Diagnostic pitfalls in fine needle aspiration of solitary pulmonary nodules: two cases with radio-cyto-histological correlation

Background

Fine needle aspiration is an important tool for diagnosis and preoperative evaluation of solitary nodules of the lung. It provides a definitive diagnosis in most patients at low cost with minimal trauma. However, because of the nature of the study and the presentation of the cells in a more distorted and incomplete tissue structure than a histological slide, false positive results can occur. Prior detailed clinical knowledge about the patient, procedures and methods of radiology in obtaining the aspirate specimen is extremely useful in the accurate interpretation of fine needle cytological specimens.

Case presentation

We report two cases of solitary pulmonary nodules in two elderly females, which were initially diagnosed as malignant by fine needle aspiration biopsy. Both cases subsequently underwent pulmonary lobectomy in which, one turned out to be a pulmonary hamartoma and the other appeared to be a middle lobe syndrome of the right lung with liver tissue contamination at the time of fine needle aspiration of the lung.

Conclusions

We are now strong believers that much care must be taken in the interpretation of fine needle aspiration of solitary nodules of the lung. Complete study of the entire specimen, including the cell block, is warranted, since what one interprets as malignant, could have different features in another part of the sample. Last but not the least, prior knowledge of the complete clinical history of the patient together with the salient radiological findings would greatly facilitate the cytopathologist to reach an accurate diagnosis.     

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.     

Necrosis of thyroid nodules after fine needle aspiration

In a series of 200 fine needle aspirations (FNA) of the thyroid, necrosis around the needle tract was histologically evident in 2 of 30 cases with surgical follow-up. In one case of a differentiated thyroid carcinoma, necrosis with involution of the nodule was the dominant finding. This suggests that FNA can induce necrosis and apparent clinical regression of thyroid neoplasms. We believe, however, that a positive cytologic diagnosis coupled with a clinical suspicion of neoplasm should lead to surgical intervention, despite clinical regression following FNA.     

Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the thyroid: correlation with histopathology in 260 cases

Objectives:  Fine needle aspiration cytology (FNAC) of the thyroid is a non-invasive, cost-effective screening procedure that is valuable for distinguishing neoplastic lesions from non-neoplastic nodules. The aim of this study was to determine the diagnostic accuracy of FNACs performed at our institution by correlating FNAC results with histopathological diagnoses.
Methods:  Two hundred and seventy-one aspiration cytology specimens followed by thyroidectomy were included in the study, and the results of 260 adequate FNACs were compared with their histological diagnoses.
Results:  The sensitivity and specificity of thyroid FNAC for detecting neoplasia were 92.6% and 91.6%, respectively. There were 15 (5.7%) false positives and six (2.3%) false negatives.
Conclusions:  The results showed that follicular cells that exhibit some of the features of papillary carcinoma could be observed in a cytology slide of Hashimoto's thyroiditis, leading to a diagnostic pitfall. In addition, cellularity and overlapping cytological criteria in hyperplasia might lead to a false diagnosis.     

Diagnostic pitfalls in fine needle aspiration cytology of pleomorphic lipoma. A case report

BACKGROUND: Pleomorphic lipoma is an unusual pseudosarcomatous condition with characteristic morphology. Despite its pleomorphic appearance, it follows a benign course and does not recur or metastasize if completely excised. CASE: A 66-year-old man presented with swelling in the back of the neck of approximately six months' duration. The focally cellular aspirate revealed round to oval, hyperchromatic cells, rare multinucleated cells and fragments of mature adipose tissue. On initial evaluation, the smear pattern suggested a malignant neoplasm. However, upon review of the cytologic material along with histology, the characteristic pattern, including floret cells, was recognized. CONCLUSION: The rarity of pleomorphic lipoma and the atypical cellular features of the aspirate can cause difficulty in diagnosing this entity. Awareness of this rare but not-uncommon entity, along with clinical correlation, is crucial in arriving at the correct diagnosis.     

Use of immunohistochemistry in fine needle aspiration of thyroid nodules in patients with a history of malignancy. A report of two cases

BACKGROUND: A history of a nonthyroid malignancy may present a diagnostic dilemma in the assessment of fine needle aspiration (FNA) of thyroid nodules. One reported series, on patients with prior malignancies and a thyroid nodule, indicated that in 17% of patients, the thyroid nodule represented metastatic malignancy, 6% were classified as primary thyroid cancers, and the remainder were benign or inconclusive lesions. The resolution of this problem is essential to patient management. CASES: We report two cases in which patients with a history of renal cell carcinoma presented with a thyroid nodule. The first patient was an 80-year-old female whose Papanicolaou-stained FNA demonstrated clusters of round to polygonal cells with round to ovoid, hyperchromatic nuclei and abundant, wispy cytoplasm. The second patient was a 55-year-old female with clusters and single cells with round to oval, eccentric nuclei and copious, granular, gray cytoplasm noted on Papanicolaou-stained material. In each case, the diagnosis was inconclusive on initial review of Papanicolaou-stained slides, and immunohistochemical staining was ordered to better characterize the lesions. Tumor cells from case 1 were positive for cytokeratin cocktail and vimentin and negative for thyroglobulin, epithelial membrane antigen and calcitonin, suggestive of metastatic renal cell carcinoma. In contrast, the tumor cells from case 2 expressed cytokeratin, thyroglobulin and vimentin, consistent with a primary thyroid neoplasm. In each case, the cytologic diagnoses were confirmed in the resected specimens. CONCLUSION: Immunohistochemistry is a helpful adjunct in the evaluation of thyroid nodules in patients with a past history of malignancy.     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

