Identification of putative oncogenes in lung adenocarcinoma by a comprehensive functional genomic approach.

Amplification and overexpression of putative oncogenes confer growth advantages for tumor development. We used a functional genomic approach that integrated simultaneous genomic and transcript microarray, proteomics, and tissue microarray analyses to directly identify putative oncogenes in lung adenocarcinoma. We first identified 183 genes with increases in both genomic copy number and transcript in six lung adenocarcinoma cell lines. Next, we used two-dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify 42 proteins that were overexpressed in the cancer cells relative to normal cells. Comparing the 183 genes with the 42 proteins, we identified four genes - PRDX1, EEF1A2, CALR, and KCIP-1 - in which elevated protein expression correlated with both increased DNA copy number and increased transcript levels (all r > 0.84, two-sided P < 0.05). These findings were validated by Southern, Northern, and Western blotting. Specific inhibition of EEF1A2 and KCIP-1 expression with siRNA in the four cell lines tested suppressed proliferation and induced apoptosis. Parallel fluorescence in situ hybridization and immunohistochemical analyses of EEF1A2 and KCIP-1 in tissue microarrays from patients with lung adenocarcinoma showed that gene amplification was associated with high protein expression for both genes and that protein overexpression was related to tumor grade, disease stage, Ki-67 expression, and a shorter survival of patients. The amplification of EEF1A2 and KCIP-1 and the presence of overexpressed protein in tumor samples strongly suggest that these genes could be oncogenes and hence potential targets for diagnosis and therapy in lung adenocarcinoma.

Ultrasound-guided fine-needle aspiration biopsy of the thyroid bed.

BACKGROUND: Ultrasound (US) has been shown to be a sensitive technique for monitoring patients for recurrent thyroid carcinoma in the thyroid bed after total thyroidectomy. However, the role of US-guided fine-needle aspiration biopsy (FNAB) in the confirmation of sonographically indeterminate or suspicious masses has not been adequately addressed. The purposes of this study were to determine the sensitivity and specificity of US-guided FNAB of the thyroid bed for diagnosing recurrent carcinoma after total thyroidectomy and to highlight potential diagnostic pitfalls. METHODS: Twenty-one patients with a history of total thyroidectomy and histologically confirmed thyroid carcinoma who had undergone US-guided FNAB of hypoechoic lesions in the thyroid bed were included in this retrospective study. Fifteen of the 21 had papillary carcinoma (PC), 5 had medullary carcinoma (MC), and 1 had Hürthle cell carcinoma (HTC). The cytologic features of the aspirates were compared with histopathologic findings of pre- and post-FNA surgery. Immunohistochemical staining for thyroglobulin, calcitonin, and parathyroid hormone was performed in four cases. RESULTS: The cytologic diagnosis from the US-guided FNABs was conclusive in 20 of 21 cases. Fifteen cases were diagnosed as recurrent tumor (12 PC, 2 MC, and 1 HTC), and 13 of the 15 were confirmed subsequently by histology. Five cases were diagnosed as benign (two residual benign thyroid tissue, one parathyroid gland [PG] tissue, and two reparative changes) and hence were not resected. There was one false-positive diagnosis in which PG was misdiagnosed as PC. Immunohistochemical studies helped to confirm the diagnosis of PG tissue in two cases and of MC in two cases. The sensitivity of US-guided FNA for diagnosing recurrent carcinoma in the thyroid bed after total thyroidectomy was 100% and the specificity was 85.7%. CONCLUSIONS: US-guided FNAB was found to be a sensitive and specific test for diagnosing sonographically indeterminate lesions in the thyroid bed. One potential diagnostic pitfall was the misdiagnosis of normal residual thyroid or PG tissue as recurrent tumor. Careful attention to cytologic details and the use of selected immunohistochemical staining may help to prevent these misdiagnoses.

Renal lymphoma. The diagnostic and therapeutic roles of fine-needle aspiration.

