Fine needle aspiration cytology; is it must to be done before all thyroid surgery? Alexandria University experience

Fine needle aspiration cytology; is it must to be done before all thyroid surgery? Alexandria University experience

Galal M Abouelnagah, MD; Haytham M Awad, MD

Surgical Oncology Unit, Alexandria University, Egypt.

Nodular enlargementis frequent and constitutes the commonestindication for thyroidectomy The vast majority of adult thyroid nodules are non-neoplastic lesions or benign neoplasm and fewer than 5% are malignant. Current guidance recommends the use of fine needle aspiration cytology  (FNAC)  as an essential  investigation in  patients  presenting  with a thyroid lump. However, only very few studies have looked specifically at the sensitivity  of FNAC in solely thyroid cancer patients. The aim of our study was to investigate the value of FNAC as a basic investigation in patients with thyroid enlargement. We aimed specifically to assess the sensitivity of FNAC  within cancer suspicious  group.  This had been done by reviewing  all cases  from January1st, 2001 to December 31st, 2012ftincludes all patients with simplenodulargoiter who underwent thyroid surgery during that period. Exclusion criteria: Patients who had recurrent goiter or secondary metastatic lesions. Total617 patients were included in the study Female to male ratio was 589 {90.6%) and 28(9.4%) respectively  Age of the patients ranged  from 15-72 years with mean age 38.5 years. Among  the 617 patients, preoperative fine needle aspiration cytology had been done to 409 cases only  Statistical analysis showed that preoperative FNAC sensitivity, specificity and accuracy are 68.27%, 87.40% and 85.89% respectively. We need to understand what a specific FNAC result means to patients management. Significant result of FNAC can provide preoperative guidance when assessing the probability of the target disorder. We had expected that a "malignant"  or "suggestive" FNAC result significantly enhances the probability of thyroid neoplasm and should be an absolute indication  for surgery

Key words: Goiter, preoperative assessment, indication  for surgery

Introduction:

Thyroid    enlargement     1s     a    common clinical finding, and it has been reported in about 4-7% of adult population. Nodular enlargement is frequent and constitutes the commonest   indication   for   thyroidectomy. The vast majority of adult thyroid nodules are non-neoplastic  lesions  or benign  neoplasms and fewer than 5% are malignant.1 Thyroid nodules may be cystic or solid, most of the cystic  nodules  are  benign  in  nature  except few cases of papillary carcinoma. Among the solid nodule only about 3% are malignant tumors.2

The problem in clinical practice is to distinguish  the  few  malignant  thyroid nodules   reliably   from  many   benign nodules.      Thyroid      carcmoma      closely

resembles its benign counterpart  in physical characteristics,             measurable          physiological parameters   such   as   serum   T3/T4   levels and           ultrasonic          characteristics.     Therefore the  surgical  excision  of  the  nodule  and its histopathological   examination   is  the  only way to differentiate between the more benign and much less frequent malignant  nodules.2

FNAC has become a common diagnostic procedure replacing other diagnostic methods as  it  requires  no  anesthesia,  it  is  easy  to perform and can be repeated without much discomfort  to the patient  and has  relatively high diagnostic accuracy. 2

Fine needle aspiration cytology (FNAC) was  first  used  as  a  method   of  diagnosis thyroid disease by Soderstrom and Franzen in the 1950s and 1960s. Since then it has been

accepted in many institutes.3

Current guidance recommends the use of fine needle aspiration cytology (FNAC) as an essential investigation in patients presenting with  a thyroid  lump. Current  literature suggests   that  the  sensitivity   of  FNAC  in thyroid nodules ranges between 80-90%. However, only very few studies have looked specifically  at  the  sensitivity   of  FNAC  in solely thyroid cancer patients. 4,5.

Benign  nodules  can  be  caused  by adenomas, colloid nodules, cysts, infectious nodules, lymphocytic or granulomatous nodules,   hyperplastic   nodules,   thyroiditis, and   congenital   anomalies.   Malignant nodules  are  classified  as:   !-Differentiated: a) papillary adenocarcinoma b) follicular adenocarcinoma.    2-Medullary    carcinoma.

