrane, fine chromatin and inconspicuous nucleoli. A diagnosis of metanephric adenoma was made and confirmed on nephrectomy. CONCLUSION: Differentiating MA from WT based on cytologic features on FNA biopsy prior to surgical resection can he difficult.     

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.     

Analysis of fine needle aspiration cytology of the breast: a review of 1,297 cases and correlation with histologic diagnoses

OBJECTIVE: To evaluate the accuracy of fine needle aspiration (FNA) cytology of the breast and to ascertain its usefulness. STUDY DESIGN: The authors reviewed 1,297 cases of FNA cytology of the breast which were performed at Chonnam National University Hospital from 1999 to 2002. Cytologic diagnoses were compared with histologic diagnoses in 457 cases that underwent both cytologic and histologic examination. RESULTS: Of 1,297 cases, 1,201 (92.6%) were satisfactory and 96 (7.4%) unsatisfactory. Subsequent histologic examination was performed on 291 cases (29.7%) out of 981 "benign" lesions, 28 (73.7%) of 38 "suspicious," 124 (68.1%) of 182 "malignant" and 14 (14.6%) of 96 "unsatisfactory." FNA cytology revealed 77.7% sensitivity, 99.2% specificity, 98.4% positive predictive value and 88.0% negative predictive value. Diagnostic accuracy was 91.1%. Of the 291 benign cases on cytology, 35 cases were malignancy on histology. Of the 124 cases reported as malignant, 2 were benign. Interpretive error was the leading cause of false positive diagnoses. CONCLUSION: Although FNA cytology is a useful diagnostic procedure for the evaluation of breast lesions, it should be combined with other diagnostic modalities, such as physical examination, ultrasonography and mammography.     

Cytologic findings of breast ductal lavage and concurrent fine needle aspiration in pleomorphic lobular carcinoma in situ: a case report

BACKGROUND: Breast ductal lavage (DL) is a noninvasive procedure for sampling ductal epithelial cells. Patients at risk for breast cancer or with prior history can be monitored by DL. This report compares cytomorphology in concurrent DL, fine needle aspiration (FNA) and histology in a case of pleomorphic lobular carcinoma in situ (PLCIS) with signet ring features. CASE: A 57-year-old woman had DL and FNA performed after quadrantectomy for lobular carcinoma in situ with signet ring cell features. DL and FNA were diagnosed as suspicious and positive for malignancy, respectively. Subsequent biopsy showed PLCIS. Cytomorphologic features of DL, FNA and histology were compared. DL showed epithelial cells in small clusters or single-file arrangement and single-lying; in FNA, single cells predominated. DL and FNA showed nuclear atypia and cytoplasmic vacuoles, the latter more prevalent in FNA. Both samples showed cells with signet ring features. The atypical epithelial cells present in DL and FNA were identical to those seen in the histologic material. CONCLUSION: Cytomorphologic findings in DL, although less striking, are comparable to those seen in FNA. Architecture, nuclear atypia and intracytoplasmic vacuoles are helpful features in DL for establishing a diagnosis of suspicious if not positive for malignancy in LCIS.     

Phyllodes tumor of the breast. A cytohistologic study of 80 cases

OBJECTIVE: To study the cytologic features of phyllodes tumor (PT) of the breast and determine the accuracy of their subclassification in fine needle aspirates. STUDY DESIGN: Eighty cases of histologically diagnosed PT between 1982 and 1997 with a previous fine needle aspiration (FNA) were evaluated. The FNA smears of each case were reviewed without knowledge of the initial cytologic diagnosis and subclassified into benign, borderline or malignant PT. RESULTS: Benign PTs were characterized by a dimorphic mixture of stromal and epithelial cells. The stromal fragments showed mild to moderate cellularity with absent to minimal pleomorphism and no mitosis. There were occasional, if any, single stromal cells. Borderline PTs had stromal fragments with moderately cellular stroma exhibiting moderate pleomorphism. Two additional features were the presence of single stromal cells and an occasional mitosis in the stromal fragments/single cells. Aspirates from malignant PT were very cellular, with a high stromal/epithelial ratio and marked stromal cellularity. The stromal cells were highly pleomorphic, with frequent mitosis and atypical single stromal cells in the background. Fifty-seven of the 80 histologically documented cases (71.3%) were diagnosed as PT on FNA (40 benign, 10 borderline and 7 malignant). In 81% (46 of 57 PTs), good cytohistologic correlation (32 benign, 8 borderline and 6 malignant) was observed. In another eight cases, one grade differentiation between cytologic and histologic grade was observed. Six of the nine malignant PTs on histology were correctly subclassified on cytology. There were one false positive and two false negative cases. CONCLUSION: Cytologic diagnosis and grading of PT on FNA is possible. Special care should be undertaken in interpreting phyllodes fragments, cellularity of stroma, pleomorphism and mitosis. Single stromal cells are also important morphologic criteria for subclassification. Multiple-site aspiration is advisable to avoid diagnostic errors.     