This study focused on 19 patients with renal lymphoma (RL) from whom 20 initial (1 patient with fine-needle aspiration [FNA] specimens of masses in both kidneys) and 1 repeated FNA specimen were obtained. Of the 19 patients, 10 had secondary RL, 8 primary RL, and 1 transplant RL. The FNA samples were studied by smears (all cases), tissues (11), phenotyping by immunostaining (13) or flow cytometry (4), and gene rearrangement (3). The final diagnoses included 1 T-cell lymphoma and 18 B-cell lymphomas. Of the 20 original specimens, 14 were reported as positive for lymphoma, 3 suggestive of lymphoma, 1 positive for transitional cell carcinoma, and 2 unsatisfactory. The follow-up specimen showed reactive changes. Tissue correlation, available in 11 cases, confirmed a positive cytodiagnosis (7), provided a final diagnosis in the cytologically inconclusive cases (3), or revised the misdiagnosis of transitional cell carcinoma from smears (1). The phenotyping elucidated the B vs T lineage of the lymphoma in all tested cases, confirmed the positive cytodiagnosis in 10 cases, confirmed the reactive cytodiagnosis in 1 case, and helped achieve a conclusive diagnosis in 2 cases suggestive of lymphoma. Gene rearrangement studies showed light chain restriction in the 2 tested cases. FNA has an essential role in treatment planning for RL. Although FNA usually is diagnostically conclusive, a high index of suspicion and awareness of atypical or misleading cytomorphologic features are important for a correct interpretation, especially for primary RL. Ancillary testing is essential for the diagnosis in problematic cases and lays the foundation for the differential diagnosis.

Detection of chromosome 11q13 breakpoints by interphase fluorescence in situ hybridization. A useful ancillary method for the diagnosis of mantle cell lymphoma.

We assessed cytologic specimens from 11 mantle cell lymphomas (MCLs) and 32 other B-cell non-Hodgkin lymphomas (NHLs) for 11q13 breakpoints using a 2-color fluorescence in situ hybridization (FISH) assay that uses an 11q13 probe centered on the CCND1 gene and a centromeric chromosome 11 probe (CEP11). The number of nuclei in 200 cells were counted, and results were expressed as an 11q13/CEP11 ratio. All MCLs showed a high percentage of interphase nuclei with 3 or more 11q13 signals (mean, 74.8%; range 57%-90%). In contrast, in other B-cell NHLs the mean percentage of cells with 3 or more 11q13 signals was 9.2%. All MCLs had an elevated 11q13/CEP11 ratio (mean, 1.38). The mean ratio for other B-cell NHLs was 0.99. Two non-MCL cases, 1 large B-cell and 1 B-cell unclassified NHL, had high 11q13/CEP11 ratios of 1.15 and 1.30, respectively. Conventional cytogenetic analysis performed on the former case revealed a t(5;11)(q31;q13). Interphase FISH analysis using 11q13 and CEP11 probes is a convenient ancillary method for assisting in the diagnosis of MCL. This commercially available assay is simple to use on cytology or imprint specimens, and results can be obtained within 24 hours.

Numeric chromosomal abnormalities in small lymphocytic and transformed large cell lymphomas detected by fluorescence in situ hybridization of fine-needle aspiration biopsies.