Circulating thyroglobulin and antithyroglobulin antibodies after fine needle aspiration of thyroid nodules

Circulating thyroglobulin and antithyroglobulin antibodies were assayed in fifteen patients affected by solitary "cold" nodules of the thyroid who had undergone fine needle aspiration for cytologic diagnosis. The aim of the study was to investigate whether a minor insult to thyroid tissue such as fine needle aspiration is able to release thyroglobulin into the circulation and to induce the formation of antithyroglobulin antibodies. The results obtained are as follows: 1. Circulating thyroglobulin increased substantially after fine needle aspiration in 11 out of 15 patients. 2. Antithyroglobulin antibodies did not appear in any patient during a follow-up period of two months. 3. The magnitude of basal thyroglobulin and thyroglobulin increase after needle aspiration were unrelated to cytologic diagnosis.     

Comparative study of fine needle aspiration and fine needle capillary sampling of thyroid lesions

OBJECTIVE: To investigate whether fine needle capillary (FNC) sampling gives quantitatively and qualitatively superior cytologic material as compared to the conventional technique of fine needle aspiration (FNA) when performed by a single aspirator. STUDY DESIGN: Cross-sectional diagnostic test evaluation study. FNA and FNC were performed by a single operator on 200 diffuse and nodular thyroid lesions. RESULTS: A statistically significant difference in favor of FNC was observed for the parameter amount of cellular material. For the rest of the parameters--background blood or clot, degree of cellular degeneration, degree of cellular trauma and retention of architecture--the average score favored FNC but was not statistically significant--i.e., smears prepared from FNC displayed cellular material that was more concentrated, less damaged and less likely to be obscured by blood. CONCLUSION: Although FNC sampling was diagnostic in a greater number of cases than FNA sampling, this study did not prove a clear superiority of FNC over FNA. Until greater experience shows clear sampling superiority of FNC alone, rather than performing only FNA in diffuse or nodular thyroid lesions, incorporating FNC into the second puncture will definitely improve the quality and quantity of material at the patient's first visit.     

Diagnostic pitfalls in fine needle aspiration cytology of atypical apocrine metaplasia in a breast lesion. A case report

BACKGROUND: Apocrine metaplastic cells are frequently encountered in fine needle aspirates of breast lesions. Atypical apocrine metaplastic cells with signet ring features can also occur, and their presence may present a diagnostic dilemma in the differentiation of benign versus malignant lesions. CASE: A fine needle aspirate of a 2.5 x 1.0-cm, subareolar mass in a 47-year-old female showed atypical cells with signet ring morphology. Also present were clusters of cells that were enlarged and showed nuclear atypia, prominent nucleoli and cytoplasmic granules. Papillary cohesive clusters of ductal cells were also identified. The fine needle aspiration diagnosis was mucinous carcinoma. The nodule was excised, and the histologic diagnosis was sclerosing ductal papilloma with atypical apocrine metaplasia. CONCLUSION: Atypical apocrine cells can be misinterpreted as mucinous carcinoma or usual duct adenocarcinoma on fine needle aspiration cytology. We present clues that may help in rendering the correct interpretation.     

Evaluation of fine needle aspiration (FNA) cytology in the diagnosis of thyroid nodules

FNA cytology of 112 patients with thyroid nodules seen in a 5-year period in a general hospital setting, and the histology obtained from the 53 operated patients, were retrospectively analysed. the inadequacy rate of FNA cytology was 11%, sensitivity was 84% (16/19), specificity was 52% (15/29), positive predictive value was 53% (16/30) and negative predictive value was 83% (15/18). Extrapolating these figures to the whole study group a negative predictive value of 95% is put forward as a more realistic figure. the results and the clinical pitfalls of the use of FNA cytology in diagnosing thyroid nodules are discussed. the authors conclude that FNA cytology is a reliable first diagnostic step in the diagnosis of thyroid nodules, even in a general hospital setting.     

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.     

Percutaneous fine needle aspiration biopsy of the lung. A study of 1,015 patients

From the time of its introduction, in 1973, through November 1983, fine needle aspiration biopsy ( FNAB ) of the lung was used in the diagnostic evaluation of 1,015 patients at the Duke University Medical Center and Durham Veterans Administration Medical Center. A diagnosis of a primary lung cancer was established in 49.4% of the cases and malignant neoplasm metastatic to the lung in 14.1%; a benign diagnosis was made in 31.1% and an inconclusive one in 5.4%. In 123 patients in whom lung tissue was also available, cancer was correctly diagnosed by FNAB in 83.8%, not diagnosed by FNAB in 14.6% and incorrectly diagnosed in 1.6%. In 37 patients without cancer, FNAB detected an infectious organism or a specific morphologic type of inflammation (abscess and granuloma).     

