Fine Needle Aspiration Cytology Biology Essay

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Thyroid swellings are a major clinical problem in general population but the majority are nonneoplastic and does not require surgery. The initial screening procedures include fine needle aspiration cytology (FNAC), radionucleotide scan and ultraonography. The aim of the present study is to correlate the cytology findings with final histopathology. Total 248 cases of thyroid lesions which underwent FNAC followed by surgery were included in this study. The cytology diagnoses were classified into insufficient for diagnosis, benign, follicular lesions of undetermined significance, follicular neoplasm, suspicious of malignancy and malignant. The results were analyzed taking final histopathology as the gold standard. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of fine needle aspiration cytology in diagnosing thyroid lesions were 97.95%, 100%, 100%, 87.09% and 98.19% respectively. Our results were comparable with other published data. Fine needle aspiration cytology is a simple, cost effective, rapid to perform procedure with high degree of accuracy and is recommended as the first line investigation for the diagnosis of thyroid lesions.

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Introduction.The majority of thyroid swellings are nonneoplastic or benign conditions and does not require surgery. Less than 5% of thyroid nodules are malignant. 1 Thyroid surgeries can be associated with complications like hypoparathyroidism and thyroid hormone dependence. If a preoperative diagnosis can be made, unnecessary surgery can be avoided in benign conditions. Among the preoperative investigations, the fine needle aspiration cytology (FNAC) is the most accurate diagnostic modality. The Bethesda system of thyroid reporting makes the cytology reports clinically relevant and helps the clinicians to take appropriate therapeutic interventions.

Materials and methods

This is a retrospective study of 248 cases of thyroid lesions which underwent fine needle aspiration followed by surgery during a period of 2009-2011 in our institution. FNAC was performed with 23 gauge needle. Smears fixed in 95% alcohol solution and papanicolaou staining was done. The cytology reports were interpreted as insufficient for diagnosis, benign, follicular lesions of undetermined significance, follicular neoplasm, suspicious of malignancy and malignant according to the recent Bethesda classification.

After the FNA diagnosis, the patients were subjected to surgery. The tissues were put in formalin, relevant areas were sampled, processed in automated tissue processing units and hematoxylin and eosin stain was done.

Correlation between FNAC and final histopathology were assessed. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were calculated taking the histopathology as the gold standard.

Results

A total of 248 cases of thyroid lesions which underwent FNAC followed by surgery were included in this study. 69 were males and 179 were females. The male: female ratio was 1:3.The age range was from 11 years to 79 years.

The FNAC diagnosis - malignancy in 148, suspicious of malignancy in 10, follicular neoplasm in 33, follicular lesion of undetermined significance in 11, benign in 31 and inconclusive in 15 cases.

FNA diagnosis

number

percentage

Malignancy

148

59.68

Suspicious of malignancy

10

4.03

Follicular neoplasm

33

13.3

FLUS

11

4.43

Benign

31

12.5

inadequate

15

6.04

Among the 148 malignant lesions, 118 were diagnosed as papillary carcinoma, 26 as follicular variant of papillary carcinoma, 3 as medullary carcinoma and 1 as poorly differentiated malignant neoplasm.

In the final histopathology, all the 148 cases were malignant. The 118 cases of papillary carcinoma were confirmed by histopathology -5 being follicular variant of papillary carcinoma. The 26 cases of follicular variant of papillary thyroid carcinoma by FNAC were diagnosed as the same by histopathology. The diagnosis of 3 cases of medullary carcinoma was confirmed histopathologically. The 1 poorly differentiated malignant neoplasm turned to be lymphoma on final histopathology.

33 cases were diagnosed as follicular neoplasm by FNAC. Histopathological examination showed 17 cases as follicular variant of papillary carcinoma, 11 as papillary carcinoma, 4 as follicular adenoma and 1 as follicular carcinoma.

Of the 10 cases which were diagnosed as suspicious of malignancy, 7 were papillary carcinoma, 2 were follicular variant of papillary carcinoma and 1 was medullary carcinoma on histopathology.

An FNA diagnosis of follicular lesion of undetermined significance was made in 11 cases. Histopathology revealed 4 cases as follicular variant of papillary carcinoma ,2 cases as papillary carcinoma, 2 cases as follicular adenoma and 1 as colloid nodule with cellular area.

A benign diagnosis was given by FNA in 31 cases. 4 turned to be papillary carcinoma. 19 were colloid nodules, 2 were multinodular goiter, 5 were lymphocytic thyroiditis and 1 was cellular nodule.