3-Undifferentiated    -a)small  cell   b)   giant

cell   c)  carcinosarcoma   4-  Miscellaneous­ a)  lymphoma,   sarcoma   b)  Squamous   cell carcinoma c) Fibrosarcoma d) mucoepithelial carcinoma    e)   metastatic   tumors.6-8       Fine needle aspiration cytology (FNAC) is simple, less expensive, readily available and reliable, time  saving,  easy to  perform,  effective  and almost   accurate   diagnostic   technique   for investigation of thyroid swelling.4,9 FNAC is widely accepted and has become cornerstone in evaluation ofthyroid nodules because it is a simple and accurate screening test with high sensitivity  and specificity in the preoperative evaluation  of thyroid  lesions.l0-12 The  role of cytology  in thyroid  swellings  is doubled ways  as it can  be therapeutic,  for  example aspirating  a large  cyst can  relieve  pressure symptoms.  Cytology  also has a part to play in pre-operative diagnosis by identifying the disease process in both solitary  nodules and in diffuse enlargement of the thyroid gland.l3

FNAC is considered  as the gold standard investigation in diagnosis of thyroid nodules. However, evenFNAChas limitations because of low yield of cells, loss of histological architecture and inability to distinguish follicular adenoma and well differentiated follicular   carcinoma.l4-16 The  aim  of  our study was to investigate the value of FNAC as  a  basic   investigation   in  patients   with thyroid  enlargement.  We aimed  specifically

to  assess  the  sensitivity   of  FNAC  within cancer susp1c1ous group.

Patients and methods:

This retrospective study was carried out in the department of surgery, Alexandria Facuity of  Medicine  reviewing  cases from  January

1St, 2001 to December 31St, 2012. It includes

all patients with simple nodular goiter who underwent thyroid surgery during that period. According  to  different  policies  of  different units in our surgical department some patients were routinely sent for cytological evaluation of nodular goiter by FNAC and some not. All patients either had or had not FNAC were counseled about their possible diagnosis and the indications and type of surgery before operation. After thyroid surgery, the excised specimens were sent to pathology department for final histological diagnosis.

Inclusion Criteria:

1. Patients with primary euthyroid nodular goiter of any age.

2. Patients with both pre-operative FNAC and postoperative histological evaluation done by the team of pathologists in pathological department, Alexandria Faculty of Medicine.

Exclusion Criteria:

1. Patients who had recurrent goiter or secondary metastatic lesions.

2. Patients who had either pre or post operative   diagnostic   evaluation   from   any other laboratory

Statistical analysis: The data was analyzed

for sensitivity, specificity and accuracy of FNAC as a predictive for thyroid surgical procedure.

Results:

In accordance with inclusion and exclusion criteria, total617 patients were included in the study. Female to male ratio was 589 (90.6%) and 28(9.4%) respectively. Age of the patients ranged from 15-72  years with mean age 38.5 years. Distribution  of patients in sub-groups for their  age is shown  in Table (1). Among the 617 patients, preoperative fine needle aspiration  cytology  had  been  done  to  409 cases only.

Neoplastic     lesions     or     susp1c10us  of

neoplasm had been showed in 53 of preoperative  FNAC patients and out ofthem histopathology proved neoplastic lesions (Benign or malignant) only in 39 (74%) patients,  while the remaining  14 (26%) patients were found to have non- neoplastic benign lesions. Therefore, 39 patients were found to be true positive and 14 patients were marked as false positive.

Cytological diagnosis showed non­ neoplastic  nodular  goiter  in 356 (87%) patients and out of them only 15 (4%) patients were found to have neoplastic nodular goiter on   post   operative   histopathology.   These

15  patients  were  marked  as  false  negative for neoplastic nodular goiter. The major proportion 341 (96%) patients, was found to have non-neoplastic nodular goiter on FNAC and histopathology  as well. All those 341 patients were true negative for neoplasm of thyroid Table (2).

On the other hand among the 208 patients who had directly their surgery without doing preoperative  FNAC  only  13  (6%)  of  them had post operative diagnosis with malignant neoplastic lesions. Of them only 8 (4%) patients need completion of thyroidectomy operations as a second operation for curative surgery.

Statistical analysis showed preoperative FNAC  sensitivity,  specificity  and  accuracy are 68.27%, 87.40% and 85.89%respectively.