BACKGROUND: Chromosomal abnormalities in some lymphomas are associated with a poor prognosis. Trisomy 12 and deletions of chromosome 13 have been described in small lymphocytic lymphoma (SLL). To determine whether chromosomal aberrations could be detected by fluorescence in situ hybridization (FISH) on fine-needle aspiration biopsies (FNABs), we analyzed and compared specimens from seven patients with SLL and nine patients with a history of SLL that had transformed to large cell lymphoma. METHODS: DNA probes specific to chromosome 12 and the chromosome 13/RB-1 gene locus were used for in situ hybridization on interphase cell nuclei. The cytologic features, ploidy, proliferation index, and conventional cytogenetic analysis findings were correlated with the FISH results. RESULTS: Trisomy 12 was detected in 2 (29%) of the 7 cases of SLL and 2 (22%) of the 9 cases of transformed large cell lymphoma. Deletion of chromosome 13/RB-1 was present in 3 (43%) of 7 cases of SLL and 3 (33%) of 9 cases of transformed large cell lymphoma. CONCLUSIONS: This study showed that interphase cytogenetic analysis by FISH is feasible on FNAB specimens. Trisomy 12 and deletions of chromosome 13/RB-1 were present in some cases of SLL and transformed large cell lymphoma, and the presence of these chromosomal abnormalities did not correlate with transformation to a higher grade of lymphoma.

Image analysis of papillary thyroid carcinoma fine-needle aspirates: significant association between aneuploidy and death from disease.

BACKGROUND: Papillary thyroid carcinoma is the most common thyroid malignancy in the U.S. As many as half of patients with papillary carcinoma present with cervical lymph node metastases at the time of diagnosis. Metastatic disease involving cervical lymph node tissue has not historically been proven to correlate with a more aggressive course; however, distant metastases worsen prognosis. METHODS: Diagnostic fine-needle aspiration (FNA) smears from 26 primary and metastatic papillary carcinomas underwent Feulgen reaction and were studied by image analysis to determine DNA pattern, proliferation index, and the percentage of cells with DNA content >5C. The medical records of all the patients were reviewed for metastatic disease pattern and survival data. For metastatic pattern, two groups were defined: 1) confined to thyroid/local lymph node metastases/soft tissues of the neck involved by tumor, and 2) distant metastases. RESULTS: Among the 26 patients, 16 had "nonaggressive" DNA patterns described as diploid, abnormal diploid, or tetraploid, and 10 had "aggressive" DNA patterns described as aneuploid. Only 2 of the 16 patients in the "nonaggressive" DNA pattern group developed distant metastases, whereas 5 of the 10 patients in the aneuploid group developed distant metastatic disease. In addition, none of the 16 patients with "nonaggressive" DNA patterns died of disease, whereas 3 of the 10 individuals with DNA histograms interpreted as aneuploid did die of metastatic disease complications. CONCLUSIONS: Aneuploidy identified by image analysis of FNA of papillary thyroid carcinoma is significantly associated with death from papillary carcinoma (log rank test, P=0.027).

Fine-needle aspiration biopsy of metastatic small cell carcinoma from extrapulmonary sites.

Like a pulmonary counterpart, extrapulmonary small cell carcinoma (SCC) is an aggressive tumor with a high rate of metastasis. Forty-nine fine-needle aspiration biopsies (FNABs) (36 patients) of various primary sites other than the lung diagnosed as metastatic SCC (including Merkel cell carcinoma) were reviewed. FNABs were derived from lymph nodes (20), liver (7), bone (2), breast (1), pancreas (1), and skin/soft tissue (18). Primary tumor sites included the prostate (14), skin (11; Merkel cell carcinoma), cervix (5), urinary bladder (3), urethra (1), ovary (1), and parotid (1). Aspirates revealed predominantly dispersed single tumor cells with occasional clustering. Tumor cells were small with scant cytoplasm, fine powdery chromatin, and inconspicuous nucleoli. Nuclear molding, mitotic figures, and apoptotic bodies were frequently observed. In four cases, findings from the FNABs were used to render the initial diagnosis of SCC. FNAB is useful for determining whether metastases contain a SCC component, a finding that may alter clinical management. Cytologically, SCC from different primary sites cannot be differentiated, and its distinction requires clinical and radiographic correlation.

Metastatic small-cell carcinoma of the prostate diagnosed by fine-needle aspiration biopsy.