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Cytological diagnosis

no

histopathplogy

no

remarks

Malignancy

Papillary carcinoma

Follicular variant PTC

Medullary carcinoma

Poorly differentiated

Malignant neoplasm

118

26

3

1

Papillary carcinoma Follicular variant PTC

Medullary carcinoma

lymphoma

118

26

3

1

TP

TP

TP

TP

Suspicious for malignancy

10

Papillarycarcinoma Follicular variant PTC

Medullary carcinoma

7

2

1

TP

TP

TP

Follicular neoplasm

33

Follicular variant PTC

Papillarycarcinoma

Follicular adenoma

Follicular carcinoma

17

11

4

1

TP

TP

TP

TP

Follicular lesion of undetermined significance (FLUS)

11

Follicular variant PTC

Papillary carcinoma

Follicular adenoma

Colloid nodule

4

2

4

1

Not included in final calculations

Benign

Nodular goiter

Thyroiditis

24

7

Colloid nodule

Multinodular goiter

Papillary carcinoma

Cellular nodule

Lymphocytic thyroiditis

Papillary carcinoma

19

2

2

1

5

2

TN

TN

FN

TN

TN

FN

inadequate

15

Papillary carcinoma

Follicular variant of papillary carcinoma

Colloid nodule

Lymphocytic thyroiditis

1

1

11

2

Not included in final calculations

TP-true positive, TN-true negative, FN- false negative.

11 cases of follicular neoplasm of undetermined significance and 15 cases of inadequate samples were excluded from final calculations because these diagnostic categories doesnot imply benign nonneoplastic or malignant nature and require repeat aspiration .

FNAC diagnosis

Histopathology-benign

Histopathology-malignant

Benign

27 (TN)

4 (FN)

malignant

0 (FP)

191 (TP)

Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of fine needle aspiration cytology were calculated.

Sensitivity- 97.95%

Specificity-100%

Positive predictive value-100%

Negative predictive value-87.09%

Diagnostic accuracy-98.19%

Discussion

Although thyroid swellings are a major clinical problem, only 5-30% cases require surgical interventions. The initial screening tests for thyroid lesions include hormonal assay,antibody levels,ultrasound, thyroid nuclear scan and fine needle aspiration cytology.2 Among these FNAC is considered as the best initial diagnostic test. FNAC will help to identify the various thyroid lesions with high degree of accuracy, thus help in avoiding unnecessary surgery in benign conditions. Thyroid surgeries can be associated with complications like hypoparathyroidism, thyroid hormone dependence and injury to recurrent laryngeal nerve.

The Bethesda system of thyroid lesion reporting aims at standardization of reports. It bridges the communication gap between clinicians and pathologists and thus helps the surgeons to take appropriate therapeutic interventions. It makes the cytology report unambiguous, clear, succinct and clinically relevant. 3 In our study the cytology of thyroid lesions were interpreted according to Bethesda classification as nondiagnostic or unsatisfactory, benign, follicular lesions of undetermined significance, follicular neoplasm,suspicious of malignancy and malignant.

A satisfactory smear should contain at least six groups of follicular cells, each group composed of at least ten cells. Adequate samples are required to reduce the false negative rates. 4 Samples with inadequate number of cells, thick smears or smears with cells obscured with blood were reported as unsatisfactory or nondiagnostic. Published studies show inadequate sample range between 2% and 20%. 5,6 In our study the inadequate samples were 6.04%.The cellularity of the sample depends on the technique of the aspirate as well as the nature of the lesion. In lesions with calcification, sclerosis or cystic degeneration it is very difficult to get an adequately cellular aspirate. The number of inadequate samples can be minimized by taking samples from different parts of the lesion and by ultrasound guided aspiration of small lesions.

In our study a benign diagnosis of nodular goiter was given in 24 cases and lymphocytic thyroiditis was diagnosed by cytology in 7 cases. Among these 4 cases turned to be papillary carcinoma on final histopathology -false negative cases. False negative rate is defined as percentage of benign cytology in which malignant lesions were later confirmed by histopathology in postsurgical specimens. False negative cytology can occur in cases with coexistence of malignant and benign lesions. In these cases due to sampling error the aspiration can be obtained from large benign lesion and missing adjacent malignant lesions. Cytomorphological overlap between benign and low grade malignant lesions can also lead to false negative reports. This false negative rate is a major pitfall and indicates the potential to miss malignant lesions. 7,8 Most published studies report a false negative rate in the range of 1-10%.9,10,11 In our series the false negative rate was 1.8% and all the four false negative cases were papillary carcinoma with the adjacent thyroid tissue showing features of thyroiditis or colloid nodules. In these cases the aspirate was from the nonmalignant parts of the lesion and the small foci of malignancy were missed. These types of errors can be minimized by using ultrasound guided aspirations and by correlating the cytology diagnosis with scan findings. A negative cytology result should never exclude malignancy if there is strong clinical suspicion. Patients with benign cytology reports should be followed up with periodic clinical examination supplemented with ultrasonography.

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A diagnosis of Follicular lesion of undetermined significance (FLUS) was given to cases that showed atypia that was not sufficient to designate as follicular neoplasm, suspicious of malignancy or malignant. Literature search shows 3-18% of thyroid FNAs reported as FLUS.5,12,13,14 In the present study, this category constituted 4.43%. This diagnostic category should not be used indiscriminately and every attempt should be made to make specific diagnosis whenever possible by correlating clinical, pathological and radiological findings.This diagnosis should be limited to less than 7% of all thyroid FNAs.5,13,14 In our study of the 11 cases of FLUS , 6 cases were malignant on histopathology. Of these malignant cases, 4 cases were follicular variant of papillary carcinoma which showed cells arranged in follicular pattern with focal nuclear clearing and occasional nuclear grooves.