Discussion:

Thyroid  nodules  and goitre  are common and often noted coincidentally  when patients are being imaged for other reasons. The vast majority (95%) of cases have benign disease.l The  decision  whether  or  not to  perform FNAC  will  depend  on  the  clinical  picture, and the responsible  clinician  needs to make an   appropriate   judgment       about   pursuing cytological                       confirmation,     in     order      to avoid   overtreatment    of   clinically   benign

conditions.l6

Despite  clinical  size  of  a  nodule  being used   as  criteria   in  some   guidelines,   the evidence does not support  size  as a reliable indicator   of  malignancy.  While  there   are some  studies  indicating  that  nodule  size  is

associated with malignancy, a larger body of evidence suggests that size is not specific in distinguishing benign from malignant thyroid

nodules. 16

US  appearances   that  are   indicative   of a benign nodule should be regarded as reassuring not requiring fine needle aspiration cytology   (FNAC),   unless  the  patient   has a statistically  high  risk  of  malignancy.  On the other hand, If the US appearances are equivocal, indeterminate or suspicious of malignancy,  an  US  guided  FN AC  should

follow.16

On the other hand the College of American Pathologists recommend no need for FNAC from, patients with a history of a nodule or goiter which has not changed for several years and who have no other worrying features (i.e. adult patient, no history of neck irradiation, no   family   history   of  thyroid   cancer,  no palpable     cervical    lymphadenopathy,     no stridor  or voice  change). Also patients with a non-palpable  asymptomatic  nodule <1 em in diameter discovered incidentally on neck ultrasound  without  other  worrying  features are considered not indicated for FNAC.17

In nodules which are discovered incidentally; nodules under 1cm should be referred to ultrasound to detect suspicious echographic  characteristics  that  would warrant FNA. In contrast, CT and MRI are relatively insensitive for the detection of primary  thyroid  carcinoma,   and  there  are little data to support FNA of nodules detected primarily through these modalities.l8

In fact, any thyroid lesion with suspicious features on ultrasound  should be considered for FNA, as should nodules larger than 1. Scm, even in the absence of suspicious features.

As  a minimum,  clinical  information relevant to thyroid pathology should be annotated on the pathology requisition. Additional useful information includes ultrasound, CT, MRI, or nuclear imaging findings; TSH levels; concurrent thyroxine therapy;  and  history  of  prior  FNA. All  of these factors can influence the interpretation of a thyroid FNA because they convey situations that change expectations for a specific   morphologic   pattern   or   for   the

probability   of  disease.   For  example,   low serum TSH levels are associated with a lower risk of thyroid carcinoma.9 Cellular changes that  mimic  malignant  processes  occur  with I131 therapy, external  beam radiation,  prior FNA,  autoimmune  thyroiditis,  and  Graves'

disease. 19-21

According to guidelines from the American Association of Clinical Endocrinologists, FNAC is "believed  to be the most effective method available for distinguishing between benign and malignant thyroid nodules,22 with an accuracy approaching 95 percent.6

In the study of Sunita and Shere et al, the correlation between fine needle aspiration cytology and the histopathological finding was high. There was 100% cyto-histopathological correlation  in  benign and  malignant  tumors of thyroid and 96.87%  correlation  in tumor like lesions ofthyroid gland.l

Therefore, to his opinion FNAC diagnosis of malignancy  is highly significant and such patients should be subjected to surgery. A benign  FNAC  diagnosis  should  be  viewed with caution as false negative results do occur and these patients should be followed up and any  clinical  suspicion  of  malignancy  even in  the  presence  of  benign  FNAC  requires

surgery.1

In  benign  disease:  in the  large  series  of

6300 thyroid aspirates from Mayo Clinic, benign disease represented 65% of the total findings. This included thyroiditis, benign colloid as well as cystic goiter.23 On the other hand   FNAC  represented   an  improvement on  the  diagnosis  of  thyroiditis  and  can  be

considered as essential in those cases.24 This

is similar  to the  experience  of others  who found that up to 63% of thyroiditis had no clinical diagnostic features.25

Similarly, in  the  series  of  Schenck, negative  findings represented  81-5%  of the

1000 thyroid aspirates.25 However, in these studies there is no reference to the relative contribution  of the benign  FNAC diagnosis to  the  ultimate  management.  In  our  series the FNAC, when compared with the initial clinical diagnosis based on non-invasive investigations,  represented  no  improvement on the  original  diagnosis  of benign  colloid/

cystic goiter and can be considered as only additional to the diagnosis.