Fourteen fine-needle aspiration biopsies (FNABs) of metastatic small-cell carcinoma done on 12 patients who had histologically documented primary small-cell carcinoma of the prostate are described. The FNABs were of lymph node (four cases), liver (four cases), bone (two cases), pancreas (one case), perirectal soft tissue (one case), perineum (one case), and lung (one case). One patient underwent three FNABs. No patient had a second primary tumor elsewhere. Cytologic smears were cellular with numerous single tumor cells, many apoptotic bodies, and variable numbers of mitotic figures. Tight cell clusters with molded nuclei and finely stippled chromatin were seen in all cases. An organoid pattern of tumor cells was seen focally in two cases. Features distinguishing small-cell carcinoma from poorly differentiated prostate carcinoma were cell size, finely stippled chromatin, inconspicuous nucleoli, and numerous single tumor cells. Distinction from small-cell carcinoma of other primary sites requires clinical and radiologic correlation. We conclude that cytologic specimens are useful for documenting metastatic small-cell carcinoma of the prostate and for differentiating between it and conventional prostate carcinoma in metastatic sites.

Blastic variant of mantle-cell lymphoma: cytomorphologic, immunocytochemical, and molecular genetic features of tissue obtained by fine-needle aspiration biopsy.

Mantel-cell lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma that has a moderately aggressive clinical course, generally between that a low-grade and intermediate-grade lymphomas. However, a small subset of MCLs, the so-called "blastic" variant, exhibits a poor prognosis and an aggressive clinical course. We describe a case of blastic MCL that occurred in a 64-yr-old man and that was diagnosed and accurately subclassified as blastic MCL on the basis of an fine-needle aspiration (FNA) biopsy. The aspirate smears showed a monotonous population of intermediate-sized lymphocytes with irregular nuclear contours, finely dispersed nuclear chromatin, and inconspicuous nucleoli. Material was obtained by FNA for ancillary studies (immunocytochemical stains, flow cytometry, cytogenetics, image analysis, and molecular studies) that supported the diagnosis of blastic MCL. Surgical biopsy confirmed the diagnosis. These findings underscore the utility of FNA in diagnosing lymphomas, particularly when the cytomorphologic examination is combined with appropriate ancillary studies.

Concomitant lymphoma and metastatic carcinoma in a lymph node: diagnosis by fine-needle aspiration biopsy in two cases.

Concomitant lymphoma and metastatic carcinoma are an unusual occurrence in a lymph node. We report two patients in whom synchronous malignancies were diagnosed by fine-needle aspiration biopsy (FNAB). In one case, the FNAB diagnoses of both small lymphocytic lymphoma and metastatic breast carcinoma were the initial diagnoses. In the second case, metastatic poorly differentiated squamous carcinoma was an unexpected finding in a patient with a history of small lymphocytic lymphoma. The aspirates in both cases showed two distinct cell populations, one consisting of a dispersed population of small uniform lymphoid cells and the other comprising large atypical single cells and cohesive clusters of epithelial cells. In both cases, the cytologic diagnoses were supported by immunohistochemical and flow cytometric studies.

Use of fine-needle aspiration biopsy in the evaluation of splenic lesions in a cancer center.

Fine-needle aspiration biopsy (FNAB) of the spleen was performed on 50 patients, of whom 40 had had a previous diagnosis of malignancy (23 lymphoproliferative disorders, 13 carcinomas, 3 melanomas, and 1 sarcoma). The cytologic diagnoses included 22 cases positive for malignancy (10 lymphomas, 9 metastatic carcinomas, 2 metastatic melanomas, and 1 sarcoma), 18 cases negative for malignancy, 4 cases suspicious for malignancy, and 6 nondiagnostic specimens. No major complications were associated with the FNAB procedure, however, one patient did develop a pneumothorax that resolved spontaneously. Subsequent splenectomy was performed in 10 of the 50 cases. There were no false-positive diagnoses, and only one false-negative diagnosis, which was attributed to sampling error. The aspirate, showing only benign splenic parenchyma, was from a patient with splenomegaly and no previous diagnosis; subsequent splenectomy showed acute myelogenous leukemia. In our study, FNAB proved to be a safe and valuable diagnostic tool for evaluating splenic lesions in oncologic patients.