Statistical analysis of fine needle aspiration cytology of the breast. A review of 678 cases plus 4,265 cases from the literature

Between 1979 and 1984, 678 breast fine needle aspiration (FNA) cytologic specimens were received in our laboratory; tissue follow-up was available for 159 cases (23%). The diagnoses rendered in cases with subsequent tissue study were benign (41%), insufficient (10.5%), atypical and/or suspicious for carcinoma (10.5%) and malignant (38%). Using the tissue diagnosis as the standard, there were four false-negative cytologic results and one false-positive result. Considering only cases with a definitive diagnosis of benign or malignant, the sensitivity of cytologic interpretation for diagnosing malignancy on adequate material was 94% while the specificity was 98%; the overall efficiency of the test was thus 96%. The predictive values were 98% for a positive test and 94% for a negative test. Of the total number of submitted cases, a correct and definitive diagnosis was rendered 76% of the time. Calculation of similar statistics from six other series in which the FNA cytologic diagnoses were compared with the histologic diagnoses yielded data almost identical to our findings. The high degree of uniformity in the data indicates that these statistical parameters can be used as standards for evaluating the efficiency of breast FNA cytology.     

Anaplastic Wilms' tumor. Initial diagnosis by fine needle aspiration

The diagnosis of a diffusely anaplastic Wilms' tumor in a ten-month-old child was first suggested by cytologic and histologic study of a fine needle aspirate. The mesenchymal component was predominant (75%) and exhibited some cells with hyaline, periodic acid-Schiff-positive, intracytoplasmic droplets. Foci of clear-cell carcinoma were also present. Only one case showing this histologic pattern in this unusual variant of Wilms' tumor has been reported previously.     

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.     

Cytomorphometry of uveal melanoma. Comparison of fine needle aspiration biopsy samples with histologic sections.

A number of approaches are being investigated to increase the prognostic accuracy for uveal melanoma patients; the standard deviation of nucleolar area measurements and the DNA content appear to correlate better with survival than do classic histologic parameters. The utility of performing cytomorphometric measurements on fine needle aspiration (FNA) biopsy samples was prospectively analyzed for 24 eyes containing uveal melanomas that were examined with both 25-gauge FNA biopsy and standard histologic techniques. "Masked" analysis of the cellular composition of the 24 cases showed the presence or absence of epithelioid cells to be accurately predicted on the FNA samples in all cases. Image analysis cytomorphometric measurements of nucleolar area showed marked variability (with r less than 0.4) when FNA and histologic samples from the same case were compared. The relationship between these measurements was affected by cell type, sampling, specimen processing and investigator experience.     

Fine needle aspiration cytology of granulomatous prostatitis induced by BCG immunotherapy of bladder cancer

Six patients treated with intravesical bacillus Calmette-Guérin (BCG) for superficial bladder cancer had granulomatous prostatitis demonstrated histologically by transperineal needle biopsy. Four of the six patients also underwent transrectal fine needle aspiration (FNA) for cytologic study. The diagnosis of granulomatous prostatitis was made cytologically in all four without knowledge of the histologic findings. Granulomatous prostatitis appears to be common following intravesical BCG treatment; these cases show that FNA cytology can be recommended as a method for diagnosing this complication.     

Atypical epithelial cells, cannot exclude papillary carcinoma, in fine needle aspiration of the thyroid

OBJECTIVE: Atypical epithelial cells, cannot exclude papillary thyroid carcinoma (AEC-PTC), in fine needle aspiration (FNA) of the thyroid is a controversial diagnostic category that might cause a dilemma in patient management. STUDY DESIGN: Eighty-eight thyroid FNA specimens from 86 patients with a diagnosis of AEC-PTC were retrieved from our files in a 10-year period from December 1996 to December 2006. Of the 86 patients, 57 had follow-up histologic diagnoses and were included in this study. The cytologic and histologic materials were reviewed and correlated. RESULTS: Of the 57 patients, all had cytologic atypical features suggestive of PTC. Twenty-five cases of PTC were identified at surgery (44%). Review of the cytologic materials identified the following cytologic features, either alone or in combination strongly associated with PTC at resection: rare intranuclear cytoplasmic invagination (INCI), squamoid cytoplasm and psammoma bodies. CONCLUSION: The most common reasons for rendering the diagnosis of AEC-PTC in FNA of thyroid include rare atypical cells in a cystic thyroid nodule or a background of Hashimoto's thyroiditis. The cytologic features of LNCI, squamoid cytoplasm and psammoma bodies should alert the pathologist. Focal cytologic features of PTC in FNA samples are strongly associated with papillary carcinoma on resection.     

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.     

