The incidence of thyroid cancer has been rapidly increasing since the mid-1990s.1FNA is the first choice for diagnosing thyroid lesions because of the high sensitivity and specificity of this method.1 Additionally, it is believed to be safe and associated with fewercomplications when compared with other methods; one of the main complications of FNA is the occurrence of minor hematomas.4Thus, for these reasons, the usage of the FNA method has increased dramatically over the years.
However, this method has some limitations. A definitive cytological diagnosis cannot be made in 10% to 25% of the thyroid FNA cases.5One of the main reasons for this is the presence of atypical cellsfor which the significance cannot be determined.5The recently updatedBethesda guidelines for the management of thyroid nodules classifies cases harboring atypicalcells that cannot be determined asAUS.6Furthermore, theyrecommend repeat FNA for a more conclusive resultbecause the reported risk for malignancy in cases with AUS is 5%–15%.6The number of patients requiring repeat FNA has increased owing to the rapid increase in the incidence of thyroid FNA biopsies. The patient in thecurrent case report underwent repeated FNA because the thyroid nodule was cytologically diagnosed as AUS.
Although the FNA method is very effective and accurate for the diagnosis of thyroid lesions, trauma caused by the aspiration needle can induce varying degrees of histological alterations.3These alterations induced by FNA have been classified into acute and chronic types based on the type of histological alteration and the interval between the FNA procedure and the surgery.7Acute alterations include hemorrhage, granulation tissue formation, siderophagia, necrosis, granulomatous inflammation, and associated cytological atypia. The most common findings are hemorrhage and granulation tissue formation, which are predominantly found with a 3-week interval between the FNA procedure and the surgery.7On the other hand, chronic alterations include fibrosis, metaplasia, infarction, capsular distortion, cyst formation, papillary degeneration, papillary endothelial proliferation, and calcification;7fibrosis and distortion of the capsuleare most frequently observedin this group with an interval period of 3 weeks to 6 months.7
For pathologists, capsular and vascular alteration due to FNA procedure has caused difficulties to diagnosis.5 Because capsular or vascular invasion is the most important factor for differentiating follicular adenoma from follicular carcinoma.5Reactive atypia due to previous FNA procedure can also be a problem in diagnosis of thyroid neoplasm.5Reactive cytologic atypia, such as nuclear clearing, mitosis, prominent nucleoli, and nuclear pleomorphism can occur in stromal and follicular cells following FNA procedure. And these cytologic features can create a confusion between papillary thyroid carcinoma, which is the most prevalent malignant tumor in thyroid gland, and benign thyroid lesion with FNA induced reactive cytologic atypia.5However, in the present case,fibrosis caused diagnostic difficulties while evaluating thyroid lesions. Although, follicular adenomas can exhibit various secondary changes including fibrosis as in our case, we suspected that the fibrosis was induced by FNA procedure because in addition to fibrosis, hemorrhage, infarction type necrosis and needle tract-like structure (Fig. 2A, arrow) were identified and most of all the patient’shistory of multiple FNA procedure before the surgery. Fibrosis is one of the most common FNA-induced chronic alterations.8It is a common reactive reaction that affects most thyroid lesions, benign or malignant.4In the study by Bolat F fibrosis was identified in 66.0% patients who underwent FNA, whereas only 15.3%of the cases without a history of FNA presented with fibrosis.8
In our present case, the fibrosis created significant challenges in distinguishing between follicular adenoma and medullary carcinoma. The tumor cells in medullary thyroid carcinomaare usually arranged in nests or trabecular patterns separated by varying amounts of fibrovascular stroma.9 The tumor stroma appears variable; however, abundant hyalinized collagen and Congo Red-positive stromal amyloid deposits have been observed in 80% of medullary thyroid carcinoma cases.9
Distinguishing medullary thyroid carcinoma from follicular adenoma with fibrosisis relatively simple because the tumor cells of the carcinoma show immunoreactivity for calcitonin and neuroendocrine markers, such as chromogranin A and synaptophysin. However, in the present case, we had to examine frozen sections without immunohistochemistry, making it extremely difficult to reach an accurate diagnosis and consequently leading to a misdiagnosis. In frozen sections, the tumor cells were arranged in a trabecular pattern due to fibrosis and the thick collagenous tissuesmimicked amyloid deposition similar to that seen in medullary thyroid carcinoma. These findings indicate the importance of ascertaining the medical history of the patient, with particular emphasis on the number of FNA procedures undergone, before diagnosing thyroid nodules.
It isvery difficult to distinguish follicular adenoma with extensive fibrosis frommedullary thyroid carcinoma without immunohistochemistry,especially when the fibrosis mimicsamyloid deposition as in the present case study. Most cases of medullary thyroid carcinomasshow infiltrative borderswith infiltration of the tumor cells into the surrounding normal tissue.9In contrast, follicular adenoma has an intact capsule, although the FNAprocedure can damage the capsule. In the current case report, the capsule was intact. Therefore, evaluating the status of the capsule could be one of the distinctive points for differentiating follicular adenoma with fibrosis from medullary thyroid carcinoma for pathologist when immunohistochemistry cannot be used.
In conclusion, we have presented a case of follicular adenoma with extensive fibrosis with features mimicking those of medullary thyroid carcinoma caused by FNA biopsy. It is important that the pathologist beaware of FNA-induced histopathological alterations in order to avoid the misdiagnosis of thyroid nodules.