Percutaneous needle biopsy diagnosis of benign neurogenic neoplasms.

Preoperative diagnosis of benign neurogenic neoplasms (BNNs) provides useful information in guiding management. To assess the effectiveness of fine-needle aspiration (FNA) and needle core biopsy (NCB) in diagnosing schwannomas and neurofibromas, 40 percutaneous biopsies interpreted as BNNs or obtained from lesions subsequently shown by excision to be BNNs were reviewed. The 13 aspirates diagnostic of BNN revealed spindle cells arranged haphazardly in irregular tissue fragments and in parallel as elongated ropy fascicles, with a myxoid to fibrillary background. The nuclei were buckled, often with intranuclear cytoplasmic inclusions. Four lesions showed nuclear pleomorphism without mitoses. Of 19 schwannomas evaluated by FNA, four (21%) were diagnosed as schwannomas and seven (37%) as BNNs. Ten neurofibromas were aspirated, revealing two (20%) BNNs. Of seven nondiagnostic FNAs accompanied by NCB, three (43%) indicated a BNN. The sensitivities of FNA, NCB, and both modalities in diagnosing BNNs were 43,60, and 71%, respectively. For the 16 FNAs showing features of BNNs, subsequent excisions revealed 11 schwannomas, two neurofibromas, one neurogenic sarcoma, one fibromyxoid neoplasm of uncertain malignant potential, and one unclassified low-grade myxoid sarcoma. FNA can be effective in diagnosing BNNs. If collagenous or myxoid lesions yield paucicellular nondiagnostic aspirates, NCB is helpful. Lowgrade sarcoma and neurofibromatous areas of neurogenic sarcoma may be misinterpreted as BNNs by percutaneous biopsy. BNNs may show nuclear pleomorphism without mitotic activity, and should not be mistaken for sarcoma.

Poorly-differentiated adenoid cystic carcinoma: cytologic appearance in fine-needle aspirates of distant metastases.

Adenoid cystic carcinoma (ACC) is a primary salivary-gland neoplasm which typically yields characteristic cytomorphology upon fine-needle aspiration (FNA). We report on the FNA findings of a case of ACC metastatic to the liver which demonstrated a predominantly solid, poorly-differentiated pattern, an unusual but well-recognized subtype associated with a poor clinical outcome. The FNA findings in 7 additional cases of ACC metastatic to distant sites were also reviewed, with 4 cases displaying a prominent poorly-differentiated component. These findings suggest that, although not commonly recognized in salivary-gland FNAs, the poorly-differentiated pattern of ACC does occur in metastatic deposits and should be recognized as such, thereby preventing a needless search for a second primary malignancy.

Serous surface carcinoma of the peritoneum: useful role of cytology in differential diagnosis and follow-up.

OBJECTIVE: To determine the role of cytology in differentiating serous surface carcinoma of the peritoneum (SSCP) from other morphologically similar tumors, including ovarian carcinoma and other peritoneal lesions, and to define the value of cytology in the follow-up of patients with SSCP. STUDY DESIGN: Twenty-one ascitic fluids and seven peritoneal washings obtained from 19 patients with histologically confirmed SSCP were reviewed and their cytologic features tabulated and analyzed. RESULTS: Eighteen of the specimens were from initial diagnostic paracenteses or exploratory laparotomies. These showed mostly three-dimensional tumor cell clusters, as well as single malignant cells, with occasional papillae. The cytoplasm was abundant and often vacuolated. The cytomorphologic features of SSCP enabled differentiation from other conditions involving the peritoneal surface, including mesothelial hyperplasia, malignant mesothelioma, endometriosis and endosalpingiosis. However, there were no characteristic features that differentiated SSCP from metastatic serous carcinoma of the ovary. Four of the peritoneal washings were from second-look operations; in each of these cases the presence of tumor cells in the cytologic preparations correlated with positive biopsy results. Furthermore, six of the paracenteses were performed for recurrent ascites and enabled detection of recurrent disease, obviating the need for invasive procedures. CONCLUSION: Cytomorphologic examination of ascitic fluids and peritoneal washings serves a valuable role in the initial diagnosis of SSCP, in the detection of recurrent disease and as a useful adjunct to multiple biopsies in the second-look operation. It can differentiate SSCP from several other lesions but not from serous carcinoma of the ovary.