Fine needle aspiration biopsy in the diagnosis of thyroid nodules

The fine needle aspiration (FNA) biopsies performed on thyroid nodules at Turku University Central Hospital from 1983 to 1988 were reviewed. Of the 1,054 total aspirated nodules, 194 were investigated histologically after thyroid surgery (191 cases) or at autopsy (3 cases). Two cases with an insufficient FNA sample, 4 with an incidental occult papillary carcinoma and 2 cases with carcinoma outside the nodule investigated by FNA biopsy were excluded from the series, leaving 186 histologically confirmed nodules in the final analysis. Three (3%) of the 107 cases with an FNA biopsy diagnosis of benign, 4 (8%) of the 52 with an FNA diagnosis of equivocal, 3 (20%) of the 15 with an FNA diagnosis of suspicious and all 12 (100%) with an FNA diagnosis of malignant were histologically malignant. If only an unequivocally malignant cytologic finding is considered positive, FNA biopsy had a diagnostic specificity of 100%, a sensitivity of 55% and an accuracy of 95% among the histologically confirmed cases. Follow-up revealed no cases of cancer among the 863 thyroids that were not explored surgically. It is concluded that FNA biopsy is a practical method with considerable diagnostic value in the evaluation of thyroid nodules.     

Fine needle aspiration diagnosis of hyperplastic and neoplastic follicular nodules of the thyroid. A morphometric study.

The differentiation of hyperplastic nodules, follicular adenomas and follicular carcinomas from fine needle aspiration (FNA) cytology smears may be difficult. To better define the diagnostic criteria, we studied the morphometric parameters of nuclear area (NA), nuclear:cytoplasmic ratio and nuclear roundness (NR) in single cells and cell aggregates. In addition, we quantitated the percentage of touching or overlapping nuclei (NO) and the percentage of extent of nuclear area of overlap (NAO) in cellular aggregates. We measured cellular samples from FNA aspirates obtained from 20 hyperplastic nodules, 21 follicular adenomas, 5 encapsulated follicular carcinomas and 22 invasive follicular carcinomas, all of which were subsequently confirmed by histologic examination. Cellular aggregates provided the maximum diagnostic information. Stepwise discriminant analysis revealed that nuclear size, nuclear roundness and the percentage NAO allow optimum differentiation of hyperplasia, adenomas and carcinomas. Clearly, all of the poorly differentiated carcinomas (large NA, low NR, high NO and NAO) could be reliably diagnosed. Discriminant analysis allowed the differentiation of carcinoma from adenoma in 20/22 carcinomas (91%) and all 21 adenomas (although 2 adenomas were called hyperplasias and 3 hyperplasias were called adenomas).     

Diagnostic accuracy of fine needle aspiration cytology of the thyroid: impact of ultrasonography and ultrasonographically guided aspiration

OBJECTIVE: To determine the impact of ultrasonography on the diagnostic accuracy of fine needle aspiration cytology (FNAC) of the thyroid. STUDY DESIGN: We compared two FNAC series. In period 1 we used neither ultrasonograph nor ultrasonographically-guided FNAC in the evaluation of thyroid nodules, while both tools were routinely applied in period 2. Moreover, in the former period all cellular follicular lesions were encountered among suspicious findings, while in period 2 we advised regular follow-up examinations instead of immediate surgery for patients with no significant atypia. The basis of follow-up examinations was ultrasonographic volumetry of the nodule and repeat FNAC on growing nodules. RESULTS: The number of FNAC, positive predictive value of FNAC, number of malignancies, sensitivity, the specificity and diagnostic accuracy were higher in period 2 as compared with period 1: 3,446 vs. 1,448; 45% vs. 16%, 39 vs. 29, 92% vs. 76%, 65% vs. 87% and 66% vs. 87%, respectively. CONCLUSION: The introduction of ultrasonography permits higher diagnostic accuracy of the evaluation process. This is achieved not only by lessening false negative reports but, more important, by decreasing false positive results.     

Metastatic tumors in fine needle aspiration biopsy of the thyroid

A series of almost 25,000 thyroids examined by fine needle aspiration (FNA) biopsy was reviewed to ascertain the incidence and presentation of metastatic cancers in thyroid FNA samples. Metastatic cancers in FNA samples from the thyroid were identified in 25 cases (0.1%); the primary tumors were carcinomas of the kidney (8 cases), lung (7 cases), breast (5 cases), cervix uteri (1 case) and colon (1 case) and 1 case each of malignant melanoma, malignant pleural mesothelioma and rhabdomyosarcoma. FNA cytology was positive in all 25 cases. In 11 cases, the primary tumor was clinically known at the time of FNA biopsy; of the other 14 cases, cytology suggested that the malignancy was metastatic in only 5. Metastases of renal and mammary adenocarcinomas were almost indistinguishable from follicular and papillary thyroid carcinomas on cytologic grounds. The results demonstrate the rarity of this finding and the difficulty of diagnosing a metastatic tumor in the thyroid by FNA biopsy, in the absence of a clinical history of a prior primary neoplasm.