Another important grey zone of fine needle aspiration cytology is the follicular lesions. The follicular lesions include a number of heterogeneous thyroid lesions -cellular adenomatous nodule, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma thyroid.15,16 Usually smears from adenomatous nodules show more colloid than that of follicular neoplasm. Few cases in this study showed confusing cellular smears in nonneoplastic adenomatous nodules. In these cases, the presence of dispersed cells, monolayered sheets of epithelial cells and degenerative changes suggested the possibility of nonneoplastic lesion.

According to Bethesda system of reporting, Follicular neoplasm refers to a cellular aspirate composed of follicular cells with significant cell crowding and or microfollicle formation. In the present study, 33 cases were diagnosed as follicular neoplasm by FNA. Tightly cohesive follicular cells favoured neoplastic condition. Of these majority turned to be follicular variant of papillary carcinoma on final histopathology. Data from literature shows 27-68% of malignancies, in which a diagnosis of follicular neoplasm was made in FNA, are interpreted as papillary carcinoma on histopathology.6,12,16,17 This may be due to focal subtle nuclear features of papillary carcinoma in some tumors which were not appreciated on the FNA samples.

To distinguish between follicular adenoma and follicular carcinoma a detailed histopathological examination for capsular and vascular invasion is mandatory. Only one case turned to be follicular carcinoma in our series

In this study, 10 cases were diagnosed as Suspicious of malignancy by FNA. This diagnosis was made in cases which showed some features of malignancy but the findings were not sufficient to make a conclusive diagnosis. The features of papillary carcinoma include nuclear enlargement,powdery chromatin,nuclear membrane irregularity,nuclear grooves,nuclear moulding, intranuclear pseudoinclusions and papillary structures with distinct anatomical borders. In cases where only some of the characteristic nuclear features are present focally, a malignant diagnosis cannot be made with certainty. Such cases were classified as suspicious of malignancy. All the 10 cases turned to be malignant on final report and most were papillary carcinoma. In most of these cases the nuclear features of papillary carcinoma was focal and subtle.

148 cases were diagnosed as malignant by FNAC. All the cases were malignant on final histopathology.The diagnoses of papillary carcinoma, follicular variant of papillary carcinoma and medullary carcinoma were confirmed by histopathological examination.There were no false positive results. False positive cytology can result in surgical overtreatment. Review of literature shows a false positive rate of 0-9%. 18

In this study, 199 cases were malignant on final histopathology. The high percentage of malignancy in this study is because our institution is a tertiary cancer centre. The majority of cases were papillary carcinoma. Of the 143 cases of papillary carcinoma, FNA diagnosis was papillary carcinoma 118 cases, suspicious of malignancy in 7 cases, follicular neoplasm in 11 and follicular lesions of undetermined significance in 2 cases. In cases which were diagnosed as follicular neoplasm and follicular lesions of undetermined significance, the cytology smears showed cell arranged in follicular patterns with subtle nuclear features of papillary carcinoma. In 4 cases a false negative diagnosis was given by FNA and these 4 cases were papillary carcinoma associated with benign lesions in the adjacent thyroid tissue. These findings indicate the high sensitivity of FNA in diagnosing the papillary carcinoma of the thyroid and show the potential causes of false negative results.

Follicular variant of papillary carcinoma is the most common variant of papillary carcinoma and constitute around 30% of PTCs in various studies. 50 cases in this study were follicular variant of papillary thyroid carcinoma. Of these cases 26 were diagnosed as follicular variant of papillary carcinoma, 17 as follicular neoplasm ,2 as suspicious of malignancy, and 4 as follicular lesion of undetermined significance by FNA .The awareness of this entity and the thorough search of nuclear features of papillary carcinoma in the follicular lesions can lead to proper identification of these malignancy and thus reducing the diagnostic category of follicular lesions of undetermined significance and follicular neoplasm which does not imply benign or malignant nature of the lesion. The presence of cytological atypia such as nuclear enlargement, fine chromatin and nuclear grooves even present focally are important clues to diagnose follicular variant of papillary thyroid carcinoma in smears. 19 According to some studies, papillary nuclear features in more than 20 cells would have a greater chance of papillary carcinoma. 18

study

year

sensitivity

specificity

PPV

NPV

Accuracy

Afroze N et al 20

2002

61.9

99.31

92.86

94.74

94.58

Handa U et al 21

2008

97

100

96

100

98.48

Bagga P K et al 8

2010

66

100

100

96

96.2

EA Sinna et al 22

2012

92.8

94.2

94.9

91.8

93.6

Current study

2012

97.95

100

100

87.09

98.2

In conclusion,fine needle aspiration cytology is cost effective,simple procedure that has great patient acceptance and as an initial screening test provides the diagnosis with high degree of accuracy thereby limiting the number of surgeries in benign conditions of thyroid gland. A negative diagnosis should be followed up with repeat ultrasound and FNA should be repeated in suspicious cases. Correlation of cytology and histopathology is an important quality assurance measure.