DNA image analysis of urinary cytology: prediction of recurrent transitional cell carcinoma.

To evaluate the utility of image analysis in monitoring patients with transitional cell carcinoma, we studied, by cytologic means and by image analysis, 78 urinary tract specimens from 66 patients, of whom 49 (74%) had a previous history of transitional cell carcinoma. The specimens consisted of 51 (65%) voided urine specimens, 12 (15%) bladder washings, 8 (10%) ureteral washings, 3 (4%) ureteral brushings, 2 (3%) renal pelvic washings, and 2 (3%) catheterized urine specimens. DNA histograms were classified into five patterns on the basis of their DNA index and the percentage of their cells with DNA content greater than 5c: diploid (single peak in the 2c region with no cells greater than 5c), intermediate (diploid with less than 10% of cells greater than 5c), aneuploid (single peak or multiple peaks between the 2c and 4c region or more than 10% of cells greater than 5c), tetraploid (at least 10% of cells in the 4c region and a corresponding peak at 8c), and polyploid (multiple peaks in the 2c, 4c, 8c, and 10c regions). Of the 78 cases, 22 were diploid, 24 were intermediate, 29 were aneuploid, one was tetraploid, and two were polyploid. Histologic confirmation or clinical follow-up was found in 29 aneuploid cases, 13 intermediate cases, and one diploid case. Most cases of carcinoma in situ (five of six) and invasive tumors (12 of 17) were aneuploid. The sensitivity was 100%, and the specificity was 73% when cytologic and image analysis results were combined. We conclude that image analysis, when combined with cytologic examination, is a reliable noninvasive diagnostic test for monitoring patients with transitional cell carcinoma; aneuploidy is specific for malignancy; and the presence of cells greater than 5c, although frequently associated with tumor recurrence, can be seen in non-neoplastic conditions.

Cytologic findings of collecting duct carcinoma of the kidney.

We report the cytologic features of eight fine-needle aspirations (FNA) and eight exfoliative specimens of collecting duct carcinoma (CDC) obtained from six patients. The four men and two women ranged in age from 27 to 69 years (mean = 45 yr) and all had advanced stage disease at presentation (one stage III, five stage IV). Five of the six patients died of widespread disease, and one is alive and well (mean survival, 28 mo; range, 11-48 mo). The smears of the FNA and exfoliative specimens were scantly to moderately cellular. Tumor cells showed moderate pleomorphism and were arranged primarily in cohesive groups that rarely had a papillary configuration. Nuclei had irregular nuclear contours, coarse chromatin, and one to three nucleoli. In the majority of cases the cytoplasm was finely vacuolated, and occasionally there were large intracytoplasmic vacuoles. Intracytoplasmic mucin was demonstrated in two aspirates. Psammoma bodies were present in four of the seven fluids. In two patients, the cytologic diagnosis was supported by positive immunostaining for high-molecular-weight keratin and Ulex europaeus agglutinin I lectin. Leu M-1 was focally positive in one case and negative in the other. The cytologic features of CDC were readily identified as malignant; however, they were not distinctive and overlapped with those of high-grade renal cell carcinoma with papillary features and transitional cell carcinoma.