Solitary nodules which are occasionally clinically suspected and cannot be clarified by means of non-invasive investigations can be diagnosed by FNAC. In the study ofGodinho, Matos et al, FNAC leads to decrease of clinically suspect lesions from 37% to 15.4% and can therefore  be considered  as essential in those  cases.26 In the  experience  of other authors approximately 3-11 % of thyroid aspirates  are cytologically  suspicious.' This group includes diagnoses "consistent with follicularneoplasm", "consistent with Hiirthle cell neoplasm" and "suggestive of papillary carcinoma". Suspicious FNAC results require histological confirmation. In the Mayo Clinic series, 27% of the cytologically suspicious lesions proved to be malignant.25

Regarding  neoplasm,  out of 53 clinically

suspicious  cases  in  Godinho,  Matos  et  al series  FNAC  led to  diagnosis  of  tumor  in

20  patients.   However,  neoplasm   was  not

diagnosed in four cases of follicular adenoma which were cytological benign but were clinically   suspicious.   The   false   negative rate of thyroid FN AC ranges from 2% up to

33%.27 False positive results are rare, one of

221 cases in the Mayo Clinic series.25

In another study, false-negative  rate for cytology  is  reported  to  be  between  0  and

29%.28 Flanaqan et al reported that the use of one repeat  FNA can increase the sensitivity for malignancy from 81.7 to 90.4% and decrease  the  false-negative   rate  from  17.1 to    11.4%.   Furthermore,    they    concluded that,   with   more   than   one   repeat   FN A, there was no improvement in performance characteristics.29

The management of thyroid disease as influenced by the FNAC is perhaps best exemplified in the low rate of surgical intervention.  Surgery was avoided mainly in benign cystic lesions and thyroiditis  as well as in anaplastic, metastatic tumours, and lymphomas.  In the experience of Hamberger et al, due to the use ofFNAC, only two thirds of patients with clinically solitary "cold" nodules have undergone surgery.30 The high proportion   of  tumors   (15%)   in  Godinho,

Table 1: Distribution  age & sex among all thyroid patients treated in our institute.

Table 2: Relations between FNAC results & final histological results.

Matos et al series is attributed to the selection of patients in anon-endemic area. In summary, they have proved  FNAC to have an essential role   in  the   diagnosis  and  management of

23%  of their  patients, a confirmatory role in

61%  of  patients,  a non-contributory role  in

13%  when specimens were inadequate and a misleading role in 3% where the results  were false  negative.  The positive  identification of thyroiditis and neoplasm stands  on its own as a justification for FNAC.27

At present,  FNAC  is a fundamental method  for  evaluation of suggestive thyroid nodules. Examination of the material obtained by FNAC  enables  clinicians to differentiate between   benign  and  malignant  processes.31

However,    FNAC   of   thyroid    nodules   has its  limitations.  First,   adequate  cytological interpretation  depends   on  correct   detection ofthe lesion and on the aspiration technique. Wrong     detection     and     poor     aspiration techniques cause  most  of  the  false-negative reports.  Second, the most important limitation of  thyroid   cytology   lies  in  the  differential diagnostics of cellular  follicular lesions.  It is especially difficult to distinguish benign from malignant follicular neoplasm by cytological evaluation because  the  diagnosis of  cancer

depends  on the  demonstration of vascular  or capsular invasion.32 In the case of follicular lesions, the cytopathological examination relatively often concludes as follicular lesion of uncertain biological character.33

We agree with the statement that the diagnostic  role ofthe FNAC  over and above the  non-invasive diagnostic procedures in benign,  clinically suspicious, and malignant lesions of the thyroid can be classified into: essential,  additional, and non-contributory/ misleading depending on the impact  that FNAC had on the clinical  management.26

From reviewing ofliterature and according to our results we could conclude that FNAC is not essential  for each thyroid  enlargement. It has a great value  in preoperative assessment of suspicious neoplasm cases either clinically as single nodules  or by US features. We need to understand what a specific FNAC result means to patient's management. Significant result of FNAC can provide preoperative guidance  when  assessing the  probability of the target disorder.  We had expected  that a "malignant" or "suggestive" FNAC  result significantly enhances  the  probability of thyroid  neoplasm and  should  be an absolute indication for surgery.

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