Accuracy of cytology vs. microbiopsy for the diagnosis of well-differentiated hepatocellular carcinoma and macroregenerative nodule. Definition of standardized criteria from a study of 100 cases

OBJECTIVE: To determine the accuracy of ultrasound (US)-guided fine needle aspiration (FNA) for the diagnosis of well-differentiated hepatocellular carcinoma (wd HCC) and macroregenerative nodule (MRN) and to identify the most useful cytologic and histologic criteria to distinguish between those two diagnoses. STUDY DESIGN: Cytologic and histologic specimens of 50 wd HCC and 50 MRN were reviewed blindly and the diagnosis compared to the final clinical diagnosis. Twenty-eight cytologic and 25 histologic criteria were examined and subjected to statistical analysis. RESULTS: Among 100 cases studied, the final diagnosis was available for 43. In those 43 cases, combining analysis of cytologic and histologic specimens, the sensitivity of US-guided FNA was of 75% and the specificity 100%. Cytologic analysis was better than isolated histologic analysis, with a sensitivity of 75% vs. 68%, respectively. Sensitivity of cytologic diagnosis was lower for smaller nodules and for those located in poorly accessible hepatic segments. With the use of stepwise logistic regression analysis, four cytologic features (increased nuclear/cytoplasmic ratio, cellular monomorphism, nuclear crowding, loss of bile duct cells) and four histologic features (increased nuclear/cytoplasmic ratio, decreased Kupffer cells, cellular monomorphism, increased trabeculae thickness) were identified as predictive of HCC.     

Frequency and rationale of fine needle aspiration biopsy conversion to core biopsy as a result of onsite evaluation

OBJECTIVE: To measure the frequency and analyze the rationale and potential diagnostic benefits of converting the fine needle aspiration (FNA) procedure to core biopsy. STUDY DESIGN: The frequency of conversion to core biopsy was calculated over 13 months. Analysis of these cases was conducted in regard to the appropriateness for conversion and whether the core biopsy provided additional specific diagnostic information. RESULTS: During this period, the onsite triaging pathologist recommended FNA conversion to core biopsy in 31 of 821 procedures (3.7%). In 3 instances, the core biopsy could not be performed. The rationale for conversion in the remaining 28 cases (3.4%) included either scant aspirated material in 9 cases (32%) or an anticipated need for additional histologic material to further characterize the lesion in the other 19 (68%). In 27 cases (96%), the rationale for conversion was considered to be appropriate, and in 3 of these (11%) the core provided a change in diagnosis. Additional useful diagnostic information was identified in 12 cases (44%). CONCLUSION: Conversion to core biopsy during FNA is infrequent but justified in most cases. Appropriate utilization of this approach is helpful and may be cost effective.     

Fine needle aspiration of metastatic and hematologic malignancies clinically mimicking pancreatic carcinoma.

The fine needle aspiration (FNA) cytology findings in 19 cases of hematopoietic and metastatic neoplasms that radiographically mimicked primary pancreatic carcinoma are reported. These cases represented 11% of 176 malignant diagnoses in a series of 304 pancreatic FNAs. The cytologic diagnoses included 7 non-Hodgkin's lymphomas, 2 Hodgkin's lymphomas, 6 small cell carcinomas (4 lung, 1 gallbladder, 1 skin), 3 squamous cell carcinomas (2 cervix, 1 esophagus) and 1 hepatocellular carcinoma. In six cases the pancreatic lesion was the initial presentation of malignant disease. These included five lymphomas, which probably involved peripancreatic lymph nodes, and a metastatic small cell carcinoma of pulmonary origin. Recognition of unusual morphologic features of pancreatic carcinoma raised the possibility of extrapancreatic malignancies. Electron microscopy and immunocytochemistry performed on FNA specimens were helpful in selected cases. The FNA diagnosis of hematopoietic and metastatic neoplasms that clinically mimic pancreatic carcinoma prompts appropriate clinical studies and treatment and eliminates the need for open pancreatic biopsy and/or resection.     

Triple test approach to inadequate fine needle aspiration biopsies of palpable breast lesions.

OBJECTIVE: To perform a retrospective study evaluating the triple test for inadequate fine needle aspiration (FNA) biopsies of palpable breast lesions with a two-year clinical follow-up. STUDY DESIGN: All aspirates were reviewed and assessed for cellular adequacy in a one-year period. Specimen adequacy was based on the most stringent criteria, the presence of six or more epithelial cell clusters composed of at least six cells each. In all cases, clinical and radiologic results were reviewed and compared with the histologic outcome. RESULTS: Aspirates from 61 of 263 (23%) patients with palpable breast lesions that yielded nondiagnostic results were examined. The study showed a misdirected FNA rate of 21% and a misinterpreted rate of 1.6%. The other 77% of cases had benign surgical biopsies and/or clinical follow-up. Three of 61 (4.9%) cases with nondiagnostic smears were found to have cancer; two were inadequate due to misdirected aspirates, and one was misinterpreted microscopically. All cancer cases underwent surgical removal of the mass as a result of clinical or radiologic suspicion. CONCLUSION: We recommend utilizing the three diagnostic parameters of cytology, clinical findings and radiology, the "triple test," to achieve the best diagnostic accuracy in breast FNAs and to enhance patient management.