Fine needle aspiration cytology of extramedullary chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) shows extramedullary involvement in 10% of cases. We report the cytologic findings of fine needle aspiration (FNA) of recurrent CML in extramedullary sites in 11 patients with CML. The patients' ages ranged from 24 to 62 years (median, 38 years). There were seven male and four female patients. The aspiration sites were mostly lymph nodes (cervical in 7, retroperitoneal in 2, axillary in 1) and abdominal wall soft tissue (1). The numbers of blasts in the aspirates ranged from 27% to over 90%. Confirmation of the myeloid nature of the blasts was done using naphthol AS-D chloroacetate esterase in one case. Cytologic and flow cytometric immunotyping was done in eight cases. Two cases were based on cytomorphologic features only. Two of the eight immunophenotyped aspirates showed evidence of T-lymphoblastic differentiation. Another showed a mixed myeloid and T-cell phenotype. Blasts were seen in the peripheral blood and bone marrow in 4 of the 11 patients. We thus conclude that extramedullary involvement by CML in our series was associated with younger age, high incidence of cervical lymphadenopathy, increased blasts and frequent lack of bone marrow and peripheral blood involvement. T-cell phenotypes appeared to be higher in our series than reported in the literature. This suggests that there is a need for phenotyping some aspirates of recurrent extramedullary CML, mainly to evaluate the possibility of dedifferentiation and its possible impact on the behavior of the neoplasm.

Fine-needle aspiration cytology of seminoma: a review of 16 cases.

We report the cytomorphologic features of 16 fine-needle aspiration (FNA) biopsies of seminoma obtained from 16 male patients. The aspirates included two primary gonadal tumors (one occurring in a cryptorchid testis), two primary mediastinal tumors, and 12 metastases (two with unknown primaries). Analysis of the aspirates revealed a primarily dispersed cell population of large cells with scant to moderately abundant cytoplasm. The nuclei were round to slightly irregular, had finely granular chromatin, and had either one central prominent nucleolus or two to three smaller nucleoli. Variable numbers of lymphocytes and plasma cells were intermingled with the tumor cells. Only a few cases had epithelioid histiocytes or the characteristic "tigroid" background. The cytologic features of the metastases were distinctive and were considered diagnostic for therapeutic management. In six cases, an initial diagnosis of seminoma by FNA biopsy identified the neoplasm as germ cell in origin rather than other neoplasms in the differential diagnosis, thereby expediting therapeutic management.

Indeterminate fine-needle aspiration biopsy of the thyroid: identification of subgroups at high risk for invasive carcinoma.

BACKGROUND: We examined the various cytologic features of indeterminate thyroid fine-needle aspirates along with known clinical and radiologic risk factors to determine whether any parameters were predictive of malignancy. METHODS: Indeterminate fine-needle aspirates were prospectively categorized into four subgroups: (1) suspicious for papillary carcinoma, (2) follicular neoplasm, (3) Hürthle cell neoplasm, and (4) hypercellular follicular aspirates with colloid. Several clinical risk factors were examined, and subgroup comparisons were performed with Fisher's exact test. RESULTS: Of 571 fine-needle aspirate cytologic findings 104 were interpreted as indeterminate for malignancy, and 81 patients underwent thyroidectomy. Invasive cancer was diagnosed in 9 of 10 lesions cytologically suspicious for papillary carcinoma, 8 of 43 follicular neoplasms, 5 of 18 Hürthle cell neoplasms, and 0 of 10 hypercellular aspirates. Cytologic subgroup (p < 0.0001) and age of 50 years or older (p = 0.008) were the only significant predictors of malignancy. When used together, age of 50 years or older and a cytologic diagnosis of follicular or Hürthle cell neoplasm also identified a subgroup of patients at high risk (9 of 20) of invasive malignancy (p = 0.01). CONCLUSIONS: The majority of invasive cancers (18 of 22, 82%) were found in patients whose lesions were suspicious for papillary carcinoma or in patients 50 years or older with follicular or Hürthle cell neoplasms. The risk of carcinoma in these combined subgroups (18 of 30, 60%) warrants early surgical intervention.